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Yang J, Guo Y, Zhang L, Gao S, Liu J. Involvement of the basolateral amygdaloid nucleus anterior part 5-HT 7 receptors in the regulation of anxiety-like behaviors in hemiparkinsonian rats. Exp Neurol 2025; 389:115239. [PMID: 40194650 DOI: 10.1016/j.expneurol.2025.115239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2024] [Revised: 03/12/2025] [Accepted: 04/01/2025] [Indexed: 04/09/2025]
Abstract
Anxiety is a common non-motor symptom of Parkinson's disease (PD), but its neurobiological mechanism is obscure. 5-hydroxytryptamine7 (5-HT7) receptor is associated with anxiety and is widely distributed in brain regions related to emotion regulation, including anterior part of basolateral amygdaloid nucleus (BLA), and monosynaptic glutamatergic BLA to ventral hippocampus (vHPC) (BLAGlu-vHPC) pathway modulates anxiety-related behaviors. Measurable pathological and pathophysiological changes within the amygdala and hippocampus have also been reported in PD patients and parkinsonian animals. Thus, we hypothesized that BLA 5-HT7 receptors might regulate PD-related anxiety through BLAGlu-vHPC pathway. In this study, we found that down-regulation of BLA 5-HT7 receptors by RNA interference produced anxiolytic effects in sham and 6-hydroxydopamine-lesioned rats. And intra-BLA injection of 5-HT7 receptor agonist AS19 and antagonist SB269970 induced anxiogenic and anxiolytic responses in the two groups of rats. Further, intra-BLA injection of AS19 and SB269970 increased and decreased the mean firing rate of BLA glutamatergic neurons and vHPC extracellular glutamate levels in sham and the lesioned rats, respectively. Compared to sham rats, the effects of AS19 and SB269970 on the anxiety-related behaviors, firing activity and transmitter levels were decreased in the lesioned rats, which are associated with decreased expression of 5-HT7 receptors on BLAGlu-vHPC pathway after substantia nigra pars compacta lesion. Collectively, these results suggest that activation and blockade of 5-HT7 receptors on the BLAGlu-vHPC pathway are involved in the regulation of PD-related anxiety, and dopaminergic lesion decreases the expression of 5-HT7 receptors on this neural pathway.
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Affiliation(s)
- Jie Yang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Yuan Guo
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Li Zhang
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Shasha Gao
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China
| | - Jian Liu
- Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an 710061, China.
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2
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Cao X, Zhang Y, Wu H, Da H, Xiao Q, Shi H. Decoding depression: How DLPFC and SMA mediate stress perception's role in mental health? J Affect Disord 2025; 379:323-331. [PMID: 40086480 DOI: 10.1016/j.jad.2025.03.036] [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: 11/02/2024] [Revised: 03/04/2025] [Accepted: 03/10/2025] [Indexed: 03/16/2025]
Abstract
BACKGROUND Depression is a common mental disorder that significantly impacts global well-being. Although stress is a major contributor to depression, not all stress leads to depressive outcomes due to differences in stress perception. Understanding the neural mechanisms of stress perception may help identify biomarkers for targeted interventions to alleviate stress-related depression. METHODS This study included 113 participants. Each participant completed a Verbal Fluency Task (VFT) while undergoing functional near-infrared spectroscopy (fNIRS) to monitor brain activity. Oxyhemoglobin (Oxy-Hb) concentration data were analyzed using Matlab, and PROCESS v4.1 to examine neural mechanisms connecting stress perception and depression. RESULTS Correlation analysis showed a significant negative association between depression severity and Oxy-Hb concentration in several brain regions, including the bilateral dorsolateral prefrontal cortex (DLPFC), bilateral Broca's area (BA), right frontal pole (FP), and right orbitofrontal cortex (OFC). Mediation and moderation analyses revealed that the bilateral DLPFC serves as a key mediator in the relationship between stress perception and depression, with the supplementary motor area (SMA) acts as a moderator. Functional differentiation was observed, with the left DLPFC and left SMA influencing the effect of nervous on depression, and the right DLPFC and right SMA influencing the effect of uncontrolled on depression. CONCLUSION The bilateral DLPFC and SMA play critical roles in mediating and moderating stress perception's impact on depression, suggesting these regions as potential targets for interventions in stress-related depressive disorders.
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Affiliation(s)
- Xiaochen Cao
- School of Education, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Yan Zhang
- School of Education, Huazhong University of Science and Technology, Wuhan 430074, China.
| | - Huifen Wu
- School of Education, Hubei Engineering University, Xiaogan 432000, China
| | - Hui Da
- School of Education, Huazhong University of Science and Technology, Wuhan 430074, China
| | - Qiang Xiao
- Department of Neurology, Hospital of Huazhong University of Science and Technology, Wuhan 430074, China
| | - Hui Shi
- The Department of Cardio-Psychiatry Liaison Consultation, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
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Li L, Sun M, Qi M, Li Y, Li D. Neural correlates of emotional working memory predict depression and anxiety. Front Neurosci 2025; 19:1574901. [PMID: 40438625 PMCID: PMC12116434 DOI: 10.3389/fnins.2025.1574901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2025] [Accepted: 04/28/2025] [Indexed: 06/01/2025] Open
Abstract
Introduction Emotional working memory (WM) plays a critical role in cognitive functions such as emotion regulation, decision-making, and learning. Understanding how emotional stimuli, particularly negative ones, affect WM performance is crucial for identifying cognitive markers of mental health issues like anxiety and depression. Our objective is to determine whether trait anxiety and depression levels are associated with specific performance outcomes in emotional WM and whether behavioral and neural indicators demonstrate statistically significant correlations with individual anxiety and depression levels in university students. Methods In our research: Experiment 1 (n = 25) tested WM performance with both positive and negative emotional stimuli under different cognitive loads (2 vs. 4 items), while Experiment 2 (n = 34) combined EEG recording to investigate the neural index of anxiety and depression during negative emotional WM. Results Results showed that negative emotional stimuli impaired WM performance, especially under higher cognitive loads, with anxiety level being linked to increased theta activity during encoding and depression level associated with decreased alpha activity during retrieval. Additionally, individuals with higher anxiety exhibited reduced sensitivity to cognitive load differences in WM tasks involving negative emotions. Discussion These results demonstrated that specific EEG patterns during negative emotional WM were significantly associated with individual anxiety and depression levels, suggesting the potential utility of EEG measures for identifying at-risk individuals of anxiety and depression in university student populations. By linking cognitive and neural indicators, the study contributes to the development of personalized interventions for mental health monitoring and treatment.
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Affiliation(s)
- Leiting Li
- Department of Psychology, Beijing Sport University, Beijing, China
- Department of Psychology, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai, China
| | - Meirong Sun
- Department of Psychology, Beijing Sport University, Beijing, China
- Laboratory of Sports Stress and Adaptation of General Administration of Sport, Beijing Sport University, Beijing, China
- Key Laboratory of Exercise and Physical Fitness (Beijing Sport University), Ministry of Education, Beijing, China
| | - Mengdi Qi
- Experimental Teaching Platform, Beijing Normal University, Zhuhai, China
| | - Yiwen Li
- State Key Laboratory of Cognitive Neuroscience and Learning & IDG/McGovern Institute for Brain Research, Beijing Normal University, Beijing, China
| | - Dongwei Li
- Department of Psychology, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai, China
- Beijing Key Laboratory of Applied Experimental Psychology, National Demonstration Center for Experimental Psychology Education, Faculty of Psychology, Beijing Normal University, Beijing, China
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Pruett DG, Hunter C, Scartozzi A, Shaw DM, Kraft SJ, Jones RM, Shuey MM, Below JE. Characterizing drug-induced stuttering in electronic health records. JOURNAL OF COMMUNICATION DISORDERS 2025; 113:106475. [PMID: 39615072 PMCID: PMC11948996 DOI: 10.1016/j.jcomdis.2024.106475] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 10/29/2024] [Accepted: 11/01/2024] [Indexed: 02/09/2025]
Abstract
PURPOSE Drug-induced stuttering is a phenomenon where the onset of stuttered speech is caused by exposure to pharmaceutical chemical substances. This acquired form of stuttering features many of the same overt speech behaviors as developmental stuttering. Investigations of drug-induced stuttering have been limited to adverse drug reaction reports and case studies. This study leveraged electronic health records (EHRs) at a major university medical center to identify drug-induced stuttering within medical notes, followed by classification of implicated drug types. METHODS A previous systematic EHR review of approximately 3 million individuals to identify cases of developmental stuttering resulted in 40 suspected cases of drug-induced stuttering. In the present study, these cases were reviewed comprehensively to evaluate: name, class, and mechanism of action of suspected drug, level of evidence for the implicated drug as a causal agent, therapeutic measures taken, and progression or remission of stuttering. RESULTS Eighteen different drugs were linked to possible drug-induced stuttering in 22 individuals. Antiseizure agents, CNS stimulants, and antidepressants were the most common drug classes implicated in drug-induced stuttering. topiramate (Topamax) was the most commonly implicated drug across all records reviewed. CONCLUSIONS This study represents the first analysis of health system data examining drugs implicated in drug-induced stuttering in a clinical setting. Augmenting previous case reports and database reviews, a variety of drugs were identified; however, improved reporting of drug-associated speech fluency changes within the EHR are needed to further amass evidence for suspected drugs and their associated epidemiological and clinical characteristics.
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Affiliation(s)
- Dillon G Pruett
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, USA.
| | - Christine Hunter
- Lipscomb University College of Pharmacy and Health Sciences, USA
| | - Alyssa Scartozzi
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, USA
| | - Douglas M Shaw
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, USA
| | - Shelly Jo Kraft
- Department of Communication Sciences and Disorders, Wayne State University, USA
| | - Robin M Jones
- Department of Hearing and Speech Sciences, Vanderbilt University Medical Center, USA
| | - Megan M Shuey
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, USA
| | - Jennifer E Below
- Vanderbilt Genetics Institute, Vanderbilt University Medical Center, USA
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Yaeger JDW, Achua JK, Booth CD, Khalid D, John MM, Ledesma LJ, Greschke TL, Potter AM, Howe CB, Krupp KT, Smith JP, Ronan PJ, Summers CH. Learned phenotypes emerge during social stress modifying hippocampal orexin receptor gene expression. Sci Rep 2024; 14:31691. [PMID: 39738291 PMCID: PMC11685668 DOI: 10.1038/s41598-024-81590-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/01/2024] [Accepted: 11/27/2024] [Indexed: 01/01/2025] Open
Abstract
Psychological distress, including anxiety or mood disorders, emanates from the onset of chronic/unpredictable stressful events. Symptoms in the form of maladaptive behaviors are learned and difficult to treat. While the origin of stress-induced disorders seems to be where learning and stress intersect, this relationship and molecular pathways involved remain largely unresolved. The hippocampus, studied for its role in learning, is divided into regions that designate the passage of neuronal signaling during memory formation, including dentate gyrus (DG), CA3, CA2, and CA1. Inputs into these hippocampal subregions, like those from hypothalamic orexinergic neurons, may modify learning outcomes. We have previously shown the orexin system to balance stress states, where receptor subtypes prompt opposing actions on behavior. Here, we explore the connection between hippocampal orexin receptors and learning during stress. In a social stress/learning paradigm separating mice into stress resilient and vulnerable populations, hippocampal Orx1R and Orx2R transcription is regulated in a phenotype-dependent fashion. We further identified Orx1R as highly expressed in the hilus of DG, while Orx2R is abundant in CA2. Finally, we designed an experiment where mice were provided prior exposure to a stressful environment, which ultimately modified behavior, as well as transcription of hippocampal orexin receptors.
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Affiliation(s)
- Jazmine D W Yaeger
- Cellular Therapies and Stem Cell Biology Group, Sanford Research, 2301 E. 60th St. N., Sioux Falls, SD, 57104, USA
| | - Justin K Achua
- Division of Urology, University of Colorado School of Medicine, Anschutz Medical Campus, Aurora, CO, 80045, USA
| | - Clarissa D Booth
- Pediatrics and Rare Diseases Group, Sanford Research, 2301 E. 60th St. N., Sioux Falls, SD, 57104, USA
| | - Delan Khalid
- School of Medicine, BMP, University of Pittsburgh, 3500 Fifth Ave., Pittsburg, PA, 12213, USA
| | - Megan M John
- Department of Biology, University of South Dakota, 414 East Clark Street, Vermillion, SD, 57069-2390, USA
- Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, 57069, USA
- Veterans Affairs Research Service, Sioux Falls VA Health Care System, Sioux Falls, SD, 57105, USA
| | - Leighton J Ledesma
- Department of Biology, University of South Dakota, 414 East Clark Street, Vermillion, SD, 57069-2390, USA
- Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, 57069, USA
| | - Trent L Greschke
- Department of Biology, University of South Dakota, 414 East Clark Street, Vermillion, SD, 57069-2390, USA
| | - Ashley M Potter
- Department of Clinical Sciences, Colorado State University, Fort Collins, CO, 80521, USA
| | - Chase B Howe
- Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, 57069, USA
| | - Kevin T Krupp
- Department of Biology, University of South Dakota, 414 East Clark Street, Vermillion, SD, 57069-2390, USA
- Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, 57069, USA
| | | | - Patrick J Ronan
- Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, 57069, USA
- Veterans Affairs Research Service, Sioux Falls VA Health Care System, Sioux Falls, SD, 57105, USA
- Department of Psychiatry, Sanford School of Medicine, University of South Dakota, Sioux Falls, SD, 57105, USA
- Laboratory for Clinical and Translational Research in Psychiatry, Department of Veterans Affairs Medical Center, Denver, CO, 80220, USA
| | - Cliff H Summers
- Department of Biology, University of South Dakota, 414 East Clark Street, Vermillion, SD, 57069-2390, USA.
- Neuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, 57069, USA.
- Veterans Affairs Research Service, Sioux Falls VA Health Care System, Sioux Falls, SD, 57105, USA.
