Objective: To characterize MRI functional patterns during resting state in asymptomatic LRRK2 mutation carriers.

Background: Mutations in the leucine-rich repeat kinase 2 (LRRK2) gene are the most common known cause of inherited Parkinson’s disease (PD). The study of asymptomatic LRRK2 mutation carriers, at high risk of developing PD, is a unique opportunity to study the early, premotor, changes of LRRK2 associated PD (LRRK2-PD) and important for defining early diagnostic biomarkers. The study of the functional connectivity by means of magnetic resonance imaging (MRI) in asymptomatic LRRK2 mutation carriers could contribute to the characterization of the prediagnostic phase of LRRK2-PD.

Methods: We acquired resting state functional MRI (fMRI) data of 18 asymptomatic LRRK2 mutation carriers and 18 noncarriers, all of them first-degree relatives of LRRK2-PD patients. Several regions of interest (ROI) were created, including thalamus, striatum and substantia nigra. Voxelwise general linear model was applied using non-parametric testing including all brain voxels. Significance level was set at p< 0.05, corrected for multiple comparisons using family-wise error (FWE) control, applied to P-value maps obtained from threshold-free cluster enhancement.

Results: Compared to noncarriers, asymptomatic LRRK2 mutation carriers had functional connectivity reductions between the left thalami and contralateral postcentral gyrus, inferior frontal gyrus, middle and inferior temporal gyrus and occipital cortex.

Conclusions: Asymptomatic LRRK2 mutation carriers, subjects at risk of developing LRRK2-PD, showed functional connectivity reductions in thalamo-cortical circuitry compared to noncarriers. The findings support that altered brain connectivity precedes the onset of classical motor symptoms in this genetic form of PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/reduced-thalamo-cortical-functional-connectivity-in-asymptomatic-lrrk2-mutation-carriers/