Neurosurgical treatment of Parkinson's disease (PD) frequently employs chronic high-frequency deep brain stimulation (DBS) within the internal segment of globus pallidus (GPi) and can very effectively reduce L-dopa-induced dyskinesias and bradykinesia, but the mechanisms are unknown. The present study examined the effects of microstimulation in GPi on the activity of neurons close to the stimulation site. Recordings were made from GPi using two fixed or independently controlled microelectrodes, with the electrode tips usually approximately 250 or >600 micrometer apart in PD patients undergoing stereotactic exploration to localize the optimal site for placement of a lesion or DBS electrode. The spontaneous activity of nearly all of the cells (22/23) recorded in GPi in three patients was inhibited by microstimulation at currents typically <10 microA (0.15-ms pulses at 5 Hz). The inhibition had a duration of 10-25 ms at threshold. These findings suggest that microstimulation within GPi preferentially excites the axon terminals of striatal and/or external pallidal neurons causing release of GABA and inhibition of GPi neurons.

Although cells firing at tremor frequency, called "tremor cells" (Guiot et al., 1962), have often been recorded in the thalamus of parkinsonian patients, the extent of correlation between these spike trains and tremor has rarely been assessed quantitatively. This paper describes spectral cross-correlation functions calculated between the activity of "tremor cells" and electromyogram (EMG) signals recorded from several muscles in the contralateral arm. The power occurring in the spike train at tremor frequency was described in absolute terms by the spike autopower, and in relation to the average for all spectral components by the spike autopower signal-to-noise ratio (spike autopower SNR). The probability of significant cross-correlation between the thalamic spike train and EMG at tremor frequency was assessed by the coherence at tremor frequency. Autopower spectra of the activity of many of these cells exhibited a concentration of power at tremor frequency, indicated by spike autopower SNRs as high as 18. Of the EMG signals studied, signals recorded from finger flexors were most often significantly correlated at tremor frequency. Significant correlation between the thalamic spike train and finger flexor EMG activity was found in 34% of cells analyzed. Tremor frequency coherence was significantly correlated with tremor frequency spike autopower (r = 0.46, p less than 0.0001) and spike autopower SNR (r = 0.533, p less than 0.0001). The proportion of cells with a spike autopower SNR greater than 2 that were significantly correlated with finger flexor EMG activity was greater than that of cells with a spike autopower SNR of less than 2 (p less than 0.001; chi-square). Therefore, cells exhibiting a large amount of power at tremor frequency were those best correlated with EMG activity during tremor. Some of these cells may be involved in the generation of tremor.

1. We have studied the functional and somatotopic properties of 531 single mechanoreceptive thalamic neurons in humans undergoing stereotactic surgery for the control of movement disorders and pain. The majority of these somatosensory cells had small receptive fields (RFs) and were activated in a reproducible manner by mechanical stimuli applied to the skin or deep tissues. These neurons, which we termed "lemniscal," could be further classified into those responding to stimulation of cutaneous (76% of lemniscal sensory cells) or deep (24%) structures. 2. The incidence of neurons having cutaneous or mucosal RFs in the perioral region, thumb, and fingers (66%) was much higher than that of neurons having RFs elsewhere on the body. Most of the deep cells were activated by movements of and/or mechanical stimuli delivered to muscles or tendons controlling the elbow, wrist, and fingers. 3. Sequences of cells spanning several millimeters in the parasagittal plane often exhibited overlapping RFs. However, RFs changed markedly for cells separated by the same distances in the mediolateral direction. This suggests that the cutaneous somatotopic representation of each region of the body is organized into relatively thin sheets of cells oriented in the parasagittal plane. 4. By comparing neuronal RFs in different parasagittal planes in thalamus of individual patients we have identified a mediolateral representation of body surface following the sequence from: intraoral structures, face, thumb through fifth finger to palm, with forearm and leg laterally. 5. Along many trajectories in the parasagittal plane the sequence of cells with overlapping RFs was interrupted by another sequence of cells with RFs corresponding to a different body region. The RFs of the intervening sequence characteristically represented body regions known to be located more medially in thalamus (see 3 above). These findings could be explained if the lamellae postulated above were laterally convex. 6. Cells responding to deep stimulation (deep cells) could be further classified into those responding to joint movement (63%), deep pressure (15%), or both (22%). Deep cells were found usually at the anterior-dorsal border and sometimes at the posterior border of the region containing cells responding to cutaneous stimuli. Although there was some overlap in the RFs, deep cells representing wrist were found medial to those representing elbow, and both of these were found medial to cells representing leg.(ABSTRACT TRUNCATED AT 400 WORDS)

