Percheron acute artery occlusion is a rare type of acute cerebral infarction.

An elderly male presented with sudden-onset near-memory and sensory impairments for 5 days. Upon admission, based on symptoms, signs, magnetic resonance imaging, and computed tomography findings, a diagnosis of Percheron syndrome was made. Subsequently, anti-platelet therapy, lipid-lowering treatment, cerebral circulation enhancement (such as the administration of calcium channel blockers to improve cerebral blood flow), and neurotrophic support (such as the use of drugs like citicoline to protect nerve cells) were immediately implemented, along with additional symptomatic treatments. The patient's symptoms were alleviated, following which he was discharged.

The diagnosis of acute occlusion of the Percheron artery requires rich clinical expertise and accurate imaging tools. Timely intervention and effective follow-up hold significant implications for optimizing patient recovery.

Neuroimaging studies have shown that striatal functional connectivity (FC) is altered in psychosis (PSY). However, the evidence remains heterogeneous, partly due to the different subregions and clinical stages considered. For this reason, we gathered available studies that evaluated FC between the striatum and the whole brain in PSY through systematic research of the literature. Then, we performed a coordinate-based activation meta-analysis of brain regions that showed dysconnectivity with the striatum to identify spatially convergent patterns (40 experiments, 4473 subjects). The analysis was replicated for the experiments including only individuals with schizophrenia, first-episode psychosis (FEP), and drug-naïve FEP, and assessing the FC of the limbic and associative striatum. Lastly, we analyzed an independent sample to assess the relationship between these changes and clinical and cognitive variables. In PSY, the striatum was hypoconnected with the anterior cingulate cortex/medial prefrontal cortex (replicated in all analyses and in the independent sample, where the FC was correlated with cognitive flexibility), and with the right thalamus, while it was hyperconnected with the right caudate and the left middle frontal gyrus. These findings of specific patterns of striatal dysconnectivity in PSY could improve our understanding of the role of the striatum in pathophysiology and provide potential biomarkers and targets for new treatments.

Flexible behavior depends on abstract rules to generalize beyond specific instances and outcome monitoring to adjust actions. Cortical circuits are posited to read out rules from high-dimensional representations of task-relevant variables in prefrontal cortex (PFC). We instead hypothesized that converging inputs from PFC, directly or via basal ganglia (BGs), enable the thalamus to select rules. We measured activity across PFC and connected thalamic nuclei of monkeys applying rules. Abstract rule information first appeared in ventroanterior thalamus (VA)-the main thalamic hub between BG and PFC. Mediodorsal thalamus (MD) also represented rule information before PFC, persisting to help maintain activation of relevant PFC cell ensembles. MD, a major recipient of midbrain dopamine input, was the first to represent information about behavioral outcomes. A PFC-BG-thalamus model reproduced key findings, and thalamic-lesion modeling disrupted PFC rule representations. This suggests that the thalamus selects high-level cognitive information from PFC and monitors behavioral outcomes of these selections.

Encoding new memories relies on functional connections between the medial temporal lobe and the frontoparietal cortices. Multi-scan fMRI showed changes in these functional connections before and after memory encoding, potentially influenced by the thalamus. As different thalamic nuclei are interconnected with distinct cortical networks, we hypothesized that variations in cortico-thalamic recruitment may impact individual memory performance.We used a multi-scan fMRI protocol including a resting-state scan followed by an associative memory task encompassing encoding and retrieval phases, in two independent samples of healthy adults (N1=29, mean age=26, males=35%; N2=108; mean age=28, males=52%). Individual activity and functional connectivity were analyzed in the native space to minimize registration bias. By modeling the direct and indirect effects of cortico-thalamic recruitment on memory using Structural Equation Modeling, we showed a positive association between resting-state functional connectivity of the medial thalamic subdivision within the frontoparietal network and memory performance across samples (effect size R2 ranging between 0.27 and 0.36; p-values between 0.01 and 4e-05). This direct relationship was mediated by decreased activation of the anterior subdivision during encoding (R2 ranging between 0.04 and 0.2; p-values between 0.05 and 0.006) and by increased activation of the medial subdivision during retrieval (R2 ranging between 0.04 and 0.2; p-values between 0.05 and 0.004). Moreover, three distinct clusters of individuals displayed different cortico-thalamic patterns across memory phases.We suggest that associative memory encoding relies on the distinct cortico-thalamic pathways involving medial thalamic recruitment and suppression of anterior subdivision to support the successful encoding of new memories.Significance statement Every person is unique in their learning process and related brain functional organization. Prior research has mainly aimed to find shared patterns in how the brain responds to external stimuli, often overlooking individual behavioral differences. We hypothesized that individuals may recruit different neural resources supporting their learning abilities. We investigated whether specific brain configurations are beneficial to individual memory performance. We found that the baseline configuration of select cortico-thalamic networks involving the medial thalamic subdivision supports memory performance via the indirect effects of the anterior thalamic subdivision deactivation and medial activation during the memory task. We propose that cortico-thalamic functioning involving the anterior and medial thalamus underlies interindividual variability in associative memory encoding.

