Association Cortex Research Articles

In vivo whole-cortex marker of excitation-inhibition ratio indexes cortical maturation and cognitive ability in youth

A balanced excitation-inhibition ratio (E/I ratio) is critical for healthy brain function. Normative development of cortex-wide E/I ratio remains unknown. Here, we noninvasively estimate a putative marker of whole-cortex E/I ratio by fitting a large-scale biophysically plausible circuit model to resting-state functional MRI (fMRI) data. We first confirm that our model generates realistic brain dynamics in the Human Connectome Project. Next, we show that the estimated E/I ratio marker is sensitive to the gamma-aminobutyric acid (GABA) agonist benzodiazepine alprazolam during fMRI. Alprazolam-induced E/I changes are spatially consistent with positron emission tomography measurement of benzodiazepine receptor density. We then investigate the relationship between the E/I ratio marker and neurodevelopment. We find that the E/I ratio marker declines heterogeneously across the cerebral cortex during youth, with the greatest reduction occurring in sensorimotor systems relative to association systems. Importantly, among children with the same chronological age, a lower E/I ratio marker (especially in the association cortex) is linked to better cognitive performance. This result is replicated across North American (8.2 to 23.0 y old) and Asian (7.2 to 7.9 y old) cohorts, suggesting that a more mature E/I ratio indexes improved cognition during normative development. Overall, our findings open the door to studying how disrupted E/I trajectories may lead to cognitive dysfunction in psychopathology that emerges during youth.

The heritability and structural correlates of resting-state fMRI complexity

The complexity of fMRI signals quantifies temporal dynamics of spontaneous neural activity, which has been increasingly recognized as providing important insights into cognitive functions and psychiatric disorders. However, its heritability and structural underpinnings are not well understood. Here, we utilize multi-scale sample entropy to extract resting-state fMRI complexity in a large healthy adult sample from the Human Connectome Project. We show that fMRI complexity at multiple time scales is heritable in broad brain regions. Heritability estimates are modest and regionally variable. We relate fMRI complexity to brain structure including surface area, cortical myelination, cortical thickness, subcortical volumes, and total brain volume. We find that surface area is negatively correlated with fine-scale complexity and positively correlated with coarse-scale complexity in most cortical regions, especially the association cortex. Most of these correlations are related to common genetic and environmental effects. We also find positive correlations between cortical myelination and fMRI complexity at fine scales and negative correlations at coarse scales in the prefrontal cortex, lateral temporal lobe, precuneus, lateral parietal cortex, and cingulate cortex, with these correlations mainly attributed to common environmental effects. We detect few significant associations between fMRI complexity and cortical thickness. Despite the non-significant association with total brain volume, fMRI complexity exhibits significant correlations with subcortical volumes in the hippocampus, cerebellum, putamen, and pallidum at certain scales. Collectively, our work establishes the genetic basis and structural correlates of resting-state fMRI complexity across multiple scales, supporting its potential application as an endophenotype for psychiatric disorders.

Different state-dependence of population codes across cortex.

During perceptual decision-making, behavioral performance varies with changes in internal states such as arousal, motivation, and strategy. Yet it is unknown how these internal states affect information coding across cortical regions involved in differing aspects of sensory perception and decision-making. We recorded neural activity from the primary auditory cortex (AC) and posterior parietal cortex (PPC) in mice performing a navigation-based sound localization task. We then modeled transitions in the behavioral strategies mice used during task performance. Mice transitioned between three latent performance states with differing decision-making strategies: an 'optimal' state and two 'sub-optimal' states characterized by choice bias and frequent errors. Performance states strongly influenced population activity patterns in association but not sensory cortex. Surprisingly, activity of individual PPC neurons was better explained by external inputs and behavioral variables during suboptimal behavioral performance than in the optimal performance state. Furthermore, shared variability across neurons (coupling) in PPC was strongest in the optimal state. In AC, shared variability was similarly weak across all performance states. Together, these findings indicate that neural activity in association cortex is more strongly linked to internal state than in sensory cortex.

