Kyushu University [Hiroshi Shigeto (Professor) Faculty of Medical Sciences, Department of Health Sciences]

I am engaged in the study of neurological disease both for clinical and research. Basically, I have been using the method of neurophysiology. For the epilepsy, I have studied the feasibility of the magnetoencephalograpy for detecting the epileptic electrical discharges in patient.We created　focal cortical dysplasia rat model，which aquires kindling phenomenon faster than normal control. These rat had spontaneous seizure arising from hippocampus. I also analysis brain epileptic magnetic activity using network analysis. We analyze the scalp electroencephalogram, stereotactic electroencephalogram and electrocorticogram in order to reveal the influences of sleep, biological rhythm, memory and higher cortical function on the relationship between limbic system and neocortex.

Research

Research Interests

Detection of microRNAs as biomarker of epileptic seizures
keyword : epilepsy, microRNA
2023.04～2028.03.
Elucidation of language processing using MEG and DC stimulation
keyword : Magnetoencephalography
2021.04～2024.03.
Mechanism of accelerating forgetting of epilepsy patients
keyword : epilepsy memory
2016.04～2020.04.
Investigate the mechanisms of epileptogenesis using animal study and human MEG study
keyword : spontaneous seizure, rat, MEG
2012.04～2015.03.
Effect of cervical carotid artery cooling on cortical epileptic activity.
keyword : epilepsy cooling cervical
2006.04～2007.12We study the cooling effect on cortical epileptic electrical activity by the cooling of cervical carotid artery, which reduced brain temperature indirectly and non-invasively. .
Investigate the epileptogenicity of focal cortical dysplasia
keyword : epilepsy focal cortical dysplasia
2001.10～2011.04We study about the epileptogenicity of focal cortical dysplasia using freeze lesion rat model..
Study the effect of electrical stimulation on the generation and suppression of epileptic activity
keyword : electrical stimulation epilepsy generation suppression
2001.10～2011.03We made the rat model producing after discharge on neo-cortex. Using this model, we test the efficacy of electrical stimulation both for preventing and provoking seizures..

Academic Activities

Books

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Reports

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Hiroshi Shigeto, Hippocampal modulation of auditory processing in epilepsy, NEUROLOGY AND CLINICAL NEUROSCIENCE, 10.1111/ncn3.12470, Vol.9, No.1, pp.17-23, 2020.11, The hippocampus is anatomically and functionally connected to other brain regions tightly. Especially in the field of memory research, it has become clear that the connections between the cerebral cortex, thalamus, and hippocampus are regulated via slow-wave rhythms and high-frequency oscillation. In addition, the hippocampus, as a limbic system, is more excitable to inputs than the cerebral cortex and has a reverberant circuit structure, which induces long-lasting neural activity. Because of such characteristics of the hippocampus, it is treated as a key structure in epilepsy. Auditory processing has been shown to be affected by hippocampal activity, and impaired auditory processing function in patients with medial temporal lobe epilepsy has been elucidated using techniques such as cognitive behavior tests and electrophysiological recordings. We recorded the auditory-induced magnetoencephalography of patients with refractory medial temporal lobe epilepsy and examined which hemisphere was more affected. In contrast to previous language studies, we only used simple tone stimulation, by which we could obtain the laterality information regarding epileptic activity and left-right difference. In this article, we reviewed the effects of hippocampal activity on brain function, including the findings of our auditory stimulus-induced magnetic field recordings of medial temporal lobe epilepsy..

Medical care of epilepsy faces to brain function
Anytime, medical care of epilepsy faces to brain function. Based on seizure semiology and findings of electroencephalography, we search for the excitable brain region and symptomatogenic zone in order to classify the seizure. Whether patient has impairment of consciousness during seizure is important not only for seizure classification but also patient’s social activity. Antiepileptic drugs are chosen based on epilepsy classification and the cause of epilepsy. Thirty to 40% of epilepsy patients are intractable against medication, which leads to increasing dose of antiepileptic drugs and induces brain dysfunction. As for intractable epilepsy, epilepsy surgery is considered. Best candidate for epilepsy surgery is medial temporal lobe epilepsy. There are memory problems before and after surgery in medial temporal lobe epilepsy. MRI negative neocortical epilepsy fails to poor outcome after epilepsy surgery, especially when the epileptogenic zone is estimated over eloquent area. Epilepsy patients feel difficulty not only from seizure itself. Stigma, brain dysfunction and inadequate therapy lead them to tragic life. To do the best and comprehensive medical care for epilepsy patients is important. This article introduces actual medical care facing to brain function with several epilepsy case presentations..