Chronic stress profoundly affects the structure and function of the prefrontal cortex (PFC), a brain region critical for executive functions and emotional regulation. This review synthesizes current knowledge on stress-induced PFC plasticity, encompassing structural, functional, and molecular changes. We examine how chronic stress leads to dendritic atrophy, spine loss, and alterations in neuronal connectivity within the PFC, particularly affecting the medial PFC. These structural changes are accompanied by disruptions in neurotransmitter systems, most notably glutamatergic and GABAergic signaling, and alterations in synaptic plasticity mechanisms. At the molecular level, we discuss the intricate interplay between stress hormones, neurotrophic factors, and epigenetic modifications that underlie these changes. The review highlights the significant behavioral and cognitive consequences of stress-induced PFC plasticity, including impairments in working memory, decision-making, and emotional regulation, which may contribute to the development of stress-related psychiatric disorders. We also explore individual differences in stress susceptibility, focusing on sex-specific effects and age-dependent variations in stress responses. The role of estrogens in conferring stress resilience in females and the unique vulnerabilities of the developing and aging PFC are discussed. Finally, we consider potential pharmacological and non-pharmacological interventions that may mitigate or reverse stress-induced changes in the PFC. The review concludes by identifying key areas for future research, including the need for more studies on the reversibility of stress effects and the potential of emerging technologies in unraveling the complexities of PFC plasticity. This comprehensive overview underscores the critical importance of understanding stress-induced PFC plasticity for developing more effective strategies to prevent and treat stress-related mental health disorders.

Exposure to childhood maltreatment can contribute to multiple behavioral and clinical manifestations, including the development of psychotic illnesses and pain-related abnormalities. Aberrant pain perception in individuals with psychosis may be associated with the worsening psychiatric symptoms, including an increase in mood episodes and a higher risk for suicidality. Despite the multiple connections between psychosis, pain, and childhood maltreatment, the combined investigation of these three domains remains limited.

In this study, patients with schizophrenia (SZ, n = 20) or bipolar I disorder (BD, n = 24) and healthy controls (HC, n = 24) underwent a comprehensive clinical evaluation followed by quantitative sensory testing (QST), where behavioral sensitivity to thermal stimuli was quantified. Central pain circuitry was probed using a combination of functional and structural magnetic resonance imaging. Neuroimaging analyses focused on thermal stimulation fMRI responses, resting-state connectivity, and gray matter morphological properties.

fMRI demonstrated diminished sensorimotor activation during an evoked pain state for both SZ and BD patients, where reduced activity in thalamic subdivisions (i.e., pulvinar nucleus) in BD patients negatively correlates with the severity of childhood maltreatment. Resting-state connectivity analyses revealed altered connectivity of various cortical regions with the postcentral gyri and thalamic nuclei, suggesting potential altered neural mechanisms underlying pain perception in patients with SZ and BD. Morphological analysis identified reduced gray matter thickness in the postcentral sulcus of BD patients, which correlated with the severity of childhood maltreatment.

These findings provide insight into the multidimensional nature of clinical presentations in SZ and BD and contribute to our understanding of the complex relationship between childhood maltreatment and central pain processing in patients with psychotic illnesses.

Flexible behavior depends on abstract rules to generalize beyond specific instances, and outcome monitoring to adjust actions. Cortical circuits are posited to read out rules from high-dimensional representations of task-relevant variables in prefrontal cortex (PFC). We instead hypothesized that converging inputs from PFC, directly or via basal ganglia (BG), enable thalamus to select rules. We measured activity across PFC and connected thalamic nuclei of monkeys applying rules. Abstract rule information first appeared in ventroanterior thalamus (VA) - the main thalamic hub between BG and PFC. Mediodorsal thalamus (MD) also represented rule information before PFC, persisting to help maintain activation of relevant PFC cell ensembles. MD, a major recipient of midbrain dopamine input, was first to represent information about behavioral outcomes. A PFC-BG-thalamus model reproduced key findings, and thalamic-lesion modeling disrupted PFC rule representations. This suggests that thalamus selects high-level cognitive information from PFC and monitors behavioral outcomes of these selections.

The default mode network (DMN), salience network (SN), and central executive control network (CEN) form the well-known triple network, providing a framework for understanding various neurodevelopmental and psychiatric disorders. However, the topology of this network remains unclear in autism spectrum disorder (ASD). To gain a more profound understanding of ASD, we explored the topology of the triple network in ASD. Additionally, the striatum and thalamus are pivotal centres of information transmission within the brain, and the realization of various brain functions requires the coordination of cortical and subcortical structures. Therefore, we also investigated the topology of the cortico-subcortical network in ASD, which consists of the DMN, SN, CEN, striatum, and thalamus. Resting-state functional magnetic resonance imaging data on 208 ASD patients and 278 typically developing (TD) controls (8-18 years old) were obtained from the Autism Brain Imaging Data Exchange database. We performed graph theory analysis on the triple network and the cortico-subcortical network. The results showed that the triple network's clustering coefficient, lambda, and network local efficiency values were significantly lower in ASD, and the nodal degree and efficiency of the medial prefrontal cortex also decreased. For the cortico-subcortical network, the sigma, clustering coefficient, gamma, and network local efficiency showed the same reduction, and the altered clustering coefficient negatively correlated with ASD manifestations. In addition, the interaction between the DMN and CEN was more robust in ASD patients. These findings enhance our understanding of ASD and suggest that subcortical structures should be more considered in future ASD related studies.

Value-based decision-making involves weighing costs and benefits. The activity of the medial prefrontal cortex reflects cost-benefit assessments, and the mediodorsal thalamus, reciprocally connected with the medial prefrontal cortex, has increasingly been recognized as an active partner in decision-making. However, the specific role of the interaction between the mediodorsal thalamus and the medial prefrontal cortex in regulating the neuronal activity underlying how costs and benefits influence decision-making remains largely unexplored. We investigated this by training the rats to perform a self-determined decision-making task, where longer nose poke durations resulted in correspondingly larger rewards. Our results showed that the inactivation of either the medial prefrontal cortex or the mediodorsal thalamus significantly impaired rat to invest more nose poke duration for larger rewards. Moreover, optogenetic stimulation of the mediodorsal thalamus-medial prefrontal cortex pathway enhanced rats' motivation for larger rewards, whereas inhibition of this pathway resulted in decreased motivation. Notably, we identified a specific population of neurons in the medial prefrontal cortex that exhibited firing patterns correlated with motivation, and these neurons were modulated by the mediodorsal thalamus-medial prefrontal cortex projection. These findings suggest that the motivation during decision-making is encoded primarily by activity of particular neurons in the medial prefrontal cortex and indicate the crucial role of the mediodorsal thalamus-medial prefrontal cortex pathway in maintaining motivation.

