Locomotor adaptation and consolidation in multiple sclerosis: Functional impact and enhancement by transcranial direct current stimulation

• Applicant: Dr. Daniel Zeller
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2015 to 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 286012902

Multiple sclerosis (MS) is a major cause of disability in younger adults. However, the extent of disability due to a given degree of brain injury is remarkably variable. Individual differences in the capacity of expressing neuronal plasticity may explain some of this variance. Additional therapeutic strategies promoting compensation of CNS damage might therefore be of great use for preventing persistent impairment in MS. Previous studies have shown that certain forms of stimulation- and training-induced rapid-onset motor plasticity are preserved in MS patients and therefore are unlikely to determine recovery. However, little is known about other subtypes of motor learning in MS patients. In view of the gradually increasing MS-related CNS injury, motor adaptation - referring to the ability to adjust to intrinsic or extrinsic perturbations of self-generated movements - might prove critical for the compensation of this damage. In particular, locomotor adaptation is of high interest, as walking ability is the most important bodily function from the patient's perspective. But it is not only the process of fast motor adaptation which may be critical for the functional compensation of brain damage. To endure over time, the acquisition of motor skills crucially depends on a process by which an initially labile memory trace becomes transformed into a more stable memory, i. e. consolidation. Notably, this process has been shown to be modifiable by a number of interventions including non-invasive brain stimulation. Here, we propose to examine (i) locomotor adaptation and (ii) its consolidation as potential factors constraining chronic functional recovery in MS patients and (iii) to enhance consolidation by transcranial direct current stimulation (tDCS). Specifically, using a multimodal approach, the hypothesis shall be tested that the ability of MS patients to functionally compensate brain injury is, to a large extent, determined by their capacity to consolidate new skills. Locomotor adaptation and its consolidation will be examined by walking tasks on a split-belt treadmill, an established paradigm tapping into cerebellum-dependent learning. Secondly, based on previous work showing that tDCS may facilitate motor consolidation in the ageing brain, we hypothesize that anodal cerebellar tDCS is able to normalize deficient consolidation of walking adaptation in MS patients. We expect our results to shed light on factors enhancing resilience toward brain injury in MS patients and to open promising new avenues to tailored treatments.

• DFG Programme: Research Grants