Clinical Neuroscience and Computational Anatomy unit

Jun Soo Kwon, MD, PhD, Dept. of Psychiatry, SNU HP

2010

* White matter neuroplastic changes in long-term trained players of the game of "Baduk" (GO): A voxel-based diffusion-tensor imaging study.
[Article (PDF)]
Currently, one of the most challenging issues in modern neuroscience is learning-induced neural plasticity. Many researchers have identified activation-dependent structural brain plasticity in gray and white matter. The game of Baduk is known to require many cognitive processes, and long-term training in such processes would be expected to cause structural changes in related brain areas. We conducted voxel-based analyses of diffusion-tensor imaging (DTI) data and found that, compared to inexperienced controls, long-term trained Baduk players developed larger regions of white matter with increased fractional anisotropy (FA) values in the frontal, cingulum, and striato-thalamic areas that are related to attentional control, working memory, executive regulation, and problem-solving. In addition, inferior temporal regions with increased FA indicate that Baduk experts tend to develop a task-specific template for the game, as compared to controls. In contrast, decreased FA found in dorsolateral premotor and parietal areas indicate that Baduk experts were less likely than were controls to use structures related to load-dependent memory capacity. Right-side dominance in Baduk experts suggests that the tasks involved are mainly spatial processes. Altogether, long-term Baduk training appears to cause structural brain changes associated with many of the cognitive aspects necessary for game play, and investigation of the mechanism underpinning such changes might be helpful for improving higher-order cognitive capacities, such as learning, abstract reasoning, and self-control, which can facilitate education and cognitive therapies

* Functional connectivity in fronto-subcortical circuitry during the resting state in obsessive-compulsive disorder.
[Article (PDF)]
Obsessions and compulsions mediated by cognitive inflexibility might be associated with abnormal resting state functional connectivity in the default mode network (DMN) that represents intrinsically generated neuronal activity. It was hypothesized that decreased functional connectivity in the DMN would occur in components of fronto-subcortical circuits in patients with obsessive-compulsive disorder (OCD). Twenty-two unmedicated OCD patients and 22 age- and sex-matched healthy controls received resting state functional scanning runs. The posterior cingulate cortex (PCC) region was chosen as the seed region for the connectivity analysis. Correlations between temporal connectivity with the seed region and scores on clinical measures and obsessive-compulsive symptom dimensions were also assessed. OCD patients demonstrated less functional connectivity within the DMN in the anterior cingulate cortex, middle frontal gyrus, and putamen compared to controls. The functional connectivity to the PCC seed region in OCD patients was in the direction opposite to that in the prefrontal areas with regard to scores on cleaning and obsessions/checking dimensions of OCD. These data provide evidence for fronto-subcortical dysfunction in OCD. Results from this study also support the notion that OCD is a heterogeneous disorder mediated by distinct circuits

2009

* Association of the glutamate transporter gene SLC1A1 with atypical antipsychotics-induced obsessive-compulsive symptoms.
[Article (PDF)]
CONTEXT: Several studies have indicated that atypical antipsychotics (AAP) induce obsessive-compulsive (OC) symptoms. Research exploring the mechanism of this phenomenon, however, has been extremely limited. Considering the indirect evidence of genetic control and difficulties in developing animal models and performing gene expression studies, genetic association studies could be an important approach to understanding the molecular mechanism of AAP-induced OC symptoms. The glutamate transporter gene SLC1A1, which was recently reported to be associated with obsessive-compulsive disorder (OCD), is a promising candidate gene for susceptibility to AAP-induced OC symptoms. OBJECTIVE: To determine whether polymorphisms in SLC1A1 are associated with AAP-induced OC symptoms in patients with schizophrenia. DESIGN: A pharmacogenetic case-control association study. SETTING: Outpatient schizophrenia clinics. PATIENTS: Clinically stable patients with schizophrenia who were receiving AAP treatment (n = 94; OC group). The OC group consisted of 40 patients with AAP-induced OC symptoms, and the non-OC group consisted of 54 patients who had received AAP for more than 24 months without developing OC symptoms. MAIN OUTCOME MEASURES: Allele, genotype, and haplotype frequencies. The association was tested with a logistic regression model using age, sex, and medication type as covariates. RESULTS: Trends of association were observed in rs2228622 and rs3780412 (nominal P = .01; adjusted permutation P = .07) for the dominant model that was the inheritance model that best fit our data. In the haplotype -based analysis, the A/C/G haplotype at rs2228622-rs3780413-rs3780412 showed a significant association with AAP-induced OC symptoms; this association withstood multiple test correction (nominal P = .01; adjusted permutation P = .04; odds ratio, 3.955; 95% confidence interval, 1.366-11.452, for dominant model). CONCLUSIONS: These results suggest that sequence variations in SLC1A1 are associated with susceptibility to AAP-induced OC symptoms. This is the first published pharmacogenetic study on this phenomenon and provides preliminary evidence of the involvement of glutamatergic neurotransmission in the pathogenesis of AAP-induced OC symptoms

