Physiological effects of subthalamic nucleus deep brain stimulation surgery in cervical dystonia

Abstract

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.

Keywords: dystonia; electrical stimulation; magnetic stimulation; physiology.

Conflict of interest statement

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.

© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Figures

Figure 1:

Figure 1 (A) Group average data on short latency afferent inhibition (SAI) in patients with cervical dystonia during DBS OFF and ON and in healthy controls. Compared with test pulse, SAI is significant only when single stimulation paradigm is applied. In comparison with healthy controls, SAI is significantly increased. SAI is found to be increased at interstimulus interval (ISI) of 20 and 30 ms in the presence of single median nerve stimulation when DBS is turned off. The x-axis indicates the groups and the ISIs studied. The y-axis shows afferent inhibition as ratios of the conditioned (test stimulus with preceding peripheral nerve stimulation) to the unconditioned (test stimulus alone) MEP amplitude. Values 1 indicate facilitation. Dark grey bar represents DBS OFF, light grey represents DBS ON, and white bar represents healthy control subjects. Error bars represent SEs. Asterisks above the bars indicate significant inhibition compared with test pulse alone. *P