Abstract
BackgroundThere has been increasing interest in the interaction of the basal ganglia with the cerebellum and the brainstem in motor control and movement disorders. In addition, it has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, thus far, there is only indirect evidence for this in humans with dystonia.Methodology/Principal FindingsIn the current study we investigated probabilistic diffusion tractography in DYT1-negative patients with cervical dystonia and matched healthy control subjects, with the goal of showing that patients exhibit altered microstructure in the connectivity between the pallidum and brainstem. The brainstem regions investigated included nuclei that are known to exhibit strong connections with the cerebellum. We observed large clusters of tractography differences in patients relative to healthy controls, between the pallidum and the brainstem. Tractography was decreased in the left hemisphere and increased in the right hemisphere in patients, suggesting a potential basis for the left/right white matter asymmetry we previously observed in focal dystonia patients.Conclusions/SignificanceThese findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.
Highlights
When thresholded to limit viewing of connections at a probability of 500 and above, the main regions of projection from the pallidum and the ansa lenticularis (AL) seed regions were (1) to the thalamus and (2) to the brainstem, running through the substantia nigra (SN) and the edge of the red nucleus (RN), and branching to (a) the cerebellum and (b) the pedunculopontine nucleus (PPN) (Figure 2, sagittal images)
We observed fractional anisotropy (FA) and tractography differences in cervical dystonia patients that were consistent with our hypothesis that pallidal output fibers to the brainstem are altered in some way in this disorder [24,25]
We cannot be certain the Type Ib fibers were the source of altered tractography in our current study, rather than other pallidal or striatal afferents or efferents, the abnormal tractography we observed spanning from the AL and pallidum to both the RN and PPN supports the potential importance of these fibers to dystonia
Summary
In addition to the basal ganglia, the pontine brainstem [1,2,3,4], and cerebellum [5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20] have been implicated in dystonia by numerous studies. We proposed that this latter set of projections helps to coordinate a network of regions involved in the neural control of posture and stabilization [24], including both static and dynamic programs, and that these programs may be affected in a number of movement disorders. Two aspects of the 2006 diffusion tensor imaging (DTI) study [25] required replication and extension to address the following: (1) The finding was identified in a small subject population, (2) Further studies were required to identify the likelihood that the white matter asymmetry reflected changes to pallidal output fibers exhibiting extensive axon collateralization, including collateral projections to the brainstem. It has been suggested that these subcortical connections with the basal ganglia may help to coordinate a network of regions involved in mediating posture and stabilization. While studies in animal models support a role for this circuitry in the pathophysiology of the movement disorder dystonia, far, there is only indirect evidence for this in humans with dystonia
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
