Our main goal is to solve so-called “clinical questions”, which have been raised in the daily clinical activity, and have remained unsolved yet.
　Based on the concept of system neuroscience, by means of established and newly developed various methods, many clinical- and basic researches are conducted as follows.

KEY WORDS
General key words: epilepsy, epilepsy surgery, higher cortical function (motor control, praxis, language, vision, will), Bereitscheftspotentials (BPs), cortico-cortical network, movement disorders, sleep disorders
Original key words: ictal DC shifts, cortico-cortical evoked potentials (CCEP), cortical tremor, ictal apraxia, ictal paresis

1) Pathogenesis of intractable epilepsy and its treatment
2) Central control mechanism of higher cortical function and its pathophysiology
3) Pathogenesis of movement disorders and its treatment

1)Pathogenesis of intractable epilepsy and its treatment

　To delineate the extent and the degree of epileptogenicity in human intractable epilepsy, broad-band EEG analysis (ictal DC shifts and high frequency analysis in subdural EEG recording) (Fig. 1), a combined scalp EEG and functional MRI analysis are investigated. Seizure control was investigated by trancranial magnetic stimulation (TMS), low frequency cortical electric stimulation and neurofeedback method of DC potentials, all as the interventional neurophysiology.
　Subtype of temporal lobe epilepsy, amygdalar enlargement, was clinically delineated recently. Many clinical studies for epilepsy surgery have been conducted such as usefulness of functional mapping, MEG and awake surgery, etc. Immune-mediated smoldering epileptic state is currently investigated. (Closely collaborated with Departments of Neurosurgery, Radiology and Pediatrics, and Human Brain Research Center (HBRC), Kyoto University.)
　Through the clinical- and animal studies of autosomal dominant lateral temporal lobe epilepsy (ADLTE), phenotype and genotype correlation is investigated. (Closely collaborated with Institute of Laboratory Animals, Kyoto University.)
　To understand the propagation mechanisms of epileptic discharges in human epilepsy, cortico-cortical evoked potentials (CCEPs) were investigated. Using CCEPs as a marker of cortico-cortical excitability, we were able to map the dynamic modulation of the seizure network in ictogenesis as well as the modulation of the excitatory-inhibitory network at the epileptic focus. (In collaboration with Epilepsy Center, Cleveland Clinic Foundation.)
　EEG signal analysis and computer-based automatic EEG interpretation for spike detection, consciousness level and abnormal brain function are also very important concern. It has been collaborated for more than 20 years with Department of Advanced Systems Control Engineering, Saga University.

Fig.1

Ictal broad-band EEG: Direct comparison between slow activity (ictal slow shift) and high frequency activity (HFO: high frequency oscillation) at the epileptic focus (D1 electrode). Ictal slow shift occurred earlier than ictal HFO.

2)Central control mechanism of higher cortical functions / network and its pahophysiology

　Central motor control mechanism (simple movements, praxis, reaching, negative motor phenomena) by means of Bereitschaftspotential was extensively conducted so far, and the function of each motor cortices (supplementary motor area proper, pre-suppmenetary motor area, negative motor area, primary motor area and posterior parietal cortex) was investigated. Functional connectivity among those areas was also delineated by CCEPs and diffusion fiber tractography.
Language function and its network mechanism were investigated by direct cortical stimulation, event-related potentials (ERPs), task-related cortical stimulation and CCEPs. Especially basal temporal language area (BTLA) is regarded important for naming, and thus it is considered to be spared at epilepsy surgery for preservation of the verbal memory. (Closely collaborated with Neuroscience and Aphasia Research Unit, School of Psychological Sciences, University of Manchester.)
For visual function, cortical localization and its functional subdivision were directly delineated in human cortices before epilepsy surgery by means of functional MRI, MEG and direct cortical stimulation. Functional plasticity caused by focal pathology was also delineated. (Closely collaborated with Graduate School of Human and Environmental Studies and HBRC, Kyoto University.)
For mapping of cortico-cortical network, recent development in the electrophysiology and neuroimaging fields have brought us an opportunity to map the cortico-cortical networks in the living human brain. By means of non-invasive diffusion fiber tractography, we delineated language and motor pathways and their network reorganization due to pathology. An invasive electrical tract-tracing method of CCEPs was used to map the functional networks (language, motor and praxis) and their reorganization at the system level in individual patients during presurgical evaluations. Standardized CCEP connectivity maps were constructed in the MNI standard space to generalize the individual findings for the field of the basic and clinical system neuroscience (Fig.2).

Fig.2

Standardized CCEP connectivity map in the MNI space.
Lateral parietal area was stimulated and CCEPs were recorded from the lateral frontal area. A near-to-near and distant-to-distant, mirror symmetric configuration across the central sulcus, ii) preserved dorso-ventral organization, iii) projections to more than one frontal cortical sites in 56% of explored connections were observed (Matsumoto et al., Hum Brain Mapp 2011).

3) Pathogenesis of movement disorders and its treatment

　BAFME(benign adult onset familial myoclonus epilepsy) has been investigated by our group since the first description of the pathomechanism in 1990 as cortical tremor. It is progressive and showed clinical anticipation. Nationwide surveys are conducted. Similarly, progressive myoclonus epilepsy (PME) syndrome, i.e.,Unverricht-Lundborg disease, is extensively investigated especially from the view point of genotype-phenotype correlation.
Pathophysiology or generator mechanism of cortical myoclonus and resting tremor (as to how and at which time resting tremor stops before voluntary movements) are investigated.

