Objective: To apply precision functional mapping (PFM) to characterize individual-specific network changes in persons with focal hand dystonia (FHD) before and after botulinum toxin (BTX) treatment.

Background: Focal dystonia is linked to basal ganglia dysfunction causing impaired inhibition of unwanted movements, yet emerging evidence suggests it is a network disorder involving multiple cortical and subcortical regions.¹ Learning how treatments modulate these brain networks may advance knowledge of underlying neural mechanisms.  BTX treatment may modulate resting-state networks at a group level,² but this approach may obscure individual-specific effects. PFM tracks altered network patterns and plasticity in individual human brains,³  avoiding averaging effects seen in group comparisons. We used PFM to study the effects of BTX on individual-specific resting-state functional connectivity (rsFC).

Method: We enrolled a 70 y.o. woman with FHD of the right hand responsive to BTX treatment. She underwent a baseline neurologic exam, standardized video assessment, and structural, task-based, and resting-state fMRI acquisition over 10 study sessions of PFM fMRI acquisition:⁴ 5 pre-BTX and 5 during peak treatment effect. Pre-processing included rigorous methods for handling motion artifact. We used task-based fMRI to identify the somatomotor cortical region with the highest task-evoked signal related to movement of the affected hand and used this region as a seed for rsFC (i.e. correlation between the seed average time course and every voxel in the brain) in the pre- and post-BTX conditions. We generated within-subject rsFC difference maps from post- minus pre-BTX rsFC to identify FC changes related to therapeutic BTX response.

Results: The right-hand tapping task evoked a strong fMRI signal in the left primary motor cortex. Seeding this region for rsFC demonstrated a somatomotor network including cortical regions, basal ganglia, thalamus, and cerebellum in both pre- and post-BTX conditions, but post-BTX showed stronger cortico-cerebellar rsFC, specifically within areas of HIX, HVIIIa, and HVIIIb belonging to cerebellar sensorimotor and directed attention networks.

Conclusion: This preliminary work demonstrates feasibility of studying individual-specific therapeutic mechanisms in FHD using PFM. BTX treatment in this individual was associated with increased cortico-cerebellar rsFC.  Further studies are necessary to validate these observations.

References: 1. Jinnah HA, Neychev V, Hess EJ. The Anatomical Basis for Dystonia: The Motor Network Model. Tremor Other Hyperkinet Mov (N Y). 2017;7:506. doi:10.7916/D8V69X3S
2. Hok P, Veverka T, Hluštík P, Nevrlý M, Kaňovský P. The Central Effects of Botulinum Toxin in Dystonia and Spasticity. Toxins (Basel). 2021;13(2). doi:10.3390/toxins13020155
3. Newbold DJ, Laumann TO, Hoyt CR, et al. Plasticity and Spontaneous Activity Pulses in Disused Human Brain Circuits. Neuron. 2020;107(3):580-589.e6. doi:10.1016/J.NEURON.2020.05.007
4. Gordon EM, Laumann TO, Gilmore AW, et al. Precision Functional Mapping of Individual Human Brains. Neuron. 2017;95(4):791-807.e7. doi:10.1016/j.neuron.2017.07.011

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MDS Abstracts - https://www.mdsabstracts.org/abstract/precision-functional-mri-mapping-of-therapeutic-response-in-focal-hand-dystonia/