Cortical inhibitory deficits in premanifest and early Huntington's disease.
Behav Brain Res
; 296: 311-317, 2016 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-26416671
ABSTRACT
Although progress has been made towards understanding the gross cortical and subcortical pathology of Huntington's disease (HD), there remains little understanding of the progressive pathophysiological changes that occur in the brain circuits underlying the disease. Transcranial magnetic stimulation (TMS) enables investigation of the functional integrity of cortico-subcortical pathways, yet it has not been widely applied in HD research to date. This study sought to characterise profiles of cortical excitability, including inhibition and facilitation, in groups of premanifest and symptomatic HD participants via the use of TMS. We also investigated the clinical, neurocognitive and psychiatric correlates of cortical excitability to better understand the development of phenotypic heterogeneity. The sample comprised 16 premanifest HD, 12 early symptomatic HD and 17 healthy control participants. Single- and paired-pulse TMS protocols were administered to the left primary motor cortex, with surface electromyography recorded from the abductor pollicis brevis muscle. Short-interval cortical inhibition was significantly reduced in symptomatic HD, compared with premanifest HD and controls, and was significantly correlated with pathological burden and neurocognitive performance. There was also reduced long-interval cortical inhibition in both premanifest and symptomatic HD, compared with controls, which was associated with pathological burden and psychiatric disturbances. Motor thresholds, cortical silent periods and intracortical facilitation did not differ across groups. Our results provide important new insights into pathophysiological changes in cortico-subcortical circuits across disease stages in HD. We propose that neurophysiological measures obtained via TMS have potential utility as endophenotypic biomarkers in HD, given their association with both pathological burden and clinical phenotype.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Huntington
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Estimulação Magnética Transcraniana
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Ácido gama-Aminobutírico
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Córtex Motor
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Inibição Neural
Tipo de estudo:
Guideline
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Behav Brain Res
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Austrália