Neuronal activity in the basal ganglia in patients with generalized dystonia and hemiballismus

Abstract

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

Mechanisms and Targets of Deep Brain Stimulation in Movement Disorders

“…During movement, most of these neurons were activated, whereas the activation-to-inactivation ratio was reversed for nonparkinsonian monkeys. 99 In dystonia, experimental recordings showed enlarged receptive fields of dystonic joints in the somatosensory cortex, 100 thalamus, 101 and globus pallidus 102,103 (but also see the 2003 article by Hutchison et al 104 ).…”

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…Based on pharmacologic studies, there seems to be a relative increase in the activity of striatal neurons of the direct pathway over those that give rise to the indirect pathway in dystonia [195,196], and single-cell recording studies in patients undergoing functional neurosurgical treatments have demonstrated low discharge rates in both GPe and GPi [197][198][199][200][201][202], in distinction to the aforementioned changes in PD where GPi discharge rates are generally increased. The presence of lowfrequency discharge in the GPi in patients with dystonia is similar to that in other hyperkinetic disorders, including chorea/ ballismus and motor tics [197,203,204]. Other studies have shown the emergence of low-frequency oscillations in single-cell and LFP activities in the basal ganglia or thalamus [200,201,[205][206][207], comparable with those found in PD.…”

Mechanisms of Deep Brain Stimulation in Movement Disorders as Revealed by Changes in Stimulus Frequency

“…41 There is an increase in the presence of bursts, low frequency oscillations, and synchronization in neurons in the basal ganglia and thalamus in movement disorders. 22,[42][43][44][45][46][47][48] Such changes in discharge patterns and synchronization play an important role in the pathophysiology of movement disorders. Motor symptoms including tremor, bradykinesia, and rigidity are associated with increased neuronal synchronization and low-frequency rhythmic oscillation, 49 -51 and bursts and oscillations parallel the appearance of motor symptoms in PD.…”