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Díaz DE, Becker HC, Fitzgerald KD. Neural Markers of Treatment Response in Pediatric Anxiety and PTSD. Curr Top Behav Neurosci 2024:10.1007/7854_2024_547. [PMID: 39673034 PMCID: PMC12166094 DOI: 10.1007/7854_2024_547] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2024]
Abstract
Pediatric anxiety disorders and post-traumatic stress disorder (PTSD) are associated with elevated threat sensitivity and impaired emotion regulation, accompanied by dysfunction in the neural circuits involved in these processes. Despite established treatments like cognitive behavioral therapy (CBT) and selective serotonin reuptake inhibitors, many children do not achieve remission, underscoring the importance of understanding the neurobiological underpinnings of these disorders. This review synthesizes current research on the neural predictors of treatment response and the neurofunctional changes associated with treatment in pediatric anxiety and PTSD during threat and reward processing. Several key findings emerged. First, enhanced threat/safety discrimination in the amygdala predicted better outcomes of pediatric anxiety and PTSD treatments. Second, differences in pretreatment activation within the lateral prefrontal and dorsal anterior cingulate cortices predicted treatment response, likely reflecting baseline executive control differences. Third, post-CBT decreases in activation in default mode, visuo-attentional, and sensorimotor areas may support treatment-related increases in task engagement. Finally, functional connectivity between the amygdala and other limbic, prefrontal, and default mode network nodes predicts treatment response in anxiety and PTSD, highlighting its potential as a biomarker for therapeutic efficacy. Understanding these neurofunctional markers could lead to more targeted interventions, optimizing treatment planning and potentially leading to the development of "pretreatment" strategies to enhance the efficacy of existing treatments. This review highlights the necessity for future research to establish more direct links between neuroimaging findings and clinical outcomes to facilitate the translation of these findings into clinical practice.
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Affiliation(s)
- Dana E Díaz
- Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA
| | - Hannah C Becker
- Department of Psychology, University of Michigan, Ann Arbor, MI, USA
| | - Kate D Fitzgerald
- Department of Psychiatry, Columbia University Irving Medical Center, New York, NY, USA.
- New York State Psychiatric Institute, New York, NY, USA.
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7
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Li Y, Yan S, Li J, Qin Y, Li L, Shen N, Xie Y, Liu D, Fang J, Tian T, Zhu W. Regional homogeneity patterns reveal the genetic and neurobiological basis of State-Trait Anxiety. BMC Psychiatry 2024; 24:837. [PMID: 39567951 PMCID: PMC11577826 DOI: 10.1186/s12888-024-06291-0] [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: 04/16/2024] [Accepted: 11/12/2024] [Indexed: 11/22/2024] Open
Abstract
OBJECTIVE State anxiety and trait anxiety are differentially mapped in brain function. However, the genetic and neurobiological basis of anxiety-related functional changes remain largely unknown. METHODS Participants aged 18-30 from the community underwent resting-state fMRI and were assessed with the State-Trait Anxiety Inventory. Using a general linear regression model, we analyzed the effects of state and trait anxiety, as well as their sum and difference (delta), on regional homogeneity (ReHo) in cortical areas. ReHo patterns denote the spatial distribution of ReHo associated with anxiety scores. We further explored the spatial correlations between ReHo patterns and neuromaps, including gene expression, neurotransmitter receptor density, myelination, and functional connectivity gradients, to elucidate the genetic and molecular substrates of these ReHo patterns. RESULTS Our findings demonstrated robust spatial correlations between whole-brain ReHo patterns for state and trait anxiety, with trait anxiety and the delta value exhibiting stronger network correlations, notably in the dorsal attention, salience, visual, and sensorimotor networks. Genes highly correlated with ReHo patterns exhibited unique spatiotemporal expression patterns, involvement in oxidative stress, metabolism, and response to stimuli, and were expressed in specific cell types. Furthermore, ReHo patterns significantly correlated with neuromaps of neurotransmitter receptor density, myelination, and functional connectivity gradients. CONCLUSIONS The ReHo patterns associated with anxiety may be driven by genetic and neurobiological traits. Our findings contribute to a deeper understanding of the pathogenesis of anxiety from a genetic and molecular perspective.
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Affiliation(s)
- Yuanhao Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, P.R. China
| | - Su Yan
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, P.R. China
| | - Jia Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, P.R. China
| | - Yuanyuan Qin
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, P.R. China
| | - Li Li
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, P.R. China
| | - Nanxi Shen
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, P.R. China
| | - Yan Xie
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, P.R. China
| | - Dong Liu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, P.R. China
| | - Jicheng Fang
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, P.R. China
| | - Tian Tian
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, P.R. China.
| | - Wenzhen Zhu
- Department of Radiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, 430030, P.R. China.
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Ristvedt SL. The risks of unconcern: low sensitivity to threat can have unfortunate consequences. Front Psychol 2024; 15:1390968. [PMID: 39606192 PMCID: PMC11598515 DOI: 10.3389/fpsyg.2024.1390968] [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: 02/24/2024] [Accepted: 10/30/2024] [Indexed: 11/29/2024] Open
Abstract
Each one of us is confronted with warnings of danger or threats to wellbeing in our everyday life, whether in the form of certain road signs, Public Service Announcements, ominous changes in bodily functioning, or cautionary tales heard from family or friends. There is great inter-individual variation in how people respond to such threats, with some people habitually tending to ignore or dismiss them, often to their peril. The first purpose of the present paper is to review several studies showing that individuals-most often men-who score very low on measures of trait anxiety are more likely to engage in behaviors that could jeopardize their physical wellbeing. The general hypothesis that is derived from that review is that when attention to everyday threats is chronically muted by way of a dispositional trait, the likelihood of proceeding down some dangerous path is increased. Those findings are then discussed within the broader context of personality theory to highlight the importance of recognizing the bipolarity of common traits. Here the case is made for replacing the term trait anxiety with the term threat sensitivity in order to capture the full breadth of this basic personality variable. A discussion of the neurobiological underpinnings of threat sensitivity is then presented with an emphasis on individual and sex differences in the workings of the defensive survival circuitry. Taken together, this paper has implications for two subfields within psychology. For the area of personality theory, this paper provides support for the adaptationist view with the argument that low threat sensitivity has both adaptive and maladaptive potential. For the area of health psychology, it is argued that some individuals who demonstrate a habitual tendency to neglect their physical wellbeing may be acting-at least in part-in accordance with their innate neurobiological constitution.
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Affiliation(s)
- Stephen L. Ristvedt
- Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO, United States
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9
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Ma K, Zhang D, McDaniel K, Webb M, Newton SS, Lee FS, Qin L. A sexually dimorphic signature of activity-dependent BDNF signaling on the intrinsic excitability of pyramidal neurons in the prefrontal cortex. Front Cell Neurosci 2024; 18:1496930. [PMID: 39569070 PMCID: PMC11576208 DOI: 10.3389/fncel.2024.1496930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2024] [Accepted: 10/25/2024] [Indexed: 11/22/2024] Open
Abstract
Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders with strong genetic heterogeneity and more prevalent in males than females. We and others hypothesize that diminished activity-dependent neural signaling is a common molecular pathway dysregulated in ASD caused by diverse genetic mutations. Brain-derived neurotrophic factor (BDNF) is a key growth factor mediating activity-dependent neural signaling in the brain. A common single nucleotide polymorphism (SNP) in the pro-domain of the human BDNF gene that leads to a methionine (Met) substitution for valine (Val) at codon 66 (Val66Met) significantly decreases activity-dependent BDNF release without affecting basal BDNF secretion. By using mice with genetic knock-in of this human BDNF methionine (Met) allele, our previous studies have shown differential severity of autism-like social deficits in male and female BDNF+/Met mice. Pyramidal neurons are the principal neurons in the prefrontal cortex (PFC), a key brain region for social behaviors. Here, we investigated the impact of diminished activity-dependent BDNF signaling on the intrinsic excitability of pyramidal neurons in the PFC. Surprisingly, diminished activity-dependent BDNF signaling significantly increased the intrinsic excitability of pyramidal neurons in male mice, but not in female mice. Notably, significantly decreased thresholds of action potentials were observed in male BDNF+/Met mice, but not in female BDNF+/Met mice. Voltage-clamp recordings revealed that the sodium current densities were significantly increased in the pyramidal neurons of male BDNF+/Met mice, which were mediated by increased transcriptional level of Scn2a encoding sodium channel NaV 1.2. Medium after hyperpolarization (mAHP), another important parameter to determine intrinsic neuronal excitability, is strongly associated with neuronal firing frequency. Further, the amplitudes of mAHP were significantly decreased in male BDNF+/Met mice only, which were mediated by the downregulation of Kcnn2 encoding small conductance calcium-activated potassium channel 2 (SK2). This study reveals a sexually dimorphic signature of diminished activity-dependent BDNF signaling on the intrinsic neuronal excitability of pyramidal neurons in the PFC, which provides possible cellular and molecular mechanisms underpinning the sex differences in idiopathic ASD patients and human autism victims who carry BDNF Val66Met SNP.
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Affiliation(s)
- Kaijie Ma
- Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States
| | - Daoqi Zhang
- Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States
| | - Kylee McDaniel
- Department of Biotechnology, Mount Marty University, Yankton, SD, United States
| | - Maria Webb
- School of Health Sciences, University of South Dakota, Vermillion, SD, United States
| | - Samuel S. Newton
- Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States
| | - Francis S. Lee
- Department of Psychiatry, Department of Pharmacology, Sackler Institute for Developmental Psychobiology, Weill Cornell Medicine, New York, NY, United States
| | - Luye Qin
- Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States
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10
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Fujimoto S, Fujimoto A, Elorette C, Choi KS, Mayberg H, Russ B, Rudebeck P. What can neuroimaging of neuromodulation reveal about the basis of circuit therapies for psychiatry? Neuropsychopharmacology 2024; 50:184-195. [PMID: 39198580 PMCID: PMC11526173 DOI: 10.1038/s41386-024-01976-2] [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: 05/17/2024] [Revised: 07/23/2024] [Accepted: 07/29/2024] [Indexed: 09/01/2024]
Abstract
Neuromodulation is increasingly becoming a therapeutic option for treatment resistant psychiatric disorders. These non-invasive and invasive therapies are still being refined but are clinically effective and, in some cases, provide sustained symptom reduction. Neuromodulation relies on changing activity within a specific brain region or circuit, but the precise mechanisms of action of these therapies, is unclear. Here we review work in both humans and animals that has provided insight into how therapies such as deep brain and transcranial magnetic stimulation alter neural activity across the brain. We focus on studies that have combined neuromodulation with neuroimaging such as PET and MRI as these measures provide detailed information about the distributed networks that are modulated and thus insight into both the mechanisms of action of neuromodulation but also potentially the basis of psychiatric disorders. Further we highlight work in nonhuman primates that has revealed how neuromodulation changes neural activity at different scales from single neuron activity to functional connectivity, providing key insight into how neuromodulation influences the brain. Ultimately, these studies highlight the value of combining neuromodulation with neuroimaging to reveal the mechanisms through which these treatments influence the brain, knowledge vital for refining targeted neuromodulation therapies for psychiatric disorders.
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Affiliation(s)
- Satoka Fujimoto
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Lipschultz Center for Cognitive Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Atsushi Fujimoto
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Lipschultz Center for Cognitive Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Catherine Elorette
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Lipschultz Center for Cognitive Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Ki Sueng Choi
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Departments of Radiology and Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Helen Mayberg
- Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Departments of Radiology and Neurosurgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
- Department of Neurology and Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Brian Russ
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Lipschultz Center for Cognitive Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Center for Biomedical Imaging and Neuromodulation, Nathan Kline Institute, Orangeburg, NY, USA.
- Department of Psychiatry, New York University at Langone, New York, NY, USA.
| | - Peter Rudebeck
- Nash Family Department of Neuroscience and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
- Lipschultz Center for Cognitive Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
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11
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Chu LH, Chau CQ, Kamel N, Thanh HHT, Yahya N. Functional excitation-inhibition ratio for social anxiety analysis and severity assessment. Front Psychiatry 2024; 15:1461290. [PMID: 39502299 PMCID: PMC11536370 DOI: 10.3389/fpsyt.2024.1461290] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2024] [Accepted: 10/07/2024] [Indexed: 11/08/2024] Open
Abstract
Introduction Social anxiety disorder (SAD) is a prevalent psychiatric condition characterized by an intense fear of and avoidance of social situations. Traditional assessment methods for SAD primarily rely on subjective self-report questionnaires and clinical interviews, which can be prone to biases and inaccuracies. This study aims to explore the functional excitation-inhibition (fEI) ratio derived from EEG data as a potential objective biomarker for assessing SAD severity. Methods Resting-state EEG data were collected from 20 control subjects and 60 individuals with varying degrees of SAD severity (mild, moderate, and severe). The fEI ratio was estimated across different EEG bands and analyzed, focusing on differences between control subjects and SAD groups. Results Significantly higher fEI ratios were observed in the alpha and low beta EEG bands in individuals with SAD compared to controls, especially within the prefrontal cortex. Additionally, a positive correlation was found between the fEI ratio and the severity of social anxiety symptoms across SAD severity levels. Discussion The findings indicate that the fEI ratio in the alpha and low beta bands may serve as a promising biomarker for assessing SAD severity. These results contribute to a deeper understanding of the neural mechanisms underlying social anxiety, offering a potentially more objective approach to SAD assessment compared to traditional methods.