Address correspondence:
3/5th laboratory, Department of Neurology,
Kyoto University Graduate School of Medicine 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto City, Kyoto 606-8507
Tel: +81-75-751-3772
Fax: +81-75-751-9416

Ikeda A, Lu¨ders HO, Burgess RC, Shibasaki H: Movement-related potentials recorded from supplementary motor area and primary motor area: role of supplementary motor area in voluntary movements. Brain 115: 1017-1043, 1992

Ikeda A, Taki W, Kunieda T, Terada K, Mikuni N, Nagamine T, Yazawa S, Ohara S, Hori T, Kaji R, Kimura J, Shibasaki H: Focal ictal DC shifts in human epilepsy as studied by subdural and scalp recording. Brain 122: 827-838, 1999

Matsumoto R, Nair DR, LaPresto E, Najm I, Bingaman W, Shibasaki H, Lu¨ders HO: Functional connectivity in the human language system: a cortico-cortical evoked potential study. Brain 127: 2316-30, 2004

Matsumoto R, Kinoshita M, Taki J, Hitomi T, Mikuni N, Shibasaki H, Fukuyama H, Ikeda A: In vivo epileptogenicity of focal cortical dysplasia: a direct cortical paired stimulation study. Epilepsia 46: 1744-1749, 2005

Imamura H, Matsumoto R, Inouchi M, Matsuhashi M, Mikuni N, Takahashi R, Ikeda A: Ictal Wideband ECoG: direct comparison between ictal slow shifts and high frequency oscillations. Clin Neurophysiol 122: 1500－1504, 2011

Hitomi T, Ikeda A, Kondo T, Imamura H, Inouchi M, Matsumoto R, Terada K, Kanda M, Matsuhashi M, Nagamine T, Shibasaki H, Takahashi R: Increased cortical hyperexcitability and exaggerated myoclonus with aging in benign adult familial myoclonus epilepsy. Mov Disord 26: 1509-14, 2011

2016
Nakatani M, Tsukino M, Takahashi R, Ikeda A. Periodic synchronous discharge occurred in an elderly with acute valacyclovir-associated encephalopathy. Rinsho Shinkeigaku. 2016;56:504-7.

Usami K, Matsumoto R, Sawamoto N, Murakami H, Inouchi M, Fumuro T, Shimotake A, Kato T, Mima T, Shirozu H, Masuda H, Fukuyama H, Takahashi R, Kameyama S, Ikeda A. Epileptic network of hypothalamic hamartoma: An EEG-fMRI study. Epilepsy Res. 2016;125:1-9.

Chen Y, Shimotake A, Matsumoto R, Kunieda T, Kikuchi T, Miyamoto S, Fukuyama H, Takahashi R, Ikeda A, Lambon Ralph MA. The ‘when’ and ‘where’ of semantic coding in the anterior temporal lobe: temporal representational similarity analysis of electrocorticogram data. Cortex. 2016;79:1-13.

Imamura H, Matsumoto R, Takaya S, Nakagawa T, Shimotake A, Kikuchi T, Sawamoto N, Kunieda T, Mikuni N, Miyamoto S, Fukuyama H, Takahashi R, Ikeda A. Network specific change in white matter integrity in mesial temporal lobe epilepsy. Epilepsy Res. 2016;120:65-72.

Ito S, Yano I, Hashi S, Tsuda M, Sugimoto M, Yonezawa A, Ikeda A, Matsubara K. Population Pharamacokinetic Modeling of Levetiracetam in Pediatric and Adult Patients With Epilepsy by Using Routinely Monitored Data. Ther Drug Monit. 2016;38:371-8.

Yamao Y, Kunieda K, Matsumoto R. Reply to commentary on “neural correlates of mirth and laughter: a direct electrical cortical stimulation study”. Cortex. 2016;75:244-6.

Hitomi T, Kobayashi K, Sakurai T, Ueda S, Jingami N, Kanazawa K, Matsumoto R, Takahashi R, Ikeda A. Benign adult familial myoclonus epilepsy is a progressive disorder: no longer idiopathic generalized epilepsy. Epileptic Disord. 2016;18:67-72.

Neshige S, Kobayashi K, Shimotake A, Iemura T, Matsumoto R, Nishinaka K, Matsumoto M, Takahashi R, Ikeda A. An elderly woman with exaggerated startle reflex and unconscious drop attack. Neurology and Clinical Neuroscience. 2016, in press.

Uneno Y, Yokoyama A, Nishikawa Y, Funakoshi T, Ozaki Y, Aoyama I, Yamaguchi D, Morita S, Mori Y, Kanai M, Kinoshita H, Inoue T, Sawamoto N, Matsumoto R, Matsumoto S, Muto M. Paraneoplastic limbic encephalitis in human epidermal growth factor receptor-2-positive gastric cancer patient treated with trastuzumab-combined chemotherapy: case report and literature review. Internal Medicine. 2016, in press.

Fukuma K, Ihara M, Miyashita K, Motoyama R, Tanaka T, Kajimoto K, Ikeda A, Nagatsuka K. Right parietal source in Mahjong-induced seizure: a system epilepsy of focal origin. Clinical Case Reports. 2016, in press.

Phantom of oscillation: Operational definition bound to improve. Kinoshita M, Ikeda A. Clin Neurophysiol. 2016;127:8-9.

Ikeda A. Commentary: We shall not lose past medical documents. Epilepsia. 2015;56:1712-3.

Usami K, Matsumoto R, Kobayashi K, Hitomi T, Shimotake A, Kikuchi T, Matsuhashi M, Kunieda T, Mikuni N, Miyamoto S, Fukuyama H, Takahashi R, Ikeda A. Sleep modulates cortical connectivity and excitability in humans: Direct evidence from neural activity induced by single-pulse electrical stimulation. Hum Brain Mapp. 2015;36:4714-29.

Yamao Y, Matsumoto R, Kunieda K, Arakawa Y, Kikuchi T, Shibata S, Ikeda A, Fukuyama H, Miyamoto S. A possible variant of negative motor seizure arising from the supplementary negative motor area. Clin Neurol Neurosurg. 2015;134:126-9.

