Many poststroke patients suffer functional limitation which is associated with diminished health-related quality of life. We performed an inpatient combination protocol of these two modalities, both low-frequency repetitive transcranial magnetic stimulation (rTMS) and intensive occupational therapy (OT) for the treatment of the affected upper limb as NEURO^(R) (NovEl intervention Using Repetitive TMS and intensive Occupational therapy) . Also, we do NEURO^(R) (NovEl Intervention Using Repetitive TMS and Intensive One-to-one Training: NEURO^(R)) for aphasia, higher brain dysfunction and others. NEURO^(R) is safe and feasible. NEURO^(R) significantly improves motor function of the affected upper limb in poststroke hemiparetic patients, the recovery mechanism became clear. In case of aphasia, the scalp area for rTMS was selected based on the findings of fMRI with language tasks and the type of aphasia. The fMRI with aphasic type-based therapeutic rTMS/intensive ST for chronic aphasia seems feasible and a potentially useful neurorehabilitative protocol. The combination of pharmacotherapy and application of newly developed neuroimaging techniques may provide additional important information for improving neurorehabilitative intervention for aphasia.

  Non-invasive brain stimulation (NBS) is a technique using electrically and magnetically induced current to stimulate the cerebral cortex through the skull. This technique is attracting attention as new treatment methods in a wide range of fields include depression and stroke. Recently, this research field is expanding its application to higher brain dysfunction. To apply this technique, we have some challenges such as (ⅰ) Establishment of effective stimulation methods in various diseases and symptom of higher brain dysfunction, (ⅱ) Establishment of safety and effectiveness and (ⅲ) Establishment of effective cognitive rehabilitation combined with Repetitive Transcranial Magnetic Stimulation (rTMS) for employment and social participation in patients with higher brain dysfunction. We introduce our past research and other studies using rTMS methods, and discusse the application of rTMS for higher brain dysfunction.

  Numerous neurocognitive studies have used functional near-infrared spectroscopy (fNIRS) due to its advantages, such as portability and tolerance to participantsʼ motion-related artifacts. The present paper focuses on developmental cognitive neuroscience addressing typical and atypical brain development involving Autism spectrum disorders (ASD) based on fNIRS data. First, an fNIRS study examined differences in tactile processing between a neurotypica (lNT) group and an ASD group. Results showed that prefrontal cortical responses and heart rate changes were weaker in the ASD group than in the NT group in both Aβ-targeted and CT-targeted tactile stimulation conditions. This result suggests that individuals with ASD do not have a specific deficit in response to the CT-targeted tactile stimulus, which is closely related to social touch. Second, from our ongoing project to assess intervention effects on ASD using fNIRS, we report some preliminary results obtained from comparisons of auditory responses between pre- and post-interventions. These results suggest a potential role of fNIRS in clinical situations as well as in basic research.

  Brain-machine interface (BMI) is a technique to decode and utilize the signals from the central nervous system, or to modify the signals by interacting with the information processing. For example, BMI can be applied to control the wheel chair of a tetraplegic patient by recording the brain activity and reading the motor intention. BMI can be achieved by invasive methods such as implanting chronic electrodes in the brain, or by noninvasive methods such as electroencephalogram recording. Thanks to the accumulated knowledge in the field of neurophysiology, the technology to decode the brain signals is much advanced. However, the technology to modify the information processing of the brain by external stimulation is still in a primitive stage. If the two-way interface of reading-out and writing-into the brain makes further development, it would become possible to treat neuropsychological patients by complimenting their compromised brain function by artificial intelligence.

  I saw many atypical and interesting dementia cases during 45 years as a neurologist. This paper describes several selected cases and studies that were very important and memorable to me. Memorable rare atypical dementias included Pick-like presenile dementia with amyotrophic lateral sclerosis (ALS) at late 1970s, the first familial case of Gerstmann-Sträussler-Scheinkerʼs disease outside Europe, and the first report of neuropathologically-verified cases of parkinsonism-dementia complex (PDC) of the Kii peninsula. Clinical, neuropathological and immunohistochemical investigations included clinicopathological study on diffuse Lewy body disease, the first report of ubiquitination of Lewy bodies, a study on demented and non-demented senile brains with tau and amyloid β immunohistochemistry, drug-induced iatrogenic dementias, and comprehensive study on Kii ALS/PDC. In addition, many drug-induced dementia syndromes and intellectually excellent centenarians attracted my attention. Training on human neuropathology in the United States helped me to find and investigate new dementia diseases (ex: GSSD, Lewy body disease and PDC) in Japan. Iʼd like to thank all the patients for their cooperation, and all the collaborators for their excellent support and assistance on research.

  A clinical research study begins once a clinical problem or question arises from the examination. Clinicians do not require special tools for clinical neuropsychology research, and can therefore start with paper and pencil. Research findings may have clinical implications for the rehabilitation of the patient, and guidance for caregivers as well. In this paper, through my clinical research experience, I would like to convey the charm.