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Affiliation(s)
- Linh Ha Chu
- College of Engineering and Computer Science, Center of Environmental Intelligence (CEI), Vin University, Hanoi, Vietnam
| | - Chi Que Chau
- College of Engineering and Computer Science, Center of Environmental Intelligence (CEI), Vin University, Hanoi, Vietnam
| | - Nidal Kamel
- College of Engineering and Computer Science, Center of Environmental Intelligence (CEI), Vin University, Hanoi, Vietnam
| | - Huong Ha Thi Thanh
- Department of Tissue Engineering and Regenerative Medicine, School of Biomedical Engineering, International University, Vietnam National University, Ho Chi Minh City, Vietnam
| | - Norashikin Yahya
- Department of Electrical and Electronics Engineering, Universiti Teknologi PETRONAS (UTP), Bandar Seri Iskandar, Malaysia
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12
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Wang C, Zhang Y, Chong JS, Zhang W, Zhang X, McIntyre RS, Li Z, Ho RCM, Tang TB, Lim LG. Altered functional connectivity subserving expressed emotion environments in schizophrenia: An fNIRS study. Schizophr Res 2024; 270:178-187. [PMID: 38917555 DOI: 10.1016/j.schres.2024.06.019] [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: 12/20/2023] [Revised: 04/16/2024] [Accepted: 06/15/2024] [Indexed: 06/27/2024]
Abstract
Living in high-expressed emotion (EE) environments, characterized by critical, hostile, or over-involved family attitudes, has been linked to increased relapse rates among individuals with schizophrenia (SZ). In our previous work (Wang et al., 2023), we conducted the first feasibility study of using functional near-infrared spectroscopy (fNIRS) with our developed EE stimuli to examine cortical hemodynamics in SZ. To better understand the neural mechanisms underlying EE environmental factors in SZ, we extended our investigation by employing functional connectivity (FC) analysis with a graph theory approach to fNIRS signals. Relative to healthy controls (N=40), individuals with SZ (N=37) exhibited altered connectivity across the medial prefrontal cortex (mPFC), left ventrolateral prefrontal cortex (vlPFC), and left superior temporal gyrus (STG) while exposed to EE environments. Notably, while individuals with SZ were exposed to high-EE environments, (i) reduced connectivity was observed in these brain regions and (ii) the left vlPFC-STG coupling was found to be associated with the negative symptom severity. Taken together, our FC findings suggest individuals with SZ experience a more extensive disruption in neural functioning and coordination, particularly indicating an increased susceptibility to high-EE environments. This further supports the potential utility of integrating fNIRS with the created EE stimuli for assessing EE environmental influences, paving the way for more targeted therapeutic interventions.
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Affiliation(s)
| | | | - Jie Sheng Chong
- Centre for Intelligent Signal and Imaging Research (CISIR), Universiti Teknologi PETRONAS, Seri Iskandar 32610, Perak, Malaysia
| | | | - Xi Zhang
- Huaibei Mental Health Center, China
| | - Roger S McIntyre
- Mood Disorders Psychopharmacology Unit, Poul Hansen Family Centre for Depression, Canada; Department of Pharmacology and Toxicology, University of Toronto, Toronto, Canada; Department of Psychiatry, University of Toronto, Toronto, Canada; Brain and Cognition Discovery Foundation, Toronto, Canada
| | - Zhifei Li
- Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, 119077, Singapore
| | - Roger C M Ho
- Institute for Health Innovation and Technology (iHealthtech), National University of Singapore, 119077, Singapore; Department of Psychological Medicine, Yong Loo Lin School of Medicine, National University of Singapore, 119228, Singapore; Division of Life Science (LIFS), Hong Kong University of Science and Technology, Hong Kong
| | - Tong Boon Tang
- Centre for Intelligent Signal and Imaging Research (CISIR), Universiti Teknologi PETRONAS, Seri Iskandar 32610, Perak, Malaysia
| | - Lam Ghai Lim
- Department of Electrical and Robotics Engineering, School of Engineering, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia; Medical Engineering & Technology Hub, School of Engineering, Monash University Malaysia, Jalan Lagoon Selatan, Bandar Sunway 47500, Selangor, Malaysia.
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13
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Kim SK, Choi H. Effects of coaches' autonomy support on athletes' aggressive behavior and athlete burnout: verification of the mediating effects of coach-athlete relationship and team efficacy. Front Psychol 2024; 15:1388185. [PMID: 39139597 PMCID: PMC11320840 DOI: 10.3389/fpsyg.2024.1388185] [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: 02/19/2024] [Accepted: 06/25/2024] [Indexed: 08/15/2024] Open
Abstract
Purpose This study investigated the relationships between perceived autonomy support, coach-athlete relationship, team efficacy, aggressive behavior, and athlete burnout among team sports athletes. It verified the mediating effects of the coach-athlete relationship and team efficacy on the relationship between autonomy support and athlete burnout. Design methodology and approach A questionnaire survey on autonomy support, coach-athlete relationships, aggressive behavior, and athlete burnout was administered to 336 team sports athletes (292 male athletes and 44 female athletes). A cross-sectional research design was used to collect the data. To analyze the collected data, frequency, reliability, descriptive statistical, and correlation analyses were performed using SPSS version 26.0. In addition, confirmatory factor analysis, convergent validity tests, and structural model analysis were conducted using AMOS version 24.0. Bootstrapping was used to examine the mediating effects. Results The fit of the measurement model was assessed by calculating the fit indices as follows: x 2 = 329.689, df = 124, p < 0.001, TLI = 0.945, CFI = 0.956, RMSEA = 0.070 (90% CI = 0.061-0.080), and SRMR = 0.060. Autonomy support positively affected the coach-athlete relationship (β = 0.841) and team efficacy (β = 0.338). The coach-athlete relationship positively affected team efficacy (β = 0.479). Furthermore, autonomy support did not significantly influence aggressive behavior (β = -0.053), and negatively affected athlete burnout (β = -0.305). The coach-athlete relationship also did not significantly affect aggressive behavior (β = 0.054), and negatively affected athlete burnout (β = -0.303). Team efficacy negatively affected aggressive behavior (β = -0.516) and athlete burnout (β = -0.201). Finally, autonomy support was found to affect athlete burnout through the coach-athlete relationship and team efficacy. Conclusion Considering that autonomy support affects athlete burnout through coach-athlete relationship and team efficacy, coaches need to enhance the quality of the coach-athlete relationship and improve team efficacy to reduce athlete burnout. Above all, the study findings suggest that coaches need to provide autonomy-supportive behaviors.
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Affiliation(s)
- Suk-Kyu Kim
- Dongguk University WISE, Gyeongju, Republic of Korea
| | - Hunhyuk Choi
- Kangwon National University, Chuncheon, Republic of Korea
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14
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Lueke NA, Assar A. Poor sleep quality and reduced immune function among college students: Perceived stress and depression as mediators. JOURNAL OF AMERICAN COLLEGE HEALTH : J OF ACH 2024; 72:1112-1119. [PMID: 35549834 DOI: 10.1080/07448481.2022.2068350] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 03/02/2022] [Accepted: 04/10/2022] [Indexed: 06/15/2023]
Abstract
OBJECTIVES Sleep problems are highly prevalent among college students and are linked to a multitude of detrimental consequences, among which are heightened perceived stress and symptoms of depression. The present study investigated the effect of poor sleep quality on the immune function of college students. A serial mediation model was developed to test the prediction that perceived stress and depression sequentially mediate the relationship between poor sleep quality and reduced immune function among college students. PARTICIPANTS 137 undergraduates were recruited from a large Midwestern university (103Females, 34Males; Mage = 19.47, SDage = ± 1.54). METHODS Cross-sectional based online survey administered in Spring 2021. RESULTS Analyses revealed a significant total effect of sleep quality on immune function. Perceived stress and depression symptoms serially mediated the relationship between sleep quality and immune function. CONCLUSIONS Results underscore the importance of college students' sleep in relation to their mental health and subsequent immune function.
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Affiliation(s)
- Niloufar A Lueke
- Department of Psychological Science, Ball State University, Muncie, IN, USA
| | - Arash Assar
- Department of Psychological Science, Ball State University, Muncie, IN, USA
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15
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Zanoaga MD, Friligkou E, He J, Pathak GA, Koller D, Cabrera-Mendoza B, Stein MB, Polimanti R. Brainwide Mendelian Randomization Study of Anxiety Disorders and Symptoms. Biol Psychiatry 2024; 95:810-817. [PMID: 37967698 PMCID: PMC10978301 DOI: 10.1016/j.biopsych.2023.11.006] [Citation(s) in RCA: 8] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2023] [Revised: 11/03/2023] [Accepted: 11/08/2023] [Indexed: 11/17/2023]
Abstract
BACKGROUND To gain insights into the role of brain structure and function on anxiety (ANX), we conducted a genetically informed investigation leveraging information from ANX genome-wide association studies available from the UK Biobank (n = 380,379), the FinnGen Program (n = 290,361), and the Million Veteran Program (n = 175,163) together with UK Biobank genome-wide data (n = 33,224) related to 3935 brain imaging-derived phenotypes (IDPs). METHODS A genetic correlation analysis between ANX and brain IDPs was performed using linkage disequilibrium score regression. To investigate ANX-brain associations, a 2-sample Mendelian randomization was performed considering multiple methods and sensitivity analyses. A subsequent multivariable Mendelian randomization was conducted to distinguish between direct and indirect effects. Finally, a generalized linear model was used to explore the associations of brain IDPs with ANX symptoms. RESULTS After false discovery rate correction (q < .05), we identified 41 brain IDPs genetically correlated with ANX without heterogeneity among the datasets investigated (i.e., UK Biobank, FinnGen, and Million Veteran Program). Six of these IDPs showed genetically inferred causal effects on ANX. In the subsequent multivariable Mendelian randomization analysis, reduced area of the right posterior middle cingulate gyrus (β = -0.09, p = 8.01 × 10-4) and reduced gray matter volume of the right anterior superior temporal gyrus (β = -0.09, p = 1.55 × 10-3) had direct effects on ANX. In the ANX symptom-level analysis, the right posterior middle cingulate gyrus was negatively associated with "tense, sore, or aching muscles during the worst period of anxiety" (β = -0.13, p = 8.26 × 10-6). CONCLUSIONS This study identified genetically inferred effects that are generalizable across large cohorts, thereby contributing to our understanding of how changes in brain structure and function can lead to ANX.
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Affiliation(s)
- Mihaela-Diana Zanoaga
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut
| | - Eleni Friligkou
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Veteran Affairs Connecticut Healthcare System, West Haven, Connecticut
| | - Jun He
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Veteran Affairs Connecticut Healthcare System, West Haven, Connecticut
| | - Gita A Pathak
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Veteran Affairs Connecticut Healthcare System, West Haven, Connecticut
| | - Dora Koller
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Department of Genetics, Microbiology, and Statistics, Faculty of Biology, University of Barcelona, Barcelona, Catalonia, Spain
| | - Brenda Cabrera-Mendoza
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Veteran Affairs Connecticut Healthcare System, West Haven, Connecticut
| | - Murray B Stein
- Department of Psychiatry, University of California, San Diego, La Jolla, California; Herbert Wertheim School of Public Health, University of California, San Diego, La Jolla, California; Veteran Affairs San Diego Healthcare System, San Diego, California
| | - Renato Polimanti
- Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut; Veteran Affairs Connecticut Healthcare System, West Haven, Connecticut; Wu Tsai Institute, Yale University, New Haven, Connecticut.
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16
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Boehme S, Herrmann MJ, Mühlberger A. Good moments to stimulate the brain - A randomized controlled double-blinded study on anodal transcranial direct current stimulation of the ventromedial prefrontal cortex on two different time points in a two-day fear conditioning paradigm. Behav Brain Res 2024; 460:114804. [PMID: 38103872 DOI: 10.1016/j.bbr.2023.114804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 11/30/2023] [Accepted: 12/06/2023] [Indexed: 12/19/2023]
Abstract
It is assumed that extinction learning is a suitable model for understanding the mechanisms underlying exposure therapy. Furthermore, there is evidence that non-invasive brain stimulation (NIBS) can elevate extinction learning by enhancing frontal brain activity and therefore NIBS can augment symptom reduction during exposure therapy in phobias. But, the underlying processes are still not well established. Open questions arise from NIBS time points and electrode placement, among others. Therefore, we investigated in a 2-day fear conditioning experiment, whether anodal transcranial direct current stimulation (tDCS) of the ventromedial prefrontal cortex (vmPFC) modulates either fear memory consolidation or dampened fear reaction during fear extinction. Sixty-six healthy participants were randomly assigned either to a group that received tDCS after fear acquisition (and before fear memory consolidation), to a group that received tDCS directly before fear extinction, or to a control group that never received active stimulation (sham). Differential skin conductance response (SCR) to CS+ vs. CS- was significantly decreased in both tDCS-groups compared to sham group. Our region of interest, the vmPFC, was stimulated best focally with a lateral anode position and a cathode on the contralateral side. But this comes along with a slightly lateral stimulation of vmPFC depending on whether anode is placed left or right. To avoid unintended effects of stimulated sides the two electrode montages (anode left or right) were mirror-inverted which led to differential effects in SCR and electrocortical (mainly late positive potential [LPP]) data in our exploratory analyses. Results indicated that tDCS-timing is relevant for fear reactions via disturbed fear memory consolidation as well as fear expression, and this depends on whether vmPFC is stimulated with either left- or right-sided anode electrode montage. Electrocortical data can shed more light on the underlying neural correlates and exaggerated LPP seems to be associated with disturbed fear memory consolidation and dampened SCR to CS+ vs. CS-, but solely in the right anode electrode montage. Further open questions addressing where and when to stimulate the prefrontal brain in the course of augmenting fear extinction are raised.
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Affiliation(s)
- Stephanie Boehme
- Department of Psychology, Chair for Clinical Psychology and Psychotherapy, Technische Universität Chemnitz, Wilhelm-Raabe-Straße 43, D-09120 Chemnitz, Germany; Department of Psychology, Clinical Psychology and Psychotherapy, University of Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany.
| | - Martin J Herrmann
- Center of Mental Health, Dept. of Psychiatry, Psychosomatics, and Psychotherapy, University Hospital of Wuerzburg, Margarete-Hoeppel-Platz 1, D-97080 Wuerzburg, Germany
| | - Andreas Mühlberger
- Department of Psychology, Clinical Psychology and Psychotherapy, University of Regensburg, Universitätsstraße 31, D-93053 Regensburg, Germany
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17
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Zhu MQ, Oliveros H, Marín C, Mora-Plazas M, Villamor E. Middle childhood and adolescence sleep duration and behavior problems in adolescence. Dev Psychopathol 2024; 36:338-348. [PMID: 36373262 DOI: 10.1017/s0954579422001237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
We examined the associations of middle childhood and adolescence nighttime sleep duration with adolescence internalizing and externalizing behavior problems per the Youth Self-Report (YSR) and the Child Behavior Checklist (CBCL) questionnaires, in a cohort of 889 Colombian schoolchildren. We estimated adjusted differences with 95% confidence intervals (CI) in mean behavior problem t-scores in standardized units between recommended sleep duration categories and as a continuous exposure using multiple linear regression and restricted cubic spline models, respectively. Compared with sleep duration within recommendations, middle childhood sleep above recommendations was related to 4.6 (95% CI: 1.6, 7.6; p = .004) and 5.4 (95% CI: 1.2, 9.7; p = .01) adjusted units higher YSR and CBCL externalizing problem scores, respectively. In continuous exposure analyses, this association seemed restricted to children aged ≥11 years. Longer sleep, both in categories and as a continuous exposure, was also associated with increased CBCL internalizing problems. Results did not differ by sex or weekend/weekday sleep. Sleeping under recommendations in middle childhood was not significantly related to behavior problems; nevertheless, shorter sleep in adolescence, in both categorical and continuous scales, was significantly related to behavior problems. In conclusion, behavior problems in adolescence are associated with longer sleep in middle childhood and shorter sleep in adolescence.
