Biomedical subjects

Vince D Calhoun

Publications and source records attributed to Vince D Calhoun.

At least 19 recordsLinked to original sources

PubMed2026

Dynamic Fusion of Genomics and Functional Network Connectivity in UK Biobank Reveals Schizophrenia-Related SNP Manifolds.

Many mental disorders show strong genetic influence. In parallel, dynamic functional network connectivity (dFNC) has shown high sensitivity to brain changes related to mental disorders. However, previous studies linking dFNC to genetics largely follow a paradigm to identify associations between one set of genetic factors and multiple sets of connectivity features from different dFNC states, ignoring the potential variability in genetic correlates across states. We propose a novel joint ICA (jICA)-based "dynamic fusion" framework to identify dynamically tuned genetic manifolds. A sliding window approach was utilized to estimate four dFNC states and compute subject-level state-average dFNC (sa-dFNC) features. The sa-dFNC features of each state were combined with schizophrenia risk single nucleotide polymorphisms (SNPs) within a jICA fusion framework, resulting in four parallel fusions in 32,861 individuals of the UK Biobank cohort. The extracted four sets of joint SNP-dFNC components were further validated for clinical relevance in a combined schizophrenia cohort of 820 individuals (348 patients). The similarity of SNP-dFNC components across four parallel fusions was evaluated as a measure of state variability. We observed a mixture of "state-invariant" and "state-variant" components for SNP and dFNC modalities. Particularly, the schizophrenia-related state-variant SNP components, or manifolds, complemented each other by capturing different SNPs involved in the same biological functions, revealing a partition of genomic risk particularly elicited by the dynamics of brain function. By augmenting the SNP factors to state-variant manifolds, this dynamic fusion framework promises additional insights into the underlying genetic risk of disease-related alterations in dynamic brain function.

Humans↗

PubMed2025

Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma.

Post-traumatic stress (PTS) encompasses a range of psychological responses following trauma, which may lead to more severe outcomes such as post-traumatic stress disorder (PTSD). Identifying early neuroimaging biomarkers that link brain function to PTS outcomes is critical for understanding PTSD risk. This longitudinal study examines the association between brain dynamic functional network connectivity (dFNC) and current/future PTS symptom severity, and the impact of sex on this relationship. By analyzing 275 participants' dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=-0.197, p corrected = 0.0079) and future (r=-0.176, p corrected = 0.0176) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.205, p corrected = 0.0079). We additionally observed that the association between the network dynamics of the inter-network and intra-network brain state with symptom severity is more pronounced in female group. Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger effect in female group, underscoring the importance of sex differences.

Journal Article↗

PubMed2021

1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans.

Low-frequency 1q21.1 distal deletion and duplication copy number variant (CNV) carriers are predisposed to multiple neurodevelopmental disorders, including schizophrenia, autism and intellectual disability. Human carriers display a high prevalence of micro- and macrocephaly in deletion and duplication carriers, respectively. The underlying brain structural diversity remains largely unknown. We systematically called CNVs in 38 cohorts from the large-scale ENIGMA-CNV collaboration and the UK Biobank and identified 28 1q21.1 distal deletion and 22 duplication carriers and 37,088 non-carriers (48% male) derived from 15 distinct magnetic resonance imaging scanner sites. With standardized methods, we compared subcortical and cortical brain measures (all) and cognitive performance (UK Biobank only) between carrier groups also testing for mediation of brain structure on cognition. We identified positive dosage effects of copy number on intracranial volume (ICV) and total cortical surface area, with the largest effects in frontal and cingulate cortices, and negative dosage effects on caudate and hippocampal volumes. The carriers displayed distinct cognitive deficit profiles in cognitive tasks from the UK Biobank with intermediate decreases in duplication carriers and somewhat larger in deletion carriers-the latter potentially mediated by ICV or cortical surface area. These results shed light on pathobiological mechanisms of neurodevelopmental disorders, by demonstrating gene dose effect on specific brain structures and effect on cognitive function.

