|
1
|
Kokubun K, Nemoto K, Yamakawa Y. Fractional Anisotropy of Cingulum Cingulate Mediates the Relationship Between Happiness and Work Performance in Healthy Individuals. Brain Behav 2025; 15:e70334. [PMID: 39957380 PMCID: PMC11831004 DOI: 10.1002/brb3.70334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 12/15/2024] [Accepted: 12/19/2024] [Indexed: 02/18/2025] Open
Abstract
INTRODUCTION As competition among companies around the world intensifies, the nature of work and the performance required are becoming more complex. In parallel with this, there is growing attention on happiness and well-being as factors related to improving employee performance. However, little is known about the relationship between happiness and the brain and work performance in healthy people. METHODS Therefore, we analyzed the correlations between the nine categories of work role performance (WRP), the subjective happiness scale (SHS), and four regions of fractional anisotropy (FA), an index reflecting brain microstructure that has been shown to be related to apathy in previous studies. RESULTS It was shown that the cingulum cingulate (CCI) and the superior longitudinal fasciculus (SLF) correlated with the WRP and its facets in a manner consistent with their respective functions. In particular, the CCI was found to be extensively correlated with the facets of the WRP and to have a partially mediating effect on the relationship between the SHS and the WRP. CONCLUSION This study is the first to show that indicators reflecting healthy individuals' happiness and brain microstructure, which are related to a variety of nonwork factors, are positively correlated with the diverse roles and performance that characterize modern work.
Collapse
Affiliation(s)
- Keisuke Kokubun
- Open Innovation InstituteKyoto UniversityKyotoJapan
- Graduate School of ManagementKyoto UniversityKyotoJapan
| | - Kiyotaka Nemoto
- Department of Psychiatry, Institute of MedicineUniversity of TsukubaTsukubaJapan
| | - Yoshinori Yamakawa
- Open Innovation InstituteKyoto UniversityKyotoJapan
- Graduate School of ManagementKyoto UniversityKyotoJapan
- Institute of Innovative ResearchTokyo Institute of TechnologyMeguroTokyoJapan
- ImPACT Program of Council for ScienceTechnology and Innovation (Cabinet Office, Government of Japan)ChiyodaTokyoJapan
- Office for Academic and Industrial InnovationKobe UniversityKobeJapan
- Brain ImpactKyotoJapan
| |
Collapse
|
|
2
|
Miranda-Barrientos J, Adiraju S, Rehg JJ, Hallock HL, Li Y, Carr GV, Martinowich K. Patterns of neural activity in prelimbic cortex neurons correlate with attentional behavior in the rodent continuous performance test. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2024:2024.07.26.605300. [PMID: 39091763 PMCID: PMC11291163 DOI: 10.1101/2024.07.26.605300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 08/04/2024]
Abstract
Sustained attention, the ability to focus on a stimulus or task over extended periods, is crucial for higher level cognition, and is impaired in individuals diagnosed with neuropsychiatric and neurodevelopmental disorders, including attention-deficit/hyperactivity disorder, schizophrenia, and depression. Translational tasks like the rodent continuous performance test (rCPT) can be used to study the cellular mechanisms underlying sustained attention. Accumulating evidence points to a role for the prelimbic cortex (PrL) in sustained attention, as electrophysiological single unit and local field (LFPs) recordings reflect changes in neural activity in the PrL in mice performing sustained attention tasks. While the evidence correlating PrL electrical activity with sustained attention is compelling, limitations inherent to electrophysiological recording techniques, including low sampling in single unit recordings and source ambivalence for LFPs, impede the ability to fully resolve the cellular mechanisms in the PrL that contribute to sustained attention. In vivo endoscopic calcium imaging using genetically encoded calcium sensors in behaving animals can address these questions by simultaneously recording up to hundreds of neurons at single cell resolution. Here, we used in vivo endoscopic calcium imaging to record patterns of neuronal activity in PrL neurons using the genetically encoded calcium sensor GCaMP6f in mice performing the rCPT at three timepoints requiring differing levels of cognitive demand and task proficiency. A higher proportion of PrL neurons were recruited during correct responses in sessions requiring high cognitive demand and task proficiency, and mice intercalated non-responsive-disengaged periods with responsive-engaged periods that resemble attention lapses. During disengaged periods, the correlation of calcium activity between PrL neurons was higher compared to engaged periods, suggesting a neuronal network state change during attention lapses in the PrL. Overall, these findings illustrate that cognitive demand, task proficiency, and task engagement differentially recruit activity in a subset of PrL neurons during sustained attention.
Collapse
Affiliation(s)
| | - Suhaas Adiraju
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
- Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
| | - Jason J. Rehg
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | | | - Ye Li
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | - Gregory V. Carr
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
- Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Keri Martinowich
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
- Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
- The Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, 21205, USA
| |
Collapse
|
|
3
|
Hallock HL, Adiraju SS, Miranda-Barrientos J, McInerney JM, Oh S, DeBrosse AC, Li Y, Carr GV, Martinowich K. Electrophysiological correlates of attention in the locus coeruleus-prelimbic cortex circuit during the rodent continuous performance test. Neuropsychopharmacology 2024; 49:521-531. [PMID: 37563281 PMCID: PMC10789747 DOI: 10.1038/s41386-023-01692-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 07/19/2023] [Accepted: 07/24/2023] [Indexed: 08/12/2023]
Abstract
Sustained attention, the ability to focus on an activity or stimulus over time, is significantly impaired in many psychiatric disorders, and there remains a major unmet need in treating impaired attention. Continuous performance tests (CPTs) were developed to measure sustained attention in humans, non-human primates, rats, and mice, and similar neural circuits are engaged across species during CPT performance, supporting their use in translational studies to identify novel therapeutics. Here, we identified electrophysiological correlates of attentional performance in a touchscreen-based rodent CPT (rCPT) in the locus coeruleus (LC) and prelimbic cortex (PrL), two inter-connected regions that are implicated in attentional processes. We used viral labeling and molecular techniques to demonstrate that neural activity is recruited in LC-PrL projections during the rCPT, and that this recruitment increases with cognitive demand. We implanted male mice with depth electrodes within the LC and PrL for local field potential (LFP) recordings during rCPT training, and identified an increase in PrL delta and theta power, and an increase in LC delta power during correct responses in the rCPT. We also found that the LC leads the PrL in theta frequencies during correct responses while the PrL leads the LC in gamma frequencies during incorrect responses. These findings may represent translational biomarkers that can be used to screen novel therapeutics for drug discovery in attention.
Collapse
Affiliation(s)
- Henry L Hallock
- Neuroscience Program, Lafayette College, Easton, PA, 18042, USA
| | - Suhaas S Adiraju
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | | | - Jessica M McInerney
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | - Seyun Oh
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | - Adrienne C DeBrosse
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | - Ye Li
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | - Gregory V Carr
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA.
- Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA.
| | - Keri Martinowich
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA.
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
- Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA.
- The Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, 21205, USA.
| |
Collapse
|
|
4
|
Zhu T, Wang Z, Wu W, Ling Y, Wang Z, Zhou C, Fang X, Huang C, Xie C, Chen J, Zhang X. Altered brain functional networks in schizophrenia with persistent negative symptoms: an activation likelihood estimation meta-analysis. Front Hum Neurosci 2023; 17:1204632. [PMID: 37954938 PMCID: PMC10637389 DOI: 10.3389/fnhum.2023.1204632] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2023] [Accepted: 10/10/2023] [Indexed: 11/14/2023] Open
Abstract
Objective To investigate brain structural and functional characteristics of three brain functional networks including default mode network (DMN), central executive network (CEN), and salience network (SN) in persistent negative symptoms (PNS) patients. Methods We performed an activation likelihood estimation (ALE) meta-analysis of functional connectivity (FC) studies and voxel-based morphometry (VBM) studies to detect specific structural and functional alterations of brain networks between PNS patients and healthy controls. Results Seventeen VBM studies and twenty FC studies were included. In the DMN, PNS patients showed decreased gray matter in the bilateral medial frontal gyrus and left anterior cingulate gyrus and a significant reduction of FC in the right precuneus. Also, PNS patients had a decrease of gray matter in the left inferior parietal lobules and medial frontal gyrus, and a significant reduction of FC in the bilateral superior frontal gyrus in the CEN. In comparison with healthy controls, PNS patients exhibited reduced gray matter in the bilateral insula, anterior cingulate gyrus, left precentral gyrus and right claustrum and lower FC in these brain areas in the SN, including the left insula, claustrum, inferior frontal gyrus and extra-nuclear. Conclusion This meta-analysis reveals brain structural and functional imaging alterations in the three networks and the interaction among these networks in PNS patients, which provides neuroscientific evidence for more personalized treatment.Systematic Review RegistrationThe PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, registration number: CRD42022335962).
Collapse
Affiliation(s)
- Tingting Zhu
- Department of Psychiatry, The Third People’s Hospital of Huai’an, Huaian, Jiangsu, China
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Zengxiu Wang
- Department of Hepatology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Weifeng Wu
- Department of Hepatology, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, China
| | - Yuru Ling
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Zixu Wang
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Chao Zhou
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Xinyu Fang
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Chengbing Huang
- Department of Psychiatry, The Third People’s Hospital of Huai’an, Huaian, Jiangsu, China
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Chunming Xie
- Department of Neurology, Affiliated Zhongda Hospital, School of Medicine Southeast University, Nanjing, China
| | - Jiu Chen
- Institute of Neuropsychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
| | - Xiangrong Zhang
- Department of Geriatric Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China
- The Affiliated Xuzhou Oriental Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| |
Collapse
|
|
5
|
Hallock HL, Adiraju S, Miranda-Barrientos J, McInerney JM, Oh S, DeBrosse AC, Li Y, Carr GV, Martinowich K. Electrophysiological correlates of attention in the locus coeruleus - anterior cingulate cortex circuit during the rodent continuous performance test. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.04.19.537406. [PMID: 37131757 PMCID: PMC10153204 DOI: 10.1101/2023.04.19.537406] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
Sustained attention, the ability to focus on an activity or stimulus over time, is significantly impaired in many psychiatric disorders, and there remains a major unmet need in treating impaired attention. Continuous performance tests (CPTs) were developed to measure sustained attention in humans, non-human primates, rats, and mice, and similar neural circuits are engaged across species during CPT performance, supporting their use in translational studies to identify novel therapeutics. Here, we identified electrophysiological correlates of attentional performance in a touchscreen-based rodent CPT (rCPT) in the locus coeruleus (LC) and anterior cingulate cortex (ACC), two inter-connected regions that are implicated in attentional processes. We used viral labeling and molecular techniques to demonstrate that neural activity is recruited in LC-ACC projections during the rCPT, and that this recruitment increases with cognitive demand. We implanted male mice with depth electrodes within the LC and ACC for local field potential (LFP) recordings during rCPT training, and identified an increase in ACC delta and theta power, and an increase in LC delta power during correct responses in the rCPT. We also found that the LC leads the ACC in theta frequencies during correct responses while the ACC leads the LC in gamma frequencies during incorrect responses. These findings may represent translational biomarkers that can be used to screen novel therapeutics for drug discovery in attention.
Collapse
Affiliation(s)
| | - Suhaas Adiraju
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | | | - Jessica M. McInerney
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | - Seyun Oh
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | - Adrienne C. DeBrosse
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | - Ye Li
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
| | - Gregory V. Carr
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
- Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, 21205, USA
| | - Keri Martinowich
- Lieber Institute for Brain Development, Johns Hopkins Medical Campus, Baltimore, MD, 21205, USA
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
- Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD, 21205, USA
- The Kavli Neuroscience Discovery Institute, Johns Hopkins University, Baltimore, MD, 21205, USA
| |
Collapse
|
|
6
|
Chen J, Wei Y, Xue K, Han S, Wang C, Wen B, Cheng J. The interaction between first-episode drug-naïve schizophrenia and age based on gray matter volume and its molecular analysis: a multimodal magnetic resonance imaging study. Psychopharmacology (Berl) 2023; 240:813-826. [PMID: 36719459 DOI: 10.1007/s00213-023-06323-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 01/19/2023] [Indexed: 02/01/2023]
Abstract
OBJECTIVES Schizophrenia is a neurodevelopmental disorder characterized by progressive and widespread gray matter (GM) atrophy. Studies have shown that normal brain development has an impact on schizophrenia-induced GM alterations. However, the neuropathology and underlying molecular mechanisms of interaction between age and schizophrenia are unclear. METHODS This study enrolled 66/84 first-episode drug-naïve patients with early-onset/adult-onset schizophrenia ((EOS)/(AOS)) and matched normal controls (NC) (46 adolescents/73 adults), undergoing T1-weighted high-resolution magnetic resonance imaging. Gray matter volume (GMV) in four groups was detected using 2-way analyses of variance with diagnosis and age as factors. Then, factors-related volume maps and neurotransmitter maps were spatially correlated using JuSpace to determine the relationship to molecular structure. RESULTS Compared to AOS, EOS and adult NC had larger GMV in right middle frontal gyrus. Compared to adolescent NC, EOS and adult NC had smaller GMV in right lingual gyrus, right fusiform gyrus, and right cerebellum_6. Disease-induced GMV reductions were mainly distributed in frontal, parietal, thalamus, visual, motor cortex, and medial temporal lobe structures. Age-induced GMV alterations were mainly distributed in visual and motor cortex. The changed GMV induced by schizophrenia, age, and their interaction was related to dopaminergic and serotonergic receptors. Age is also related to glutamate receptors, and schizophrenia is also associated with GABAaergic and noradrenergic receptors. CONCLUSIONS Our results revealed the multimodal neural mechanism of interaction between disease and age. We emphasized age-related GM abnormalities of ventral stream of visual perceptual pathways and high-level cognitive brain in EOS, which may be affected by imbalance of excitatory and inhibitory neurotransmitters.
