George Andrew James

Brain activation by disgust-inducing pictures in obsessive-compulsive disorder

BACKGROUND There is growing interest in the role of disgust in the pathogenesis of obsessive-compulsive disorder (OCD). METHODS Eight OCD subjects with contamination preoccupations and eight gender- and age-matched healthy volunteers viewed pictures from the International Affective Picture System during functional magnetic resonance imaging scans. RESULTS A different distribution of brain activations was found during disgust-inducing visual stimulation in several areas, most notably the insula, compared with neutral stimulation in both OCD subjects and healthy volunteers. Furthermore, whereas activation during the threat-inducing task in OCD subjects showed a pattern similar to that in healthy volunteers, the pattern of activation during the disgust-inducing task was significantly different, including greater increases in the right insula, parahippocampal region, and inferior frontal sites. CONCLUSIONS This pilot study supports the relevance of disgust in the neurocircuitry of OCD with contamination-preoccupation symptoms; future studies looking at non-OCD individuals with high disgust ratings, non-contamination-preoccupied OCD individuals, and individuals with other anxiety disorders are needed.

Multivariate Granger causality analysis of fMRI data.

This article describes the combination of multivariate Granger causality analysis, temporal down‐sampling of fMRI time series, and graph theoretic concepts for investigating causal brain networks and their dynamics. As a demonstration, this approach was applied to analyze epoch‐to‐epoch changes in a hand‐gripping, muscle fatigue experiment. Causal influences between the activated regions were analyzed by applying the directed transfer function (DTF) analysis of multivariate Granger causality with the integrated epoch response as the input, allowing us to account for the effects of several relevant regions simultaneously. Integrated responses were used in lieu of originally sampled time points to remove the effect of the spatially varying hemodynamic response as a confounding factor; using integrated responses did not affect our ability to capture its slowly varying affects of fatigue. We separately modeled the early, middle, and late periods in the fatigue. We adopted graph theoretic concepts of clustering and eccentricity to facilitate the interpretation of the resultant complex networks. Our results reveal the temporal evolution of the network and demonstrate that motor fatigue leads to a disconnection in the related neural network. Hum Brain Mapp, 2009.

Satiety dysfunction in Prader-Willi syndrome demonstrated by fMRI.

The neurobiology relating to the insatiable appetite observed in Prader-Willi syndrome (PWS) has not been fully characterised. Two functional magnetic resonance imaging (fMRI) scans were performed on each of three adults with PWS. The scans were carried out pre- and post-treatment with the antiepileptic topiramate, which had little effect on body weight and appetite in these subjects. Subjects fasted overnight and drank a 75 g dextrose solution prior to fMRI scans for measurement of brain activation levels during/after glucose ingestion. Following glucose administration, there was a significant delay in activation at the hypothalamus and other brain regions associated with satiety compared with previous data on obese volunteers. These regions include the insula, ventromedial prefrontal cortex, and nucleus accumbens. Individuals with PWS showed a mean latency of 24 min while in a previous study obese volunteers had shown a latency of 15 min and lean volunteers a latency of 10 min in the hypothalamus. Our results provide evidence towards a satiety dysfunction in the central nervous system of PWS patients.

Differential functional connectivity within an emotion regulation neural network among individuals resilient and susceptible to the depressogenic effects of early life stress

