研究者詳細 - 野田　賀大

論文 - 野田　賀大

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A combined TMS-EEG study of short-latency afferent inhibition in the motor and dorsolateral prefrontal cortex

Y Noda, RFH Cash, R Zomorrodi, LG Dominguez, F Farzan, TK Rajji, ...

Journal of neurophysiology 116 (3), 938-948 （Journal of Neurophysiology） 116 （ 3 ） 938 - 948 2016年

研究論文（学術雑誌）, 査読有り, ISSN 00223077

© 2016 the American Physiological Society. Combined transcranial magnetic stimulation and electroencephalography (TMS-EEG) enables noninvasive neurophysiological investigation of the human cortex. A TMS paradigm of short-latency afferent inhibition (SAI) is characterized by attenuation of the motor-evoked potential (MEP) and modulation of N100 of the TMS-evoked potential (TEP) when TMS is delivered to motor cortex (M1) following median nerve stimulation. SAI is a marker of cholinergic activity in the motor cortex; however, the SAI has not been tested from the prefrontal cortex. We aimed to explore the effect of SAI in dorsolateral prefrontal cortex (DLPFC). SAI was examined in 12 healthy subjects with median nerve stimulation and TMS delivered to M1 and DLPFC at interstimulus intervals (ISIs) relative to the individual N20 latency. SAI in M1 was tested at the optimal ISI of N20 + 2 ms. SAI in DLPFC was investigated at a range of ISI from N20 + 2 to N20 + 20 ms to explore its temporal profile. For SAI in M1, the attenuation of MEP amplitude was correlated with an increase of TEP N100 from the left central area. A similar spatiotemporal neural signature of SAI in DLPFC was observed with a marked increase of N100 amplitude. SAI in DLPFC was maximal at ISI N20 + 4 ms at the left frontal area. These findings establish the neural signature of SAI in DLPFC. Future studies could explore whether DLPFC-SAI is neurophysiological marker of cholinergic dysfunction in cognitive disorders.

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POTENTIAL EEG BIOMARKERS FOR NEUROPLASTICITY INDUCTION BY A SERIES OF PREFRONTAL REPETITIVE TRANSCRANIAL MAGNETIC STIMULATION (rTMS) FOR MAJOR DEPRESSION

M Nakamura, Y Noda

AUSTRALIAN AND NEW ZEALAND JOURNAL OF PSYCHIATRY 50, 41-42 2016年

Magnetic seizure therapy-induced mania

Noda Y., Daskalakis Z.J., Fitzgerald P.B., Downar J., Rajji T.K., Blumberger D.M.

Journal of ECT （Journal of ECT） 31 （ 1 ） e4 - e6 2015年03月

研究論文（学術雑誌）, 査読有り, ISSN 10950680

Background Magnetic seizure therapy (MST) is a novel brain stimulation modality used to treat refractory depression through the induction of seizures. It is currently being investigated as a potential alternative treatment to electroconvulsive therapy. To our knowledge, there have not been any previous reports of MST-induced mania. Objective We aim to describe 2 cases of patients with a major depressive episode who developed acute symptoms of mania during a course of MST. Methods The current report describes 2 cases of mania that occurred in the context of an ongoing open-label study of MST in treatment-resistant depression. The MST was administered 2 or 3 times per week and applied directly over the left and right dorsolateral prefrontal cortex. Treatment is administered until patients achieve remission or a maximum of 24 treatments. A MagVenture Twin coil and MST stimulator were used for treatment. The center of each coil was placed over F3 and F4 according to the 10-20 electroencephalography system. Results Patient 1 had developed manic symptoms precipitously after the sixth MST treatment, and patient 2 developed manic symptoms after the 23rd MST treatment. In both patients, the MST treatment course was stopped. Their manic symptoms resolved rapidly with pharmacotherapy after cessation of MST treatments. Conclusions As with electroconvulsive therapy, switches to mania or hypomania should be considered as potential adverse effects of MST.