  Despite Broca difined Brocaʼs area (Brodmann area-44, 45) as the seat of articulate speech, most aphasiologists defined Brocaʼs area as the language center. Whether Brocaʼs area has articulate function is still mystery. While Wernicke difined Wernickeʼs area (posteruior part of superior temporal lobe) as the seat of auditory image of language, many aphasiologists defined Wernickeʼs area as the seat of language comprehension. The true function of Wernickeʼs area and the seat of language comprehension are still controrversial. Scince the advent of DTI, many studies reported the long association fibers including arcuate fasciculus in the humann brain. Although DTI studies can provide evidence about majour fibers, current methodological limitations do not allow pricise deliniation of the origins and terminations of these fibers. So, the connectivity of arcuate fasciculus is still controversial.

  The metaphor comprehension task was administered in 20 probable Alzheimerʼs disease patients with mild to moderate dementia (AD group) . We selected 30 low-familiarity simile sentences. For each sentence, the subjects were asked to choose one written statement that best represented its meaning from four choices (Fujimoto et al. 2016) . The scores of the task and of the Token Test (TT) were compared with those of 20 healthy elderly (elderly group) or 15 aphasic patients (aphasic group) . In addition, correlations between the scores of the task and those of the Mini-Mental State Examination (MMSE) or the Frontal Assessment Battery (FAB) were analyzed for the AD group. On the metaphor comprehension task, the AD group exhibited significantly lower scores than the control group, but the difference between the AD and the aphasic group was not significant. On the TT, the AD group exhibited significantly lower scores than the control group, but it exhibited significantly higher scores than the aphasic group.

The scores of the metaphor comprehension task in the AD group significantly correlated with the total scores of the MMSE. The scores of “attention and calculation” domain and “writing” on the MMSE and “affinity” and “word fluency” on the FAB significantly correlated with the scores of the metaphor comprehension task. The nature of disorders of metaphor comprehension in Alzheimerʼs disease may differ from those of aphasia, and deficits of executive function and semantic memory may affect such disorders.

  We report a patient with a left medial occipital infarction who showed pure alexia. She often could not read a Kana letter even after she traced the letter by her finger with complete letter form and correct stroke order. We examined this phenomenon using several tasks of Kana letter reading which contain some combinations of following stimuli；visual letter-form stimulus (written kana letter on the paper) , visual motion stimulus (visually presented motion during an examiner directs the patientʼs finger to trace the letter) , and kinesthetic motion stimulus (kinesthetic input of the motion during the passive finger tracing of letter) . She could read kana letter when only kinesthetic motion stimulus was presented (passive letter tracing with eye closure) , and also could read when visual motion and kinesthetic motion stimuli were presented (passive letter tracing on a blank sheet of paper with eye opening) . However, she often could not read kana letter when, visual letter-form, visual motion and kinesthetic motion stimuli were presented (passive tracing of a written letter on a sheet of paper with eye opening) , as well as when she actively traced the letter. These results suggest that her kinesthetic reading is disturbed because visual letter-form stimulus (a written letter) to interfere with the function of the process from kinesthetic input to letter cognition. Based on this hypothesis, we employed a therapeutic practice which encouraged retracing a letter with eye closure immediately after she failed to read with finger tracing, and obtained a positive effect for her reading disability.

  We conducted a validation study examining the clock drawing test (CDT) utilizing a video teleconference system (remote-CDT) compared to in-person testing. We also analyzed the effect of age-related hearing loss, and examined the acceptability of remote-CDT by 5-point Likert scale. A total of 77 subjects (normal elderly controls［NC］, 38；mild cognitive impairment［MCI］, 15；patients with Alzheimerʼs disease［AD］, 24) participated in the study. Each participant went through CDT twice, i.e. remote-CDT and in-person CDT in random order. Based on all subjects, the interclass correlation coefficient (ICC) of the two testing sessions was ≥ 0.83. When analyzing each diagnosis group separately, ICCs were ≥ 0.67 for the NC group, ≥ 0.59 for the MCI group, and ≥ 0.84 for the AD group, respectively showing sufficient concordance. Moreover, ICCs were ≥ 0.81 for both subgroups that conducted in-person or remote-CDT first, indicating no impact on the scores by testing order. Among the subjects with suspected hearing impairment, ICC was ≥ 0.91, which indicated a high level of concordance. Based on a questionnaire, 70% of the subjects felt slight fear and nervousness during the test, and 70% of the subjects felt that the remote-CDT was as easy to answer or even easier to answer compared to in-person testing；these figures indicate that remote-CDT was not rejected by the participants.

  Perseveration is frequently observed in aphasic patients and it can be an obstruction for aphasic evaluations and rehabilitations. In this study, we employed a one-month training program to reduce perseveration for an aphasic patient who showed perseverations as a main complaint throughout the 6-month conventional aphasic therapies. The training program was made based on the error-control method of the Treatment of Aphasic Perseveration (TAP) . Additionally, we studied the underlying mechanism for the recovery of perseverations by qualitative analysis of perseverative errors during the TAP program. As a result, the perseveration had been remarkably reduced and naming scores had been improved even in the un-trained word-set. Furthermore, the word-expressive function in daily life had also been improved after training. That is to say, the effect of the training had generalized in every day life. Also, qualitative analysis of perseverative errors showed that TAP program had effect on reducing immediate type of perseveration.