BACKGROUND Early life stress (ELS) is a significant risk factor for depression. The effects of ELS exposure on neural network organization have not been differentiated from the effect of depression. Furthermore, many individuals exposed to ELS do not develop depression, yet the network organization patterns differentiating resiliency versus susceptibility to the depressogenic effects of ELS are not clear. METHOD Women aged 18-44 years with either a history of ELS and no history of depression (n = 7), a history of ELS and current or past depression (n = 19), or a history of neither ELS nor depression (n = 12) underwent a resting-state 3-T functional magnetic resonance imaging (fMRI) scan. An emotion regulation brain network consisting of 21 nodes was described using graph analyses and compared between groups. RESULTS Group differences in network topology involved decreased global connectivity and hub-like properties for the right ventrolateral prefrontal cortex (vlPFC) and decreased local network connectivity for the dorsal anterior cingulate cortex (dACC) among resilient individuals. Decreased local connectivity and increased hub-like properties of the left amygdala, decreased hub-like properties of the dACC and decreased local connectivity of the left vlPFC were observed among susceptible individuals. Regression analyses suggested that the severity of ELS (measured by self-report) correlated negatively with global connectivity and hub-like qualities for the left dorsolateral PFC (dlPFC). CONCLUSIONS These preliminary results suggest functional neural connectivity patterns specific to ELS exposure and resiliency versus susceptibility to the depressogenic effects of ELS exposure.

Altered functional connectivity of the insular cortex across prefrontal networks in cocaine addiction

Interoception is theorized to be an important process mediating substance use disorders, and the insular cortex is recognized as a core neural region supporting interoception. The purpose of this study was to compare the integration of the insular cortex into prefrontal-related resting-state networks between individuals with cocaine dependence and healthy controls. Participants comprised 41 patients with cocaine dependence and 19 controls who underwent a resting-state 3-T functional magnetic resonance imaging scan. Individuals with cocaine dependence demonstrated altered functional connectivity of the insular cortex, predominantly the right insular cortex, with all eight prefrontal-related resting-state networks identified through Independent Component Analysis (ICA). A conjunction analysis demonstrated that the right insular cortex was the neural region with the highest number of common group differences across the networks. There was no evidence that insular cortex connectivity commonly differed between groups for non-prefrontal-related networks. Further, seed-based functional connectivity analyses extended the network analyses and indicated that cocaine dependence was associated with greater connectivity of the right insula with the dorsomedial prefrontal cortex, inferior frontal gyrus, and bilateral dorsolateral prefrontal cortex. These data support the hypothesis that cocaine dependence is related to altered functional interactions of the insular cortex with prefrontal networks. The results suggest possible neural mechanisms by which the insular cortex and interoceptive information influence cognitive control and decision-making processes presumably mediated by prefrontal networks in the cocaine dependence process.

Keeping the Faith: African American Faith Leaders’ Perspectives and Recommendations for Reducing Racial Disparities in HIV/AIDS Infection

In Philadelphia, 66% of new HIV infections are among African Americans and 2% of African Americans are living with HIV. The city of Philadelphia has among the largest numbers of faith institutions of any city in the country. Although faith-based institutions play an important role in the African American community, their response to the AIDS epidemic has historically been lacking. We convened 38 of Philadelphia’s most influential African American faith leaders for in-depth interviews and focus groups examining the role of faith-based institutions in HIV prevention. Participants were asked to comment on barriers to engaging faith-based leaders in HIV prevention and were asked to provide normative recommendations for how African American faith institutions can enhance HIV/AIDS prevention and reduce racial disparities in HIV infection. Many faith leaders cited lack of knowledge about Philadelphia’s racial disparities in HIV infection as a common reason for not previously engaging in HIV programs; others noted their congregations’ existing HIV prevention and outreach programs and shared lessons learned. Barriers to engaging the faith community in HIV prevention included: concerns about tacitly endorsing extramarital sex by promoting condom use, lack of educational information appropriate for a faith-based audience, and fear of losing congregants and revenue as a result of discussing human sexuality and HIV/AIDS from the pulpit. However, many leaders expressed a moral imperative to respond to the AIDS epidemic, and believed clergy should play a greater role in HIV prevention. Many participants noted that controversy surrounding homosexuality has historically divided the faith community and prohibited an appropriate response to the epidemic; many expressed interest in balancing traditional theology with practical public health approaches to HIV prevention. Leaders suggested the faith community should: promote HIV testing, including during or after worship services and in clinical settings; integrate HIV/AIDS topics into health messaging and sermons; couch HIV/AIDS in social justice, human rights and public health language rather than in sexual risk behavior terms; embrace diverse approaches to HIV prevention in their houses of worship; conduct community outreach and host educational sessions for youth; and collaborate on a citywide, interfaith HIV testing and prevention campaign to combat stigma and raise awareness about the African American epidemic. Many African American faith-based leaders are poised to address racial disparities in HIV infection. HIV prevention campaigns should integrate leaders’ recommendations for tailoring HIV prevention for a faith-based audience.