Shimotake A, Matsumoto R, Ueno T, Kunieda T, Saito S, Hoffman P, Kikuchi T, Fukuyama H, Miyamoto S, Takahashi R, Ikeda A, Lambon Ralph MA. Direct Exploration of the Role of the Ventral Anterior Temporal Lobe in Semantic Memory: Cortical Stimulation and Local Field Potential Evidence From Subdural Grid Electrodes. Cereb Cortex. 2015;25:3802-17.

Yamao Y, Matsumoto R, Kunieda T, Shibata S, Shimotake A, Kikuchi T, Satow T, Mikuni N, Fukuyama H, Ikeda A, Miyamoto S. Neural correlates of mirth and laughter: a direct electrical cortical stimulation study. Cortex. 2015;66:134-40.

Kobayashi K, Matsumoto R, Matsuhashi M, Usami K, Shimotake A, Kunieda T, Kikuchi T, Mikuni N, Miyamoto S, Fukuyama H, Takahashi R, Ikeda A. Different Mode of Afferents Determines the Frequency Range of High Frequency Activities in the Human Brain: Direct Electrocorticographic Comparison between Peripheral Nerve and Direct Cortical Stimulation. PLoS One. 2015;10:e0130461.

Inoue Y, Yagi K, Ikeda A, Sasagawa M, Ishida S, Suzuki A, Yoshida K, and Japan Levetiracetam N01221 Study Group. Efficacy and tolerability of levetiracetam as adjunctive therapy in Japanese patients with uncontrolled partial- onset seizures. Psychiatry Clin Neurosci. 2015;69:640-8.

Fumuro T, Matsumoto R, Shimotake A, Matsuhashi M, Inouchi M, Urayama S, Sawamoto N, Fukuyama H, Takahashi R, Ikeda A. Network hyperexcitability in a patient with partial reading epilepsy: Converging evidence from magnetoencephalography, diffusion tractography, and functional magnetic resonance imaging. Clin Neurophysiol. 2015;126: 675-81.

Shibata S, Kunieda T, Inano R, Sawada M, Yamao Y, Kikuchi T, Matsumoto R, Ikeda A, Takahashi R, Mikuni N, Takahashi J, Miyamoto S. Risk factors for infective complications with long term subdural electrode implantation in patients with medically intractable partial epilepsy. World Neurosurg. 2015;84:320-6.

Hashi S, Yano I, Shibata M, Masuda S, Kinoshita M, Matsumoto R, Ikeda A, Takahashi R, Matsubara K. Effect of CYP2C19 polymorphisms on the clinical outcome of low-dose clobazam therapy in Japanese patients with epilepsy. Eur J Clin Pharmacol. 2015;71:47-59.

Kunieda T, Yamao Y, Kikuchi T, Matsumoto R. New Approach for Exploring Cerebral Functional Connectivity: Review of CCEP (Cortico-cortical evoked potential). Neurol Med Chir. 2015;55:374-82.

Matsumoto R, Mikuni N, Tanaka K, Usami K, Fukao K, Kunieda T, Takahashi Y, Miyamoto S, Fukuyama H, Takahashi R, Ikeda A. Possible induction of multiple seizure foci due to parietal tumour and anti-NMDAR antibody. Epileptic Disord. 2015;17:89-94.

Fumuro T, Matsuhashi M, Miyazaki T, Inouchi M, Hitomi T, Matsumoto R, Takahashi R, Fukuyama H, Ikeda A. Alpha- band desynchronization in human parietal area during reach planning. Clin Neurophysiol. 2015;126:756-62.

Kanazawa K, Matsumoto R, Imamura H, Matsuhashi M, Kikuchi T, Kunieda T, Mikuni N, Miyamoto S, Takahashi R, Ikeda A. Intracranially recorded ictal direct current shifts may precede high frequency oscillations in human epilepsy. Clin Neurophysiol. 2015;126:47-59.

Ota M, Shimizu T, Yoshida H, Kawata A, Kinoshita M, Nakano S, Isozaki E, Matsubara S. Clinical features and therapeutic responses of idiopathic orbital myositis. Neurology and Clinical Neuroscience. 2015;3:63-7.

Kanazawa K, Matsumoto R, Shimotake A, Kinoshita M, Otsuka A, Watanabe O, Tanaka K, Takahashi R, Ikeda A. Persistent frequent subclinical seizures and memory impairment after clinical remission in smoldering limbic encephalitis. Epileptic Disord. 2014;16:312-7.

Kobayashi K, Hitomi T, Matsumoto R, Kondo T, Kawamata J, Matsuhashi M, Hashimoto S, Ikeda H, Koide Y, Inoue Y, Takahashi R, Ikeda A. Long-term follow-up of cortical hyperexcitability in Japanese Unverricht-Lundborg disease. Seizure. 2014;23:746-50.

Takeuchi Y, Arakawa Y, Mikami Y, Matsumoto R, Miyamoto S. Dysembryoplastic neuroepithelial tumor with rapid recurrence of pilocytic astrocytoma component. Brain Tumor Pathol. 2014;31:144-8.

Yamao Y, Matsumoto R, Kunieda T, Arakawa Y, Kobayashi K, Usami K, Shibata S, Kikuchi T, Sawamoto N, Mikuni N, Ikeda A, Fukuyama H, Miyamoto S. Intraoperative dorsal language network mapping by using single-pulse electrical stimulation. Hum Brain Mapp. 2014;35:4345-61.

Fumoto N, Mashimo T, Masui A, Ishida S, Mizuguchi Y, Minamimoto S, Ikeda A, Takahashi R, Serikawa T, Ohno Y. Evaluation of seizure foci and genes in the Lgi1L385R/+ mutant rat. Neuroscience Research. 2014;80:69-75.