An Unusual Case of Hypothalamic Hamartoma With Nongelastic Seizures and Posterior Cortex Connectivity

BackgroundTo describe a rare seizure semiology originating from a hypothalamic hamartoma in a child, along with unusual ictal onset and connectivity pattern, and provide a review of the pathophysiology of epilepsy associated with hypothalamic hamartoma and management. MethodsA detailed retrospective chart review and literature search were performed using Pubmed and Embase. ResultsWe present a case of a three-year-old male who presented with dyscognitive seizures with onset at age 22 months. Stereoelectroencephalography exploration confirmed the onset in hypothalamic hamartoma with rapid propagation to the temporal-parietal-occipital association cortex and precuneus. The patient's epilepsy was cured with laser ablation of the hamartoma. ConclusionPublished literature mostly describes a more anterior frontal or temporal epileptic network with primarily gelastic seizures being the hallmark type of seizures associated with hypothalamic hamartoma. We highlight a rare posterior cortex network with an atypical presentation of focal nonmotor seizures with impaired awareness in the setting of a hypothalamic hamartoma. Stereotactic laser ablation of the hamartoma rendered seizure freedom. Early diagnosis and appropriate treatment can lead to seizure freedom.

Further characterisation of late somatosensory evoked potentials using electroencephalogram and magnetoencephalogram source imaging.

Beside the well-documented involvement of secondary somatosensory area, the cortical network underlying late somatosensory evoked potentials (P60/N60 and P100/N100) is still unknown. Electroencephalogram and magnetoencephalogram source imaging were performed to further investigate the origin of the brain cortical areas involved in late somatosensory evoked potentials, using sensory inputs of different strengths and by testing the correlation between cortical sources. Simultaneous high-density electroencephalograms and magnetoencephalograms were performed in 19 participants, and electrical stimulation was applied to the median nerve (wrist level) at intensity between 1.5 and 9 times the perceptual threshold. Source imaging was undertaken to map the stimulus-induced brain cortical activity according to each individual brain magnetic resonance imaging, during three windows of analysis covering early and late somatosensory evoked potentials. Results for P60/N60 and P100/N100 were compared with those for P20/N20 (early response). According to literature, maximal activity during P20/N20 was found in central sulcus contralateral to stimulation site. During P60/N60 and P100/N100, activity was observed in contralateral primary sensorimotor area, secondary somatosensory area (on both hemispheres) and premotor and multisensory associative cortices. Late responses exhibited similar characteristics but different from P20/N20, and no significant correlation was found between early and late generated activities. Specific clusters of cortical activities were activated with specific input/output relationships underlying early and late somatosensory evoked potentials. Cortical networks, partly common to and distinct from early somatosensory responses, contribute to late responses, all participating in the complex somatosensory brain processing.

Key morphological features of human pyramidal neurons.

The basic building block of the cerebral cortex, the pyramidal cell, has been shown to be characterized by a markedly different dendritic structure among layers, cortical areas, and species. Functionally, differences in the structure of their dendrites and axons are critical in determining how neurons integrate information. However, within the human cortex, these neurons have not been quantified in detail. In the present work, we performed intracellular injections of Lucifer Yellow and 3D reconstructed over 200 pyramidal neurons, including apical and basal dendritic and local axonal arbors and dendritic spines, from human occipital primary visual area and associative temporal cortex. We found that human pyramidal neurons from temporal cortex were larger, displayed more complex apical and basal structural organization, and had more spines compared to those in primary sensory cortex. Moreover, these human neocortical neurons displayed specific shared and distinct characteristics in comparison to previously published human hippocampal pyramidal neurons. Additionally, we identified distinct morphological features in human neurons that set them apart from mouse neurons. Lastly, we observed certain consistent organizational patterns shared across species. This study emphasizes the existing diversity within pyramidal cell structures across different cortical areas and species, suggesting substantial species-specific variations in their computational properties.

Development of segregation and integration of functional connectomes during the first 1,000 days

The first 1,000days of human life lay the foundation for brain development and later cognitive growth. However, the developmental rules of the functional connectome during this critical period remain unclear. Using high-resolution, longitudinal, task-free functional magnetic resonance imaging data from 930 scans of 665 infants aged 28 postmenstrual weeks to 3 years, we report the early maturational process of connectome segregation and integration. We show the dominant development of local connections alongside a few global connections, the shift of brain hubs from primary regions to high-order association cortices, the developmental divergence of network segregation and integration along the anterior-posterior axis, the prediction of neurocognitive outcomes, and their associations with gene expression signatures of microstructural development and neuronal metabolic pathways. These findings advance our understanding of the principles of connectome remodeling during early life and its neurobiological underpinnings and have implications for studying typical and atypical development.