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Clinical Application of the K–Style Acupuncture Score (KSAS): Towards the Establishment of a Novel Rating Scale for Depression in Acupuncture Medicine

野田賀大

Neuropsychiatry (London) 5 (1), 50-58 2015年

Clinical application of repetitive transcranial magnetic stimulation and magnetic seizure therapy to　 patients with treatment-resistant depression.

野田賀大

The Journal of Japanese Society of General Hospital Psychiatry. 2015年

Neurobiological predictors of response to dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation in depression: a systematic review

野田賀大

Depression and anxiety 32 (12), 871-891 （Depression and Anxiety） 32 （ 12 ） 871 - 891 2015年

研究論文（学術雑誌）, 査読有り, ISSN 10914269

Background A significant proportion of patients with depression fail to respond to psychotherapy and standard pharmacotherapy, leading to treatment-resistant depression (TRD). Due to the significant prevalence of TRD, alternative therapies for depression have emerged as viable treatments in the armamentarium for this disorder. Repetitive transcranial magnetic stimulation (rTMS) is now being offered in clinical practice in broader numbers. Many studies have investigated various different neurobiological predictors of response of rTMS. However, a synthesis of this literature and an understanding of what biological targets predict response is lacking. This review aims to systematically synthesize the literature on the neurobiological predictors of rTMS in patients with depression. Methods Medline (1996-2014), Embase (1980-2014), and PsycINFO (1806-2014) were searched under set terms. Two authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually. Results The search identified 1,673 articles, 41 of which met both inclusion and exclusion criteria. Various biological factors at baseline appear to predict response to rTMS, including levels of certain molecular factors, blood flow in brain regions implicated in depression, electrophysiological findings, and specific genetic polymorphisms. Conclusions Significant methodological variability in rTMS treatment protocols limits the ability to generalize conclusions. However, response to treatment may be predicted by baseline frontal lobe blood flow, and presence of polymorphisms of the 5-hydroxytryptamine (5-HT) -1a gene, the LL genotype of the serotonin transporter linked polymorphic region (5-HTTLPR) gene, and Val/Val homozygotes of the brain-derived neurotrophic factor (BDNF) gene.

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Neurobiological mechanisms of repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex in depression: a systematic review

野田賀大

Psychological medicine 45 (16), 3411-3432 （Psychological Medicine） 45 （ 16 ） 3411 - 3432 2015年

研究論文（学術雑誌）, 査読有り, ISSN 00332917

Depression is one of the most prevalent mental illnesses worldwide and a leading cause of disability, especially in the setting of treatment resistance. In recent years, repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising alternative strategy for treatment-resistant depression and its clinical efficacy has been investigated intensively across the world. However, the underlying neurobiological mechanisms of the antidepressant effect of rTMS are still not fully understood. This review aims to systematically synthesize the literature on the neurobiological mechanisms of treatment response to rTMS in patients with depression. Medline (1996-2014), Embase (1980-2014) and PsycINFO (1806-2014) were searched under set terms. Three authors reviewed each article and came to consensus on the inclusion and exclusion criteria. All eligible studies were reviewed, duplicates were removed, and data were extracted individually. Of 1647 articles identified, 66 studies met both inclusion and exclusion criteria. rTMS affects various biological factors that can be measured by current biological techniques. Although a number of studies have explored the neurobiological mechanisms of rTMS, a large variety of rTMS protocols and parameters limits the ability to synthesize these findings into a coherent understanding. However, a convergence of findings suggest that rTMS exerts its therapeutic effects by altering levels of various neurochemicals, electrophysiology as well as blood flow and activity in the brain in a frequency-dependent manner. More research is needed to delineate the neurobiological mechanisms of the antidepressant effect of rTMS. The incorporation of biological assessments into future rTMS clinical trials will help in this regard.

