Nobuo Miyashita

Effects of caudate nucleus stimulation on substantia nigra cell activity in monkey

The present study provides evidence that the saccadic signals in the caudate nucleus (caudate) are transmitted to the substantia nigra pars reticulata (SNr). We inserted two microelectrodes into the caudate and SNr of monkeys trained to perform saccade tasks. After identifying the functional characteristics of a SNr neuron recorded, we stimulated the caudate (single pulse, <100 μA) to see whether its discharge rate changed. Among 138 SNr cells tested, 60 showed responses to stimulation of the caudate: inhibition only (n=21), inhibition-excitation (n=17), excitation only (n=9), and excitation-inhibition (n=13). The latencies were 9.0–32.5 ms (mean 16.7 ms) for the initial inhibitory responses and 6.5–35.0 ms (mean 16.7 ms) for the initial excitatory responses. Pars compacta cells (n=10) were unresponsive. The effect of caudate stimulation was selective in terms of (1) functional type of SNr cells, (2) location of SNr cells, and (3) stimulation site within the caudate. Functional type of SNr cells: saccadic, visual, expectation-related cells were more responsive than auditory, mouth/hand/ arm movement-related, and reward-related cells. Many of the cells whose functional characteristics were unidentified responded to the caudate stimulation. The preferential effects were seen among the functional subtypes: cells related to memory-guided saccades, not visually guided saccades; cells with conditioned visual responses, not simple visual responses. Location of SNr cells: the stimulus effects were seen preferentially in cells in the central part of the SNr, not in the dorsal part. Stimulus site: stronger effects, whether inhibition or excitation, were obtained when the stimulation was applied to the head-body transitional zone where visuooculomotor cells were clustered. Behaviorally contingent correlation of spike activity was found between the caudate-nigral pair of cells. For example when a SNr cell with memorycontingent saccadic activity was inhibited by the caudate stimulation, a caudate cell at or close to the stimulation site may show memory-contingent saccadic activity with a similar movement field.

Minimal synaptic delay in the saccadic output pathway of the superior colliculus studied in awake monkey.

The synaptic organization of the saccade-related neuronal circuit between the superior colliculus (SC) and the brainstem saccade generator was examined in an awake monkey using a saccadic, midflight electrical-stimulation method. When microstimulation (50–100 μA, single pulse) was applied to the SC during a saccade, a small, conjugate contraversive eye movement was evoked with latencies much shorter than those obtained by conventional stimulation. Our results may be explained by the tonic inhibition of premotor burst neurons (BNs) by omnipause neurons that ceases during saccades to allow BNs to burst. Thus, during saccades, signals originating from the SC can be transmitted to motoneurons and seen in the saccade trajectory. Based on this hypothesis, we estimated the number of synapses intervening between the SC and motoneurons by applying midflight stimulation to the SC, the BN area, and the abducens nucleus. Eye position signals were electronically differentiated to produce eye velocity to aid in detecting small changes. The mean latencies of the stimulus-evoked eye movements were: 7.9±1.0 ms (SD; ipsilateral eye) and 7.8±0.9 ms (SD; contralateral eye) for SC stimulation; 4.8±0.5 ms (SD; ipsilateral eye) and 5.1±0.7 ms (SD; contralateral eye) for BN stimulation; and 3.6±0.4 ms (SD; ipsilateral eye) and 5.2±0.8 ms (SD; contralateral eye) for abducens nucleus stimulation. The time difference between SC- and BN-evoked eye movements (about 3 ms) was consistent with a disynaptic connection from the SC to the premotor BNs.

Visual hemineglect induced by unilateral striatal dopamine deficiency in monkeys

Unilateral dopamine deficiency of the basal ganglia produced a profound impairment of visual search. Dopaminergic innervation of the monkey striatum was deprived unilaterally by infusing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) into the caudate nucleus. The monkeys were shown a mirror in which they saw their own image and surroundings. Compared with the concentric and symmetrical distribution of visual search before MPTP infusion, the gaze after MPTP infusion was confined and sometimes frozen in peripheral regions in the hemispace ipsilateral to the infusion; the contralateral side was largely neglected. An experiment using a choice saccade task indicated that the contralateral visual signal, which alone was processed normally, was suppressed by the ipsilateral signal.

Contrasting genotypes of the tau gene in two phenotypically distinct patients with P301L mutation of frontotemporal dementia and parkinsonism linked to chromosome 17

Abstract. Association between clinical characteristics and types of the tau gene mutation has been observed in frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). P301L mutation seldom causes parkinsonism as a leading symptom; instead it usually causes personality changes with aggressiveness and disinhibition. We experienced two patients of FTDP-17 from separate families (designated as patient 1 from family 1 and patient 2 from family 2). They had P301L mutation in common. However, their phenotypes were distinct from each other. Aggressive behaviors and disinhibition were the main symptoms in patient 1, whereas parkinsonism was the most prominent feature in patient 2. Their genotypes of the tau gene were different at three sites, i. e. in exon 6, in intron segment before exon 10, and in exon 13, though they do not bring amino acid change. Patient 1 had more prevalent C/C, C/C, and rare T/C respectively. Patient 2 had less prevalent T/T, A/A, and more prevalent T/T respectively. These findings suggest two things. Firstly, they do not share a common founder for P301L mutation. Secondly, either of the two less prevalent genotypes observed in patient 2 may be the factor to modify the phenotype of P301L mutation into those unusual clinical features with prominent parkinsonism. Accumulation of information as to phenotype-genotype association will settle this hypothesis.

