Yoshinari Abe

Distinct Subcortical Volume Alterations in Pediatric and Adult OCD: A Worldwide Meta- and Mega-Analysis.

OBJECTIVE Structural brain imaging studies in obsessive-compulsive disorder (OCD) have produced inconsistent findings. This may be partially due to limited statistical power from relatively small samples and clinical heterogeneity related to variation in illness profile and developmental stage. To address these limitations, the authors conducted meta- and mega-analyses of data from OCD sites worldwide. METHOD T1 images from 1,830 OCD patients and 1,759 control subjects were analyzed, using coordinated and standardized processing, to identify subcortical brain volumes that differ between OCD patients and healthy subjects. The authors performed a meta-analysis on the mean of the left and right hemisphere measures of each subcortical structure, and they performed a mega-analysis by pooling these volumetric measurements from each site. The authors additionally examined potential modulating effects of clinical characteristics on morphological differences in OCD patients. RESULTS The meta-analysis indicated that adult patients had significantly smaller hippocampal volumes (Cohens d=-0.13; % difference=-2.80) and larger pallidum volumes (d=0.16; % difference=3.16) compared with adult controls. Both effects were stronger in medicated patients compared with controls (d=-0.29, % difference=-4.18, and d=0.29, % difference=4.38, respectively). Unmedicated pediatric patients had significantly larger thalamic volumes (d=0.38, % difference=3.08) compared with pediatric controls. None of these findings were mediated by sample characteristics, such as mean age or scanning field strength. The mega-analysis yielded similar results. CONCLUSIONS The results indicate different patterns of subcortical abnormalities in pediatric and adult OCD patients. The pallidum and hippocampus seem to be of importance in adult OCD, whereas the thalamus seems to be key in pediatric OCD. These findings highlight the potential importance of neurodevelopmental alterations in OCD and suggest that further research on neuroplasticity in OCD may be useful.

Hyper-influence of the orbitofrontal cortex over the ventral striatum in obsessive-compulsive disorder.

Dysfunction of the fronto-striato-thalamic circuit routing through the orbitofrontal cortex (OFC) is thought to play the main role in the pathophysiology of obsessive-compulsive disorder (OCD). Repetitious stimulation of the OFC-ventral striatum (VS) projections in mice has been shown to increase the firing of the postsynaptic VS cells and the frequency of OCD-like symptoms. Moreover, increased functional connectivity (FC) between the OFC and the VS has been reported in patients with OCD. While FC is a synchronous, non-directed correlation, the directed influence between these brain regions remains unclear in patients with OCD. We obtained resting state functional magnetic resonance imaging scans from 37 non-medicated patients with OCD and 38 matched healthy volunteers, and calculated bivariative voxel-wise Granger Causality (GC) to and from three striatal regions of interest (ROI) using a blind deconvolution procedure. Additionally, we conducted multivariative GC analysis to determine if the effect revealed by the bivariative voxel-wise GCA is mediated by another seed ROI. We found a significant hyper-influence of the OFC over the VS of subjects with OCD (p<.05, corrected). Multivariative GC analysis confirmed this effect (p<.05, corrected) and that it was not mediated by another brain area within the striatum. This is the first study investigating the directed influence of the fronto-striato-thalamic loop in non-medicated patients with OCD. We confirmed the hyperactive connection from the OFC to the VS that is consistent with previous animal studies. These findings provide evidence for the more detailed pathophysiology of OCD.

Altered fronto-striatal fiber topography and connectivity in obsessive-compulsive disorder.

Fronto-striatal circuits are hypothesized to be involved in the pathophysiology of obsessive-compulsive disorder (OCD). Within this circuitry, ventral frontal regions project fibers to the ventral striatum (VS) and dorsal frontal regions to the dorsal striatum. Resting state fMRI research has shown higher functional connectivity between the orbitofrontal cortex (OFC) and the dorsal part of the VS in OCD patients compared to healthy controls (HC). Therefore, we hypothesized that in OCD the OFC predominantly project fibers to the more dorsal part of the VS, and that the structural connectivity between the OFC and VS is higher compared to HC. A total of 20 non-medicated OCD patients and 20 HC underwent diffusion-weighted imaging. Connectivity-based parcellation analyses were performed with the striatum as seed region and the OFC, dorsolateral prefrontal cortex, and dorsal anterior cingulate cortex as target regions. Obtained connectivity maps for each frontal region of interest (ROI) were normalized into standard space, and Z-component (dorsal–ventral) coordinate of center-of-gravity (COG) were compared between two groups. Probabilistic tractography was performed to investigate diffusion indices of fibers between the striatum and frontal ROIs. COG Z-component coordinates of connectivity maps for OFC ROI were located in the more dorsal part of the VS in OCD patients compared to HC. Fractional anisotropy of fibers between the OFC and the striatum was higher in OCD patients compared to HC. Part of the pathophysiology of OCD might be understood by altered topography and structural connectivity of fibers between the OFC and the striatum.