Self-regulation (SR) dysfunction is a crucial risk factor for major depressive disorder (MDD). However, neural substrates of SR linking MDD remain unclear.

Sixty-eight healthy controls and 75 MDD patients were recruited to complete regulatory orientation assessments with the Regulatory Focus Questionnaire (RFQ) and Regulatory Mode Questionnaire (RMQ). Nodal intra and inter-network functional connectivity (FC) was defined as FC sum within networks of 46 thalamic subnuclei (TS) or 88 AAL brain regions, and between the two networks separately. Group-level volumetric and functional difference were compared by two sample t-tests. Pearson's correlation analysis and mediation analysis were utilized to investigate the relationship among imaging parameters and the two behaviors. Canonical correlation analysis (CCA) was conducted to explore the inter-network FC mode of TS related to behavioral subscales. Network-based Statistics with machine learning combining powerful brain imaging features was applied to predict individual behavioral subscales.

MDD patients showed no group-level volumetric difference in 46 TS but represented significant correlation of TS volume and nodal FC with behavioral subscales. Specially, inter-network FC of the orbital part of the right superior frontal gyrus and the left supplementary motor area mediated the correlation between RFQ/RMQ subscales and depressive severity. Furthermore, CCA identified how the two behaviors are linked via the inter-network FC mode of TS. More crucially, thalamic functional subnetworks could predict RFQ/RMQ subscales and psychomotor retardation for MDD individuals.

These findings provided neurological evidence for SR affecting depressive severity in the MDD patients and proposed potential biomarkers to identify the SR-based risk phenotype of MDD individuals.

Previous studies have suggested that the morphology and function of the thalamus and cortex are abnormal in patients with knee osteoarthritis (KOA). However, whether the thalamocortical network is differentially affected in this disorder is unknown. In this study, we examined functional and effective connectivity between the thalamus and major divisions of the cortex in 27 healthy controls and 27 KOA patients using functional magnetic resonance imaging. We also explored the topological features of the brain via graph theory analysis. The results suggested that patients with KOA had significantly reduced resting-state functional connectivity (rsFC) of the thalamo-sensorimotor pathway; enhanced rsFC of the thalamo-medial/lateral frontal cortex (mFC/LFC), parietal, temporal and occipital pathways; reduced effective connectivity of the left sensorimotor-to-thalamus pathway; and enhanced effective connectivity of the right thalamus-to-sensorimotor pathway compared with healthy controls. The functional connectivity of the thalamo-sensorimotor and thalamo-mFC pathways was enhanced when patients performed the multisource interference task. Moreover, patients with KOA presented altered nodal properties associated with thalamocortical circuits, including the thalamus, amygdala, and regions in default mode networks, compared with healthy controls. The correlation analysis suggested a significant negative correlation between thalamo-mFC rsFC and pain intensity, between thalamo-sensorimotor task-related connectivity and disease duration/depression scores, and a positive correlation between right frontal nodal properties and pain intensity in KOA patients. Taken together, these findings establish abnormal and differential alterations in the thalamocortical network associated with pain characteristics in KOA patients, which extends our understanding of their role in the pathophysiology of KOA.

The prefrontal cortex (PFC) has been strongly implicated in the pathophysiology of schizophrenia. Here, we combined high-resolution single-nuclei RNA sequencing data from the human PFC with large-scale genomic data for schizophrenia to identify constituent cell populations likely to mediate genetic liability to the disorder.

Gene expression specificity values were calculated from a single-nuclei RNA sequencing dataset comprising 84 cell populations from the human PFC, spanning gestation to adulthood. Enrichment of schizophrenia common variant liability and burden of rare protein-truncating coding variants were tested in genes with high expression specificity for each cell type. We also explored schizophrenia common variant associations in relation to gene expression across the developmental trajectory of implicated neurons.

Common risk variation for schizophrenia was prominently enriched in genes with high expression specificity for a population of mature layer 4 glutamatergic neurons emerging in infancy. Common variant liability to schizophrenia increased along the developmental trajectory of this neuronal population. Fine-mapped genes at schizophrenia genome-wide association study risk loci had significantly higher expression specificity than other genes in these neurons and in a population of layer 5/6 glutamatergic neurons. People with schizophrenia had a higher rate of rare protein-truncating coding variants in genes expressed by cells of the PFC than control individuals, but no cell population was significantly enriched above this background rate.

We identified a population of layer 4 glutamatergic PFC neurons likely to be particularly affected by common variant genetic risk for schizophrenia, which may contribute to disturbances in thalamocortical connectivity in the condition.

Synaptic plasticities, such as long-term potentiation (LTP) and depression (LTD), tune synaptic efficacy and are essential for learning and memory. Current studies of synaptic plasticity in humans are limited by a lack of adequate human models. Here, we modeled the thalamocortical system by fusing human induced pluripotent stem cell-derived thalamic and cortical organoids. Single-nucleus RNA sequencing revealed that >80% of cells in thalamic organoids were glutamatergic neurons. When fused to form thalamocortical assembloids, thalamic and cortical organoids formed reciprocal long-range axonal projections and reciprocal synapses detectable by light and electron microscopy, respectively. Using whole-cell patch-clamp electrophysiology and two-photon imaging, we characterized glutamatergic synaptic transmission. Thalamocortical and corticothalamic synapses displayed short-term plasticity analogous to that in animal models. LTP and LTD were reliably induced at both synapses; however, their mechanisms differed from those previously described in rodents. Thus, thalamocortical assembloids provide a model system for exploring synaptic plasticity in human circuits.