Papers

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1.	Shimmura M, Uehara T, Ogata K, Shigeto H, Maeda T, Sakata A, Yamasaki R, Kira JI., Higher postictal parasympathetic activity following greater ictal heart rate increase in right- than left-sided seizures., Epilepsy Behav, 10.1016/j.yebeh.2019.05.026., 97, 161-168, 2019.08, 心拍から側頭葉てんかん性活動の側在性を推定できる。.
2.	Hiroshi Shigeto, 鎌田崇嗣, Spontaneous seizures in a rat model of multiple prenatal freeze lesioning, Epilepsy Res., 10.1016/j.eplepsyres.2013.03.003, 105, 3, 280-291, 2013.08, Focal cortical dysplasia (FCD) is an important cause of intractable epilepsy. Previous rat studies have utilized freeze lesioning of neonatal animals to model FCD; however, such models are unable to demonstrate spontaneous seizures without seizure-provoking events. Therefore, we created an animal model with multiple FCD, produced during embryonic development, and observed whether spontaneous seizures occurred. Furthermore, we examined the relationship between FCD and epileptogenesis using immunohistochemistry. At 18 days postconception, a frozen metal probe was placed bilaterally on the scalps of Sprague-Dawley rat embryos through the uterus wall to produce multiple FCD. Electroencephalogram (EEG) and video recording were performed from postnatal day (P) 35 to P77. Brain tissues were examined immunohistochemically at P28 and P78 using semiquantitative densitometry. Eleven of 16 rats (68.8%) showed spontaneous seizures arising in the hippocampus from P47. Movement cessation followed by sniffing and mastication, culminating in wet-dog shaking, was seen during the hippocampal EEG discharges. FCD was observed in the bilateral frontoparietal lobes. The expression levels of N-methyl-d-aspartate receptor (NMDAR) subunits 1, 2A, 2B, the glutamate/aspartate transporter and the glial glutamate transporter 1 (GLT1) at FCD sites were increased at P28 and P78. There were no major histological abnormalities in the hippocampi compared with those in the cortex. However, the expression levels of NMDAR 2A and 2B were increased at P28. Levels of NMDAR1, 2A and 2B, the glutamate/aspartate transporter and GLT1 were also increased at P78. We created an animal model showing spontaneous seizures without a provoking event except for the existence of cortical dysplasia, and without a genetic or general systematic cause like MAM injection or irradiation. The seizures resembled human temporal lobe epilepsy both clinically and on EEG. Alterations in the levels of glutamatergic and GABAergic receptors were investigated during growth. This model should enable better clarification of the mechanisms underlying the development of human epilepsy..
3.	Yuji Kanamori, Hiroshi Shigeto, Minimum norm estimates in MEG can delineate the onset of interictal epileptic discharges: A comparison with ECoG findings, Neuroimage Clin., 2013.04.
4.	Hiroshi Shigeto, Atthaporn Boongird, Kenneth Baker, Christoph Kellinghaus, Imad Najm, Hans Lüders, Systematic study of the effects of stimulus parameters and stimulus location on afterdischarges elicited by electrical stimulation in the rat., Epilepsy research, 10.1016/j.eplepsyres.2012.10.002, 104, 1-2, 17-25, 2013.03, Electrical brain stimulation is used in a variety of clinical situations, including cortical mapping for epilepsy surgery, cortical stimulation therapy to terminate seizure activity in the cortex, and in deep brain stimulation therapy. However, the effects of stimulus parameters are not fully understood. In this study, we systematically tested the impact of various stimulation parameters on the generation of motor symptoms and afterdischarges (ADs). Focal electrical stimulation was delivered at subdural cortical, intracortical, and hippocampal sites in a rat model. The effects of stimulus parameter on the generation of motor symptoms and on the occurrence of ADs were examined. The effect of stimulus irregularity was tested using random or regular 50Hz stimulation through subdural electrodes. Hippocampal stimulation produced ADs at lower thresholds than neocortical stimulation. Hippocampal stimulation also produced significantly longer ADs. Both in hippocampal and cortical stimulation, when the total current was kept constant with changing pulse width, the threshold for motor symptom or AD was lowest between 50 and 100Hz and higher at both low and high frequencies. However, if the pulse width was fixed, the threshold did not increase above 100Hz and it apparently continued to decrease through 800Hz even if the difference did not reach statistical significance. There was no significant difference between random and regular stimulation. Overall, these results indicate that electrode location and several stimulus parameters including frequency, pulse width, and total electricity are important in electrical stimulation to produce motor symptoms and ADs..
5.	A late-onset case of nonconvulsive status epilepticus of generalized epilepsy We report a 78-year-old woman who had episodes of nonconvulsive status epilepticus (NCSE) with dizziness. At 75 years of age, she had first seizure, but was not well examined. At 78 years of age, she had brief myoclonic jerks of her arms, soon after awakening, in May. She suffered from strong dizziness and was admitted in our hospital at the end of June. The symptoms regressed with bed rest in few days and she was discharged. However, she was admitted again with dizziness in the middle of July. There were no myoclonic jerks of her arms or legs and she could converse and interact normally, but was slightly disoriented (JCS: 2). Blood test, Cerebrospinal fluid analyses and brain MRI were normal. An EEG showed frequent intermittent generalized multiple spikes and slow wave complexes and a 3-4Hz generalized spike and slow wave complexes every 2-4 seconds during whole 20 minutes record. Intravenous injection of 5mg diazepam terminated status immediately. Thereafter, she was treated with sodium valproate (400mg/day). Her symptoms improved, and interictal epileptic discharges extremely decreased. Late-onset NCSE of generalized epilepsy is rare. We discussed this case as an important case for diagnosis of NCSE with subtle symptom of dizziness. .
6.	てんかんのビデオ脳波モニタ.