Brain↗

PubMed2007

Functional neural circuits for mental timekeeping.

Theories of mental timekeeping suggest frontostriatal networks may mediate performance of tasks requiring precise timing. We assessed whether frontostriatal networks are functionally integrated during the performance of timing tasks. Functional magnetic resonance imaging (fMRI) data from 31 healthy adults were collected during performance of several different types of discrete interval timing tasks. Independent component analysis (ICA) was used to examine functional connectivity within frontostriatal circuits. ICA identifies groups of spatially discrete brain regions sharing similar patterns of hemodynamic signal change over time. The results confirm the existence of a frontostriatal neural timing circuit that includes anterior cingulate gyrus, supplementary motor area, bilateral anterior insula, bilateral putamen/globus pallidus, bilateral thalamus, and right superior temporal gyrus and supramarginal gyrus. Several other distinct neural circuits were identified that may represent the neurobiological substrates of different information processing stages of mental timekeeping. Small areas of right cerebellum were engaged in several of these circuits, suggesting that cerebellar function may be important in, but not the primary substrate of, the mental timing tasks used in this experiment. These findings are discussed within the context of current biological and information processing models of neural timekeeping.

Acoustic Stimulation↗

PubMed2007

Interparticipant correlations: a model free FMRI analysis technique.

FMRI analysis techniques can be broadly divided into model based and data driven techniques. The most widely used approach assumes an explicit temporal hemodynamic model based upon the experimental paradigm. Such an approach has proven very useful and powerful even though it is limited by the accuracy of the prespecified model. An alternative approach is to use data driven techniques like independent component analysis or fuzzy cluster analysis. These approaches have proven useful for exploratory analysis in a multivariate sense; however, they can present additional difficulties in the interpretation of the results. An alternative to these approaches is to take advantage of similarities in the patterns of the hemodynamics between participants [i.e., interparticipant correlation (IPC)]. This FMRI analysis technique enjoys the parsimony of the general linear model (GLM) but does not assume a specific FMRI time course. The technique consists of calculating voxel-wise correlations between participants resulting in IPC maps, which indicate the activated regions the participants have in common. We applied the IPC approach to data collected from healthy controls in an auditory oddball task. As expected, high inter-participant correlations were detected in auditory cortical regions in the temporal lobes where highest correlations were evident. In addition, areas that appear to be involved in the task were detected using IPC's but not the GLM regression. This technique, designed to have increased sensitivity to inter-subject correlations that are not necessarily task-related, may potentially be useful as a compliment to model-based approaches.

Acoustic Stimulation↗

PubMed2006

Alterations in memory networks in mild cognitive impairment and Alzheimer's disease: an independent component analysis.

Memory function is likely subserved by multiple distributed neural networks, which are disrupted by the pathophysiological process of Alzheimer's disease (AD). In this study, we used multivariate analytic techniques to investigate memory-related functional magnetic resonance imaging (fMRI) activity in 52 individuals across the continuum of normal aging, mild cognitive impairment (MCI), and mild AD. Independent component analyses revealed specific memory-related networks that activated or deactivated during an associative memory paradigm. Across all subjects, hippocampal activation and parietal deactivation demonstrated a strong reciprocal relationship. Furthermore, we found evidence of a nonlinear trajectory of fMRI activation across the continuum of impairment. Less impaired MCI subjects showed paradoxical hyperactivation in the hippocampus compared with controls, whereas more impaired MCI subjects demonstrated significant hypoactivation, similar to the levels observed in the mild AD subjects. We found a remarkably parallel curve in the pattern of memory-related deactivation in medial and lateral parietal regions with greater deactivation in less-impaired MCI and loss of deactivation in more impaired MCI and mild AD subjects. Interestingly, the failure of deactivation in these regions was also associated with increased positive activity in a neocortical attentional network in MCI and AD. Our findings suggest that loss of functional integrity of the hippocampal-based memory systems is directly related to alterations of neural activity in parietal regions seen over the course of MCI and AD. These data may also provide functional evidence of the interaction between neocortical and medial temporal lobe pathology in early AD.