Task-dependent recruitment of intrinsic brain networks reflects normative variance in cognition.

Functional neuroimaging has great potential to inform clinical decisions, whether by identifying neural biomarkers of illness progression and severity, predicting therapeutic response, or selecting suitable patients for surgical interventions. Yet a persisting barrier to functional neuroimagings clinical translation is our incomplete understanding of how normative variance in cognition, personality, and behavior shape the brains structural and functional organization. We propose that modeling individual differences in these brain–behavior relationships is crucial for improving the accuracy of neuroimaging biomarkers for neurologic and psychiatric disorders.

Prolonged insula activation during perception of aftertaste

Although a critical component of taste perception, the neural basis of aftertaste perception has yet to be elucidated with neuroimaging. This functional neuroimaging study assessed the temporal dynamics of neural responses to sucrose and aspartame in eight healthy volunteers. Aspartame has a sweetness flavor profile similar to sucrose but a longer temporal profile. Participants underwent functional magnetic resonance imaging while tasting sucrose and aspartame solutions administered through a magnetic resonance imaging compatible delivery device. The insula showed significantly longer activation to aspartame than sucrose, whereas other regions activated by the task (somatosensory cortex, thalamus, amygdala, and basal ganglia) did not show a prolonged response to either tastant. These findings implicate the insula in aftertaste perception.

African American community leaders' policy recommendations for reducing racial disparities in HIV infection, treatment, and care: results from a community-based participatory research project in Philadelphia, Pennsylvania.

African Americans account for 45% of new HIV infections in the United States. Little empirical research investigates African American community leaders’ normative recommendations for addressing these disparities. Philadelphia’s HIV infection rate is 5 times the national average, nearly 70% of new infections are among African Americans, and 2% of African Americans in Philadelphia are living with HIV/AIDS. Using a community-based participatory research approach, we convened focus groups among 52 African American community leaders from diverse backgrounds to solicit normative recommendations for reducing Philadelphia’s racial disparities in HIV infection. Leaders recommended that (a) Philadelphia’s city government should raise awareness about HIV/AIDS with media campaigns featuring local leaders, (b) local HIV-prevention interventions should address social and structural factors influencing HIV risks rather than focus exclusively on mode of HIV transmission, (c) resources should be distributed to the most heavily affected neighborhoods of Philadelphia, and (d) faith institutions should play a critical role in HIV testing, treatment, and prevention efforts. We developed a policy memo highlighting these normative recommendations for how to enhance local HIV prevention policy. This policy memo led to Philadelphia City Council hearings about HIV/AIDS in October 2010 and subsequently informed local HIV/AIDS prevention policy and development of local HIV prevention interventions. This community-based participatory research case study offers important lessons for effectively engaging community leaders in research to promote HIV/AIDS policy change.

Recognizing Sign Language from Brain Imaging

Classification of complex motor activities from brain imaging is relatively new in the fields of neuroscience and brain-computer interfaces (BCIs). We report sign language classification results for a set of three contrasting pairs of signs. Executed sign accuracy was 93.3%, and imagined sign accuracy was 76.7%. For a full multiclass problem, we used a decision directed acyclic graph of pairwise support vector machines, resulting in 63.3% accuracy for executed sign and 31.4% accuracy for imagined sign. Pairwise comparison of phrases composed of these signs yielded a mean accuracy of 73.4%. These results suggest the possibility of BCIs based on sign language.