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Affiliation(s)
- Mia Q Zhu
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
| | - Henry Oliveros
- Facultad de Medicina, Universidad de La Sabana, Chía, Colombia
| | - Constanza Marín
- Facultad de Medicina, Universidad de La Sabana, Chía, Colombia
| | | | - Eduardo Villamor
- Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA
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18
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Riis T, Feldman D, Losser A, Mickey B, Kubanek J. Device for Multifocal Delivery of Ultrasound Into Deep Brain Regions in Humans. IEEE Trans Biomed Eng 2024; 71:660-668. [PMID: 37695955 PMCID: PMC10803076 DOI: 10.1109/tbme.2023.3313987] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/13/2023]
Abstract
Low-intensity focused ultrasound provides the means to noninvasively stimulate or release drugs in specified deep brain targets. However, successful clinical translations require hardware that maximizes acoustic transmission through the skull, enables flexible electronic steering, and provides accurate and reproducible targeting while minimizing the use of MRI. We have developed a device that addresses these practical requirements. The device delivers ultrasound through the temporal and parietal skull windows, which minimize the attenuation and distortions of the ultrasound by the skull. The device consists of 252 independently controlled elements, which provides the ability to modulate multiple deep brain targets at a high spatiotemporal resolution, without the need to move the device or the subject. And finally, the device uses a mechanical registration method that enables accurate deep brain targeting both inside and outside of the MRI. Using this method, a single MRI scan is necessary for accurate targeting; repeated subsequent treatments can be performed reproducibly in an MRI-free manner. We validated these functions by transiently modulating specific deep brain regions in two patients with treatment-resistant depression.
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19
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Cai Y, Ge J, Pan ZZ. The projection from dorsal medial prefrontal cortex to basolateral amygdala promotes behaviors of negative emotion in rats. Front Neurosci 2024; 18:1331864. [PMID: 38327845 PMCID: PMC10847313 DOI: 10.3389/fnins.2024.1331864] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2023] [Accepted: 01/10/2024] [Indexed: 02/09/2024] Open
Abstract
Brain circuits between medial prefrontal cortex (mPFC) and amygdala have been implicated in cortical control of emotion, especially anxiety. Studies in recent years focus on differential roles of subregions of mPFC and amygdala, and reciprocal pathways between mPFC and amygdala in regulation of emotional behaviors. It has been shown that, while the projection from ventral mPFC to basomedial amygdala has an anxiolytic effect, the reciprocal projections between dorsal mPFC (dmPFC) and basolateral amygdala (BLA) are generally involved in an anxiogenic effect in various conditions with increased anxiety. However, the function of the projection from dmPFC to BLA in regulation of general emotional behaviors under normal conditions remains unclear. In this study, we used optogenetic analysis to identify how this dmPFC-BLA pathway regulates various emotional behaviors in normal rats. We found that optogenetic stimulation of the dmPFC-BLA pathway promoted a behavioral state of negative emotion, increasing anxiety-like and depressive-like behaviors and producing aversive behavior of place avoidance. Conversely, optogenetic inhibition of this pathway produced opposite effects, reducing anxiety-like and depressive-like behaviors, and inducing behaviors of place preference of reward. These findings suggest that activity of the dmPFC-BLA pathway is sufficient to drive a negative emotion state and the mPFC-amygdala circuit is tonically active in cortical regulation of emotional behaviors.
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Affiliation(s)
| | | | - Zhizhong Z. Pan
- Department of Anesthesiology and Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, United States
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20
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Kim OY, Song J. Important roles of linoleic acid and α-linolenic acid in regulating cognitive impairment and neuropsychiatric issues in metabolic-related dementia. Life Sci 2024; 337:122356. [PMID: 38123015 DOI: 10.1016/j.lfs.2023.122356] [Citation(s) in RCA: 12] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2023] [Revised: 12/02/2023] [Accepted: 12/13/2023] [Indexed: 12/23/2023]
Abstract
Metabolic syndrome (MetS), which is characterized by insulin resistance, high blood glucose, obesity, and dyslipidemia, is known to increase the risk of dementia accompanied by memory loss and depression. The direct pathways and specific mechanisms in the central nervous system (CNS) for addressing fatty acid imbalances in MetS have not yet been fully elucidated. Among polyunsaturated acids, linoleic acid (LA, n6-PUFA) and α-linolenic acid (ALA, n3-PUFA), which are two essential fatty acids that should be provided by food sources (e.g., vegetable oils and seeds), have been reported to regulate various cellular mechanisms including apoptosis, inflammatory responses, mitochondrial biogenesis, and insulin signaling. Furthermore, inadequate intake of LA and ALA is reported to be involved in neuropathology and neuropsychiatric diseases as well as imbalanced metabolic conditions. Herein, we review the roles of LA and ALA on metabolic-related dementia focusing on insulin resistance, dyslipidemia, synaptic plasticity, cognitive function, and neuropsychiatric issues. This review suggests that LA and ALA are important fatty acids for concurrent treatment of both MetS and neurological problems.
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Affiliation(s)
- Oh Yoen Kim
- Department of Food Science and Nutrition, Dong A University, Busan, Republic of Korea; Department of Health Sciences, Graduate School of Dong-A University, Busan, Republic of Korea.
| | - Juhyun Song
- Department of Anatomy, Chonnam National University Medical School, Seoul, Republic of Korea.
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21
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Ringenbach SDR, Arnold NE, Tucker K, Rand MK, Studenka BE, Ringenbach SB, Chen CC. Assisted Cycle Therapy (ACT) Improved Self-Efficacy and Exercise Perception in Middle-Age Adults with Down Syndrome. Brain Sci 2023; 13:1719. [PMID: 38137167 PMCID: PMC10741653 DOI: 10.3390/brainsci13121719] [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: 11/06/2023] [Revised: 11/30/2023] [Accepted: 12/12/2023] [Indexed: 12/24/2023] Open
Abstract
Alzheimer's disease is prevalent in persons with Down syndrome (DS) as early as their 30s and presents as decreased social interaction, coordination, and physical activity. Therefore, changing attitudes and beliefs about exercise is key to increasing motivation for physical activity especially in middle-age adults with DS. The aim of this study was to examine the effects of Assisted Cycle Therapy (ACT) on self-efficacy and exercise perception in middle-age adults with Down syndrome (DS) following an exercise intervention three times a week for 8 weeks. Twelve participants were in the ACT group in which a motor assisted their cycling to be performed at least 30% faster than voluntary cycling (VC), 10 participants were in the voluntary cycling group, and two participants were in the no cycling (NC) group. The results showed that both exercise groups (i.e., ACT and VC) improved in their self-efficacy after the 8-week intervention. In addition, exercise perception improved following ACT, but not VC or NC. Our results are discussed with respect to their future implications for exercise in the DS population. The results can be attributed to differences in effort required by each intervention group as well as the neurotrophic factors that occur when muscle contractions create synaptic connections resulting in improvement in cognition and feelings of satisfaction.
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Affiliation(s)
- Shannon D. R. Ringenbach
- College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; (N.E.A.); (K.T.); (M.K.R.); (S.B.R.)
| | - Nathaniel E. Arnold
- College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; (N.E.A.); (K.T.); (M.K.R.); (S.B.R.)
| | - Kori Tucker
- College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; (N.E.A.); (K.T.); (M.K.R.); (S.B.R.)
| | - Miya K. Rand
- College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; (N.E.A.); (K.T.); (M.K.R.); (S.B.R.)
| | - Breanna E. Studenka
- Department of Kinesiology and Health Science, Utah State University, Logan, UT 84322, USA;
| | - Stockton B. Ringenbach
- College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA; (N.E.A.); (K.T.); (M.K.R.); (S.B.R.)
| | - Chih-Chia Chen
- Department of Kinesiology, Mississippi State University, Starkville, MS 39762, USA;
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Zhang S, Yang Q, Wei C, Shi X, Zhang Y. Study on the influence mechanism of perceived benefits on unsafe behavioral decision-making based on ERPs and EROs. Front Neurosci 2023; 17:1231592. [PMID: 38156269 PMCID: PMC10752936 DOI: 10.3389/fnins.2023.1231592] [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: 05/30/2023] [Accepted: 11/29/2023] [Indexed: 12/30/2023] Open
Abstract
Introduction Perceived benefits are considered one of the significant factors affecting an individual's decision-making process. Our study aimed to explore the influence mechanism of perceived benefits in the decision-making process of unsafe behaviors. Methods Our study used the "One Stimulus-Two Key Choice (S-K1/K2)" paradigm to conduct an EEG experiment. Participants (N = 18) made decisions in risky scenarios under high perceived benefits (HPB), low perceived benefits (LPB), and control conditions (CC). Time domain analysis and time-frequency analysis were applied to the recorded EEG data to extract ERPs (event-related potentials) and EROs (event-related oscillations), which include the P3 component, theta oscillations, alpha oscillations, and beta oscillations. Results Under the HPB condition, the theta power in the central (p = 0.016*) and occipital regions (p = 0.006**) was significantly decreased compared to the CC. Similarly, the alpha power in the frontal (p = 0.022*), central (p = 0.037*), and occipital regions (p = 0.014*) was significantly reduced compared to the CC. Under the LPB condition, theta power in the frontal (p = 0.026*), central (p = 0.028*), and occipital regions (p = 0.010*) was significantly reduced compared to the CC. Conversely, alpha power in the frontal (p = 0.009**), central (p = 0.012*), and occipital regions (p = 0.040*) was significantly increased compared to the HPB condition. Discussion The high perceived benefits may reduce individuals' internal attention and evoke individuals' positive emotions and motivation, leading individuals to underestimate risks. Consequently, they exhibited a greater inclination toward unsafe behaviors. However, the low perceived benefits may reduce individuals' memory review, resulting in a simple decision-making process, and they are more inclined to make fast decisions to avoid loss. The research results can help to provide targeted intervention measures, which are beneficial to reducing workers' unsafe behaviors.
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Affiliation(s)
- Shu Zhang
- School of Resources and Safety Engineering, Central South University, Changsha, China
| | - Qiyu Yang
- School of Resources and Safety Engineering, Central South University, Changsha, China
| | - Cong Wei
- School of Resources and Safety Engineering, Central South University, Changsha, China
| | - Xiuzhi Shi
- School of Resources and Safety Engineering, Central South University, Changsha, China
| | - Yan Zhang
- School of Educational Science, Huazhong University of Science and Technology, Wuhan, China
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23
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Zanoaga MD, Friligkou E, He J, Pathak GA, Koller D, Cabrera-Mendoza B, Stein MB, Polimanti R. Brain-Wide Mendelian Randomization Study of Anxiety Disorders and Symptoms. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2023:2023.09.12.23295448. [PMID: 37745546 PMCID: PMC10516096 DOI: 10.1101/2023.09.12.23295448] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/26/2023]
Abstract
Background To gain insights into the role of brain structure and function on anxiety (ANX), we conducted a genetically informed investigation leveraging information from ANX genome-wide association studies available from UK Biobank (UKB; N=380,379), FinnGen Program (N=290,361), and Million Veteran Program (MVP; N=199,611) together with UKB genome-wide data (N=33,224) related to 3,935 brain imaging-derived phenotypes (IDP). Methods A genetic correlation analysis between ANX and brain IDPs was performed using linkage disequilibrium score regression. To investigate ANX-brain associations, a two-sample Mendelian randomization (MR) was performed considering multiple methods and sensitivity analyses. A subsequent multivariable MR (MVMR) was executed to distinguish between direct and indirect effects. Finally, a generalized linear model was used to explore the associations of brain IDPs with ANX symptoms. Results After false discovery rate correction (FDR q<0.05), we identified 41 brain IDPs genetically correlated with ANX without heterogeneity among the datasets investigated (i.e., UKB, FinnGen, and MVP). Six of these IDPs showed genetically inferred causal effects on ANX. In the subsequent MVMR analysis, reduced area of the right posterior middle-cingulate gyrus (rpMCG; beta=-0.09, P= 8.01×10 -4 ) and reduced gray-matter volume of the right anterior superior temporal gyrus (raSTG; beta=-0.09, P=1.55×10 -3 ) had direct effects on ANX. In the ANX symptom-level analysis, rpMCG was negatively associated with "tense sore oraching muscles during the worst period of anxiety" (beta=-0.13, P=8.26×10 -6 ). Conclusions This study identified genetically inferred effects generalizable across large cohorts, contributing to understand how changes in brain structure and function can lead to ANX.
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24
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Saragosa-Harris NM, Guassi Moreira JF, Waizman YH, Sedykin A, Silvers JA, Peris TS. Neural representations of ambiguous affective stimuli and resilience to anxiety in emerging adults. Biol Psychol 2023; 182:108624. [PMID: 37394090 DOI: 10.1016/j.biopsycho.2023.108624] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/16/2022] [Revised: 04/18/2023] [Accepted: 06/26/2023] [Indexed: 07/04/2023]
Abstract
The tendency to interpret ambiguous stimuli as threatening has been associated with a range of anxiety disorders. Responses to ambiguity may be particularly relevant to mental health during the transition from adolescence to adulthood ("emerging adulthood"), when individuals encounter unfamiliar challenges and navigate novel social situations. However, it remains unclear whether neural representations of ambiguity relate to risk for anxiety. The present study sought to examine whether multivariate representations of ambiguity - and their similarity to representations of threat - relate to appraisals of ambiguity or anxiety in a sample of emerging adults. Participants (N = 41) viewed threatening (angry), nonthreatening (happy), and ambiguous (surprised) facial stimuli while undergoing fMRI. Outside of the scanner, participants were presented with the same stimuli and categorized the ambiguous faces as positive or negative. Using representational similarity analyses (RSA), we investigated whether the degree of pattern similarity in responses to ambiguous, nonthreatening, and threatening faces within the amygdala related to appraisals of ambiguous stimuli and anxiety symptomatology. We found that individuals who evidenced greater similarity (i.e., less differentiation) in neural representations of ambiguous and nonthreatening faces within the left amygdala reported lower concurrent anxiety. Additionally, trial-level pattern similarity predicted subsequent appraisals of ambiguous stimuli. These findings provide insight into how neural representations of ambiguity relate to risk or resilience for the development of anxiety.
