Adaptives lokomotorisches Lernen und seine Konsolidierung bei Multipler Sklerose: Funktionelle Bedeutung und Verstärkung durch transkranielle Gleichstromstimulation
Zusammenfassung der Projektergebnisse
Multiple Sclerosis (MS) is a chronic inflammatory disease that affects the central nervous system (CNS) by demyelination and neurodegeneration. The course of the disease shows high interindividual heterogeneity, but eventually results in substantial functional impairments and disease burden. Several decades of research have achieved considerable progress with respect to the management of relapses and the development of diseasemodifying therapies. However, those treatments have little to no impact on permanent cognitive and motor impairments. The work of several investigators, including ours, has increased the awareness that the individual course of MS might not only be governed by neuroimmunological properties of the disease but also determined by the innate capacity of the CNS to compensate for functional constraints related to the disease. Accordingly, brain plasticity and the patient’s individual adaptive reserve would play a crucial role in determining individual functional outcomes. Therefore, an improved understanding of the processes underlying neuroplastic adaptation and its subsequent consolidation in people with MS (PwMS) constitute an important step toward the development of novel interventions to enhance these processes. In the current project, we examined locomotor adaptation and consolidation in PwMS using a split-belt treadmill (SBT) which is composed of two independently-controlled belts (one under each leg) which can be set such that the two belts move at different speeds simultaneously. The dominant leg walked on the fast belt with a ratio 3:1 relative to the slow leg for a total of 15 min. This motor adaptation paradigm was combined with non-invasive transcranial direct current stimulation (tDCS) applied over the cerebellum after the training. The SBT paradigm was repeated 24 hours and 72 hours after the stimulation in order to evaluate its effects on consolidation. Fourty PwMS and 30 age-matched controls were randomized to participate in this sham controlled experiment. The data were collected using pressure insoles that allowed analyzing the progression of the centre of pressure along the sole of the foot during each step (gait line length). Mean gait line length asymmetry was used as the main parameter to investigate adaptation to the split belt walking and the aftereffects. PwMS showed similar behavior on the SBT compared to healthy controls, independently of their lesion load and their motor function. This indicates that MS did not impair adaptive abilities and did not disrupt storage of new interlimb relationships (i.e. after-effects) in this locomotor adaptation paradigm. Furthermore, we found no effects of offline cerebellar anodal tDCS on locomotor adaptation and consolidation. Participants who received the active stimulation showed the same retention index as sham-stimulated subjects at 24 h and 72 h after stimulation. We conclude that locomotor adaptation is preserved in people with mild-to-moderate MS, while cerebellar anodal tDCS applied immediately post-training does not further enhance this ability. Overall we believe that our study highlights the potential of SBT for adaptation training in PwMS. The transfer and the persistence of this ability overground would have a significant impact in the rehabilitation of PwMS. Our results also underline the urge to develop clear references and standards for the application of cerebellar tDCS. This step is an absolute requirement for the successful application of the technique in clinical routine where a robust effect across behaviors is mandatory. Therefore, based on the findings from this project, we have developped the LaufGast-MS study to investigate effects of locomotor adaptation training and complementary application of tDCS in PwMS. Moreover, we have started a study to address the impact of the timing of cerebellar tDCS. In future, more studies are needed to define the neurobiological substrates of maintained plasticity in PwMS and how these substrates can be enhanced to improve compensation of MS-related impairment.
Projektbezogene Publikationen (Auswahl)
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Adaptive motor learning and its consolidation in Multiple Sclerosis. 35th Congress of the ECTRIMS, Berlin, Oktober 2018
Nakchbandi L, Nguemeni C, Zeller D
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The impact of timing of cerebellar anodal transcranial direct current stimulation on motor performance in a sequential finger tapping task. 62. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Klinische Neurophysiologie und Funktionelle Bildgebung (DGKN), Berlin, März 2018
Stiehl A, Nguemeni C, Zeller D
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A single session of anodal cerebellar transcranial direct current stimulation does not induce facilitation of locomotor consolidation in patients with multiple sclerosis. Front Hum Neurosci 2020;14:588671
Nguemeni C, Homola GA, Nakchbandi L, Pham M, Volkmann J, Zeller D
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Anodal cerebellar transcranial direct current stimulation does not induce facilitation of locomotor consolidation in patients with multiple sclerosis. 64. Wissenschaftliche Jahrestagung der Deutschen Gesellschaft für Klinische Neurophysiologie und Funktionelle Bildgebung (DGKN), virtuell, November 2020
Nguemeni C, Homola GA, Nakchbandi L, Pham M, Volkmann J, Zeller D
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Impaired consolidation of visuomotor adaptation in patients with multiple sclerosis. Eur J Neurol 2021;28:884-892
Nguemeni C, Nakchbandi L, Homola G, Zeller D
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No impact of cerebellar anodal transcranial direct current stimulation at three different timings on motor learning in a sequential finger tapping task. Front Hum Neurosci 2021;15:631517
Nguemeni C, Stiehl A, Hiew S, Zeller D
