Faculty Bibliography

BACKGROUND: Research on the neural correlates of risk-related behaviors and personality traits has provided insight into mechanisms underlying both normal and pathological decision-making. Task-based neuroimaging studies implicate a distributed network of brain regions in risky decision-making. What remains to be understood are the interactions between these regions and their relation to individual differences in personality variables associated with real-world risk-taking. METHODOLOGY/PRINCIPAL FINDINGS: We employed resting state functional magnetic resonance imaging (R-fMRI) and resting state functional connectivity (RSFC) methods to investigate differences in the brain's intrinsic functional architecture associated with beliefs about the consequences of risky behavior. We obtained an individual measure of expected benefit from engaging in risky behavior, indicating a risk seeking or risk-averse personality, for each of 21 participants from whom we also collected a series of R-fMRI scans. The expected benefit scores were entered in statistical models assessing the RSFC of brain regions consistently implicated in both the evaluation of risk and reward, and cognitive control (i.e., orbitofrontal cortex, nucleus accumbens, lateral prefrontal cortex, dorsal anterior cingulate). We specifically focused on significant brain-behavior relationships that were stable across R-fMRI scans collected one year apart. Two stable expected benefit-RSFC relationships were observed: decreased expected benefit (increased risk-aversion) was associated with 1) stronger positive functional connectivity between right inferior frontal gyrus (IFG) and right insula, and 2) weaker negative functional connectivity between left nucleus accumbens and right parieto-occipital cortex. CONCLUSIONS/SIGNIFICANCE: Task-based activation in the IFG and insula has been associated with risk-aversion, while activation in the nucleus accumbens and parietal cortex has been associated with both risk seeking and risk-averse tendencies. Our results suggest that individual differences in attitudes toward risk-taking are reflected in the brain's functional architecture and may have implications for engaging in real-world risky behaviors

Intolerance of uncertainty (IU) has contributed to our understanding of excessive worry and adult anxiety disorders, but there is a paucity of research on IU in child samples. This gap is due to the absence of a psychometrically sound measure of IU in youth. The present study adapted parallel child- and parent-report forms of the Intolerance of Uncertainty Scale (IUS) and examined the internal consistency, convergent validity, and classification properties of these forms in youth aged 7-17 (M = 11.6 years, SD = 2.6). Participating youth (N = 197; 100 girls, 97 boys) either met diagnostic criteria for an anxiety disorder (n = 73) or were nonreferred community participants (n = 124). The child-report form (i.e., IUS for Children, or IUSC), and to a lesser extent the parent-report form, demonstrated strong internal consistency and convergent validity, evidenced by significant associations with anxiety and worry (and reassurance-seeking in the case of the child-report form). Children diagnosed with anxiety disorders scored higher than nonreferred community youth on both forms. Receiver operating characteristic (ROC) analysis demonstrated acceptable overall utility in distinguishing the 2 groups of youth. Findings provide preliminary support for use of the IUSC for continuous measurement of children's ability to tolerate uncertainty

Recent years have witnessed an upsurge in the usage of resting-state functional magnetic resonance imaging (fMRI) to examine functional connectivity (fcMRI), both in normal and pathological populations. Despite this increasing popularity, concerns about the psychologically unconstrained nature of the 'resting-state' remain. Across studies, the patterns of functional connectivity detected are remarkably consistent. However, the test-retest reliability for measures of resting state fcMRI measures has not been determined. Here, we quantify the test-retest reliability, using resting scans from 26 participants at 3 different time points. Specifically, we assessed intersession (>5 months apart), intrasession (<1 h apart), and multiscan (across all 3 scans) reliability and consistency for both region-of-interest and voxel-wise analyses. For both approaches, we observed modest to high reliability across connections, dependent upon 3 predictive factors: 1) correlation significance (significantly nonzero > nonsignificant), 2) correlation valence (positive > negative), and 3) network membership (default mode > task positive network). Short- and long-term measures of the consistency of global connectivity patterns were highly robust. Finally, hierarchical clustering solutions were highly reproducible, both across participants and sessions. Our findings provide a solid foundation for continued examination of resting state fcMRI in typical and atypical populations

