Neurophysiological hallmarks of Huntington's disease progression: an EEG and fMRI connectivity study

Natalya V Ponomareva; Sergey A Klyushnikov; Natalia Abramycheva; Rodion N Konovalov; Marina Krotenkova; Ekaterina Kolesnikova; Daria Malina; Gusel Urazgildeeva; Elena Kanavets; Andrey Mitrofanov; Vitaly Fokin; Evgeny Rogaev; Sergey N Illarioshkin

doi:10.3389/fnagi.2023.1270226

Neurophysiological hallmarks of Huntington's disease progression: an EEG and fMRI connectivity study

Front Aging Neurosci. 2023 Dec 15:15:1270226. doi: 10.3389/fnagi.2023.1270226. eCollection 2023.

Authors

Affiliations

¹ Research Center of Neurology, Moscow, Russia.
² Center for Genetics and Life Science, Sirius University of Science and Technology, Sochi, Russia.
³ Research Center of Mental Health, Moscow, Russia.
⁴ Department of Psychiatry, Umass Chan Medical School, Shrewsbury, MA, United States.

Abstract

Electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can provide corroborative data on neurophysiological alterations in Huntington's disease (HD). However, the alterations in EEG and fMRI resting-state functional connectivity (rsFC), as well as their interrelations, at different stages of HD remain insufficiently investigated. This study aimed to identify neurophysiological alterations in individuals with preclinical HD (preHD) and early manifest HD (EMHD) by analyzing EEG and fMRI rsFC and examining their interrelationships. We found significant differences in EEG power between preHD individuals and healthy controls (HC), with a decrease in power in a specific frequency range at the theta-alpha border and slow alpha activity. In EMHD patients, in addition to the decrease in power in the 7-9 Hz range, a reduction in power within the classic alpha band compared to HC was observed. The fMRI analysis revealed disrupted functional connectivity in various brain networks, particularly within frontal lobe, putamen-cortical, and cortico-cerebellar networks, in individuals with the HD mutation compared to HC. The analysis of the relationship between EEG and fMRI rsFC revealed an association between decreased alpha power, observed in individuals with EMHD, and increased connectivity in large-scale brain networks. These networks include putamen-cortical, DMN-related and cortico-hippocampal circuits. Overall, the findings suggest that EEG and fMRI provide valuable information for monitoring pathological processes during the development of HD. A decrease in inhibitory control within the putamen-cortical, DMN-related and cortico-hippocampal circuits, accompanied by a reduction in alpha and theta-alpha border oscillatory activity, could potentially contribute to cognitive decline in HD.

Keywords: CAG repeats; EEG; HTT gene; Huntington’s disease; cognitive functions; functional MRI; preclinical stage.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was supported by Russian Science Foundation (Project N 22-15-00448 to NP, SK, VF, RK, EK and GU).