Heteromodal Association Cortex Research Articles

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.

Identifying subgroups of eating behavior traits unrelated to obesity using functional connectivity and feature representation learning.

Eating behavior is highly heterogeneous across individuals and cannot be fully explained using only the degree of obesity. We utilized unsupervised machine learning and functional connectivity measures to explore the heterogeneity of eating behaviors measured by a self-assessment instrument using 424 healthy adults (mean ± standard deviation [SD] age = 47.07 ± 18.89 years; 67% female). We generated low-dimensional representations of functional connectivity using resting-state functional magnetic resonance imaging and estimated latent features using the feature representation capabilities of an autoencoder by nonlinearly compressing the functional connectivity information. The clustering approaches applied to latent features identified three distinct subgroups. The subgroups exhibited different levels of hunger traits, while their body mass indices were comparable. The results were replicated in an independent dataset consisting of 212 participants (mean ± SD age = 38.97 ± 19.80 years; 35% female). The model interpretation technique of integrated gradients revealed that the between-group differences in the integrated gradient maps were associated with functional reorganization in heteromodal association and limbic cortices and reward-related subcortical structures such as the accumbens, amygdala, and caudate. The cognitive decoding analysis revealed that these systems are associated with reward- and emotion-related systems. Our findings provide insights into the macroscopic brain organization of eating behavior-related subgroups independent of obesity.

Global diversity in individualized cortical network topography.

Individualized cortical network topography (ICNT) varies between people and exhibits great variability in the association networks in the human brain. However, these findings were mainly discovered in Western populations. It remains unclear whether and how ICNT is shaped by the non-Western populations. Here, we leveraged a multisession hierarchical Bayesian model to define individualized functional networks in White American and Han Chinese populations with data from both US and Chinese Human Connectome Projects. We found that both the size and spatial topography of individualized functional networks differed between White American and Han Chinese groups, especially in the heteromodal association cortex (including the ventral attention, control, language, dorsal attention, and default mode networks). Employing a support vector machine, we then demonstrated that ethnicity-related ICNT diversity can be used to identify an individual's ethnicity with high accuracy (74%, pperm < 0.0001), with heteromodal networks contributing most to the classification. This finding was further validated through mass-univariate analyses with generalized additive models. Moreover, we reveal that the spatial heterogeneity of ethnic diversity in ICNT correlated with fundamental properties of cortical organization, including evolutionary cortical expansion, brain myelination, and cerebral blood flow. Altogether, this case study highlights a need for more globally diverse and publicly available neuroimaging datasets.

Structural Brain Architectures Match Intrinsic Functional Networks and Vary across Domains: A Study from 15 000+ Individuals.

Brain structural networks have been shown to consistently organize in functionally meaningful architectures covering the entire brain. However, to what extent brain structural architectures match the intrinsic functional networks in different functional domains remains under explored. In this study, based on independent component analysis, we revealed 45 pairs of structural-functional (S-F) component maps, distributing across nine functional domains, in both a discovery cohort (n = 6005) and a replication cohort (UK Biobank, n = 9214), providing a well-match multimodal spatial map template for public use. Further network module analysis suggested that unimodal cortical areas (e.g., somatomotor and visual networks) indicate higher S-F coherence, while heteromodal association cortices, especially the frontoparietal network (FPN), exhibit more S-F divergence. Collectively, these results suggest that the expanding and maturing brain association cortex demonstrates a higher degree of changes compared with unimodal cortex, which may lead to higher interindividual variability and lower S-F coherence.

