Single-cell recording of the subthalamic nucleus (STN) was undertaken in 14 patients with Parkinson's disease submitted to surgery. Three hundred and fifty neurones were recorded and assessed for their response to passive and active movements. Thirty-two per cent were activated by passive and active movement of the limbs, oromandibular region and abdominal wall. All neurones with sensorimotor responses were in the dorsolateral region of the STN. Arm-related neurones were lateral (> or =14 mm plane) to leg-related neurones, which were found more medially (< or =12 mm). Representation of the oromandibular musculature was in the middle of the sensorimotor region (approximately 13 mm plane) and ventral to the arm and leg. Two hundred neurones were adequately isolated for 'off-line' analysis. The mean frequency of discharge was 33 +/- 17 Hz (13-117 Hz). Three types of neuronal discharges were distinguished: irregular (60.5%), tonic (24%) and oscillatory (15.5 %). They were statistically differentiated on the basis of their mean firing frequency and the coefficient of variation of the interspike interval. Neurones responding to movement were of the irregular or tonic type, and were found in the dorsolateral region of the STN. Neurones with oscillatory and low frequency activity did not respond to movement and were in the ventral one-third of the nucleus. Thirty-eight tremor-related neurones were recorded. The majority (84%) of these were sensitive to movement and were located in the dorsolateral region of the STN. Cross power analysis (n = 16) between the rhythmic neuronal activity and tremor in the limbs showed a peak frequency of 5 Hz (4-8 Hz). Neuronal activity of the substantia nigra pars reticulata was recorded 0.5-3 mm below the STN. Eighty neurones were recorded 'on-line' and 27 were isolated for 'off-line' analysis. A tonic pattern of discharge characterized by a mean firing rate of 71 +/- 28 Hz (35-122 Hz) with a mean coefficient of variation of the interspike interval of 0.85 +/- 0.29 ms was found. In only three neurones (11%) was there a response to sensorimotor stimulation. The findings of this study indicate that the somatotopic arrangement and electrophysiological features of the STN in Parkinson's disease patients are similar to those found in monkeys.

Microelectrode recording was performed in the basal ganglia of 3 patients with generalized dystonia and 1 patient with hemiballismus secondary to a brainstem hemorrhage. Neuronal activity was recorded from the internal and external segments of the globus pallidus and assessed for mean discharge rate and pattern of spontaneous activity. The responses of neurons in the internal segment of the globus pallidus to passive and active movements were also evaluated. Mean discharge rates of neurons in both segments of the pallidum in patients with dystonia and the patient with hemiballismus were considerably lower than those reported for patients with idiopathic Parkinson's disease. In addition, the pattern of spontaneous neuronal activity was highly irregular, occurring in intermittent grouped discharges separated by periods of pauses. Although receptive fields in the dystonia patients were widened and less specific than those reported in normal monkeys, neuronal responses to movement were uncommon in the hemiballismus patient. Before surgery, patients with dystonia experienced abnormal posturing and involuntary movements. Coactivation of agonist–antagonist muscle groups was observed both at rest and during the performance of simple movements. After pallidotomy there was a significant reduction in the involuntary movement associated with these disorders and a more normal pattern of electromyographic activity during rest and movement. Given the improvement in dystonic and hemiballistic movements in these patients after ablation of the sensorimotor portion of the internal segment of the globus pallidus, we suggest that pallidotomy can be an effective treatment for patients with dystonia and also for patients with medically intractable hemiballismus. Based on the finding of decreased neuronal discharge rates in pallidal neurons, we propose that physiologically dystonia most closely resembles a hyperkinetic movement disorder. A model for dystonia is proposed that incorporates the observed changes in the rate and pattern of neuronal activity in the pallidum with data from neuroimaging with positron emission tomography and 2‐deoxyglucose studies. Ann Neurol 1999;46:22–35

These data provide important information concerning target identification for ablative or deep brain stimulation procedures in idiopathic Parkinson's disease and other movement disorders.

Thirty-six patients with Parkinson's disease (PD) were randomized to either medical therapy (N ‫؍‬ 18) or unilateral GPi pallidotomy (N ‫؍‬ 18). The primary outcome variable was the change in total Unified Parkinson's Disease Rating Scale (UPDRS) score at 6 months. Secondary outcome variables included subscores and individual parkinsonian symptoms as determined from the UPDRS. At the six month follow-up, patients receiving pallidotomy had a statistically significant reduction (32% decrease) in the total UPDRS score compared to those randomized to medical therapy (5% increase). Following surgery, patients' showed improvement in all the cardinal motor signs of PD including tremor, rigidity, bradykinesia, gait and balance. Drug-induced dyskinesias were also markedly improved. Although the greatest improvement occurred on the side contralateral to the lesion, significant ipsilateral improvement was also observed for bradykinesia, rigidity and drug-induced dyskinesias. A total of twenty patients have been followed for 2 years to assess the effect of time on clinical outcome. These patients have shown sustained improvement in the total UPDRS ( p < 0.0001), "off" motor ( p < 0.0001) and complications of therapy subscores ( p < 0.0001). Sustained improvement was also seen for tremor, rigidity, bradykinesia, percent on time and drug-induced dyskinesias. Neurol 2003;53:558 -569 Over the past decade, there has been a marked resurgence of interest in surgery for Parkinson's disease (PD). Several factors have contributed to this: (1) the need for better therapies to treat the continued worsening of parkinsonian motor symptomatology and the development of drug-induced dyskinesias and motor fluctuations, (2) advances in our understanding of the physiological basis of parkinsonism and the rationale for surgery, 1,2,4 and (3) the report by Laitinen and colleagues of improvement in parkinsonian motor signs after pallidotomy. 3 Although there are now numerous reports on the benefits of pallidotomy for PD, 5-15 there has been only one randomized clinical trial comparing the effects of pallidotomy to best medical therapy. 16 In some of the previous studies, nontremulous 7 or predominately asymmetric 6 patients were selected, whereas in others nonstandardized methods of clinical evaluation were used. 10,12,13 Therefore, it is difficult to compare the results of pallidotomy across studies and to assess the effect of pallidotomy for patients regardless of symptom profile. AnnWe present here the results of a randomized, prospective clinical trial comparing the effectiveness of pallidotomy to best medical management in patients followed up for 6 months. In addition, we present data for the first 20 patients who have been followed up for 2 years. Patients and Methods Patient Recruitment and AssessmentPatients were recruited from the Movement Disorders Center at Emory and Grady Memorial Hospital Clinics. To limit patient attrition, we limited the geographical location for patient recruitment to a 500-mile radius from the City of Atlanta...

Deep brain stimulation (DBS) surgery can significantly improve the quality of life for patients suffering from movement disorders, but the success of the procedure depends on the implantation accuracy of the DBS electrode array. Pre-operative surgical planning and navigation are based on the assumption that the brain tissue is rigid between the time of the acquisition of the pre-operative image set and the time of surgery. A shift of deep brain structures by only a few millimeters can potentially increase the number of required microelectrode and/or macroelectrode tracks and decrease implantation accuracy. We studied 25 subjects that underwent DBS surgery and analyzed brain shift between pre-operative and post-operative 3D MRI scans. Brain shift of up to 4 mm was observed in deep brain structures. On average, the recorded shift was in the direction of gravity, with deeper structures experiencing smaller shift than more superficial structures. The main conclusion of the study is that the brain shift is comparable to the size of the targets in deep brain stimulation surgery and should not be ignored. Techniques that minimize the amount of brain shift may therefore lead to increased accuracy of DBS lead implantation.