Faculty Bibliography

Obsessive-compulsive disorder (OCD) is characterized by excessive absorption with internally-generated distressing thoughts and urges, with difficulty incorporating external information running counter to their fears and concerns. In the present study, we experimentally probed this core feature of OCD through the use of a novel attention switching task that investigates transitions between internally focused (IF) and externally focused (EF) attentional states. Eighteen OCD patients and 18 controls imagined positive and negative personal event scenarios (IF state) or performed a color-word Stroop task (EF state). The IF/EF states were followed by a target detection (TD) task requiring responses to external stimuli. Compared to controls, OCD patients made significantly more errors and showed reduced activation of superior and inferior occipital cortex, thalamus, and putamen during TD following negative IF, with the inferior occipital hypoactivation being significantly greater for TD following negative IF compared to TD following the other conditions. Patients showed stronger functional connectivity between the inferior occipital region and dorsomedial prefrontal cortex. These findings point to an OCD-related impairment in the visual processing of external stimuli specifically when they follow a period of negative internal focus, and suggest that future treatments may wish to target the transition between attentional states.

BACKGROUND: There has been growing interest under the Research Domain Criteria initiative to investigate behavioral constructs and their underlying neural circuitry. Abnormalities in reward processes are salient across psychiatric conditions and may precede future psychopathology in youth. However, the neural circuitry underlying such deficits has not been well defined. Therefore, in this pilot, we studied youth with diverse psychiatric symptoms and examined the neural underpinnings of reward anticipation, attainment, and positive prediction error (PPE, unexpected reward gain). Clinically, we focused on anhedonia, known to reflect deficits in reward function. METHODS: Twenty-two psychotropic medication-free youth, 16 with psychiatric symptoms, exhibiting a full range of anhedonia, were scanned during the Reward Flanker Task. Anhedonia severity was quantified using the Snaith-Hamilton Pleasure Scale. Functional magnetic resonance imaging analyses were false discovery rate corrected for multiple comparisons. RESULTS: Anticipation activated a broad network, including the medial frontal cortex and ventral striatum, while attainment activated memory and emotion-related regions such as the hippocampus and parahippocampal gyrus, but not the ventral striatum. PPE activated a right-dominant fronto-temporo-parietal network. Anhedonia was only correlated with activation of the right angular gyrus during anticipation and the left precuneus during PPE at an uncorrected threshold. LIMITATIONS: Findings are preliminary due to the small sample size. CONCLUSIONS: This pilot characterized the neural circuitry underlying different aspects of reward processing in youth with diverse psychiatric symptoms. These results highlight the complexity of the neural circuitry underlying reward anticipation, attainment, and PPE. Furthermore, this study underscores the importance of RDoC research in youth.

Obsessive-compulsive disorder (OCD) patients show increased insula activation to disgust-inducing images compared to healthy controls (HC). We explored whether this disgust reactivity was also present in the olfactory domain by conducting the first fMRI study of olfaction in OCD. Neural activation in response to pleasant and unpleasant odors (vs. unscented air) was investigated in 15 OCD and 15 HC participants using fMRI. OCD participants (vs. HC) had increased left anterior insula activation to unpleasant odors (vs. unscented air), which positively correlated with their disgust sensitivity and ratings of the unpleasantness and intensity of those odors. OCD participants (vs. HC) showed increased activation of caudate nucleus and left anterior and posterior insula to pleasant odors (vs. unscented air), which positively correlated with their OCD symptom severity, trait anxiety, frequency of feeling disgust, and odor intensity ratings. OCD participants had increased anterior insula activation to both pleasant and unpleasant odors, which correlated with their OCD symptoms, anxiety, disgust sensitivity, and frequency of feeling disgust. OCD patients might have a negative cognitive bias and experience all stimuli, regardless of valence, as being more unpleasant than healthy people. These findings further elucidate the neural underpinnings of OCD and may contribute to more effective treatments.

Introduction/UNASSIGNED:Obsessive-compulsive disorder (OCD) patients show abnormalities in decision-making and, clinically, appear to show heightened sensitivity to potential negative outcomes. Despite the importance of these cognitive processes in OCD, few studies have examined the disorder within an economic decision-making framework. Here, we investigated loss aversion, a key construct in the prospect theory that describes the tendency for individuals to be more sensitive to potential losses than gains when making decisions. Methods/UNASSIGNED: = 34) accepted or rejected a series of 50/50 gambles containing varying loss/gain values. Loss aversion was calculated as the ratio of the likelihood of rejecting a gamble with increasing potential losses to the likelihood of accepting a gamble with increasing potential gains. Decision times to accept or reject were also examined and correlated with loss aversion. Results/UNASSIGNED:analyses further indicated that unmedicated patients' increased likelihood to reject a gamble as its loss value increased could not be explained solely by greater risk aversion among patients. Unmedicated patients were also slower to accept than reject gambles, effects that were not found in the other two groups. Loss aversion was correlated with decision times in unmedicated patients but not in the other two groups. Discussion/UNASSIGNED:These data identify abnormalities of decision-making in a subgroup of OCD patients not taking psychotropic medication. The findings help elucidate the cognitive mechanisms of the disorder and suggest that future treatments could aim to target abnormalities of loss/gain processing during decision-making in this population.