Resting state auditory-language cortex connectivity is associated with hallucinations in clinical and biological subtypes of psychotic disorders

BackgroundAuditory hallucinations are prevalent across the major psychotic disorders, but their underlying mechanism is poorly understood. Limited prior work supports a hypothesis of altered auditory/language brain systems. To more definitively assess this, we examined whether alterations in resting state connectivity of auditory and language cortices are associated with hallucination severity in a large sample of individuals in the schizo-bipolar spectrum. MethodsWhole brain resting state connectivity of auditory and language cortex (primary auditory cortex, unimodal auditory association cortex, Wernicke’s area [speech and heteromodal association cortex] and Broca’s area [speech production motor]) was evaluated for 243 subjects with schizophrenia, schizoaffective, or bipolar disorder with psychosis and 186 healthy controls from the Bipolar Schizophrenia Network on Intermediate Phenotypes (B-SNIP) study. Regression analyses were conducted to evaluate whether resting state connectivity of auditory and language cortex was a significant predictor of current overall hallucination severity (information about specific modality of hallucinations experienced was not available). ResultsIncreased connectivity between lower and higher order regions of left temporal-parietal auditory/language processing cortex was associated with worse hallucination severity for all psychosis patients. Additionally, within bipolar subjects, increased interhemispheric connectivity between higher order temporal-parietal auditory/language regions was related to greater hallucination severity. When patients were categorized by B-SNIP biomarker-based Biotype groups, interhemispheric connectivity between left auditory association cortex and right core auditory cortex was related to greater hallucination severity for Biotype 1 patients. Exploratory analyses resulted in different patterns of connectivity of auditory/language cortex in patients and controls, unrelated to current hallucination severity. ConclusionsAlthough the findings cannot be precisely attributed to auditory hallucination severity or possible differences in such experiences between groups, increased connectivity among the left hemisphere auditory and receptive language cortex may represent a significant factor contributing to hallucination severity across psychotic disorders, and additional subgroup specific connectivity alterations may also be present.

Alterations in the fronto-limbic network and corpus callosum in borderline-personality disorder

Neuroimaging research provides evidence of grey matter changes in the prefrontal-limbic network in borderline personality disorder (BPD), yet research scarcely examines the white matter (WM) within this circuitry. The present study aimed to explore WM in prefrontal-limbic brain networks within BPD. Quantitative diffusion tensor imaging (DTI-MRI) measures of fractional anisotropy (FA) and mean diffusion (MD) were used to analyze the neural pathways in fifteen individuals with BPD (M = 25, SD = 6.76), in comparison to thirteen healthy individuals (M = 27.92, SD = 8.41). Quantitative DTI-MRI measures of FA and MD were evaluated for the cingulum, the fornix, the corpus callosum (CC), the inferior longitudinal fasciculus (ILF), the superior longitudinal fasciculus (SLF) and the uncinate fasciculus (UF). Lower FA values for both the left and the right cingulum, the genu, body, and splenium of the CC, left ILF and right SLF were found in BPD, compared to healthy individuals. MD values were higher for the genu and splenium of the CC in BPD. The findings indicate that a large-scale emotional brain network is affected in BPD with alterations in MD and FA of WM prefrontal-limbic pathways of the heteromodal association cortex involved in emotion processing and emotion regulation.

Associating Psychotic Symptoms with Altered Brain Anatomy in Psychotic Disorders Using Multidimensional Item Response Theory Models.

Reduced cortical thickness has been demonstrated in psychotic disorders, but its relationship to clinical symptoms has not been established. We aimed to identify the regions throughout neocortex where clinical psychosis manifestations correlate with cortical thickness. Rather than perform a traditional correlation analysis using total scores on psychiatric rating scales, we applied multidimensional item response theory to identify a profile of psychotic symptoms that was related to a region where cortical thickness was reduced. This analysis was performed using a large population of probands with psychotic disorders (N= 865), their family members (N= 678) and healthy volunteers (N= 347), from the 5-site Bipolar-Schizophrenia Network for Intermediate Phenotypes. Regional cortical thickness from structural magnetic resonance scans was measured using FreeSurfer; individual symptoms were rated using the Positive and Negative Syndrome Scale, Montgomery-Asberg Depression Rating Scale, and Young Mania Rating Scale. A cluster of cortical regions whose thickness was inversely related to severity of psychosis symptoms was identified. The regions turned out to be located contiguously in a large region of heteromodal association cortex including temporal, parietal and frontal lobe regions, suggesting a cluster of contiguous neocortical regions important to psychosis expression. When we tested the relationship between reduced cortical surface area and high psychotic symptoms we found no linked regions describing a related cortical set.

