Task-Free Functional MRI in Cervical Dystonia Reveals Multi-Network Changes That Partially Normalize with Botulinum Toxin

Abstract

Cervical dystonia is characterized by involuntary, abnormal movements and postures of the head and neck. Current views on its pathophysiology, such as faulty sensorimotor integration and impaired motor planning, are largely based on studies of focal hand dystonia. Using resting state fMRI, we explored whether cervical dystonia patients have altered functional brain connectivity compared to healthy controls, by investigating 10 resting state networks. Scans were repeated immediately before and some weeks after botulinum toxin injections to see whether connectivity abnormalities were restored. We here show that cervical dystonia patients have reduced connectivity in selected regions of the prefrontal cortex, premotor cortex and superior parietal lobule within a distributed network that comprises the premotor cortex, supplementary motor area, primary sensorimotor cortex, and secondary somatosensory cortex (sensorimotor network). With regard to a network originating from the occipital cortex (primary visual network), selected regions in the prefrontal and premotor cortex, superior parietal lobule, and middle temporal gyrus areas have reduced connectivity. In selected regions of the prefrontal, premotor, primary motor and early visual cortex increased connectivity was found within a network that comprises the prefrontal cortex including the anterior cingulate cortex and parietal cortex (executive control network). Botulinum toxin treatment resulted in a partial restoration of connectivity abnormalities in the sensorimotor and primary visual network. These findings demonstrate the involvement of multiple neural networks in cervical dystonia. The reduced connectivity within the sensorimotor and primary visual networks may provide the neural substrate to expect defective motor planning and disturbed spatial cognition. Increased connectivity within the executive control network suggests excessive attentional control and while this may be a primary trait, perhaps contributing to abnormal motor control, this may alternatively serve a compensatory function in order to reduce the consequences of the motor planning defect inflicted by the other network abnormalities.

Increased interhemispheric resting-state functional connectivity in paroxysmal kinesigenic dyskinesia: A resting-state fMRI study

“…Nowadays movement disorders have been viewed as circuitry disorders which are not confined to localized structure or functional abnormalities [18]. Robust disease and symptom specific functional networks have been identified in movement disorders using different paradigms [19,20]. Hence identification of functional connectivity alterations in PKD is urgently warranted.…”

Dynamic cortical gray matter volume changes after botulinum toxin in cervical dystonia

“…a neuroplastic response to peripheral sensory alterations (Curra et al, 2004). Indeed, functional reorganization after BoNT treatment has been demonstrated in primary sensorimotor and lateral premotor areas, both electrophysiologically and by means of fMRI (Delnooz et al, 2013a;Kojovic et al, 2011). Based on our own fMRI data, we recently hypothesized that the BoNT-related functional organization of these higher order motor areas reflects a "reorganization" of primary motor planning defects in CD (Delnooz et al, 2013a).…”

“…Indeed, functional reorganization after BoNT treatment has been demonstrated in primary sensorimotor and lateral premotor areas, both electrophysiologically and by means of fMRI (Delnooz et al, 2013a;Kojovic et al, 2011). Based on our own fMRI data, we recently hypothesized that the BoNT-related functional organization of these higher order motor areas reflects a "reorganization" of primary motor planning defects in CD (Delnooz et al, 2013a). Since there is partial overlap between the functionally altered regions identified earlier and the regions that exhibit GMV alteration in our longitudinal BoNT-related analysis, we suggest that the observed GMV changes here may be a structural reflection of this previously hypothesized "reorganization".…”

“…Although CD patients have several abnormalities in motor system physiology (Cakmur et al, 2004), its precise pathophysiology still remains to be clarified. In recent years, several functional cerebral abnormalities have been found in CD by means of functional magnetic resonance imaging (fMRI) (Naumann et al, 2000;Delnooz et al, 2013a;de Vries et al, 2012), which may originate from underlying structural abnormalities.…”

“…Despite several reports on structural differences between dystonia patients and healthy controls at baseline, few studies exist on longitudinal structural changes. Interestingly, several electrophysiological and functional imaging studies in focal dystonia have reported on cerebral reorganization after BoNT treatment (Delnooz et al, 2013a;Kojovic et al, 2011;Thickbroom et al, 2003). Even more, Blood et al reported on structural white matter alterations after BoNT injections (Blood et al, 2006).…”