Presentations

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1.	Hiroshi Shigeto, How to choose AED in newly diagnosed epilepsy, 13th Asia Oceania Epilepsy Conference, 2021.06.
2.	Mukaino T, Uehara T1, Yokoyama J, Okadome T, Sakata A, Arakawa T, Yokoyama S, Akamatsu 6, Shigeto H, Kira J-I, Time-dependent functional specialization of hippocampal subfields detected by MRI in patients with temporal lobe epilepsy, American Epilepsy Society Annual Meeting 2019, 2019.12.
3.	Hideaki Tanaka, MD; Hiroshi Shigeto, MD, PhD; Shinji Ohara, MD, PhD; Toshio Matsushima, MD, PhD; Tooru Inoue, MD, PhD; Naoki Akamatsu, MD, PhD, Predictors of postsurgical seizure relapse and post-relapse after surgery of temporal lobe epilepsy in the era of new antiepileptic drugs, 33rd International Epilepsy Congress, 2019.06, [URL], Objective: To assess prognostic factors predicting seizure recurrence after resective surgery for temporal lobe epilepsy patients who had chance to use new antiepileptic drugs (AEDs). Methods: We retrospectively investigated surgical outcomes in patients with neocortical or medial temporal lobe epilepsy who underwent temporal lobe resection between May 2014 and June 2017, and were observed for a minimum of one and half year after the surgery. To identify independent predictors for seizure relapse, we first used the univariate analysis (gender, seizure-onset age, using preoperative AEDs treatment, surgical side, pathology, etc.) to find significance differences and then used Cox’s proportional hazards analyses for multivariate analysis using results of univariate analyses. Results: A total of 41 consecutive patients were included in this study. Estimated epileptogenic zone in neocortex, existence of inter-ictal epileptiform discharges after operation, and duration of disease before surgery were significantly associated with seizure relapse, whereas preoperative treatment of new AEDs did not change the outcome: (1) Neocortical temporal lobe epilepsy compared to medial temporal lobe epilepsy (hazard ratio [HR] 0.363, 95% confidence interval [CI] 0.162-0.809; p=0.013), (2) Postoperative inter-ictal epileptiform discharges on EEG (HR 0.475, 95% CI 0.240-0.939, p=0.032), (3) Shorter duration of disease (HR 0.965, 95% CI 0.942-0.990, p=0.005). Conclusions: Our study disclosed that the patients with estimated epileptogenic zone in neocortex, postoperative inter-ictal epileptiform discharges, and shorter duration of disease before surgery are more likely to experience seizure recurrence postoperatively. Our results may be useful for selecting candidates for resective surgery in patients with temporal lobe epilepsy..

Membership in Academic Society

Japanese society of sleep research

Educational

Educational Activities

In the undergraduate teaching curriculum, lectures and practical training on neurophysiology, respiratory physiology, and cardiovascular physiology are given. For the postgraduate education, we provide guidance on research based on neurophysiology and molecular biology.

Social

Professional and Outreach Activities

Chief of the committee regarding regional and international relationship .

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