Michelle Hampson

Brain Connectivity Related to Working Memory Performance

Several brain areas show signal decreases during many different cognitive tasks in functional imaging studies, including the posterior cingulate cortex (PCC) and a medial frontal region incorporating portions of the medial frontal gyrus and ventral anterior cingulate cortex (MFG/vACC). It has been suggested that these areas are components in a default mode network that is engaged during rest and disengaged during cognitive tasks. This study investigated the functional connectivity between the PCC and MFG/vACC during a working memory task and at rest by examining temporal correlations in magnetic resonance signal levels between the regions. The two regions were functionally connected in both conditions. In addition, performance on the working memory task was positively correlated with the strength of this functional connection not only during the working memory task, but also at rest. Thus, it appears these regions are components of a network that may facilitate or monitor cognitive performance, rather than becoming disengaged during cognitive tasks. In addition, these data raise the possibility that the individual differences in coupling strength between these two regions at rest predict differences in cognitive abilities important for this working memory task.

Detection of functional connectivity using temporal correlations in MR images

Functional connectivity among brain regions has been investigated via an analysis of correlations between regional signal fluctuations recorded in magnetic resonance (MR) images obtained in a steady state. In comparison with studies of functional connectivity that utilize task manipulations, the analysis of correlations in steady state data is less susceptible to confounds arising when functionally unrelated brain regions respond in similar ways to changes in task. A new approach to identifying interregional correlations in steady state data makes use of two independent data sets. Regions of interest (ROIs) are defined and hypotheses regarding their connectivity are generated in one data set. The connectivity hypotheses are then evaluated in the remaining (independent) data set by analyzing low frequency temporal correlations between regions. The roles of the two data sets are then reversed and the process repeated, perhaps multiple times. This method was illustrated by application to the language system. The existence of a functional connection between Brocas area and Wernickes area was confirmed in healthy subjects at rest. An increase in this functional connection when the language system was actively engaged (when subjects were continuously listening to narrative text) was also confirmed. In a second iteration of analyses, a correlation between Brocas area and a region in left premotor cortex was found to be significant at rest and to increase during continuous listening. These findings suggest that the proposed methodology can reveal the presence and strength of functional connections in high‐level cognitive systems. Hum. Brain Mapping 15:247–262, 2002.

Measuring brain connectivity: Diffusion tensor imaging validates resting state temporal correlations

Diffusion tensor imaging (DTI) and resting state temporal correlations (RSTC) are two leading techniques for investigating the connectivity of the human brain. They have been widely used to investigate the strength of anatomical and functional connections between distant brain regions in healthy subjects, and in clinical populations. Though they are both based on magnetic resonance imaging (MRI) they have not yet been compared directly. In this work both techniques were employed to create global connectivity matrices covering the whole brain gray matter. This allowed for direct comparisons between functional connectivity measured by RSTC with anatomical connectivity quantified using DTI tractography. We found that connectivity matrices obtained using both techniques showed significant agreement. Connectivity maps created for a priori defined anatomical regions showed significant correlation, and furthermore agreement was especially high in regions showing strong overall connectivity, such as those belonging to the default mode network. Direct comparison between functional RSTC and anatomical DTI connectivity, presented here for the first time, links two powerful approaches for investigating brain connectivity and shows their strong agreement. It provides a crucial multi-modal validation for resting state correlations as representing neuronal connectivity. The combination of both techniques presented here allows for further combining them to provide richer representation of brain connectivity both in the healthy brain and in clinical conditions.

Functional connectivity between task-positive and task-negative brain areas and its relation to working memory performance

Functional brain imaging studies have identified a set of brain areas typically activated during cognitive tasks (task-positive brain areas) and another set of brain areas typically deactivated during cognitive tasks (task-negative brain areas). Negative correlations, or anticorrelations, between task-positive and task-negative brain areas have been reported at rest. Furthermore, the strength of these anticorrelations appears to be related to cognitive function. However, studies examining anticorrelations have typically employed global regression or similar analysis steps that force anticorrelated relationships to exist between brain areas. Therefore the validity of these findings has been questioned. Here we examine anticorrelations between a task-negative region in the medial frontal gyrus/anterior cingulate cortex and dorsolateral prefrontal cortex, a classic task-positive area, using an analysis that does not include global regression. Instead, we control for whole-brain correlations in the group-level analysis. Using this approach, we demonstrate that the strength of the functional connection between the medial frontal cortex and the dorsolateral prefrontal cortex is related to cognitive function and that this relationship is not an artifact of global regression.