Jingami N, Matsumoto R, Ito H, Ishii A, Ihara Y, Hirose S, Ikeda A, Takahashi R. A novel SCN1A mutation in a cytoplasmic loop in intractable juvenile myoclonic epilepsy without febrile seizures. Epileptic Disord. 2014;16:227-31.

Murai T, Tohyama T, Kinoshita M. Recurrent diarrhea as a manifestation of temporal lobe epilepsy case report. Epilepsy & behavior Case Report. 2014;2:57-9.

Takaya S, Ikeda A, Mitsueda-Ono T, Matsumoto R, Inouchi M, Namiki C, Oishi N, Mikuni N, Ishizu K, Takahashi R, Fukuyama H. Temporal Lobe Epilepsy with Amygdala Enlargement: A Morphologic and Functional Study. J Neuroimaging. 2014;24:54-62.

Wang B, Wang X, Ikeda A, Nagamine T, Shibasaki H, Nakamura M. Automatic reference selection for quantitative EEG interpretation: Identification of diffuse/localised activity and the active earlobe reference, iterative detection of the distribution of EEG rhythms. Med Eng Phys. 2014;36:88-95.

Hitomi T, Takahashi R, Ikeda A. Recent advance in research of benign adult familial myoclonus epilepsy (BAFME): is BAFME a progressive disorder?. Rinsho Shinkeigaku. 2014;54:1142-5. Japanese.

Tojima M, Hitomi T, Jingami N, Tanioka K, Yamakado H, Matsumoto R, Takahashi Y, Ikeda A, Takahashi R. Two cases of acute onset of focal cortical reflex myoclonus following acute aseptic meningoencephalitis with positive anti-glutamate receptor autoantibody. Rinsho Shinkeigaku. 2014;54:543-9. Japanese.

Lu¨ders H, Amina S, Bailey C, Baumgartner C, Benbadis S, Bermeo A, Carreno M, Devereaux M, Diehl B, Eccher M, Edwards J, Fastenau P, Fernandez Baca-Vaca G, Godoy J, Hamer H, Hong SB, Ikeda A, Kahane P, Kaiboriboon K, Kalamangalam G, Lardizabal D, Lhatoo S, Lu¨ders J, Mani J, Mayor C, Mesa Latorre T, Miller J, Morris HH, Noachtar S, O’Donovan C, Park J, Perez-Jimenez MA, Rona S, Rosenow F, Shahid A, Schuele S, Skidmore C, Steinhoff B, Szabo´ CA´, Sweet J, Tandon N, Tanner A, Tsuji S. Proposal: different types of alteration and loss of consciousness in epilepsy. Epilepsia. 2014;55:1140-4.

Inoue T, Matsumoto R, Ikeda A. Treatment of epilepsy in patients of adolescence and adulthood. Nihon Rinsho. 2014;72:853-8. Japanese.

Shibasaki H, Nakamura M, Sugi T, Nishida S, Nagamine T, Ikeda A. Automatic interpretation and writing report of the adult waking electroencephalogram. Clin Neurophysiol. 2014;125:1081-94.

Enatsu R, Matsumoto R, Piao Z, O’Connor T, Horning K, Burgess RC, Bulacio J, Bingaman W, Nair DR. Cortical negative motor network in comparison with sensorimotor network: A cortico-cortical evoked potential study. Cortex. 2013;49:2080-96.

Hitomi T, Kobayashi K, Jingami N, Nakagawa T, Imamura H, Matsumoto R, Kondo T, Chin K, Takahashi R, Ikeda A. Increased clinical anticipation with maternal transmission in benign adult familial myoclonus epilepsy in Japan. Epileptic Disorders. 2013;15:428-32.

Inouchi M, Matsumoto R, Taki J, Kikuchi T, Mitsueda-Ono T, Mikuni N, Wheaton L, Hallett M, Fukuyama H, Shibasaki H, Takahashi R, Ikeda A. Role of posterior parietal cortex in reaching movements in humans: Clinical implication for ‘optic ataxia’. Clin Neurophysiol. 2013;124:2230-41.

Kunieda T, Mikuni N, Shibata S, Inano R, Yamao Y, Kikuchi T, Matsumoto R, Takahashi J, Ikeda A, Fukuyama H, Miyamoto S. Long-term seizure outcome following resective surgery for epilepsy: To be or not to be completely cured? Neurol Med Chir (Tokyo). 2013;53:805-13.

Mitsueda-Ono T, Ikeda A, Sawamoto N, Aso T, Hanakawa T, Kinoshita M, Matsumoto R, Mikuni N, Amano S, Fukuyama H, Takahashi R. Internal structural changes in the hippocampus observed on 3-Tesla MRI in patients with mesial temporal lobe epilepsy. Internal Medicine. 2013;52:877-85.

Morimoto E, Kanagaki M, Okada T, Yamamoto A, Mori N, Matsumoto R, Ikeda A, Mikuni N, Kunieda T, Paul D, Miyamoto S, Takahashi R, Togashi K. Anterior temporal lobe white matter abnormal signal (ATLAS) as an indicator of seizure focus laterality in temporal lobe epilepsy: comparison of double inversion-recovery, FLAIR and T2W MR imaging. Eur Radiol. 2013;23:3-11.

Morimoto E, Okada T, Kanagaki M, Yamamoto A, Fushimi Y, Matsumoto R, Takaya S, Ikeda A, Kunieda T, Kikuchi T, Paul D, Miyamoto S, Takahashi R, Togashi K. Evaluation of Focus Laterality in Temporal Lobe Epilepsy: A Quantitative Study Comparing Double Inversion-Recovery MR Imaging at 3T with FDG-PET. Epilepsia. 2013;54:2174-83.

Murahara T, Kinoshita M, Matsui M, Yamashita K, Ikeda A, Takahashi R. Prolonged ictal monoparesis with parietal PLEDs. Epileptic Disord. 2013;15:197-202.