Collapse
Affiliation(s)
- Jingli Chen
- Department of Magnetic Resonance Imaging, Two Seven District, The First Affiliated Hospital of Zhengzhou University, 1St Construction of E Rd, Zhengzhou, 450052, China
- Key Laboratory for Functional Magnetic Resonance Imaging and Molecular Imaging of Henan Province, Zhengzhou, China
- Engineering Technology Research Center for Detection and Application of Brain Function of Henan Province, Zhengzhou, China
- Engineering Research Center of Medical Imaging Intelligent Diagnosis and Treatment of Henan Province, Zhengzhou, China
- Key Laboratory of Magnetic Resonance and Brain Function of Henan Province, Zhengzhou, China
- Key Laboratory of Brain Function and Cognitive Magnetic Resonance Imaging of Zhengzhou, Zhengzhou, China
- Key Laboratory of Imaging Intelligence Research Medicine of Henan Province, Zhengzhou, China
| | - Yarui Wei
- Department of Magnetic Resonance Imaging, Two Seven District, The First Affiliated Hospital of Zhengzhou University, 1St Construction of E Rd, Zhengzhou, 450052, China
- Key Laboratory for Functional Magnetic Resonance Imaging and Molecular Imaging of Henan Province, Zhengzhou, China
- Engineering Technology Research Center for Detection and Application of Brain Function of Henan Province, Zhengzhou, China
- Engineering Research Center of Medical Imaging Intelligent Diagnosis and Treatment of Henan Province, Zhengzhou, China
- Key Laboratory of Magnetic Resonance and Brain Function of Henan Province, Zhengzhou, China
- Key Laboratory of Brain Function and Cognitive Magnetic Resonance Imaging of Zhengzhou, Zhengzhou, China
- Key Laboratory of Imaging Intelligence Research Medicine of Henan Province, Zhengzhou, China
| | - Kangkang Xue
- Department of Magnetic Resonance Imaging, Two Seven District, The First Affiliated Hospital of Zhengzhou University, 1St Construction of E Rd, Zhengzhou, 450052, China
- Key Laboratory for Functional Magnetic Resonance Imaging and Molecular Imaging of Henan Province, Zhengzhou, China
- Engineering Technology Research Center for Detection and Application of Brain Function of Henan Province, Zhengzhou, China
- Engineering Research Center of Medical Imaging Intelligent Diagnosis and Treatment of Henan Province, Zhengzhou, China
- Key Laboratory of Magnetic Resonance and Brain Function of Henan Province, Zhengzhou, China
- Key Laboratory of Brain Function and Cognitive Magnetic Resonance Imaging of Zhengzhou, Zhengzhou, China
- Key Laboratory of Imaging Intelligence Research Medicine of Henan Province, Zhengzhou, China
| | - Shaoqiang Han
- Department of Magnetic Resonance Imaging, Two Seven District, The First Affiliated Hospital of Zhengzhou University, 1St Construction of E Rd, Zhengzhou, 450052, China
- Key Laboratory for Functional Magnetic Resonance Imaging and Molecular Imaging of Henan Province, Zhengzhou, China
- Engineering Technology Research Center for Detection and Application of Brain Function of Henan Province, Zhengzhou, China
- Engineering Research Center of Medical Imaging Intelligent Diagnosis and Treatment of Henan Province, Zhengzhou, China
- Key Laboratory of Magnetic Resonance and Brain Function of Henan Province, Zhengzhou, China
- Key Laboratory of Brain Function and Cognitive Magnetic Resonance Imaging of Zhengzhou, Zhengzhou, China
- Key Laboratory of Imaging Intelligence Research Medicine of Henan Province, Zhengzhou, China
| | - Caihong Wang
- Department of Magnetic Resonance Imaging, Two Seven District, The First Affiliated Hospital of Zhengzhou University, 1St Construction of E Rd, Zhengzhou, 450052, China
- Key Laboratory for Functional Magnetic Resonance Imaging and Molecular Imaging of Henan Province, Zhengzhou, China
- Engineering Technology Research Center for Detection and Application of Brain Function of Henan Province, Zhengzhou, China
- Engineering Research Center of Medical Imaging Intelligent Diagnosis and Treatment of Henan Province, Zhengzhou, China
- Key Laboratory of Magnetic Resonance and Brain Function of Henan Province, Zhengzhou, China
- Key Laboratory of Brain Function and Cognitive Magnetic Resonance Imaging of Zhengzhou, Zhengzhou, China
- Key Laboratory of Imaging Intelligence Research Medicine of Henan Province, Zhengzhou, China
| | - Baohong Wen
- Department of Magnetic Resonance Imaging, Two Seven District, The First Affiliated Hospital of Zhengzhou University, 1St Construction of E Rd, Zhengzhou, 450052, China
| | - Jingliang Cheng
- Department of Magnetic Resonance Imaging, Two Seven District, The First Affiliated Hospital of Zhengzhou University, 1St Construction of E Rd, Zhengzhou, 450052, China.
- Key Laboratory for Functional Magnetic Resonance Imaging and Molecular Imaging of Henan Province, Zhengzhou, China.
- Engineering Technology Research Center for Detection and Application of Brain Function of Henan Province, Zhengzhou, China.
- Engineering Research Center of Medical Imaging Intelligent Diagnosis and Treatment of Henan Province, Zhengzhou, China.
- Key Laboratory of Magnetic Resonance and Brain Function of Henan Province, Zhengzhou, China.
- Key Laboratory of Brain Function and Cognitive Magnetic Resonance Imaging of Zhengzhou, Zhengzhou, China.
- Key Laboratory of Imaging Intelligence Research Medicine of Henan Province, Zhengzhou, China.
| |
Collapse
|
|
7
|
Xie Y, Guan M, He Y, Wang Z, Ma Z, Fang P, Wang H. The Static and dynamic functional connectivity characteristics of the left temporoparietal junction region in schizophrenia patients with auditory verbal hallucinations during low-frequency rTMS treatment. Front Psychiatry 2023; 14:1071769. [PMID: 36761865 PMCID: PMC9907463 DOI: 10.3389/fpsyt.2023.1071769] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Accepted: 01/09/2023] [Indexed: 01/27/2023] Open
Abstract
BACKGROUND Auditory verbal hallucinations (AVH) are a core symptom of schizophrenia. Low-frequency (e.g., 1 Hz) repetitive transcranial magnetic stimulation (rTMS) targeting language processing regions (e.g., left TPJ) has been evident as a potential treatment for AVH. However, the underlying neural mechanisms of the rTMS treatment effect remain unclear. The present study aimed to investigate the effects of 1 Hz rTMS on functional connectivity (FC) of the temporoparietal junction area (TPJ) seed with the whole brain in schizophrenia patients with AVH. METHODS Using a single-blind placebo-controlled randomized clinical trial, 55 patients with AVH were randomly divided into active treatment group (n = 30) or placebo group (n = 25). The active treatment group receive 15-day 1 Hz rTMS stimulation to the left TPJ, whereas the placebo group received sham rTMS stimulation to the same site. Resting-state fMRI scans and clinical measures were acquired for all patients before and after treatment. The seed-based (left TPJ) static and DFC was used to assess the connectivity characteristics during rTMS treatment in patients with AVH. RESULTS Overall, symptom improvement following 1 Hz rTMS treatment was found in the active treatment group, whereas no change occurred in the placebo group. Moreover, decreased static FC (SFC) of the left TPJ with the right temporal lobes, as well as increased SFC with the prefrontal cortex and subcortical structure were observed in active rTMS group. Increased dynamic FC (DFC) of the left TPJ with frontoparietal areas was also found in the active rTMS group. However, seed-based SFC and DFC were reduced to a great extent in the placebo group. In addition, these changed FC (SFC) strengths in the active rTMS group were associated with reduced severity of clinical outcomes (e.g., positive symptoms). CONCLUSION The application of 1 Hz rTMS over the left TPJ may affect connectivity characteristics of the targeted region and contribute to clinical improvement, which shed light on the therapeutic effect of rTMS on schizophrenia with AVH.
Collapse
Affiliation(s)
- Yuanjun Xie
- School of Education, Xinyang College, Xinyang, China.,Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Muzhen Guan
- Department of Mental Health, Xi'an Medical University, Xi'an, China
| | - Ying He
- Department of Psychiatry, Second Affiliated Hospital, Army Medical University, Chongqing, China
| | - Zhongheng Wang
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| | - Zhujing Ma
- Department of Clinical Psychology, Fourth Military Medical University, Xi'an, China
| | - Peng Fang
- Department of Military Medical Psychology, Fourth Military Medical University, Xi'an, China
| | - Huaning Wang
- Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi'an, China
| |
Collapse
|
|
8
|
Cao H, Hong X, Tost H, Meyer-Lindenberg A, Schwarz E. Advancing translational research in neuroscience through multi-task learning. Front Psychiatry 2022; 13:993289. [PMID: 36465289 PMCID: PMC9714033 DOI: 10.3389/fpsyt.2022.993289] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2022] [Accepted: 10/24/2022] [Indexed: 11/18/2022] Open
Abstract
Translational research in neuroscience is increasingly focusing on the analysis of multi-modal data, in order to account for the biological complexity of suspected disease mechanisms. Recent advances in machine learning have the potential to substantially advance such translational research through the simultaneous analysis of different data modalities. This review focuses on one of such approaches, the so-called "multi-task learning" (MTL), and describes its potential utility for multi-modal data analyses in neuroscience. We summarize the methodological development of MTL starting from conventional machine learning, and present several scenarios that appear particularly suitable for its application. For these scenarios, we highlight different types of MTL algorithms, discuss emerging technological adaptations, and provide a step-by-step guide for readers to apply the MTL approach in their own studies. With its ability to simultaneously analyze multiple data modalities, MTL may become an important element of the analytics repertoire used in future neuroscience research and beyond.
Collapse
Affiliation(s)
- Han Cao
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Xudong Hong
- Department of Computer Vision and Machine Learning, Max Planck Institute for Informatics, Saarbrücken, Germany
- Department of Language Science and Technology, Saarland University, Saarbrücken, Germany
| | - Heike Tost
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Andreas Meyer-Lindenberg
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| | - Emanuel Schwarz
- Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
| |
Collapse
|
|
9
|
Effects of the Mindfulness-Based Blood Pressure Reduction (MB-BP) program on depression and neural structural connectivity. J Affect Disord 2022; 311:31-39. [PMID: 35594968 DOI: 10.1016/j.jad.2022.05.059] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 05/05/2022] [Accepted: 05/12/2022] [Indexed: 11/17/2022]
Abstract
BACKGROUND Hypertension-related illnesses are a leading cause of disability and death in the United States, where hypertension prevalence in adults is 46%, with only half of those afflicted having it under control. Due to the significant challenges in long-term efficacy and adverse effects associated with pharmacological interventions, there is an eminent need for complimentary approaches for treating hypertension. Although initial studies of the Mindfulness-Based Blood Pressure Reduction program (MB-BP) indicate that this novel 8-week intervention is effective at inducing lasting decreases in blood pressure, the neural correlates are unknown. METHODS The objectives of this study were to identify structural neural correlates of MB-BP using diffusion tensor magnetic resonance imaging (DTI) and assess potential correlations with key clinical outcomes. RESULTS In a subset of participants (14 MB-BP, 22 controls) from a larger stage IIa randomized controlled trial, MB-BP participants exhibited increased interoception and decreased depressive symptoms compared to controls. Analyses of DTI data revealed significant group differences in multiple white matter neural tracts associated with the limbic system and/or blood pressure. Specific changes in neural structural connectivity were significantly associated with measures of interoception and depression. LIMITATIONS Limitations include small sample size (leading to insufficient power in the analysis of blood pressure) and the study duration (3 months). The main MRI limitation is suboptimal resolution in areas of extensive neural tract crossings. CONCLUSIONS It is concluded that MB-BP induces alterations in brain structural connectivity which could mediate beneficial changes in depression and interoceptive awareness in individuals with hypertension.
Collapse
|
|
10
|
Sharaev M, Malashenkova I, Maslennikova A, Zakharova N, Bernstein A, Burnaev E, Mamedova G, Krynskiy S, Ogurtsov D, Kondrateva E, Druzhinina P, Zubrikhina M, Arkhipov A, Strelets V, Ushakov V. Diagnosis of Schizophrenia Based on the Data of Various Modalities: Biomarkers and Machine Learning Techniques (Review). Sovrem Tekhnologii Med 2022; 14:53-75. [PMID: 37181835 PMCID: PMC10171060 DOI: 10.17691/stm2022.14.5.06] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2022] [Indexed: 05/16/2023] Open
Abstract
Schizophrenia is a socially significant mental disorder resulting frequently in severe forms of disability. Diagnosis, choice of treatment tactics, and rehabilitation in clinical psychiatry are mainly based on the assessment of behavioral patterns, socio-demographic data, and other investigations such as clinical observations and neuropsychological testing including examination of patients by the psychiatrist, self-reports, and questionnaires. In many respects, these data are subjective and therefore a large number of works have appeared in recent years devoted to the search for objective characteristics (indices, biomarkers) of the processes going on in the human body and reflected in the behavioral and psychoneurological patterns of patients. Such biomarkers are based on the results of instrumental and laboratory studies (neuroimaging, electro-physiological, biochemical, immunological, genetic, and others) and are successfully being used in neurosciences for understanding the mechanisms of the emergence and development of nervous system pathologies. Presently, with the advent of new effective neuroimaging, laboratory, and other methods of investigation and also with the development of modern methods of data analysis, machine learning, and artificial intelligence, a great number of scientific and clinical studies is being conducted devoted to the search for the markers which have diagnostic and prognostic value and may be used in clinical practice to objectivize the processes of establishing and clarifying the diagnosis, choosing and optimizing treatment and rehabilitation tactics, predicting the course and outcome of the disease. This review presents the analysis of the works which describe the correlates between the diagnosis of schizophrenia, established by health professionals, various manifestations of the psychiatric disorder (its subtype, variant of the course, severity degree, observed symptoms, etc.), and objectively measured characteristics/quantitative indicators (anatomical, functional, immunological, genetic, and others) obtained during instrumental and laboratory examinations of patients. A considerable part of these works has been devoted to correlates/biomarkers of schizophrenia based on the data of structural and functional (at rest and under cognitive load) MRI, EEG, tractography, and immunological data. The found correlates/biomarkers reflect anatomic disorders in the specific brain regions, impairment of functional activity of brain regions and their interconnections, specific microstructure of the brain white matter and the levels of connectivity between the tracts of various structures, alterations of electrical activity in various parts of the brain in different EEG spectral ranges, as well as changes in the innate and adaptive links of immunity. Current methods of data analysis and machine learning to search for schizophrenia biomarkers using the data of diverse modalities and their application during building and interpretation of predictive diagnostic models of schizophrenia have been considered in the present review.