Intrinsic functional connectivity of motor and heteromodal association cortex predicts individual differences in regulatory focus.

Regulatory focus theory (RFT) describes two cognitive-motivational systems for goal pursuit-the promotion and prevention systems-important for self-regulation and previously implicated in vulnerability to psychopathology. According to RFT, the promotion system is engaged in attaining ideal goals (e.g. hopes and dreams), whereas the prevention system is associated with accomplishing ought goals (e.g. duties and obligations). Prior task-based functional magnetic resonance imaging (fMRI) studies have mostly explored the mapping of these two systems onto the activity of a priori brain regions supporting motivation and executive control in both healthy and depressed adults. However, complex behavioral processes such as those guided by individual differences in regulatory focus are likely supported by widely distributed patterns of intrinsic functional connectivity. We used data-driven connectome-based predictive modeling to identify patterns of distributed whole-brain intrinsic network connectivity associated with individual differences in promotion and prevention system orientation in 1,307 young university volunteers. Our analyses produced a network model predictive of prevention but not promotion orientation, specifically the subjective experience of successful goal pursuit using prevention strategies. The predictive model of prevention success was highlighted by decreased intrinsic functional connectivity of both heteromodal association cortices in the parietal and limbic networks and the primary motor cortex. We discuss these findings in the context of strategic inaction, which drives individuals with a strong dispositional prevention orientation to inhibit their behavioral tendencies in order to shield the self from potential losses, thus maintaining the safety of the status quo but also leading to trade-offs in goal pursuit success.

Dorsal dentate gyrus mediated enriched environment-induced anxiolytic and antidepressant effects in cortical infarcted mice

Anxiety and depression are the most common mental health disorders worldwide, each affecting around 30% stroke survivors. These complications not only affect the functional recovery and quality of life in stroke patients, but also are distressing for caregivers. However, effective treatments are still lacking. Enriched environment (EE), characterized with novel and multi-dimensional stimulation, has been reported to exert therapeutic effects on physical and cognitive function. In addition, EE also had potential positive effects on emotional disorders after ischemic stroke; however, the underling mechanisms have not been well elucidated. This study aimed to explore the effectiveness of EE on emotional disorders after cerebral ischemia and its underling mechanism. Sensorimotor cortical infarction was induced by photothrombosis with stable infarct location and volume, resulting in motor dysfunction, anxiety and depression-like behaviors in mice, with decreased ALFF and ReHo values and decreased c-fos expression in the infarction area and adjacent regions. Seven days' EE treatment significantly improved motor function of contralateral forelimb and exhibited anxiolytic and antidepressant effects in infarcted mice. Compared to the mice housing in a standard environment, those subjected to acute EE stimulation had significantly increased ALFF and ReHo values in the bilateral somatosensory cortex (S1, S2), dorsal dentate gyrus (dDG), dorsal CA1 of hippocampus (dCA1), lateral habenular nucleus (LHb), periaqueductal gray (PAG), ipsilateral primary motor cortex (M1), retrosplenial cortex (RSC), parietal association cortex (PtA), dorsal CA3 of hippocampus (dCA3), claustrum (Cl), ventral pallidum (VP), amygdala (Amy), and contralateral auditory cortex (Au). Some of, but not all, the ipsilateral brain regions mentioned above showed accompanying increases in c-fos expression with the most significant changes in the dDG. The number of FosB positive cells in the dDG, decreased in infarcted mice, was significantly increased after chronic EE treatment. Chemogenetic activation of dDG neurons reduced anxiety and depressive-like behaviors in infarcted mice, while neuronal inhibition resulted in void of the anxiolytic and antidepressant effects of EE. Altogether, these findings indicated that dDG neurons may mediate EE-triggered anxiolytic and antidepressant effects in cortical infarcted mice.

