Project ID NS-MH2024_15

ThemeNS-MH

Co Supervisor 1A Faculty of Life Sciences & Medicine, School of Life Course & Population Sciences, Department of Population Health SciencesWebsite

Co Supervisor 1B Institute of Psychiatry, Psychology & Neuroscience, School of Neuroscience, Department of Basic & Clinical NeuroscienceWebsite

Modulating cortical connectivity with transcranial magnetic stimulation to enhance sensorimotor function in movement disorders

Scientific basis and translational potential
The generation of skilled upper limb movements relies on a complex neuronal network including several cerebral cortical and sub-cortical areas. The processing of multi-modal sensory information and its efficient transfer across this network are critical to produce precise and adaptable movements in an ever-changing environment. Damage to regions of this network during critical windows of neurodevelopment impacts dramatically on sensorimotor function, leading to devastating movement disorders such as dystonic-dyskinetic cerebral palsy (DCP). Our own work has recently demonstrated impaired cortical sensorimotor processing in children and young people with dystonia and DCP.

Using novel transcranial magnetic stimulation (TMS) techniques, we have recently measured the connectivity between two cortical nodes of this network, allowing us to test whether sensorimotor information is transferred efficiently and what alterations occur following cortical damage. Recent findings also reveal that up-regulation of cortical connectivity via TMS-induced Hebbian-like neuroplasticity mechanisms can lead to improved performance of perceptual tasks. However, it is unknown whether these TMS-induced perceptual gains can be translated into improved motor control. We hypothesise that up-regulating the connectivity between specific sensorimotor areas will improve sensorimotor integration and, consequently, the definition of motor commands in healthy volunteers, with the potential to restore sensorimotor function in children/adults with disabling movement disorders.

Aims/Objectives
Year1: Determine TMS parameters for inducing neuroplastic changes in cortical sensorimotor connectivity with parallel gains in motor function in healthy volunteers.
Year2: Use TMC to measure cortical connectivity in children with DCP and compare connectivity patterns with healthy volunteers.
Year 3-4: Determine TMS parameters for modulating cortical connectivity in young people with DCP; Investigate whether modulating cortical connectivity patterns in children with DCP leads to improved sensorimotor function and goal achievement.

Skills
Transcranial magnetic stimulation, electroencephalo- and myography (EEG, EMG), time- and frequency-based analysis of neurophysiological signals.

Representative Publications

Romero MC, Merken L, Janssen P, Davare M. Neural effects of continuous theta-burst stimulation in macaque parietal neurons. Elife. 2022 Sep 13;11:e65536. doi: 10.7554/eLife.65536.

van Polanen V, Buckingham G, Davare M. The effects of TMS over the anterior intraparietal area on anticipatory fingertip force scaling and the size-weight illusion. J Neurophysiol. 2022 Aug 1;128(2):290-301. doi: 10.1152/jn.00265.2021.

Rens G, van Polanen V, Botta A, Gann MA, Orban de Xivry JJ, Davare M. Sensorimotor Expectations Bias Motor Resonance during Observation of Object Lifting: The Causal Role of pSTS. J Neurosci. 2020 May 13;40(20):3995-4009. https://doi.org/10.1523/JNEUROSCI.2672-19.2020

McClelland VM, Fischer P, Foddai E, Dall’Orso, S, Burdet E, Brown P, Lin JP. EEG measures of sensorimotor processing and their development are abnormal in children with isolated dystonia and dystonic cerebral palsy. Neuroimage: Clinical 2021 30;102569. https://doi.org/10.1016/j.nicl.2021.102569

Sakellariou DF, Dall’Orso S, Burdet E, Lin JP, Richardson MP, McClelland VM. Abnormal microscale neuronal connectivity triggered by a proprioceptive stimulus in dystonia. Scientific Reports 2020 10 (1):20758. https://doi.org/10.1038/s41598-020-77533-w

McClelland VM, Cvetkovic Z. Lin J-P, Mills KR, Brown P. Abnormal patterns of corticomuscular and intermuscular coherence in childhood dystonia. Clinical Neurophysiology 2020 131(4):967-977. https://doi.org/10.1016/j.clinph.2020.01.012