Collapse
Affiliation(s)
- M.G. Sharaev
- Senior Researcher; Skolkovo Institute of Science and Technology (Skoltech), Territory of Skolkovo Innovation Center, Bldg 1, 30 Bolshoy Boulevard, Moscow, 121205, Russia; Department Senior Researcher; N.A. Alekseyev Psychiatric Clinical Hospital No.1, 2 Zagorodnoye Shosse, Moscow, 117152, Russia
- Corresponding author: Maksim G. Sharaev, e-mail:
| | - I.K. Malashenkova
- Head of the Laboratory of Molecular Immunology and Virology; National Research Center “Kurchatov Institute”, 1 Akademika Kurchatova Square, Moscow, 123182, Russia; Senior Researcher, Laboratory of Clinical Immunology; Federal Research and Clinical Center of Physical-Chemical Medicine, Federal Medical Biological Agency of Russia, 1A Malaya Pirogovskaya St., Moscow, 119435, Russia
| | - A.V. Maslennikova
- Researcher, Laboratory of Human Higher Nervous Activity; Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5A Butlerova St., Moscow, 117485, Russia
| | - N.V. Zakharova
- Head of the Laboratory for Fundamental Research Methods, Research Clinical Center of Neuropsychiatry; N.A. Alekseyev Psychiatric Clinical Hospital No.1, 2 Zagorodnoye Shosse, Moscow, 117152, Russia
| | - A.V. Bernstein
- Professor, Professor of the Center of Applied Artificial Intelligence; Skolkovo Institute of Science and Technology (Skoltech), Territory of Skolkovo Innovation Center, Bldg 1, 30 Bolshoy Boulevard, Moscow, 121205, Russia
| | - E.V. Burnaev
- Associate Professor, Professor of the Center of Applied Artificial Intelligence; Skolkovo Institute of Science and Technology (Skoltech), Territory of Skolkovo Innovation Center, Bldg 1, 30 Bolshoy Boulevard, Moscow, 121205, Russia
| | - G.S. Mamedova
- Junior Researcher, Laboratory for Fundamental Research Methods, Research Clinical Center of Neuropsychiatry; N.A. Alekseyev Psychiatric Clinical Hospital No.1, 2 Zagorodnoye Shosse, Moscow, 117152, Russia
| | - S.A. Krynskiy
- Researcher, Laboratory of Molecular Immunology and Virology; National Research Center “Kurchatov Institute”, 1 Akademika Kurchatova Square, Moscow, 123182, Russia
| | - D.P. Ogurtsov
- Researcher, Laboratory of Molecular Immunology and Virology; National Research Center “Kurchatov Institute”, 1 Akademika Kurchatova Square, Moscow, 123182, Russia
| | - E.A. Kondrateva
- PhD Student; Skolkovo Institute of Science and Technology (Skoltech), Territory of Skolkovo Innovation Center, Bldg 1, 30 Bolshoy Boulevard, Moscow, 121205, Russia
| | - P.V. Druzhinina
- PhD Student; Skolkovo Institute of Science and Technology (Skoltech), Territory of Skolkovo Innovation Center, Bldg 1, 30 Bolshoy Boulevard, Moscow, 121205, Russia
| | - M.O. Zubrikhina
- PhD Student; Skolkovo Institute of Science and Technology (Skoltech), Territory of Skolkovo Innovation Center, Bldg 1, 30 Bolshoy Boulevard, Moscow, 121205, Russia
| | - A.Yu. Arkhipov
- Researcher, Laboratory of Human Higher Nervous Activity; Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5A Butlerova St., Moscow, 117485, Russia
| | - V.B. Strelets
- Chief Researcher, Laboratory of Human Higher Nervous Activity; Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 5A Butlerova St., Moscow, 117485, Russia
| | - V.L. Ushakov
- Associate Professor, Chief Researcher, Institute for Advanced Brain Research; Lomonosov Moscow State University, 27/1 Lomonosov Avenue, Moscow, 119192, Russia; Head of the Department; N.A. Alekseyev Psychiatric Clinical Hospital No.1, 2 Zagorodnoye Shosse, Moscow, 117152, Russia; Senior Researcher; National Research Nuclear University MEPhI, 31 Kashirskoye Shosse, Moscow, 115409, Russia
| |
Collapse
|
|
11
|
Palmer D, Dumont JR, Dexter TD, Prado MAM, Finger E, Bussey TJ, Saksida LM. Touchscreen cognitive testing: Cross-species translation and co-clinical trials in neurodegenerative and neuropsychiatric disease. Neurobiol Learn Mem 2021; 182:107443. [PMID: 33895351 DOI: 10.1016/j.nlm.2021.107443] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2020] [Revised: 02/06/2021] [Accepted: 02/26/2021] [Indexed: 01/06/2023]
Abstract
Translating results from pre-clinical animal studies to successful human clinical trials in neurodegenerative and neuropsychiatric disease presents a significant challenge. While this issue is clearly multifaceted, the lack of reproducibility and poor translational validity of many paradigms used to assess cognition in animal models are central contributors to this challenge. Computer-automated cognitive test batteries have the potential to substantially improve translation between pre-clinical studies and clinical trials by increasing both reproducibility and translational validity. Given the structured nature of data output, computer-automated tests also lend themselves to increased data sharing and other open science good practices. Over the past two decades, computer automated, touchscreen-based cognitive testing methods have been developed for non-human primate and rodent models. These automated methods lend themselves to increased standardization, hence reproducibility, and have become increasingly important for the elucidation of the neurobiological basis of cognition in animal models. More recently, there have been increased efforts to use these methods to enhance translational validity by developing task batteries that are nearly identical across different species via forward (i.e., translating animal tasks to humans) and reverse (i.e., translating human tasks to animals) translation. An additional benefit of the touchscreen approach is that a cross-species cognitive test battery makes it possible to implement co-clinical trials-an approach developed initially in cancer research-for novel treatments for neurodegenerative disorders. Co-clinical trials bring together pre-clinical and early clinical studies, which facilitates testing of novel treatments in mouse models with underlying genetic or other changes, and can help to stratify patients on the basis of genetic, molecular, or cognitive criteria. This approach can help to determine which patients should be enrolled in specific clinical trials and can facilitate repositioning and/or repurposing of previously approved drugs. This has the potential to mitigate the resources required to study treatment responses in large numbers of human patients.
Collapse
Affiliation(s)
- Daniel Palmer
- Robarts Research Institute, The University of Western Ontario, Ontario, Canada; Department of Physiology and Pharmacology, The University of Western Ontario, Ontario, Canada.
| | - Julie R Dumont
- Robarts Research Institute, The University of Western Ontario, Ontario, Canada; BrainsCAN, The University of Western Ontario, Ontario, Canada
| | - Tyler D Dexter
- Department of Physiology and Pharmacology, The University of Western Ontario, Ontario, Canada; Graduate Program in Neuroscience, The University of Western Ontario, Ontario, Canada
| | - Marco A M Prado
- Robarts Research Institute, The University of Western Ontario, Ontario, Canada; Department of Physiology and Pharmacology, The University of Western Ontario, Ontario, Canada; Graduate Program in Neuroscience, The University of Western Ontario, Ontario, Canada; Department of Anatomy and Cell Biology, The University of Western Ontario, Ontario, Canada
| | - Elizabeth Finger
- Robarts Research Institute, The University of Western Ontario, Ontario, Canada; Department of Clinical Neurological Sciences, The University of Western Ontario, Ontario, Canada; Lawson Health Research Institute, Ontario, Canada; Parkwood Institute, St. Josephs Health Care, Ontario, Canada
| | - Timothy J Bussey
- Robarts Research Institute, The University of Western Ontario, Ontario, Canada; Department of Physiology and Pharmacology, The University of Western Ontario, Ontario, Canada; Brain and Mind Institute, The University of Western Ontario, Ontario, Canada
| | - Lisa M Saksida
- Robarts Research Institute, The University of Western Ontario, Ontario, Canada; Department of Physiology and Pharmacology, The University of Western Ontario, Ontario, Canada; Brain and Mind Institute, The University of Western Ontario, Ontario, Canada
| |
Collapse
|
|
12
|
Tseng CEJ, Gilbert TM, Catanese MC, Hightower BG, Peters AT, Parmar AJ, Kim M, Wang C, Roffman JL, Brown HE, Perlis RH, Zürcher NR, Hooker JM. In vivo human brain expression of histone deacetylases in bipolar disorder. Transl Psychiatry 2020; 10:224. [PMID: 32641695 PMCID: PMC7343804 DOI: 10.1038/s41398-020-00911-5] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/29/2020] [Revised: 06/11/2020] [Accepted: 06/18/2020] [Indexed: 02/08/2023] Open
Abstract
The etiology of bipolar disorder (BD) is unknown and the neurobiological underpinnings are not fully understood. Both genetic and environmental factors contribute to the risk of BD, which may be linked through epigenetic mechanisms, including those regulated by histone deacetylase (HDAC) enzymes. This study measures in vivo HDAC expression in individuals with BD for the first time using the HDAC-specific radiotracer [11C]Martinostat. Eleven participants with BD and 11 age- and sex-matched control participants (CON) completed a simultaneous magnetic resonance - positron emission tomography (MR-PET) scan with [11C]Martinostat. Lower [11C]Martinostat uptake was found in the right amygdala of BD compared to CON. We assessed uptake in the dorsolateral prefrontal cortex (DLPFC) to compare previous findings of lower uptake in the DLPFC in schizophrenia and found no group differences in BD. Exploratory whole-brain voxelwise analysis showed lower [11C]Martinostat uptake in the bilateral thalamus, orbitofrontal cortex, right hippocampus, and right amygdala in BD compared to CON. Furthermore, regional [11C]Martinostat uptake was associated with emotion regulation in BD in fronto-limbic areas, which aligns with findings from previous structural, functional, and molecular neuroimaging studies in BD. Regional [11C]Martinostat uptake was associated with attention in BD in fronto-parietal and temporal regions. These findings indicate a potential role of HDACs in BD pathophysiology. In particular, HDAC expression levels may modulate attention and emotion regulation, which represent two core clinical features of BD.
Collapse
Affiliation(s)
- Chieh-En J. Tseng
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129 USA
| | - Tonya M. Gilbert
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129 USA
| | - Mary C. Catanese
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129 USA
| | - Baileigh G. Hightower
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129 USA
| | - Amy T. Peters
- grid.32224.350000 0004 0386 9924Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 USA
| | - Anjali J. Parmar
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129 USA
| | - Minhae Kim
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129 USA
| | - Changning Wang
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129 USA
| | - Joshua L. Roffman
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129 USA ,grid.32224.350000 0004 0386 9924Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 USA
| | - Hannah E. Brown
- grid.475010.70000 0004 0367 5222Department of Psychiatry, Boston University School of Medicine, Boston, MA 02118 USA
| | - Roy H. Perlis
- grid.32224.350000 0004 0386 9924Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 USA ,grid.32224.350000 0004 0386 9924Center for Genomic Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114 USA
| | - Nicole R. Zürcher
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129 USA
| | - Jacob M. Hooker
- Athinoula A. Martinos Center for Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129 USA
| |
Collapse
|
|
13
|
Bai Y, Pascal Z, Calhoun V, Wang YP. Optimized Combination of Multiple Graphs With Application to the Integration of Brain Imaging and (epi)Genomics Data. IEEE TRANSACTIONS ON MEDICAL IMAGING 2020; 39:1801-1811. [PMID: 31825864 PMCID: PMC7394342 DOI: 10.1109/tmi.2019.2958256] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/04/2023]
Abstract
With the rapid development of high-throughput technologies, a growing amount of multi-omics data are collected, giving rise to a great demand for combining such data for biomedical discovery. Due to the cost and time to label the data manually, the number of labelled samples is limited. This motivated the need for semi-supervised learning algorithms. In this work, we applied a graph-based semi-supervised learning (GSSL) to classify a severe chronic mental disorder, schizophrenia (SZ). An advantage of GSSL is that it can simultaneously analyse more than two types of data, while many existing models focus on pairwise data analysis. In particular, we applied GSSL to the analysis of single nucleotide polymorphism (SNP), functional magnetic resonance imaging (fMRI) and DNA methylation data, which accounts for genetics, brain imaging (endophenotypes), and environmental factors (epigenomics) respectively. While parameter selection has been an open challenge for most models, another key contribution of this work is that we explored the parameter space to interpret their meaning and established practical guidelines. Based on the practical significance of each hyper-parameter, a relatively small range of candidate values can be determined in a data-driven way to both optimize and speed up the parameter tuning process. We validated the model through both synthetic data and a real SZ dataset of 184 subjects from the Mental Illness and Neuroscience Discovery (MIND) Clinical Imaging Consortium. In comparison to several existing approaches, our algorithm achieved better performance in terms of classification accuracy. We also confirmed the significance of several brain regions associated with SZ.
Collapse
|
|
14
|
Mulet B, Valero J, Gutiérrez-Zotes A, Montserrat C, Cortés MJ, Jariod M, Martorell L, Vilella E, Labad A. Sustained and selective attention deficits as vulnerability markers to psychosis. Eur Psychiatry 2020; 22:171-6. [PMID: 17127037 DOI: 10.1016/j.eurpsy.2006.07.005] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2005] [Revised: 06/22/2006] [Accepted: 07/01/2006] [Indexed: 11/26/2022] Open
Abstract
AbstractThe first descriptions of schizophrenia emphasized attention problems patients with schizophrenia have but recent results evidence that other psychotic disorders share them.We compared the performance in sustained and selective attention between psychotic patients (P), their healthy first degree relatives (R) and healthy volunteers (C) to prove whether these alterations could be an endophenotype of vulnerability to psychosis. We also compared the performance of schizophrenic patients (SZP) and that of patients with other functional psychoses (OP) in order to prove whether these alterations are specific of any psychotic disorder.Seventy-six P, 70 R and 39 C were included in the study. A selective attention index, comprising TMT A and B and Stroop Test, and a sustained attention index comprising the Continuous Performance Test were calculated. We conducted an univariant general linear model to compare three group performances in these indexes, with age, sex and years of education as a covariables.We found significant differences between the indexes when we compared P, R and C. No differences in performance were found between SZP and OP. Our data showed that sustained and selective attention alterations could be a vulnerability factor to psychotic disorders in general, but they were not specific of schizophrenia.
Collapse
Affiliation(s)
- B Mulet
- Departament de Formació i Investigació, Hospital Psiquiàtric Universitari Institut Pere Mata, Ctra. de l'Institut, s/n, 43206 Reus, Tarragona, Spain.
| | | | | | | | | | | | | | | | | |
Collapse
|
|
15
|
Huang AS, Rogers BP, Woodward ND. Disrupted modulation of thalamus activation and thalamocortical connectivity during dual task performance in schizophrenia. Schizophr Res 2019; 210:270-277. [PMID: 30630706 PMCID: PMC6612476 DOI: 10.1016/j.schres.2018.12.022] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2018] [Revised: 12/07/2018] [Accepted: 12/16/2018] [Indexed: 01/12/2023]
Abstract
Despite considerable evidence showing thalamus anatomy and connectivity abnormalities in schizophrenia, how these abnormalities are reflected in thalamus function during cognition is relatively understudied. Modulation of thalamic connectivity with the prefrontal cortex (PFC) is required for higher-order cognitive processes, which are often impaired in schizophrenia. To address this gap, we investigated how thalamus function and thalamus-PFC connectivity under different levels of cognitive demand may be disrupted in schizophrenia. Participants underwent fMRI scanning while performing an event-related two-alternative forced choice task under Single and Dual task conditions. In the Single task condition, participants responded either to a visual cue with a well-learned motor response, or an audio cue with a well-learned vocal response. In the Dual task condition, participants performed both tasks. Thalamic connectivity with task relevant regions of the PFC for each condition was measured using beta-series correlation. Individuals with schizophrenia demonstrated less modulation of both mediodorsal thalamus activation and thalamus-PFC connectivity with increased cognitive demand. In contrast, their ability to modulate PFC function during task performance was maintained. These results suggest that the pathophysiology of cognitive impairment in schizophrenia is associated with thalamus-PFC circuitry and suggests that the thalamus, along with the PFC, should be a focus of investigation.
Collapse
Affiliation(s)
- Anna S. Huang
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center
| | | | - Neil D. Woodward
- Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center
| |
Collapse
|
|
16
|
Curtin A, Sun J, Zhao Q, Onaral B, Wang J, Tong S, Ayaz H. Visuospatial task-related prefrontal activity is correlated with negative symptoms in schizophrenia. Sci Rep 2019; 9:9575. [PMID: 31270354 PMCID: PMC6610077 DOI: 10.1038/s41598-019-45893-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2018] [Accepted: 06/14/2019] [Indexed: 01/15/2023] Open
Abstract
Control of attention is thought to be specifically impaired in schizophrenia due to abnormal function in the prefrontal cortex (PFC). The PFC plays a critical role in the identification of relevant stimuli and the development of appropriate biases for the identified signals, including selection of an appropriate attentional 'zoom'. We examined how demands associated with changes in attentional requirements in a Sustained Attention Task (SAT) may contribute to differences in functional involvement of the PFC and relation to clinical status. A group of 24 individuals with schizophrenia and 16 healthy controls (N = 40) performed the SAT and a visuospatial condition (vSAT) while activity in the bilateral anterior PFC was monitored using functional Near Infrared Spectroscopy (fNIRS). The results confirm that the right frontopolar region plays a role in control of attention for both patients and healthy controls. However, patients with schizophrenia exhibited a general attentional deficit and inefficient right-medial PFC activation. Additionally, we observed a strong regional association between left Middle Frontal Gyrus (MFG) activity during the vSAT task and the PANSS score driven by the negative symptom subscale. The presence of aberrant activation differences within the left-MFG region may describe a dysregulation of attentional networks linked to the clinical expression of negative and general symptoms.
