Paradoxical Effects of Gp Dbs on Distorted Temporal Memory in PD

Alternative Treatment for Parkinson Disease

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The STn DBS work was followed up with pallidal DBS (Benabid et al., 1991; Filion et al., 1991; Tronnier et al., 1997). Given the sophisticated DBS technique used by our collaborators, we were fortunate to identify distinct effects related to the altered neural activity in either the globus pallidus external capsule (GPe) or globus pallidus internal capsule (GPi) portions of the globus pallidus in PD, as compared to STn DBS. Details on the technique and clinical electrophysiological and anatomical data for each patient (N = 5) included in our study are published by Yelnik et al. (2000). The beneficial effects of the STn DBS were not reproduced when DBS targeted the GPi. Rather, inaccuracies in the form of migrated estimates were worse, whereas slowed encode was found to be highly variable among subjects. When in contrast, the plots targeting the external part of the pallidum (GPe) were the ones stimulated in the same patients, neither improvement nor aggravation was observed (data not shown). Those results are striking and yet difficult to reconcile with the proposed "classical" model of basal ganglia circuitry (Albin et al., 1989; DeLong, 1990). An initial explanation would be that the "classical" model is incomplete insofar as motor behavior is concerned and therefore may be inadequate to explain higher cognitive functions (Ches-selet and Delfs, 1996; Levy et al., 1997; Marsden and Obeso, 1994; Obeso et al., 1997, 2000). It is to be considered, however, that the exact mechanism by which high-frequency stimulation (as DBS) acts on those nuclei is unclear (Yelnik et al., 2000).

A brief description of the "classical" model of basal ganglia function (to be challenged by the DBS results in both their contrast to the L-Dopa effects as well as in their intrinsic inconsistencies) is described in the functional anatomy section below. This is followed by a proposal for a revised model of cortico-striatal circuits.

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