Symposium

Symposium 13 Translational research of TMS-induced cognitive modulation シンポジウム13 TMSによる認知機能修飾のトランスレーショナル研究

SY13-1 Neurophysiological study in psychiatric disorders using combined TMS-EEG 精神疾患におけるTMS-EEG同時計測を用いた神経生理学的研究 Noda Yoshihiro（野田賀大） Department of Neuropsychiatry, Keio University School of Medicine Postmortem studies and magnetic resonance spectroscopy studies in schizophrenia have noted that GABAergic, glutamatergic, and cholinergic functions are closely involved in the pathophysiology of this devastating disorder. However, in patients with schizophrenia, there are few studies on these neurotransmitters-related pathophysiological neural basis in detail from a neurophysiological point of view. Furthermore, the relationships between these neurophysiological functions and clinical symptoms or cognitive functions have not been sufficiently investigated. At this symposium, the presenter will show the findings of these neurophysiological indicators measured by using combined TMS-EEG method from the dorsolateral prefrontal cortex (DLPFC) in patients with chronic schizophrenia and the relationships among these neurophysiological functions and clinical symptoms or cognitive functions. TMS-EEG measurement of each neurophysiological index was performed on 12 patients and 12 healthy subjects. As a result, it was found that patients with chronic schizophrenia had significantly reduced GABAergic, glutamatergic, and cholinergic functions in the DLPFC compared to healthy subjects. Furthermore, in patients with schizophrenia, the extent of decline in GABAergic and cholinergic function in the DLPFC was significantly associated with the degree of deterioration of execution function, respectively. In addition, activation of glutamatergic function in the DLPFC was significantly associated with the severity of clinical symptoms.		SY13-2 Pioneering a new field of translational primate research by TMS TMSで拓く霊長類研究の新たな展開：トランスレーショナブルな高次脳機能研究を目指して Tsutsui Ken-Ichiro（筒井健一郎） Graduate School of Life Sciences, Tohoku University By taking advantage of invasive approaches possible in monkey electrophysiology, we first measured the change of neural activity induced by repetitive rTMS in the cerebral cortex. With the high-frequency (10 Hz) rTMS, which increases the cortical excitability indicated by the increase of the amplitude of motor evoked potential (MEP), we observed the increase of gamma band power in the electrocorticogram (ECoG), whereas with the low-frequency (1 Hz) rTMS, which decreases the cortical excitability, we observed the decrease of beta band power int eECoG. We thus find a consistent change of cortical neural activity after high- and low-frequency after rTMS. We then applied high- and low-frequency rTMS to various subregions of the prefrontal cortex to see how the facilitation or inhibition of local neural activity in its subregions may induce behavioral and physiological changes. The most evident change we observed was the dramatic induction of depressive mood after inhibiting the activity of the ventral part of the medial frontal cortex (vMFC) by the low-frequency rTMS. (We used a double-cone coil to stimulate the deep part of the brain and used a normal figure-of-eight coil to stimulate only the shallow part of the brain with the same coil location.) We observed changes behavioral change such as reduction of within-cage spontaneous activity, reduction of motivation to perform tasks, and social withdrawal, together with increase of blood cortisol level, which indicate the critical involvement of vMFC in the regulation of mood and emotion.

