EEG Functional Connectivity and Cognitive Variables in Premanifest and Manifest Huntington's Disease: EEG Low-Resolution Brain Electromagnetic Tomography (LORETA) Study.

Background: Scientific literature does not offer sufficient data on electroencephalography (EEG) functional connectivity and its correlations with clinical and cognitive features in premanifest and manifest HD.

Aim: This study tries to identify abnormal EEG patterns of functional connectivity, in conditions of "brain resting state" and correlations with motor decline and cognitive variable in Huntington's disease (HD), in premanifest and manifest phase, looking for a reliable marker measuring disease progression.

Method: This was an observational cross-sectional study; 105 subjects with age ≥18 years submitted to HD genetic test. Each subject underwent a neurological, psychiatric, and cognitive assessment, EEG recording and genetic investigation for detecting the expansion of the CAG trait. EEG connectivity analysis was performed by means of exact Low Resolution Electric Tomography (eLORETA) in 18 premanifest HD (pHD), 49 manifest HD (mHD), and 38 control (C) subjects.

Results: HD patients showed a Power Spectral Density reduced in the alpha range and increased in delta band compared to controls; no difference was detectable between pHD and mHD; the Global Connectivity in pHD revealed no significant differences if compared to mHD. The Current Source Density was similar among groups. No statistically significant results when comparing pHD with C group, even in comparison of mHD with Controls, and pHD with mHD. mHD compared to Controls showed a significant increase in delta, alpha1, alpha2, beta2, and beta3. Lagged Phase Synchronization in delta, alpha1, alpha2, beta2, and beta3 bands was increased in HD compared to controls ( = -3.921, < 0.05). A significant correlation was found in Regression Analysis: statistically significant results in pHD for the "Symbol Digit Modality Test and lagged phase synchronization" in the Beta1 ( = -0.806, < 0.05) in the prefrontal regions. The same correlation was found in mHD for the Stroop Word Reading Test (SWRT) in the Alpha2 band ( = -0.759, < 0.05).

Conclusion: Increased phase synchronization in main bands characterized EEG in HD patients, as compared to controls. pHD were not dissimilar from mHD as regard to this EEG pattern. Increased phase synchronization correlated to cognitive decline in HD patients, with a similar trend in pHD, suggesting that it would be a potential biomarker of early phenotypical expression.