Aged↗

PubMed2006

Neural correlates of the object-recall process in semantic memory.

The recall of an object from features is a specific operation in semantic memory in which the thalamus and pre-supplementary motor area (pre-SMA) are integrally involved. Other higher-order semantic cortices are also likely to be involved. We used the object-recall-from-features paradigm, with more sensitive scanning techniques and larger sample size, to replicate and extend our previous results. Eighteen right-handed healthy participants performed an object-recall task and an association semantic task, while undergoing functional magnetic resonance imaging. During object-recall, subjects determined whether words pairs describing object features combined to recall an object; during the association task they decided if two words were related. Of brain areas specifically involved in object recall, in addition to the thalamus and pre-SMA, other regions included the left dorsolateral prefrontal cortex, inferior parietal lobule, and middle temporal gyrus, and bilateral rostral anterior cingulate and inferior frontal gyri. These regions are involved in semantic processing, verbal working memory and response-conflict detection and monitoring. The thalamus likely helps to coordinate activity of these different brain areas. Understanding the circuit that normally mediates this process is relevant for schizophrenia, where many regions in this circuit are functionally abnormal and semantic memory is impaired.

Adult↗

PubMed2006

A functional magnetic resonance imaging study of working memory abnormalities in schizophrenia.

BACKGROUND: Previous neuroimaging studies of working memory (WM) in schizophrenia, typically focusing on dorsolateral prefrontal cortex, yield conflicting results, possibly because of varied choice of tasks and analysis techniques. We examined neural function changes at several WM loads to derive a more complete picture of WM dysfunction in schizophrenia. METHODS: We used a version of the Sternberg Item Recognition Paradigm to test WM function at five distinct loads. Eighteen schizophrenia patients and 18 matched healthy controls were scanned with functional magnetic resonance imaging at 3 Tesla. RESULTS: Patterns of both overactivation and underactivation in patients were observed depending on WM load. Patients' activation was generally less responsive to load changes than control subjects', and different patterns of between-group differences were observed for memory encoding and retrieval. In the specific case of successful retrieval, patients recruited additional neural circuits unused by control subjects. Behavioral effects were generally consistent with these imaging results. CONCLUSIONS: Differential findings of overactivation and underactivation may be attributable to patients' decreased ability to focus and allocate neural resources at task-appropriate levels. Additionally, differences between encoding and retrieval suggest that WM dysfunction may be manifested differently during the distinct phases of encoding, maintenance, and retrieval.

Adult↗

PubMed2006

A method for multitask fMRI data fusion applied to schizophrenia.

It is becoming common to collect data from multiple functional magnetic resonance imaging (fMRI) paradigms on a single individual. The data from these experiments are typically analyzed separately and sometimes directly subtracted from one another on a voxel-by-voxel basis. These comparative approaches, although useful, do not directly attempt to examine potential commonalities between tasks and between voxels. To remedy this we propose a method to extract maximally spatially independent maps for each task that are "coupled" together by a shared loading parameter. We first compute an activation map for each task and each individual as "features," which are then used to perform joint independent component analysis (jICA) on the group data. We demonstrate our approach on a data set derived from healthy controls and schizophrenia patients, each of which carried out an auditory oddball task and a Sternberg working memory task. Our analysis approach revealed two interesting findings in the data that were missed with traditional analyses. First, consistent with our hypotheses, schizophrenia patients demonstrate "decreased" connectivity in a joint network including portions of regions implicated in two prevalent models of schizophrenia. A second finding is that for the voxels identified by the jICA analysis, the correlation between the two tasks was significantly higher in patients than in controls. This finding suggests that schizophrenia patients activate "more similarly" for both tasks than do controls. A possible synthesis of both findings is that patients are activating less, but also activating with a less-unique set of regions for these very different tasks. Both of the findings described support the claim that examination of joint activation across multiple tasks can enable new questions to be posed about fMRI data. Our approach can also be applied to data using more than two tasks. It thus provides a way to integrate and probe brain networks using a variety of tasks and may increase our understanding of coordinated brain networks and the impact of pathology upon them.