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Acupuncture-induced changes of vagal function in patients with depression: a preliminary sham-controlled study with press needles

野田賀大

Complementary therapies in clinical practice 21 (3), 193-200 （Complementary Therapies in Clinical Practice） 21 （ 3 ） 193 - 200 2015年

研究論文（学術雑誌）, 査読有り, ISSN 17443881

© 2015 Elsevier Ltd. To study the biological effects of acupuncture on depression, we hypothesized that acupuncture will exert its antidepressant effect through a bottom-up neuromodulation of the autonomic dysfunction in depression. The participants received press needle (PN) acupuncture for 72 h continuously in a sham-controlled design. Psychological assessments and Holter electrocardiography were performed before and after PN acupuncture. We evaluated their autonomic functions through the heart rate variability (HRV). As a result, following PN acupuncture participants showed significant improvement in the Beck's Depression Inventory scores (P = 0.031), systolic/diastolic blood pressures (P = 0.002/P = 0.011), and coefficient of variation of the R-R interval (P < 0.0001), compared to sham PN. The present findings showed PN acupuncture induced alterations in vagal function, blood pressure, and Beck's Depression Inventory scores. It was suggested that vagal stabilization effect by acupuncture may be associated with the therapeutic mechanism in depression.

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Clinical Application of the K-Style Acupuncture Score (KSAS): Towards the Establishment of a Novel Rating Scale for Depression in Acupuncture Medicine

Y Noda, K Matsumoto, H Murakami, A Ito, Y Shinse, A Suzuki, Y Sawada, ...

Neuropsychiatry 5 (1), 50-58 2015年

研究論文（学術雑誌）, 査読有り

Magnetic seizure therapy-induced mania: a report of 2 cases

野田賀大

The journal of ECT 31 (1), e4-e6 2014年

研究論文（学術雑誌）, 査読有り

Magnetic seizure therapy in an adolescent with refractory bipolar depression: a case report

野田賀大

Neuropsychiatric disease and treatment 10, 2049 （Neuropsychiatric Disease and Treatment） 10 2049 - 2055 2014年

研究論文（学術雑誌）, 査読有り, ISSN 11766328

Magnetic seizure therapy (MST) has shown efficacy in adult patients with treatment-resistant depression with limited impairment in memory. To date, the use of MST in adolescent depression has not been reported. Here we describe the first successful use of MST in the treatment of an adolescent patient with refractory bipolar depression. This patient received MST in an ongoing open-label study for treatment-resistant major depression. Treatments employed a twin-coil MST apparatus, with the center of each coil placed over the frontal cortex (ie, each coil centered over F3 and F4). MST was applied at 100 Hz and 100% machine output at progressively increasing train durations. Depressive symptoms were assessed using the 24-item Hamilton Depression Rating Scale and cognitive function was assessed with a comprehensive neuropsychological battery. This adolescent patient achieved full remission of clinical symptoms after an acute course of 18 MST treatments and had no apparent cognitive decline, other than some autobiographical memory impairment that may or may not be related to the MST treatment. This case report suggests that MST may be a safe and well tolerated intervention for adolescents with treatment-resistant bipolar depression. Pilot studies to further evaluate the effectiveness and safety of MST in adolescents warrant consideration.

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Variation in the DRD2 gene affects impulsivity in intertemporal choice

野田賀大

Scientific Research Publishing 3 （ 1 ） 26 - 31 2013年

研究論文（学術雑誌）, 査読有り

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Potentiation of Quantitative Electroencephalograms Following Prefrontal Repetitive Transcranial Magnetic Stimulation in Major Depression.

野田賀大

Neuroscience Research. 2013年

Repetitive transcranial magnetic stimulation to maintain treatment response to electroconvulsive therapy in depression: a case series

