Mechanisms of Action of DBS

A second important consideration relates to the mechanism of DBS in the parkinsonian brain that still remains unknown (Benabid et al., 2002). With the advancing use of DBS as the primary surgical tool not only in PD, but also in other basal ganglia diseases (i.e., dystonia, Huntington's disease) (Lenz et al., 1998), there is increasing interest in the mechanisms underlying its effects from both clinicians and researchers.

The STn stimulation is regarded as essentially correcting (attenuating) the abnormally high neural activity of this nucleus associated with the parkinsonian state (Dostrovsky and Lozano, 2002; Limousin et al., 1998). One could say that DBS induces a functional inhibition of a nucleus it targets, as its effects mimic what is functionally obtained when the nucleus is destroyed. Yet there are data suggesting that rather than inhibition, the stimulated site is activated (Benazzouz and Hallett, 2000; Vitek, 2002).

Although most recent evidence appears to weigh heavily in favor of DBS inhibiting neural activity and decreasing neuronal output in the case of the STn (Beurrier et al., 2001; Boraud et al., 1996; Wu et al., 2002), how stimulation acts on the pallidum — either the GPe or GPi — remains unclear. For instance, it might be the case that DBS has differential outcomes when applied in the STn or the GP. The anatomical (low vs. high neuronal density), biochemical (GABAergic vs. glutamater-gic content), and electrophysiological (continuous vs. burst discharge) differences between the two nuclei may indeed challenge the generally accepted concept that high-frequency stimulation inactivates neurons in the region stimulated. An intriguing hypothesis is that DBS inhibits neural activity in the STn, but increases neurotransmission in the GP (Dostrovsky and Lozano, 2002; Yelnik et al., 2000).

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