Background Subthalamic nucleus deep brain stimulation (STN DBS) surgery is clinically effective for treatment of cervical dystonia; however, the underlying physiology has not been examined. We used transcranial magnetic stimulation (TMS) to examine the effects of STN DBS on sensorimotor integration, sensorimotor plasticity and motor cortex excitability, which are identified as the key pathophysiological features underlying dystonia.
Methods TMS paradigms of short latency afferent inhibition (SAI) and long latency afferent inhibition (LAI) were used to examine the sensorimotor integration. Sensorimotor plasticity was measured with paired associative stimulation paradigm, and motor cortex excitability was examined with short interval intracortical inhibition and intracortical facilitation. DBS was turned off and on to record these measures.
Results STN DBS modulated SAI and LAI, which correlated well with the acute clinical improvement. While there were no changes seen in the motor cortex excitability, DBS was found to normalise the sensorimotor plasticity; however, there was no clinical correlation.
Conclusion Modulation of sensorimotor integration is a key contributor to clinical improvement with acute stimulation of STN. Since the motor cortex excitability did not change and the change in sensorimotor plasticity did not correlate with clinical improvement, STN DBS demonstrates restricted effects on the underlying physiology.
Clinical trial registration NCT01671527.
- magnetic stimulation
- electrical stimulation
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Contributors AWS: study concept and design, research project execution, acquisition of data, data processing and statistical analysis, manuscript preparation. JLO: manuscript preparation, study collaboration, manuscript critique. DEV: manuscript preparation, manuscript critique. RC: manuscript critique. KDF: manuscript preparation. MSO: study supervision, manuscript preparation.
Funding NIH KL2 TR000065 (AWS).
Competing interests AWS reports grants from the NIH and has received grant support from Benign Essential Blepharospasm Research Foundation, Dystonia Coalition, Dystonia Medical Research Foundation, National Organization for Rare Disorders and NIH (NIH KL2 TR000065). JLO received research support from St Jude Medical, Boston Scientific, Cala Health and Google, and received educational grant support from Medtronic, Boston Scientific, Merz, Allergan and AbbVie. She has also received grant support from the Michael J Fox Parkinson’s Disease Foundation. DEV reports grant support from NIH, Bachmann-Strauss Foundation and Tyler’s Hope Foundation. He is cofounder and manager of Neuroimaging Solutions. RC received research support from the Canadian Institutes of Health Research, Catherine Manson Chair in Movement Disorders, the Weston Foundation, Medtronic and Merz. He was a consultant for Merz, Allergan and UCB. KDF received research support and fellowship support from Medtronic and has received an honorarium from Medtronic for chairing an expert DBS practitioners' symposium. He has received research support from and serves on the neurosurgery advisory board for NeuroPace. He has also received research support from St Jude, Boston Scientific and Functional Neuromodulation. All listed research support has been granted to the University of Florida. MSO serves as consultant for the National Parkinson’s Foundation and has received research grants from the National Institutes of Health, National Parkinson’s Foundation, Michael J Fox Foundation, Parkinson Alliance, Smallwood Foundation, Bachmann-Strauss Foundation, Tourette Syndrome Association and UF Foundation. MSO has previously received honoraria, but in the past >60 months has received no support from industry. MSO has received royalties for publications with Demos, Manson, Amazon, Smashwords, Books4patients and Cambridge (movement disorders books). MSO is an associate editor for the New England Journal of Medicine Journal Watch Neurology. MSO has participated in CME and educational activities on movement disorders (in the last 36 months) sponsored by PeerView, Prime, Quantia, Henry Stewart and the Vanderbilt University. The institution and not MSO receives grants from Medtronic, AbbVie and ANS/St Jude, and the PI has no financial interest in these grants. MSO has participated as a site PI and/or co-I for several NIH, foundation and industry-sponsored trials over the years but has not received honoraria.
Ethics approval University of Florida.
Provenance and peer review Not commissioned; externally peer reviewed.
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