A Neural Marker of Obsessive-Compulsive Disorder from Whole-Brain Functional Connectivity

Obsessive-compulsive disorder (OCD) is a common psychiatric disorder with a lifetime prevalence of 2–3%. Recently, brain activity in the resting state is gathering attention for exploring altered functional connectivity in psychiatric disorders. Although previous resting-state functional magnetic resonance imaging studies investigated the neurobiological abnormalities of patients with OCD, there are concerns that should be addressed. One concern is the validity of the hypothesis employed. Most studies used seed-based analysis of the fronto-striatal circuit, despite the potential for abnormalities in other regions. A hypothesis-free study is a promising approach in such a case, while it requires researchers to handle a dataset with large dimensions. Another concern is the reliability of biomarkers derived from a single dataset, which may be influenced by cohort-specific features. Here, our machine learning algorithm identified an OCD biomarker that achieves high accuracy for an internal dataset (AUC = 0.81; N = 108) and demonstrates generalizability to an external dataset (AUC = 0.70; N = 28). Our biomarker was unaffected by medication status, and the functional networks contributing to the biomarker were distributed widely, including the frontoparietal and default mode networks. Our biomarker has the potential to deepen our understanding of OCD and to be applied clinically.

The detection of white matter alterations in obsessive–compulsive disorder revealed by TRActs Constrained by UnderLying Anatomy (TRACULA)

Purpose In recent years, a large number of studies have investigated obsessive–compulsive disorder (OCD) using diffusion-weighted images (DWIs) and have reported microstructural abnormalities in various regions, mainly the corpus callosum and cingulum. In the present study, we aimed to detect microstructural changes in the white matter using whole-brain tractography. Patients and methods We obtained MRI data from 25 adult non-medicated OCD patients and 27 healthy controls. DWI data from MRI scans were analyzed by the automated probabilistic tractography method referred to as TRActs Constrained by UnderLying Anatomy (TRACULA). We investigated diffusivity parameters: fractional anisotropy, radial diffusivity (RD), axial diffusivity, and mean diffusivity in 18 major white matter tracts and examined indices to know which measurements in which fibers can predict the diagnosis of OCD. Results Compared to healthy controls, OCD patients had significantly increased RD in the forceps major and a reduction of RD in the right cingulum angular (infracallosal) bundle. There was no correlation between these values and the clinical features. Conclusion We found RD alterations in the forceps major and the right cingulum angular (infracallosal) bundle, which might be associated with myelination changes in the temporal and occipital regions in OCD. Our results suggest that the pathogenesis of OCD may include abonormality of myelination status in not only the fronto-striato-thalamic circuit but also the posterior and temporal regions.

FREQUENCY SPECIFIC ANALYSIS REVEALED THE IMBALANCED FUNCTIONAL NETWORKS IN OBSESSIVE-COMPULSIVE DISORDER

. Dysfunction of the fronto-striatal circuit is repeatedly reported in obsessive-compulsive disorder. The abnormality of the functional connectivity (FC) of this circuit is also reported and the deep brain stimulation is showed to restore it. However, the directions of the reported abnormalities are not consistent and the more detailed analysis is needed. The blood-oxygen-level-dependent (BOLD) signal obtained from the functional magnetic resonance imaging (fMRI) scans is usually analyzed after some preprocessing steps including band-pass filtering (typically, 0.010-0.080 Hz). The frequency of the filtering is decided considering the signal-noise ratio, while this band width involve two bands having different functions; slow-4 band (0.027-0.073 Hz) and slow-5 band (0.010-0.027 Hz) (Buzsaki et al., 2004). Here we conducted the frequency specific analysis of the functional networks. The participants are 37 non-medicated patients with OCD and 38 matched healthy volunteers. We obtained resting state fMRI scans and preprocessed BOLD data with slow-4 band and slow-5 band. Then we calculated voxelwise statistical parametric maps testing strength of functional connectivity of three striatal seed regions of interest (ROIs) in each hemisphere with remaining brain regions between groups. We found the significantly decreased FC between the dorsal caudate and the dorsolateral prefrontal cortex only with the slow-5 band data (peak level corrected p

A case of Hashimoto's encephalopathy successfully treated with oral steroid therapy, resistant to high-dose methylprednisolone, plasma exchange and intravenous immunoglobulin.

A 30-year-old woman was admitted to the first institution with subacutely progressive aphasia and depression. Despite of lacking conclusive evidence on magnetic resonance imaging, cerebrospinal fluid examination, or electroencephalogram, we tentatively diagnosed her disease as limbic encephalopathy due to its acute progression. High-dose methylprednisolone was started on admission. However, symptoms did not improve. To make matters worse, psychiatric symptoms, such as hallucinations and emotional incontinence, appeared on the same day. Additional treatment with plasma exchange and intravenous immunoglobulin administration was also ineffective. Therefore, we could not manage the patient in a general ward due to severe psychiatric symptoms. The patient was transferred to a psychiatric ward in the second institution. She received both psychiatric treatment and steroid therapy, including a second course of intravenous high-dose methylprednisolone, followed by long-term oral prednisolone. Her symptoms gradually improved. A final diagnosis of Hashimotos encephalopathy was made based on the patients clinical course and positive results for both serum anti-thyroid antibody and anti-NAE antibody. In our case, long-term oral steroid therapy under psychiatric treatment was effective for good outcome.