Collapse
Affiliation(s)
- Adrian Curtin
- Drexel University, School of Biomedical Engineering, Science and Health Systems, Philadelphia, PA, USA
- Shanghai Jiao Tong University, School of Biomedical Engineering, Shanghai, China
| | - Junfeng Sun
- Shanghai Jiao Tong University, School of Biomedical Engineering, Shanghai, China
| | - Qiangfeng Zhao
- Shanghai Jiao Tong University, School of Biomedical Engineering, Shanghai, China
| | - Banu Onaral
- Drexel University, School of Biomedical Engineering, Science and Health Systems, Philadelphia, PA, USA
| | - Jijun Wang
- Shanghai Mental Health Center, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
| | - Shanbao Tong
- Shanghai Jiao Tong University, School of Biomedical Engineering, Shanghai, China.
| | - Hasan Ayaz
- Drexel University, School of Biomedical Engineering, Science and Health Systems, Philadelphia, PA, USA.
- University of Pennsylvania, Department of Family and Community Health, Philadelphia, PA, USA.
- Children's Hospital of Philadelphia, Center for Injury Research and Prevention, Philadelphia, PA, USA.
| |
Collapse
|
|
17
|
Wu D, Jiang T. Schizophrenia-related abnormalities in the triple network: a meta-analysis of working memory studies. Brain Imaging Behav 2019; 14:971-980. [PMID: 30820860 DOI: 10.1007/s11682-019-00071-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/27/2022]
Abstract
Previous meta-analyses found abnormal brain activations in schizophrenia patients compared with normal controls when performing working memory tasks. Although most studies focused on dysfunction of the working memory activation network in schizophrenia patients, deactivation abnormalities of the working memory in the default mode network have also been reported in schizophrenia but have received less attention. Our goal was to discover whether deactivation abnormalities can also be consistently found in schizophrenia during working memory tasks and, further, to consider both activation and deactivation abnormalities. Fifty-two English language peer-reviewed studies were included in this meta-analysis. Compared with normal controls, the schizophrenia patients showed activation dysfunction of the bilateral dorsolateral prefrontal cortex and posterior parietal cortex as well as the anterior insula, anterior cingulate cortex, and supplementary motor area, which are core nodes of the central executive and salience network. In addition to dysfunction of the activation networks, the patients showed deactivation abnormalities in the ventral medial prefrontal cortex and posterior cingulate cortex, which are core nodes of the default mode network. These results suggest that both activation and deactivation abnormalities exist in schizophrenia patients and that these abnormalities should both be considered when investigating the pathophysiological mechanism of schizophrenia.
Collapse
Affiliation(s)
- Dongya Wu
- Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Hai Dian District, Zhong Guan Cun East Road 95, Beijing, 100190, China.,National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China.,University of Chinese Academy of Sciences, Beijing, China
| | - Tianzi Jiang
- Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Hai Dian District, Zhong Guan Cun East Road 95, Beijing, 100190, China. .,National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. .,University of Chinese Academy of Sciences, Beijing, China. .,CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Automation, Chinese Academy of Sciences, Beijing, 100190, China. .,The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Lab for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, 625014, China. .,The Queensland Brain Institute, University of Queensland, Brisbane, QLD, 4072, Australia.
| |
Collapse
|
|
18
|
Han W, Sorg C, Zheng C, Yang Q, Zhang X, Ternblom A, Mawuli CB, Gao L, Luo C, Yao D, Li T, Liang S, Shao J. Low-rank network signatures in the triple network separate schizophrenia and major depressive disorder. Neuroimage Clin 2019; 22:101725. [PMID: 30798168 PMCID: PMC6389685 DOI: 10.1016/j.nicl.2019.101725] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2018] [Revised: 01/30/2019] [Accepted: 02/18/2019] [Indexed: 02/05/2023]
Abstract
Brain imaging studies have revealed that functional and structural brain connectivity in the so-called triple network (i.e., default mode network (DMN), salience network (SN) and central executive network (CEN)) are consistently altered in schizophrenia. However, similar changes have also been found in patients with major depressive disorder, prompting the question of specific triple network signatures for the two disorders. In this study, we proposed Supervised Convex Nonnegative Matrix Factorization (SCNMF) to extract distributed multi-modal brain patterns. These patterns distinguish schizophrenia and major depressive disorder in a latent low-dimensional space of the triple brain network. Specifically, 21 patients of schizophrenia and 25 patients of major depressive disorder were assessed by T1-weighted, diffusion-weighted, and resting-state functional MRIs. Individual structural and functional connectivity networks, based on pre-defined regions of the triple network were constructed, respectively. Afterwards, SCNMF was employed to extract the discriminative patterns. Experiments indicate that SCNMF allows extracting the low-rank discriminative patterns between the two disorders, achieving a classification accuracy of 82.6% based on the extracted functional and structural abnormalities with support vector machine. Experimental results show the specific brain patterns for schizophrenia and major depressive disorder that are multi-modal, complex, and distributed in the triple network. Parts of the prefrontal cortex including superior frontal gyri showed variation between patients with schizophrenia and major depression due to structural properties. In terms of functional properties, the middle cingulate cortex, inferior parietal lobule, and cingulate cortex were the most discriminative regions.
Collapse
Affiliation(s)
- Wei Han
- Data Mining Lab, University of Electronic Science and Technology of China, 611731 Chengdu, China; School of Computer Science and Engineering, University of Electronic Science and Technology of China, 611731 Chengdu, China
| | - Christian Sorg
- Department of Neuroradiology, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany; Department of Psychiatry, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany; TUM-Neuroimaging Center of Klinikum rechts der Isar, Technische Universität München, Ismaninger Strasse 22, 81675 Munich, Germany
| | - Changgang Zheng
- Data Mining Lab, University of Electronic Science and Technology of China, 611731 Chengdu, China
| | - Qinli Yang
- Data Mining Lab, University of Electronic Science and Technology of China, 611731 Chengdu, China
| | - Xiaosong Zhang
- Data Mining Lab, University of Electronic Science and Technology of China, 611731 Chengdu, China; School of Computer Science and Engineering, University of Electronic Science and Technology of China, 611731 Chengdu, China
| | - Arvid Ternblom
- Data Mining Lab, University of Electronic Science and Technology of China, 611731 Chengdu, China; School of Computer Science and Engineering, University of Electronic Science and Technology of China, 611731 Chengdu, China
| | - Cobbinah Bernard Mawuli
- Data Mining Lab, University of Electronic Science and Technology of China, 611731 Chengdu, China; School of Computer Science and Engineering, University of Electronic Science and Technology of China, 611731 Chengdu, China
| | - Lianli Gao
- School of Computer Science and Engineering, University of Electronic Science and Technology of China, 611731 Chengdu, China
| | - Cheng Luo
- Center for Information in BioMedicine, University of Electronic Science and Technology of China, 611731 Chengdu, China
| | - Dezhong Yao
- Center for Information in BioMedicine, University of Electronic Science and Technology of China, 611731 Chengdu, China
| | - Tao Li
- West China Mental Health Centre, Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Sugai Liang
- West China Mental Health Centre, Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu 610041, China
| | - Junming Shao
- Data Mining Lab, University of Electronic Science and Technology of China, 611731 Chengdu, China; School of Computer Science and Engineering, University of Electronic Science and Technology of China, 611731 Chengdu, China; Center for Information in BioMedicine, University of Electronic Science and Technology of China, 611731 Chengdu, China.
| |
Collapse
|
|
19
|
Reading the (functional) writing on the (structural) wall: Multimodal fusion of brain structure and function via a deep neural network based translation approach reveals novel impairments in schizophrenia. Neuroimage 2018; 181:734-747. [PMID: 30055372 DOI: 10.1016/j.neuroimage.2018.07.047] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2017] [Revised: 07/16/2018] [Accepted: 07/18/2018] [Indexed: 01/01/2023] Open
Abstract
This work presents a novel approach to finding linkage/association between multimodal brain imaging data, such as structural MRI (sMRI) and functional MRI (fMRI). Motivated by the machine translation domain, we employ a deep learning model, and consider two different imaging views of the same brain like two different languages conveying some common facts. That analogy enables finding linkages between two modalities. The proposed translation-based fusion model contains a computing layer that learns "alignments" (or links) between dynamic connectivity features from fMRI data and static gray matter patterns from sMRI data. The approach is evaluated on a multi-site dataset consisting of eyes-closed resting state imaging data collected from 298 subjects (age- and gender matched 154 healthy controls and 144 patients with schizophrenia). Results are further confirmed on an independent dataset consisting of eyes-open resting state imaging data from 189 subjects (age- and gender matched 91 healthy controls and 98 patients with schizophrenia). We used dynamic functional connectivity (dFNC) states as the functional features and ICA-based sources from gray matter densities as the structural features. The dFNC states characterized by weakly correlated intrinsic connectivity networks (ICNs) were found to have stronger association with putamen and insular gray matter pattern, while the dFNC states of profuse strongly correlated ICNs exhibited stronger links with the gray matter pattern in precuneus, posterior cingulate cortex (PCC), and temporal cortex. Further investigation with the estimated link strength (or alignment score) showed significant group differences between healthy controls and patients with schizophrenia in several key regions including temporal lobe, and linked these to connectivity states showing less occupancy in healthy controls. Moreover, this novel approach revealed significant correlation between a cognitive score (attention/vigilance) and the function/structure alignment score that was not detected when data modalities were considered separately.
Collapse
|
|
20
|
Parvalbumin-containing GABA cells and schizophrenia: experimental model based on targeted gene delivery through adeno-associated viruses. Behav Pharmacol 2018; 28:630-641. [PMID: 29120948 DOI: 10.1097/fbp.0000000000000360] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Understanding the contribution of transmitter systems in behavioural pharmacology has a long tradition. Multiple techniques such as transmitter-specific lesions, and also localized administration of pharmacological toxins including agonists and antagonists of selected receptors have been applied. More recently, modern genetic tools have permitted cell-type selective interferences, for example by expression of light-sensitive channels followed by optogenetic stimulation in behaviourally meaningful settings or by engineered channels termed DREADDS that respond to peripherally administered drugs. We here took a similar approach and employed a Cre recombinase-dependent viral delivery system (adeno-associated virus) to express tetanus toxin light chain (TeLc) and thus, block neural transmission specifically in parvalbumin-positive (PV+) neurons of the limbic and infralimbic prefrontal circuitry. PV-TeLc cohorts presented with normal circadian activity as recorded in PhenoTyper home cages, but a reproducible increase in anxiety was extracted in both the open field and light-dark box. Interestingly, working memory assessed in a spontaneous alternation Y-maze task was impaired in PV-TeLc mice. We also recorded local field potentials from a separate cohort and found no global changes in brain activity, but found a behaviourally relevant lack of modulation in the gamma spectral band. These anomalies are reminiscent of endophenotypes of schizophrenia and appear to be critically dependent on GABAergic signalling through PV neurones. At the same time, these observations validate the use of viral vector delivery and its expression in Cre-lines as a useful tool for understanding the role of selective components of the brain in behaviour and the underpinning physiology.
Collapse
|
|
21
|
Zaytseva Y, Fajnerová I, Dvořáček B, Bourama E, Stamou I, Šulcová K, Motýl J, Horáček J, Rodriguez M, Španiel F. Theoretical Modeling of Cognitive Dysfunction in Schizophrenia by Means of Errors and Corresponding Brain Networks. Front Psychol 2018; 9:1027. [PMID: 30026711 PMCID: PMC6042473 DOI: 10.3389/fpsyg.2018.01027] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2017] [Accepted: 05/31/2018] [Indexed: 01/22/2023] Open
Abstract
The current evidence of cognitive disturbances and brain alterations in schizophrenia does not provide the plausible explanation of the underlying mechanisms. Neuropsychological studies outlined the cognitive profile of patients with schizophrenia, that embodied the substantial disturbances in perceptual and motor processes, spatial functions, verbal and non-verbal memory, processing speed and executive functioning. Standardized scoring in the majority of the neurocognitive tests renders the index scores or the achievement indicating the severity of the cognitive impairment rather than the actual performance by means of errors. At the same time, the quantitative evaluation may lead to the situation when two patients with the same index score of the particular cognitive test, demonstrate qualitatively different performances. This may support the view why test paradigms that habitually incorporate different cognitive variables associate weakly, reflecting an ambiguity in the interpretation of noted cognitive constructs. With minor exceptions, cognitive functions are not attributed to the localized activity but eventuate from the coordinated activity in the generally dispersed brain networks. Functional neuroimaging has progressively explored the connectivity in the brain networks in the absence of the specific task and during the task processing. The spatio-temporal fluctuations of the activity of the brain areas detected in the resting state and being highly reproducible in numerous studies, resemble the activation and communication patterns during the task performance. Relatedly, the activation in the specific brain regions oftentimes is attributed to a number of cognitive processes. Given the complex organization of the cognitive functions, it becomes crucial to designate the roles of the brain networks in relation to the specific cognitive functions. One possible approach is to identify the commonalities of the deficits across the number of cognitive tests or, common errors in the various tests and identify their common "denominators" in the brain networks. The qualitative characterization of cognitive performance might be beneficial in addressing diffuse cognitive alterations presumably caused by the dysconnectivity of the distributed brain networks. Therefore, in the review, we use this approach in the description of standardized tests in the scope of potential errors in patients with schizophrenia with a subsequent reference to the brain networks.
Collapse
Affiliation(s)
- Yuliya Zaytseva
- National Institute of Mental Health, Klecany, Czechia
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | | | | | - Eva Bourama
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | - Ilektra Stamou
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | - Kateřina Šulcová
- National Institute of Mental Health, Klecany, Czechia
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | - Jiří Motýl
- National Institute of Mental Health, Klecany, Czechia
| | - Jiří Horáček
- National Institute of Mental Health, Klecany, Czechia
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
| | | | - Filip Španiel
- National Institute of Mental Health, Klecany, Czechia
- 3rd Faculty of Medicine, Charles University in Prague, Prague, Czechia
| |
Collapse
|
|
22
|
Goñi M, Basu N, Murray AD, Waiter GD. Neural Indicators of Fatigue in Chronic Diseases: A Systematic Review of MRI Studies. Diagnostics (Basel) 2018; 8:diagnostics8030042. [PMID: 29933643 PMCID: PMC6163988 DOI: 10.3390/diagnostics8030042] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/24/2018] [Revised: 06/11/2018] [Accepted: 06/20/2018] [Indexed: 02/08/2023] Open
Abstract
While fatigue is prevalent in chronic diseases, the neural mechanisms underlying this symptom remain unknown. Magnetic resonance imaging (MRI) has the potential to enable us to characterize this symptom. The aim of this review was to gather and appraise the current literature on MRI studies of fatigue in chronic diseases. We systematically searched the following databases: MedLine, PsycInfo, Embase and Scopus (inception to April 2016). We selected studies according to a predefined inclusion and exclusion criteria. We assessed the quality of the studies and conducted descriptive statistical analyses. We identified 26 studies of varying design and quality. Structural and functional MRI, alongside diffusion tensor imaging (DTI) and functional connectivity (FC) studies, identified significant brain indicators of fatigue. The most common regions were the frontal lobe, parietal lobe, limbic system and basal ganglia. Longitudinal studies offered more precise and reliable analysis. Brain structures found to be related to fatigue were highly heterogeneous, not only between diseases, but also for different studies of the same disease. Given the different designs, methodologies and variable results, we conclude that there are currently no well-defined brain indicators of fatigue in chronic diseases.