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Affiliation(s)
- Natalie M Saragosa-Harris
- Department of Psychology, University of California Los Angeles, Los Angeles, CA 90095, United States.
| | - João F Guassi Moreira
- Department of Psychology, University of California Los Angeles, Los Angeles, CA 90095, United States
| | - Yael H Waizman
- Department of Psychology, University of California Los Angeles, Los Angeles, CA 90095, United States
| | - Anna Sedykin
- Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, United States
| | - Jennifer A Silvers
- Department of Psychology, University of California Los Angeles, Los Angeles, CA 90095, United States
| | - Tara S Peris
- Jane and Terry Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA 90095, United States
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25
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Klein RJ, Gyorda JA, Lekkas D, Jacobson NC. Dysregulated Emotion and Trying Substances in Childhood: Insights from a Large Nationally Representative Cohort Study. Subst Use Misuse 2023; 58:1625-1633. [PMID: 37572018 PMCID: PMC11000575 DOI: 10.1080/10826084.2023.2223290] [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] [Indexed: 08/14/2023]
Abstract
OBJECTIVE Transdiagnostic perspectives on the shared origins of mental illness posit that dysregulated emotion may represent a key driving force behind multiple forms of psychopathology, including substance use disorders. The present study examined whether a link between dysregulated emotion and trying illicit substances could be observed in childhood. METHOD In a large (N = 7,418) nationally representative sample of children (Mage = 9.9), individual differences in emotion dysregulation were indexed using child and parent reports of frequency of children's emotional outbursts, as well as children's performance on the emotional N-Back task. Two latent variables, derived from either parental/child-report or performance-based indicators, were evaluated as predictors of having ever tried alcohol, tobacco, or marijuana. RESULTS Results showed that reports of dysregulated emotion were linked to a greater likelihood of trying both alcohol and tobacco products. These findings were also present when controlling for individual differences in executive control and socioeconomic status. CONCLUSIONS These results suggest that well-established links between dysregulated negative emotion and substance use may emerge as early as in childhood and also suggest that children who experience excessive episodes of uncontrollable negative emotion may be at greater risk for trying substances early in life.
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Affiliation(s)
- Robert J. Klein
- Center for technology and behavioral Health, Geisel School of Medicine, Dartmouth college, Hanover, new Hampshire, USA
| | - Joseph A. Gyorda
- Center for technology and behavioral Health, Geisel School of Medicine, Dartmouth college, Hanover, new Hampshire, USA
- Mathematical Data Science Program, Dartmouth college, Hanover, new Hampshire, USA
| | - Damien Lekkas
- Center for technology and behavioral Health, Geisel School of Medicine, Dartmouth college, Hanover, new Hampshire, USA
- Quantitative biomedical Sciences Program, Dartmouth college, Hanover, new Hampshire, USA
| | - Nicholas C. Jacobson
- Center for technology and behavioral Health, Geisel School of Medicine, Dartmouth college, Hanover, new Hampshire, USA
- Quantitative biomedical Sciences Program, Dartmouth college, Hanover, new Hampshire, USA
- Department of biomedical Data Science, Geisel School of Medicine, Dartmouth college, Hanover, new Hampshire, USA
- Department of Psychiatry, Geisel School of Medicine, Dartmouth college, Hanover, new Hampshire, USA
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26
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Zhang X, Lai H, Li Q, Yang X, Pan N, He M, Kemp GJ, Wang S, Gong Q. Disrupted brain gray matter connectome in social anxiety disorder: a novel individualized structural covariance network analysis. Cereb Cortex 2023; 33:9627-9638. [PMID: 37381581 DOI: 10.1093/cercor/bhad231] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2023] [Revised: 05/11/2023] [Accepted: 06/10/2023] [Indexed: 06/30/2023] Open
Abstract
Phenotyping approaches grounded in structural network science can offer insights into the neurobiological substrates of psychiatric diseases, but this remains to be clarified at the individual level in social anxiety disorder (SAD). Using a recently developed approach combining probability density estimation and Kullback-Leibler divergence, we constructed single-subject structural covariance networks (SCNs) based on multivariate morphometry (cortical thickness, surface area, curvature, and volume) and quantified their global/nodal network properties using graph-theoretical analysis. We compared network metrics between SAD patients and healthy controls (HC) and analyzed the relationship to clinical characteristics. We also used support vector machine analysis to explore the ability of graph-theoretical metrics to discriminate SAD patients from HC. Globally, SAD patients showed higher global efficiency, shorter characteristic path length, and stronger small-worldness. Locally, SAD patients showed abnormal nodal centrality mainly involving left superior frontal gyrus, right superior parietal lobe, left amygdala, right paracentral gyrus, right lingual, and right pericalcarine cortex. Altered topological metrics were associated with the symptom severity and duration. Graph-based metrics allowed single-subject classification of SAD versus HC with total accuracy of 78.7%. This finding, that the topological organization of SCNs in SAD patients is altered toward more randomized configurations, adds to our understanding of network-level neuropathology in SAD.
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Affiliation(s)
- Xun Zhang
- Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China
| | - Han Lai
- Department of Medical Psychology, Army Medical University, Chongqing 400038, China
| | - Qingyuan Li
- Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China
| | - Xun Yang
- School of Public Affairs, Chongqing University, Chongqing 400044, China
| | - Nanfang Pan
- Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China
| | - Min He
- Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China
| | - Graham J Kemp
- Liverpool Magnetic Resonance Imaging Centre (LiMRIC) and Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, United Kingdom
| | - Song Wang
- Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China
- Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu 610041, China
| | - Qiyong Gong
- Department of Radiology and Huaxi MR Research Center (HMRRC), Functional and Molecular Imaging Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China
- Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen 361000, China
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27
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Ji C, Tang Y, Zhang Y, Huang X, Li C, Yang Y, Wu Q, Xia X, Cai Q, Qi XR, Zheng JC. Glutaminase 1 deficiency confined in forebrain neurons causes autism spectrum disorder-like behaviors. Cell Rep 2023; 42:112712. [PMID: 37384529 DOI: 10.1016/j.celrep.2023.112712] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Revised: 04/21/2023] [Accepted: 06/13/2023] [Indexed: 07/01/2023] Open
Abstract
An abnormal glutamate signaling pathway has been proposed in the mechanisms of autism spectrum disorder (ASD). However, less is known about the involvement of alterations of glutaminase 1 (GLS1) in the pathophysiology of ASD. We show that the transcript level of GLS1 is significantly decreased in the postmortem frontal cortex and peripheral blood of ASD subjects. Mice lacking Gls1 in CamKIIα-positive neurons display a series of ASD-like behaviors, synaptic excitatory and inhibitory (E/I) imbalance, higher spine density, and glutamate receptor expression in the prefrontal cortex, as well as a compromised expression pattern of genes involved in synapse pruning and less engulfed synaptic puncta in microglia. A low dose of lipopolysaccharide treatment restores microglial synapse pruning, corrects synaptic neurotransmission, and rescues behavioral deficits in these mice. In summary, these findings provide mechanistic insights into Gls1 loss in ASD symptoms and identify Gls1 as a target for the treatment of ASD.
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Affiliation(s)
- Chenhui Ji
- Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China
| | - Yalin Tang
- Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China
| | - Yanyan Zhang
- Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China
| | - Xiaoyan Huang
- Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China
| | - Congcong Li
- Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China
| | - Yuhong Yang
- Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China
| | - Qihui Wu
- Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200081, China
| | - Xiaohuan Xia
- Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200081, China; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Shanghai Frontiers Science Center of Nanocatalytic Medicine, Tongji University, Shanghai 200331, China
| | - Qingyuan Cai
- Franklin and Marshall College, 415 Harrisburg Avenue, Lancaster, PA 17603, USA
| | - Xin-Rui Qi
- Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China.
| | - Jialin C Zheng
- Center for Translational Neurodegeneration and Regenerative Therapy, Tongji Hospital Affiliated to Tongji University School of Medicine, Shanghai 200065, China; Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital Affiliated to Tongji University School of Medicine, Shanghai 200081, China; Collaborative Innovation Center for Brain Science, Tongji University, Shanghai 200092, China; Shanghai Key Laboratory of Anesthesiology and Brain Functional Modulation, Clinical Research Center for Anesthesiology and Perioperative Medicine, Translational Research Institute of Brain and Brain-Like Intelligence, Shanghai Fourth People's Hospital, School of Medicine, Tongji University, Shanghai 200434, China; Shanghai Frontiers Science Center of Nanocatalytic Medicine, Tongji University, Shanghai 200331, China.
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28
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Wang G, Zhou Y, Duan J, Kan Q, Cheng Z, Tang S. Effects of adverse childhood health experiences on cognitive function in Chinese middle-aged and older adults: mediating role of depression. BMC Public Health 2023; 23:1293. [PMID: 37407916 DOI: 10.1186/s12889-023-16169-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Accepted: 06/21/2023] [Indexed: 07/07/2023] Open
Abstract
BACKGROUND Adverse childhood experiences are critical factors in depression and cognitive decrease, but the effect of adverse childhood health experiences (ACHEs) on cognitive function and the role of depression have not been fully studied. METHODS Data were taken from the China Health and Retirement Longitudinal Study (CHARLS) of 2014 and 2018. This study used indicators of situational memory ability and mental status to measure cognitive capacity. Besides analyzing the different types of ACHEs, scores for ACHEs were calculated to represent the severity of ACHEs. The Center for Epidemiologic Studies Depression Scale (CES-D) was used to assess depression. The analysis of this study employed two different analytical strategies in order to examine the mediated effects of depression. We used Sobel's test and Baron and Kenny's causal step approach, which utilized a generalized least squares regression model. Furthermore, a logistic regression model was used to evaluate the robustness of the Karlson-Holm-Breen (KHB) approach. RESULTS In this study, 6301 individuals who met the requirements of the study were included. We found that being confined to bed (ACHE3) (β=-0.3846, p = 0.022) in childhood had a negative impact on cognitive function. Similarly, ACHEs had a negative effect on cognitive function (β=-0.0819, p = 0.090). And after the depression had been introduced into the model, the regression coefficient of ACHEs on cognitive function was no longer significant (β=-0.0170, p = 0.727). The Sobel test showed that for ACHE3, the mediated proportion of the total effect of depression was 36.92%. While for ACHEs, the proportion of the mediated effect of depression was 70.11%. Finally, a robustness test of the mediating effect using the KHB method revealed that the mediating effect still existed. Further, based on different gender, age, and educational levels, the heterogeneity test indicated that the relationship between ACHEs and cognitive function and mediating effects of the depression were different as well as passing the robustness test of the interaction. CONCLUSION The decline in cognition had been shown to be correlated with ACHEs and depression mediated this relationship. Positive interventions might help to improve cognitive performance in individuals suffering from ACHEs and depression.
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Affiliation(s)
- Gaoling Wang
- School of Health Economics and Management, Nanjing University of Chinese Medicine, 138 Xianlin Road, Qixia District, Nanjing, China
| | - Yuqin Zhou
- School of Health Economics and Management, Nanjing University of Chinese Medicine, 138 Xianlin Road, Qixia District, Nanjing, China
| | - Jing Duan
- School of Health Economics and Management, Nanjing University of Chinese Medicine, 138 Xianlin Road, Qixia District, Nanjing, China
| | - Qianqian Kan
- School of Health Economics and Management, Nanjing University of Chinese Medicine, 138 Xianlin Road, Qixia District, Nanjing, China
| | - Zhaopeng Cheng
- School of Health Economics and Management, Nanjing University of Chinese Medicine, 138 Xianlin Road, Qixia District, Nanjing, China
| | - Shaoliang Tang
- School of Health Economics and Management, Nanjing University of Chinese Medicine, 138 Xianlin Road, Qixia District, Nanjing, China.
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29
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Briones-Buixassa L, Montañés-Masias B, Milà-Villaroel R, Arrufat FX, Aragonès JM, Norton S, Bort-Roig J, Moss-Morris R. The bidirectional effect of stress and functionality in multiple sclerosis and the interaction role of anxiety, coping and social support. J Psychosom Res 2023; 170:111375. [PMID: 37196585 DOI: 10.1016/j.jpsychores.2023.111375] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Revised: 03/27/2023] [Accepted: 05/10/2023] [Indexed: 05/19/2023]
Abstract
OBJECTIVE The present study aims to analyse the bidirectional hypothesis between stress and multiple sclerosis with several measures of stress, impairment and functionality, considering also the interaction role of stress-related psychosocial factors such as anxiety, coping and social support. METHODS A one-year follow-up was conducted with 26 people with multiple sclerosis. Participants reported i) at baseline, anxiety (State-Trait Anxiety Inventory), and social support (Multidimensional Scale of Perceived Social Support); ii) daily, Ecological Momentary Assessment through self-reported diaries of stressful events and coping strategies; iii) monthly, the perceived stress (Perceived Stress Scale), iv) trimonthly, the self-reported functionality (Functionality Assessment in multiple sclerosis) and v) at baseline and at the end, neurologist rated impairment (Expanded Disability Status Scale). Mixed-effect regression models were conducted. RESULTS The bidirectional hypothesis was confirmed with perceived stress and self-reported functionality, which were negatively related in both directions. Coping and anxiety showed an interaction effect: active coping increased functionality only with high levels of stress, and high-trait anxiety showed lower functionality whereas low-trait anxiety showed higher functionality but only with low stress levels. CONCLUSION People with multiple sclerosis may benefit from different types of psychological therapies, from gold-standard therapies like Cognitive Behavioural Therapy to third-waves therapies like Dialectical Behaviour Therapy or mindfulness, that focus on dealing with stress and affective symptoms, adjusting to the disease, and to improving their overall quality of life. More research is needed in this field under the biopsychosocial model.
