Cervical Dystonia Is Associated With Aberrant Inhibitory Signaling Within the Thalamus.

Objective: The objective of this study is to investigate whether alterations in the neurotransmission of gamma-aminobutyric acid (GABA) in the thalamus are present in patients with cervical dystonia compared to healthy controls. Methods: GABA magnetic resonance spectroscopy was used to investigate concentration levels of GABA in the thalamus of cervical dystonia patients ( n = 17) compared to healthy controls ( n = 18). Additionally, a focused post hoc analysis of thalamic GABA _A receptor availability data in a similar cohort ( n = 15 for both groups) using data from a previously collected ¹¹ C-flumazenil positron emission tomography study was performed. Group comparisons for all evaluations were performed using two-sided t -tests with adjustments for age and sex, and Bonferroni correction for multiple comparisons was applied. Spearman's coefficient was used to test correlations. Results: We found significantly reduced GABA+/Cre levels in the thalamus of cervical dystonia patients compared to controls, and these levels positively correlated with disease duration. Although mean thalamic GABA _A receptor availability did not differ between patients and controls, GABA _A availability negatively correlated with both disease duration and dystonia severity. Conclusions: These findings support that aberrant inhibitory signaling within the thalamus contributes to the pathophysiology of cervical dystonia. Additionally, these results suggest that an inadequate ability to compensate for the loss of GABA through upregulation of GABA _A receptors may underlie more severe symptoms.
Competing Interests: CG has received research grant support from the Dystonia Medical Research Foundation. BB has received research grant support from the Dana Foundation, NIH (NIH/NCATS Colorado CTSI Grant Number KL2 TR001080), Dystonia Coalition (receives the majority of its support through NIH grant NS065701 from the Office of Rare Diseases Research in the National Center for Advancing Translational Science and National Institute of Neurological Disorders and Stroke), and from Mary Rossick Kern and Jerome H. Kern. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2021 Groth, Brown, Honce, Shelton, Sillau and Berman.)