Figure 5.

Cerebellothalamic pathway involvement in dystonia. (A) Left: comparison of the DTI scans from inherited dystonia subjects and healthy volunteers revealed a significant cluster in which FA was reduced in the disease group (Supplementary Table 2). This region (red) was located in paravermian cerebellar white matter, in proximity to the cluster (yellow) identified independently in a previous study of dystonia gene carriers and control subjects (see Materials and Methods). Right: FA values (Supplementary Table 2) measured in prespecified cerebellar (CER) and subrolandic white matter (SWM) volumes, located, respectively, along the proximal and distal motor cerebellothalamocortical (CbTC) pathway segments. CER FA was abnormally low in the current group of inherited dystonia patients (P < 0.0001, Student's t-test) with reductions of 1 SD or more below the normal mean in 11/13 (85%) of these subjects. SWM FA, in contrast, was normal in this group. At the individual subject level, FA values for affected gene carriers (horizontal lines) were consistently higher (more intact) in the distal relative to the proximal CbTC pathway segments (P < 0.0001, paired Student's t-test). [Individual subject FA values for each region were z-transformed with respect to corresponding healthy control values]. (B) Display of reconstructed cerebellothalamic fiber tracts from healthy volunteers and from inherited (LEG and NLEG) and sporadic (NLEG) dystonia subjects. Projection pathways were reconstructed using the cerebellar white matter (red) and ventral thalamic activation (blue) clusters described above (see Materials and Methods). On average, cerebellothalamic fiber numbers were reduced by 61% in the inherited dystonia group, with nearly identical changes (−61%) for LEG and NLEG subjects. A mean reduction of 70% was noted for the sporadic subjects (see Results). [The fiber number for each group is presented to the right of the reconstructed tract].