Figure 3.

Schematic model of the basal ganglia in IPD with and without modulation by HFS (coronar view). Left column (A,C,E): basal ganglia model of hypokinetic IPD. Right column (B,D,F): basal ganglia model of the hyperkinetic state in IPD after years of levodopa treatment. First row (A,B): basal ganglia model without DBS modulation. Second row (C,D): modulation of the network by pallidal HFS (yellow circle). Third row (E,F): modulation of the basal ganglia network by STN-HFS (yellow circle). The GABAergic hypothesis illustrates why pallidal HFS is not effective in the hypokinetic state of IPD (C), since the efferent GABAergic axons are maximally recruited, whereas STN-HFS shows good efficacy (E). (D) displays that in the hyperkinetic state (i.e., levodopa-induced hyperkinesia) pallidal HFS is quite effective by producing an anti-hyperkinetic effect via enhanced GABAergic outflow on the thalamus, whereas STN-HFS per se is not effective to treat levodopa-induced dyskinesia (F). The reason for this failure of STN-HFS is that the afferent fibers to STN are already maximally active. Note, however, that STN-HFS allows the reduction of the dosage of levodopa and thereby diminishes hyperkinesia. Blue circle in (C) indicates stimulation of the striato-pallidal fibers within the GPi as reconsidered in the discussion section. Abbreviations and symbols are as in Figures 1 and 2.