Collapse
Affiliation(s)
- María Goñi
- Aberdeen Biomedical Imaging Centre (ABIC), Lilian Sutton Building, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZN, UK.
| | - Neil Basu
- Health Science Building, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZN, UK.
| | - Alison D Murray
- Aberdeen Biomedical Imaging Centre (ABIC), Lilian Sutton Building, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZN, UK.
| | - Gordon D Waiter
- Aberdeen Biomedical Imaging Centre (ABIC), Lilian Sutton Building, Foresterhill, University of Aberdeen, Aberdeen AB25 2ZN, UK.
| |
Collapse
|
|
23
|
Hvoslef-Eide M, Nilsson SR, Hailwood JM, Robbins TW, Saksida LM, Mar AC, Bussey TJ. Effects of anterior cingulate cortex lesions on a continuous performance task for mice. Brain Neurosci Adv 2018; 2. [PMID: 31168482 PMCID: PMC6546594 DOI: 10.1177/2398212818772962] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Important tools in the study of prefrontal cortical-dependent executive functions are cross-species behavioural tasks with translational validity. A widely used test of executive function and attention in humans is the continuous performance task (CPT). Optimal performance in variations of this task is associated with activity along the medial wall of the prefrontal cortex, including the anterior cingulate cortex (ACC), for its essential components such as response control, target detection and processing of false alarm errors. We assess the validity of a recently developed rodent touchscreen continuous performance task (rCPT) that is analogous to typical human CPT procedures. Here we evaluate the performance of mice with quinolinic acid-induced lesions centred on the ACC in the rCPT following a range of task parameter manipulations designed to challenge attention and impulse control. Lesioned mice showed a disinhibited response profile expressed as a decreased response criterion and increased false alarm rates. ACC lesions also resulted in a milder increase in inter-trial interval responses ('ITI touches') and hit rate. Lesions did not affect discriminative sensitivity d'. The disinhibited behaviour of ACC lesioned animals was stable and not affected by the manipulation of variable task parameter manipulations designed to increase task difficulty. The results are in general agreement with human studies implicating the ACC in the processing of inappropriate responses. We conclude that the rCPT may be useful for studying prefrontal cortex function in mice and has the capability of providing meaningful links between animal and human cognitive tasks.
Collapse
Affiliation(s)
- Martha Hvoslef-Eide
- Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK.,MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK.,Department of Biosciences, University of Oslo, PO Box 1066, Blindern, 0371 Oslo, Norway
| | - Simon Ro Nilsson
- Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK.,MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK.,Neuroscience Institute, New York University Medical Center, New York, NY, USA.,Department of Neuroscience and Physiology, New York University Medical Center, New York, NY, USA
| | - Jonathan M Hailwood
- Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK.,MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK
| | - Trevor W Robbins
- Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK.,MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK
| | - Lisa M Saksida
- Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK.,MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK.,Molecular Medicine Research Group, Robarts Research Institute & Department of Physiology, Western University, London, ON, Canada.,Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.,The Brain and Mind Institute, Western University, London, ON, Canada
| | - Adam C Mar
- Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK.,MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK.,Neuroscience Institute, New York University Medical Center, New York, NY, USA.,Department of Neuroscience and Physiology, New York University Medical Center, New York, NY, USA
| | - Timothy J Bussey
- Department of Psychology, University of Cambridge, Cambridge, CB2 3EB, UK.,MRC and Wellcome Trust Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, CB2 3EB, UK.,Molecular Medicine Research Group, Robarts Research Institute & Department of Physiology, Western University, London, ON, Canada.,Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, ON, Canada.,The Brain and Mind Institute, Western University, London, ON, Canada
| |
Collapse
|
|
24
|
Grey matter reduction in the caudate nucleus in patients with persistent negative symptoms: An ALE meta-analysis. Schizophr Res 2018; 192:9-15. [PMID: 28390850 DOI: 10.1016/j.schres.2017.04.005] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 03/20/2017] [Accepted: 04/01/2017] [Indexed: 10/19/2022]
Abstract
OBJECTIVES In the present study, we used Activation Likelihood Estimation (ALE) meta-analysis to quantitatively examine brain grey matter reduction in schizophrenia patients with persistent negative symptoms (PNS). METHOD A total of 12 voxel-based morphometry (VBM) studies were included in ALE meta-analysis using more stringent criterion of PNS. RESULTS Significant grey matter reduction in the PNS group relative to controls was observed in the left caudate nucleus, the left precentral region, the left middle frontal region, the bilateral parahippocampal region, the left anterior cingulate region, the bilateral medial frontal gyrus, the thalamus and the insula. CONCLUSION Our results suggest that brain regions in the reward network may be specifically related to PNS, especially the left caudate nucleus. It is possible that abnormality in reward processing may constitute the neural basis of PNS.
Collapse
|
|
25
|
McLoughlin G, Palmer J, Makeig S, Bigdely-Shamlo N, Banaschewski T, Laucht M, Brandeis D. EEG Source Imaging Indices of Cognitive Control Show Associations with Dopamine System Genes. Brain Topogr 2017; 31:392-406. [PMID: 29222686 PMCID: PMC5889775 DOI: 10.1007/s10548-017-0601-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2017] [Accepted: 10/10/2017] [Indexed: 01/09/2023]
Abstract
Cognitive or executive control is a critical mental ability, an important marker of mental illness, and among the most heritable of neurocognitive traits. Two candidate genes, catechol-O-methyltransferase (COMT) and DRD4, which both have a roles in the regulation of cortical dopamine, have been consistently associated with cognitive control. Here, we predicted that individuals with the COMT Met/Met allele would show improved response execution and inhibition as indexed by event-related potentials in a Go/NoGo task, while individuals with the DRD4 7-repeat allele would show impaired brain activity. We used independent component analysis (ICA) to separate brain source processes contributing to high-density EEG scalp signals recorded during the task. As expected, individuals with the DRD4 7-repeat polymorphism had reduced parietal P3 source and scalp responses to response (Go) compared to those without the 7-repeat. Contrary to our expectation, the COMT homozygous Met allele was associated with a smaller frontal P3 source and scalp response to response-inhibition (NoGo) stimuli, suggesting that while more dopamine in frontal cortical areas has advantages in some tasks, it may also compromise response inhibition function. An interaction effect emerged for P3 source responses to Go stimuli. These were reduced in those with both the 7-repeat DRD4 allele and either the COMT Val/Val or the Met/Met homozygous polymorphisms but not in those with the heterozygous Val/Met polymorphism. This epistatic interaction between DRD4 and COMT replicates findings that too little or too much dopamine impairs cognitive control. The anatomic and functional separated maximally independent cortical EEG sources proved more informative than scalp channel measures for genetic studies of brain function and thus better elucidate the complex mechanisms in psychiatric illness.
Collapse
Affiliation(s)
- G McLoughlin
- MRC Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, PO80, London, UK.
| | - J Palmer
- Swartz Center for Computational Neuroscience, Institute for Neural Computation, University of California San Diego, La Jolla, CA, USA
| | - S Makeig
- Swartz Center for Computational Neuroscience, Institute for Neural Computation, University of California San Diego, La Jolla, CA, USA
| | - N Bigdely-Shamlo
- Swartz Center for Computational Neuroscience, Institute for Neural Computation, University of California San Diego, La Jolla, CA, USA
| | - T Banaschewski
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
| | - M Laucht
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
- Department of Psychology, University of Potsdam, Potsdam, Germany
| | - D Brandeis
- Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Mannheim, Medical Faculty Mannheim / Heidelberg University, Mannheim, Germany
- Department of Child and Adolescent Psychiatry and Psychotherapy, Psychiatric Hospital, University of Zürich, Zurich, Switzerland
- Zurich Center for Integrative Human Physiology, University of Zürich, Zurich, Switzerland
- Neuroscience Center Zurich, University and ETH Zürich, Zurich, Switzerland
| |
Collapse
|
|
26
|
A neuroanatomical account of mental time travelling in schizophrenia: A meta-analysis of functional and structural neuroimaging data. Neurosci Biobehav Rev 2017; 80:211-222. [DOI: 10.1016/j.neubiorev.2017.05.027] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Accepted: 05/29/2017] [Indexed: 01/29/2023]
|
|
27
|
Meng X, Jiang R, Lin D, Bustillo J, Jones T, Chen J, Yu Q, Du Y, Zhang Y, Jiang T, Sui J, Calhoun VD. Predicting individualized clinical measures by a generalized prediction framework and multimodal fusion of MRI data. Neuroimage 2016; 145:218-229. [PMID: 27177764 DOI: 10.1016/j.neuroimage.2016.05.026] [Citation(s) in RCA: 71] [Impact Index Per Article: 7.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2015] [Revised: 04/13/2016] [Accepted: 05/07/2016] [Indexed: 12/24/2022] Open
Abstract
Neuroimaging techniques have greatly enhanced the understanding of neurodiversity (human brain variation across individuals) in both health and disease. The ultimate goal of using brain imaging biomarkers is to perform individualized predictions. Here we proposed a generalized framework that can predict explicit values of the targeted measures by taking advantage of joint information from multiple modalities. This framework also enables whole brain voxel-wise searching by combining multivariate techniques such as ReliefF, clustering, correlation-based feature selection and multiple regression models, which is more flexible and can achieve better prediction performance than alternative atlas-based methods. For 50 healthy controls and 47 schizophrenia patients, three kinds of features derived from resting-state fMRI (fALFF), sMRI (gray matter) and DTI (fractional anisotropy) were extracted and fed into a regression model, achieving high prediction for both cognitive scores (MCCB composite r=0.7033, MCCB social cognition r=0.7084) and symptomatic scores (positive and negative syndrome scale [PANSS] positive r=0.7785, PANSS negative r=0.7804). Moreover, the brain areas likely responsible for cognitive deficits of schizophrenia, including middle temporal gyrus, dorsolateral prefrontal cortex, striatum, cuneus and cerebellum, were located with different weights, as well as regions predicting PANSS symptoms, including thalamus, striatum and inferior parietal lobule, pinpointing the potential neuromarkers. Finally, compared to a single modality, multimodal combination achieves higher prediction accuracy and enables individualized prediction on multiple clinical measures. There is more work to be done, but the current results highlight the potential utility of multimodal brain imaging biomarkers to eventually inform clinical decision-making.
Collapse
Affiliation(s)
- Xing Meng
- Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
| | - Rongtao Jiang
- Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
| | - Dongdong Lin
- The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87106, USA
| | - Juan Bustillo
- Dept. of Psychiatry and Neuroscience, University of New Mexico, Albuquerque, NM 87131, USA
| | - Thomas Jones
- Dept. of Psychiatry and Neuroscience, University of New Mexico, Albuquerque, NM 87131, USA
| | - Jiayu Chen
- The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87106, USA
| | - Qingbao Yu
- The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87106, USA
| | - Yuhui Du
- The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87106, USA
| | - Yu Zhang
- Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
| | - Tianzi Jiang
- Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; CAS Center for Excellence in Brain Science, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China
| | - Jing Sui
- Brainnetome Center and National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87106, USA; CAS Center for Excellence in Brain Science, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
| | - Vince D Calhoun
- The Mind Research Network and Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87106, USA; Dept. of Psychiatry and Neuroscience, University of New Mexico, Albuquerque, NM 87131, USA; Dept. of Electronic and Computer Engineering, University of New Mexico, Albuquerque, NM 87131, USA
| |
Collapse
|
|
28
|
Jagtap P, Diwadkar VA. Effective connectivity of ascending and descending frontalthalamic pathways during sustained attention: Complex brain network interactions in adolescence. Hum Brain Mapp 2016; 37:2557-70. [PMID: 27145923 DOI: 10.1002/hbm.23196] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2015] [Revised: 03/10/2016] [Accepted: 03/14/2016] [Indexed: 02/04/2023] Open
Abstract
Frontal-thalamic interactions are crucial for bottom-up gating and top-down control, yet have not been well studied from brain network perspectives. We applied network modeling of fMRI signals [dynamic causal modeling (DCM)] to investigate frontal-thalamic interactions during an attention task with parametrically varying levels of demand. fMRI was collected while subjects participated in a sustained continuous performance task with low and high attention demands. 162 competing model architectures were employed in DCM to evaluate hypotheses on bilateral frontal-thalamic connections and their modulation by attention demand, selected at a second level using Bayesian model selection. The model architecture evinced significant contextual modulation by attention of ascending (thalamus → dPFC) and descending (dPFC → thalamus) pathways. However, modulation of these pathways was asymmetric: while positive modulation of the ascending pathway was comparable across attention demand, modulation of the descending pathway was significantly greater when attention demands were increased. Increased modulation of the (dPFC → thalamus) pathway in response to increased attention demand constitutes novel evidence of attention-related gain in the connectivity of the descending attention pathway. By comparison demand-independent modulation of the ascending (thalamus → dPFC) pathway suggests unbiased thalamic inputs to the cortex in the context of the paradigm. Hum Brain Mapp 37:2557-2570, 2016. © 2016 Wiley Periodicals, Inc.
Collapse
Affiliation(s)
- Pranav Jagtap
- Brain Imaging Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Tolan Park Medical Building, Suite 5B, Detroit, Michigan, 48201
| | - Vaibhav A Diwadkar
- Brain Imaging Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Tolan Park Medical Building, Suite 5B, Detroit, Michigan, 48201
| |
Collapse
|
|
29
|
Calhoun VD, Sui J. Multimodal fusion of brain imaging data: A key to finding the missing link(s) in complex mental illness. BIOLOGICAL PSYCHIATRY. COGNITIVE NEUROSCIENCE AND NEUROIMAGING 2016; 1:230-244. [PMID: 27347565 PMCID: PMC4917230 DOI: 10.1016/j.bpsc.2015.12.005] [Citation(s) in RCA: 182] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
It is becoming increasingly clear that combining multi-modal brain imaging data is able to provide more information for individual subjects by exploiting the rich multimodal information that exists. However, the number of studies that do true multimodal fusion (i.e. capitalizing on joint information among modalities) is still remarkably small given the known benefits. In part, this is because multi-modal studies require broader expertise in collecting, analyzing, and interpreting the results than do unimodal studies. In this paper, we start by introducing the basic reasons why multimodal data fusion is important and what it can do, and importantly how it can help us avoid wrong conclusions and help compensate for imperfect brain imaging studies. We also discuss the challenges that need to be confronted for such approaches to be more widely applied by the community. We then provide a review of the diverse studies that have used multimodal data fusion (primarily focused on psychosis) as well as provide an introduction to some of the existing analytic approaches. Finally, we discuss some up-and-coming approaches to multi-modal fusion including deep learning and multimodal classification which show considerable promise. Our conclusion is that multimodal data fusion is rapidly growing, but it is still underutilized. The complexity of the human brain coupled with the incomplete measurement provided by existing imaging technology makes multimodal fusion essential in order to mitigate against misdirection and hopefully provide a key to finding the missing link(s) in complex mental illness.
Collapse
Affiliation(s)
- Vince D Calhoun
- The Mind Research Network & LBERI, Albuquerque, New Mexico.; Dept. of ECE, University of New Mexico, Albuquerque, New Mexico
| | - Jing Sui
- The Mind Research Network & LBERI, Albuquerque, New Mexico.; Brainnetome Center and National Laboratory of Pattern Recognition, Beijing, China; CAS Center for Excellence in Brain Science, Institute of Automation, Chinese Academy of Sciences, Beijing, China
| |
Collapse
|
|
30
|
Antonucci LA, Taurisano P, Fazio L, Gelao B, Romano R, Quarto T, Porcelli A, Mancini M, Di Giorgio A, Caforio G, Pergola G, Popolizio T, Bertolino A, Blasi G. Association of familial risk for schizophrenia with thalamic and medial prefrontal functional connectivity during attentional control. Schizophr Res 2016; 173:23-9. [PMID: 27012899 DOI: 10.1016/j.schres.2016.03.014] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2015] [Revised: 03/08/2016] [Accepted: 03/14/2016] [Indexed: 10/22/2022]
Abstract
Anomalies in behavioral correlates of attentional processing and related brain activity are crucial correlates of schizophrenia and associated with familial risk for this brain disorder. However, it is not clear how brain functional connectivity during attentional processes is key for schizophrenia and linked with trait vs. state related variables. To address this issue, we investigated patterns of functional connections during attentional control in healthy siblings of patients with schizophrenia, who share with probands genetic features but not variables related to the state of the disorder. 356 controls, 55 patients with schizophrenia on stable treatment with antipsychotics and 40 healthy siblings of patients with this brain disorder underwent the Variable Attentional Control (VAC) task during fMRI. Independent Component Analysis (ICA) is allowed to identify independent components (IC) of BOLD signal recorded during task performance. Results indicated reduced connectivity strength in patients with schizophrenia as well as in their healthy siblings in left thalamus within an attentional control component and greater connectivity in right medial prefrontal cortex (PFC) within the so-called Default Mode Network (DMN) compared to healthy individuals. These results suggest a relationship between familial risk for schizophrenia and brain functional networks during attentional control, such that this biological phenotype may be considered a useful intermediate phenotype in order to link genes effects to aspects of the pathophysiology of this brain disorder.