* A 12-week, naturalistic switch study of the efficacy and tolerability of aripiprazole in stable outpatients with schizophrenia or schizoaffective disorder.
[Article (PDF)]
The objectives of this 12-week multicenter open-label switching study were to evaluate the overall clinical efficacy, safety, and tolerability of aripiprazole in stable patients with schizophrenia or schizoaffective disorder, and to assess, in a naturalistic setting, whether such patients experience symptom worsening when switched from D2 receptor antagonists to aripiprazole (a D2 receptor partial agonist). Patients with schizophrenia or schizoaffective disorder in a symptomatically stable state were randomized to aripiprazole or standard-of-care antipsychotics. The Clinical Global Impression (CGI), Positive and Negative Syndrome Scale, and Investigator's Assessment Questionnaire were used monthly. The Udvalg for Kliniske Undersogelser side-effect rating scale scores and treatment emergent adverse events were recorded to assess the safety and tolerability of switching to aripiprazole from other antipsychotics. A total of 292 patients were randomly assigned to receive aripiprazole (N = 245) or non-aripiprazole antipsychotics (N = 47). Mean CGI-Improvement score at 12 weeks was 3.56+/-1.29 (95% confidence interval: 3.39-3.73) in the aripiprazole group, indicating that aripiprazole was effective in treating schizophrenic patients. Aripiprazole treatment resulted in improvement from baseline on all efficacy outcome measures, including Positive and Negative Syndrome Scale total, positive, negative, and general subscale, and CGI-Severity scores. In addition, after aripiprazole treatment, the remission rate was increased from 43.9% at baseline to 51.7% at 12 weeks. The proportion of patients with symptom worsening at 12 weeks was low (12.4%). Both Investigator's Assessment Questionnaire and Udvalg for Kliniske Undersogelser scores showed that there were fewer prolactin-related adverse events in the aripiprazole group than in the standard-of-care antipsychotics group (P<0.05). There were no significant between-group differences in time to failure to maintain remission and time to dropout. In the naturalistic setting, symptomatically stable outpatients with schizophrenia who were switched to aripiprazole showed clinically meaningful treatment benefits. The majority of patients was successfully switched from other antipsychotics without serious symptom exacerbation or adverse events over a course of 12 weeks.

* Proton magnetic resonance spectroscopy in subjects with high genetic risk of schizophrenia: investigation of anterior cingulate, dorsolateral prefrontal cortex and thalamus.
[Article (PDF)]
OBJECTIVE: Reduced N-acetylaspartate levels in regions of the frontal cortex, including the anterior cingulate cortex, dorsolateral prefrontal cortex, and thalamus, involved in the pathophysiology of schizophrenia suggest that brain metabolite abnormalities may be a marker of genetic vulnerability to schizophrenia. We used proton magnetic resonance spectroscopy (H-MRS) to acquire absolute concentrations of brain metabolites in subjects with a high genetic risk of schizophrenia to investigate the potential relationship between unexpressed genetic liability to schizophrenia and neuronal dysfunction. METHOD: Included in the study were 22 subjects who had at least two relatives with schizophrenia (high genetic risk group) and 22 controls with no second-degree relatives with schizophrenia. Absolute concentrations of N-acetylaspartate, creatine, choline, glutamate/glutamine, and myo-inositol and the ratios of metabolites in the anterior cingulate cortex, left dorsolateral prefrontal cortex, and left thalamus were measured using H-MRS at 1.5 Tesla. RESULTS: Relative to the controls, the high genetic risk group showed significant differences in absolute metabolite levels in the spectra of the regions of the left thalamus, including significant decreases in N-acetylaspartate, creatine, and choline concentrations. CONCLUSIONS: The study points to neuronal dysfunction, and in particular thalamic dysfunction, as a key region of the vulnerability marker of schizophrenia. Further studies should examine the nature of the thalamus more intensively to further our understanding of thalamic dysfunction as a vulnerability marker.

* White matter alterations in male patients with obsessive- compulsive disorder.
[Article (PDF)]
To investigate white matter abnormalities in patients with obsessive-compulsive disorder and to clarify the relationship between discrete white matter alterations and obsessive-compulsive symptom dimensions, the fractional anisotropy obtained from 25 male patients and 25 matched normal controls were analyzed. The patients had a significantly lower fractional anisotropy in the left anterior cingulate white matter than the controls. When stratified by clinical symptom dimensions, patients with a predominant aggressive/checking symptom dimension exhibited a significantly lower fractional anisotropy in the left anterior cingulate white matter, whereas patients with a predominant contamination/cleaning symptom dimension showed a significantly higher fractional anisotropy in the bilateral prefrontal white matter. Our findings provide evidence that obsessive-compulsive disorder may be a heterogeneous disease with distinct white matter changes.

Moo K. Chung, PhD, Dept. of Biostatistics & Medical Informatics, U of Wisconsin-Madison HP

2010

* The Encyclopedia of Research Design -R square
[Article (PDF)]

* Characterization of structural connectivity in autism using graph networks with DTI
[Article (PDF)]

* Structural Connectivity Mapping via the Tensor-Based Morphometry
[Article (PDF)]

* Cosine series representation of 3D curves and its application to white matter fiber bundles in diffusion tensor imaging.
[Article (PDF) ]

2009

* Classification in DTI using shapes of white matter tracts.
[Article (PDF)]

* Efficient parametric encoding scheme for white matter fiber bundles.
[Article (PDF)]

* Robust atlas-based brain segmentation using multi-structure confidence-weighted registration.
[Article (PDF)]

* Persistence diagrams of cortical surface data.
[Article (PDF)]

* 3D functional representation of spasely sampled 2D cortical data.
[Article (PDF)]

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