Shifts in myeloarchitecture characterise adolescent development of cortical gradients.

We studied an accelerated longitudinal cohort of adolescents and young adults (n = 234, two time points) to investigate dynamic reconfigurations in myeloarchitecture. Intracortical profiles were generated using magnetization transfer (MT) data, a myelin-sensitive magnetic resonance imaging contrast. Mixed-effect models of depth specific intracortical profiles demonstrated two separate processes i) overall increases in MT, and ii) flattening of the MT profile related to enhanced signal in mid-to-deeper layers, especially in heteromodal and unimodal association cortices. This development was independent of morphological changes. Enhanced MT in mid-to-deeper layers was found to spatially co-localise specifically with gene expression markers of oligodendrocytes. Interregional covariance analysis revealed that these intracortical changes contributed to a gradual differentiation of higher-order from lower-order systems. Depth-dependent trajectories of intracortical myeloarchitectural development contribute to the maturation of structural hierarchies in the human neocortex, providing a model for adolescent development that bridges microstructural and macroscopic scales of brain organisation.

Endless Fluctuations: Temporal Dynamics of the Amplitude of Low Frequency Fluctuations.

Intrinsic neural activity ubiquitously persists in all physiological states. However, how intrinsic brain activity (iBA) changes over a short time remains unknown. To uncover the brain dynamics' theoretic underpinning, electrophysiological relevance, and neuromodulation, we identified iBA dynamics on simulated data, electroencephalogram-functional magnetic resonance imaging (EEG-fMRI) data, and repetitive transcranial magnetic stimulation (rTMS) fMRI data using sliding-window analysis. The temporal variability (dynamics) of iBA were quantified using the variance of the amplitude of low-frequency fluctuations (ALFF) over time. We first used simulated fMRI data to examine the effects of various parameters including window length, and step size on dynamic ALFF. Second, using EEG-fMRI data, we found that the heteromodal association cortex had the most variable dynamics while the limbic regions had the least, consistent with previous findings. In addition, the temporal variability of dynamic ALFF depended on EEG power fluctuations. Moreover, using rTMS fMRI data, we found that the temporal variability of dynamic ALFF could be modulated by rTMS. Taken together, these results provide evidence about the theory, relevance, and adjustability of iBA dynamics.

Altered neuroplasticity of prefrontal cortex in adult autism spectrum disorder

Introduction: Stimulation-induced plastic changes in human prefrontal region have not been sufficiently elucidated due to lack of reliable biomarkers like motor evoked potentials (MEP). The study was aimed to establish reliable biomarkers of TMS-evoked potentials (TEP), which could evaluate the neuroplasticity in the heteromodal association cortices.

Gradients of connectivity distance are anchored in primary cortex

Connectivity between distant cortical areas is a valuable, yet costly feature of cortical organization and is predominantly found between regions of heteromodal association cortex. The recently proposed ‘tethering hypothesis’ describes the emergence of long-distance connections in association cortex as a function of their spatial separation from primary cortical regions. Here, we investigate this possibility by characterizing the distance between functionally connected areas along the cortical surface. We found a systematic relationship between an area’s characteristic connectivity distance and its distance from primary cortical areas. Specifically, the further a region is located from primary sensorimotor regions, the more distant are its functional connections with other areas of the cortex. The measure of connectivity distance also captured major functional subdivisions of the cerebral cortex: unimodal, attention, and higher-order association regions. Our findings provide evidence for the anchoring role of primary cortical regions in establishing the spatial distribution of cortical properties that are related to functional specialization and differentiation.

A case of episodic derealisation in focal cortical dysplasia: First looks at the whole elephant?