Collapse
Affiliation(s)
- Linda A Antonucci
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy; Department of Educational Science, Psychology and Communication Science, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy
| | - Paolo Taurisano
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy
| | - Leonardo Fazio
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy
| | - Barbara Gelao
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy
| | - Raffaella Romano
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy
| | - Tiziana Quarto
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy; Cognitive Brain Research Unit, Institute of Behavioural Sciences, University of Helsinki, Helsinki, Finland
| | - Annamaria Porcelli
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy
| | - Marina Mancini
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy
| | | | - Grazia Caforio
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy; Psychiatry Unit, Bari University Hospital, 70124 Bari, Italy
| | - Giulio Pergola
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy
| | - Teresa Popolizio
- IRCCS "Casa Sollievo della Sofferenza", 71013 S. Giovanni Rotondo (FG), Italy
| | - Alessandro Bertolino
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy; Psychiatry Unit, Bari University Hospital, 70124 Bari, Italy
| | - Giuseppe Blasi
- Department of Basic Medical Sciences, Neuroscience and Sense Organs, Università degli Studi di Bari "Aldo Moro", 70124 Bari, Italy; Psychiatry Unit, Bari University Hospital, 70124 Bari, Italy.
| |
Collapse
|
|
31
|
Lee JS, Park G, Song MJ, Choi KH, Lee SH. Early visual processing for low spatial frequency fearful face is correlated with cortical volume in patients with schizophrenia. Neuropsychiatr Dis Treat 2016; 12:1-14. [PMID: 26730192 PMCID: PMC4694689 DOI: 10.2147/ndt.s97089] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Patients with schizophrenia present with dysfunction of the magnocellular pathway, which might impair their early visual processing. We explored the relationship between functional abnormality of early visual processing and brain volumetric changes in schizophrenia. Eighteen patients and 16 healthy controls underwent electroencephalographic recordings and high-resolution magnetic resonance imaging. During electroencephalographic recordings, participants passively viewed neutral or fearful faces with broad, high, or low spatial frequency characteristics. Voxel-based morphometry was performed to investigate brain volume correlates of visual processing deficits. Event related potential analysis suggested that patients with schizophrenia had relatively impaired P100 processing of low spatial frequency fearful face stimuli compared with healthy controls; patients' gray-matter volumes in the dorsolateral and medial prefrontal cortices positively correlated with this amplitude. In addition, patients' gray-matter volume in the right cuneus positively correlated with the P100 amplitude in the left hemisphere for the high spatial frequency neutral face condition and that in the left dorsolateral prefrontal cortex negatively correlated with the negative score of the Positive and Negative Syndrome Scale. No significant correlations were observed in healthy controls. This study suggests that the cuneus and prefrontal cortex are significantly involved with the early visual processing of magnocellular input in patients with schizophrenia.
Collapse
Affiliation(s)
- Jung Suk Lee
- Department of Psychiatry, National Health Insurance Service Ilsan Hospital, Goyang, Republic of Korea
| | - Gewnhi Park
- Department of Psychology, Azusa Pacific University, Azusa, CA, USA
| | - Myeong Ju Song
- Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea
| | - Kee-Hong Choi
- Department of Psychology, Korea University, Seoul, Republic of Korea
| | - Seung-Hwan Lee
- Clinical Emotion and Cognition Research Laboratory, Goyang, Republic of Korea; Department of Psychiatry, Inje University, Ilsan-Paik Hospital, Goyang, Republic of Korea
| |
Collapse
|
|
32
|
Jonas RK, Jalbrzikowski M, Montojo CA, Patel A, Kushan L, Chow CC, Vesagas T, Bearden CE. Altered Brain Structure-Function Relationships Underlie Executive Dysfunction in 22q11.2 Deletion Syndrome. MOLECULAR NEUROPSYCHIATRY 2015; 1:235-46. [PMID: 27606315 DOI: 10.1159/000441979] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
22q11.2 deletion syndrome (22q11DS) is a neurogenetic disorder associated with elevated rates of developmental neuropsychiatric disorders and impaired executive function (EF). Disrupted brain structure-function relationships may underlie EF deficits in 22q11DS. We administered the Behavior Rating Inventory of Executive Function (BRIEF) to assess real-world EF in patients with 22q11DS and matched controls (n = 86; age 6-17 years), along with cognitive measures that tap behavioral regulation and metacognition aspects of EF. Using FreeSurfer's whole-brain vertex cortical thickness pipeline, we investigated brain structure-EF relationships in patients with 22q11DS and controls. Behaviorally, patients with 22q11DS were impaired on multiple EF measures. Right orbitofrontal cortical thickness showed a differential relationship between real-world EF in patients with 22q11DS and controls. We also observed a group difference in the relationship between behavioral regulation and metacognition measures with thickness of ventral and dorsolateral prefrontal regions, respectively. Our findings suggest that executive dysfunction characteristic of 22q11DS is underscored by altered prefrontal cortical structure.
Collapse
Affiliation(s)
- Rachel K Jonas
- Semel Institute for Neuroscience and Human Behavior, University of California-Los Angeles, Los Angeles, Calif., USA
| | - Maria Jalbrzikowski
- Semel Institute for Neuroscience and Human Behavior, University of California-Los Angeles, Los Angeles, Calif., USA
| | - Caroline A Montojo
- Semel Institute for Neuroscience and Human Behavior, University of California-Los Angeles, Los Angeles, Calif., USA
| | - Arati Patel
- Semel Institute for Neuroscience and Human Behavior, University of California-Los Angeles, Los Angeles, Calif., USA
| | - Leila Kushan
- Semel Institute for Neuroscience and Human Behavior, University of California-Los Angeles, Los Angeles, Calif., USA
| | - Carolyn C Chow
- Semel Institute for Neuroscience and Human Behavior, University of California-Los Angeles, Los Angeles, Calif., USA
| | - Therese Vesagas
- Semel Institute for Neuroscience and Human Behavior, University of California-Los Angeles, Los Angeles, Calif., USA
| | - Carrie E Bearden
- Semel Institute for Neuroscience and Human Behavior, University of California-Los Angeles, Los Angeles, Calif., USA
| |
Collapse
|
|
33
|
The role of the thalamus in schizophrenia from a neuroimaging perspective. Neurosci Biobehav Rev 2015; 54:57-75. [DOI: 10.1016/j.neubiorev.2015.01.013] [Citation(s) in RCA: 122] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2014] [Revised: 12/19/2014] [Accepted: 01/12/2015] [Indexed: 02/06/2023]
|
|
34
|
John JP, Lukose A, Bagepally BS, Halahalli HN, Moily NS, Vijayakumari AA, Jain S. A systematic examination of brain volumetric abnormalities in recent-onset schizophrenia using voxel-based, surface-based and region-of-interest-based morphometric analyses. J Negat Results Biomed 2015; 14:11. [PMID: 26065881 PMCID: PMC4464994 DOI: 10.1186/s12952-015-0030-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Accepted: 06/01/2015] [Indexed: 12/11/2022] Open
Abstract
Background Brain morphometric abnormalities in schizophrenia have been extensively reported in the literature. Whole-brain volumetric reductions are almost universally reported by most studies irrespective of the characteristics of the samples studied (e.g., chronic/recent-onset; medicated/neuroleptic-naïve etc.). However, the same cannot be said of the reported regional morphometric abnormalities in schizophrenia. While certain regional morphometric abnormalities are more frequently reported than others, there are no such abnormalities that are universally reported across studies. Variability of socio-demographic and clinical characteristics across study samples as well as technical and methodological issues related to acquisition and analyses of brain structural images may contribute to inconsistency of brain morphometric findings in schizophrenia. The objective of the present study therefore was to systematically examine brain morphometry in patients with recent-onset schizophrenia to find out if there are significant whole-brain or regional volumetric differences detectable at the appropriate significance threshold, after attempting to control for various confounding factors that could impact brain volumes. Methods Structural magnetic resonance images of 90 subjects (schizophrenia = 45; healthy subjects = 45) were acquired using a 3 Tesla magnet. Morphometric analyses were carried out following standard analyses pipelines of three most commonly used strategies, viz., whole-brain voxel-based morphometry, whole-brain surface-based morphometry, and between-group comparisons of regional volumes generated by automated segmentation and parcellation. Results In our sample of patients having recent-onset schizophrenia with limited neuroleptic exposure, there were no significant whole brain or regional brain morphometric abnormalities noted at the appropriate statistical significance thresholds with or without including age, gender and intracranial volume or total brain volume in the statistical analyses. Conclusions In the background of the conflicting findings in the literature, our findings indicate that brain morphometric abnormalities may not be directly related to the schizophrenia phenotype. Analysis of the reasons for the inconsistent results across studies as well as consideration of alternate sources of variability of brain morphology in schizophrenia such as epistatic and epigenetic mechanisms could perhaps advance our understanding of structural brain alterations in schizophrenia. Electronic supplementary material The online version of this article (doi:10.1186/s12952-015-0030-z) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- John P John
- Additional Professor of Psychiatry & Adjunct Faculty of Clinical Neurosciences, Multimodal Brain Image Analysis Laboratory (MBIAL), National Institute of Mental Health and Neurosciences (NIMHANS), P.B. No. 2900, Dharmaram P.O., Hosur Road, Bangalore, 560 029, Karnataka, India. .,Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India. .,Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
| | - Ammu Lukose
- Additional Professor of Psychiatry & Adjunct Faculty of Clinical Neurosciences, Multimodal Brain Image Analysis Laboratory (MBIAL), National Institute of Mental Health and Neurosciences (NIMHANS), P.B. No. 2900, Dharmaram P.O., Hosur Road, Bangalore, 560 029, Karnataka, India. .,Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
| | - Bhavani Shankara Bagepally
- Additional Professor of Psychiatry & Adjunct Faculty of Clinical Neurosciences, Multimodal Brain Image Analysis Laboratory (MBIAL), National Institute of Mental Health and Neurosciences (NIMHANS), P.B. No. 2900, Dharmaram P.O., Hosur Road, Bangalore, 560 029, Karnataka, India. .,Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India. .,Department of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
| | - Harsha N Halahalli
- Additional Professor of Psychiatry & Adjunct Faculty of Clinical Neurosciences, Multimodal Brain Image Analysis Laboratory (MBIAL), National Institute of Mental Health and Neurosciences (NIMHANS), P.B. No. 2900, Dharmaram P.O., Hosur Road, Bangalore, 560 029, Karnataka, India. .,Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India. .,Department of Neurophysiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
| | - Nagaraj S Moily
- Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India. .,Molecular Genetics Laboratory, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
| | - Anupa A Vijayakumari
- Additional Professor of Psychiatry & Adjunct Faculty of Clinical Neurosciences, Multimodal Brain Image Analysis Laboratory (MBIAL), National Institute of Mental Health and Neurosciences (NIMHANS), P.B. No. 2900, Dharmaram P.O., Hosur Road, Bangalore, 560 029, Karnataka, India. .,Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
| | - Sanjeev Jain
- Department of Psychiatry, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India. .,Molecular Genetics Laboratory, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India.
| |
Collapse
|
|
35
|
Pettersson-Yeo W, Benetti S, Frisciata S, Catani M, Williams SC, Allen P, McGuire P, Mechelli A. Does neuroanatomy account for superior temporal dysfunction in early psychosis? A multimodal MRI investigation. J Psychiatry Neurosci 2015; 40:100-7. [PMID: 25338016 PMCID: PMC4354815 DOI: 10.1503/jpn.140082] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022] Open
Abstract
BACKGROUND Neuroimaging studies of ultra-high risk (UHR) and first-episode psychosis (FEP) have revealed widespread alterations in brain structure and function. Recent evidence suggests there is an intrinsic relationship between these 2 types of alterations; however, there is very little research linking these 2 modalities in the early stages of psychosis. METHODS To test the hypothesis that functional alteration in UHR and FEP articipants would be associated with corresponding structural alteration, we examined brain function and structure in these participants as well as in a group of healthy controls using multimodal MRI. The data were analyzed using statistical parametric mapping. RESULTS We included 24 participants in the FEP group, 18 in the UHR group and 21 in the control group. Patients in the FEP group showed a reduction in functional activation in the left superior temporal gyrus relative to controls, and the UHR group showed intermediate values. The same region showed a corresponding reduction in grey matter volume in the FEP group relative to controls. However, while the difference in grey matter volume remained significant after including functional activation as a covariate of no interest, the reduction in functional activation was no longer evident after including grey matter volume as a covariate of no interest. LIMITATIONS Our sample size was relatively small. All participants in the FEP group and 2 in the UHR group had received antipsychotic medication, which may have impacted neurofunction and/or neuroanatomy. CONCLUSION Our results suggest that superior temporal dysfunction in early psychosis is accounted for by a corresponding alteration in grey matter volume. This finding has important implications for the interpretation of functional alteration in early psychosis.
Collapse
Affiliation(s)
- William Pettersson-Yeo
- Correspondence to: W. Pettersson-Yeo, Department of Psychosis Studies, PO Box 67, Institute of Psychiatry, King’s College London, De Crespigny Park, London UK SE5 8AF;
| | | | | | | | | | | | | | | |
Collapse
|
|
36
|
Barnes SA, Sawiak SJ, Caprioli D, Jupp B, Buonincontri G, Mar AC, Harte MK, Fletcher PC, Robbins TW, Neill JC, Dalley JW. Impaired limbic cortico-striatal structure and sustained visual attention in a rodent model of schizophrenia. Int J Neuropsychopharmacol 2014; 18:pyu010. [PMID: 25552430 PMCID: PMC4368881 DOI: 10.1093/ijnp/pyu010] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/01/2014] [Accepted: 06/09/2014] [Indexed: 12/26/2022] Open
Abstract
BACKGROUND N-methyl-d-aspartate receptor (NMDAR) dysfunction is thought to contribute to the pathophysiology of schizophrenia. Accordingly, NMDAR antagonists such as phencyclidine (PCP) are used widely in experimental animals to model cognitive impairment associated with this disorder. However, it is unclear whether PCP disrupts the structural integrity of brain areas relevant to the profile of cognitive impairment in schizophrenia. METHODS Here we used high-resolution magnetic resonance imaging and voxel-based morphometry to investigate structural alterations associated with sub-chronic PCP treatment in rats. RESULTS Sub-chronic exposure of rats to PCP (5mg/kg twice daily for 7 days) impaired sustained visual attention on a 5-choice serial reaction time task, notably when the attentional load was increased. In contrast, sub-chronic PCP had no significant effect on the attentional filtering of a pre-pulse auditory stimulus in an acoustic startle paradigm. Voxel-based morphometry revealed significantly reduced grey matter density bilaterally in the hippocampus, anterior cingulate cortex, ventral striatum, and amygdala. PCP-treated rats also exhibited reduced cortical thickness in the insular cortex. CONCLUSIONS These findings demonstrate that sub-chronic NMDA receptor antagonism is sufficient to produce highly-localized morphological abnormalities in brain areas implicated in the pathogenesis of schizophrenia. Furthermore, PCP exposure resulted in dissociable impairments in attentional function.
