Neural and behavioral effects of modification of visual attention in body dysmorphic disorder.

In individuals with body dysmorphic disorder (BDD), perceptual appearance distortions may be related to selective attention biases and aberrant visual scanning, contributing to imbalances in global vs. detailed visual processing. Treatments for the core symptom of perceptual distortions are underexplored in BDD; yet understanding their mechanistic effects on brain function is critical for rational treatment development. This study tested a behavioral strategy of visual-attention modification on visual system brain connectivity and eye behaviors. We acquired fMRI data in 37 unmedicated adults with BDD and 30 healthy controls. Participants viewed their faces naturalistically (naturalistic viewing), and holding their gaze on the image center (modulated viewing), monitored with an eye-tracking camera. We analyzed dynamic effective connectivity and visual fixation duration. Modulated viewing resulted in longer mean visual fixation duration compared to during naturalistic viewing, across groups. Further, modulated viewing resulted in stronger connectivity from occipital to parietal dorsal visual stream regions, also evident during the subsequent naturalistic viewing, compared with the initial naturalistic viewing, in BDD. Longer fixation duration was associated with a trend for stronger connectivity during modulated viewing. Those with more severe BDD symptoms had weaker dorsal visual stream connectivity during naturalistic viewing, and those with more negative appearance evaluations had weaker connectivity during modulated viewing. In sum, holding a constant gaze on a non-concerning area of one's face may confer increased communication in the occipital/parietal dorsal visual stream, facilitating global/holistic visual processing. This effect shows persistence during subsequent naturalistic viewing. Results have implications for perceptual retraining treatment designs.

The thalamus and its subnuclei-a gateway to obsessive-compulsive disorder.

Larger thalamic volume has been found in children with obsessive-compulsive disorder (OCD) and children with clinical-level symptoms within the general population. Particular thalamic subregions may drive these differences. The ENIGMA-OCD working group conducted mega- and meta-analyses to study thalamic subregional volume in OCD across the lifespan. Structural T1-weighted brain magnetic resonance imaging (MRI) scans from 2649 OCD patients and 2774 healthy controls across 29 sites (50 datasets) were processed using the FreeSurfer built-in ThalamicNuclei pipeline to extract five thalamic subregions. Volume measures were harmonized for site effects using ComBat before running separate multiple linear regression models for children, adolescents, and adults to estimate volumetric group differences. All analyses were pre-registered ( https://osf.io/73dvy ) and adjusted for age, sex and intracranial volume. Unmedicated pediatric OCD patients (<12 years) had larger lateral (d = 0.46), pulvinar (d = 0.33), ventral (d = 0.35) and whole thalamus (d = 0.40) volumes at unadjusted p-values <0.05. Adolescent patients showed no volumetric differences. Adult OCD patients compared with controls had smaller volumes across all subregions (anterior, lateral, pulvinar, medial, and ventral) and smaller whole thalamic volume (d = -0.15 to -0.07) after multiple comparisons correction, mostly driven by medicated patients and associated with symptom severity. The anterior thalamus was also significantly smaller in patients after adjusting for thalamus size. Our results suggest that OCD-related thalamic volume differences are global and not driven by particular subregions and that the direction of effects are driven by both age and medication status.

Mapping Cortical and Subcortical Asymmetry in Obsessive-Compulsive Disorder: Findings From the ENIGMA Consortium.

BACKGROUND: Lateralized dysfunction has been suggested in obsessive-compulsive disorder (OCD). However, it is currently unclear whether OCD is characterized by abnormal patterns of brain structural asymmetry. Here we carried out what is by far the largest study of brain structural asymmetry in OCD. METHODS: We studied a collection of 16 pediatric datasets (501 patients with OCD and 439 healthy control subjects), as well as 30 adult datasets (1777 patients and 1654 control subjects) from the OCD Working Group within the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium. Asymmetries of the volumes of subcortical structures, and of measures of regional cortical thickness and surface areas, were assessed based on T1-weighted magnetic resonance imaging scans, using harmonized image analysis and quality control protocols. We investigated possible alterations of brain asymmetry in patients with OCD. We also explored potential associations of asymmetry with specific aspects of the disorder and medication status. RESULTS: In the pediatric datasets, the largest case-control differences were observed for volume asymmetry of the thalamus (more leftward; Cohen's d = 0.19) and the pallidum (less leftward; d = -0.21). Additional analyses suggested putative links between these asymmetry patterns and medication status, OCD severity, or anxiety and depression comorbidities. No significant case-control differences were found in the adult datasets. CONCLUSIONS: The results suggest subtle changes of the average asymmetry of subcortical structures in pediatric OCD, which are not detectable in adults with the disorder. These findings may reflect altered neurodevelopmental processes in OCD.

Cingulate and thalamic metabolites in obsessive-compulsive disorder.