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Affiliation(s)
- Laia Briones-Buixassa
- Department of basic health sciences, Innovation in Mental Health and Social Wellbeing Research Group (ISaMBeS), Centre for Health and Social Care Research (CESS), Universitat de Vic - Universitat Central de Catalunya, C/ Sagrada Familia, 7, Vic 08500 - Spain; Department of Health Sciences, Universitat de Vic-Universitat Central de Catalunya, Vic, Catalonia, Spain.
| | - Brenda Montañés-Masias
- Department of basic health sciences, Innovation in Mental Health and Social Wellbeing Research Group (ISaMBeS), Centre for Health and Social Care Research (CESS), Universitat de Vic - Universitat Central de Catalunya, C/ Sagrada Familia, 7, Vic 08500 - Spain
| | - Raimon Milà-Villaroel
- Global Research on Wellbeing (GRoW), Blanquerna School of Health Sciences-Ramon Llull University, Barcelona, Spain
| | | | - Josep Mª Aragonès
- Neurology Department, Consorci Hospitalari de Vic, Vic, Catalonia, Spain
| | - Sam Norton
- Psychology Department, Health Psychology Section, Institute for Psychiatry, Psychology and Neuroscience, King's College London, London, UK
| | - Judit Bort-Roig
- Sport and Physical Activity Research Group, Centre for Health and Social Care Research, Universitat de Vic - Universitat Central de Catalunya, Vic, Catalonia, Spain
| | - Rona Moss-Morris
- Psychology Department, Health Psychology Section, Institute for Psychiatry, Psychology and Neuroscience, King's College London, London, UK
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30
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Xie H, Moraczewski D, McNaughton KA, Warnell KR, Alkire D, Merchant JS, Kirby LA, Yarger HA, Redcay E. Social reward network connectivity differs between autistic and neurotypical youth during social interaction. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.06.05.543807. [PMID: 37333161 PMCID: PMC10274709 DOI: 10.1101/2023.06.05.543807] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/20/2023]
Abstract
A core feature of autism is difficulties with social interaction. Atypical social motivation is proposed to underlie these difficulties. However, prior work testing this hypothesis has shown mixed support and has been limited in its ability to understand real-world social-interactive processes in autism. We attempted to address these limitations by scanning neurotypical and autistic youth (n = 86) during a text-based reciprocal social interaction that mimics a "live" chat and elicits social reward processes. We focused on task-evoked functional connectivity (FC) of regions responsible for motivational-reward and mentalizing processes within the broader social reward circuitry. We found that task-evoked FC between these regions was significantly modulated by social interaction and receipt of social-interactive reward. Compared to neurotypical peers, autistic youth showed significantly greater task-evoked connectivity of core regions in the mentalizing network (e.g., posterior superior temporal sulcus) and the amygdala, a key node in the reward network. Furthermore, across groups, the connectivity strength between these mentalizing and reward regions was negatively correlated with self-reported social motivation and social reward during the scanner task. Our results highlight an important role of FC within the broader social reward circuitry for social-interactive reward. Specifically, greater context-dependent FC (i.e., differences between social engagement and non-social engagement) may indicate an increased "neural effort" during social reward and relate to differences in social motivation within autistic and neurotypical populations.
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Affiliation(s)
- Hua Xie
- Neuroscience and Cognitive Science Program, University of Maryland, College Park, Maryland, USA
- Department of Psychology, University of Maryland, College Park, Maryland, USA
- Center for Neuroscience Research, Children’s National Hospital, Washington, D.C., USA
- The George Washington University School of Medicine, Washington, D.C., USA
| | - Dustin Moraczewski
- Data Science and Sharing Team, National Institute of Mental Health, Bethesda, Maryland, USA
| | - Kathryn A. McNaughton
- Neuroscience and Cognitive Science Program, University of Maryland, College Park, Maryland, USA
- Department of Psychology, University of Maryland, College Park, Maryland, USA
| | | | - Diana Alkire
- Neuroscience and Cognitive Science Program, University of Maryland, College Park, Maryland, USA
- Department of Psychology, University of Maryland, College Park, Maryland, USA
| | - Junaid S. Merchant
- Neuroscience and Cognitive Science Program, University of Maryland, College Park, Maryland, USA
- Department of Psychology, University of Maryland, College Park, Maryland, USA
| | - Laura A. Kirby
- Department of Psychology, University of Maryland, College Park, Maryland, USA
| | - Heather A. Yarger
- Neuroscience and Cognitive Science Program, University of Maryland, College Park, Maryland, USA
- Department of Psychology, University of Maryland, College Park, Maryland, USA
| | - Elizabeth Redcay
- Neuroscience and Cognitive Science Program, University of Maryland, College Park, Maryland, USA
- Department of Psychology, University of Maryland, College Park, Maryland, USA
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31
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Shi HJ, Wang S, Wang XP, Zhang RX, Zhu LJ. Hippocampus: Molecular, Cellular, and Circuit Features in Anxiety. Neurosci Bull 2023; 39:1009-1026. [PMID: 36680709 PMCID: PMC10264315 DOI: 10.1007/s12264-023-01020-1] [Citation(s) in RCA: 44] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 11/13/2022] [Indexed: 01/22/2023] Open
Abstract
Anxiety disorders are currently a major psychiatric and social problem, the mechanisms of which have been only partially elucidated. The hippocampus serves as a major target of stress mediators and is closely related to anxiety modulation. Yet so far, its complex anatomy has been a challenge for research on the mechanisms of anxiety regulation. Recent advances in imaging, virus tracking, and optogenetics/chemogenetics have permitted elucidation of the activity, connectivity, and function of specific cell types within the hippocampus and its connected brain regions, providing mechanistic insights into the elaborate organization of the hippocampal circuitry underlying anxiety. Studies of hippocampal neurotransmitter systems, including glutamatergic, GABAergic, cholinergic, dopaminergic, and serotonergic systems, have contributed to the interpretation of the underlying neural mechanisms of anxiety. Neuropeptides and neuroinflammatory factors are also involved in anxiety modulation. This review comprehensively summarizes the hippocampal mechanisms associated with anxiety modulation, based on molecular, cellular, and circuit properties, to provide tailored targets for future anxiety treatment.
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Affiliation(s)
- Hu-Jiang Shi
- Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Histology and Embryology, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Shuang Wang
- Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Histology and Embryology, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Xin-Ping Wang
- Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Histology and Embryology, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Rui-Xin Zhang
- Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Histology and Embryology, School of Medicine, Southeast University, Nanjing, 210009, China
| | - Li-Juan Zhu
- Key Laboratory of Developmental Genes and Human Diseases, MOE, Department of Histology and Embryology, School of Medicine, Southeast University, Nanjing, 210009, China.
- Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 201108, China.
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Song J. Amygdala activity and amygdala-hippocampus connectivity: Metabolic diseases, dementia, and neuropsychiatric issues. Biomed Pharmacother 2023; 162:114647. [PMID: 37011482 DOI: 10.1016/j.biopha.2023.114647] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 03/30/2023] [Accepted: 03/31/2023] [Indexed: 04/04/2023] Open
Abstract
With rapid aging of the population worldwide, the number of people with dementia is dramatically increasing. Some studies have emphasized that metabolic syndrome, which includes obesity and diabetes, leads to increased risks of dementia and cognitive decline. Factors such as insulin resistance, hyperglycemia, high blood pressure, dyslipidemia, and central obesity in metabolic syndrome are associated with synaptic failure, neuroinflammation, and imbalanced neurotransmitter levels, leading to the progression of dementia. Due to the positive correlation between diabetes and dementia, some studies have called it "type 3 diabetes". Recently, the number of patients with cognitive decline due to metabolic imbalances has considerably increased. In addition, recent studies have reported that neuropsychiatric issues such as anxiety, depressive behavior, and impaired attention are common factors in patients with metabolic disease and those with dementia. In the central nervous system (CNS), the amygdala is a central region that regulates emotional memory, mood disorders, anxiety, attention, and cognitive function. The connectivity of the amygdala with other brain regions, such as the hippocampus, and the activity of the amygdala contribute to diverse neuropathological and neuropsychiatric issues. Thus, this review summarizes the significant consequences of the critical roles of amygdala connectivity in both metabolic syndromes and dementia. Further studies on amygdala function in metabolic imbalance-related dementia are needed to treat neuropsychiatric problems in patients with this type of dementia.
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Affiliation(s)
- Juhyun Song
- Department of Anatomy, Chonnam National University Medical School, Hwasun 58128, Jeollanam-do, Republic of Korea.
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Yan Y, Li M, Jia H, Fu L, Qiu J, Yang W. Amygdala-based functional connectivity mediates the relationship between thought control ability and trait anxiety. Brain Cogn 2023; 168:105976. [PMID: 37086555 DOI: 10.1016/j.bandc.2023.105976] [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: 01/12/2023] [Revised: 04/02/2023] [Accepted: 04/04/2023] [Indexed: 04/24/2023]
Abstract
Thought control ability (TCA) refers to the ability to exclude unwanted thoughts. There has been consistent evidence on the protective effect of TCA on anxiety, that higher TCA is associated with lower anxiety. However, the underlying neural mechanism remains unclear. In this study, with a large sample (N = 495), we investigated how seed-based resting-state functional connectivity (RSFC) mediates the relationship between TCA and anxiety. Our behaviour results replicated previous findings that TCA is negatively associated with trait anxiety after controlling for gender, age, and depression. More importantly, the RSFC results revealed that TCA is negatively associated with the left amygdala - left frontal pole (LA-LFP), left amygdala - left inferior temporal gyrus (LA-LITG), and left hippocampus - left inferior frontal gyrus (LH-LIFG) connectivity. In addition, a mediation analysis demonstrated that the LA-LFP and LA-LITG connectivity in particular mediated the influence of TCA on trait anxiety. Overall, our study extends previous research by revealing the neural bases underlying the protective effect of TCA on anxiety and pinpointing specific mediating RSFC pathways. Future studies could explore whether targeted TCA training (behavioural or neural) can help alleviate anxiety.
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Affiliation(s)
- Yuchi Yan
- Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing 400715, China; Faculty of Psychology, Southwest University (SWU), Chongqing 400715, China
| | - Min Li
- Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing 400715, China; Faculty of Psychology, Southwest University (SWU), Chongqing 400715, China
| | - Hui Jia
- Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing 400715, China; Faculty of Psychology, Southwest University (SWU), Chongqing 400715, China
| | - Lei Fu
- Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing 400715, China; Faculty of Psychology, Southwest University (SWU), Chongqing 400715, China
| | - Jiang Qiu
- Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing 400715, China; Faculty of Psychology, Southwest University (SWU), Chongqing 400715, China.
| | - Wenjing Yang
- Key Laboratory of Cognition and Personality (SWU), Ministry of Education, Chongqing 400715, China; Faculty of Psychology, Southwest University (SWU), Chongqing 400715, China.
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Hammad AM, Alhusban AA, Alzaghari LF, Alasmari F, Sari Y. Effect of Cigarette Smoke Exposure and Aspirin Treatment on Neurotransmitters’ Tissue Content in Rats’ Hippocampus and Amygdala. Metabolites 2023; 13:metabo13040515. [PMID: 37110173 PMCID: PMC10145483 DOI: 10.3390/metabo13040515] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Revised: 03/26/2023] [Accepted: 03/31/2023] [Indexed: 04/07/2023] Open
Abstract
Cigarette smoke withdrawal can cause anxiety-like behavior and modulate neurotransmitter-related proteins in the brain. We examined the effects of cigarette smoke with and without aspirin treatment on the concentrations of neurotransmitters, including dopamine, serotonin, glutamate, glutamine, and GABA in the amygdala and hippocampus. Sprague-Dawley rats were randomly assigned to four different groups: (1) control group exposed only to standard room air, (2) cigarette smoke exposed group treated with saline vehicle, (3) cigarette smoke exposed group treated with aspirin (30 mg/kg), and (4) control group treated only with aspirin (30 mg/kg). Cigarette smoke exposure was performed for 2 h/day, 5 days/week, for 31 days. Behavioral testing was carried out weekly, 24 h after cigarette smoke exposure, during acute withdrawal. At the end of week 4, rats were given either distilled water (1 mL) or aspirin 45 min before cigarette exposure for 11 days. Dopamine, serotonin, glutamate, glutamine, and GABA were extracted from both the amygdala and hippocampus and were separated and quantified using a developed and validated HPLC-MS/MS method. Cigarette smoke withdrawal induced anxiety behaviors, and aspirin treatment reduced this effect. Cigarette smoke exposure increased tissue content of dopamine, serotonin, glutamate, glutamine, and GABA, and aspirin treatment reversed this effect. Cigarette smoke caused an increase in tissue content of several neurotransmitters as well as anxiety-like behavior, and these effects were normalized by aspirin treatment.
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Affiliation(s)
- Alaa M. Hammad
- Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan
| | - Ala A. Alhusban
- Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan
| | - Lujain F. Alzaghari
- Department of Pharmacy, Faculty of Pharmacy, Al-Zaytoonah University of Jordan, Amman 11733, Jordan
| | - Fawaz Alasmari
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
| | - Youssef Sari
- Department of Pharmacology and Experimental Therapeutics, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43606, USA
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Gellisch M, Morosan-Puopolo G, Wolf OT, Moser DA, Zaehres H, Brand-Saberi B. Interactive teaching enhances students' physiological arousal during online learning. Ann Anat 2023; 247:152050. [PMID: 36693546 DOI: 10.1016/j.aanat.2023.152050] [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: 10/21/2022] [Revised: 12/16/2022] [Accepted: 01/06/2023] [Indexed: 01/22/2023]
Abstract
The pure transfer of face-to-face teaching to a digital learning environment can be accompanied by a significant reduction in the physiological arousal of students, which in turn can be associated with passivity during the learning process, often linked to insufficient levels of concentration and engagement in the course work. Therefore, the aim of this study was to investigate whether students' psychobiological stress responses can be enhanced in the context of anatomical online learning and how increased physiological parameters correlate with characteristics of learning experiences in a digital learning environment. Healthy first-year medical students (n = 104) experienced a regular practical course in Microscopic Anatomy either in face-to-face learning, in passive online learning or in an interaction-enhanced version of online learning. Compared to passive online learning, students engaged in the interaction-enhanced version of online learning displayed a significantly reduced Heart Rate Variability (P 0.001, partial η2 = 0.381) along with a strong increase in salivary cortisol (P 0.001, partial η2 = 0.179) and salivary alpha-amylase activity (P 0.001, partial η2 = 0.195). These results demonstrated that the physiological arousal of students engaged in online learning can be enhanced via interactive teaching methods and pointed towards clear correlations between higher physiological responses and elementary criteria of learning experience such as engagement and attention.
