Youngwoo Bryan Yoon

Aberrant temporal behavior of mismatch negativity generators in schizophrenia patients and subjects at clinical high risk for psychosis

OBJECTIVE Although disconnection syndrome has been considered a core pathophysiologic mechanism of schizophrenia, little is known about the temporal behavior of mismatch negativity (MMN) generators in individuals with schizophrenia or clinical high risk (CHR) for psychosis. METHODS MMN was assessed in 29 schizophrenia patients, 40 CHR subjects, and 47 healthy controls (HCs). Individual realistic head models and the minimum L2 norm algorithm were used to generate a current source density (CSD) model of MMN. The strength and time course of MMN CSD activity were calculated separately for the frontal and temporal cortices and were compared across brain regions and groups. RESULTS Schizophrenia patients and CHR subjects displayed lower MMN CSD strength than HCs in both the temporal and frontal cortices. We found a significant time delay in MMN generator activity in the frontal cortex relative to that in the temporal cortex in HCs. However, the sequential temporo-frontal activities of MMN generators were disrupted in both the schizophrenia and CHR groups. CONCLUSIONS Impairments and altered temporal behavior of MMN multiple generators were observed even in individuals at risk for psychosis. SIGNIFICANCE These findings suggest that aberrant MMN generator activity might be helpful in revealing the pathophysiology of schizophrenia.

Predicting Remission in Subjects at Clinical High Risk for Psychosis Using Mismatch Negativity

Background The declining transition rate to psychotic disorder and the increasing rate of nonpsychotic poor outcomes among subjects at clinical high risk (CHR) for psychosis have increased the need for biomarkers to predict remission regardless of transition. This study investigated whether mismatch negativity (MMN) predicts the prognosis of CHR individuals during a 6-year follow-up period. Methods A total of 47 healthy control (HC) subjects and 48 subjects at CHR for psychosis participated in the MMN assessment. The clinical statuses of the CHR subjects were examined at baseline and regularly for up to 6 years. The CHR subjects were divided into remitter and nonremitter groups, and the baseline MMN amplitudes and latencies were compared across the remitter, nonremitter, and HC groups. Regression analyses were performed to identify the predictive factors of remission, the improvement of attenuated positive symptoms, and functional recovery. Results CHR nonremitters showed reduced MMN amplitudes at baseline compared to CHR remitters and HC subjects. A logistic regression analysis revealed that the baseline MMN amplitude at the frontal electrode site was the only significant predictor of remission. In a multiple regression analysis, the MMN amplitude, antipsychotic use, and years of education predicted an improvement in attenuated positive symptoms. The MMN amplitude at baseline predicted functional recovery. Conclusions These results suggest that MMN is a putative predictor of prognosis regardless of the transition to psychotic disorder in subjects at CHR. Early prognosis prediction and the provision of appropriate interventions based on the initial CHR status might be aided using MMN.

Brain Structural Networks Associated with Intelligence and Visuomotor Ability

Increasing evidence indicates that multiple structures in the brain are associated with intelligence and cognitive function at the network level. The association between the grey matter (GM) structural network and intelligence and cognition is not well understood. We applied a multivariate approach to identify the pattern of GM and link the structural network to intelligence and cognitive functions. Structural magnetic resonance imaging was acquired from 92 healthy individuals. Source-based morphometry analysis was applied to the imaging data to extract GM structural covariance. We assessed the intelligence, verbal fluency, processing speed, and executive functioning of the participants and further investigated the correlations of the GM structural networks with intelligence and cognitive functions. Six GM structural networks were identified. The cerebello-parietal component and the frontal component were significantly associated with intelligence. The parietal and frontal regions were each distinctively associated with intelligence by maintaining structural networks with the cerebellum and the temporal region, respectively. The cerebellar component was associated with visuomotor ability. Our results support the parieto-frontal integration theory of intelligence by demonstrating how each core region for intelligence works in concert with other regions. In addition, we revealed how the cerebellum is associated with intelligence and cognitive functions.

Higher extrinsic and lower intrinsic connectivity in resting state networks for professional Baduk (Go) players

Dedication and training to a profession results in a certain level of expertise. This expertise, like any other skill obtained in our lifetime, is encoded in the brain and may be reflected in our brains connectome. This property can be observed by mapping resting state connectivity. In this study, we examine the differences in resting state functional connectivity in four major networks between professional “Baduk” (Go) players and normal subjects.