Derealisation remains a bewildering and obscure phenomenological entity with shifting identities on the dissociation spectrum of disorders. A consensus seems to have emerged that the symptom can be produced by a variety of agents which finally act through a common pathway whose identity remains elusive and whose components have thus far only emerged piecemeal. Temporal lobe dysfunction, a covert epileptogenic process and aberrations within a network comprising the amygdala, the anterior cingulate and the prefrontal cortices have all been implicated, however independently none account holistically for the peculiar phenomenology of derealisation. We present a case of focal cortical dysplasia of the right supramarginal gyrus, who reported with three distinct symptoms – panic episodes, a heightening of baseline anxiety and recurrent derealisation, all of which responded well to antiepileptic drugs. This represents the first case with evidence of dysfunction in all areas of the heteromodal association cortex (HASC), a neural network responsible for integration of sensory input and required to understand the significance of events and objects in the external environment. Derangements in the HASC have produced non-modality specific neuropsychiatric deficits, and the component anatomy can account well for the aberrations in emotion, perception and memory characteristic of derealisation. Collectively, the model provides a credible basis with which to explain the curious symptoms encountered in derealisation and provides a promising line of enquiry.

Schneiderian first rank symptoms in schizophrenia: A developmental neuroscience evaluation

IntroductionSelf disorders in schizophrenia have been suggested to have distinct neurobiological underpinnings. Using comprehensive neuro-scientific assessments including a neurophysiological, a neurochemical and a neuropsychological marker, this study assesses disordered-“self” in schizophrenia. MethodsTwenty schizophrenia patients with first rank symptoms (FRS;FRS+), 20 patients without FRS (FRS−) and 20 healthy controls (HC) were assessed for psychopathology, especially on specially designed FRS score sheets with a narrow and a broad definition. Resting state electroencephalography was acquired using 256-electrodes; gamma spectral-power was measured in 8 regions of interest. Serum BDNF and self-monitoring were also assessed. Comparative and correlation analysis were conducted in addition to a step-wise discriminant function analysis. ResultsFRS+ group with greater positive symptom score and a lower negative symptom score, showed significantly increased gamma spectral power, especially on right hemispheric regions, along with lower BDNF levels and lower scores on self-monitoring compared to FRS− and HC. Serum BDNF levels and gamma spectral power in the region corresponding right inferior parietal lobule were identified as predictors that most accurately classified the defined groups. ConclusionsSchizophrenia patients satisfying the criteria of presence of first rank symptoms represent a distinct neurodevelopmental subgroup with associated features of predominantly positive symptoms, significantly lower neurotrophin levels, aberrant resting state brain activity in the heteromodal association cortex and performing poorer on self-monitoring tasks.

Age-related cortical thinning in cognitively healthy individuals in their 60s: the PATH Through Life study

Although it is recognized that the human cortex thins with age, longitudinal estimates of thinning patterns specific to healthy young-old age (<75 years) individuals are lacking. Importantly, many neurodegenerative disorders first manifest between midlife and old age, and normative estimates may provide a reference for differential change associated with such disorders. Here, we provide longitudinal estimates of cortical thinning observed over 12 years in a large group (n = 396) of healthy individuals, aged 60–66 years at baseline scan, who were scanned with magnetic resonance imaging (1.5T) on 4 occasions. Longitudinal age-related thinning was observed across most of the cortices, with a mean change of −0.3% per year. We measured significant thinning in heteromodal association cortex, with less thinning in regions expected to atrophy later in life (e.g., primary sensory cortex). Men showed more extensive thinning than women. Our comparison of cross-sectional and longitudinal estimates adds to growing evidence that cross-sectional designs may underestimate age-related changes in cortical thickness.

