Rationale for targeting the thalamic centre-median parafascicular complex in the surgical treatment of Parkinson's disease

Abstract

The thalamic centre median-parafascicular complex (CM/Pf), a main input and output station of the basal ganglia, is attracting increasing interest in the field of movement disorders, including Parkinson's disease (PD). CM/Pf undergoes partial neurodegeneration in PD patients and some rodent models. Cellular evidence has been provided in experimental animals that thalamic degeneration may not aggravate but rather counteract the effects of dopamine lesion. But functional changes in the circuits involving the spared neurons could play a detrimental role. This view fits with converging anecdotic and recent direct experience in patients that stress the potential of CM/PF deep brain stimulation (DBS) to alleviate motor disorders, notably tremor and dyskinesias. As a preclinical contribution to the characterization of this target, we investigated the functional impact of CM/Pf-DBS in the 6-hydroxydopamine hemiparkinsonian rat model of PD. When testing different frequencies (25, 60, 130 Hz), only high frequency stimulation (HFS) had significant antiakinetic action as evidenced by alleviation of limb use asymmetry in the cylinder test. Although less efficient than HFS of the subthalamic nucleus in the latter task, CM/PF-HFS completely corrected lateralized neglect in the corridor task. Unlike subthalamic nucleus, CM/Pf-HFS did not induce per se dyskinesias. Finally, the benefits provided by CM/Pf-HFS were associated with widespread impact on the changes in neuronal metabolic activity induced by the dopamine depletion in the basal ganglia. These data point to own particular outcome of CM/Pf-DBS that may be of interest in currently developing multi-target strategies.