ABSTRACT
The effect of high-frequency stimulation of the subthalamic nucleus on parkinsonian-like resting tremor was investigated in two monkeys (Macaca fascicularis). Unilateral tremor of the arm and leg was induced by electrical coagulation of the brainstem area including the substantia nigra and the red nucleus. The tremor was only seen at rest condition with a very stable frequency of 4.46+/-0.59 Hz (mean+/-S.D.). Apomorphine (0.10-0.4 mg/kg, s.c.) completely blocked the tremor, suggesting that it was a dopaminergic-dependent symptom just like the parkinsonian tremor. When the stimulating frequency varied from 20 to 1000 Hz, both mono- and bipolar stimulation (square pulses, 0-5 mA, 0.06 ms) of the subthalamic nucleus suppressed resting tremor in a frequency-dependent manner but monopolar stimulation was more effective. These effects remained stable for more than two years. The present results suggest that the subthalamic nucleus is involved in the control and mechanism of resting tremor and that the high-frequency stimulation of the subthalamic nucleus can be used as an alternative therapy in parkinsonian patients with akinesia, rigidity and resting tremor.
Subject(s)
Electric Stimulation Therapy , Thalamic Nuclei/physiopathology , Tremor/therapy , Animals , Apomorphine/pharmacology , Brain Stem/physiology , Cerebral Ventriculography , Electrocoagulation , Functional Laterality , Macaca fascicularis , Male , Parkinson Disease, Secondary/pathology , Parkinson Disease, Secondary/physiopathology , Parkinson Disease, Secondary/therapy , Red Nucleus/physiology , Substantia Nigra/physiology , Thalamic Nuclei/diagnostic imaging , Thalamic Nuclei/drug effects , Thalamus/pathology , Tremor/pathology , Tremor/physiopathologyABSTRACT
High-frequency electrical stimulation of deep brain structures has recently been developed for the surgical approach of neurologic disorders. Applied to the thalamus in tremors or to the subthalamic nucleus in Parkinson's disease, high-frequency stimulation has been demonstrated to exert a local inhibiting influence, leading to symptoms alleviation. In the present study, bilateral high-frequency stimulations (130 Hz) of the subthalamic nuclei suppressed ongoing spontaneous absence seizures in rats. This effect was dissociated from motor side-effects and appears specific to the subthalamic nucleus. Bilateral excitotoxic lesions of the subthalamic nuclei only partially suppressed absence-seizures. These results confirm the involvement of the basal ganglia system in the control of generalized seizures and suggest that high-frequency stimulations could be used in the treatment of some forms of seizures.
Subject(s)
Epilepsy, Absence/physiopathology , Epilepsy, Absence/therapy , Neurotoxins/pharmacology , Thalamic Nuclei/drug effects , Thalamic Nuclei/physiology , Animals , Disease Models, Animal , Electric Stimulation/methods , Electrodes, Implanted , Electroencephalography , Evoked Potentials/physiology , Kainic Acid/administration & dosage , Kainic Acid/pharmacology , Male , Microinjections , Organ Specificity , Rats , Rats, WistarABSTRACT
The effects of high frequency stimulation of the subthalamic nucleus (STN) and of iontophoretic application of different neurotransmitters on neuronal activities of the ventromedial thalamic nucleus (VM) were investigated in rats. GABA, when applied iontophoretically, inhibited VM neuronal activity while bicuculline, L-glutamic acid and acetylcholine enhanced the firing rates of the same VM neurons. High frequency stimulation of the STN increased VM neuronal activity in a frequency-dependent manner, which could be blocked by MK801. These results suggest that GABAergic, cholinergic and glutamatergic input information converge in the same VM neurons and that an increase in the delivery of glutamatergic neurotransmitter activities in the VM is involved in the process of high frequency stimulation of the STN.