The reuniens (Re) nucleus is located in the ventral midline thalamus. It has fostered increasing interest, not only for its participation in a variety of cognitive functions (e.g., spatial working memory, systemic consolidation, reconsolidation, extinction of fear or generalization), but also for its neuroanatomical positioning as a bidirectional relay between the prefrontal cortex (PFC) and the hippocampus (HIP). In this review we compile and discuss recent studies having tackled a possible implication of the Re nucleus in behavioral flexibility, a major PFC-dependent executive function controlling goal-directed behaviors. Experiments considered explored a possible role for the Re nucleus in perseveration, reversal learning, fear extinction, and set-shifting. They point to a contribution of this nucleus to behavioral flexibility, mainly by its connections with the PFC, but possibly also by those with the hippocampus, and even with the amygdala, at least for fear-related behavior. As such, the Re nucleus could be a crucial crossroad supporting a PFC-orchestrated ability to cope with new, potentially unpredictable environmental contingencies, and thus behavioral flexibility and adaption.

The brain exhibits a remarkable ability to learn and execute context-appropriate behaviors. How it achieves such flexibility, without sacrificing learning efficiency, is an important open question. Neuroscience, psychology, and engineering suggest that reusing and repurposing computations are part of the answer. Here, we review evidence that thalamocortical architectures may have evolved to facilitate these objectives of flexibility and efficiency by coordinating distributed computations. Recent work suggests that distributed prefrontal cortical networks compute with flexible codes, and that the mediodorsal thalamus provides regularization to promote efficient reuse. Thalamocortical interactions resemble hierarchical Bayesian computations, and their network implementation can be related to existing gating, synchronization, and hub theories of thalamic function. By reviewing recent findings and providing a novel synthesis, we highlight key research horizons integrating computation, cognition, and systems neuroscience.

Major depressive disorder (MDD) is characterized by deficient reward functions in the brain. However, existing findings on functional alterations during reward anticipation, reward processing, and learning among MDD patients are inconsistent, and it was unclear whether a common reward system implicated in multiple reward functions is altered in MDD. Here we meta-analyzed 18 past studies that compared brain reward functions between adult MDD patients (N = 477, mean age = 26.50 years, female = 59.40%) and healthy controls (N = 506, mean age = 28.11 years, females = 55.58%), and particularly examined group differences across multiple reward functions. Jack-knife sensitivity and subgroup meta-analyses were conducted to test robustness of findings across patient comorbidity, task paradigm, and reward nature. Meta-regression analyses assessed the moderating effect of patient symptom severity and anhedonia scores. We found during reward anticipation, MDD patients showed lower activities in the lateral prefrontal-thalamus circuitry. During reward processing, patients displayed reduced activities in the right striatum and prefrontal cortex, but increased activities in the left temporal cortex. During reward learning, patients showed reduced activity in the lateral prefrontal-thalamic-striatal circuitry and the right parahippocampal-occipital circuitry but higher activities in bilateral cerebellum and the left visual cortex. MDD patients showed decreased activity in the right thalamus during both reward anticipation and learning, and in the right caudate during both reward processing and learning. Larger functional changes in MDD were observed among patients with more severe symptoms and higher anhedonia levels. The thalamic-striatal circuitry functional alterations could be the key neural mechanism underlying MDD patients overarching reward function deficiencies.

Research into ascending sensory pathways and cortical networks has generated detailed models of perception. These same cortical regions are strongly connected to subcortical structures, such as the basal ganglia (BG), which have been conceptualized as playing key roles in reinforcement learning and action selection. However, because the BG amasses experiential evidence from higher and lower levels of cortical hierarchies, as well as higher-order thalamus, it is well positioned to dynamically influence perception. Here, we review anatomical, functional, and clinical evidence to demonstrate how the BG can influence perceptual processing and conscious states. This depends on the integrative relationship between cortex, BG, and thalamus, which allows contributions to sensory gating, predictive processing, selective attention, and representation of the temporal structure of events.

Beliefs-attitudes toward some state of the environment-guide action selection and should be robust to variability but sensitive to meaningful change. Beliefs about volatility (expectation of change) are associated with paranoia in humans, but the brain regions responsible for volatility beliefs remain unknown. The orbitofrontal cortex (OFC) is central to adaptive behavior, whereas the magnocellular mediodorsal thalamus (MDmc) is essential for arbitrating between perceptions and action policies. We assessed belief updating in a three-choice probabilistic reversal learning task following excitotoxic lesions of the MDmc (n = 3) or OFC (n = 3) and compared performance with that of unoperated monkeys (n = 14). Computational analyses indicated a double dissociation: MDmc, but not OFC, lesions were associated with erratic switching behavior and heightened volatility belief (as in paranoia in humans), whereas OFC, but not MDmc, lesions were associated with increased lose-stay behavior and reward learning rates. Given the consilience across species and models, these results have implications for understanding paranoia.

In the COGNitive in Focused UltraSound (COGNIFUS) study, we examined the 6-month cognitive outcomes of patients undergoing MRgFUS thalamotomy. This study endorsed the safety profile of the procedure in terms of cognitive functions that cannot be evaluated in real-time during the procedure unlike other aspects. The aim of the COGNIFUS Part 2 study was to investigate the cognitive trajectory of MRgFUS patients over a 1-year period, in order to confirm long-term safety and satisfaction.