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Affiliation(s)
- Morris Gellisch
- Department of Anatomy and Molecular Embryology, Institute of Anatomy, Medical Faculty, Ruhr University Bochum, Bochum, Germany.
| | - Gabriela Morosan-Puopolo
- Department of Anatomy and Molecular Embryology, Institute of Anatomy, Medical Faculty, Ruhr University Bochum, Bochum, Germany
| | - Oliver T Wolf
- Department of Cognitive Psychology, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany
| | - Dirk A Moser
- Department of Genetic Psychology, Faculty of Psychology, Ruhr University Bochum, Bochum, Germany
| | - Holm Zaehres
- Department of Anatomy and Molecular Embryology, Institute of Anatomy, Medical Faculty, Ruhr University Bochum, Bochum, Germany
| | - Beate Brand-Saberi
- Department of Anatomy and Molecular Embryology, Institute of Anatomy, Medical Faculty, Ruhr University Bochum, Bochum, Germany
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Moses TE, Gray E, Mischel N, Greenwald MK. Effects of neuromodulation on cognitive and emotional responses to psychosocial stressors in healthy humans. Neurobiol Stress 2023; 22:100515. [PMID: 36691646 PMCID: PMC9860364 DOI: 10.1016/j.ynstr.2023.100515] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Revised: 12/19/2022] [Accepted: 01/09/2023] [Indexed: 01/12/2023] Open
Abstract
Physiological and psychological stressors can exert wide-ranging effects on the human brain and behavior. Research has improved understanding of how the sympatho-adreno-medullary (SAM) and hypothalamic-pituitary-adrenocortical (HPA) axes respond to stressors and the differential responses that occur depending on stressor type. Although the physiological function of SAM and HPA responses is to promote survival and safety, exaggerated psychobiological reactivity can occur in psychiatric disorders. Exaggerated reactivity may occur more for certain types of stressors, specifically, psychosocial stressors. Understanding stressor effects and how the body regulates these responses can provide insight into ways that psychobiological reactivity can be modulated. Non-invasive neuromodulation is one way that responding to stressors may be altered; research into these interventions may provide further insights into the brain circuits that modulate stress reactivity. This review focuses on the effects of acute psychosocial stressors and how neuromodulation might be effective in altering stress reactivity. Although considerable research into stress interventions focuses on treating pathology, it is imperative to first understand these mechanisms in non-clinical populations; therefore, this review will emphasize populations with no known pathology and consider how these results may translate to those with psychiatric pathologies.
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Affiliation(s)
| | | | | | - Mark K. Greenwald
- Corresponding author. Department of Psychiatry and Behavioral Neurosciences, Tolan Park Medical Building, 3901 Chrysler Service Drive, Suite 2A, Detroit, MI, 48201, USA.
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Beaugrand M, Muehlematter C, Markovic A, Camos V, Kurth S. Sleep as a protective factor of children's executive functions: A study during COVID-19 confinement. PLoS One 2023; 18:e0279034. [PMID: 36630329 PMCID: PMC9833525 DOI: 10.1371/journal.pone.0279034] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Accepted: 11/29/2022] [Indexed: 01/12/2023] Open
Abstract
Confinements due to the COVID-19 outbreak affected sleep and mental health of adults, adolescents and children. Already preschool children experienced acutely worsened sleep, yet the possible resulting effects on executive functions remain unexplored. Longitudinally, sleep quality predicts later behavioral-cognitive outcomes. Accordingly, we propose children's sleep behavior as essential for healthy cognitive development. By using the COVID-19 confinement as an observational-experimental intervention, we tested whether worsened children's sleep affects executive functions outcomes 6 months downstream. We hypothesized that acutely increased night awakenings and sleep latency relate to reduced later executive functions. With an online survey during the acute confinement phase we analyzed sleep behavior in 45 children (36-72 months). A first survey referred to the (retrospective) time before and (acute) situation during confinement, and a follow-up survey assessed executive functions 6 months later (6 months retrospectively). Indeed, acutely increased nighttime awakenings related to reduced inhibition at FOLLOW-UP. Associations were specific to the confinement-induced sleep-change and not the sleep behavior before confinement. These findings highlight that specifically acute changes of children's nighttime sleep during sensitive periods are associated with behavioral outcome consequences. This aligns with observations in animals that inducing poor sleep during developmental periods affects later brain function.
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Affiliation(s)
| | | | - Andjela Markovic
- University of Fribourg, Department of Psychology, Fribourg, Switzerland
- University Hospital Zurich, Department of Pulmonology, Zurich, Switzerland
| | - Valérie Camos
- University of Fribourg, Department of Psychology, Fribourg, Switzerland
| | - Salome Kurth
- University of Fribourg, Department of Psychology, Fribourg, Switzerland
- University Hospital Zurich, Department of Pulmonology, Zurich, Switzerland
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38
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Banfi JT, Randall JG. A meta-analysis of trait mindfulness: Relationships with the big five personality traits, intelligence, and anxiety. JOURNAL OF RESEARCH IN PERSONALITY 2022. [DOI: 10.1016/j.jrp.2022.104307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/05/2022]
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Evaluation of the effect of alpha-tocopherol on anxiety and the neuroinflammatory process during alcohol withdrawal in a model of forced and chronic self-administration of liquid diet containing ethanol: Behavioral and neurochemical evidence. Alcohol 2022; 104:31-44. [PMID: 35987315 DOI: 10.1016/j.alcohol.2022.08.002] [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: 12/03/2021] [Revised: 07/13/2022] [Accepted: 08/06/2022] [Indexed: 01/26/2023]
Abstract
Alcoholism affects about 2 billion people worldwide. Withdrawal causes a neuroinflammatory response that increases anxiety. α-tocopherol is the most important antioxidant that has its in vivo action currently known. Therefore, this study aimed to evaluate the effect of α-tocopherol on the neuroinflammatory process in brain regions involved in anxiety and its anxiolytic potential during alcohol withdrawal. For this, male Wistar rats were divided into four groups and submitted to a procedure of forced and chronic self-administration of liquid diet containing 6% and 8% ethanol for 15 days, followed by abrupt interruption of treatment. Animals in the control group received the liquid diet without ethanol. Twenty-four or 48 h after ethanol discontinuation, and 30 min after the last administration of α-tocopherol or saline, animals were evaluated in the elevated plus maze, light/dark box, and open field tests. At the end of the tests, each experimental group underwent brain tissue collection for analysis of cytokine levels. The results showed that: alcohol induces the neuroinflammatory process and anxiety; the stress generated by withdrawal can induce oxidative stress, which alters the production of inflammatory cytokines in the amygdaloid nuclei (AN) and medial hypothalamic nucleus (mHN); α-tocopherol exhibited anxiolytic and anti-inflammatory activity, attenuating the anxious behavior of abstinent animals and reducing neuroinflammation in AN and mHN; and the intensity of the anxiolytic and anti-inflammatory effect of α-tocopherol is dose-dependent. These results identify α-tocopherol as a potential therapeutic target supporting the fight against relapse during alcohol withdrawal.
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40
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Coehoorn CJ, Patrick Neary J, Krigolson OE, Stuart-Hill LA. Firefighter Pre-Frontal Cortex and Hemodynamics during Rapid Heat Stress. Brain Res 2022; 1798:148156. [DOI: 10.1016/j.brainres.2022.148156] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2022] [Revised: 10/31/2022] [Accepted: 11/01/2022] [Indexed: 11/06/2022]
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Li W, Cong X, Fan Z, Li F. A Study on Intergenerational Transmission of Dark Triad and Emotion Reactivity. Psychol Res Behav Manag 2022; 15:2941-2956. [PMID: 36237372 PMCID: PMC9552791 DOI: 10.2147/prbm.s378078] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2022] [Accepted: 09/23/2022] [Indexed: 11/06/2022] Open
Abstract
INTRODUCTION Moderate emotion reactivity in the face of daily stress is of positive significance regarding individuals' psychological well-being and environmental adaptation. The study on intergenerational transmission of Dark Triad and emotion reactivity has confirmed the existence of higher levels of Dark Triad and emotion reactivity in college students in the Chinese sample, which may provide a reference for future related studies. PURPOSE The study examined the intergenerational transmission effects of Dark Triad and Emotion Reactivity in families. And based on this, it further analyzed the mediating role of parental emotion reactivity and children's Dark Triad in the influence of parental Dark Triad on children's emotion reactivity. METHODS The questionnaire was administered to 486 families inclusive of fathers, mothers, and children utilizing the Emotion Reactivity Scale (ERS) and the Dirty Dozen (DD). RESULTS 1) The intergenerational transmission was presented in the three Dark Triad traits and emotion reactivity. 2) The level of Dark Triad and emotion reactivity of children was remarkably higher than that of their parents. 3) The Dark Triad scores of males were considerably higher than those of females, while there were no significant differences in the scores of emotion reactivity between them. 4) The actor and partner effects of Dark Triad and emotion reactivity between father and mother were established. 5) Parental emotion reactivity and children's Dark Triad exerted mediating effects on the impact of parental Dark Triad on children's emotion reactivity. CONCLUSION The effect of parental three Dark Triad on their children's emotion reactivity as well as its mediation mechanism were examined respectively by the present study in the light of APIM and intergenerational transmission analysis. It was concluded that the findings carried both theoretical and reference value for developing moderate emotion reactive ability toward college students.
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Affiliation(s)
- Wei Li
- Department of Education, Jilin International Studies University, Changchun, People’s Republic of China
| | - Xiangxin Cong
- Department of Education, Jilin International Studies University, Changchun, People’s Republic of China
| | - Zhiguang Fan
- Department of Education, Jilin International Studies University, Changchun, People’s Republic of China
| | - Fei Li
- Department of Marxism, Changchun University of Chinese Medicine, Changchun, People’s Republic of China
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Hermens DF, Jamieson D, Fitzpatrick L, Sacks DD, Iorfino F, Crouse JJ, Guastella AJ, Scott EM, Hickie IB, Lagopoulos J. Sex differences in fronto-limbic white matter tracts in youth with mood disorders. Psychiatry Clin Neurosci 2022; 76:481-489. [PMID: 35730893 DOI: 10.1111/pcn.13440] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/12/2022] [Revised: 05/22/2022] [Accepted: 06/14/2022] [Indexed: 11/29/2022]
Abstract
AIMS Patients with depression and bipolar disorder have previously been shown to have impaired white matter (WM) integrity compared with healthy controls. This study aimed to investigate potential sex differences that may provide further insight into the pathophysiology of these highly debilitating mood disorders. METHODS Participants aged 17 to 30 years (168 with depression [60% females], 107 with bipolar disorder [74% females], and 61 controls [64% females]) completed clinical assessment, self-report measures, and a neuropsychological assessment battery. Participants also underwent magnetic resonance imaging from which diffusion tensor imaging data were collected among five fronto-limbic WM tracts: cingulum bundle (cingulate gyrus and hippocampus subsections), fornix, stria terminalis, and the uncinate fasciculus. Mean fractional anisotropy (FA) scores were compared between groups using analyses of variance with sex and diagnosis as fixed factors. RESULTS Among the nine WM tracts analyzed, one revealed a significant interaction between sex and diagnosis, controlling for age. Male patients with bipolar disorder had significantly lower FA scores in the fornix compared with the other groups. Furthermore, partial correlations revealed a significant positive association between FA scores for the fornix and psychomotor speed. CONCLUSIONS Our findings suggest that males with bipolar disorder may be at increased risk of disruptions in WM integrity, especially in the fornix, which is thought to be responsible for a range of cognitive functions. More broadly, our findings suggest that sex differences may exist in WM integrity and thereby alter our understanding of the pathophysiology of mood disorders.
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Affiliation(s)
- Daniel F Hermens
- Thompson Institute, University of the Sunshine Coast, Birtinya, Queensland, Australia
| | - Daniel Jamieson
- Thompson Institute, University of the Sunshine Coast, Birtinya, Queensland, Australia
| | - Lauren Fitzpatrick
- Youth Mental Health & Technology Team, Brain and Mind Centre, University of Sydney, Camperdown, New South Wales, Australia
| | - Dashiell D Sacks
- Thompson Institute, University of the Sunshine Coast, Birtinya, Queensland, Australia
| | - Frank Iorfino
- Youth Mental Health & Technology Team, Brain and Mind Centre, University of Sydney, Camperdown, New South Wales, Australia
| | - Jacob J Crouse
- Youth Mental Health & Technology Team, Brain and Mind Centre, University of Sydney, Camperdown, New South Wales, Australia
| | - Adam J Guastella
- Youth Mental Health & Technology Team, Brain and Mind Centre, University of Sydney, Camperdown, New South Wales, Australia
| | - Elizabeth M Scott
- Youth Mental Health & Technology Team, Brain and Mind Centre, University of Sydney, Camperdown, New South Wales, Australia
| | - Ian B Hickie
- Youth Mental Health & Technology Team, Brain and Mind Centre, University of Sydney, Camperdown, New South Wales, Australia
| | - Jim Lagopoulos
- Thompson Institute, University of the Sunshine Coast, Birtinya, Queensland, Australia
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Floreani ED, Orlandi S, Chau T. A pediatric near-infrared spectroscopy brain-computer interface based on the detection of emotional valence. Front Hum Neurosci 2022; 16:938708. [PMID: 36211121 PMCID: PMC9540519 DOI: 10.3389/fnhum.2022.938708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2022] [Accepted: 09/05/2022] [Indexed: 11/27/2022] Open
Abstract
Brain-computer interfaces (BCIs) are being investigated as an access pathway to communication for individuals with physical disabilities, as the technology obviates the need for voluntary motor control. However, to date, minimal research has investigated the use of BCIs for children. Traditional BCI communication paradigms may be suboptimal given that children with physical disabilities may face delays in cognitive development and acquisition of literacy skills. Instead, in this study we explored emotional state as an alternative access pathway to communication. We developed a pediatric BCI to identify positive and negative emotional states from changes in hemodynamic activity of the prefrontal cortex (PFC). To train and test the BCI, 10 neurotypical children aged 8–14 underwent a series of emotion-induction trials over four experimental sessions (one offline, three online) while their brain activity was measured with functional near-infrared spectroscopy (fNIRS). Visual neurofeedback was used to assist participants in regulating their emotional states and modulating their hemodynamic activity in response to the affective stimuli. Child-specific linear discriminant classifiers were trained on cumulatively available data from previous sessions and adaptively updated throughout each session. Average online valence classification exceeded chance across participants by the last two online sessions (with 7 and 8 of the 10 participants performing better than chance, respectively, in Sessions 3 and 4). There was a small significant positive correlation with online BCI performance and age, suggesting older participants were more successful at regulating their emotional state and/or brain activity. Variability was seen across participants in regards to BCI performance, hemodynamic response, and discriminatory features and channels. Retrospective offline analyses yielded accuracies comparable to those reported in adult affective BCI studies using fNIRS. Affective fNIRS-BCIs appear to be feasible for school-aged children, but to further gauge the practical potential of this type of BCI, replication with more training sessions, larger sample sizes, and end-users with disabilities is necessary.
