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Evidence for altered basal ganglia-brainstem connections in cervical dystonia.

Blood AJ, Kuster JK, Woodman SC, Kirlic N, Makhlouf ML, Multhaupt-Buell TJ, Makris N, Parent M, Sudarsky LR, Sjalander G, Breiter H, Breiter HC, Sharma N - PLoS ONE (2012)

Bottom Line: 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.These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.

View Article: PubMed Central - PubMed

Affiliation: Mood and Motor Control Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America. ablood@nmr.mgh.harvard.edu

ABSTRACT

Background: There 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 findings: In 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/significance: These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.

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Related in: MedlinePlus

Significant FA differences in cervical dystonia patients relative to control subjects.(A) Reduced FA in the left cerebellar white matter in patients. (B) Increased FA adjacent to and overlapping with the left substantia nigra in patients. MNI talairach coordinates are indicated for each image. t maps are superimposed on the average FA map for all 24 subjects in the study, and are thresholded at t = +/−2.5 here for illustrative purposes. The color bar indicates the range of t values in this figure for FA contrasts, from +/−2.5 to the peak positive and negative t values for this contrast. Warm tones (red, orange, yellow) indicate regions in which cervical dystonia patients exhibited elevated FA relative to control subjects. Cool tones (blues) indicate regions in which cervical dystonia patients exhibited reduced FA relative to control subjects. LH: left hemisphere; RH: right hemisphere.
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pone-0031654-g001: Significant FA differences in cervical dystonia patients relative to control subjects.(A) Reduced FA in the left cerebellar white matter in patients. (B) Increased FA adjacent to and overlapping with the left substantia nigra in patients. MNI talairach coordinates are indicated for each image. t maps are superimposed on the average FA map for all 24 subjects in the study, and are thresholded at t = +/−2.5 here for illustrative purposes. The color bar indicates the range of t values in this figure for FA contrasts, from +/−2.5 to the peak positive and negative t values for this contrast. Warm tones (red, orange, yellow) indicate regions in which cervical dystonia patients exhibited elevated FA relative to control subjects. Cool tones (blues) indicate regions in which cervical dystonia patients exhibited reduced FA relative to control subjects. LH: left hemisphere; RH: right hemisphere.

Mentions: Within our a priori AOEs for the voxel-wise contrast, cervical dystonia patients exhibited reduced FA in white matter overlying the left SCP and a trend toward reduced FA in the right SCP, at the entry to the cerebellum (Table 2; Figure 1A). There was also a trend toward significantly reduced FA overlying the left ansa lenticularis (AL) in patients. Finally, FA was elevated anterior to and within the left substantia nigra (SN) in patients (Figure 1B, left column). There were no group differences in MD in any of our a priori AOEs.


Evidence for altered basal ganglia-brainstem connections in cervical dystonia.

Blood AJ, Kuster JK, Woodman SC, Kirlic N, Makhlouf ML, Multhaupt-Buell TJ, Makris N, Parent M, Sudarsky LR, Sjalander G, Breiter H, Breiter HC, Sharma N - PLoS ONE (2012)

Significant FA differences in cervical dystonia patients relative to control subjects.(A) Reduced FA in the left cerebellar white matter in patients. (B) Increased FA adjacent to and overlapping with the left substantia nigra in patients. MNI talairach coordinates are indicated for each image. t maps are superimposed on the average FA map for all 24 subjects in the study, and are thresholded at t = +/−2.5 here for illustrative purposes. The color bar indicates the range of t values in this figure for FA contrasts, from +/−2.5 to the peak positive and negative t values for this contrast. Warm tones (red, orange, yellow) indicate regions in which cervical dystonia patients exhibited elevated FA relative to control subjects. Cool tones (blues) indicate regions in which cervical dystonia patients exhibited reduced FA relative to control subjects. LH: left hemisphere; RH: right hemisphere.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3285161&req=5

pone-0031654-g001: Significant FA differences in cervical dystonia patients relative to control subjects.(A) Reduced FA in the left cerebellar white matter in patients. (B) Increased FA adjacent to and overlapping with the left substantia nigra in patients. MNI talairach coordinates are indicated for each image. t maps are superimposed on the average FA map for all 24 subjects in the study, and are thresholded at t = +/−2.5 here for illustrative purposes. The color bar indicates the range of t values in this figure for FA contrasts, from +/−2.5 to the peak positive and negative t values for this contrast. Warm tones (red, orange, yellow) indicate regions in which cervical dystonia patients exhibited elevated FA relative to control subjects. Cool tones (blues) indicate regions in which cervical dystonia patients exhibited reduced FA relative to control subjects. LH: left hemisphere; RH: right hemisphere.
Mentions: Within our a priori AOEs for the voxel-wise contrast, cervical dystonia patients exhibited reduced FA in white matter overlying the left SCP and a trend toward reduced FA in the right SCP, at the entry to the cerebellum (Table 2; Figure 1A). There was also a trend toward significantly reduced FA overlying the left ansa lenticularis (AL) in patients. Finally, FA was elevated anterior to and within the left substantia nigra (SN) in patients (Figure 1B, left column). There were no group differences in MD in any of our a priori AOEs.

Bottom Line: 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.These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.

View Article: PubMed Central - PubMed

Affiliation: Mood and Motor Control Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts, United States of America. ablood@nmr.mgh.harvard.edu

ABSTRACT

Background: There 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 findings: In 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/significance: These findings support the hypothesis that connections between the basal ganglia and brainstem play a role in the pathophysiology of dystonia.

Show MeSH
Related in: MedlinePlus