We prospectively evaluated the cognitive and neurobehavioral profile of patients with essential tremor (ET) or Parkinson's Disease (PD) related tremor undergoing MRgFUS thalamotomy at 1 year-follow-up following the treatment.

The sample consists of 50 patients (male 76%; mean age ± SD 69.0 ± 8.56; mean disease duration ± SD 12.13 ± 12.59; ET 28, PD 22 patients). A significant improvement was detected at the 1 year-follow-up assessment in anxiety and mood feelings (Hamilton Anxiety rating scale 5.66 ± 5.02 vs. 2.69 ± 3.76, p ≤ <0.001; Beck depression Inventory II score 3.74 ± 3.80 vs. 1.80 ± 2.78, p = 0.001), memory domains (Rey Auditory Verbal Learning Test, immediate recall 31.76 ± 7.60 vs. 35.38 ± 7.72, p = 0.001 and delayed recall scores 5.57 ± 2 0.75 vs. 6.41 ± 2.48), frontal functions (Frontal Assessment Battery score 14.24 ± 3.04 vs. 15.16 ± 2.74) and in quality of life (Quality of life in Essential Tremor Questionnaire 35.00 ± 12.08 vs. 9.03 ± 10.64, p ≤ 0.001 and PD Questionnaire -8 7.86 ± 3.10 vs. 3.09 ± 2.29, p ≤ 0.001).

Our study supports the long-term efficacy and cognitive safety of MRgFUS treatment for ET and PD.

Parkinson's disease (PD) patients experience improvement in motor symptoms after deep brain stimulation (DBS) and before initiating stimulation. This is called the microlesion effect. However, the mechanism remains unclear. The study aims to comprehensively explore the changes in functional connectivity (FC) patterns in movement-related brain regions in PD patients during the microlesion phase through seed-based FC analysis.

The study collected the resting functional magnetic resonance imaging data of 49 PD patients before and after DBS surgery (off stimulation). The cortical and subcortical areas related to motor function were selected for seed-based FC analysis. Meanwhile, their relationship with the motor scale was investigated.

The motor-related brain regions were selected as the seed point, and we observed various FC declines within the motor network brain regions. These declines were primarily in the left middle temporal gyrus, bilateral middle frontal gyrus, right supplementary motor area, left precentral gyrus, left postcentral gyrus, left inferior frontal gyrus, and right superior frontal gyrus after DBS.

The movement-related network was extensively reorganized during the microlesion period. The study provided new information on enhancing motor function from the network level post-DBS.

Consciousness can be conceptualized as varying along at least two dimensions: the global state of consciousness and the content of conscious experience. Here, we highlight the cellular and systems-level contributions of the thalamus to conscious state and then argue for thalamic contributions to conscious content, including the integrated, segregated, and continuous nature of our experience. We underscore vital, yet distinct roles for core- and matrix-type thalamic neurons. Through reciprocal interactions with deep-layer cortical neurons, matrix neurons support wakefulness and determine perceptual thresholds, whereas the cortical interactions of core neurons maintain content and enable perceptual constancy. We further propose that conscious integration, segregation, and continuity depend on the convergent nature of corticothalamic projections enabling dimensionality reduction, a thalamic reticular nucleus-mediated divisive normalization-like process, and sustained coherent activity in thalamocortical loops, respectively. Overall, we conclude that the thalamus plays a central topological role in brain structures controlling conscious experience.

Whether patients with myasthenia gravis (MG) exhibit cognitive impairment is controversial. Also the underlying mechanisms are unknown. We aimed to investigate alterations in cognitive function, neurometabolite levels, and brain function in patients with MG and to explore the associations between abnormal regional brain functional activity, neurometabolite concentrations in the MPFC and left thalamus, and cognitive activity in patients with MG. Neuropsychological tests, proton magnetic resonance spectroscopy, and resting-state functional magnetic resonance imaging were performed on 41 patients with MG and 45 race-, sex-, age-, and education-matched healthy controls (HCs). The results suggest that MG is accompanied by cognitive decline, as indicated by global cognitive function, visual-spatial function, language, memory, abnormalities in regional brain functional activity, and neurometabolite alterations (including GABA, NAA, and Cho) in the medial prefrontal cortex (MPFC) and left thalamus. Cognitive impairment in patients with MG may be related to abnormal regional brain functional activity and changes in neurometabolites, and regional brain functional activity may be modulated by specific neurometabolites.

Transcranial alternating current stimulation (tACS) is an efficient neuromodulation technique that enhances cognitive function in a non-invasive manner. Using functional magnetic resonance imaging, we investigated whether tACS with different phase lags (0° and 180°) between the dorsal anterior cingulate and left dorsolateral prefrontal cortices modulated inhibitory control performance during the Stroop task. We found out-of-phase tACS mediated improvements in task performance, which was neurodynamically reflected as putamen, dorsolateral prefrontal, and primary motor cortical activation as well as prefrontal-based top-down functional connectivity. Our observations uncover the neurophysiological bases of tACS-phase-dependent neuromodulation and provide a feasible non-invasive approach to effectively modulate inhibitory control.

Executive control, the ability to organize thoughts and action plans in real time, is a defining feature of higher cognition. Classical theories have emphasized cortical contributions to this process, but recent studies have reinvigorated interest in the role of the thalamus. Although it is well established that local thalamic damage diminishes cognitive capacity, such observations have been difficult to inform functional models. Recent progress in experimental techniques is beginning to enrich our understanding of the anatomical, physiological, and computational substrates underlying thalamic engagement in executive control. In this review, we discuss this progress and particularly focus on the mediodorsal thalamus, which regulates the activity within and across frontal cortical areas. We end with a synthesis that highlights frontal thalamocortical interactions in cognitive computations and discusses its functional implications in normal and pathological conditions.