Spatial patterns of atrophy, hypometabolism, and amyloid deposition in Alzheimer's disease correspond to dissociable functional brain networks

Recent neuroimaging studies of Alzheimer's disease (AD) have emphasized topographical similarities between AD-related brain changes and a prominent cortical association network called the default-mode network (DMN). However, the specificity of distinct imaging abnormalities for the DMN compared to other intrinsic connectivity networks (ICNs) of the limbic and heteromodal association cortex has not yet been examined systematically. We assessed regional amyloid load using AV45-PET, neuronal metabolism using FDG-PET, and gray matter volume using structural MRI in 473 participants from the Alzheimer's Disease Neuroimaging Initiative, including preclinical, predementia, and clinically manifest AD stages. Complementary region-of-interest and voxel-based analyses were used to assess disease stage- and modality-specific changes within seven principle ICNs of the human brain as defined by a standardized functional connectivity atlas. Amyloid deposition in AD dementia showed a preference for the DMN, but high effect sizes were also observed for other neocortical ICNs, most notably the frontoparietal-control network. Atrophic changes were most specific for an anterior limbic network, followed by the DMN, whereas other neocortical networks were relatively spared. Hypometabolism appeared to be a mixture of both amyloid- and atrophy-related profiles. Similar patterns of modality-dependent network specificity were also observed in the predementia and, for amyloid deposition, in the preclinical stage. These quantitative data confirm a high vulnerability of the DMN for multimodal imaging abnormalities in AD. However, rather than being selective for the DMN, imaging abnormalities more generally affect higher order cognitive networks and, importantly, the vulnerability profiles of these networks markedly differ for distinct aspects of AD pathology.

Reduced cortical thickness and its association with social reactivity in children with autism spectrum disorder

Symptomatology and behavioral characteristics in autism spectrum disorders (ASD) have increasingly been linked to abnormalities in early brain growth patterns of affected children. Studies investigating specific components of gray matter structure, such as cortical thickness (CT), have produced conflicting results, and have rarely included additional measures of social impairment. In the present study, we applied a surface-based whole brain analysis to investigate CT in a sample of 36 pre-adolescent children [18 subjects with ASD (IQ mean: 111) and 18 healthy controls (IQ mean: 112.8), age range 6–12 years]. The CT analysis revealed widespread, but mostly left-hemispheric thinning in frontal, temporal, parietal and occipital brain areas related to the theory-of-mind network and the heteromodal association cortex. In an exploratory analysis, CT was observed to be differently associated with social impairment in children with ASD compared with typically developing children. The affected neuroanatomical regions are related to characteristic deficits in language, cognition and behavior that are often observed in the disorder. The relationship between social impairment and CT in children with ASD and controls seems to indicate aberrant developmental trajectories in ASD emerging early in life.

Altered Gray Matter Structural Covariance Networks in Early Stages of Alzheimer's Disease.

Clinical symptoms observed in Alzheimer's disease (AD) patients may reflect variations within specific large-scale brain networks, modeling AD as a disconnection syndrome. The present magnetic resonance imaging study aims to compare the organization of gray matter structural covariance networks between 109 cognitively unimpaired controls (CTRL) and 109 AD patients positive to beta-amyloid at the early stages of the disease, using voxel-based morphometry. The default-mode network (DMN; medial temporal lobe subsystem) was less extended in AD patients in comparison with CTRL, with a significant decrease in the structural association between the entorhinal cortex and the medial prefrontal and the dorsolateral prefrontal cortices. The DMN (midline core subsystem) was also less extended in AD patients. Trends toward increased structural association were observed in the salience and executive control networks. The observed changes suggest that early disruptions in structural association between heteromodal association cortices and the entorhinal cortex could contribute to an isolation of the hippocampal formation, potentially giving rise to the clinical hallmark of AD, progressive memory impairment. It also provides critical support to the hypothesis that the reduced connectivity within the DMN in early AD is accompanied by an enhancement of connectivity in the salience and executive control networks.

