Hyperconnectivity in resting-state fMRI as a marker of disease severity in Myotonic Dystrophy Type 1

Myotonic dystrophy type 1 (DM1) patients show both structural and functional brain alterations, including abnormal resting-state (RS) functional connectivity. Although some studies have investigated RS functional connectivity in DM1, methodological differences make it challenging to draw consistent conclusions.

This study aims to analyze 1) RS functional connectivity in DM1 patients compared to healthy controls (HC), 2) graph theory metrics, 3) longitudinal connectivity variations, and 4) the relationship between connectivity and clinical, cognitive, and structural brain data.

Twenty-one DM1 patients and 21 matched HCs underwent 3 T MRI scans, including RS fMRI. Of these, 15 DM1 patients and 13 HCs participated in the follow-up after 3 years. Additionally, DM1 patients underwent baseline clinical, molecular and cognitive assessments. Functional connectivity analysis (ROI-to-ROI) and graph theory measures were employed. Longitudinal changes in connectivity were examined, and total hyperconnectivity and hypoconnectivity values were calculated to explore correlations with clinical, brain, and cognitive correlates.

DM1 patients showed widespread hyperconnectivity compared to HCs. Although no statistically significant differences were found in graph theory measures, patients tended to show decreased efficiency, strength, and clustering (with moderate effect sizes). Patients remained hyperconnected over time, with a progression similar to HCs. Hyperconnectivity was associated with more severe disease, greater muscular impairment, and molecular defects, as well as lower cognitive performance. Conversely, hypoconnectivity was associated with less severe disease.

DM1 patients are characterized by brain hyperconnectivity and a less efficient brain network organization. Hyperconnectivity is discussed as a compensatory mechanism and is suggested as a disease severity marker.