Functional connectivity development along the sensorimotor-association axis enhances the cortical hierarchy

Human cortical maturation has been posited to be organized along the sensorimotor-association axis, a hierarchical axis of brain organization that spans from unimodal sensorimotor cortices to transmodal association cortices. Here, we investigate the hypothesis that the development of functional connectivity during childhood through adolescence conforms to the cortical hierarchy defined by the sensorimotor-association axis. We tested this pre-registered hypothesis in four large-scale, independent datasets (total n = 3355; ages 5–23 years): the Philadelphia Neurodevelopmental Cohort (n = 1207), Nathan Kline Institute-Rockland Sample (n = 397), Human Connectome Project: Development (n = 625), and Healthy Brain Network (n = 1126). Across datasets, the development of functional connectivity systematically varied along the sensorimotor-association axis. Connectivity in sensorimotor regions increased, whereas connectivity in association cortices declined, refining and reinforcing the cortical hierarchy. These consistent and generalizable results establish that the sensorimotor-association axis of cortical organization encodes the dominant pattern of functional connectivity development.

Stress and Psychosocial Distress Scale with Blunted Oscillatory Dynamics Serving Abstract Reasoning

Background. Chronic stress is associated with a multitude of psychopathological disorders that share similar alterations in neural dynamics and symptomatology. Applying the National Institute of Mental Health’s Research Domain Criteria (RDoC) framework, we probed the stress-diathesis model by identifying how a transdiagnostic psychosocial distress index representing high-dimensional patterns of stress-related aberrations was coupled to the neural oscillatory dynamics serving abstract reasoning. Methods. The sample consisted of 69 adults (mean age=44.77 years, SD=13.66) who completed the NIH Toolbox Emotion Battery (NIHTB-EB) and a matrix reasoning task during magnetoencephalography (MEG). A transdiagnostic psychosocial distress index was computed using exploratory factor analysis with assessments from the NIHTB-EB. Whole-brain correlations were conducted using the resulting psychosocial distress index for each oscillatory response, and the resulting peak voxels were extracted for mediation analyses to assess the degree to which neural oscillatory activity mediates the interplay between perceived stress and psychosocial distress. Results. We found that elevated psychosocial distress was associated with blunted oscillatory alpha/beta and gamma responses in key cortical association regions. Further, we found that only alpha/beta activity in the right superior temporal sulcus partially mediated the relationship between perceived stress and psychosocial distress. Conclusions. The present study is among the first to couple perceived stress and psychosocial distress with alterations in oscillatory activity during a matrix reasoning task. These findings illuminate the relationship between perceived stress and neural alterations associated with psychopathology.

Association cortical areas in the mouse contain a large population of fast-spiking GABAergic neurons that do not express parvalbumin.

GABAergic neurons represent 10-15% of the neuronal population of the cortex but exert a powerful control over information flow in cortical circuits. The largest GABAergic class in the neocortex is represented by the parvalbumin-expressing fast-spiking neurons, which provide powerful somatic inhibition to their postsynaptic targets. Recently, the density of parvalbumin interneurons has been shown to be lower in associative areas of the mouse cortex as compared with sensory and motor areas. Modelling work based on these quantifications linked the low-density of parvalbumin interneurons with specific computations of associative cortices. However, it is still unknown whether the total GABAergic population of association cortices is smaller or whether another GABAergic type can compensate for the low density of parvalbumin interneurons. In the present study, we investigated these hypotheses using a combination of neuroanatomy, mouse genetics and neurophysiology. We found that the GABAergic population of association areas is comparable with that of primary sensory areas, and it is enriched of fast-spiking neurons that do not express parvalbumin and were not accounted for by previous quantifications. We developed an intersectional viral strategy to demonstrate that the population of fast-spiking neurons is comparable across cortical regions. Our results provide quantifications of the density of fast-spiking GABAergic neurons and offers new biological constrains to refine current models of cortical computations.

