Motor cortex plasticity induction by pairing subthalamic nucleus deep brain stimulation and dorsal premotor cortical transcranial magnetic stimulation in Parkinsons disease
Final Report Abstract
Background: In patients with Parkinson’s disease the dorsal premotor cortex appears to be abnormally active which also affects connections to the primary motor cortex with a shift towards increased facilitation. Dopaminergic therapy can normalise such pathologically facilitated interaction and strengthen intracortical inhibitory circuits. Deep brain stimulation is an effective treatment option that has shown to increase primary motor cortex inhibition in Parkinson’s disease in various transcranial magnetic stimulation studies. However, the clear mechanism of action of DBS, as well as its influences on premotor-motor interaction is still a matter of debate. Methods: In this project, we investigated eight Parkinson’s disease patients in whom we time-locked single deep brain stimulation pulses of the subthalamic nucleus to MR-neuronavigated transcranial magnetic dual-coil, paired-pulse stimulation of the dorsal premotor area and the primary motor cortex. These experiments were complemented by transcranial magnetic stimulation measurements of the premotor-motor interaction when the deep brain stimulation was switched off and compared to 11 healthy age and sex-matched control subjects. Results: Parkinson’s disease patients showed facilitated premotor-motor interaction with deep brain stimulation being switched off and compared to healthy controls. This increased premotor-motor excitation was reduced when deep brain stimulation was switched on and further resulted in premotor-motor inhibition when subthalamic nucleus stimulation preceded premotor pulses by 25 ms. Conclusions: Dorsal premotor cortex influences on the primary motor cortex are abnormally facilitated in Parkinson’s disease patients. Subthalamic nucleus deep brain stimulation is able to reverse this pathologic premotor excitation at a medium interstimulus interval, which most likely represent an othodromic indirect subthalamicpallidal-thalamic-premotor-motor cortex circuits in our study design. Future plans: The applicant will continue her research work at the University of Lübeck and will further investigate the possibility of inducing primary motor cortex plasticity through paired associative stimulation at the identified ISI of subthalamic nucleus deep brain stimulation and dorsal premotor cortex transcranial magnetic stimulation. Her research scholarship at the University of Toronto helped her to establish a novel neurophysiological paradigm relevant for the understanding of deep brain stimulation in Parkinson's disease, increase her scientific knowledge and proficiency and lay the foundation for receiving additional funding from the University of Lübeck to continue her research work and further explore basal ganglia-premotor-motor cortex connectivity.
Publications
- (2017) Alcohol improves cerebellar learning deficit in myoclonus-dystonia: A clinical and electrophysiological investigation. Annals of neurology 82 (4) 543–553
Weissbach, Anne; Werner, Elisa; Bally, Julien F.; Tunc, Sinem; Löns, Sebastian; Timmann, Dagmar; Zeuner, Kirsten E.; Tadic, Vera; Brüggemann, Norbert; Lang, Anthony; Klein, Christine; Münchau, Alexander; Bäumer, Tobias
(See online at https://doi.org/10.1002/ana.25035) - (2017) Influence of L-dopa on subtle motor signs in heterozygous Parkin- and PINK1 mutation carriers. Parkinsonism & related disorders 42 95–99
Weissbach, Anne; König, Inke R.; Hückelheim, Katja; Pramstaller, Peter P.; Werner, Elisa; Brüggemann, Norbert; Tadic, Vera; Lohmann, Katja; Bäumer, Tobias; Münchau, Alexander; Kasten, Meike; Klein, Christine
(See online at https://doi.org/10.1016/j.parkreldis.2017.07.003) - Abnormal premotor-motor interaction in heterozygous Parkin- and Pink1 mutation carriers. Clin. Neurophysiol. 2017;128(1):275-280
Weissbach A, Bäumer T, Pramstaller P, et al.
(See online at https://doi.org/10.1016/J.clinph.2016.10.007) - Dystonie. In: Hans-Christoph Diener, Helmuth Steinmetz, Oliver Kastrup (editor), Referenz Neurologie, Thieme Verlag; 2017, S 233-241
Weissbach A, Bäumer B