Takeuchi Y, Arakawa Y, Mikami Y, Matsumoto R, Miyamoto S. Dysembryoplastic neuroepithelial tumor with rapid recurrence of pilocytic astrocytoma component. Brain Tumor Pathol. 2013;31:144-8.

Usami K, Matsumoto R, Kunieda T, Shimotake A, Matsuhashi M, Miyamoto S, Fukuyama H, Takahashi R, Ikeda A. Pre-SMA actively engages in conflict processing in human: A combined study of epicortical ERPs and direct cortical stimulation. Neuropsychologia. 2013;51:1011-7.

Kinoshita M, Ikeda A. Paroxysmal symptoms in the elderly; epileptic seizures or not. Nihon Rinsho. 2013;71:1858-63. Japanese.

Nakaoku Y, Maki T, Kanazawa K, Matsumoto R, Fukuyama H, Takahashi R, Ikeda A. A case of smoldering anti-leucine-rich glioma-inactivated 1 (LGI1) antibody-associated limbic encephalitis with faciobrachial dystonic seizure. Rinsho Shinkeigaku. 2013;53:706-11. Japanese.

Yamao Y, Kunieda T, Kikuchi T, Matsuhashi M, Sawamoto N, Matsumoto R, Okada T, Miyamoto S, Ikeda A. Neuroimaging in epilepsy. Brain Nerve. 2013;65:573-81. Japanese.

Toma K, Taguchi K, Ikeda A, Nishinaka K, Udaka F, Kameyama M. The medial temporal area and parietal lobe are involved in epileptic polyopia and palinopsia: A case report. Rinsho Shinkeigaku. 2012;52:651-5. Japanese.

Hitomi T, Oga T, Tsuboi T, Yoshimura C, Kato T, Ikeda A, Takahashi R, Chin K. Transient increase in epileptiform discharges after the introduction of nasal continuous positive airway pressure in a patient with obstructive sleep apnea and epilepsy. Intern Med. 2012;51:2453-6.

Matsumoto R, Kunieda T, Ikeda A. In vivo investigation of human brain networks by using cortico-cortical evoked potentials. Brain Nerve. 2012;64:979-91. Japanese.

Baulac S, Ishida S, Mashimo T, Boillot M, Fumoto N, Kuwamura M, Ohno Y, Takizawa A, Aoto T, Ueda M, Ikeda A, LeGuern E, Takahashi R, Serikawa T. A rat model for LGI1-related epilepsies. Hum Mol Genet. 2012;21:3546-57.

Lu¨ders HO, Amina S, Baumgartner C, Benbadis S, Bermeo-Ovalle A, Devereaux M, Diehl B, Edwards J, Baca-Vaca GF, Hamer H, Ikeda A, Kaiboriboon K, Kellinghaus C, Koubeissi M, Lardizabal D, Lhatoo S, Lu¨ders J, Mani J, Mayor LC, Miller J, Noachtar S, Pestana E, Rosenow F, Sakamoto A, Shahid A, Steinhoff BJ, Syed T, Tanner A, Tsuji S. Modern technology calls for a modern approach to classification of epileptic seizures and the epilepsies. Epilepsia. 2012;53:405-11.

Hitomi T, Kondo T, Kobayashi K, Matsumoto R, Takahashi R, Ikeda A. Clinical anticipation in Japanese families of benign adult familial myoclonus epilepsy. Epilepsia. 2012;53:e33-6.

Matsumoto R, Nair DR, Ikeda A, Fumuro T, Lapresto E, Mikuni N, Bingaman W, Miyamoto S, Fukuyama H, Takahashi R, Najm I, Shibasaki H, Lu¨ders HO. Parieto-frontal network in humans studied by cortico-cortical evoked potential. Hum Brain Mapp. 2012;33:2856-72.

Kikuchi T, Matsumoto R, Mikuni N, Yokoyama Y, Matsumoto A, Ikeda A, Fukuyama H, Miyamoto S, Hashimoto N. Asymmetric bilateral effect of the supplementary motor area proper in the human motor system. Clin Neurophysiol. 2012;123:324-34.

Tanioka K, Nagao M, Yamamoto M, Matsumura Y, Tabu H, Matsushima A, Uemura K, Matsumoto R, Ito Y, Takakura S, Takahashi R, Ichiyama S. Disseminated Nocardia farcinica infection in a patient with myasthenia gravis successfully treated by linezolid: a case report and literature review. J Infect Chemother. 2012;18:390-4.

Hitomi T, Ikeda A, Inouchi M, Imamura H, Nakagawa T, Fumuro T, Matsumoto R, Takahashi R :Transient myoclonic state with asterixis: Primary motor cortex hyperexcitability is correlated with myoclonus. Intern Med 50: 2303-2309, 2011

Hitomi T, Ikeda A, Kondo T, Imamura H, Inouchi M, Matsumoto R, Terada K, Kanda M, Matsuhashi M, Nagamine T , Shibasaki H, Takahashi R: Increased cortical hyperexcitability and exaggerated myoclonus with aging in benign adult familial myoclonus epilepsy. Mov Disord 26: 1509-1514, 2011

Imamura H, Matsumoto R, Inouchi M, Matsuhashi M, Mikuni N, Takahashi R, Ikeda A: Ictal wideband ECoG: Direct comparison between ictal slow shifts and high frequency oscillations. Clin Neurophysiol 122: 1500-1504, 2011

Ji Z, Sugi T, Goto S, Wang X, Ikeda A, Nagamine T, Shibasaki H, Nakamura M. An automatic spike detection system based on elimination of false positives using the large-area context in the scalp EEG, IEEE Trans Biomed Eng. 58:2478-88, 2011