野田賀大

Frontiers in psychiatry 4, 73 （Frontiers in Psychiatry） 4 （ JUL ） 73 - 31 2013年

研究論文（学術雑誌）, 査読有り

Electroconvulsive therapy (ECT) is the most effective treatment for a refractory major depression in the context of both unipolar and bipolar affective disorders. However, the relapse rate within the first 6 months after a successful course of ECT to treat a depressive episode can be as high 50%. Evidence-based strategies to prevent relapse have partial efficacy and are associated with problematic adverse effects limiting their use as long-term treatments. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated efficacy in treatment-resistant depression with a favorable adverse effect profile. Herein, we describe six patients, four with unipolar and two with bipolar depression, where rTMS was used to maintain response after a successful course of acute and continuation ECT. rTMS was administered once or twice weekly, at 120% of the resting motor threshold. Patients received sequential bilateral rTMS (low frequency right: 600 pulses, then high frequency left: 3000 pulses). The site of stimulation was 6 cm anterior and 1 cm lateral from the site of maximum stimulation of the abductor pollicis brevis muscle. Depressive symptoms were monitored with the quick inventory of depressive symptoms-self rated. Five of the six patients were able to maintain their response status from 6 to 13 months at the time of last observation. The use of rTMS may be an important relapse prevention strategy following an acute course of ECT. Controlled studies comparing rTMS to current evidence-based relapse prevention strategies are warranted. ©2013 Noda, Daskalakis, Ramos and Blumberger.

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DNA polymorphism in the FKBP5 gene affects impulsivity in intertemporal choice

野田賀大

Asia‐Pacific Psychiatry 5 (1), 31-38 （Asia-Pacific Psychiatry） 5 （ 1 ） 31 - 38 2013年

研究論文（学術雑誌）, 査読有り, ISSN 17585864

Introduction: Impulsivity in intertemporal choice has been operationalized as "delay discounting", referring to the preference for a sooner, smaller reward. FK506 binding protein 5 (FKBP5) is a co-chaperone of the glucocorticoid receptor (GR). FKBP5 overexpression causes GR resistance, resulting in increased plasma cortisol levels. High cortisol levels are associated with low impulsivity in intertemporal choice. The aim of this study was to explore the effect of single nucleotide polymorphisms (SNPs) in FKBP5 on delay discounting. Methods: The participants consisted of 91 healthy Japanese people (66 males and 25 females with a mean age of 40.9±6.9 years). Each participant completed Kirby's monetary choice questionnaire (MCQ) and donated a whole blood sample. Five SNPs in FKBP5 were genotyped using the DigiTag2. SNP linear regression analyses with 100,000 permutations were conducted for the hyperbolic time-discount rate (k). Results: Two SNPs were excluded from analysis because of their low minor allelic frequencies. The SNP rs1360780 showed a significant association; participants with more minor alleles (T) were less impulsive in intertemporal choice for delayed gain (multiplicity-corrected P=0.047). Discussion: The significant SNP rs1360780 is located in the region adjacent to the hormone response element (HRE)-binding sequence where transcription factors bind and alter the transcription of FKBP5. A minor allele (T) of rs1360780, which causes FKBP5 overexpression, may reduce impulsivity in intertemporal choice (i.e. delay discounting) via GR resistance and the subsequent high cortisol levels. This is the first study to demonstrate an association between FKBP5 and impulsivity in intertemporal choice. © 2012 Wiley Publishing Asia Pty Ltd.

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Localized potentiation of sleep slow-wave activity induced by prefrontal repetitive transcranial magnetic stimulation in patients with a major depressive episode

T Saeki, M Nakamura, N Hirai, Y Noda, S Hayasaka, H Iwanari, ...

Brain stimulation 6 (3), 390-396 （Brain Stimulation） 6 （ 3 ） 390 - 396 2013年

研究論文（学術雑誌）, 査読有り, ISSN 1935861X

Background: The effects of repetitive transcranial magnetic stimulation (rTMS) on sleep structure in major depression are currently unknown. Objective: To determine the effects of prefrontal rTMS on sleep electroencephalography (EEG) in major depression. Methods: In this open-label pilot study, twelve male patients with relatively mild depression, who had been medication-resistant, underwent 10 daily rTMS sessions over the left dorsolateral prefrontal cortex (DLPFC). Polysomnographic (PSG) data were recorded over four nights: Adaptation, Baseline, Post-1 (after the fifth rTMS session), and Post-2 (after the tenth rTMS session). Discrete Fourier Transform (DFT) band power analyses were performed to quantify delta and sigma band activities during Stages II-IV, and determine time courses of these activities between Baseline and Post-1 (first five sessions) and between Post-1 and Post-2 (last five sessions). Results: Post-hoc tests based on a three-way ANOVA model indicated significant delta power increase at F3 (t11 = -2.762, P = 0.018) during the first five sessions; however, sigma power was unchanged. No significant band power changes were observed during the second half. Stages II-IV (percent total sleep time) increased significantly during the first half (t12 = -2.43, P = 0.033). No other significant changes in sleep parameters or clinical correlations were observed. Conclusions: The first five sessions of high frequency rTMS to the left DLPFC increase slow-wave activity (SWA) at F3, possibly reflecting locally enhanced synaptic plasticity induced by rTMS. This increased activity was not observed during the last half, possibly due to a homeostatic regulation mechanism intrinsic to SWA. © 2013 Elsevier Inc. All rights reserved.

