Program

Executive Summary：
Takenobu Murakami is a neurologist in the Tottori University Hospital, Japan. He graduated from the Faculty of Medicine, Tottori University in 2002, and he received medical training related to internal medicine and neurology for several years. He was conferred Ph.D. (medicine) in the Graduate School, Tottori University in 2008 and moved to the Johann Wolfgang Goethe-University, Germany (Prof. Ulf Ziemann’s lab) as a postdoctoral research fellow of the Alexander von Humboldt foundation. He worked with the dearest Taiwanese friend, Prof. Ming-Kuei Lu, there. In 2012, he returned to Japan and joined Prof. Yoshikazu Ugawa’s lab in the Fukushima Medical University, and then he has been a staff physician in Prof. Ritsuko Hanajima’s lab in the Tottori University since 2021.
His research interest is to unveil human brain function neurophysiologically or pathophysiologically by combining TMS and neuroimaging methods (e.g. MRI, PET etc.). He has currently focused on synaptic plasticity impairment in patients with mild cognitive declines underlying Alzheimer’s disease pathology. In addition, he has conducted a new challenge to enhance neurorehabilitation effects of the brain-machine interface using TMS. He has also continued great educational contributions to the international young doctors in clinical and research aspects. He would like to have chances to interact with a lot of doctors and researchers in the Asian and Oceanian countries.

Lecture Abstract：
Alzheimer’s disease (AD) has been known as the most prevalent dementing disorder, and the number of patients has dramatically increased in hyper-aging societies. Recently, strategy of AD diagnosis has shifted from clinical-based to biomarker-based focusing on the specific pathological features, e.g. amyloid-beta and phosphorylated tau proteins. The biomarker-based diagnosis is helpful to find patients at early stage or even preclinical condition.
Neurophysiological approach is also available to detect abnormalities of neural functions associated with cognitive decline. Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique extensively used in the field of clinical neurophysiology. Several TMS parameters can unveil unique functional features of dementing disorders. For example, short-latency afferent inhibition, which can evaluate the central cholinergic function, decreases in AD and dementia with Lewy bodies but not frontotemporal dementia. A novel technique combining TMS with electroencephalogram allows the evaluation of functional brain networks. Neural activity propagation from precuneus to frontal lobe is disrupted in patients with AD. The long-term potentiation (LTP)-like synaptic plasticity induced by quadripulse stimulation is impaired in patients having AD pathology, and its severity correlates with degrees of cognitive declines, AD-related biomarkers including amyloid-beta 42 in the cerebrospinal fluid and amyloid accumulation in precuneus detected by amyloid positron emission tomography.
In conclusion, TMS holds significant promise as a useful tool for understanding the pathophysiology of AD from the aspects of synaptic function and neural network.

Executive Summary：
Dr. Yi-Jen Wu is a neurologist and neurophysiologist specializing in epilepsy, cortical excitability, and non-invasive neuromodulation. Her research focuses on how weak direct currents modulate brain function, with implications for seizure control and cognitive recovery. She has led both animal and clinical studies investigating brain oscillations, hippocampal neurogenesis, and electrophysiological biomarkers of seizure disorders, while exploring the neurophysiological mechanisms of neuromodulation techniques including transcranial direct current stimulation (tDCS), vagus nerve stimulation (VNS), and focused ultrasound.
Her work has been published in leading journals such as the Journal of Physiology, Brain Stimulation, Journal of Neuroscience, and Neuropharmacology. She also holds a patent for detecting high-density polymorphic epileptic spikes and has contributed as a chapter author to Taiwan’s foundational textbook on non-invasive brain stimulation.
Dr. Wu is actively involved in academic societies, serving on the boards and committees of the Taiwan Society of Clinical Neurophysiology, the Taiwan Neurological Society, and the Taiwan Epilepsy Society. Her work exemplifies the integration of clinical neurophysiology with translational neuroscience, advancing therapeutic strategies for epilepsy and brain disorders characterized by hyperexcitability.