Atypical connectome topography and signal flow in temporal lobe epilepsy

Temporal lobe epilepsy (TLE) is the most common pharmaco-resistant epilepsy in adults. While primarily associated with mesiotemporal pathology, recent evidence suggests that brain alterations in TLE extend beyond the paralimbic epicenter and impact macroscale function and cognitive functions, particularly memory. Using connectome-wide manifold learning and generative models of effective connectivity, we examined functional topography and directional signal flow patterns between large-scale neural circuits in TLE at rest. Studying a multisite cohort of 95 patients with TLE and 95 healthy controls, we observed atypical functional topographies in the former group, characterized by reduced differentiation between sensory and transmodal association cortices, with most marked effects in bilateral temporo-limbic and ventromedial prefrontal cortices. These findings were consistent across all study sites, present in left and right lateralized patients, and validated in a subgroup of patients with histopathological validation of mesiotemporal sclerosis and post-surgical seizure freedom. Moreover, they were replicated in an independent cohort of 30 TLE patients and 40 healthy controls. Further analyses demonstrated that reduced differentiation related to decreased functional signal flow into and out of temporolimbic cortical systems and other brain networks. Parallel analyses of structural and diffusion-weighted MRI data revealed that topographic alterations were independent of TLE-related cortical thinning but partially mediated by white matter microstructural changes that radiated away from paralimbic circuits. Finally, we found a strong association between the degree of functional alterations and behavioral markers of memory dysfunction. Our work illustrates the complex landscape of macroscale functional imbalances in TLE, which can serve as intermediate markers bridging microstructural changes and cognitive impairment.

Functional Neurologic Disorders: The Role of Limbic System

IntroductionFunctional Neurological Disorders (FND), also called hysteria or conversion disorder, have represented a challenge over the centuries in terms of comprehension of the mechanisms responsible for symptoms which mimic neurological diseases without organic damage. Charcot considered hysteria primarily a hereditary disorder, but also considered that environmental factors including physical and emotional stress served as provoking factors. The prevailing etiologic theories of FND are psychosocial and still strongly dominated by the Freudian concept of conversion – a psychologic symptom is converted into a somatic symptom as a way of dealing with the distress of the symptom. However, physiologic studies with fMRI are necessary to understand the neurological mechanisms involved in FND symptoms. Convergent neuroimaging findings have implicated abnormal limbic-motor interactions in response to emotional stimuli in FND patients, demonstrated a possible role of the limbic system (LS) in FND neurophysiology.ObjectivesUnderstand the role of LS in the neurophysiologic mechanisms involve in FND.MethodsSystematic review of the literature published in PubMed, using the terms “Functional Neurological Disorders”, “Limbic System”, “Emotions”.ResultsPhysiologic studies of functional weakness and sensory loss reveal normal functioning of primary motor and sensory cortex, but abnormalities of premotor cortex and association cortices. This suggests a top-down influence creating the dysfunction during the action control. Indeed, fMRI studies with FND motor patients show a hypoactivation of cortical and subcortical motor pathways, and a hyperactivity in limbic areas related with an abnormal limbic regulation with increased amygdala activity. In fact, studies have found a dysfunction in the medial prefrontal areas in FDN patients suggesting that they might have an abnormal affective representation (AR) of self-relevant information encoded in this region, which can later induce specific behavioral patterns of thought interaction with sensorimotor circuits. The abnormal AR could be influence by a dysfunction in LS regulation. Indeed, emotions are one of the major factors influencing movement choice. Moreover, limbic structures, such as the amygdala, can be influenced by genetic factors and/or early life stress. Thus, abnormal functioning of LS could lead to functional disorders by deranged top-down control.ConclusionsIn conclusion, FND patients may have an abnormal AR and/or emotion regulation mechanisms possibly due to prior experience or partly genetically determined which interact with lower-order functions leading to the production of the functional symptoms, where LS have an important role. However, much further empiric research is needed to better understand this fascinating and debilitating condition, as well as to derive new perspectives for more efficient therapeutic interventions in these patients.Disclosure of InterestNone Declared

Altered excitatory and inhibitory ionotropic receptor subunit expression in the cortical visuospatial working memory network in schizophrenia.