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A prospective review of 75 of 190 parkinsonian patients undergoing unilateral thalamotomy was displayed with a computer graphics technique examining three equal consecutive groups from the pre-, early, and late L-dopa eras. Histograms for average function and scattergrams of individual patient''s performance preoperatively and up to 2 years postoperatively were prepared. No ipsilateral effects or consistent iatrogenic deterioration of any function were identified. 2 years after surgery, 82% had no tremor in the contralateral fingers or hand and 7% had almost no tremor; contralateral tremor elsewhere was infrequent. Rigidity and manual dexterity improved less strikingly, the latter only reflecting abolition of tremor; locomotion, speech, facial movement and handwriting did not improve. There was no mortality, but 8% had persistent significant complications. VIM thalamotomy remains the treatment of choice for severe drug-resistant parkinsonian tremor.

1. Responses suggesting activation of the vestibular system, elicited by electrical stimulation of the human thalamus during 22 routine stereotaxic neurosurgical procedures, were examined in a retrospective study to determine the possible existence of vestibulothalamo-cortical projections in man. 2. Such responses were most frequently described as sensations of movement through space and were associated with two distinct vestibulothalamic projections: a) an anterior relay was situated ventral to the medial lemniscus, passing lateral to the red nucleus and dorsal to the subthalamic nucleus prior to terminating in the nucleus ventrointermedius (Vim) (comparable to VPLo in primates); b) a posterior relay associated with the auditory pathway (lateral lemniscus and brachium of the inferior colliculus) projected to the medial geniculate body. 3. The production of sensations of motion in conscious patients by stimulating areas that are similar to those reported constituting vestibulothalamic pathways in cats and primates implies a distinct primary sensory cortical projection for processing information from the vestibular receptors pertaining to the recognition of spatial movements.

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The extent of participation of supraspinal structures in the generation of the long latency (M2) electromyographic (EMG) response to imposed joint displacement may be reflected in the effect of lesions of the central nervous system. M2 activity has been reported in a variety of studies to be either present or absent following supraspinal lesions. Since other studies have shown different characteristics of long latency activity in proximal as compared to distal upper limb muscles in primates, the present experiments were conducted to determine the effect of motor cortical (area 4) lesions on reflex activity generated in a proximal versus a distal upper limb muscle.Chronic experiments were performed on squirrel monkeys with unilateral lesions of the forelimb motor cortex (area 4) which was mapped with the aid of electrical stimulation.Input-output relationships were determined between torque motor-imposed joint rotation and the EMG response in the stretched muscles (flexor digitorum profundus (FDP) and short head of biceps (SHB)). The EMG responses were reported as a percentage of maximum EMG output and controlled for base line EMG level. The "gain" (slope of EMG response versus torque load) for FDP M2 activity was markedly decreased in the limb contralateral to the area 4 lesion as compared to the opposite limb. This decrease was independent of base line EMG levels. In SHB, early latency (Ml) EMG activity was significantly increased, but M2 activity appeared unaffected on the side contralateral to the lesion.The results demonstrate that the central and peripheral mechanisms generating M2 activity in FDP differ from those in SHB in terms of motor cortical dependency.