Lecture Abstract：
Alzheimer’s disease (AD) is increasingly recognized not only as a
neurodegenerative disease but also as a disorder of network hyperexcitability.
This arises from impaired inhibitory–excitatory balance, driven by dysfunction
of interneurons, pyramidal cells, astrocytes, and synaptic property in
association with amyloid-β and tau pathology.
EEG and local field potential studies reveal characteristic signatures:
background slowing, increased delta/theta power, reduced alpha/beta power,
pathological high-frequency oscillations (ripples, fast ripples), and disrupted
gamma synchrony essential for cognition. These abnormalities can precede
dementia by years, particularly in mild cognitive impairment or in patients with
subclinical epileptiform discharges. They are associated with memory decline,
altered sleep physiology, and disease progression. The presence of
epileptiform discharge defines a subgroup of AD with elevated seizure risk,
underscoring the bidirectional AD–epilepsy relationship.
Clinical neurophysiological tools including quantitative EEG, event-related
oscillations/potentials, and combined TMS- or tACS-EEG, allow precise
measurement of these network dynamics. Beyond pharmacology, therapeutic
strategies emerge including anti-seizure medications and non-invasive
neuromodulation (TMS, tACS, gamma sensory stimulation) to entrain
physiological rhythms. Experimental phase-dependent closed-loop deep brain
stimulation modulates hippocampal theta oscillations in animal models, with
potential implications to enhance memory circuits.
This talk will present recent advances in neural oscillatory biomarkers in
AD, the underlying mechanisms, and rhythm-based interventions with
potential to alter disease progression.

Executive Summary：
Dr. Ming-Kai Pan is an Associate Professor at the Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan. He is currently running the Cerebellar Research Center at National Taiwan University Hospital and is the deputy director of the Molecular Imaging Center at National Taiwan University. He is currently leading several national grants in the Brain Technology Project in Taiwan and a cerebellar deep-learning project supported by Nvidia.
He is a movement disorder specialist with a dual focus on cerebellar motor and cognitive control and their related disorders. His work has significantly advanced our understanding of the pathophysiology of essential tremor, the most common movement disorder, and has unraveled how the cerebellum controls the detailed motor kinematics via frequency coding, and provided a unifying theory explaining normal motor control, tremors and ataxias.
In his lab, Dr. Pan drives innovation by employing cutting-edge neural dynamic technologies, bridging clinical neurology with basic neuroscience. His expertise spans cerebellar electroencephalography with dynamic spatial mapping, intraoperative cerebellar recordings, and advanced mouse-based methodologies, including tissue clearing, optogenetics, fiber photometry, calcium imaging, optical coherence tomography, and electrophysiology.
Additionally, he has made significant contributions to bioengineering, particularly in the development of novel motion-tracking technologies and volumetric super-speed microscopy.
Dr. Pan's research has been published in leading journals, including Nature Biomedical Engineering, Science Translational Medicine, Journal of Clinical Investigation, Bioengineering & Translational Medicine, Science Advances, Advanced Science, PNAS, and Acta Neuropathologica, reflecting his impact on both medical and neural dynamic advancements.

Lecture Abstract：
Cerebellar ataxia is a group of genetic and non-genetic disorders that share the core symptom of involuntary movement with dysrhythmia (loss of rhythm) and imprecision. This talk will briefly describe the common pathophysiology of neural dynamic deficits directly causing dysrhythmia and imprecision. By investigating cerebellar pathology in patients with spinocerebellar ataxia (SCA) type 1, 2, 6, and Multiple system atrophy (MSA), we found that early denervation of cerebellar climbing fibers (CFs) is a shared pathophysiology across all SCA patients. Optogenetic silencing CFs in healthy mice sufficiently induced both dysrhythmia and imprecise motion. Compatible with the motor rhythm loss, these optogenetically-induced ataxic mice developed cerebellar rhythm loss. The mouse results led to the discovery of cerebellar rhythm loss as a common pathophysiology of cerebellar ataxic patients, and the degree of rhythm loss is compatible with the severity of symptoms. Notably, PC loss alone did not cause dysrhythmia; it only caused motor imprecision. This observation opens a potential therapeutic window of CF-based therapy for dysrhythmic and imprecision in motion. Using chemogenetic stimulation to enhance CF activities, SCA1 mice showed improved motor performance. In summary, CF-dependent cerebellar rhythm loss contributes to dysrhythmia and imprecision of motion, the core features defined as ataxia. In a preclinical mouse study, CF-based therapy supported a potential therapeutic opportunity shared in a wide range of ataxic syndromes.

Executive Summary：
Dr. Sung-Pin, Fan is currently the attending physician in Department of Neurology, National Taiwan University Hospital. He received comprehensive Neurology training in Neurology Department of National Taiwan University Hospital. Dr. Fan retrieved his master’s degree in Institute of Clinical Medicine of National Taiwan University. His research interests focused on Parkinson’s disease, Wilson’s disease and their neuroimage, serum biomarkers, as well as the application of machine learning in the field. He is also interested in the application of Quantitative Susceptibility Mapping on neurodegeneration disease. Dr. Fan has published articles in exploration of the clinical features and neuroimage biomarkers on domestic Wilson’s disease population.

