Category: Neuroimaging (Non-PD)
Objective: To determine whether functional connectivity changes are already present in non-manifesting carriers (NMCs) of the TAF1 gene mutation causing X-linked dystonia-parkinsonism (XDP).
Background: XDP is characterized by rapidly progressive adult-onset dystonia accompanied or followed by parkinsonism over the disease course. At the time of the clinical diagnosis, up to 40% of the striatal volume is already degenerated, indicating a long-lasting prodromal phase without overt clinical symptoms. In NMC, the predicted age at disease onset (AAO) can be calculated by combining effects of different genetic modifiers.
Method: Resting-state functional MRI (rs-fMRI) was performed at 1.5T in 10 male NMCs, 15 XDP patients (XDP), and 25 matched controls negative for the disease-causing mutation (HC). Group-independent component analyses (ICA) were performed using the CONN toolbox. Two movement disorder specialists blinded to the genetic status performed standardized neurological examinations.
Results: We found no differences in motor signs, global cognition, and activities of daily living between NMCs and HCs (all p≥0.579). In NMCs, the predicted time to disease manifestation was on average 9.1 years (SD=7.7). ICA demonstrated decreased connectivity within the default mode network (DMN; FWEc p≤0.01) and increased functional connectivity in the sensorimotor network (SMN; FWEc p≤0.001), including parts of the cerebellum (FWEc p≤0.023) in NMCs when compared to HCs. Decreased functional connectivity within the thalamus and subparts of the cerebellum (FWEc p≤0.01) was found in NMCs compared to XDP patients. In NMCs, the increased cerebellar connectivity correlated with the estimated AAO (FDRcorr p=0.033), whereas functional connectivity alterations within DMN and SMN correlated with time to manifestation (FDRcorr p<0.001).
Conclusion: Rs-fMRI can be used to demonstrate alterations in functional connectivity within cognitive and motor networks in TAF1 NMC. This is in keeping with striatal volume loss that we have recently identified in this group. The relationship with time to the estimated AAO allows more precise predictions for disease trajectories which may be useful for prospective disease-modifying therapies.
To cite this abstract in AMA style:
J. Steinhardt, C. Diesta, M. Heldmann, J. Dy, J. Tantianpact, H. Hanssen, R. Tuazon, R. Rosales, A. Westenberger, J. Oropilla, N. Brüggemann. Functional brain network alterations in the prodromal phase of X-linked dystonia-parkinsonism [abstract]. Mov Disord. 2023; 38 (suppl 1). https://www.mdsabstracts.org/abstract/functional-brain-network-alterations-in-the-prodromal-phase-of-x-linked-dystonia-parkinsonism/. Accessed July 18, 2025.« Back to 2023 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/functional-brain-network-alterations-in-the-prodromal-phase-of-x-linked-dystonia-parkinsonism/