Specialization and integration of functional thalamocortical connectivity in the human infant

Connections between the thalamus and cortex develop rapidly before birth, and aberrant cerebral maturation during this period may underlie a number of neurodevelopmental disorders. To define functional thalamocortical connectivity at the normal time of birth, we used functional MRI (fMRI) to measure blood oxygen level-dependent (BOLD) signals in 66 infants, 47 of whom were at high risk of neurocognitive impairment because of birth before 33 wk of gestation and 19 of whom were term infants. We segmented the thalamus based on correlation with functionally defined cortical components using independent component analysis (ICA) and seed-based correlations. After parcellating the cortex using ICA and segmenting the thalamus based on dominant connections with cortical parcellations, we observed a near-facsimile of the adult functional parcellation. Additional analysis revealed that BOLD signal in heteromodal association cortex typically had more widespread and overlapping thalamic representations than primary sensory cortex. Notably, more extreme prematurity was associated with increased functional connectivity between thalamus and lateral primary sensory cortex but reduced connectivity between thalamus and cortex in the prefrontal, insular and anterior cingulate regions. This work suggests that, in early infancy, functional integration through thalamocortical connections depends on significant functional overlap in the topographic organization of the thalamus and that the experience of premature extrauterine life modulates network development, altering the maturation of networks thought to support salience, executive, integrative, and cognitive functions.

Converging evidence for the neuroanatomic basis of combinatorial semantics in the angular gyrus.

Human thought and language rely on the brain's ability to combine conceptual information. This fundamental process supports the construction of complex concepts from basic constituents. For example, both "jacket" and "plaid" can be represented as individual concepts, but they can also be integrated to form the more complex representation "plaid jacket." Although this process is central to the expression and comprehension of language, little is known about its neural basis. Here we present evidence for a neuroanatomic model of conceptual combination from three experiments. We predicted that the highly integrative region of heteromodal association cortex in the angular gyrus would be critical for conceptual combination, given its anatomic connectivity and its strong association with semantic memory in functional neuroimaging studies. Consistent with this hypothesis, we found that the process of combining concepts to form meaningful representations specifically modulates neural activity in the angular gyrus of healthy adults, independent of the modality of the semantic content integrated. We also found that individual differences in the structure of the angular gyrus in healthy adults are related to variability in behavioral performance on the conceptual combination task. Finally, in a group of patients with neurodegenerative disease, we found that the degree of atrophy in the angular gyrus is specifically related to impaired performance on combinatorial processing. These converging anatomic findings are consistent with a critical role for the angular gyrus in conceptual combination.

Altered cortical maturation in adolescent cannabis users with and without schizophrenia

During late adolescence, progressive cortical thinning occurs in heteromodal association cortex (HASC) that is thought to subserve cognitive development. However, the impact of cannabis use disorder (CUD) upon cortical gray matter development in both healthy adolescents and adolescents with early-onset schizophrenia (EOS) is unclear. T1-weighted magnetic resonance images were acquired from 79 adolescents at baseline and after an 18-month follow-up: 17 with EOS, 17 with CUD, 11 with EOS+CUD, and 34 healthy controls (HC). Mean age at baseline was 16.4years (CUD+) and 17.0years (CUD−). Using FreeSurfer, measures of cortical thickness for ROIs within HASC were obtained. A 2 (EOS versus no EOS)×2 (CUD versus no CUD) multivariate analysis of covariance was applied to change scores from baseline to follow-up to test for main effects of EOS and CUD and an interaction effect. After adjusting for covariates, a significant main effect of CUD was observed. Adolescents with CUD showed an attenuated loss of cortical thickness in the left and right supramarginal, left and right inferior parietal, right pars triangularis, left pars opercularis, left superior frontal, and left superior temporal regions compared to non-using subjects. Stepwise linear regression analysis indicated that greater cumulative cannabis exposure predicted greater cortical thickness in both the left (p=.008) and right (p=.04) superior frontal gyri at study endpoint after adjusting for baseline cortical thickness for the entire sample. These preliminary longitudinal data demonstrate an atypical pattern of cortical development in HASC in adolescents with CUD relative to non-using subjects, across diagnostic groups. Additional studies are needed to replicate these data and to clarify the clinical significance of these findings.