Lecture Abstract：
Wilson's disease (WD) is a rare autosomal recessive hereditary disorder. The dysfunction of ATP7B protein induces the dysfunction of metabolism to cellular copper, which causes deposition of copper in multiple organs. Hepatic and central nervous system are the major organ systems involved in the disease population. However, there is high variability to the disease presentations and its severity. The variation is not only displayed among different ethnicity but also within the family. The interaction between the genotype and the clinical presentation is still under a lot of discussion.
Because of the variability of WD patients, development of biomarkers to monitor or predict the disease is a critical issue to the diseased population. Aside from the traditional serum copper biomarkers, neuroinflammatory markers, neuroimage markers and other image markers have being proposed to be the potential choice in monitoring the disease. However, the alteration of electrophysiology has usually been lacking of discussion.
In this topic, we will go through the current understanding and development in the research in the field of WD. We will also review about the electrophysiology features and the potential as biomarkers in displaying the progression or severity of WD.

Executive Summary：
John Rothwell is currently Emeritus Professor of Human Neurophysiology at UCL Queen Square Institute of Neurology. His work has focused on developing novel non-invasive methods to probe the central control of movement in health and disease, particularly in the field of movement disorders and stroke. Studies in his group provided the theoretical rationale and methodological developments underpinning the use of transcranial magnetic stimulation (TMS). They have revealed some of the details of how TMS interacts with ongoing brain activity, and have been used to devise techniques to probe synaptic connections between brain areas that are now used as biomarkers in neurological disease and movement disorders. The work has also pioneered methods of repetitive stimulation that modulate synaptic plasticity and opened up new therapeutic opportunities in neurology and psychiatry.

Lecture Abstract：
Bradykinesia and rigidity are two of the cardinal features of Parkinson’s disease. An important contributor to bradykinesia is thought to be tonic levels of dopamine in the basal ganglia, which regulate the coupling between motivation to move and the final movement speed. Low levels in Parkinson’s disease are associated with a reduced output speed. The relationship between this and high levels of beta synchronisation, which are also characteristic of the bradykinetic state is currently unclear. In contrast to bradykinesia there are relatively few studies on the pathophysiology of rigidity. Although there may be minor changes in muscle properties, and difficulties in obtaining complete relaxation in patients, rigidity is due mainly to aberrant reflex contraction produced by muscle stretch. However, the precise pathways responsible for this are still unclear. I will discuss the possible involvement of transcortical pathways, spinal reflexes or brainstem/cerebellar pathways.

Executive Summary：
Ritsuko Hanajima has studied neurophysiology of movement disorders, mainly using TMS. She received PhD from the University of Tokyo in 1999. From 2001 to 2003. she studied in Toronto Western Hospital. From 2003, she worked at the University of Tokyo. In 2017, she became a Director and Professor of Division of Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University. She is an executive committee member of Japanese Society of Neurology, an executive committee member of Japanese Society of Clinical Neurophysiology, President of Japanese Movement Disorder Society.

Lecture Abstract：
Parkinson’s disease (PD) is a neurodegenerative disorder classically considered to be produced by dopamine deficiency due to nigral degeneration. The Parkinsonian motor symptoms, such as bradykinesia or rigidity, are generated by disfunctions of the cortico-basal ganglia loops due to dopamine deficiency. Transcranial magnetic stimulation (TMS) techniques can detect the final motor cortical (M1) abnormalities in PD, some of which may be used as a biomarker of PD.
1. Single pulse TMS: The motor threshold is abnormally larger, the silent period after TMS is shorter, but central motor conduction time is normal.
2. Paired stimulation TMS: Cortical excitability abnormalities probably due to the dysfunction of the cortico-basal ganglia loops can be detected by several paired pulse TMS techniques, such as short interval intracortical inhibition (SICI), intracortical facilitation (ICF), short interval intracortical facilitation (SICF), sensory afferent inhibition (SAI), and inter-hemispheric inhibition (IHI). The most frequently used SICI could reflect GABAergic function of M1. The degree of SICI reduction can be used as a biomarker of PD pathology.
3. Background oscillatory abnormality of M1 is another neurophysiological parameter of PD. Local field potentials recorded from the basal ganglia or cortex showed abnormally enhanced beta rhythms in PD. These abnormal oscillations can be detected by EEG or MEG.
4. Abnormal synaptic plasticity, long-term potentiation and depression (LTP/LTD), is another biomarker of PD. The plasticity reduction at the striatum or M1 was reported in animal PD models, and they were restored by L-dopa. On the other hand, synaptic over function, lack of depotentiation, related with dyskinesia. The same findings are shown in PD patients using repetitive TMS methods, especially with quadripluse stimulation (QPS).
In this symposium, I would present several above-mentioned findings.