INTRODUCTION: The habenula (Hb) is postulated to play a critical role in reward and aversion processing across species, including humans, and has been increasingly implicated in depression. However, technical constraints have limited in vivo investigation of the human Hb, and its function remains poorly characterized. We sought to overcome these challenges by examining the whole-brain resting-state functional connectivity of the Hb and its possible relationship to depressive symptomatology using the high-resolution WU-Minn Human Connectome Project (HCP) dataset. METHODS: Anatomical and resting-state functional MRI data from 50 healthy subjects with low or high subclinical depression scores (n = 25 each) were analyzed. Using novel semi-automated segmentation and optimization techniques, we generated individual-specific Hb seeds and calculated whole-brain functional connectivity for the entire cohort and the contrast of high vs. low depression groups. RESULTS: In the entire cohort, the Hb exhibited significant connectivity with key brainstem structures (i.e., ventral tegmental area, substantia nigra, pons) as well as the anterior and posterior cingulate cortices, precuneus, thalamus, and sensorimotor cortex. Multiple regions showed differential Hb connectivity based on subclinical depression scores, including the amygdala, insula, and prefrontal, mid-cingulate, and entorhinal cortices. CONCLUSIONS: Hb connectivity findings converged on areas associated with salience processing, sensorimotor systems, and the default mode network. We also detected substantial Hb-brainstem connectivity, consistent with prior histological and animal research. High and low subclinical depression groups exhibited differences in Hb connectivity with multiple regions previously linked to depression, suggesting the relationship between these structures as a potential target for future research and treatment. Hum Brain Mapp, 2016. (c) 2016 Wiley Periodicals, Inc.

Despite the fact that OCD patients show altered decision making in everyday life, few studies have investigated how patients make risky decisions and what contextual factors impact choices. We investigated cognitive context with the use of the "framing effect" task, which investigates decision making based on whether monetarily equivalent choice options are framed in terms of a potential to either lose (lose $20 out of $50) or gain (gain $30 out of $50) money. In addition, we manipulated social context by providing positive or neutral feedback on subjects' choices. Overall, participants were risk taking for options framed in terms of potential loss and risk averse for options framed in terms of potential gain (the classic framing effect). Although OCD patients were generally more risk averse, the effect of the frame on choices did not differ significantly from healthy participants and choices were not impacted by social context. Within OCD patients, greater self-reported indecisiveness was associated with a larger effect of the frame on choices. OCD patients were also significantly slower to make choices in the loss compared to gain frame, an effect that was not observed among healthy participants. Overall, our results suggest that the framing of choice options has a differential effect on decision times but not the actual choices made by OCD patients, and that patients are not sensitive to social feedback when making choices. The correlation between indecisiveness and the framing effect in OCD suggests that further work interrogating the relationship between specific symptoms and decision making among patients may yield new insights into the disorder.

BACKGROUND: In recent years, diffusion tensor imaging (DTI) studies have detected subtle microstructural abnormalities of white matter (WM) in obsessive-compulsive disorder (OCD). However, findings have been inconsistent, and it is unclear whether WM abnormalities are related to cognitive processes. The aim of this study was to explore the relationship of WM alterations with cognitive variables in OCD in order to investigate the structural correlates of behaviorally relevant features of the disorder. METHODS: We compared DTI-derived fractional anisotropy (FA), mean diffusivity (MD), and radial diffusivity (RD) measures between OCD patients (n = 16) and healthy controls (n = 18) using a whole-brain tract-based spatial statistics (TBSS) approach. We also explored the correlations of WM alterations with clinical and cognitive variables. RESULTS: Patients with OCD demonstrated increases in MD in the bilateral posterior corona radiata; left anterior corona radiata; bilateral superior longitudinal fasciculus; genu, body, and splenium of the corpus callosum; and left posterior limb of the internal capsule. An increase in RD values was also found in some of the same tracts (right posterior corona radiata, right superior longitudinal fasciculus, left anterior corona radiata, and corpus callosum). Furthermore, increased MD value in the internal capsule was correlated with the percentage of errors made during a target detection task, which was greater in the OCD group overall. CONCLUSIONS: These findings indicate that OCD patients show greater diffusivity in several white-matter regions. The correlation between cognitive performance and diffusivity in the internal capsule suggests that microstructural WM alternations may have functional consequences for the disorder.

Efficient, adaptive behavior relies on the ability to flexibly move between internally focused (IF) and externally focused (EF) attentional states. Despite evidence that IF cognitive processes such as event imagination comprise a significant amount of awake cognition, the consequences of internal absorption on the subsequent recruitment of brain networks during EF tasks are unknown. The present functional magnetic resonance imaging (fMRI) study employed a novel attentional state switching task. Subjects imagined positive and negative events (IF task) or performed a working memory task (EF task) before switching to a target detection (TD) task also requiring attention to external information, allowing for the investigation of neural functioning during external attention based on prior attentional state. There was a robust increase of activity in frontal, parietal, and temporal regions during TD when subjects were previously performing the EF compared with IF task, an effect that was most pronounced following negative IF. Additionally, dorsolateral prefrontal cortex was less negatively coupled with ventromedial prefrontal and posterior cingulate cortices during TD following IF compared with EF. These findings reveal the striking consequences for brain activity following immersion in an IF attentional state, which have strong implications for psychiatric disorders characterized by excessive internal focus.