OBJECTIVE: The Social Responsiveness Scale-Adult Version (SRS-A) measures autistic traits that are continuously distributed in the general population. Based on increased recognition of the dimensional nature of autistic traits, the authors examined the neural correlates of these traits in neurotypical individuals using the SRS-A and established a novel approach to assessing the neural basis of autistic characteristics, attempting to directly relate SRS-A scores to patterns of functional connectivity observed in the pregenual anterior cingulate cortex, a region commonly implicated in social cognition. METHOD: Resting state functional magnetic resonance imaging scans were collected for 25 neurotypical adults. All participants provided SRS-A ratings completed by an informant who had observed them in natural social settings. Whole brain-corrected connectivity analyses were then conducted using SRS-A scores as a covariate of interest. RESULTS: Across participants, a significant negative relationship between SRS-A scores and the functional connectivity of the pregenual anterior cingulate cortex with the anterior portion of the mid-insula was found. Specifically, low levels of autistic traits were observed when a substantial portion of the anterior mid-insula showed positive connectivity with the pregenual anterior cingulate cortex. In contrast, elevated levels of autistic traits were associated with negative connectivity between these two regions. CONCLUSIONS: Resting state functional connectivity of the pregenual anterior cingulate cortex-insula social network was related to autistic traits in neurotypical adults. Application of this approach in samples with autism spectrum disorders is needed to confirm whether this circuit is dimensionally related to the severity of autistic traits in clinical populations

Electrophysiological studies have long demonstrated a high degree of correlated activity between the left and right hemispheres, however little is known about regional variation in this interhemispheric coordination. Whereas cognitive models and neuroanatomical evidence suggest differences in coordination across primary sensory-motor cortices versus higher-order association areas, these have not been characterized. Here, we used resting-state functional magnetic resonance imaging data acquired from 62 healthy volunteers to examine interregional correlation in spontaneous low-frequency hemodynamic fluctuations. Using a probabilistic atlas, we correlated probability-weighted time series from 112 regions comprising the entire cerebrum. We then examined regional variation in correlated activity between homotopic regions, contrasting primary sensory-motor cortices, unimodal association areas, and heteromodal association areas. Consistent with previous studies, robustly correlated spontaneous activity was noted between all homotopic regions, which was significantly higher than that between nonhomotopic (heterotopic and intrahemispheric) regions. We further demonstrated substantial regional variation in homotopic interhemispheric correlations that was highly consistent across subjects. Specifically, there was a gradient of interhemispheric correlation, with highest correlations across primary sensory-motor cortices (0.758, SD=0.152), significantly lower correlations across unimodal association areas (0.597, SD=0.230) and still lower correlations across heteromodal association areas (0.517, SD=0.226). These results demonstrate functional differences in interhemispheric coordination related to the brain's hierarchical subdivisions. Synchrony across primary cortices may reflect networks engaged in bilateral sensory integration and motor coordination, whereas lower coordination across heteromodal association areas is consistent with functional lateralization of these regions. This novel method of examining interhemispheric coordination may yield insights regarding diverse disease processes as well as healthy development

BACKGROUND: Pediatric anxiety disorders, although highly prevalent, are understudied with little known about their pathophysiology. Intolerance of uncertainty (IU) is a trait associated with worry, a key characteristic of these disorders. Neural responses to uncertainty in healthy subjects involve the same frontal-limbic circuits that are hyper-responsive in pediatric anxiety. As such, the present study examines the relationship between IU and neural responses to uncertainty in anxious adolescents. METHODS: Sixteen adolescents (ages 13-17) diagnosed with generalized anxiety disorder and/or social phobia (ANX) and 13 non-anxious control subjects completed a decision-making task while functional magnetic resonance imaging scans were acquired. RESULTS: The ANX group endorsed greater task-related anxiety and less certainty than control subjects on a post-task questionnaire. Compared with control subjects, the ANX group did not demonstrate hyper-responsivity of brain regions as hypothesized. Across groups, IU was positively correlated with activity in several frontal and limbic regions. Further analyses identified subgroups within the ANX group: those with high IU activated frontal/limbic regions, whereas those with low IU and less anxiety during the task deactivated the same regions in response to uncertainty. CONCLUSIONS: Results substantiate the hypothesized link between IU and neural responses to uncertainty in some adolescents with anxiety disorders. Our findings, if replicated, suggest that trait measures, such as IU, can significantly improve our understanding of the neurobiological basis of pediatric anxiety disorders