Collapse
Affiliation(s)
- Samuel A Barnes
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill)
| | - Stephen J Sawiak
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill)
| | - Daniele Caprioli
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill)
| | - Bianca Jupp
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill)
| | - Guido Buonincontri
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill)
| | - Adam C Mar
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill)
| | - Michael K Harte
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill)
| | - Paul C Fletcher
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill)
| | - Trevor W Robbins
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill)
| | - Jo C Neill
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill)
| | - Jeffrey W Dalley
- Department of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA (Dr Barnes); Behavioural and Clinical Neuroscience Institute and Department of Psychology, University of Cambridge, Downing St, Cambridge UK (Drs Sawiak, Caprioli, Jupp, Mar, Fletcher, Robbins, and Dalley); Wolfson Brain Imaging Centre, Department of Clinical Neurosciences, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Sawiak and Buonincontri); Department of Psychiatry, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK (Drs Fletcher and Dalley); Manchester Pharmacy School, University of Manchester, UK (Drs Harte and Neill).
| |
Collapse
|
|
37
|
Bossong MG, Jansma JM, Bhattacharyya S, Ramsey NF. Role of the endocannabinoid system in brain functions relevant for schizophrenia: an overview of human challenge studies with cannabis or ∆9-tetrahydrocannabinol (THC). Prog Neuropsychopharmacol Biol Psychiatry 2014; 52:53-69. [PMID: 24380726 DOI: 10.1016/j.pnpbp.2013.11.017] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/16/2013] [Revised: 10/16/2013] [Accepted: 11/25/2013] [Indexed: 12/30/2022]
Abstract
Accumulating evidence suggests involvement of the endocannabinoid system in the pathophysiology of schizophrenia, which signifies a potential application for this system in the treatment of this disorder. However, before new research can focus on potential treatments that work by manipulating the endocannabinoid system, it needs to be elucidated how this system is involved in symptoms of schizophrenia. Here we review human studies that investigated acute effects of cannabis or ∆9-tetrahydrocannabinol (THC) on brain functions that are implicated in schizophrenia. Results suggest that the impact of THC administration depends on the difficulty of the task performed. Impaired performance of cognitive paradigms is reported on more challenging tasks, which is associated with both activity deficits in temporal and prefrontal areas and a failure to deactivate regions of the default mode network. Comparable reductions in prefrontal activity and impairments in deactivation of the default mode network are seen in patients during performance of cognitive paradigms. Normal performance levels after THC administration demonstrated for less demanding tasks are shown to be related to either increased neural effort in task-specific regions ('neurophysiological inefficiency'), or recruitment of alternative brain areas, which suggests a change in strategy to meet cognitive demands. Particularly a pattern of performance and brain activity corresponding with an inefficient working memory system is consistently demonstrated in patients. These similarities in brain function between intoxicated healthy volunteers and schizophrenia patients provide an argument for a role of the endocannabinoid system in symptoms of schizophrenia, and further emphasize this system as a potential novel target for treatment of these symptoms.
Collapse
Affiliation(s)
- Matthijs G Bossong
- Institute of Psychiatry, Department of Psychosis Studies, King's College London, 16 De Crespigny Park, London SE5 8AF, United Kingdom.
| | - J Martijn Jansma
- Rudolf Magnus Institute of Neuroscience, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| | - Sagnik Bhattacharyya
- Institute of Psychiatry, Department of Psychosis Studies, King's College London, 16 De Crespigny Park, London SE5 8AF, United Kingdom
| | - Nick F Ramsey
- Rudolf Magnus Institute of Neuroscience, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands
| |
Collapse
|
|
38
|
The continuous performance test, identical pairs: norms, reliability and performance in healthy controls and patients with schizophrenia in Singapore. Schizophr Res 2014; 156:233-40. [PMID: 24819191 DOI: 10.1016/j.schres.2014.04.016] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2013] [Revised: 04/08/2014] [Accepted: 04/11/2014] [Indexed: 11/22/2022]
Abstract
AIM To provide normative values for the healthy ethnic Chinese Singaporean population and a large sample of patients with schizophrenia for the Continuous Performance Task-Identical Pairs (CPT-IP). Participants Data were collected on 1011 healthy ethnic Chinese and 654 patients diagnosed with schizophrenia, all between 21 and 55 years of age. METHODS Data were stratified by age and gender. The effects of age, gender and education were explored in patients and controls. Performance indices were assessed in their ability to predict group inclusion. Controls' performance was compared with that reported in a US sample. RESULTS Performance was affected by age, sex, and education, with youth, male sex and higher education providing a performance advantage. Patients' performance was lower than controls' by more than 1 standard deviation, with the 3-digit d' score most significantly discriminating between controls and patients. The effects of socio-demographic factors on performance were in line with those conducted in the US and previously reported in the literature. CONCLUSIONS This is the largest norming study ever conducted on the CPT-IP. It will enable investigators and clinicians to select appropriate indices to assess severity of cognitive decline and/or evaluate cognitive remediation therapy outcomes after taking into account age, gender and education factors.
Collapse
|
|
39
|
Sepede G, Spano MC, Lorusso M, Berardis DD, Salerno RM, Giannantonio MD, Gambi F. Sustained attention in psychosis: Neuroimaging findings. World J Radiol 2014; 6:261-273. [PMID: 24976929 PMCID: PMC4072813 DOI: 10.4329/wjr.v6.i6.261] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2013] [Revised: 02/07/2014] [Accepted: 05/16/2014] [Indexed: 02/06/2023] Open
Abstract
To provide a systematic review of scientific literature on functional magnetic resonance imaging (fMRI) studies on sustained attention in psychosis. We searched PubMed to identify fMRI studies pertaining sustained attention in both affective and non-affective psychosis. Only studies conducted on adult patients using a sustained attention task during fMRI scanning were included in the final review. The search was conducted on September 10th, 2013. 15 fMRI studies met our inclusion criteria: 12 studies were focused on Schizophrenia and 3 on Bipolar Disorder Type I (BDI). Only half of the Schizophrenia studies and two of the BDI studies reported behavioral abnormalities, but all of them evidenced significant functional differences in brain regions related to the sustained attention system. Altered functioning of the insula was found in both Schizophrenia and BDI, and therefore proposed as a candidate trait marker for psychosis in general. On the other hand, other brain regions were differently impaired in affective and non-affective psychosis: alterations of cingulate cortex and thalamus seemed to be more common in Schizophrenia and amygdala dysfunctions in BDI. Neural correlates of sustained attention seem to be of great interest in the study of psychosis, highlighting differences and similarities between Schizophrenia and BDI.
Collapse
|
|
40
|
Tully LM, Lincoln SH, Liyanage-Don N, Hooker CI. Impaired cognitive control mediates the relationship between cortical thickness of the superior frontal gyrus and role functioning in schizophrenia. Schizophr Res 2014; 152:358-64. [PMID: 24388000 DOI: 10.1016/j.schres.2013.12.005] [Citation(s) in RCA: 47] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Revised: 11/28/2013] [Accepted: 12/05/2013] [Indexed: 10/25/2022]
Abstract
Structural abnormalities in the lateral prefrontal cortex (LPFC) are well-documented in schizophrenia and recent evidence suggests that these abnormalities relate to functional outcome. Cognitive control mechanisms, reliant on the LPFC, are impaired in schizophrenia and predict functional outcome, thus impaired cognitive control could mediate the relationship between neuroanatomical abnormalities in the LPFC and functional outcome. We used surface-based morphometry to investigate relationships between cortical surface characteristics, cognitive control, and measures of social and role functioning in 26 individuals with schizophrenia and 29 healthy controls. Results demonstrate that schizophrenia participants had thinner cortex in a region of the superior frontal gyrus (BA10). Across all participants, decreased cortical thickness in this region related to decreased cognitive control and decreased role functioning. Moreover, cognitive control fully mediated the relationship between cortical thickness in the superior frontal gyrus and role functioning, indicating that neuroanatomical abnormalities in the LPFC adversely impact role functioning via impaired cognitive control processes.
Collapse
Affiliation(s)
- Laura M Tully
- Harvard University, Department of Psychology, 33 Kirkland St., Cambridge, MA 02138, USA.
| | - Sarah Hope Lincoln
- Harvard University, Department of Psychology, 33 Kirkland St., Cambridge, MA 02138, USA
| | - Nadia Liyanage-Don
- Harvard University, Department of Psychology, 33 Kirkland St., Cambridge, MA 02138, USA
| | - Christine I Hooker
- Harvard University, Department of Psychology, 33 Kirkland St., Cambridge, MA 02138, USA
| |
Collapse
|
|
41
|
Diwadkar VA, Bakshi N, Gupta G, Pruitt P, White R, Eickhoff SB. Dysfunction and Dysconnection in Cortical-Striatal Networks during Sustained Attention: Genetic Risk for Schizophrenia or Bipolar Disorder and its Impact on Brain Network Function. Front Psychiatry 2014; 5:50. [PMID: 24847286 PMCID: PMC4023040 DOI: 10.3389/fpsyt.2014.00050] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2013] [Accepted: 04/28/2014] [Indexed: 01/08/2023] Open
Abstract
Abnormalities in the brain's attention network may represent early identifiable neurobiological impairments in individuals at increased risk for schizophrenia or bipolar disorder. Here, we provide evidence of dysfunctional regional and network function in adolescents at higher genetic risk for schizophrenia or bipolar disorder [henceforth higher risk (HGR)]. During fMRI, participants engaged in a sustained attention task with variable demands. The task alternated between attention (120 s), visual control (passive viewing; 120 s), and rest (20 s) epochs. Low and high demand attention conditions were created using the rapid presentation of two- or three-digit numbers. Subjects were required to detect repeated presentation of numbers. We demonstrate that the recruitment of cortical and striatal regions are disordered in HGR: relative to typical controls (TC), HGR showed lower recruitment of the dorsal prefrontal cortex, but higher recruitment of the superior parietal cortex. This imbalance was more dramatic in the basal ganglia. There, a group by task demand interaction was observed, such that increased attention demand led to increased engagement in TC, but disengagement in HGR. These activation studies were complemented by network analyses using dynamic causal modeling. Competing model architectures were assessed across a network of cortical-striatal regions, distinguished at a second level using random-effects Bayesian model selection. In the winning architecture, HGR were characterized by significant reductions in coupling across both frontal-striatal and frontal-parietal pathways. The effective connectivity analyses indicate emergent network dysconnection, consistent with findings in patients with schizophrenia. Emergent patterns of regional dysfunction and dysconnection in cortical-striatal pathways may provide functional biological signatures in the adolescent risk-state for psychiatric illness.
Collapse
Affiliation(s)
- Vaibhav A Diwadkar
- Department of Psychiatry and Behavioral Neurosciences, Wayne State University , Detroit, MI , USA
| | - Neil Bakshi
- Department of Psychiatry and Behavioral Neurosciences, Wayne State University , Detroit, MI , USA
| | - Gita Gupta
- Department of Psychiatry and Behavioral Neurosciences, Wayne State University , Detroit, MI , USA
| | - Patrick Pruitt
- Department of Psychiatry and Behavioral Neurosciences, Wayne State University , Detroit, MI , USA
| | - Richard White
- Department of Psychiatry and Behavioral Neurosciences, Wayne State University , Detroit, MI , USA
| | - Simon B Eickhoff
- Institute of Clinical Neuroscience and Medical Psychology, Heinrich-Heine University Düsseldorf , Düsseldorf , Germany ; Institute of Neuroscience and Medicine (INM-1), Research Center Jülich , Jülich , Germany
| |
Collapse
|
|
42
|
Garg R, Trivedi JK, Dalal PK, Nischal A, Sinha PK, Varma S. Assessment of cognition in non-affected full biological siblings of patients with schizophrenia. Indian J Psychiatry 2013; 55:331-7. [PMID: 24459302 PMCID: PMC3890917 DOI: 10.4103/0019-5545.120543] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/29/2022] Open
Abstract
BACKGROUND Schizophrenia is a devastating psychotic illness which is like the most mental disorders, shows complex inheritance; the transmission of the disorder most likely involves several genes and environmental factors. It is difficult to judge whether a particular person without schizophrenia has predisposing factors for the said disease. A few studies have shown the relative sensitivity and reliability of cognitive and psychophysiological markers of brain function as the susceptibility factors for schizophrenia which may aid us to find people with an increased risk of complex disorders like schizophrenia. The present work is an exploration on cognitive impairments in unaffected siblings of patients suffering from schizophrenia with a framework to explore why a mental disorder occurs in some families but not in others. MATERIALS AND METHODS This is a single point non-invasive study of non-affected full biological siblings of patients with schizophrenia, involving administration of a battery of neuropsychological tests to assess the cognitive function in the sibling group and a control group of volunteers with no history of psychiatric illness. The control group was matched for age, gender, and education. The siblings were also divided on the basis of the type of schizophrenia their siblings (index probands) were suffering from and their results compared with each other. RESULTS The siblings performed significantly poorly as compared to the controls on Wisconsin card sorting test (WCST), continuous performance test (CPT), and spatial working memory test (SWMT). The comparison between the sibling subgroups based on the type of schizophrenia in the index probands did not reveal any significant difference. CONCLUSION These findings suggest that there is a global impairment in the cognition of the non-affected siblings of patients of schizophrenia. Cognitive impairment might be one of the factors which will help us to hit upon people who are predisposed to develop schizophrenia in the future.
Collapse
Affiliation(s)
- Rohit Garg
- Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
| | - J K Trivedi
- Department of Psychiatry, King George's Medical University, Uttar Pradesh, Lucknow, India
| | - P K Dalal
- Department of Psychiatry, King George's Medical University, Uttar Pradesh, Lucknow, India
| | - Anil Nischal
- Department of Psychiatry, King George's Medical University, Uttar Pradesh, Lucknow, India
| | - P K Sinha
- Department of Psychiatry, King George's Medical University, Uttar Pradesh, Lucknow, India
| | - Sannidhya Varma
- Department of Psychiatry, King George's Medical University, Uttar Pradesh, Lucknow, India
| |
Collapse
|
|
43
|
Sui J, Huster R, Yu Q, Segall JM, Calhoun VD. Function-structure associations of the brain: evidence from multimodal connectivity and covariance studies. Neuroimage 2013; 102 Pt 1:11-23. [PMID: 24084066 DOI: 10.1016/j.neuroimage.2013.09.044] [Citation(s) in RCA: 119] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2013] [Revised: 09/18/2013] [Accepted: 09/20/2013] [Indexed: 12/13/2022] Open
Abstract
Despite significant advances in multimodal imaging techniques and analysis approaches, unimodal studies are still the predominant way to investigate brain changes or group differences, including structural magnetic resonance imaging (sMRI), functional MRI (fMRI), diffusion tensor imaging (DTI) and electroencephalography (EEG). Multimodal brain studies can be used to understand the complex interplay of anatomical, functional and physiological brain alterations or development, and to better comprehend the biological significance of multiple imaging measures. To examine the function-structure associations of the brain in a more comprehensive and integrated manner, we reviewed a number of multimodal studies that combined two or more functional (fMRI and/or EEG) and structural (sMRI and/or DTI) modalities. In this review paper, we specifically focused on multimodal neuroimaging studies on cognition, aging, disease and behavior. We also compared multiple analysis approaches, including univariate and multivariate methods. The possible strengths and limitations of each method are highlighted, which can guide readers when selecting a method based on a given research question. In particular, we believe that multimodal fusion approaches will shed further light on the neuronal mechanisms underlying the major structural and functional pathophysiological features of both the healthy brain (e.g. development) or the diseased brain (e.g. mental illness) and, in the latter case, may provide a more sensitive measure than unimodal imaging for disease classification, e.g. multimodal biomarkers, which potentially can be used to support clinical diagnosis based on neuroimaging techniques.
