Functional activity of the sensorimotor cortex and cerebellum relates to cervical dystonia symptoms

Abstract

Cervical dystonia (CD) is the most common type of focal dystonia, causing abnormal movements of the neck and head. In this study, we used noninvasive imaging to investigate the motor system of patients with CD and uncover the neural correlates of dystonic symptoms. Furthermore, we examined whether a commonly prescribed anticholinergic medication in CD has an effect on the dystonia-related brain abnormalities. Participants included 16 patients with CD and 16 healthy age-matched controls. We collected functional MRI scans during a force task previously shown to extensively engage the motor system, and diffusion and T1-weighted MRI scans from which we calculated free-water and brain tissue densities. The dystonia group was also scanned ca. 2 h after a 2-mg dose of trihexyphenidyl. Severity of dystonia was assessed pre- and post-drug using the Burke-Fahn-Marsden Dystonia Rating Scale. Motor-related activity in CD was altered relative to controls in the primary somatosensory cortex, cerebellum, dorsal premotor and posterior parietal cortices, and occipital cortex. Most importantly, a regression model showed that increased severity of symptoms was associated with decreased functional activity of the somatosensory cortex and increased activity of the cerebellum. Structural imaging measures did not differ between CD and controls. The single dose of trihexyphenidyl altered the fMRI signal in the somatosensory cortex but not in the cerebellum. Symptom severity was not significantly reduced post-treatment. Findings show widespread changes in functional brain activity in CD and most importantly that dystonic symptoms relate to disrupted activity in the somatosensory cortex and cerebellum. Hum Brain Mapp 38:4563-4573, 2017. © 2017 Wiley Periodicals, Inc.

Keywords: MRI; cerebellum; cervical dystonia; sensorimotor cortex; trihexyphenidyl.

Figure 1

Regions of interest (ROIs) for the diffusion MRI analysis. Abbreviations: ASN = anterior substantia nigra; CC = corpus callosum; DN = dentate nucleus; GP = globus pallidus; ICP = inferior cerebellar peduncle; IVermis = inferior portion of the cerebellar vermis; MCP; middle cerebellar peduncle; Lob V = lobule V of the cerebellum; Lob VI = lobule VI of the cerebellum; PSN = posterior substantia nigra; RN = red nucleus; SCP = superior cerebellar peduncle; STN = subthalamic nucleus; SVermis = superior portion of the cerebellar vermis. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 2

Differences in task‐related fMRI activity between controls and CD patients tested off medication (A). Regression model illustrating the relation between dystonic symptoms off medication as assessed by BFMDRS and the predicted values for BFMDRS off medication based on the percent signal change in the right primary somatosensory cortex, and right lobule VI of the cerebellum (B). Abbreviations: CD OFF = cervical dystonia off medication; CON = controls; ITG = inferior temporal gyrus; L = left; MOG = middle occipital gyrus; PMd = dorsal premotor cortex; R = right; S1 = primary somatosensory cortex; SMG = supramarginal gyrus. [Color figure can be viewed at http://wileyonlinelibrary.com]

Figure 3

The two plots show the percent signal change at each TR (averaged across task/rest blocks) in the regions that differed between CD OFF and controls in the voxel‐wise analysis, and where functional brain activity related to dystonic symptoms (i.e., right S1 and right lobule VI of the cerebellum) plotted for CD OFF and ON medication. The bracket indicates the time window (6 TRs) used to evaluate the effect of 2 mg of trihexyphenidyl on the functional activity in the dystonia‐related brain regions. This interval toward the end of the task was chosen based on previous work using a force production fMRI protocol [Burciu et al., 2016a]. The asterisk indicates a significant drug effect on the functional activity of S1 during the a priori selected 6‐TR time window. Abbreviations: CD OFF = cervical dystonia off medication; CD ON = cervical dystonia on medication; n.s. = nonsignificant; s = seconds; S1 = primary somatosensory cortex. [Color figure can be viewed at http://wileyonlinelibrary.com]