Jose Maria Tormos, Juan Luis Barcia, Maria Dolores Catala, Alvaro Pascual-Leone
Thursday April 17 3:00 pm / Exhibit Hall A

OBJECTIVE:
The present study was undertaken to enhance our understanding about the mechanisms of action of chronic deep brain stimulation (DBS) of GPi in PD.

BACKGROUND:
Functional neurosurgical techniques enjoy a renewed interest for the treatment of PD. Chronic, high-frequency DBS of the GPi can improve bradykinesia, rigidity, and dyskinesias in PD. However, the mechanisms of action of DBS remain uncertain.

DESIGN/METHODS:
We have studied 20 patients with bradykinetic-rigid PD treated by GPi stimulation. Transcranial magnetic stimulation (TMS) and H-reflexes were used to evaluate the effects of different DBS parameters on cortico-spinal excitability. Single pulse, focal TMS was applied to the motor cortex and contralateral motor evoked potentials (MEPs) were recorded in hand and leg muscles using surface electrodes. All studies were conducted with the patients OFF antiparkinsonian medications. The effects of DBS on cortico-spinal excitability were correlated with the clinical effects (UPDRS) and various quantitative measures of motor performance (tapping test, timed walking task, simple reaction time test, grooved pegboard test).

RESULTS:
High-frequency stimulation of the GPi results in an increase of the amplitude of the MEPs (facilitation or disinhibition). This effect is bilateral, but significantly greater for MEPs induced from the ipsilateral than the contralateral motor cortex to the stimulated GPi. The degree of this facilitation depends on the DBS stimulation intensity. These facilitatory effects are maximal for the lower or the upper extremity depending on which DBS electrode contacts are used as cathode (monopolar stimulation technique). Low-frequency stimulation of the GPi results in a reduction of the amplitude of the MEPs (disfacilitation or inhibition). H-reflex studies reveal a lack of effects of DBS on spinal excitability. Correlation of clinical and neurophysiologic measures show that optimal clinical effects on bradykinesia and rigidity are obtained with DBS settings that lead to a maximal increase in MEP amplitude.

CONCLUSION:
GPi stimulation modulates cortico-spinal excitability depending on DBS parameters. Clinically effective GPi stimulation appears to enhance cortico-spinal excitability by effects at cortical level. In addition to illustrating the mechanisms of action of GPi stimulation and enhancing our understanding about the physiology of cortical-basal ganglia loops, TMS studies of cortico-spinal excitability might be useful to identify the DBS parameters most suited for optimal clinical results of GPi stimulation in PD.

Sponsored by: Generalitat Valenciana and Spanish Ministerio de Educaci-n y Ciencia (DGICYT).