Adult↗

PubMed2006

Simulated driving and brain imaging: combining behavior, brain activity, and virtual reality.

INTRODUCTION: Virtual reality in the form of simulated driving is a useful tool for studying the brain. Various clinical questions can be addressed, including both the role of alcohol as a modulator of brain function and regional brain activation related to elements of driving. OBJECTIVE: We reviewed a study of the neural correlates of alcohol intoxication through the use of a simulated-driving paradigm and wished to demonstrate the utility of recording continuous-driving behavior through a new study using a programmable driving simulator developed at our center. METHODS: Functional magnetic resonance imaging data was collected from subjects while operating a driving simulator. Independent component analysis (ICA) was used to analyze the data. Specific brain regions modulated by alcohol, and relationships between behavior, brain function, and alcohol blood levels were examined with aggregate behavioral measures. Fifteen driving epochs taken from two subjects while also recording continuously recorded driving variables were analyzed with ICA. RESULTS: Preliminary findings reveal that four independent components correlate with various aspects of behavior. An increase in braking while driving was found to increase activation in motor areas, while cerebellar areas showed signal increases during steering maintenance, yet signal decreases during steering changes. Additional components and significant findings are further outlined. CONCLUSION: In summary, continuous behavioral variables conjoined with ICA may offer new insight into the neural correlates of complex human behavior.

Automobile Driving↗

PubMed2005

Abnormal object recall and anterior cingulate overactivation correlate with formal thought disorder in schizophrenia.

BACKGROUND: The neural basis of formal thought disorder (FTD) is unknown. An influential theory is that FTD results from impaired semantic memory processing. We explored the neural correlates of semantic memory retrieval in schizophrenia using an imaging task assessing semantic object recall. METHOD: Sixteen healthy control subjects and sixteen schizophrenia patients whose FTD symptoms were measured with the Thought Disorder Index completed a verbal object-recall task during functional magnetic resonance imaging. Participants viewed two words describing object features that either evoked (object recall) or did not evoke a semantic concept. RESULTS: Schizophrenia patients tended to overrecall objects for feature pairs that did not describe the same object. Functionally, rostral anterior cingulate cortex (ACC) activation in patients positively correlated with FTD severity during both correct recalled and overrecalled trials. Compared with control subjects, during object recalling, patients overactivated bilateral ACC, temporooccipital junctions, temporal poles and parahippocampi, right inferior frontal gyrus, and dorsolateral prefrontal cortex, but underactivated inferior parietal lobules. CONCLUSIONS: Our results support impaired semantic memory retrieval as underlying FTD pathophysiology. Schizophrenia patients showed abnormal activations of brain areas involved in semantic memory, verbal working memory, and initiation and suppression of conflicting responses, which were associated with semantic overrecall and FTD.

Adult↗

PubMed2005

Voxel-based morphometry versus region of interest: a comparison of two methods for analyzing gray matter differences in schizophrenia.

Many previous studies exploring cortical gray matter (GM) differences in schizophrenia have used "region of interest" (ROI) measurements to manually delineate GM volumes. Recently, some investigators have instead employed voxel-based morphometry (VBM), an automated whole-brain magnetic resonance image measurement technique. The purpose of the current study was to compare the above methods in calculating GM distributions in schizophrenia patients relative to matched controls. Using ROIs, Buchanan et al. (Buchanan, R.W., Francis, A., Arango, C., Miller, K., Lefkowitz, D.M., McMahon, R.P., Barta, P.E. and Pearlson, G.D., 2004. Morphometric assessment of the heteromodal association cortex in schizophrenia. Am J Psychiatry. 161 (2), 322-331.) found decreased dorsolateral prefrontal GM volume and altered symmetry of inferior parietal GM in schizophrenia patients. We hypothesized that VBM analyses of the same data would complement the ROI findings. As predicted, VBM analyses replicated results of less left inferior and right superior frontal cortical GM in schizophrenia. Additionally, VBM uncovered a significantly lower concentration of GM in the middle and superior temporal gyri, sought but not detected using ROIs, but did not replicate the parietal changes. The principal explanation for these differences may be the methodological differences between voxel-averaged, landmark-based ROI analyses and the single, voxel-by-voxel whole brain VBM measurements. Although VBM is rapid and fully automated, it is not a replacement for manual ROI-based analyses. Both methods provide different types of information and should thus be used in tandem.

