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

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Cervical Dystonia Is Associated With Aberrant Inhibitory Signaling Within the Thalamus

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Cervical Dystonia Is Associated With Aberrant Inhibitory Signaling Within the Thalamus

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

Frontiers in neurology, Vol.11, pp.575879-575879

02/09/2021

DOI: 10.3389/fneur.2020.575879

PMCID: PMC7900407

PMID: 33633655

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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 C-11-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.

Clinical Neurology

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Title: Subtitle: Cervical Dystonia Is Associated With Aberrant Inhibitory Signaling Within the Thalamus
Creators: Christopher L. Groth - University of Iowa Hospitals and Clinics
Mark Brown - University of Colorado Anschutz Medical Campus
Justin M. Honce - University of Colorado Anschutz Medical Campus
Erika Shelton - University of Colorado Anschutz Medical Campus
Stefan H. Sillau - University of Colorado Anschutz Medical Campus
Brian D. Berman - University of Colorado Anschutz Medical Campus
Resource Type: Journal article
Publication Details: Frontiers in neurology, Vol.11, pp.575879-575879
DOI: 10.3389/fneur.2020.575879
PMID: 33633655
PMCID: PMC7900407
NLM abbreviation: Front Neurol
ISSN: 1664-2295
eISSN: 1664-2295
Publisher: Frontiers Media Sa
Number of pages: 9
Grant note: University of Colorado Movement Disorder Center Pilot Grant Dystonia Medical Research Foundation, Clinical Fellowship Training Program Grant
Language: English
Date published: 02/09/2021
Academic Unit: Neurology
Record Identifier: 9984302211102771

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