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Potentiation of quantitative electroencephalograms following prefrontal repetitive transcranial magnetic stimulation in patients with major depression

Y Noda, M Nakamura, T Saeki, M Inoue, H Iwanari, K Kasai

Neuroscience Research 77 (1-2), 70-77 （Neuroscience Research） 77 （ 1-2 ） 70 - 77 2013年

研究論文（学術雑誌）, 査読有り, ISSN 01680102

The long-lasting effects of repetitive transcranial magnetic stimulation (rTMS) on electroencephalogram (EEG) activity are not clear. We aimed to investigate the cumulative rTMS effects on EEG and clinical outcomes in patients with major depression. Twenty-five patients with medication-resistant depression underwent 10 daily rTMS sessions over the left dorsolateral prefrontal cortex. We measured resting EEG and spectrum-power before and after the rTMS course. Clinical efficacy was evaluated with the Hamilton's Depression Rating Scale (HAM-D) and Wisconsin Card Sorting Test (WCST). In an ANOVA model, including all prefrontal electrodes, post hoc analyses revealed significant time effects on the theta (F1,24=7.89, P=0.010; +43%), delta (F1,24=6.58, P=0.017; +26%), and alpha (F1,24=4.64, P=0.042; 31%) bands without site specificity. Clinical correlations were observed between F4 alpha power increases and improvements in HAM-D retardation, F3 alpha power increases and improvements of the absolute changes in perseveration and error number on the WCST, and C3 and C4 theta power increases and improvements of the percent change in perseveration and error number on the WCST following rTMS. Consecutive prefrontal rTMS could induce long-lasting EEG potentiations beyond the aftereffects, resulting in improved cognitive and depressive symptoms. © 2013 Elsevier Ireland Ltd and the Japan Neuroscience Society.

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大うつ病性障害の左背外側前頭前野への反復性高頻度経頭蓋磁気刺激法による定量脳波増強効果についての研究

野田賀大

東京大学 - 31 2012年03月

査読有り

本研究では薬物治療抵抗性の大うつ病性障害を対象に反復性高頻度経頭蓋磁気刺激法(rTMS)による定量脳波(qEEG)への影響及び臨床効果について調べた。うつ病患者25名に対して、計10回のrTMSセッションを左背外側前頭前野に施行した。その前後で安静覚醒閉眼脳波を計測し、パワースペクトラム解析を行った。rTMSによる臨床効果はハミルトンうつ病評価尺度とウィスコンシンカードソーティングテストで評価した。前頭前野領域を対象としたqEEGパワー変化の分散分析では、rTMS治療後にシータパワーの有意な増加を認めた。F3, Fz, F4を対象とした相関分析では、F3/F4のシータパワーの増高と認知機能改善との間に有意な臨床相関を認めた。本研究結果からは、うつ病に対するrTMS治療により、長期増強様変化を反映したqEEG変化が引き起こされている可能性が示唆された。

Localized potentiation of sleep slow-wave activity induced by prefrontal repetitive transcranial magnetic stimulation in patients with a depressive episode.

野田賀大

Brain Stimulation. 2012年

P3‐071: SOD1 loss accelerates Aß oligomerization and memory impairment in Tg2576 mice

N Kinoshita, KJ Barnham, H Hatsuta, K Murakami, Y Noda, T Shirasawa, ...

Alzheimer's & Dementia 8 2012年

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