Abnormal Transcallosal Motor Projections in Cervical Dystonia: An fMRI and Tractographic Analysis (S57.001)

Objective: To understand the role of transcallosal projections in the cortical hyperactivity seen in cervical dystonia. Background: Cervical dystonia is a neurological disorder characterized by unwanted dynamic twisting or abnormal fixed positions of the neck. The majority of cases remain idiopathic, and even in those cases associated with known gene mutations, the pathogenesis is uncertain. Functional abnormalities in dystonia include an overabundance of muscle activity in response to motor tasks. Transcallosal projections from premotor and primary motor cortical areas to their contralateral corresponding (and other) areas regulate contralateral motor cortical function. It is unknown if any of these contralateral projections are abnormal in dystonia, and if so, how putative abnormalities might explain cortical hyperactivation with motor tasks. Prior transcranial magnetic stimulation studies have described abnormalities in transcallosal spread of activation in dystonia. We hypothesized that patients with cervical dystonia have deficient transcallosal projections and resulting inadequate inhibitory modulation of contralateral cortical motor regions. Methods: Seventeen DYT-1 negative patients with cervical dystonia and matched controls were characterized by diffusion tensor imaging and functional MRI (fMRI), just prior to therapeutic injection of botulinum toxin. fMRI signal at rest and during finger tapping was collected for independent left and right hands. Probabalistic diffusion-based tractography was conducted, pairing premotor, primary motor, primary somatosensory, and sensory association cortices with a restrictive midline mask of the corpus callosum. Tractography was compared between patients and controls for each cortical-callosal pairing. Results: Patients with cervical dystonia had robust decreases in probabilistic connectivity in premotor > primary motor > primary sensory = sensory association cortices. This correlates with the degree of functional activation seen in each cortical region with ipsilateral finger tapping, suggesting that impaired or deficient transcallosal inhibitory projections may, in part, underlie the motor cortical hyperactivity in cervical dystonia. Conclusions: Our study suggests a mechanism underlying the most common adult-onset form of dystonia, and may offer a new avenue for disease treatment. Disclosure: Dr. Waugh has nothing to disclose. Dr. Kuster has nothing to disclose. Dr. Levenstein has nothing to disclose. Dr. Sandra has nothing to disclose. Dr. Multhaupt-Buell has nothing to disclose. Dr. Nikos has nothing to disclose. Dr. Sudarsky has nothing to disclose. Dr. Breiter has nothing to disclose. Dr. Sharma has received personal compensation for activities with Merz Pharma and Allergan, Inc. Dr. Blood has nothing to disclose.