Dysfunction of the cortical dorsal visual stream and visuospatial working memory (vsWM) network in individuals with schizophrenia (SZ) likely reflects alterations in both excitatory and inhibitory neurotransmission within nodes responsible for information transfer across the network, including primary visual (V1), visual association (V2), posterior parietal (PPC), and dorsolateral prefrontal (DLPFC) cortices. However, the expression patterns of ionotropic glutamatergic and GABAergic receptor subunits across these regions, and alterations of these patterns in SZ, have not been investigated. We quantified transcript levels of key subunits for excitatory N-methyl-D-aspartate receptors (NMDARs), excitatory alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs), and inhibitory GABAA receptors (GABAARs) in postmortem total gray matter from V1, V2, PPC, and DLPFC of unaffected comparison (UC) and matched SZ subjects. In UC subjects, levels of most AMPAR and NMDAR mRNAs exhibited opposite rostral-to-caudal gradients, with AMPAR GRIA1 and GRIA2 mRNA levels highest in DLPFC and NMDAR GRIN1 and GRIN2A mRNA levels highest in V1. GABRA5 and GABRA1 mRNA levels were highest in DLPFC and V1, respectively. In SZ, most transcript levels were lower relative to UC subjects, with these differences largest in V1, intermediate in V2 and PPC, and smallest in DLPFC. In UC subjects, these distinct patterns of receptor transcript levels across the cortical vsWM network suggest that the balance between excitation and inhibition is achieved in a region-specific manner. In SZ subjects, the large deficits in excitatory and inhibitory receptor transcript levels in caudal sensory regions suggest that abnormalities early in the vsWM pathway might contribute to altered information processing in rostral higher-order regions.

Atypical co-development of the thalamus and cortex in autism: Evidence from age-related white-gray contrast change.

Recent studies have shown that white-gray contrast (WGC) of either cortical or subcortical gray matter provides for accurate predictions of age in typically developing (TD) children, and that, at least for the cortex, it changes differently with age in subjects with autism spectrum disorder (ASD) compared to their TDpeers. Our previous study showed different patterns of contrast change between ASD and TD in sensorimotor and association cortices. While that study was confined to the cortex, we hypothesized that subcortical structures, particularly the thalamus, were involved in the observed cortical dichotomy between lower and higher processing. The current paper investigates that hypothesis using the WGC measures from the thalamus in addition to those from the cortex. We compared age-related WGC changes in the thalamus to those in the cortex. To capture the simultaneity of this change across the two structures, we devised a metric capturing the co-development of the thalamus and cortex (CoDevTC), proportional to the magnitude of cortical and thalamic age-related WGC change. We calculated this metric for each of the subjects in a large homogeneous sample taken from the Autism Brain Imaging Data Exchange (ABIDE) (N = 434). We used structural MRI data from the largest high-quality cross-sectional sample (NYU) as well as two other large high-quality sites, GU and OHSU, all three using Siemens 3T scanners. We observed that the co-development features in ASD and TD exhibit contrasting patterns; specifically, some higher-order thalamic nuclei, such as the lateral dorsal nucleus, exhibited reduction in codevelopment with most of the cortex in ASD compared to TD. Moreover, this difference in the CoDevTC pattern correlates with a number of behavioral measures across multiple cognitive and physiological domains. The results support previous notions of altered connectivity in autism, but add more specific evidence about the heterogeneity in thalamocortical development that elucidates the mechanisms underlying the clinical features of ASD.

Visual Deprivation during Mouse Critical Period Reorganizes Network-Level Functional Connectivity.

A classic example of experience-dependent plasticity is ocular dominance (OD) shift, in which the responsiveness of neurons in the visual cortex is profoundly altered following monocular deprivation (MD). It has been postulated that OD shifts also modify global neural networks, but such effects have never been demonstrated. Here, we use wide-field fluorescence optical imaging (WFOI) to characterize calcium-based resting-state functional connectivity during acute (3 d) MD in female and male mice with genetically encoded calcium indicators (Thy1-GCaMP6f). We first establish the fundamental performance of WFOI by computing signal to noise properties throughout our data processing pipeline. Following MD, we found that Δ band (0.4-4 Hz) GCaMP6 activity in the deprived visual cortex decreased, suggesting that excitatory activity in this region was reduced by MD. In addition, interhemispheric visual homotopic functional connectivity decreased following MD, which was accompanied by a reduction in parietal and motor homotopic connectivity. Finally, we observed enhanced internetwork connectivity between the visual and parietal cortex that peaked 2 d after MD. Together, these findings support the hypothesis that early MD induces dynamic reorganization of disparate functional networks including the association cortices.

Human striatal association megaclusters.