Presaccadic omnidirectional burst activity in the basal interstitial nucleus in the monkey cerebellum

Abstract We recorded saccade-related neurons in the vicinity of the dentate nucleus of the cerebellum in two monkeys trained to perform visually guided saccades and memory-guided saccades. Among 76 saccade-related neurons, 38 showed presaccadic bursts in all directions. More than 80% of such burst neurons were located in the area ventral to, not inside, the dentate nucleus, which corresponded to the basal interstitial nucleus (BIN as previously described). We found that the activity of the BIN neurons was correlated with saccade duration but not with saccade amplitude or velocity. Thus, when tested with visually guided saccades, the burst started about 16 ms before saccade onset and ended about 33 ms before saccade offset, regardless of saccade amplitude. The characteristic timing of the BIN cell activity was maintained for different types of saccades (visually guided, memory-guided and spontaneous saccades), which had different dynamics. Although the number of spikes in a burst for each neuron was linearly correlated with saccade amplitude for a given type of saccade, the slope varied depending on the type of saccade. Peak burst frequency was uncorrelated with saccadic peak velocity. In contrast, burst duration was highly correlated with saccade duration regardless of the type of saccade. These results suggest that BIN neurons may carry information to determine the timing of saccades.

Monoataxia of upper extremity in motor cortical infarction

Recent studies using functional imaging have demonstrated that the anatomic location of the primary motor hand area is topographically localized in a specific segment of the precentral gyrus. MRI reveals that such cortical area protrudes posterolaterally from the precentral gyrus to the central sulcus, thus forming a characteristic knoblike shape similar to that of an inverted omega or epsilon in the axial plane.1 Lesions in the precentral knob cause isolated motor weakness or clumsiness of the corresponding hand.2 Recently, we encountered two patients who presented with ataxia after a cerebral infarction that selectively involved the motor cortex located at the medial part of the precentral knob. ### Patient 1. A 69-year-old right-handed-man with a history of hypertension and diabetes mellitus was admitted because of sudden difficulties in voluntary movement in his upper left limb. On neurologic examination, he was alert and oriented and there was no sensory extinction. Cranial nerves were all intact. There was no weakness in …

Eyelid motor extinction

Sirs: The inability to close the eyes voluntarily is known as “apraxia” of eye closure, although it remains uncertain whether this phenomenon is true apraxia [1]. Recently we encountered a man with a right anterior cerebral artery infarction who developed a distinct disorder of the eyelid motor control. He could not close his left eye when asked to close both eyes voluntarily, although he was able to close them involuntarily or reflexively. The 56-year-old diabetic man was admitted after a sudden onset of weakness of the left upper and lower limb muscles. On admission, he was awake but apathetic. Left motor hemiparesis was present, and the muscles of the left lower extremity and proximal part of the left upper extremities were predominantly involved. The plantar response was extensor in the left side. Grasp reflex was marked in the left hand. Computed tomography and magnetic resonance imaging of the brain showed a large infarction on the right anterior cerebral artery territory (Fig. 1A, B). A few days later a characteristic disorder of eyelid control was observed. The patient was unable close both eyes together, although he was able to blink or close both eyes reflexively while sleeping, yawning or responding to invasive stimuli (Fig. 1C, D). When he was requested to close or wink either eye, he could close only his right eye, not his left eye. He could keep his eyes closed when his eyelids were closed passively. He could keep his mouth open, or keep fixation of his gaze for at least 10 s, thus suggesting that he had no motor impersistence. Two weeks later he became able to close his left eye voluntarily but was still unable to close both eyes simultaneously when requested. After another 3–4 weeks the weakness in the limb muscles had gradually improved, and his difficulty in closing both eyes voluntary also disappeared simultaneously. His disorder of eyelid control was characteristic of unilateral apraxia of eye closure, but it should not be interpreted as the disorder itself because unilateral apraxia of eye closure involves the inability to close one eye voluntarily, sparing ability to close both eyes simultaneously [2]. The present patient could after some time voluntarily close either eye and could reflexly or involuntarily close both eyes together, but he could not simultaneously close both eyes when requested to do so. Therefore his symptom is not paretic but may be apraxic. Currently the pathophysiological mechanisms underlying apraxia of eye closure are speculated to be closely related to those of eyelid motor impersistence, since it has been reported that patients with apraxia of eye closure later are unable to maintain the eyes closed, i. e. eyelid motor impersistence [1, 3–6]. However, his symptom is not likely to be an atypical presentation of motor impersistence since he had never shown any motor impersistence during the course of his illness. InLETTER TO THE EDITORS

Retrograde Axonal Transport of MPTP after Unilateral Caudate Nucleus Infusion in the Monkey

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) elicits selective destruction of nigrostriatal dopamine neurons in human and non-human primates along with clinical symptoms of Parkinson’s disease (Langston et al., 1983; Burns et al., 1983). Systemically administered MPTP is biotransformed into 1-methyl-4-phenylpyridium ion (MPP+), which then enters dopaminergic neurons via the dopamine uptake system to destroy nigral cells.