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A tapping test in which the tasks required a synchronous response to a periodic sound signal by the finger tapping was performed by 27 normal subjects and 146 patients with Parkinson's disease. Some patients could not maintain a synchronous response at a critical frequency of 2.5 or 5 Hz (taps per second) and showed a hastened tapping of 5 6 Hz, independent of the input signal frequencies, i.e., the 'hastening phenomenon.' The other patients and normal subjects could respond synchronously up to 5 7 Hz. Autocorrelational analysis of the sequential tapping intervals suggested that the synchronized response was performed by a feedback control with the input signal as target except at 2.5 and 5 Hz, whereas the hastened tapping of patients was a random process. The frequency-dependence of the error in the tapping was interpreted as representing an intrinsic oscillation in the central nervous system, which would be masked in normal subjects but released in patients with Parkinson's disease. Around 2.5 or 5 Hz the error or response becomes so large that some patients can no longer maintain the synchronized response and show a hastened tapping due to this intrinsic oscillation.

Unitary or a group of unitary responses recorded extracellularly in the rostral part of the thalamic sensory nucleus during the course of thalamotomy for parkinsonian and other kinds of tremor were studied. They were the first sensory neurons encountered in the frontocaudal approach of the stereotaxic needle to the therapeutic target at the lower border of the ventralis intermedius nucleus. The spike discharges, isolated from high neural noise background, responded to passive and/or active movement of joint or muscle on the contralateral extremity but never to light tactile stimuli. In five cases, electrical stimulation of the corresponding peripheral nerves elicited the same spike discharge at short and fixed latency of about 12 msec. Weak electrical stimulation given to each thalamic point produced paresthetic or electric sensation around the receptive field, and stronger stimulation induced tremor-like movement in the area involving the receptive field. Finally, a small coagulation lesion in this thalamic point resulted in immediate relief of tremor without any sensory deficit. From these findings, the possibility is considered that in the human, this particular thalamic zone could be the ventralis intermedius nucleus, which is separable from the surrounding nuclei and is related to tremor mechanism.

Recent medical treatment of Parkinson's disease (PA) has been focused mainly on how to compensate dopamine (DA) deficiency in the striatum efficiently by using L-DOPA with/without peripheral DOPA-decarboxylase inhibitor. Norepinephrine (NE) has been also known as lowered in parkinsonism since start of pharmacological study around 1960. Marked decrease of dopamine-~3-hydroxylase