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Affiliation(s)
- Erica D. Floreani
- Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada
- Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
- *Correspondence: Erica D. Floreani
| | - Silvia Orlandi
- Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada
- Department of Biomedical Engineering, University of Bologna, Bologna, Italy
| | - Tom Chau
- Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada
- Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
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Perchtold-Stefan CM, Fink A, Rominger C, Szabó E, Papousek I. Enjoying others' distress and indifferent to threat? Changes in prefrontal-posterior coupling during social-emotional processing are linked to malevolent creativity. Brain Cogn 2022; 163:105913. [PMID: 36087513 DOI: 10.1016/j.bandc.2022.105913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2022] [Revised: 07/29/2022] [Accepted: 08/30/2022] [Indexed: 11/20/2022]
Abstract
Malevolent creativity is characterized by malicious interpersonal goals aimed at damaging others. Neurocognitive processing patterns of negative social-emotional signals may explain variance in this disruptive phenomenon. This study examined whether individuals' brain responses to emotional expressions of others are linked to their capacity of malevolent creativity in a psychometric test. State-dependent changes of prefrontal-posterior EEG coherence were recorded while n = 60 participants listened to other people's anger, desperate crying, and laughter. These EEG measures were used to indicate affective dispositions towards emotional absorption (decreased coherence) or detachment (increased coherence) from others' emotional states. Results showed that higher malevolent creativity was reflected in relatively greater increases of EEG coherence during others' expressions of anger, and conversely, relatively greater decreases of EEG coherence during others' desperate crying. This pattern suggests that the generation of creative ideas for malicious, antisocial purposes may be partly attributed to an indifference towards others' aggression and potential retaliation, and partly to finding others' adversity rewarding on a neuronal level, increasing the quantity of ideas and the chances of hurting others. This first study linking malevolent creativity to social-emotional brain functions may offer novel insights into affective dispositions that may help understand individuals' potential for creative destruction.
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Affiliation(s)
| | - Andreas Fink
- Department of Psychology, University of Graz, Universitätsplatz 2, 8010 Graz, Austria.
| | - Christian Rominger
- Department of Psychology, University of Graz, Universitätsplatz 2, 8010 Graz, Austria.
| | - Enikő Szabó
- Oradea Maximum Security Penitentiary, Parcul Traian 3, 410100 Oradea, Romania
| | - Ilona Papousek
- Department of Psychology, University of Graz, Universitätsplatz 2, 8010 Graz, Austria.
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Sawada M, Adolphs R, Dlouhy BJ, Jenison RL, Rhone AE, Kovach CK, Greenlee JDW, Howard Iii MA, Oya H. Mapping effective connectivity of human amygdala subdivisions with intracranial stimulation. Nat Commun 2022; 13:4909. [PMID: 35987994 PMCID: PMC9392722 DOI: 10.1038/s41467-022-32644-y] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2021] [Accepted: 08/08/2022] [Indexed: 01/21/2023] Open
Abstract
The primate amygdala is a complex consisting of over a dozen nuclei that have been implicated in a host of cognitive functions, individual differences, and psychiatric illnesses. These functions are implemented through distinct connectivity profiles, which have been documented in animals but remain largely unknown in humans. Here we present results from 25 neurosurgical patients who had concurrent electrical stimulation of the amygdala with intracranial electroencephalography (electrical stimulation tract-tracing; es-TT), or fMRI (electrical stimulation fMRI; es-fMRI), methods providing strong inferences about effective connectivity of amygdala subdivisions with the rest of the brain. We quantified functional connectivity with medial and lateral amygdala, the temporal order of these connections on the timescale of milliseconds, and also detail second-order effective connectivity among the key nodes. These findings provide a uniquely detailed characterization of human amygdala functional connectivity that will inform functional neuroimaging studies in healthy and clinical populations.
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Affiliation(s)
- Masahiro Sawada
- Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Department of Neurosurgery, Tazuke Kofukai Medical Research Institute and Kitano Hospital, Osaka, Japan
| | - Ralph Adolphs
- Division of Humanities and Social Sciences, California Institute of Technology, Pasadena, CA, USA
| | - Brian J Dlouhy
- Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA
| | - Rick L Jenison
- Department of Neuroscience, University of Wisconsin - Madison, Madison, WI, USA
| | - Ariane E Rhone
- Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Christopher K Kovach
- Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
| | - Jeremy D W Greenlee
- Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA
| | - Matthew A Howard Iii
- Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, IA, USA
- Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA
- Pappajohn Biomedical Institute, University of Iowa, Iowa City, IA, USA
| | - Hiroyuki Oya
- Department of Neurosurgery, Carver College of Medicine, University of Iowa, Iowa City, IA, USA.
- Iowa Neuroscience Institute, University of Iowa, Iowa City, IA, USA.
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46
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Unraveling the Contribution of Serotonergic Polymorphisms, Prefrontal Alpha Asymmetry, and Individual Alpha Peak Frequency to the Emotion-Related Impulsivity Endophenotype. Mol Neurobiol 2022; 59:6062-6075. [PMID: 35854179 PMCID: PMC9463349 DOI: 10.1007/s12035-022-02957-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Accepted: 07/04/2022] [Indexed: 12/03/2022]
Abstract
The unique contribution of the serotonin transporter-linked polymorphic region (5-HTTLPR), intronic region 2 (STin2), and monoamine oxidase A (MAO-A) genes to individual differences in personality traits has been widely explored, and research has shown that certain forms of these polymorphisms relate to impulsivity and impulsivity-related disorders. Humans showing these traits are also described as having an asymmetrical prefrontal cortical activity when compared to others. In this explorative study, we examine the relationship between serotonergic neurotransmission polymorphisms, cortical activity features (prefrontal alpha asymmetry, individual alpha peak frequency [iAPF]), emotion-related and non-emotion-related impulsivity in humans. 5-HTTLPR, MAO-A, and STin2 polymorphisms were assessed in blood taken from 91 participants with high emotion-related impulsivity levels. Sixty-seven participants completed resting electroencephalography and a more comprehensive impulsivity index. In univariate analyses, iAPF correlated with both forms of emotion-related impulsivity. In multiple linear regression models, 5-HTTLPR polymorphism (model 1, adj. R2 = 15.2%) and iAPF were significant interacting predictors of emotion-related impulsivity, explaining a large share of the results’ variance (model 2, adj. R2 = 21.2%). Carriers of the low transcriptional activity 5-HTTPLR and MAO-A phenotypes obtained higher emotion-related impulsivity scores than others did. No significant results were detected for non-emotion-related impulsivity or for a form of emotion-related impulsivity involving cognitive/motivational reactivity to emotion. Our findings support an endophenotypic approach to impulsivity, showing that tri-allelic 5-HTTLPR polymorphism, iAPF, and their interaction are relevant predictors of one form of emotion-related impulsivity.
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Baroreflex sensitivity derived from the Valsalva manoeuvre: A physiological protective factor for anxiety induced by breathing CO 2-enriched air. Int J Psychophysiol 2022; 179:101-109. [PMID: 35809687 DOI: 10.1016/j.ijpsycho.2022.06.019] [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: 10/05/2021] [Revised: 06/29/2022] [Accepted: 06/30/2022] [Indexed: 11/23/2022]
Abstract
This study aimed to determine the capacity of baroreflex sensitivity, derived from the Valsalva manoeuvre (BRS_v), to predict state anxiety induced by a biological stressor (CO2 inhalation). Healthy adults (n = 50) breathed 7.5 % CO2-enriched air for 8 min, preceded and followed by breathing medical air for 5 min. State anxiety was evaluated with a visual analogue scale. Anxiety sensitivity (Anxiety Sensitivity Index-3; ASI-3) and trait anxiety (Trait form of the State-Trait Anxiety Inventory; STAI_T) served as cognitive-affective predictors. BRS_v was adopted as a physiological predictor. Multiple regression analysis revealed that BRS_v predicted lower anxiety during CO2 exposure, and attenuated the effect of ASI-3 in increasing anxiety. No significant effects were found for STAI_T. This is the first study to identify baroreflex sensitivity as a strong protective physiological factor for anxiety beyond the effect of anxiety sensitivity.
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48
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Wong JJ, Wong NML, Chang DHF, Qi D, Chen L, Lee TMC. Amygdala-pons connectivity is hyperactive and associated with symptom severity in depression. Commun Biol 2022; 5:574. [PMID: 35688901 PMCID: PMC9187701 DOI: 10.1038/s42003-022-03463-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2021] [Accepted: 05/09/2022] [Indexed: 11/18/2022] Open
Abstract
Knowledge of the neural underpinnings of processing sad information and how it differs in people with depression could elucidate the neural mechanisms perpetuating sad mood in depression. Here, we conduct a 7 T fMRI study to delineate the neural correlates involved only in processing sad information, including pons, amygdala, and corticolimbic regions. We then conduct a 3 T fMRI study to examine the resting-state connectivity in another sample of people with and without depression. Only clinically depressed people demonstrate hyperactive amygdala–pons connectivity. Furthermore, this connectivity is related to depression symptom severity and is a significant indicator of depression. We speculate that visual sad information reinforces depressed mood and stimulates the pons, strengthening the amygdala–pons connectivity. The relationship between this connectivity and depressive symptom severity suggests that guiding one’s visual attention and processing of sad information may benefit mood regulation. A study on patients with major depressive disorder (MDD) suggests that a specific sadness-processing connection between the amygdala and pons appears to be dysfunctional among people with MDD and associated with severity of depression.
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Affiliation(s)
- Jing Jun Wong
- State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.,Laboratory of Neuropsychology and Human Neuroscience, The University of Hong Kong, Hong Kong, China
| | - Nichol M L Wong
- State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.,Department of Psychology, The University of Hong Kong, Hong Kong, China
| | - Dorita H F Chang
- State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.,Department of Psychology, The University of Hong Kong, Hong Kong, China
| | - Di Qi
- State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China.,Laboratory of Neuropsychology and Human Neuroscience, The University of Hong Kong, Hong Kong, China
| | - Lin Chen
- State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.
| | - Tatia M C Lee
- State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong, China. .,Laboratory of Neuropsychology and Human Neuroscience, The University of Hong Kong, Hong Kong, China. .,Center for Brain Science and Brain-Inspired Intelligence, Guangdong-Hong Kong-Macao Greater Bay Area, Hong Kong, China.
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49
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Roy DS, Zhang Y, Aida T, Shen C, Skaggs KM, Hou Y, Fleishman M, Mosto O, Weninger A, Feng G. Anterior thalamic circuits crucial for working memory. Proc Natl Acad Sci U S A 2022; 119:e2118712119. [PMID: 35537049 PMCID: PMC9171768 DOI: 10.1073/pnas.2118712119] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2021] [Accepted: 04/15/2022] [Indexed: 11/22/2022] Open
Abstract
Alterations in the structure and functional connectivity of anterior thalamic nuclei (ATN) have been linked to reduced cognition during aging. However, ATN circuits that contribute to higher cognitive functions remain understudied. We found that the anteroventral (AV) subdivision of ATN is necessary specifically during the maintenance phase of a spatial working memory task. This function engages the AV→parasubiculum (PaS)→entorhinal cortex (EC) circuit. Aged mice showed a deficit in spatial working memory, which was associated with a decrease in the excitability of AV neurons. Activation of AV neurons or the AV→PaS circuit in aged mice was sufficient to rescue their working memory performance. Furthermore, rescued aged mice showed improved behavior-induced neuronal activity in prefrontal cortex (PFC), a critical site for working memory processes. Although the direct activation of PFC neurons in aged mice also rescued their working memory performance, we found that these animals exhibited increased levels of anxiety, which was not the case for AV→PaS circuit manipulations in aged mice. These results suggest that targeting AV thalamus in aging may not only be beneficial for cognitive functions but that this approach may have fewer unintended effects compared to direct PFC manipulations.
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Affiliation(s)
- Dheeraj S. Roy
- Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142
| | - Ying Zhang
- McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
| | - Tomomi Aida
- McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
| | - Chenjie Shen
- McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
| | - Keith M. Skaggs
- McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
| | - Yuanyuan Hou
- McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
| | - Morgan Fleishman
- Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142
| | - Olivia Mosto
- McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
| | - Alyssa Weninger
- McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
| | - Guoping Feng
- Stanley Center for Psychiatric Research, Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, MA 02142
- McGovern Institute for Brain Research, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139
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50
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Systemic Administration of Lipopolysaccharide Induces Hyperexcitability of Prelimbic Neurons via modulation of Sodium and Potassium Currents. Neurotoxicology 2022; 91:128-139. [DOI: 10.1016/j.neuro.2022.05.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 05/10/2022] [Accepted: 05/11/2022] [Indexed: 11/18/2022]
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