Connectivity-behavior analysis reveals that functional connectivity between left BA39 and Broca's area varies with reading ability.

Correlations between temporal fluctuations in MRI signals may reveal functional connectivity between brain regions within individual subjects. Such correlations would be especially useful indices of functional connectivity if they covary with behavioral performance or other subject variables. This study investigated whether such a relationship could be demonstrated in the context of the reading circuit in the brain. The method proved sufficiently powerful to reveal significant correlations between the reading abilities of subjects and the strength of their functional connection between left Brodmanns area 39 and Brocas area during reading. This suggests that the disconnection of the angular gyrus previously reported for dyslexic readers is part of a larger continuum in which poor (but nonimpaired readers) also show reduced connectivity to the region. In addition, it illustrates the potential power of paradigms that examine correlations between behavior and functional brain connections.

PRETERM BIRTH RESULTS IN ALTERATIONS IN NEURAL CONNECTIVITY AT AGE 16 YEARS

Very low birth weight preterm (PT) children are at high risk for brain injury. Employing diffusion tensor imaging (DTI), we tested the hypothesis that PT adolescents would demonstrate microstructural white matter disorganization relative to term controls at 16 years of age. Forty-four PT subjects (600-1250 g birth weight) without neonatal brain injury and 41 term controls were evaluated at age 16 years with DTI, the Wechsler Intelligence Scale for Children-III (WISC), the Peabody Picture Vocabulary Test-Revised (PPVT), and the Comprehensive Test of Phonological Processing (CTOPP). PT subjects scored lower than term subjects on WISC full scale (p=0.003), verbal (p=0.043), and performance IQ tests (p=0.001), as well as CTOPP phonological awareness (p=0.004), but scored comparably to term subjects on PPVT and CTOPP Rapid Naming tests. PT subjects had lower fractional anisotropy (FA) values in multiple regions including bilateral uncinate fasciculi (left: p=0.01; right: p=0.004), bilateral external capsules (left: p<0.001; right: p<0.001), the splenium of the corpus callosum (p=0.008), and white matter serving the inferior frontal gyrus bilaterally (left: p<0.001; right: p=0.011). FA values in both the left and right uncinate fasciculi correlated with PPVT scores (a semantic language task) in the PT subjects (left: r=0.314, p=0.038; right: r=0.336, p=0.026). FA values in the left and right arcuate fasciculi correlated with CTOPP Rapid Naming scores (a phonologic task) in the PT subjects (left: r=0.424, p=0.004; right: r=0.301, p=0.047). These data support for the first time that dual pathways underlying language function are present in PT adolescents. The striking bilateral dorsal correlations for the PT group suggest that prematurely born subjects rely more heavily on the right hemisphere than typically developing adults for performance of phonological language tasks. These findings may represent either a delay in maturation or the engagement of alternative neural pathways for language in the developing PT brain.

Alterations in neural connectivity in preterm children at school age.