Focal brain metabolic effects detected by proton magnetic resonance spectroscopy (MRS) in obsessive-compulsive disorder (OCD) represent prospective indices of clinical status and guides to treatment design. Sampling bilateral pregenual anterior cingulate cortex (pACC), anterior middle cingulate cortex (aMCC), and thalamus in 40 adult patients and 16 healthy controls, we examined relationships of the neurometabolites glutamate+glutamine (Glx), creatine+phosphocreatine (Cr), and choline-compounds (Cho) with OCD diagnosis and multiple symptom types. The latter included OC core symptoms (Yale-Brown Obsessive-Compulsive Scale - YBOCS), depressive symptoms (Montgomery-Åsberg Depression Rating Scale - MADRS), and general functioning (Global Assessment Scale - GAS). pACC Glx was 9.7% higher in patients than controls. Within patients, Cr and Cho correlated negatively with YBOCS and MADRS, while Cr correlated positively with the GAS. In aMCC, Cr and Cho correlated negatively with MADRS, while Cr in thalamus correlated positively with GAS. These findings present moderate support for glutamatergic and cingulocentric perspectives on OCD. Based on our prior metabolic model of OCD, we offer one possible interpretation of these group and correlational effects as consequences of a corticothalamic state of elevated glutamatergic receptor activity alongside below-normal glutamatergic transporter activity.

Effects of cranial electrotherapy stimulation on resting state brain activity.

Cranial electrotherapy stimulation (CES) is a U.S. Food and Drug Administration (FDA)-approved treatment for insomnia, depression, and anxiety consisting of pulsed, low-intensity current applied to the earlobes or scalp. Despite empirical evidence of clinical efficacy, its mechanism of action is largely unknown. The goal was to characterize the acute effects of CES on resting state brain activity. Our primary hypothesis was that CES would result in deactivation in cortical and subcortical regions. Eleven healthy controls were administered CES applied to the earlobes at subsensory thresholds while being scanned with functional magnetic resonance imaging in the resting state. We tested 0.5- and 100-Hz stimulation, using blocks of 22 sec "on" alternating with 22 sec of baseline (device was "off"). The primary outcome measure was differences in blood oxygen level dependent data associated with the device being on versus baseline. The secondary outcome measures were the effects of stimulation on connectivity within the default mode, sensorimotor, and fronto-parietal networks. Both 0.5- and 100-Hz stimulation resulted in significant deactivation in midline frontal and parietal regions. 100-Hz stimulation was associated with both increases and decreases in connectivity within the default mode network (DMN). Results suggest that CES causes cortical brain deactivation, with a similar pattern for high- and low-frequency stimulation, and alters connectivity in the DMN. These effects may result from interference from high- or low-frequency noise. Small perturbations of brain oscillations may therefore have significant effects on normal resting state brain activity. These results provide insight into the mechanism of action of CES, and may assist in the future development of optimal parameters for effective treatment.

A pilot study of cranial electrotherapy stimulation for generalized anxiety disorder.

BACKGROUND: Cranial electrotherapy stimulation (CES) is a noninvasive procedure that has been used for decades in the United States to treat anxiety, depression, and insomnia in the general population. Whether CES is an effective treatment for patients with a DSM-IV diagnosis of generalized anxiety disorder (GAD) has not previously been explored. The goal of this study was to evaluate the efficacy of CES in alleviating anxiety in patients with DSM-IV-diagnosed GAD. METHOD: Twelve patients from 29 to 58 years of age with a DSM-IV diagnosis of GAD were enrolled from August 2005 to March 2006 through the University of California, Los Angeles (UCLA) Anxiety Disorders Program. Cranial electrotherapy stimulation treatment was administered for 6 weeks using the Alpha-Stim Stress Control System at 0.5-Hz frequency and 300-muA intensity. The primary efficacy measures were the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions-Improvement (CGI-I) scale. Response to treatment was defined as a reduction of 50% or more on the HAM-A and a CGI-I score of 1 or 2 ("much improved" or "very much improved," respectively). RESULTS: Cranial electrotherapy stimulation was associated with a significant decrease in HAM-A scores (t = 3.083, p = .01). At endpoint, 6 patients (50% of the intent-to-treat sample and 67% of completers) had a 50% decrease in HAM-A score and a CGI-I score of 1 or 2. One additional patient significantly improved in anxiety scores but did not meet criteria for response. Adverse events were generally mild in severity, mostly consisting of headache and nausea. CONCLUSION: This preliminary study suggests that CES may reduce symptoms of anxiety in GAD. We hope that these preliminary results will encourage further research to explore the use of CES in clinical settings. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00539357.

A pilot study of Rhodiola rosea (Rhodax) for generalized anxiety disorder (GAD).

BACKGROUND: Rhodiola rosea is an herbal supplement that many in the general population in Russia and elsewhere in the world have used for decades to alleviate everyday anxiety, depression, and insomnia. Whether R. rosea is effective in reducing similar symptoms in clinical samples is unknown. The goal of this pilot study was to evaluate whether R. rosea is effective in reducing symptoms of generalized anxiety disorder (GAD). METHOD: Ten (10) participants with a DSM-IV diagnosis of GAD, recruited from the UCLA Anxiety Disorders Program and between the ages of 34 and 55, were enrolled in this study from November 2005 to May 2006. Participants received a total daily dose of 340 mg of R. rosea extract for 10 weeks. Assessments included the Hamilton Anxiety Rating Scale (HARS), the Four-Dimensional Anxiety and Depression Scale, and the Clinical Global Impressions of Severity/Improvement Scale. RESULTS: Individuals treated with R. rosea showed significant decreases in mean HARS scores at endpoint (t=3.27, p=0.01). Adverse events were generally mild or moderate in severity, the most common being dizziness and dry mouth. CONCLUSIONS: Significant improvement in GAD symptoms was found with R. rosea, with a reduction in HARS scores similar to that found in clinical trials. These preliminary findings warrant further exploration of treatment with R. rosea in clinical samples.