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Jerrold L Vitek

Publications and source records attributed to Jerrold L Vitek.

25 records · Page 2Linked to original sources
PubMed2002

A template subtraction method for stimulus artifact removal in high-frequency deep brain stimulation.

Deep brain stimulation (DBS) is a neurosurgical technique that has been widely applied for the treatment of tremor or motor symptoms associated with advanced Parkinson's disease. Large stimulus artifacts, however, have hampered investigations of physiological mechanisms underlying DBS effects using extracellular recording techniques. We have developed an off-line procedure for removing stimulus artifacts from recorded neuronal signals (monopolar) and applied this method of artifact subtraction to DBS studies using extracellular recording techniques in a nonhuman primate. The procedure consists of developing a template of the artifact by averaging the artifact signals triggered by its onset. The template is then subtracted from the individual triggered signals. The experimental results indicate that this method is highly effective in removing the majority of the stimulus artifact, while leaving recorded neuronal activity intact. In fact, removal of stimulation artifact using this technique has revealed a short-latency neuronal response to stimulation that was previously obscured by the stimulus artifact. Thus, this technique may not only improve the quality of electrophysiological studies employing DBS techniques, but may also help to elucidate neuronal mechanisms underlying the effect of DBS.

Action Potentials↗
PubMed2002

Pathophysiology of dystonia: a neuronal model.

Dystonia has commonly been thought to represent a disorder of basal ganglia function. Although long considered a hyperkinetic movement disorder, the evidence to support such a classification was based on the presence of excessive involuntary movement, not on physiological data. Only recently, with the return of surgical procedures using microelectrode guidance for the treatment of dystonia, has electrophysiological data demonstrated an alteration in mean discharge rate, somatosensory responsiveness and the pattern of neuronal activity in the basal ganglia thalamocortical motor circuit. Previous models of dystonia suggested that reduced mean discharge rates in the globus pallidus internus (GPi) led to unopposed increases in activity in the thalamocortical circuit that precipitated the development of involuntary movement associated with dystonia. This model has subsequently been modified given the clear improvement in dystonic symptoms following lesions in the GPi, a procedure that is associated with a further reduction in pallidal output. The improvement in dystonia following pallidal lesions is difficult to reconcile with the "rate" hypothesis for hypokinetic and hyperkinetic movement disorders and has led to the development of alternative models that, in addition to rate, incorporate changes in pattern, somatosensory responsiveness and degree of synchronization of neuronal activity. Present models of dystonia, however, must not only take these changes into account but must reconcile these changes with the reported changes in cortical excitability reported with transcranial magnetic stimulation, the changes in metabolic activity in cortical and subcortical structures documented by positron emission tomography (PET), and the alterations in spinal and brainstem reflexes. A model incorporating these changes together with the reported changes in neuronal activity in the basal ganglia and thalamus is presented.

Animals↗
PubMed2002

Mechanisms of deep brain stimulation: excitation or inhibition.

There is little debate that deep brain stimulation (DBS) has been an effective tool in the treatment of Parkinson's disease as well as other movement disorders. There remains however, considerable debate concerning the mechanism(s) underlying its beneficial effect. The comparable effect of stimulation to ablation in the thalamus on tremor, and in the subthalamic nucleus (STN) and internal segment of the globus pallidus (GPi) on the motor signs associated with PD, have led many investigators to conclude that DBS acts to suppress neuronal activity, decreasing output from the stimulated site. There are, however, data that do not support this argument. Microdialysis studies in GPi showed increased levels of glutamate during STN stimulation, suggesting activation of glutamatergic output from the STN to the GPi. Studies in parkinsonian primates have demonstrated increased mean discharge rates of neurons in GPi during chronic stimulation in STN, and GPi stimulation in humans has been associated with a suppression of neuronal activity in the thalamus. Contrary to what one would expect if stimulation inhibits output from the stimulated structure, stimulation in GPe has been demonstrated to improve bradykinesia. Although arguments for increased output from the stimulated structure seem to conflict with the hypothesis that stimulation acts to inhibit neuronal activity, it is possible to explain these observations through a common mechanism, e.g. activation of fiber pathways. Based on this mechanism, the effect of stimulation on cellular activity in the stimulated site would be increased or decreased dependent on the neurotransmitter of the afferent fibers projecting to that site. However, in addition to activation of afferent fibers, projection axons from neurons in the stimulated structure, also readily excitable by electrical stimulation, would also be tonically activated and discharge independently of the soma, thereby increasing output from the structure during extracellular stimulation. Thus, although high frequency stimulation may inhibit neurons via activation of inhibitory afferents, the output from that structure may be increased as the result of activation of axonal elements leaving the target structure. This hypothesis would explain the present experimental results, is consistent with excitability profiles of neuronal elements based on their biophysical properties, and fits with more recent models emphasizing the role of altered patterns of neuronal activity in the development of hypokinetic and hyperkinetic movement disorders.

Animals↗
PubMed2002

Deep brain stimulation for Parkinson's disease. A critical re-evaluation of STN versus GPi DBS.

Deep brain stimulation (DBS) in the subthalamic nucleus (STN) and the internal segment of the globus pallidus (GPi) is increasingly being used for the treatment of advanced Parkinson's disease (PD). Although both targets have demonstrated clinical efficacy in the treatment of the cardinal motor signs of PD, the STN has gained greater popularity and is now considered the site of choice by most centers performing these procedures. This preference stems predominately from the belief that STN DBS provides greater improvement in reducing the motor manifestations of PD and allows a reduction in dopaminergic medication not permitted with GPi DBS. There are, however, a number of issues that must be considered before abandoning GPi in favor of STN as the surgical target of choice for DBS. The maximal benefit reported for GPi stimulation is not significantly different than that reported for the STN, 67 versus 71%, and while reductions in medication are required with STN stimulation to avoid inducing dyskinesia, GPi stimulation may directly suppress dyskinesia obviating any need to reduce medication. As such, many centers may not attempt to reduce antiparkinsonian medication with GPi DBS. In addition, there are significantly more reports of changes in mood, behavior and a higher incidence of adverse events reported for STN stimulation. Most studies of DBS are nonrandomized, assessment protocols are not standardized, and lead locations are not reported. Thus, before drawing conclusions regarding the optimal site for DBS for advanced PD we must take a critical eye to the present data and address the outstanding questions that remain with well-designed clinical trials that evaluate motor, nonmotor and adverse events and address the above clinical variables by randomizing patients, using standardized methods of assessment and defining the lead location.

Clinical Trials as Topic↗
PubMedDate not supplied

How does deep brain stimulation work? Present understanding and future questions.

High-frequency deep brain stimulation (DBS) of the thalamus or basal ganglia represents an effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been vaulted forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address the present knowledge of the effects of high frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS. Four general hypotheses have been developed to explain the mechanism(s) of DBS: depolarization blockade, synaptic inhibition, synaptic depression, and stimulation-induced modulation of pathologic network activity. Using the results from microdialysis, neural recording, functional imaging, and neural modeling experiments, the authors address the main hypotheses and attempt to reconcile what have been considered conflicting results from different research modalities.

Basal Ganglia↗