P 173. Motor skill acquisition in neurofibromatosis type 1 patients

Abstract

Neurofibromatosis type 1 (NF-1) is the most common single gene disorder affecting the human nervous system, with an estimated prevalence of two to three cases per 10,000 population. The disorder is inherited in an autosomal dominant manner with equal sex incidence. Cognitive deficits and academic learning difficulties are the most common neurological complication, and can be responsible for significant lifetime morbidity. Recent animal studies proposed increased GABA-mediated inhibition with concomitant deficits in long-term potentiation as a potential mechanism for the learning impairment in these patients. The aim of the present study was to investigate the acquisition of a new motor skill in a group of young NF-1 patients without any neurological impairment. Furthermore, we used double-pulse TMS (dpTMS) in order to determine NF1-related effects on inhibitory (GABAergic) and facilitatory (Glutamatergic) motorcortical circuits during the process of motor skill acquisition. In this Pilot study, a group of NF-1 patients without any cognitive or learning deficit and healthy controls participated in an explicit motor learning experiment (for details see Zimerman et al. 2012), composed of a sequential pressing of nine-elements sequence on a four-button electronic keyboard with the left hand. All participants attended five consecutive days of training and two follow-up measurements 10 and 20 days after training, where the task was re-evaluated. dpTMS measurements were performed at baseline, immediately after the training days and before the follow-up times. Additionally, factors that might potentially influence motor learning, such as level of attention, perception of fatigue or discomfort were evaluated. Preliminary results suggested an impairment in motor skill acquisition in NF-1 patients ( F = 2.8; p = .05), driven mainly by a decrease on ‘offline improvement’ in NF-1 compared to healthy subjects ( T = − 2.9; p = .03). In healthy subjects a reduction of intracortical inhibition in the motor cortex was apparent after the learning task compared to baseline, this was not the case for the NF-1 patients, who did not show any change due to learning. Furthermore, reduced intracortical facilitation was obvious in the patients. The present pilot study provides a first hint that the acquisition of a skill might be impaired in even clinically intact NF-1 patients. One potential mechanism that could at least in part contribute to explain these behavioural deficits observed in NF1-patients is alteration of intracortical circuits related to GABAergic and/or glutamatergic neurotransmission. Further experiments are necessary to support the present findings and to gather greater understanding of the pathophysiological mechanisms of NF1, an important basis to design appropriate interventions to support skill acquisition in these patients.