SY13-3 Durability of rTMS-induced cognitive enhancement in human rTMSによるヒト認知機能修飾の持続効果 Nakamura Motoaki（中村元昭）^1,2 ¹Medical Institute of Developmental Disabilities Research, Showa University, Tokyo, Japan ²Laboratory of Neuromodulation, Kanagawa Psychiatric Center, Yokohama, Japan Repetitive transcranial magnetic stimulation (rTMS), as a low-invasive brain stimulation, has been expected its clinical potential of cognitive modulation, especially for executive function. However, its long-lasting or cumulative effects on cognition have not been fully elucidated. Firstly, cognitive changes right after a single rTMS session will be demonstrated in healthy volunteers, as compared with a sham condition. Temporal enhancement of working memory was observed at around 20 to 40 minutes following intermittent theta burst stimulation (iTBS) over left dorsolateral prefrontal cortex (DLPFC). Secondly, in an open trial, cumulative cognitive changes will be shown following a series of 10 high frequency rTMS sessions over left DLPFC applied to major depression. Scores of executive functions were significantly improved, independently of antidepressant effects, after a series of rTMS sessions. Thirdly, in a randomized controlled trial of major depression, placebo or practice effects on executive function will be illustrated in active sham rTMS condition, as compared with high frequency rTMS over left DLPFC and low frequency rTMS over right DLPFC. Finally, durability of rTMS-induced cognitive modulation will be discussed in terms of neuroplasticity and clinical application. All three clinical studies presented in this presentation were approved by the institutional review board and ethical committee, and all patients gave the informed consent before study participation.		SY13-4 Correlation between the frontal lobe funciton and the white matter structure in patients with depression うつ病における前頭葉機能と白質構造の相関 Tateishi Hiroshi（立石洋）¹，西原正志²，川口淳³，松島淳⁴，溝口義人⁴，前川敏彦⁵，原口祥典⁴，村川徹⁴，國武裕¹，加藤隆弘⁵ ¹Department of Psychiatry, Saga University Hospital ²Department of Radiology, Saga University Hospital ³Center of Comprehensive Community Medicine, Faculty of Medicine, Saga University ⁴Department of Psychiatry, Faculty of Medicine, Saga University ⁵Department of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University ObjectiveWhite matter abnormalities are thought to cause network dysfunction underlying treatment-resistant depression (TRD). Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation method providing a promising technique for cognitive enhancement in TRD. In the present study, we investigated the relationship between the cognitive enhancement of frontal lobe function in TRD by rTMS and improvements of white matter integrity revealed by diffusion tensor imaging (DTI).MethodsA total of 17 patients with TRD were enrolled in a high-frequency (10 Hz) rTMS study. Frontal lobe function and depressive symptoms were assessed at baseline and at the endpoint of rTMS treatment. Fractional anisotropy (FA) as a measure of white matter integrity obtained from DTI was investigated using a region-of-interest (ROI) approach and tract-based spatial statistics (TBSS).ResultsrTMS treatment significantly improved depressive symptom scores (p < 0.05) and some subscales of frontal lobe dysfunction (p < 0.05). The total number of errors in the Wisconsin Card Sorting Test was improved independently of the improvement of depressive symptoms. FA increases detected using the ROI approach in the left and right middle frontal gyrus and in the right superior frontal gyrus were correlated with improvements on some subscales of frontal lobe dysfunction (p < 0.05). Conclusions After rTMS, we found a positive correlation between improved frontal lobe dysfunction and improved white matter integrity in TRD patients.

SY13-5 DeepTMS modulates mood and cognitive function in patients with mood disorder Deep TMSは気分障害患者に対して気分と認知機能を修飾する Matsuda Yuki（松田勇紀）¹，鬼頭伸輔¹，五十嵐良雄²，繁田雅弘¹ ¹Department of psychiatry, Jikei University School of Medicine, Tokyo, Japan ²Medicalcare Toranomon, Tokyo, Japan Cognitive dysfunction is common in patients with mood disorders including major depressive disorder (MDD) and bipolar disorder, facing various psychosocial problems. To date, there are few proven treatments for cognitive dysfunction and mood.Repetitive transcranial magnetic stimulation (rTMS), a noninvasive stimulation technique for modulating cortical and subcortical activities, has been shown to be effective in treatment-resistant depression and bipolar depression. A recent systematic review suggest that rTMS might be a promising technique for improving cognitive dysfunction in patient with mood disorder.Deep TMS (dTMS) with Hesed coil (H-coil) is a next-generation stimulator. H-coil is able to stimulate neuronal pathways that lie deeper in the targeted brain areas than those reached by conventional rTMS coils. Recent randomized controlled trials show that dTMS was effective and well-tolerated in patients with treatment-resistant depression and bipolar depression. However, there are few studies on changes in cognitive function by using dTMS in mood disorders. Therefore, we aimed to investigate before and after dTMS to examine changes in severity of depression and cognitive function by using dTMS in patients with treatment-resistant depression and bipolar depression who did not respond to medications in the current study. To our knowledge, this is the first randomized controlled trial if dTMS safely and effectively treats those patients attending a return to work program. The findings of this study have shown that dTMS might be a potential therapeutic option to treat depressed mood and cognitive dysfunction in patients with treatment-resistant depression and bipolar depression.