Depression is a commonly occurring symptom in obsessive-compulsive disorder (OCD), and is associated with worse functional impairment, poorer quality of life, and poorer treatment response. ...Understanding the underlying neurochemical and connectivity-based brain mechanisms of this important symptom domain in OCD is necessary for development of novel, more globally effective treatments. To investigate biopsychological mechanisms of comorbid depression in OCD, we examined effective connectivity and neurochemical signatures in the pregenual anterior cingulate cortex (pACC), a structure known to be involved in both OCD and depression. Resting-state functional magnetic resonance imaging (fMRI) and 1 H magnetic resonance spectroscopy (MRS) data were obtained from participants with OCD (n=49) and healthy individuals of equivalent age and sex (n=25). Granger causality-based effective (directed) connectivity was used to define causal networks involving the right and left pACC. The interplay between fMRI connectivity, 1 H MRS and clinical data was explored by applying moderation and mediation analyses. We found that the causal influence of the right dorsal anterior midcingulate cortex (daMCC) on the right pACC was significantly lower in the OCD group and showed significant correlation with depressive symptom severity in the OCD group. Lower and moderate levels of glutamate (Glu) in the right pACC significantly moderated the interaction between right daMCC-pACC connectivity and depression severity. Our results suggest a biochemical-connectivity-psychological model of pACC dysfunction contributing to depression in OCD, particularly involving intracingulate connectivity and glutamate levels in the pACC. These findings have implications for potential molecular and network targets for treatment of this multi-faceted psychiatric condition.
Intensive cognitive-behavioral therapy (CBT) can effectively reduce symptoms in obsessive-compulsive disorder (OCD). However, many relapse after treatment. Few studies have investigated biological ...markers predictive of follow-up clinical status. The objective was to determine if brain network connectivity patterns prior to intensive CBT predict worsening of clinical symptoms during follow-up.
We acquired resting-state functional magnetic resonance imaging data from 17 adults with OCD prior to and following 4 weeks of intensive CBT. Functional connectivity data were analyzed to yield graph-theory metrics. We examined the relationship between pre-treatment connectome properties and OCD clinical symptoms before and after treatment and during a 12-month follow-up period.
Mean OCD symptom decrease was 40.4 ± 16.4% pre- to post-treatment (64.7% responded; 58.8% remitted), but 35.3% experienced clinically significant worsening during follow-up. From pre- to post-treatment, small-worldness and clustering coefficient significantly increased. Decreases in modularity correlated with decreases in OCD symptoms. Higher pre-treatment small-world connectivity was significantly associated with worsening of OCD symptoms during the follow-up period. Psychometric and neurocognitive measures pre- and post-treatment were not significant predictors.
This is the first graph-theory connectivity study of the effects of CBT in OCD, and the first to test associations with follow-up clinical status. Results show functional network efficiency as a biomarker of CBT response and relapse in OCD. CBT increases network efficiency as it alleviates symptoms in most patients, but those entering therapy with already high network efficiency are at greater risk of relapse. Results have potential clinical implications for treatment selection.
Recent evidence suggests that putting feelings into words activates the prefrontal cortex (PFC) and suppresses the response of the amygdala, potentially helping to alleviate emotional distress. To ...further elucidate the relationship between brain structure and function in these regions, structural and functional magnetic resonance imaging (MRI) data were collected from a sample of 20 healthy human subjects. Structural MRI data were processed using cortical pattern-matching algorithms to produce spatially normalized maps of cortical thickness. During functional scanning, subjects cognitively assessed an emotional target face by choosing one of two linguistic labels (label emotion condition) or matched geometric forms (control condition). Manually prescribed regions of interest for the left amygdala were used to extract percentage signal change in this region occurring during the contrast of label emotion versus match forms. A correlation analysis between left amygdala activation and cortical thickness was then performed along each point of the cortical surface, resulting in a color-coded r value at each cortical point. Correlation analyses revealed that gray matter thickness in left ventromedial PFC was inversely correlated with task-related activation in the amygdala. These data add support to a general role of the ventromedial PFC in regulating activity of the amygdala.
Advances in resting state fMRI and diffusion weighted imaging (DWI) have led to much interest in studies that evaluate hypotheses focused on how brain connectivity networks show variations across ...clinically disparate groups. However, various sources of error (e.g., tractography errors, magnetic field distortion, and motion artifacts) leak into the data, and make downstream statistical analysis problematic. In small sample size studies, such noise have an unfortunate effect that the differential signal may not be identifiable and so the null hypothesis cannot be rejected. Traditionally, smoothing is often used to filter out noise. But the construction of convolving with a Gaussian kernel is not well understood on arbitrarily connected graphs. Furthermore, there are no direct analogues of scale-space theory for graphs--ones which allow to view the signal at multiple resolutions. We provide rigorous frameworks for performing 'multi-resolutional' analysis on brain connectivity graphs. These are based on the recent theory of non-Euclidean wavelets. We provide strong evidence, on brain connectivity data from a network analysis study (structural connectivity differences in adult euthymic bipolar subjects), that the proposed algorithm allows identifying statistically significant network variations, which are clinically meaningful, where classical statistical tests, if applied directly, fail.
CONTEXT Body dysmorphic disorder (BDD) is a psychiatric disorder in which individuals are preoccupied with perceived defects in their appearance, often related to their face. Little is known about ...its pathophysiology, although early research provides evidence of abnormal visual processing. OBJECTIVE To determine whether patients with BDD have abnormal patterns of brain activation when visually processing their own face with high, low, or normal spatial resolution. DESIGN Case-control study. SETTING A university hospital. PARTICIPANTS Seventeen right-handed medication-free subjects with BDD and 16 matched healthy control subjects. INTERVENTION Functional magnetic resonance imaging while viewing photographs of face stimuli. Stimuli were neutral-expression photographs of the patient's own face and a familiar face (control stimuli) that were unaltered, altered to include only high spatial frequency (fine spatial resolution), or altered to include only low spatial frequency (low spatial resolution). MAIN OUTCOME MEASURE Blood oxygen level–dependent signal changes in the BDD and control groups during each stimulus type. RESULTS Subjects with BDD showed relative hyperactivity in the left orbitofrontal cortex and bilateral head of the caudate for the unaltered own-face vs familiar-face condition. They showed relative hypoactivity in the left occipital cortex for the low spatial frequency faces. Differences in activity in frontostriatal systems but not visual cortex covaried with aversiveness ratings of the faces. Severity of BDD symptoms correlated with activity in frontostriatal systems and visual cortex. CONCLUSIONS These results suggest abnormalities in visual processing and frontostriatal systems in BDD. Hypoactivation in the occipital cortex for low spatial frequency faces may indicate either primary visual system abnormalities for configural face elements or top-down modulation of visual processing. Frontostriatal hyperactivity may be associated both with aversion and with symptoms of obsessive thoughts and compulsive behaviors.Arch Gen Psychiatry. 2010;67(2):197-205-->
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