Song E. Kim

Interaction of motor training and intermittent theta burst stimulation in modulating motor cortical plasticity: influence of BDNF Val66Met polymorphism.

Cortical physiology in human motor cortex is influenced by behavioral motor training (MT) as well as repetitive transcranial magnetic stimulation protocol such as intermittent theta burst stimulation (iTBS). This study aimed to test whether MT and iTBS can interact with each other to produce additive changes in motor cortical physiology. We hypothesized that potential interaction between MT and iTBS would be dependent on BDNF Val66Met polymorphism, which is known to affect neuroplasticity in the human motor cortex. Eighty two healthy volunteers were genotyped for BDNF polymorphism. Thirty subjects were assigned for MT alone, 23 for iTBS alone, and 29 for MT + iTBS paradigms. TMS indices for cortical excitability and motor map areas were measured prior to and after each paradigm. MT alone significantly increased the motor cortical excitability and expanded the motor map areas. The iTBS alone paradigm also enhanced excitability and increased the motor map areas to a slightly greater extent than MT alone. A combination of MT and iTBS resulted in the largest increases in the cortical excitability, and the representational motor map expansion of MT + iTBS was significantly greater than MT or iTBS alone only in Val/Val genotype. As a result, the additive interaction between MT and iTBS was highly dependent on BDNF Val66Met polymorphism. Our results may have clinical relevance in designing rehabilitative strategies that combine therapeutic cortical stimulation and physical exercise for patients with motor disabilities.

Cortico-Cortical Modulation Induced by 1-Hz Repetitive Transcranial Magnetic Stimulation of the Temporal Cortex

Background and Purpose Repetitive transcranial magnetic stimulation (rTMS) has potential as a noninvasive neuromodulation treatment method for various neuropsychiatric disorders, and repeated sessions of rTMS are more likely to enhance the therapeutic efficacy. This study investigated neurophysiologic and spatiodynamic changes induced by repeated 1-Hz rTMS of the temporal cortex using transcranial magnetic stimulation (TMS) indices and fluorodeoxyglucose positron emission tomography (FDG-PET). Methods Twenty-seven healthy subjects underwent daily 1-Hz active or sham rTMS of the right temporal cortex for 5 consecutive days. TMS indices of motor cortical excitability were measured in both hemispheres daily before and after each rTMS session, and 2 weeks after the last stimulation. FDG-PET was performed at baseline and after the 5 days of rTMS sessions. Results All subjects tolerated all of the sessions well, with only three of them (11.1%) reporting mild transient side effects (i.e., headache, tinnitus, or local irritation). One-Hz rTMS decreased motor evoked potential amplitudes and delayed cortical silent periods in the stimulated hemisphere. Statistical parametric mapping of FDG-PET data revealed a focal reduction of glucose metabolism in the stimulated temporal area and an increase in the bilateral precentral, ipsilateral superior and middle frontal, prefrontal and cingulate gyri. Conclusions Repeated rTMS sessions for 5 consecutive days were tolerated in all subjects, with only occasional minor side effects. Focal 1-Hz rTMS of the temporal cortex induces cortico-cortical modulation with widespread functional changes in brain neural networks via long-range neural connections.

Gray and White Matter Volumes and Cognitive Dysfunction in Drug-Naïve Newly Diagnosed Pediatric Epilepsy.

Epilepsy patients often have cognitive dysfunction even at early stages of disease. We investigated the relationship between structural findings and neuropsychological status in drug-naïve newly diagnosed pediatric epilepsy patients. Thirty newly diagnosed pediatric epilepsy patients and 25 healthy control subjects aged 7~16 years were enrolled, who were assessed by the Korean version of the Wechsler Intelligence Scale for Children (K-WISC-III), the Stroop test, and the trail making test (TMT). Optimized voxel-based morphometry (VBM) was performed for both Gray Matter (GM) and White Matter (WM) volumes. Lower performance levels of verbal intelligence quotient, freedom from distractibility, and executive function were observed in epilepsy group. Interestingly, poor performance in these cognitive subdomains was correlated with regional VBM findings involving both GM and WM volumes, but with different patterns between groups. GM volumes revealed clear differences predominantly in the bilateral frontal regions. These findings indicate that certain cognitive functions may be affected in the early stage of epilepsy, not related to the long-standing epilepsy or medication, but more related to the neurocognitive developmental process in this age. Epilepsy can lead to neuroanatomical alterations in both GM and WM, which may affect cognitive functions, during early stages even before commencement of AED medication.

Direct and Indirect Effects of Five Factor Personality and Gender on Depressive Symptoms Mediated by Perceived Stress

This study was designed to investigate associations among five factor personality traits, perceived stress, and depressive symptoms and to examine the roles of personality and perceived stress in the relationship between gender and depressive symptoms. The participants (N = 3,950) were part of a cohort study for health screening and examination at the Kangbuk Samsung Hospital. Personality was measured with the Revised NEO Personality Inventory (NEO-PI-R). Depressive symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D). Perceived stress level was evaluated with a self-reported stress questionnaire developed for the Korea National Health and Nutrition Examination Survey. A higher degree of neuroticism and lower degrees of extraversion, agreeableness, and conscientiousness were significantly associated with greater perceived stress and depressive symptoms. Neuroticism and extraversion had significant direct and indirect effects (via stress as a mediator) on depressive symptoms in both genders. Agreeableness and conscientiousness had indirect effects on depression symptoms in both genders. Multiple mediation models were used to examine the mediational roles of each personality factor and perceived stress in the link between gender and depressive symptoms. Four of the personality factors (except openness) were significant mediators, along with stress, on the relationship between gender and depressive symptoms. Our findings suggest that the links between personality factors and depressive symptoms are mediated by perceived stress. As such, personality is an important factor to consider when examining the link between gender and depression.

