Toshihide Harada

Role of human SII cortices in sensorimotor integration

OBJECTIVES To elucidate the functional properties of neurons in the human primary (SI) and ipsilateral and contralateral secondary (iSII or cSII) cortices in response to stimuli during finger movement. METHODS We measured somatosensory evoked fields (SEFs) produced by electric stimuli delivered to the median nerve at 0.2 Hz in 6 healthy subjects. RESULTS The amplitudes of evoked fields from both iSII and cSII were gradually attenuated with time. Consecutive blocks of trials were obtained to assess the habituation of each evoked field. Complex finger movements with attention (gating session) increased the amplitude of evoked fields from the iSII cortices but reduced the amplitudes of evoked fields from the cSII cortices (P<0.01). In contrast, the amplitude of P30 m from the SI did not show habituation effects but decreased significantly in the gating session (P<0.01). CONCLUSIONS The enhanced iSII as well as suppressed cSII cortices during complex finger movements with attention are not only considered to be result of gating effect but also attention.

Clinical features of malignant syndrome in Parkinson's disease and related neurological disorders

INTRODUCTION We elucidated the cause and clinical characteristics of malignant syndrome (MS) in patients with Parkinsons disease (PD), early-onset parkinsonism (EOP), and other neurological disorders. MATERIALS AND METHODS Subjects were 260 patients with PD or EOP, and three patients with other neurological disorders associated with MS. We studied clinical symptoms before and after the onset of MS, and evaluated autonomic function particularly before the onset of MS. RESULTS The overall incidence of MS accompanying PD and EOP in our department was eight of 260 patients (3.1%). The incidence of MS in EOP was significantly higher than that in PD. All patients with MS showed comparatively longer duration of illness and advanced stage of PD and EOP. Factors triggering MS included reduced dosage or discontinuation of anti-parkinsonian drugs, reduction of oral intake, dehydration, infectious disease, postoperative state, and treatment with major tranquilizers. Although patients demonstrated marked autonomic symptoms at the onset of MS, in many cases autonomic dysfunction developed before the onset of MS. Even EOP patients, who usually demonstrated milder autonomic dysfunction, showed abnormalities in the correlation between circadian rhythm of blood pressure and pulse rate, and/or abnormal gastric emptying test, suggesting that autonomic dysfunction plays an important role in the cause of MS. Cooling the body, fluid replacement, resumption or increasing the dosage of anti-parkinsonian drugs and administration of dantrolene sodium overcame MS in all cases. CONCLUSION Autonomic dysfunction is related to the cause and clinical features of MS in PD, EOP and some other neurological disorders.

An abnormal relationship between blood pressure and pulse rate in amyotrophic ateral sclerosis

Objectives ‐ To clarify the autonomic dysfunctions in amyotrophic lateral sclerosis (ALS) patients, we investigated the relationship between blood pressure (BP) and pulse rate (PR), QTc interval, and coefficient of variation in the R‐R interval (CVR‐R) in ALS patients. Materials and methods ‐ BP and PR were determined automatically every 30 min for 24 h in 6 patients with ALS and in 18 healthy age‐matched volunteers. The QTc interval and CVR‐R were also evaluated using an electrocardiogram. Results ‐ The relationship between BP and PR was lost in the ALS group. There was no significant difference in the QTc interval or CVR‐R between the ALS and control groups. Conclusion ‐ We speculate that the imbalance between BP and PR observed in the ALS group reflects a disorder in the balance between the sympathetic and parasympathetic nervous systems.

Autonomic dysfunction in Parkinson's disease and vascular parkinsonism

Objectives ‐ To clarify the autonomic dysfunction in idiopathic Parkinsons disease (PD) and vascular parkinsonism (VP), we investigated the relationship between blood pressure (BP) and pulse rate (PR), the standing test, and the coefficient of variation in the R‐R interval (CVR‐R). Materials and methods ‐ BP and PR were determined automatically every 30 min for 24 h in 15 PD patients, 15 VP patients and 15 healthy volunteers. The CVR‐R values evaluated by an electrocardiogram and the standing test were also performed. Results ‐ The BP‐PR relationship was lost in the patient groups. There was no significant difference in the standing test between the control and patient groups. A significantly decreased CVR‐R was observed in the VP group. Conclusion ‐ We speculate that our results may reflect an imbalance between the sympathetic and parasympathetic nervous systems in PD and VP.

Effects of movement on somatosensory N20m fields and high-frequency oscillations.

Somatosensory evoked fields were recorded to determine the effects of movement and attention on high-frequency oscillations during active finger movements of the ipsilateral and contralateral sides in response to electrical stimulation of the median nerve. A whole-scalp neuromagnetometer was used to record somatosensory evoked fields from eight subjects following electric median nerve stimulation at the wrist. The following three sessions were performed: (1) rest, (2) movement of fingers on the ipsilateral in response to stimulation and (3) movement of fingers on the contralateral in response to stimulation. The somatosensory evoked fields with a wide-bandpass (0.1–1000 Hz) were recorded. High-frequency oscillations and N20m were separated by subsequent high-pass (> 300 Hz) and low-pass (< 300 Hz) filtering. The maximum amplitude of high-frequency oscillations decreased during finger movements accompanying a decrease in somatosensory N20m dipole strength. Activation of the motor cortex appeared to suppress both the amplitude of high-frequency oscillations and the N20m dipole strength.