Adult↗

PubMed2005

An adaptive reflexive processing model of neurocognitive function: supporting evidence from a large scale (n = 100) fMRI study of an auditory oddball task.

Recent hemodynamic imaging studies have shown that processing of low probability task-relevant target stimuli (i.e., oddballs) and low probability task-irrelevant novel stimuli elicit widespread activity in diverse, spatially distributed cortical and subcortical systems. The nature of this distributed response supports the model that processing of salient and novel stimuli engages many brain regions regardless of whether said regions were necessary for task performance. However, these latter neuroimaging studies largely employed small sample sizes and fixed-effect analyses, limiting the characterization and inference of the results. The present study addressed these issues by collecting a large sample size (n = 100) and employed random effects statistical models. Analyses were also conducted to determine the inter-subject reliability of the hemodynamic response and the effects of gender and age on target detection and novelty processing. Group data demonstrated highly significant activation in all 34 specified regions of interest for target detection and all 24 specified regions of interest for processing of novel stimuli. Neither age nor gender systematically influenced the results. These data are discussed within the context of a model that proposes that the mammalian brain has evolved to adopt a strategy of engaging distributed neuronal systems when processing salient stimuli despite the low probability that many of these brain regions are required for successful task performance. This process may be termed 'adaptive reflexive processing.' The implications of these results for interpreting functional MRI studies are discussed.

Adolescent↗

PubMed2005

Hemispheric differences in hemodynamics elicited by auditory oddball stimuli.

Evidence from neuroimaging studies suggests that the right hemisphere of the human brain might be more specialized for attention than the left hemisphere. However, differences between right and left hemisphere in the magnitude of hemodynamic activity (i.e., 'functional asymmetry') rarely have been explicitly examined in previous neuroimaging studies of attention. This study used a new voxel-based comparison method to examine hemispheric differences in the amplitude of the hemodynamic response in response to infrequent target, infrequent novel, and frequent standard stimuli during an event-related fMRI auditory oddball task in 100 healthy adult participants. Processing of low probability task-relevant target stimuli, or 'oddballs', and low probability task-irrelevant novel stimuli is believed to engage in orienting and attentional processes. It was hypothesized that greater right-hemisphere activation compared to left would be observed to infrequent target and novel stimuli. Consistent with predictions, greater right hemisphere than left frontal, temporal, and parietal lobe activity was observed for target detection and novelty processing. Moreover, asymmetry effects did not differ with respect to age or gender of the participants. The results (1) support the proposal that the right hemisphere is differentially engaged in processing salient stimuli and (2) demonstrate the successful use of a new voxel-based laterality analysis technique for fMRI data.

Acoustic Stimulation↗

PubMed2005

Source density-driven independent component analysis approach for fMRI data.