Converging data suggest recovery from injury in the preterm brain. We used functional magnetic resonance imaging (fMRI) to test the hypothesis that cerebral connectivity involving Wernickes area and other important cortical language regions would differ between preterm (PT) and term (T) control school age children during performance of an auditory language task. Fifty-four PT children (600-1250 g birth weight) and 24 T controls were evaluated using an fMRI passive language task and neurodevelopmental assessments including: the Wechsler Intelligence Scale for Children - III (WISC-III), the Peabody Individual Achievement Test - Revised (PIAT-R) and the Peabody Picture Vocabulary Test - Revised (PPVT-R) at 8 years of age. Neural activity was assessed for language processing and the data were evaluated for connectivity and correlations to cognitive outcomes. We found that PT subjects scored significantly lower on all components of the WISC-III (p<0.009), the PIAT-R Reading Comprehension test (p=0.013), and the PPVT-R (p=0.001) compared to term subjects. Connectivity analyses revealed significantly stronger neural circuits in PT children between Wernickes area and the right inferior frontal gyrus (R IFG, Brocas area homologue) and both the left and the right supramarginal gyri (SMG) components of the inferior parietal lobules (p</=0.02 for all). We conclude that PT subjects employ neural systems for auditory language function at school age differently than T controls; these alterations may represent a delay in maturation of neural networks or the engagement of alternate circuits for language processing.

Functional connectivity between ventral prefrontal cortex and amygdala at low frequency in the resting state in bipolar disorder

Trait abnormalities in bipolar disorder (BD) within the ventral prefrontal cortex (vPFC) and the amygdala suggest dysfunction in their connectivity. This study employed low frequency resting state functional magnetic resonance imaging (LFRS-fMRI) to analyze functional connectivity between the vPFC and the amygdala in BD. LFRS-fMRI identified a negative correlation in vPFC-amygdala activity, and the magnitude of this correlation was greater in healthy participants than in subjects with BD. Additionally, whole-brain analysis revealed higher correlations between left and right vPFC in BD, as well as with ventral striatum.

Neurobiological Substrates of Tourette's Disorder

OBJECTIVE This article reviews the available scientific literature concerning the neurobiological substrates of Tourettes disorder (TD). METHODS The electronic databases of PubMed, ScienceDirect, and PsycINFO were searched for relevant studies using relevant search terms. RESULTS Neuropathological as well as structural and functional neuroimaging studies of TD implicate not only the sensorimotor corticostriatal circuit, but also the limbic and associative circuits as well. Preliminary evidence also points to abnormalities in the frontoparietal network that is thought to maintain adaptive online control. Evidence supporting abnormalities in dopaminergic and noradrenergic neurotransmission remains strong, although the precise mechanisms remain the subject of speculation. CONCLUSION Structural and functional abnormalities in multiple parallel corticostriatal circuits may underlie the behavioral manifestations of TD and related neuropsychiatric disorders over the course of development. Further longitudinal research is needed to elucidate these neurobiological substrates.

Elevated Functional Connectivity Along a Corticostriatal Loop and the Mechanism of Auditory/Verbal Hallucinations in Patients with Schizophrenia

BACKGROUND Higher levels of inter-region functional coordination can facilitate emergence of neural activity as conscious percepts. We consequently tested the hypothesis that auditory/verbal hallucinations (AVHs) arise from elevated functional coordination within a speech processing network. METHODS Functional coordination was indexed with functional connectivity (FC) computed from functional magnetic resonance imaging data. Thirty-two patients with schizophrenia reporting AVHs, 24 similarly diagnosed patients without hallucinations, and 23 healthy control subjects were studied. FC was seeded from a bilateral Wernickes region delineated according to activation detected during AVHs in a prior study. RESULTS Wernickes-seeded FC with Brodmann area 45/46 of the left inferior frontal gyrus (IFG) was significantly greater for hallucinating patients compared with nonhallucinating patients but not compared with healthy control subjects. In contrast, Wernickes-seeded FC with a large subcortical region that included the thalamus, midbrain, and putamen was significantly greater for the combined patient group compared with healthy control subjects after false discovery rate correction, but not when comparing the two patient groups. Within that subcortical domain, the putamen demonstrated significantly greater FC relative to a secondary left IFG seed region when hallucinators were compared with nonhallucinating patients. A follow-up analysis found that FC summed along a loop linking the Wernickes and IFG seed regions and the putamen was robustly greater for hallucinating patients compared with nonhallucinating patients and healthy control subjects. CONCLUSIONS These findings suggest that higher levels of functional coordination intrinsic to a corticostriatal loop comprise a causal factor leading to AVHs in schizophrenia.