Assessment of cardiovascular autonomic dysfunction in multiple system atrophy

Because heart rate is controlled mainly by the autonomic nervous system, cardiovascular autonimic dysfunction may contribute to the prognosis of patients with multiple system atrophy (MSA). To clarify cardiovascular autonomic dysfunctions in MSA, the authors investigated the relation between blood pressure (BP) and pulse rate (PR), and assessed a power spectral analysis of heart rate variability (HRV) during the clinical course using ambulatory BP and a heart rate monitor for 24 hours. The authors studied seven patients with MSA (five men and two women, aged 61.0±5.8 years) and seven healthy volunteers (four men and three women, aged 58.0±6.6 years) without hypertension, heart disease, or intracranial lesions. The MSA group showed abnormal circadian variations of BP and PR and a significantly decreased correlation coefficient between BP and PR. A significant decrease and altered circadian variation also existed in the number of changes in successive R-R intervals greater than 50 msec (RR50) and in the power of the high- and low-frequency component of HRV. The authors observed a significant negative correlation between the duration of illness and the number of changes in successive R-R intervals greater than 50 msec. The characteristic dysautonomia in MSA was a decrease in sympathetic and parasympathetic activity, with an abnormal circadian rhythm of BP and HRV. The balance between sympathetic and parasympathetic activity was also impaired. The parasympathetic modulation represented by RR50 worsened according to the development of the illness. Those autonomic dysfunctions may have affected the cardiovascular systems, which may indicate a poor prognosis in patients with MSA. An analysis of HRV and the circadian rhythm of BP and HRV are useful in evaluating cardiac autonomic dysfunctions in MSA.

QTc interval, and autonomic and somatic nerve function in diabetic neuropathy.

QTc intervals were measured using an electrocardiogram and other autonomic function tests, in 66 neuropathy patients with non-insulin-dependent diabetes mellitus (59.0±12.5 years; mean ± SD). The change in R-R interval did not influence the QTc interval, as calculated by the equation: QTc =QT+(1000-R-R)/7 (ms), compared with the conventional Bazetts equation which appeared to overcompensate in the case of a small R-R interval. The QTc interval in the diabetic patients was significantly longer than that in age-matched controls. The QTc interval showed an inverse correlation with the coefficient of variation of the R-R interval and skin blood flow at rest. However, no correlation was found between QTc interval and blood pressure change, change in heart rate on standing, or results of the sympathetic skin response. The QTc interval did not correlate significantly with motor or sensory nerve conduction parameters. We conclude that the QTc interval can be a simple and useful autonomic indicator for diabetic neuropathy relatively independent of other abnormalities of autonomic and somatic nervous system function. Clin Auton Res 8:139–143

Genetic and clinical studies of japanese patients with familial amyloid polyneuropathy

We examined the DNA analysis of familial amyloid polyneuropathy (FAP) patients and their families from Nagano and Hiroshima prefectures in Japan using recombinant DNA techniques and compared the results with the clinical features. This study indicated that the valine-methionine change prealbumin gene was closely related to the clinical features of type 1 FAP. The DNA analysis was valuable for the definite diagnosis of type 1 FAP even in sporadic and asymptomatic cases. FAP patients from Iiyama city and Ogawa village area in the Nagano prefecture had the same mutation despite differences in clinical features. The onset of the sporadic FAP cases was later than that of the FAP patients who had family histories.

Difference in somatosensory evoked fields elicited by mechanical and electrical stimulations: Elucidation of the human homunculus by a noninvasive method.

We recently recorded somatosensory evoked fields (SEFs) elicited by compressing the glabrous skin of the finger and decompressing it by using a photosensor trigger. In that study, the equivalent current dipoles (ECDs) for these evoked fields appeared to be physiologically similar to the ECDs of P30m in median nerve stimulation. We sought to determine the relations of evoked fields elicited by mechanically stimulating the glabrous skin of the great toe and those of electrically produced P40m. We studied SEFs elicited by mechanical and electrical stimulations from the median and tibial nerves. The orientations of dipoles from the mechanical stimulations were from anterior‐to‐posterior, similar to the orientations of dipoles for P30m. The direction of the dipole around the peak of N20m from median nerve electrical stimulation was opposite to these directions. The orientations of dipoles around the peak of P40m by tibial nerve stimulation were transverse, whereas those by the compression and decompression stimulation of the toe were directed from anterior‐to‐posterior. The concordance of the orientations in ECDs for evoked fields elicited by mechanical and electrical stimulations suggests that the ECDs of P40m are physiologically similar to those of P30m but not to those of N20m. The discrepancy in orientations in ECDs for evoked field elicited by these stimulations in the lower extremity suggests that electrical and compression stimulations elicit evoked fields responding to fast surface rubbing stimuli and/or stimuli to the muscle and joint. Hum. Brain Mapping 24:274–283, 2005.

Human reactions to physical stimulus and the removal of such stimulus as recorded by magnetoencephalography

We studied the cortical evoked fields elicited by the examiners touch on glabrous skin of the subjects index finger. Two main components of evoked fields were elicited, and these dipoles were located in the primary somatosensory cortex contralateral to the side of the subjects index finger touched by the examiner. When the timing of removal of the examiners finger triggered the data acquisition using the photosensor, the strength of the dipole from early evoked fields was stronger than that from late ones. We showed that these evoked fields were elicited by removal and touch of the examiners finger respectively in response to the mechanical compression and decompression of the skin.