Changes in sensorimotor network activation after botulinum toxin type A injections in patients with cervical dystonia: a functional MRI study

Abstract

Botulinum toxin type A (BoNT) is considered an effective therapeutic option in cervical dystonia (CD). The pathophysiology of CD and other focal dystonias has not yet been fully explained. Results from neurophysiological and imaging studies suggest a significant involvement of the basal ganglia and thalamus, and functional abnormalities in premotor and primary sensorimotor cortical areas are considered a crucial factor in the development of focal dystonias. Twelve BoNT-naïve patients with CD were examined with functional MRI during a skilled hand motor task; the examination was repeated 4 weeks after the first BoNT injection to the dystonic neck muscles. Twelve age- and gender-matched healthy controls were examined using the same functional MRI paradigm without BoNT injection. In BoNT-naïve patients with CD, BoNT treatment was associated with a significant increase of activation in finger movement-induced fMRI activation of several brain areas, especially in the bilateral primary and secondary somatosensory cortex, bilateral superior and inferior parietal lobule, bilateral SMA and premotor cortex, predominantly contralateral primary motor cortex, bilateral anterior cingulate cortex, ipsilateral thalamus, insula, putamen, and in the central part of cerebellum, close to the vermis. The results of the study support observations that the BoNT effect may have a correlate in the central nervous system level, and this effect may not be limited to cortical and subcortical representations of the treated muscles. The results show that abnormalities in sensorimotor activation extend beyond circuits controlling the affected body parts in CD even the first BoNT injection is associated with changes in sensorimotor activation. The differences in activation between patients with CD after treatment and healthy controls at baseline were no longer present.

Cause or effect: Altered brain and network activity in cervical dystonia is partially normalized by botulinum toxin treatment

“…3). Conveniently for this interpretation, the CD patients with BNT treatment expressed lower levels of basal ganglia activation in a finger tapping task (Nevrlý et al, 2018; Opavský et al, 2011).…”

Central Effects of Botulinum Neurotoxin—Evidence from Human Studies

“…In dystonia, cerebral activation patterns are not confounded by stroke-related parenchymal injury. Here, BoNT treatment was associated with widespread changes on fMRI-measured activation (i.e., BOLD signal) within several brain regions, such as the bilateral primary and secondary somatosensory cortex, the bilateral supplementary motor area, the contralateral primary motor cortex and the cerebellum in drug-naïve CD patients [65]. Hence, only the first BoNT injection session resulted in changes to sensorimotor activation patterns.…”

Neuroimaging Applications in Dystonia

“…Additionally, some studies pointed to abnormal sensory processing by primary somatosensory cortex that may contribute to the pathophysiology of dystonia (Dresel, Haslinger, Castrop, Wohlschlaeger, & Ceballos-Baumann, 2006; Haslinger et al, 2010; Simonyan & Ludlow, 2010), whereas others mapped abnormal somatotopy of digit representation in primary somatosensory cortex and putamen in focal hand dystonia (Butterworth et al, 2003; Delmaire et al, 2005; Nelson, Blake, & Chen, 2009). Studies examining the effects of botulinum toxin injections on brain activity in patients with focal dystonia provided largely controversial results, showing either modulated or non-modulated brain activity following the treatment (Ali et al, 2006; Dresel et al, 2011; Haslinger et al, 2005; Nevrly et al, 2018). On the other hand, subclinical abnormalities in sensory discrimination were described as a mediational endophenotype of dystonia (Hutchinson et al, 2013) and linked to alterations in primary somatosensory and middle frontal cortices (Termsarasab et al, 2016).…”