Decreased neural response for facial emotion processing in subjects with high genetic load for schizophrenia

BACKGROUND Patients with schizophrenia show impairment in facial emotion processing which is essential for successful social cognition. Using a functional magnetic resonance imaging (fMRI), this study aimed to investigate the implicit facial emotion recognition processing in participants with high genetic load for schizophrenia (GHR) as a possible trait marker of developing schizophrenia. METHODS Block design fMRI of implicit facial emotion processing was used in 20 participants with GHR aged 16-35, and 17 age, sex, and education year-matched healthy controls (HC). During the facial emotional processing for fearful, happy, and neutral face stimuli, participants were asked to explicitly determine the gender per stimuli. RESULTS Occipito-temporo-limbic area in fearful face condition and involvement of broader region including prefrontal cortex in neutral face condition revealed significant attenuation of BOLD signal activation in GHR compared to HC. The GHR demonstrated less activity in right amygdala during fearful and neutral face condition. CONCLUSION The study presented that GHR displayed abnormal brain activity in occipito-temporo-limbic-frontal network implicated in facial emotion processing. It indicates that abnormal facial emotion processing may be influenced by a genetic factor and could be a trait marker in schizophrenia.

Aberrant within- and between-network connectivity of the mirror neuron system network and the mentalizing network in first episode psychosis

INTRODUCTION It has been suggested that the mentalizing network and the mirror neuron system network support important social cognitive processes that are impaired in schizophrenia. However, the integrity and interaction of these two networks have not been sufficiently studied, and their effects on social cognition in schizophrenia remain unclear. METHODS Our study included 26 first-episode psychosis (FEP) patients and 26 healthy controls. We utilized resting-state functional connectivity to examine the a priori-defined mirror neuron system network and the mentalizing network and to assess the within- and between-network connectivities of the networks in FEP patients. We also assessed the correlation between resting-state functional connectivity measures and theory of mind performance. RESULTS FEP patients showed altered within-network connectivity of the mirror neuron system network, and aberrant between-network connectivity between the mirror neuron system network and the mentalizing network. The within-network connectivity of the mirror neuron system network was noticeably correlated with theory of mind task performance in FEP patients. CONCLUSION The integrity and interaction of the mirror neuron system network and the mentalizing network may be altered during the early stages of psychosis. Additionally, this study suggests that alterations in the integrity of the mirror neuron system network are highly related to deficient theory of mind in schizophrenia, and this problem would be present from the early stage of psychosis.

T180. LOWER GLUTAMATE LEVEL IN TEMPORO-PARIETAL AREA MAY PREDICT A BETTER RESPONSE TO TDCS IN SCHIZOPHRENIA: A PILOT STUDY

Abstract Background Transcranial Direct Current Stimulation (tDCS) is a non-invasive neuromodulation technique which uses a weak electric current from electrodes across the scalp to modulate targeted brain areas. It has been suggested that tDCS may be useful in reducing psychotic symptoms such as auditory hallucination. The aim of this study was to find alteration of key neurotransmitters in schizophrenia in temporo-parietal area (TPA) after tDCS intervention, using magnetic resonance spectroscopy (MRS) technique. Methods Ten schizophrenia patients with auditory hallucination were recruited from the outpatient clinic of Seoul National University Hospital (SNUH). The anode was placed over the left dorsolateral prefrontal cortex (DLPFC), and the cathode was placed over the left TPA. Patients underwent MRS scan with the very short echo time phase rotation STEAM sequence before and after the tDCS sessions, respectively. Results Seven of the participants completed MRS scans before and after the tDCS sessions. Positive and Negative Symptom Scale (PANSS) total and general psychophathology scale showed a significant improvement after tDCS. There was no significant difference between glutamate/creatinine (Cr) level before and after tDCS sessions. However, a significant positive correlation between the pre-tDCS glutamate/Cr value in left TPA and the improvement in auditory hallucination measured by Auditory Hallucination Rating Scale (AHRS) after tDCS was found. Discussion The results of this investigation show that the schizophrenia patients whose auditory hallucination benefits the most from tDCS treatment had lower glutamate/Cr level in left TPA. Previous studies regarding the relationship between glutamatergic system and treatment response mostly have only focused on the frontal area and striatum. However, this study suggests a potential role of glutamatergic system in TPA in predicting treatment response of auditory hallucination.

Node Identification Using Inter-Regional Correlation Analysis for Mapping Detailed Connections in Resting State Networks

Brain function is often characterized by the connections and interactions between highly interconnected brain regions. Pathological disruptions in these networks often result in brain dysfunction, which manifests as brain disease. Typical analysis investigates disruptions in network connectivity based correlations between large brain regions. To obtain a more detailed description of disruptions in network connectivity, we propose a new method where functional nodes are identified in each region based on their maximum connectivity to another brain region in a given network. Since this method provides a unique approach to identifying functionally relevant nodes in a given network, we can provide a more detailed map of brain connectivity and determine new measures of network connectivity. We applied this method to resting state fMRI of Alzheimers disease patients to validate our method and found decreased connectivity within the default mode network. In addition, new measure of network connectivity revealed a more detailed description of how the network connections deteriorate with disease progression. This suggests that analysis using key relative network hub regions based on regional correlation can be used to detect detailed changes in resting state network connectivity.