Independent component analysis (ICA) has become a popular tool for functional magnetic resonance imaging (fMRI) data analysis. Conventional ICA algorithms including Infomax and FAST-ICA algorithms employ the underlying assumption that data can be decomposed into statistically independent sources and implicitly model the probability density functions of the underlying sources as highly kurtotic or symmetric. When source data violate these assumptions (e.g., are asymmetric), however, conventional ICA methods might not work well. As a result, modeling of the underlying sources becomes an important issue for ICA applications. We propose a source density-driven ICA (SD-ICA) method. The SD-ICA algorithm involves a two-step procedure. It uses a conventional ICA algorithm to obtain initial independent source estimates for the first-step and then, using a kernel estimator technique, the source density is calculated. A refitted nonlinear function is used for each source at the second step. We show that the proposed SD-ICA algorithm provides flexible source adaptivity and improves ICA performance. On SD-ICA application to fMRI signals, the physiologic meaningful components (e.g., activated regions) of fMRI signals are governed typically by a small percentage of the whole-brain map on a task-related activation. Extra prior information (using a skewed-weighted distribution transformation) is thus additionally applied to the algorithm for the regions of interest of data (e.g., visual activated regions) to emphasize the importance of the tail part of the distribution. Our experimental results show that the source density-driven ICA method can improve performance further by incorporating some a priori information into ICA analysis of fMRI signals.

Adult↗

PubMed2005

Effect of age on visuomotor functional MR imaging.

RATIONALE AND OBJECTIVES: We sought to determine the effect of age on functional MR imaging experiments performed with visual and motor stimulation. We hypothesized that there would be a diminution in the amplitude of fMRI activation with increasing subjects' age. MATERIALS AND METHODS: We used fixed effects models to study the amplitude of activation during a block design visuomotor task in three different age groups: old (mean: 75 years; standard deviation: 6 years), middle-aged (mean: 52 years; standard deviation: 9 years) and young (mean: 29 years; standard deviation: 5 years). Each group included 7 subjects. Regions of interest (ROI) were left primary motor area (LM1), supplementary motor area (SMA), and right and left occipital (RO, LO) visual areas. Individual subjects and group statistical parametric maps (SPMs) were generated for each ROI, and then the mean amplitude of activation was compared using the group analysis and t test. RESULTS: The young age group showed higher amplitude of activation than middle and old age groups in all ROI (P < 0.01 uncorrected). Unpaired two tailed t test results between the groups showed significant differences between middle and young, and old and young age groups in all ROIs (P < or = 0.05), with the exception of old and young age groups in RO region (P = 0.11). CONCLUSION: The group analysis, and unpaired t test results reveal higher amplitude of fMRI activation in the young versus the old and middle-aged groups.

Adult↗

PubMed2005

fMRI in an oddball task: effects of target-to-target interval.

The amplitude of the P3 event-related potential (ERP) elicited by task-relevant target ("oddball") stimuli has been shown to vary in proportion to the length of time between targets. Here we use functional magnetic resonance imaging (fMRI) to identify neural systems modulated by target interval in a large sample of healthy adults (n=100) during performance of an auditory oddball task that included both target and novel stimuli. A positive relationship was found between target interval and hemodynamic activity in the anterior cingulate and in bilateral lateral prefrontal cortex, temporal-parietal junction, postcentral gryi, thalamus, and cerebellum. This modulation likely represents updating of the working memory template for the target stimuli. There was no such effect of novel interval, suggesting that neuronal modulation may only occur for task-relevant stimuli, possibly in the service of strategic resource allocation processes.

Adolescent↗

PubMed2004

Functional MRI study of a serial reaction time task in Huntington's disease.

The aim of this study was to investigate pathophysiological changes at an early stage of clinical Huntington's disease (HD) using a functional magnetic resonance imaging (fMRI) study and a serial reaction time task paradigm. Mildly affected and presymptomatic HD subjects (n = 8) and healthy normal controls (NC, n = 12) were studied. A group behavioral effect of implicit learning was seen only in the control population. Individual statistical parametric mapping (SPM) analysis showed more consistent activation of the caudate nucleus and putamen in the NC group. In the HD group, the group average SPM showed significant activation in the right head of caudate nucleus, as well as bilateral thalami, left middle temporal, right superior temporal, right superior frontal, right middle and inferior frontal and right postcentral gyri. In the comparison of between-group differences (NC-HD), reduced activation in the HD group relative to NC was observed in the right middle frontal, left middle occipital, left precuneus, and left middle frontal gyri. The variable striatal activity in the Huntington's group suggests early functional loss possibly associated with previously demonstrated early atrophy of these same neural structures.

Adult↗