Altered thalamic glucose metabolism in cerebellar projections in Parkinson’s disease

Abstract

A pathological communication between the basal ganglia (BG) and the cerebellum (Cb) at the level of the thalamus has been proposed to be causative for the generation of parkinsonian tremor. Recent studies, however, indicated, that altered Cb-thalamic circuitry is not only underlying the genesis of tremor, but is involved in the generation of other parkinsonian symptoms like bradykinesia and rigor.Hence, we studied the glucose metabolism of akinetic-rigid parkinsonian patients in (i) anatomical (anterior, medial, lateral, posterior) and (ii) projection territory-based (Cb- and BG-thalamic) subdivision of the human thalamus and compared them with healthy controls in order to predict disease progression irrespective of the symptom tremor. The dentate nucleus was representatively chosen as output station for Cb regions, BG regions comprised the pallidum.Regarding (i) the anatomical subdivision we found no significant difference between patients and controls in the glucose metabolism for the anterior and medial group (p > 0.05), but an increase of glucose metabolism for the lateral and posterior group (p < 0.05). The glucose metabolism under (ii) the tractography-based subdivision revealed significant differences between patients and controls in the left (p < 0.05) and right (p < 0.01) Cb-thalamic, but not the BG-thalamic projection territory (p > 0.05). In order to test for disease specific alterations, we correlated bihemispherically averaged thalamic glucose metabolism for the anterior, medial, lateral and posterior thalamic group with disease progress (reflected by the Hoehn & Yahr score) and found a significant prediction of the glucose metabolism of the lateral thalamic group and the disease progression (p < 0.05; r = 0.4). A further subdivision into patients with right and left symptom onset evoked a group of 14 right- and 13 left affected patients. Again, we correlated clinical parameters of disease progression with the results of glucose metabolism and found a significant correlation of the right affected patients (p < 0.05) with the right Cb-thalamic region reflected by an up-regulation of glucose metabolism; right affected patients frequently show slower disease progression than left affected patients.Hence our results support a critical (maybe compensatory) role of the Cb-thalamic projections and forces a more straightforward thinking away from a pure “symptom-oriented” to a “dynamic-circuitry” approach due to functional changes in glucose metabolism with Cb and BG as one of the circuitry key elements defining the clinical parkinsonian phenotype.