Collapse
Affiliation(s)
- Jing Sui
- The Mind Research Network, Albuquerque, NM 87106, USA; Brainnetome Center, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China; National Laboratory of Pattern Recognition, Institute of Automation, Chinese Academy of Sciences, Beijing 100190, China.
| | - Rene Huster
- Experimental Psychology Lab, Carl von Ossietzky University, Oldenburg, Germany
| | - Qingbao Yu
- The Mind Research Network, Albuquerque, NM 87106, USA
| | | | - Vince D Calhoun
- The Mind Research Network, Albuquerque, NM 87106, USA; Dept. of ECE, University of New Mexico, Albuquerque, NM 87131, USA.
| |
Collapse
|
|
44
|
Koelkebeck K, Hirao K, Miyata J, Kawada R, Saze T, Dannlowski U, Ubukata S, Ohrmann P, Bauer J, Pedersen A, Fukuyama H, Sawamoto N, Takahashi H, Murai T. Impact of gray matter reductions on theory of mind abilities in patients with schizophrenia. Soc Neurosci 2013; 8:631-9. [PMID: 24047258 DOI: 10.1080/17470919.2013.837094] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
To identify the brain regions involved in the interpretation of intentional movement by patients with schizophrenia, we investigated the association between cerebral gray matter (GM) volumes and performance on a theory of mind (ToM) task using voxel-based morphometry. Eighteen patients with schizophrenia and thirty healthy controls participated in the study. Participants were given a moving shapes task that employs the interpretation of intentional movement. Verbal descriptions were rated according to intentionality. ToM performance deficits in patients were found to be positively correlated with GM volume reductions in the superior temporal sulcus and medial prefrontal cortex. Our findings confirm that divergent brain regions contribute to mentalizing abilities and that GM volume reductions impact behavioral deficits in patients with schizophrenia.
Collapse
Affiliation(s)
- Katja Koelkebeck
- a Department of Psychiatry and Psychotherapy, School of Medicine , University of Muenster , Muenster , Germany
| | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
45
|
Bossong MG, Jansma JM, van Hell HH, Jager G, Kahn RS, Ramsey NF. Default mode network in the effects of Δ9-Tetrahydrocannabinol (THC) on human executive function. PLoS One 2013; 8:e70074. [PMID: 23936144 PMCID: PMC3729458 DOI: 10.1371/journal.pone.0070074] [Citation(s) in RCA: 50] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2013] [Accepted: 06/16/2013] [Indexed: 12/31/2022] Open
Abstract
Evidence is increasing for involvement of the endocannabinoid system in cognitive functions including attention and executive function, as well as in psychiatric disorders characterized by cognitive deficits, such as schizophrenia. Executive function appears to be associated with both modulation of active networks and inhibition of activity in the default mode network. In the present study, we examined the role of the endocannabinoid system in executive function, focusing on both the associated brain network and the default mode network. A pharmacological functional magnetic resonance imaging (fMRI) study was conducted with a placebo-controlled, cross-over design, investigating effects of the endocannabinoid agonist Δ9-tetrahydrocannabinol (THC) on executive function in 20 healthy volunteers, using a continuous performance task with identical pairs. Task performance was impaired after THC administration, reflected in both an increase in false alarms and a reduction in detected targets. This was associated with reduced deactivation in a set of brain regions linked to the default mode network, including posterior cingulate cortex and angular gyrus. Less deactivation was significantly correlated with lower performance after THC. Regions that were activated by the continuous performance task, notably bilateral prefrontal and parietal cortex, did not show effects of THC. These findings suggest an important role for the endocannabinoid system in both default mode modulation and executive function. This may be relevant for psychiatric disorders associated with executive function deficits, such as schizophrenia and ADHD.
Collapse
Affiliation(s)
- Matthijs G Bossong
- Rudolf Magnus Institute of Neuroscience, Department of Neurology and Neurosurgery, University Medical Center Utrecht, Utrecht, The Netherlands.
| | | | | | | | | | | |
Collapse
|
|
46
|
Ohi K, Hashimoto R, Yasuda Y, Fukumoto M, Nemoto K, Ohnishi T, Yamamori H, Takahashi H, Iike N, Kamino K, Yoshida T, Azechi M, Ikezawa K, Tanimukai H, Tagami S, Morihara T, Okochi M, Tanaka T, Kudo T, Iwase M, Kazui H, Takeda M. The AKT1 gene is associated with attention and brain morphology in schizophrenia. World J Biol Psychiatry 2013; 14:100-13. [PMID: 22150081 DOI: 10.3109/15622975.2011.591826] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
OBJECTIVES A meta-analysis of the associations between genetic variants in the AKT1 gene and schizophrenia found that a single nucleotide polymorphism (SNP5; rs2494732) was associated with schizophrenia in Asian populations. METHODS In this study, we investigated the effects of this SNP on memory and attentional performance and brain structure using magnetic resonance imaging in a Japanese population (117 patients with schizophrenia and 189 healthy subjects). RESULTS The memory performance, particularly attention/concentration score, measured by the Wechsler Memory Scale-Revised in A carriers of SNP5, which was found to be enriched in patients with schizophrenia, was lower than that in individuals with the G/G genotype. We confirmed the association of the SNP with attentional performance using the Continuous Performance Test, which assessed sustained attention and vigilance of attentional function. Patients with A allele demonstrated lower attentional performance than patients with the G/G genotype. Patients with the A allele had smaller gray matter volumes in the right inferior parietal lobule related to attentional processes and in the frontostriatal region related to different SNPs in AKT1 than patients with the G/G genotype. CONCLUSIONS Our results suggest that a genetic variant of AKT1 might be associated with attentional deficits and brain morphological vulnerability in patients with schizophrenia.
Collapse
Affiliation(s)
- Kazutaka Ohi
- Department of Psychiatry, Osaka University Graduate school of Medicine, Osaka, Japan
| | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | | |
Collapse
|
|
47
|
Kirenskaya AV, Myamlin VV, Novototsky-Vlasov VY, Pletnikov MV, Kozlovskaya IB. The Contingent Negative Variation Laterality and Dynamics in Antisaccade Task in Normal and Unmedicated Schizophrenic Subjects. SPANISH JOURNAL OF PSYCHOLOGY 2013; 14:869-83. [DOI: 10.5209/rev_sjop.2011.v14.n2.34] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
Contingent negative variation (CNV) topography, hemispheric asymmetry and time-course were investigated in healthy subjects and non-medicated paranoid schizophrenic patients in two antisaccade paradigms with the short (800-1000 ms) and long (1200-1400 ms) durations of the fixation period. EEG and electrooculogram (EOG) were recorded. Saccade characteristics and mean amplitudes of slow cortical potentials time-locked to peripheral target were analyzed in 23 healthy volunteers and 19 schizophrenic patients. Compared to healthy control subjects, schizophrenic patients had significantly slower antisaccades and committed significantly more erroneous saccades in the both antisaccade tasks. The prolongation of the fixation period resulted in noticeable decrease of error percent in patients group. The analysis of CNV time-course has revealed two distinct stages in both groups. The early CNV stage was represented by a negative wave with the maximal amplitude over midline fronto-central area, and the late stage was characterized by increased CNV amplitude at the midline and left parietal electrode sites. In healthy subjects the simultaneous activation of frontal and parietal areas was observed in the paradigm with the shorter fixation interval; the increase of the fixation period produced consecutive activation of these areas. Schizophrenic patients' CNV amplitude was generally smaller than that of healthy subjects. The most pronounced between-group differences of the negative shift amplitude were revealed at frontal electrode sites during the early CNV stage in both modifications of the antisaccade task. The deficit of frontal activation revealed in patients at the early stage of antisaccade preparatory set in both antisaccadic paradigms may be related to pathogenesis of paranoid schizophrenia.
Collapse
|
|
48
|
Langner R, Eickhoff SB. Sustaining attention to simple tasks: a meta-analytic review of the neural mechanisms of vigilant attention. Psychol Bull 2012; 139:870-900. [PMID: 23163491 DOI: 10.1037/a0030694] [Citation(s) in RCA: 429] [Impact Index Per Article: 33.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Maintaining attention for more than a few seconds is essential for mastering everyday life. Yet, our ability to stay focused on a particular task is limited, resulting in well-known performance decrements with increasing time on task. Intriguingly, such decrements are even more likely if the task is cognitively simple and repetitive. The attentional function that enables our prolonged engagement in intellectually unchallenging, uninteresting activities has been termed vigilant attention. Here we synthesized what we have learned from functional neuroimaging about the mechanisms of this essential mental faculty. To this end, a quantitative meta-analysis of pertinent neuroimaging studies was performed, including supplementary analyses of moderating factors. Furthermore, we reviewed the available evidence on neural time-on-task effects, additionally considering information obtained from patients with focal brain damage. Integrating the results of both meta-analysis and review, we identified a set of mainly right-lateralized brain regions that may form the core network subserving vigilant attention in humans, including dorsomedial, mid- and ventrolateral prefrontal cortex, anterior insula, parietal areas (intraparietal sulcus, temporoparietal junction), and subcortical structures (cerebellar vermis, thalamus, putamen, midbrain). We discuss the potential functional roles of different nodes of this network as well as implications of our findings for a theoretical account of vigilant attention. It is conjectured that sustaining attention is a multicomponent, nonunitary mental faculty, involving a mixture of (a) sustained/recurrent processes subserving task-set/arousal maintenance and (b) transient processes subserving the target-driven reorienting of attention. Finally, limitations of previous studies are considered and suggestions for future research are provided.
Collapse
Affiliation(s)
- Robert Langner
- Institute of Clinical Neuroscience and Medical Psychology, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
| | | |
Collapse
|
|
49
|
Schultz CC, Fusar-Poli P, Wagner G, Koch K, Schachtzabel C, Gruber O, Sauer H, Schlösser RGM. Multimodal functional and structural imaging investigations in psychosis research. Eur Arch Psychiatry Clin Neurosci 2012; 262 Suppl 2:S97-106. [PMID: 22940744 DOI: 10.1007/s00406-012-0360-5] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2012] [Accepted: 08/15/2012] [Indexed: 12/15/2022]
Abstract
Substantial pathophysiological questions about the relationship of brain pathologies in psychosis can only be answered by multimodal neuroimaging approaches combining different imaging modalities such as structural MRI (sMRI), functional MRI (fMRI), diffusion tensor imaging (DTI), positron emission tomography (PET) and magnetic-resonance spectroscopy. In particular, the multimodal imaging approach has the potential to shed light on the neuronal mechanisms underlying the major brain structural and functional pathophysiological features of schizophrenia and high-risk states such as prefronto-temporal gray matter reduction, altered higher-order cognitive processing, or disturbed dopaminergic and glutamatergic neurotransmission. In recent years, valuable new findings have been revealed in these fields by multimodal imaging studies mostly reflecting a direct and aligned correlation of brain pathologies in psychosis. However, the amount of multimodal studies is still limited, and further efforts have to be made to consolidate previous findings and to extend the scope to other pathophysiological parameters contributing to the pathogenesis of psychosis. Here, investigating the genetic foundations of brain pathology relationships is a major challenge for future multimodal imaging applications in psychosis research.
Collapse
Affiliation(s)
- C Christoph Schultz
- Department of Psychiatry and Psychotherapy, Jena University Hospital, Philosophenweg 3, 07740 Jena, Germany.
| | | | | | | | | | | | | | | |
Collapse
|
|
50
|
Lee TMC, Leung MK, Hou WK, Tang JCY, Yin J, So KF, Lee CF, Chan CCH. Distinct neural activity associated with focused-attention meditation and loving-kindness meditation. PLoS One 2012; 7:e40054. [PMID: 22905090 PMCID: PMC3419705 DOI: 10.1371/journal.pone.0040054] [Citation(s) in RCA: 69] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2011] [Accepted: 06/05/2012] [Indexed: 11/29/2022] Open
Abstract
This study examined the dissociable neural effects of ānāpānasati (focused-attention meditation, FAM) and mettā (loving-kindness meditation, LKM) on BOLD signals during cognitive (continuous performance test, CPT) and affective (emotion-processing task, EPT, in which participants viewed affective pictures) processing. Twenty-two male Chinese expert meditators (11 FAM experts, 11 LKM experts) and 22 male Chinese novice meditators (11 FAM novices, 11 LKM novices) had their brain activity monitored by a 3T MRI scanner while performing the cognitive and affective tasks in both meditation and baseline states. We examined the interaction between state (meditation vs. baseline) and expertise (expert vs. novice) separately during LKM and FAM, using a conjunction approach to reveal common regions sensitive to the expert meditative state. Additionally, exclusive masking techniques revealed distinct interactions between state and group during LKM and FAM. Specifically, we demonstrated that the practice of FAM was associated with expertise-related behavioral improvements and neural activation differences in attention task performance. However, the effect of state LKM meditation did not carry over to attention task performance. On the other hand, both FAM and LKM practice appeared to affect the neural responses to affective pictures. For viewing sad faces, the regions activated for FAM practitioners were consistent with attention-related processing; whereas responses of LKM experts to sad pictures were more in line with differentiating emotional contagion from compassion/emotional regulation processes. Our findings provide the first report of distinct neural activity associated with forms of meditation during sustained attention and emotion processing.
Collapse
Affiliation(s)
- Tatia M. C. Lee
- Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong, China
- Laboratory of Cognitive Affective Neuroscience, The University of Hong Kong, Hong Kong, China
- The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China
- Social Neuroscience Research Network, The University of Hong Kong, Hong Kong, China
- * E-mail: (TMCL); (CCHC)
| | - Mei-Kei Leung
- Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong, China
- Laboratory of Cognitive Affective Neuroscience, The University of Hong Kong, Hong Kong, China
| | - Wai-Kai Hou
- Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong, China
- Laboratory of Cognitive Affective Neuroscience, The University of Hong Kong, Hong Kong, China
- Social Neuroscience Research Network, The University of Hong Kong, Hong Kong, China
| | - Joey C. Y. Tang
- Laboratory of Neuropsychology, The University of Hong Kong, Hong Kong, China
- Number Laboratory, The University of Hong Kong, Hong Kong, China
| | - Jing Yin
- Social Neuroscience Research Network, The University of Hong Kong, Hong Kong, China
- Centre of Buddhist Studies, The University of Hong Kong, Hong Kong, China
| | - Kwok-Fai So
- The State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China
- Social Neuroscience Research Network, The University of Hong Kong, Hong Kong, China
- Department of Anatomy, The University of Hong Kong, Hong Kong, China
| | - Chack-Fan Lee
- Social Neuroscience Research Network, The University of Hong Kong, Hong Kong, China
- Centre of Buddhist Studies, The University of Hong Kong, Hong Kong, China
| | - Chetwyn C. H. Chan
- Social Neuroscience Research Network, The University of Hong Kong, Hong Kong, China
- Applied Cognitive Neuroscience Laboratory, Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong, China
- * E-mail: (TMCL); (CCHC)
| |
Collapse
|