Synaptic plasticities, such as long-term potentiation (LTP) and depression (LTD), tune synaptic efficacy and are essential for learning and memory. Current studies of synaptic plasticity in humans are limited by a lack of adequate human models. Here, we modeled the thalamocortical system by fusing human induced pluripotent stem cell-derived thalamic and cortical organoids. Single-nucleus RNA-sequencing revealed that most cells in mature thalamic organoids were glutamatergic neurons. When fused to form thalamocortical assembloids, thalamic and cortical organoids formed reciprocal long-range axonal projections and reciprocal synapses detectable by light and electron microscopy, respectively. Using whole-cell patch-clamp electrophysiology and two-photon imaging, we characterized glutamatergic synaptic transmission. Thalamocortical and corticothalamic synapses displayed short-term plasticity analogous to that in animal models. LTP and LTD were reliably induced at both synapses; however, their mechanisms differed from those previously described in rodents. Thus, thalamocortical assembloids provide a model system for exploring synaptic plasticity in human circuits.

Abnormal white matter has been reported in patients with end-stage renal disease (ESRD). However, few studies have investigated the relationship between specific damage segments and cognition in ESRD. This study aimed to delineate white matter alterations in ESRD and its relationship with cognition.

A total of 36 patients undergoing hemodialysis and 25 healthy controls underwent diffusion tensor imaging (DTI) and a series of neuropsychiatric tests. Automated fiber quantification was used to extract distinct DTI indices, and the relationship between the specific segment of the white matter and clinical properties was investigated. Furthermore, a support vector machine was applied to differentiate patients with ESRD from healthy controls.

Fractional anisotropy values decreased in multiple fiber bundles, including bilateral thalamic radiata, cingulum cingulate, inferior fronto-occipital fasciculus (IFOF), uncinate, Callosum_Forceps_Major/Callosum_Forceps_Minor (CFMaj/CFMin), and left uncinate from the tract level in patients with ESRD. Specific damaged segments were detected in 8 fiber bundles, including bilateral thalamic radiation, cingulum cingulate, IFOF, CFMin, and left corticospinal tract. Few alterations in these fiber bundles were correlated with cognition impairment and hemoglobin levels. The tract profiles of the left thalamic radiata and left cingulum cingulate could be used to differentiate hemodialysis patients from healthy controls, with an accuracy of 76.9% and 67.6%, respectively.

This study revealed white matter damage in hemodialysis patients. This damage occurred in specific segments of the tract, especially in the left thalamic radiata and left cingulum cingulate, which might become a new biomarker for patients with ESRD and cognition impairment.

In the primate brain, the lateral prefrontal cortex (LPF) is a large, heterogeneous region critically involved in the cognitive control of behavior, consisting of several connectionally and functionally distinct areas. Studies in macaques provided evidence for distinctive patterns of cortical connectivity between architectonic areas located at different dorsoventral levels and for rostrocaudal gradients of parietal and frontal connections in the three main architectonic LPF areas: 46d, 46v, and 12r. In the present study, based on tracer injections placed at different dorsoventral and rostrocaudal cortical levels, we have examined the thalamic projections to the LPF to examine to what extent fine-grained connectional gradients of cortical connectivity are reflected in the topography of thalamo-LPF projections. The results showed mapping onto the nucleus medialis dorsalis (MD), by far the major source of thalamic input to the LPF, of rostral-to-caudal LPF zones, in which MD zones projecting to more caudal LPF sectors are located more rostral than those projecting to intermediate LPF sectors. Furthermore, the MD zones projecting to the rostral LPF sectors tended to be much more extensive in the rostrocaudal direction. One rostrolateral MD sector appeared to be a common source of projections to caudal prefrontal areas involved in the oculomotor frontal domain, a more caudal and ventral MD sector to a large extent of the ventral LPF, and middle and dorsal MD sectors to most of the dorsal LPF. Additional topographically organized projections to LPF areas originated from the nucleus pulvinaris medialis and projections from the nucleus anterior medialis selectively targeted more rostral sectors of LPF. Thus, the present data suggest that the topography of the MD-LPF projections does not adhere to simple topological rules, but is mainly organized according to functional criteria.

The involvement of specific basal ganglia-thalamocortical circuits in response inhibition has been extensively mapped in animal models. However, the pivotal nodes and directed causal regulation within this inhibitory circuit in humans remains controversial.

The main aim of the present study was to determine the causal information flow and critical nodes in the basal ganglia-thalamocortical inhibitory circuits and also to examine whether these are modulated by biological factors (i.e. sex) and behavioral performance.

Here, we capitalize on the recent progress in robust and biologically plausible directed causal modeling (DCM-PEB) and a large response inhibition dataset (n = 250) acquired with concomitant functional magnetic resonance imaging to determine key nodes, their causal regulation and modulation via biological variables (sex) and inhibitory performance in the inhibitory circuit encompassing the right inferior frontal gyrus (rIFG), caudate nucleus (rCau), globus pallidum (rGP), and thalamus (rThal).

The entire neural circuit exhibited high intrinsic connectivity and response inhibition critically increased causal projections from the rIFG to both rCau and rThal. Direct comparison further demonstrated that response inhibition induced an increasing rIFG inflow and increased the causal regulation of this region over the rCau and rThal. In addition, sex and performance influenced the functional architecture of the regulatory circuits such that women displayed increased rThal self-inhibition and decreased rThal to GP modulation, while better inhibitory performance was associated with stronger rThal to rIFG communication. Furthermore, control analyses did not reveal a similar key communication in a left lateralized model.

