Increases in functional connectivity between the default mode network and sensorimotor network correlate with symptomatic improvement after transcranial direct current stimulation for obsessive-compulsive disorder.

BACKGROUND: Non-invasive neuromodulation is a promising intervention for obsessive-compulsive disorder (OCD), although its neurobiological mechanisms of action are still poorly understood. Recent evidence suggests that abnormalities in the connectivity of the default mode network (DMN) and the supplementary motor area (SMA) with other brain regions and networks are involved in OCD pathophysiology. We examined if transcranial direct current stimulation (tDCS) alters these connectivity patterns and if they correlate with symptom improvement in treatment-resistant OCD. METHODS: In 23 patients from a larger clinical trial (comparing active tDCS to sham) who underwent pre- and post-treatment MRI scans, we assessed resting-state functional MRI (rs-fMRI) data. The treatment involved 30-minute daily tDCS sessions for four weeks (weekdays only), with the cathode over the SMA and the anode over the left deltoid. We conducted whole-brain connectivity analysis comparing active tDCS-treated to sham-treated patients. RESULTS: We found that active tDCS, but not sham, led to connectivity increasing between the DMN and the bilateral pre/postcentral gyri (p = 0.004, FDR corrected) and temporal-auditory areas plus the SMA (p = 0.028, FDR corrected). Also, symptom improvement was directly associated with connectivity increasing between the left lateral sensorimotor network and the left precuneus (r = 0.589, p = 0.034). LIMITATIONS: Limited sample size (23 participants with resting-state neuroimaging), inability to analyze specific OCD symptom dimensions (e.g., harm, sexual/religious, symmetry/checking, cleaning/contamination). CONCLUSIONS: These data offer novel information concerning functional connectivity changes associated with non-invasive neuromodulation interventions in OCD and can guide new brain stimulation interventions in the framework of personalized interventions.

Gamma knife capsulotomy for intractable OCD: Neuroimage analysis of lesion size, location, and clinical response.

Obsessive-compulsive disorder (OCD) affects 2-3% of the population. One-third of patients are poorly responsive to conventional therapies, and for a subgroup, gamma knife capsulotomy (GKC) is an option. We examined lesion characteristics in patients previously treated with GKC through well-established programs in Providence, RI (Butler Hospital/Rhode Island Hospital/Alpert Medical School of Brown University) and São Paulo, Brazil (University of São Paolo). Lesions were traced on T1 images from 26 patients who had received GKC targeting the ventral half of the anterior limb of the internal capsule (ALIC), and the masks were transformed into MNI space. Voxel-wise lesion-symptom mapping was performed to assess the influence of lesion location on Y-BOCS ratings. General linear models were built to compare the relationship between lesion size/location along different axes of the ALIC and above or below-average change in Y-BOCS ratings. Sixty-nine percent of this sample were full responders (≥35% improvement in OCD). Lesion occurrence anywhere within the targeted region was associated with clinical improvement, but modeling results demonstrated that lesions occurring posteriorly (closer to the anterior commissure) and dorsally (closer to the mid-ALIC) were associated with the greatest Y-BOCS reduction. No association was found between Y-BOCS reduction and overall lesion volume. GKC remains an effective treatment for refractory OCD. Our data suggest that continuing to target the bottom half of the ALIC in the coronal plane is likely to provide the dorsal-ventral height required to achieve optimal outcomes, as it will cover the white matter pathways relevant to change. Further analysis of individual variability will be essential for improving targeting and clinical outcomes, and potentially further reducing the lesion size necessary for beneficial outcomes.

Hippocampal formation volume, its subregions, and its specific contributions to visuospatial memory tasks.

Visuospatial memory (VSM) is the ability to represent and manipulate visual and spatial information. This cognitive function depends on the functioning of the hippocampal formation (HF), located in the medial portion of the temporal cortex. The present study aimed to investigate whether there is an association between the volume of the HF and performance in VSM tests. High-resolution structural images (T1) and neuropsychological tests evaluating VSM were performed on 31 healthy individuals. A VSM index was created by grouping 5 variables from 5 tasks (4 from the CANTAB battery and 1 from the Rey-Osterrieth Complex Figure test). Multiple linear regression models using the volumes of HF subregions as independent variables and the VSM index as the dependent variable were conducted to test the hypothesis that memory performance could be predicted by HF volumes. We also conducted analyses to explore the role of covariates that may mediate this relationship, specifically age and intelligence quotient (IQ). We found significant associations between the hippocampal subregions of the left hemisphere and the VSM index (F(7,22)=2.758, P=0.032, R2a=0.298). When IQ was accounted for as a covariate, we also found significant results for the right hemisphere (F(8,21)=2.804, P=0.028, R2a=0.517). We concluded that the bilateral hippocampal formations contributed to performance on VSM tasks. Also, VSM processing is essential for a diverse set of daily activities and may be influenced by demographic variables in healthy subjects.

Hippocampal formation volume, its subregions, and its specific contributions to visuospatial memory tasks

Visuospatial memory (VSM) is the ability to represent and manipulate visual and spatial information. This cognitive function depends on the functioning of the hippocampal formation (HF), located in the medial portion of the temporal cortex. The present study aimed to investigate whether there is an association between the volume of the HF and performance in VSM tests. High-resolution structural images (T1) and neuropsychological tests evaluating VSM were performed on 31 healthy individuals. A VSM index was created by grouping 5 variables from 5 tasks (4 from the CANTAB battery and 1 from the Rey-Osterrieth Complex Figure test). Multiple linear regression models using the volumes of HF subregions as independent variables and the VSM index as the dependent variable were conducted to test the hypothesis that memory performance could be predicted by HF volumes. We also conducted analyses to explore the role of covariates that may mediate this relationship, specifically age and intelligence quotient (IQ). We found significant associations between the hippocampal subregions of the left hemisphere and the VSM index (F(7,22)=2.758, P=0.032, R2a=0.298). When IQ was accounted for as a covariate, we also found significant results for the right hemisphere (F(8,21)=2.804, P=0.028, R2a=0.517). We concluded that the bilateral hippocampal formations contributed to performance on VSM tasks. Also, VSM processing is essential for a diverse set of daily activities and may be influenced by demographic variables in healthy subjects.