The striatum receives projections from multiple regions of the cerebral cortex consistent with the role of the basal ganglia in diverse motor, affective, and cognitive functions. Within the striatum, the caudate receives projections from association cortex, including multiple distinct regions of prefrontal cortex. Building on recent insights about the details of how juxtaposed cortical networks are specialized for distinct aspects of higher-order cognition, we revisited caudate organization using within-individual precision neuroimaging initially in two intensively scanned individuals (each scanned 31 times). Results revealed that the caudate has side-by-side regions that are coupled to at least five distinct distributed association networks, paralleling the organization observed in the cerebral cortex. We refer to these spatial groupings of regions as striatal association megaclusters. Correlation maps from closely juxtaposed seed regions placed within the megaclusters recapitulated the five distinct cortical networks, including their multiple spatially distributed regions. Striatal association megaclusters were explored in 15 additional participants (each scanned at least 8 times), finding that their presence generalizes to new participants. Analysis of the laterality of the regions within the megaclusters further revealed that they possess asymmetries paralleling their cortical counterparts. For example, caudate regions linked to the language network were left lateralized. These results extend the general notion of parallel specialized basal ganglia circuits with the additional discovery that, even within the caudate, there is fine-grained separation of multiple distinct higher-order networks that reflects the organization and lateralization found in the cerebral cortex.NEW & NOTEWORTHY An individualized precision neuroimaging approach reveals juxtaposed zones of the caudate that are coupled with five distinct networks in association cortex. The organization of these caudate zones recapitulates organization observed in the cerebral cortex and extends the notion of specialized basal ganglia circuits.

Functional features of the mirror neuron system during action observation and execution in patients with anxiety and depressive symptoms

The perception and comprehension of non-verbal information and body language in humans and higher primates are realized by the mirror neuron system (MNS). Anxiety and depressive symptoms may change social perception, which could manifest as functional changes in the MNS. In this paper, using the inverse electroencephalography (EEG) problem and rhythm suppression, we investigated spatial and frequency distortions of the MNS in 24 patients exhibiting depressive and anxiety symptoms and 23 controls. EEG was recorded during four motor tasks: action observation (where participants observed a hand gesture performed by a demonstrator), imagination, execution, and joint execution (simultaneous execution with the demonstrator). Mu suppression was employed across a wide frequency and spatial range to assess the level of MNS activity, while the sLORETA method was employed to localize the activity sources. The results indicate that the patients demonstrated task-selective mu suppression mainly during observation and joint execution in the frontal, central, and occipital areas of the cortex across a wide frequency range. In contrast, the controls demonstrated clear and pronounced mu rhythm suppression in the central regions of the brain in the upper-frequency range (10.5 – 13 Hz) during all mirroring tasks. These results suggest that patients with anxiety and depressive symptoms engage additional neural resources to complete social tasks, particularly involving auxiliary neural networks located in the frontal associative arrays and visual cortex.

Monosynaptic Rabies Tracing Reveals Sex- and Age-Dependent Dorsal Subiculum Connectivity Alterations in an Alzheimer's Disease Mouse Model.

The subiculum (SUB), a hippocampal formation structure, is among the earliest brain regions impacted in Alzheimer's disease (AD). Toward a better understanding of AD circuit-based mechanisms, we mapped synaptic circuit inputs to dorsal SUB using monosynaptic rabies tracing in the 5xFAD mouse model by quantitatively comparing the circuit connectivity of SUB excitatory neurons in age-matched controls and 5xFAD mice at different ages for both sexes. Input-mapped brain regions include the hippocampal subregions (CA1, CA2, CA3), medial septum and diagonal band, retrosplenial cortex, SUB, postsubiculum (postSUB), visual cortex, auditory cortex, somatosensory cortex, entorhinal cortex, thalamus, perirhinal cortex (Prh), ectorhinal cortex, and temporal association cortex. We find sex- and age-dependent changes in connectivity strengths and patterns of SUB presynaptic inputs from hippocampal subregions and other brain regions in 5xFAD mice compared with control mice. Significant sex differences for SUB inputs are found in 5xFAD mice for CA1, CA2, CA3, postSUB, Prh, lateral entorhinal cortex, and medial entorhinal cortex: all of these areas are critical for learning and memory. Notably, we find significant changes at different ages for visual cortical inputs to SUB. While the visual function is not ordinarily considered defective in AD, these specific connectivity changes reflect that altered visual circuitry contributes to learning and memory deficits. Our work provides new insights into SUB-directed neural circuit mechanisms during AD progression and supports the idea that neural circuit disruptions are a prominent feature of AD.