Together, these findings indicate a pivotal role of the rIFG as input and causal regulator of subcortical response inhibition nodes.

Each cortical area has a distinct pattern of anatomical connections within the thalamus, a central subcortical structure composed of functionally and structurally distinct nuclei. Previous studies have suggested that certain cortical areas may have more extensive anatomical connections that target multiple thalamic nuclei, which potentially allows them to modulate distributed information flow. However, there is a lack of quantitative investigations into anatomical connectivity patterns within the thalamus. Consequently, it remains unknown if cortical areas exhibit systematic differences in the extent of their anatomical connections within the thalamus. To address this knowledge gap, we used diffusion magnetic resonance imaging (dMRI) to perform brain-wide probabilistic tractography for 828 healthy adults from the Human Connectome Project. We then developed a framework to quantify the spatial extent of each cortical area's anatomical connections within the thalamus. Additionally, we leveraged resting-state functional MRI, cortical myelin, and human neural gene expression data to test if the extent of anatomical connections within the thalamus varied along the cortical hierarchy. Our results revealed two distinct corticothalamic tractography motifs: 1) a sensorimotor cortical motif characterized by focal thalamic connections targeting posterolateral thalamus, associated with fast, feed-forward information flow; and 2) an associative cortical motif characterized by diffuse thalamic connections targeting anteromedial thalamus, associated with slow, feed-back information flow. These findings were consistent across human subjects and were also observed in macaques, indicating cross-species generalizability. Overall, our study demonstrates that sensorimotor and association cortical areas exhibit differences in the spatial extent of their anatomical connections within the thalamus, which may support functionally-distinct cortico-thalamic information flow.

Epilepsy is a common, often debilitating disease of hyperexcitable neural networks. While medically intractable cases may benefit from surgery, there may be no single, well-localized focus for resection or ablation. In such cases, approaching the disease from a network-based perspective may be beneficial.

Herein, the authors provide a narrative review of normal thalamic anatomy and physiology and propose general strategies for preventing and/or aborting seizures by modulating this structure. Additionally, they make specific recommendations for targeting the thalamus within different contexts, motivated by a more detailed discussion of its distinct nuclei and their respective connectivity. By describing important principles governing thalamic function and its involvement in seizure networks, the authors aim to provide a primer for those now entering this fast-growing field of thalamic neuromodulation for epilepsy.

The thalamus is critically involved with the function of many cortical and subcortical areas, suggesting it may serve as a compelling node for preventing or aborting seizures, and so it has increasingly been targeted for the surgical treatment of epilepsy. As various thalamic neuromodulation strategies for seizure control are developed, there is a need to ground such interventions in a mechanistic, circuit-based framework.

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an innovative method for the unilateral treatment of essential tremor (ET) and Parkinson's disease (PD) related tremor. Our aim was to assess cognitive changes following MRgFUS thalamotomy to better investigate its safety profile.

We prospectively investigated the cognitive and neurobehavioral profile of patients consecutively undergoing MRgFUS within a 2-year period. Patients had a comprehensive clinical and neuropsychological assessment before and six months after MRgFUS thalamotomy.

The final sample consisted of 40 patients (males 38; mean age±SD 67.7 ± 10.7; mean disease duration±SD 9.3 ± 5.6; ET 22, PD 18 patients). For the whole sample, improvements were detected in tremor (Fahn-Tolosa-Marin Clinical Rating Scale for tremor 35.79 ± 14.39 vs 23.03 ± 10.95; p < 0.001), anxiety feelings (Hamilton Anxiety rating scale 5.36 ± 3.80 vs 2.54 ± 3.28, p < 0.001), in the overall cognitive status (MMSE 25.93 ± 3.76 vs 27.54 ± 2.46, p 0.003; MOCA 22.80 ± 4.08 vs 24.48 ± 3.13, p < 0.001), and in quality of life (Quality of life in Essential Tremor Questionnaire 36.14 ± 12.91 vs 5.14 ± 6.90, p < 0.001 and PD Questionnaire-8 5.61 ± 4.65 vs 1.39 ± 2.33, p 0.001). No changes were detected in frontal and executive functions, verbal fluency and memory, abstract reasoning and problem-solving abilities.

Our study moves a step forward in establishing the cognitive sequelae of MRgFUS thalamotomy and in endorsing effectiveness and safety.

Psychosis spectrum disorder (PSD) affects 1% of the world population and results in a lifetime of chronic disability, causing devastating personal and economic consequences. Developing new treatments for PSD remains a challenge, particularly those that target its core cognitive deficits. A key barrier to progress is the tenuous link between the basic neurobiological understanding of PSD and its clinical phenomenology. In this perspective, we focus on a key opportunity that combines innovations in non-invasive human neuroimaging with basic insights into thalamic regulation of functional cortical connectivity. The thalamus is an evolutionary conserved region that forms forebrain-wide functional loops critical for the transmission of external inputs as well as the construction and update of internal models. We discuss our perspective across four lines of evidence: First, we articulate how PSD symptomatology may arise from a faulty network organization at the macroscopic circuit level with the thalamus playing a central coordinating role. Second, we discuss how recent animal work has mechanistically clarified the properties of thalamic circuits relevant to regulating cortical dynamics and cognitive function more generally. Third, we present human neuroimaging evidence in support of thalamic alterations in PSD, and propose that a similar "thalamocortical dysconnectivity" seen in pharmacological imaging (under ketamine, LSD and THC) in healthy individuals may link this circuit phenotype to the common set of symptoms in idiopathic and drug-induced psychosis. Lastly, we synthesize animal and human work, and lay out a translational path for biomarker and therapeutic development.