Spatiotemporal dynamics and functional correlates of evoked neural oscillations with different spectral powers in human visual cortex

OBJECTIVE To investigate spatiotemporal characteristics and functional correlates of evoked oscillations (EOs) at different frequency bands in human visual cortex. METHODS Flash visual evoked potentials (FVEPs) were recorded from 11 epilepsy patients with intracranial electrodes placed over the occipital and adjacent cortices. Spatiotemporal characteristics of spectral powers and correlation with various visual responses elicited by electrical cortical stimulations were analyzed in the same electrodes. RESULTS High γ (60-150 Hz) EOs were first recorded in the cuneus and lingual gyri around the calcarine sulcus. Low γ (30-60 Hz) EOs appeared also in the mesial occipital cortex slightly later and lasted longer than high γ EGOs. In contrast, lower frequency (LF) <30 Hz EOs were recorded more diffusely from occipital surfaces with delayed onset and longer duration. High γ EOs were predominantly associated with simple form visual responses, whereas low γ and LF EOs were with intermediate form and LF EOs with complex form responses. CONCLUSIONS FVEP spectral power analysis directly recorded from human visual cortex showed distinct spatiotemporal distributions in high and low γ, or LF bands that have different functional correlates. SIGNIFICANCE Phase-locked EOs in these frequency bands may have special neuroanatomical and functional organization during early visual processing.

Meta-analysis of genome-wide SNP- and pathway-based associations for facets of neuroticism

Neuroticism is a heritable personality trait that is comprised of distinct sub-factors, or facets. Sub-factors of neuroticism are linked to different emotional states or psychiatric symptoms and studying the genetic variants associated with these facets may help reveal the biological mechanisms underlying psychiatric disorders. In the present study, a meta-analysis of genome-wide association studies for six facets of neuroticism was performed in 5584 participants from three cohorts. Additionally, a Gene Set Enrichment Analysis was conducted to find biological pathways associated with each facet. Six neuroticism facets (N1: anxiety, N2: angry hostility, N3: depression, N4: self-consciousness, N5: impulsivity and N6: vulnerability) were assessed using the Korean version of the Revised NEO Personality Inventory. In the single-nucleotide polymorphism-based analysis, results showed genome-wide significance for N2 within the MIR548H3 gene (rs1360001, P=4.14 × 10−9). Notable genes with suggestive associations (P<1.0 × 10−6) were ITPR1 for N1, WNT7A for N2, FGF10 and FHIT for N3, DDR1 for N4, VGLL4 for N5 and PTPRD for N6. In the pathway-based analysis, the axon guidance pathway was identified to be associated with multiple facets of neuroticism (N2, N4 and N6). The focal adhesion and extracellular matrix receptor interaction pathways were significantly associated with N2 and N3. Our findings revealed genetic influences and biological pathways that are associated with facets of neuroticism.

Social Behavioral Problems and the Health-Related Quality of Life in Children and Adolescents with Epilepsy

Objective The purpose of this study was to investigate the impact of specific behavioral problems on the health-related quality of life (HRQOL) in children and adolescents with epilepsy. Methods Children and adolescents with epilepsy (n=92; age range=6–17 years) and their mothers completed questionnaires about behavioral problems, HRQOL, socio-demographics, and epilepsy-related variables. To determine significant predictor variables of the HRQOL, the stepwise regression analyses and partial correlations were performed to adjust for other behavioral problems and covariates. Results The analyses revealed that an increase in social behavioral problems and delinquent behavior was associated with a decrease in the HRQOL. Lower levels of maternal education and the number of antiepileptic drugs were also associated with a decline in the HRQOL; the HRQOL and social behavioral problems remained significantly correlated after adjusting for maternal education level, number of antiepileptic drugs, and non-social behavioral problems. Conclusion Parents and practitioners should provide intervention if behavioral problems, particularly social behavioral problems, are observed in children or adolescents with epilepsy.

Acute and chronic effects of repeated 1 Hz rTMS on the temporal cortex.

Electroencephalography amplitude, phase synchronization, and directionality of phase coupling within and between hemispheres were compared for different frequency components in 27 healthy individuals before and after 5 days of daily 1 Hz repetitive transcranial magnetic stimulation (rTMS), and at 2 weeks after the last session. Instantaneous amplitudes of &agr; (8–13 Hz) and &bgr; (13–30 Hz) frequency components were increased after daily rTMS, the effects of which were declining over time, suggesting an adapting response with repeated rTMS sessions. The phase synchronization of electroencephalography increased significantly in the &agr; frequency, especially the upper-&agr; band (11–13 Hz), in both the frontal and the temporal areas, predominantly in the ipsilateral hemisphere. Asymmetric directional interactions of the upper-&agr; band were stronger from the stimulated area to the contralateral hemisphere. No significant differences were found at 2 weeks after rTMS in any of these values. Focal 1 Hz rTMS induces an enhancement in the ipsilateral dominant corticocortical interaction drastically by interhemispheric asymmetric coupling from the stimulated cortical area with an adapting response with repeated sessions. This kind of method can be valuable for possible clinical applications in various neuropsychiatric conditions to study the therapeutic mechanisms of 1 Hz rTMS.