Cervical Dystonia Is Associated With Aberrant Inhibitory Signaling Within the Thalamus

Christopher L Groth; Mark Brown; Justin M Honce; Erika Shelton; Stefan H Sillau; Brian D Berman

doi:10.3389/fneur.2020.575879

Cervical Dystonia Is Associated With Aberrant Inhibitory Signaling Within the Thalamus

Front Neurol. 2021 Feb 9:11:575879. doi: 10.3389/fneur.2020.575879. eCollection 2020.

Authors

Christopher L Groth^{1

2}, Mark Brown³, Justin M Honce³, Erika Shelton², Stefan H Sillau², Brian D Berman^{2

3

4}

Affiliations

¹ Department of Neurology, University of Iowa Hospitals and Clinics, Iowa City, IA, United States.
² Department of Neurology, University of Colorado Anschutz Medical, Aurora, CO, United States.
³ Department of Radiology, University of Colorado Anschutz Medical, Aurora, CO, United States.
⁴ Neurology Section, Denver VA Medical Center, Aurora, CO, United States.

Abstract

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 ¹¹C-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.

Keywords: GABA; cervical dystonia; inhibition; magnetic resonance spectroscopy; positron emission tomography; thalamus.