Despite the previous inconsistent findings of structural and functional abnormalities of the thalamus in patients with major depressive disorder (MDD), the disruption of the thalamic nuclei in the pathophysiology of this disorder has not yet been adequately studied. Therefore, we investigated the volumetric changes of thalamic subregions and their nuclei in drug-naïve, first-episode MDD patients. We also investigated the association between HAM-D scores, a clinical scale frequently used to evaluate the severity of depression and thalamic nuclei volumes in MDD patients.

This study included 76 drug-naïve MDD patients and an equal number of healthy subjects. Magnetic resonance imaging (MRI) data were obtained using a 3T MR system and thalamic nuclei volumes were evaluated using FreeSurfer ver.7.11. The volumetric differences were compared by one-way analysis of covariance (ANCOVA) and to ensure that effects were not accounted for by other factors, age, sex, and ETICV variables were included as covariates.

We observed significant volume reductions of the left whole thalamus (p < 0.003) and several thalamic nuclei mostly on the left side in the MDD group compared with healthy controls (HCs). Furthermore, we have revealed weak negative correlations between several thalamic nuclei volumes and HAM-D total and subscale scores.

This is the first research study to investigate alterations of the various thalamic nuclei volumes in MDD patients compared with HCs. Moreover, we first analyzed the association between individual thalamic nuclei volumes and HAM-D subscale scores. Though our study may be restricted at certain levels, especially by the demographic difference between the two groups, they possibly contribute at a preliminary level to understanding the thalamic structural changes at its subregions in patients with drug-naïve, first-episode MDD.

A shared mechanism across species heralds the arrival of self-generated sensations, helping the brain to anticipate, and therefore distinguish, self-generated from externally generated sensations. In mammals, this sensory prediction mechanism is supported by communication within a cortico-ponto-cerebellar-thalamo-cortical loop. Schizophrenia is associated with impaired sensory prediction as well as abnormal structural and functional connections between nodes in this circuit. Despite the pons' principal role in relaying and processing sensory information passed from the cortex to cerebellum, few studies have examined pons connectivity in schizophrenia. Here, we first briefly describe how the pons contributes to sensory prediction. We then summarize schizophrenia-related abnormalities in the cortico-ponto-cerebellar-thalamo-cortical loop, emphasizing the dearth of research on the pons relative to thalamic and cerebellar connections. We conclude with recommendations for advancing our understanding of how the pons relates to sensory prediction failures in schizophrenia.

Specific thalamic nuclei are implicated in healthy aging and age-related neurodegenerative diseases. However, few methods are available for robust automated segmentation of thalamic nuclei. The threefold aims of this study were to validate the use of a modified thalamic nuclei segmentation method on standard T1 MRI data, to apply this method to quantify age-related volume declines, and to test functional meaningfulness by predicting performance on motor testing. A modified version of THalamus Optimized Multi-Atlas Segmentation (THOMAS) generated 22 unilateral thalamic nuclei. For validation, we compared nuclear volumes obtained from THOMAS parcellation of white-matter-nulled (WMn) MRI data to T1 MRI data in 45 participants. To examine the effects of age/sex on thalamic nuclear volumes, T1 MRI available from a second data set of 121 men and 117 women, ages 20-86 years, were segmented using THOMAS. To test for functional ramifications, composite regions and constituent nuclei were correlated with Grooved Pegboard test scores. THOMAS on standard T1 data showed significant quantitative agreement with THOMAS from WMn data, especially for larger nuclei. Sex differences revealing larger volumes in men than women were accounted for by adjustment with supratentorial intracranial volume (sICV). Significant sICV-adjusted correlations between age and thalamic nuclear volumes were detected in 20 of the 22 unilateral nuclei and whole thalamus. Composite Posterior and Ventral regions and Ventral Anterior/Pulvinar nuclei correlated selectively with higher scores from the eye-hand coordination task. These results support the use of THOMAS for standard T1-weighted data as adequately robust for thalamic nuclear parcellation.

Medial prefrontal cortex (mPFC) interacts with distributed networks that give rise to goal-directed behavior through afferent and efferent connections with multiple thalamic nuclei and recurrent basal ganglia-thalamocortical circuits. Recent studies have revealed individual roles for different thalamic nuclei: mediodorsal (MD) regulation of signaling properties in mPFC neurons, intralaminar control of cortico-basal ganglia networks, ventral medial facilitation of integrative motor function, and hippocampal functions supported by ventral midline and anterior nuclei. Large scale mapping studies have identified functionally distinct cortico-basal ganglia-thalamocortical subnetworks that provide a structural basis for understanding information processing and functional heterogeneity within the basal ganglia. Behavioral analyses comparing functional deficits produced by lesions or inactivation of specific thalamic nuclei or subregions of mPFC or the basal ganglia have elucidated the interdependent roles of these areas in adaptive goal-directed behavior. Electrophysiological recordings of mPFC neurons in rats performing delayed non-matching-to position (DNMTP) and other complex decision making tasks have revealed populations of neurons with activity related to actions and outcomes that underlie these behaviors. These include responses related to motor preparation, instrumental actions, movement, anticipation and delivery of action outcomes, memory delay, and spatial context. Comparison of results for mPFC, MD, and ventral pallidum (VP) suggest critical roles for mPFC in prospective processes that precede actions, MD for reinforcing task-relevant responses in mPFC, and VP for providing feedback about action outcomes. Synthesis of electrophysiological and behavioral results indicates that different networks connecting mPFC with thalamus and the basal ganglia are organized to support distinct functions that allow organisms to act efficiently to obtain intended outcomes.