Kobayashi K, Matsumoto R, Kondo T, Kawamata J, Hitomi T, Inouchi M, Matsuhashi M, Takahashi R, Ikeda A: Decreased cortical excitability in Unverricht-Lundborg disease in the long-term follow-up: A consecutive SEP study. Clin Neurophysiol 122: 1617-1621, 2011

Matsumoto R, Imamura H, Inouchi M, Nakagawa T, Yokoyama Y, Matsuhashi M, Mikuni N, Miyamoto S, Fukuyama H, Takahashi R and Ikeda A: Left anterior temporal cortex actively engages in speech perception: A direct cortical stimulation study. Neuropsychologia 49: 1350-1354, 2011

Matsumoto R, Nair DR, Ikeda A, Fumuro T, Lapresto E, Mikuni N, Bingaman W, Miyamoto S, Fukuyama H, Takahashi R , Najm I, Shibasaki H and Lu¨ders HO: Parieto-frontal network in humans studied by cortico-cortical evoked potential. Hum Brain Mapp. E-pub. doi: 10.1002/hbm.21407, 2011

Mitsueda-Ono T, Ikeda A, Inouchi M, Takaya S, Matsumoto R, Hanakawa T, Sawamoto N, Mikuni N, Fukuyama H, Takahashi R: Amygdalar enlargement in patients with temporal lobe epilepsy. J Neurol Neurosurg Psychiatry 82: 652-657, 2011

Naito E, Matsumoto R, Hagura N, Oouchida Y, Tomimoto H, Hanakawa T: Importance of precentral motor regions in human kinesthesia: A single case study. Neurocase 17: 133-147, 2011

Tanioka K, Nagao M, Yamamoto M, Matsumura Y, Tabu H, Matsushima A, Uemura K, Matsumoto R, Ito Y, Takakura S, Takahashi R and Ichiyama S: Disseminated Nocardia farcinica infection in a patient with myasthenia gravis successfully treated by linezolid: a case report and literature review. J Infection and Chemotherapy:1-5, 2011

Zhang X, Wang X, Sugi T, Ikeda A, Nagamine T, Shibasaki H, Nakamura M. Automatic interpretation of hyperventilation-induced electroencephalogram constructed in the way of qualified electroencephalographer’s visual inspection. Med Biol Eng Comput. 49:171-80, 2011

Kawamata J, Ikeda A, Fujita Y, Usui K, Shimohama S, Takahashi R: Mutations in LGI1 gene in Japanese families with autosomal dominant lateral temporal lobe epilepsy: the first report from Asian families. Epilepsia 51: 690-3, 2010

Kinoshita M, Hitomi T, Matsuhashi M, Nakagawa T, Nagamine T, Sawada H, Shibasaki H, Takahashi R, Ikeda A: How does voluntary movement stop resting tremor? Clin Neurophysiol 121: 983-5, 2010

Maki T, Matsumoto R, Kohara N, Kondo T, Son I, Mezaki T, Nishino I, Ikeda A, Takahashi R: Rippling is not always electrically silent in rippling muscle disease: a case report. Muscle Nerve 43: 601-5, 2010

Ikeda A, Hirasawa KI, Kinoshita M, Hitomi T, Matsumoto R, Mitsueda T, Taki JY, Inouch M, Mikuni N, Hori T , Fukuyama H, Hashimoto N, Shibasaki H and Takahashi R: Negative motor seizure arising from the negative motor area: Is it ictal apraxia? Epilepsia 50: 2072-2084, 2009

Iseki K, Ikeda A, Kihara T, Kawamoto Y, Mezaki T, Hanakawa T, Hashikawa K, Fukuyama, Shibasaki H: Impairment of the cortical GABAergic inhibitory system in catatonic stupor. A case report with neuroimaging. Epileptic Diord 11: 126-31, 2009

Minakawa EN, Matsumoto R, Kinoshita M. Topiramate induced agranulocytosis. BMJ Case Rep. 2009;2009. pii: bcr11.2008.1273. Epub 2009 Jun 5

Takaya S, Mikuni N, Mitsueda T, Satow T, Taki J, Kinoshita M, Miyamoto S, Hashimoto N, Ikeda A, Fukuyama H: Improved cerebral function in mesial temporal lobe epilepsy after subtemporal amydgalohoppocampectomy. Brain 132: 185-194, 2009

Usui K, Ikeda A, Nagamine T, Matsubayashi J, Matsumoto R, Hiraumi H, Kawamata J, Matsuhashi M, Takahashi R, Fukuyama H: Abnormal auditory cortex with giant N100m signal in patients with autosomal dominant lateral temporal lobe epilepsy. Clin Neurophysiol 120:1923-1926, 2009

Usui K, Ikeda A, Nagamine T, Matsuhashi M, Kinoshita M, Mikuni N, Miyamoto S, Hashimoto N, Fukuyama H, Shibasaki H: Temporal dynamics of Japanese morphogram and syllabogram processing in the left basal temporal area studied by event-related potentials. J Clin Neurophysiolol 26: 160-166, 2009

Kinoshita M, Takahashi R, Ikeda A: Application of the 2001 diagnostic scheme and the 2006 ILAE report of seizure and epilepsy: a feedback from the clinical practice of adult epilepsy. Epileptic Disord 10: 206-12, 2008

Matsumoto R, Okada T, Mikuni N, Mitsueda-Ono T, Taki J, Sawamoto N, Hanakawa T, Miki Y, Hashimoto N, Fukuyama H , Takahashi R and Ikeda A: Hemispheric asymmetry of the arcuate fasciculus: A preliminary diffusion tensor tractography study in patients with unilateral language dominance defined by Wada test. J Neurol 255:1703-1711, 2008

Komori M, Tanaka M, Muramoto E, Ohno M, Matsumoto R, Murase N, Kitagawa N, Saida T. (2007): Mitoxantrone for the treatment of Japanese patients with multiple sclerosis. Clin Neurology 47: 401-406, 2007

