Sensorimotor inhibition in Dystonia

• Applicant: Privatdozent Dr. Christos Ganos
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2013 to 2015
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 245458566

Dystonia is a movement disorder characterised by twisting and repetitive movements or abnormal postures caused by sustained muscle contractions. Despite remarkable advances in genetic research in recent time, the pathophysiology of primary adult-onset focal dystonia remains unclear. However, insufficient inhibition at spinal, brainstem and cortical levels is a key finding. Previous studies reported inhibitory deficits (e.g., in intracortical inhibition and surround inhibition) in motor and somatosensory systems, but most studies involved only one measure and very few patients. Thus, it is unclear whether the inhibitory deficits are system- specific or reflect a general abnormality of cortical circuits. This study therefore aims at a more systematic investigation and improved understanding of cortical inhibitory deficits in dystonia.Inhibitory circuits allow the cortex to separate irrelevant environmental events from information relevant to controlling behaviour. Sensory brain areas must prevent overload of higher cortical functions by isolating important signals from background noise events. The motor system faces an analogous problem of focusing motor commands on a single muscle or set of muscles. This requires inhibiting excitability of other, adjacent muscles, to prevent spread of motor activity. Both functions depend on short-range inhibitory interneurons in sensorimotor cortices, and also on inhibitory pathways from thalamus to cortex. These mechanisms provide the pervasive but crucial function of fine- tuning cortical activity to achieve precise perceptual coding and motor control. This study therefore aims to clarifying how cortical inhibitory mechanisms defend high-level processing against excessive reactivity to irrelevant noise, in health and in diseaseWe will investigate patterns of cortical inhibitory deficits in focal hand dystonia (FHD) and cervical dystonia (CD) patients, and matched healthy volunteers. Each patient performs a simple but comprehensive test battery comprising 6 tasks, and multiple measures. The battery covers different cortical systems (motor and somatosensory), different body parts both affected and unaffected, and both spatial and temporal aspects of inhibition. Statistical analysis will identify which tests best capture insufficient inhibition in dystonia. Multivariate approaches are used to model factors that explain shared variance across tests and cortical systems.Our project will provide a systematic account of inhibitory processing in dystonia. This may provide a reliable endophenotype, which could allow identification of new genes by exome sequencing. Moreover, it would facilitate future studies comparing carriers of candidate genes for adult-onset focal dystonia with manifesting patients, if such genes are discovered. Finally, it may enable future treatment studies based on training or enhancing inhibitory cortical functions in dystonia.

• DFG Programme: Research Fellowships
• International Connection: United Kingdom
• Hosts: Professor Kailash Bhatia; Professor Dr. Patrick Haggard