Increased sensorimotor network activity in DYT1 dystonia: a functional imaging study
Open Access
- 5 March 2010
- journal article
- research article
- Published by Oxford University Press (OUP) in Brain
- Vol. 133 (3) , 690-700
- https://doi.org/10.1093/brain/awq017
Abstract
Neurophysiological studies have provided evidence of primary motor cortex hyperexcitability in primary dystonia, but several functional imaging studies suggest otherwise. To address this issue, we measured sensorimotor activation at both the regional and network levels in carriers of the DYT1 dystonia mutation and in control subjects. We used 15Oxygen-labelled water and positron emission tomography to scan nine manifesting DYT1 carriers, 10 non-manifesting DYT1 carriers and 12 age-matched controls while they performed a kinematically controlled motor task; they were also scanned in a non-motor audio-visual control condition. Within- and between-group contrasts were analysed with statistical parametric mapping. For network analysis, we first identified a normal motor-related activation pattern in a set of 39 motor and audio-visual scans acquired in an independent cohort of 18 healthy volunteer subjects. The expression of this pattern was prospectively quantified in the motor and control scans acquired in each of the gene carriers and controls. Network values for the three groups were compared with ANOVA and post hoc contrasts. Voxel-wise comparison of DYT1 carriers and controls revealed abnormally increased motor activation responses in the former group (P < 0.05, corrected; statistical parametric mapping), localized to the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and the inferior parietal cortex. Network analysis of the normative derivation cohort revealed a significant normal motor-related activation pattern topography (P < 0.0001) characterized by covarying neural activity in the sensorimotor cortex, dorsal premotor cortex, supplementary motor area and cerebellum. In the study cohort, normal motor-related activation pattern expression measured during movement was abnormally elevated in the manifesting gene carriers (P < 0.001) but not in their non-manifesting counterparts. In contrast, in the non-motor control condition, abnormal increases in network activity were present in both groups of gene carriers (P < 0.001). In this condition, normal motor-related activation pattern expression in non-manifesting carriers was greater than in controls, but lower than in affected carriers. In the latter group, measures of normal motor-related activation pattern expression in the audio-visual condition correlated with independent dystonia clinical ratings (r = 0.70, P = 0.04). These findings confirm that overexcitability of the sensorimotor system is a robust feature of dystonia. The presence of elevated normal motor-related activation pattern expression in the non-motor condition suggests that abnormal integration of audio-visual input with sensorimotor network activity is an important trait feature of this disorder. Lastly, quantification of normal motor-related activation pattern expression in individual cases may have utility as an objective descriptor of therapeutic response in trials of new treatments for dystonia and related disorders.Keywords
This publication has 56 references indexed in Scilit:
- Cerebellothalamocortical Connectivity Regulates Penetrance in DystoniaJournal of Neuroscience, 2009
- Abnormal striatal and thalamic dopamine neurotransmissionNeurology, 2009
- Sensory functions in dystonia: Insights from behavioral studiesMovement Disorders, 2009
- Abnormal structure-function relationships in hereditary dystoniaNeuroscience, 2009
- Outcome predictors of pallidal stimulation in patients with primary dystonia: the role of disease durationBrain, 2008
- Experimental Therapeutics for DystoniaNeurotherapeutics, 2008
- Microstructural white matter changes in primary torsion dystoniaMovement Disorders, 2008
- Modulation of metabolic brain networks after subthalamic gene therapy for Parkinson's diseaseProceedings of the National Academy of Sciences, 2007
- Sporadic adult onset dystonia: sensory abnormalities as an endophenotype in unaffected relativesJournal of Neurology, Neurosurgery & Psychiatry, 2007
- Bilateral Deep-Brain Stimulation of the Globus Pallidus in Primary Generalized DystoniaNew England Journal of Medicine, 2005