Kinoshita M, Ikeda A, Begum T, Terada K, Shibasaki H: Efficacy of low-dose, add-on therapy of clobazam (CLB) is produced by its major metabolite, N-desmethyl-CLB. J Neurol Sci 263: 44-8, 2007

Matsumoto R, Nair DR, LaPresto E, Bingaman W, Shibasaki H, Lu¨ders HO: Functional connectivity in human cortical motor system: A cortico-cortical evoked potential study. Brain 130: 181-197, 2007

Mikuni N, Okada T, Taki J, Matsumoto R, Nishida N, Enatsu R, Hanakawa T, Ikeda A, Miki Y, Urayama S, Fukuyama H and Hashimoto N: Fibers from the dorsal premotor cortex elicit motor-evoked potential in a cortical dysplasia. Neuroimage 34:12-18, 2007

Mikuni N, Okada T, Nishida N, Taki J, Enatsu R, Ikeda A, Miki Y, Hanakawa T, Fukuyama H, Hashimoto N: Comparison between motor evoked potential recording and fiber tracking for estimating pyramidal tracts near brain tumors. J Neurosurg 106:128-133, 2007

Begum T, Ikeda A, Yoshioka A, Sawada H, Fukuyama H, Shibasaki H: Rapid recovery from coma with multifocal PLEDs in a patient with severe dementia. Intern Med 45; 141-144, 2006

Begum T, Ikeda A, Matsuhashi M, Mikuni N, Miyamoto S, Hashimoto N, Nagamine T, Fukuyama H, Shibasaki H: Ipsilateral facial sensory and motor response to basal fronoto-temporal cortical stimulation: evidence suggesting direct activation of cranial nerves. Epilepsy Res 71: 216-222, 2006

Hitomi T, Ikeda A, Matsumoto R, Kinoshita M, Taki J, Usui K, Mikuni N, Nagamine T, Hashimoto N, Shibasaki H and Takahashi R: Generators and temporal succession of giant somatosensory evoked potentials in cortical reflex myoclonus: Epicortical recording from sensorimotor cortex. Clin Neurophysiol 117: 1481-1486, 2006

Ikeda A, Matsui M, Hase Y, Hitomi T, Takahashi Y, Shibasaki H, Shimohama S: “Burst and slow complexes” in nonconvulsive, epileptic status. Epileptic Disord 8: 61-64, 2006

Kinoshita M, Ikeda A, Taki J, Usui K, Matsumoto R, Mikuni N, Takahashi JB, Fukuyama H, Hashimoto N, Takahashi R: Heterogeneous epileptogenicity and cortical function within malformations of cortical development: A case report. J Neurol Sci 251:129-133, 2006

Lu¨ders HO, Acharya J, Alexopoulos A, Baumgartner C, Bautista J, Burgess R, Carreno M, Diehl B, Dinner D, Ebner A, Foldvary N, Godoy J, Hamer H, Ikeda A, Ka¨lle´n K, Kellinqhaus C, Kotaqal P, Lachhwani D, Loddenkemper T, Mani J, Matsumoto R, Mo¨ddel G, Nair D, Noachtar S, O’Donovan CA, Rona S, Rosenow F, Sshuele S, Szabo CA, Tandon N, Tanner A and Widdess-Walsh P: Are epilepsy classifications based on epileptic syndromes and seizure types outdated? Epileptic Disord 8: 81-85, 2006

Mikuni N, Ohara S, Ikeda A, Hayashi N, Nishida N, Taki J, Enatsu R, Matsumoto R, Shibasaki H, Hashimoto N: Evidence for a wide distribution of negative motor areas in the perirolandic cortex. Clin Neurophysiol 117: 33-40, 2006

Nakagawa Y, Matsumoto R, Ikeda A, Mikuni N, Matsuhashi M, Hanakawa T, Fukuyama H, Shimohama S: Focal cortical dysplasia at the primary somatosensory cortex could manifest both intractable partial epilepsy and cortical reflex myoclonus. Clin Neurology 46: 335-338, 2006

Ueki Y, Mima T, Koth MA, Sawada H, Saiki H, Ikeda A, Begum T, Reza F, Nagamine T, Fukuyama H: Altered plasticity of the human motor cortex in pakinson’s disease. Ann Neurol 59: 60-71, 2006

Yamamoto J, Ikeda A, Kinoshita M, Matsumoto R, Satow T, Takeshita K, Matsuhashi M, Mikuni N, Miyamoto S, Hashimoto N and Shibasaki H: Low-frequency electric cortical stimulation decreases interictal and ictal activity in human epilepsy. Seizure 15:520-527, 2006

Ohara S, Ikeda A, Matsuhashi M, Satow T, Kunieda T, Mikuni N, Baba K, Mihara T, Miyamoto S, Shibasaki H: Bereitschaftspotentials recorded from the lateral part of the superior frontal gyrus in humans. Neurosci Lett 399: 1-5, 2006

Begum T, Ikeda A, Yoshioka A, Sawada H, Fukuyama H, Shibasaki H: Rapid recovery from coma with multifocal PLEDs in a patient with severe dementia. Intern Med 45:141-144, 2006

Oka Y, Inoue Y, Kanbayashi T, Kuroda K, Miyamoto M, Miyamoto T, Horiuchi F, Ikeda A, Shimizu T, Shibasaki H: Narcolepsy without cataplexy: two subtypes based on CSF hypoicretin-1/ orexin-A findings. Sleep 29:1439-1443, 2006

Mitsueda-Ono T, Ikeda A, Noguchi E, Takaya S, Fukuyama H, Shimohama S, Takahashi R: Epileptic polyopia with right temporal lobe epilepsy as studied by FDG-PET and MRI: a case report. J Neurol Sci 247: 109-111, 2006

Mikuni N, Miyamoto S, Ikeda A, Satow T, Taki J, Takahashi J, Ohigashi Y, Hashimoto N: Subtemporal hippocampectomy preserving the basal temporal language area for intractable mesial temporal lobe epilepsy- preliminary results. Epilepsia 47:1347-53, 2006

Takaya S, Hanakawa T, Hashikawa K, Ikeda A, Sawamoto N, Nagamine T, Ishizu K, Fukuyama H: Prefrontal hypofunction in patients with intractable mesial temporal lobe epilepsy. Neurology 67:1674-1676, 2006

Iinuma K, Morimoto K, Akiyama T, Ikeda A, Kurimoto M: Proposed diagnostic schema for the classification of epileptic seizures and eipilepsies (ILAE, 2001): proposal from Japan Epilepsy Society. Epilepsia 47: 1588-1591, 2006

Mikuni N, Ikeda A, Takahashi JA Nozaki K, Miyamoto S, taki W, Hashimoto N: A tsep-by-step resection guided by electrocorticography for nonmalignant brain tumors associated with long-term intractable epilepsy. Epilepsy Behav 8: 560-564, 2006

Ikeda A, Miyamoto S, Tomimoto H, Mikuni N, Fukuyama N, Hashimoto N: Effects of trans-sylvian approach on basal forebrain projection fibers: verbal memory decline in selective amygdalohippocampectomy. Epilepsia 46: 334, 2005

Ikeda A, Kurihara S, Shibasaki H: Possible anticipation in BAFME: examined three generations in a Japanese family. Mov Disord 20: 1076-1077, 2005

Kinoshita M, Ikeda A, Matsuhashi M, Matsumoto R, Hitomi T, Begum T, Usui K, Takayama M, Mikuni N, Miyamoto S, Hashimoto N and Shibasaki H: Electric cortical stimulation suppresses epileptic and background activities in neocortical epilepsy and mesial temporal lobe epilepsy. Clin Neurophysiol 116:1291-1299, 2005

Kinoshita K, Ikeda A, Begum T, Yamamoto J, Hitomi T, Shibasaki H: Low frequency repetitive transcranial magnetic stimulation for seizure suppression in patients with extratemporal lobe epilepsy – a pilot study. Seizure 14: 387-392, 2005

Matsumoto R, Ikeda A, Hitomi T, Aoki T, Hanakawa T, Miki Y, Tomimoto H, Shimohama S, Shibasaki H: Ictal monoparesis associated with lesions in the primary somatosensory area. Neurology 65: 1476-1478, 2005

Matsumoto R, Kinoshita M, Taki J, Hitomi T, Mikuni N, Shibasaki H, Fukuyama H, Hashimoto N, Ikeda A: In vivo epileptogenicity of focal cortical dysplasia: A direct cortical paired stimulation study. Epilepsia 46: 1744-1749, 2005

Matsumoto R, Nair DR, Bingaman W, Ikeda A, Shibasaki H, Lu¨ders HO: Interareal connectivity in the human language system: a cortico-cortical evoked potential study. Brain 127:2316-30, 2004

Mikuni N, Takayama M, Satow T, Yamada S, Hayashi H, Nishida N, Taki J, Enatsu R, Ikeda A, Miyamoto S, Hashimoto N: Evaluation of adverse effects in intracarotid propofol injection for Wada test. Neurology 65: 1813-6, 2005

Mikuni N, Ikeda A, Hayase Y, Amano S, Hanakawa T, Fukuyama H, Hashimoto N: Surgical resection of an epileptogenic cortical dysplasia in the deep foot sensorimotor area: a case report. Epilepsy Behav 7: 559-62, 2005

Murase N, Rothwell JC, Kaji R, Urushihara R, Nakamura K, Murayama N, Igasaki T, Sakata-Igasaki M, Mima T, Ikeda A, Shibasaki H: Subthreshold low-frequency repetitive transcranial magnetic stimulation over the premotor cortex modulates writer’s cramp. Brain 128: 104-115, 2005

Nakamura M, Chen Q, Sugi T, Ikeda A, Shibaasaki H: Technical quality evaluation of EEG recording based on electtroencephalographers’ knowledge. Med Eng Physics 27: 93-100, 2005

Nakaji K, Ikeda A, Oka Y, Tomimoto H, Shimohama S, Kanbayashi T, Shibasaki H: Hypersomnia caused by isolated angitis of the CNS. Intern Med 44: 883-885, 2005

Nishida N, Hayase, Y, Mikuni N, Enatsu R, Hayashi N, Takahashi JA, Nakashima Y, Ikeda A, Amano S, Hashimoto N: A nonspecific form of dysembryoplastic neuroepithelial tumor presenting　with intractable epilepsy. Brain Tumor Pathol 22: 35－40, 2005

Takaya S, Matsumoto R, Namiki C, Kiyosu H, Isono O, Hashikawa K, Ikeda A, Fukuyama H: Frontal nonconvulsive status epilepticus manifesting somatic hallucinations. J Neurol Sci 234: 25-29, 2005

Usui N, Kotagal P, Matsumoto R, Kellinghaus C, Lu¨ders HO: Focal semiologic and electroencephalographic features in patients with juvenile myoclonic epilepsy. Epilepsia 46: 1668-1676, 2005

Ueki Y, Mima T, Oga T, Ikeda A, Hitomi T, Fukuyama H, Nagamine T, Shibasaki H: Dominance of ipsilateral coorticospinal pathway in congenital mirror movements. J Neurol Neurosurg Psychiatry 76: 276-279, 2005

Usui K, Ikeda A, Takayama M, Matsuhashi M, Satow T, Begum T, Kinoshita M, Miyamoto S, Hashimoto N, Nagamine T, Fukuyama H, Shibasaki H: Processing of Japanese morphogram and syllabogram in the left basal temporal area: electrical cortical stimulation studies. Cog Brain Res 24: 274-283, 2005