Sensation of effort is altered in Huntington's disease

In this study, we investigated sensation of effort in Huntington disease (HD). We tested the hypothesis that the basal ganglia are involved in processing effort sensation. The experimental paradigm consisted in a contralateral matching procedure where normal subjects (N=6) and HD patients (N=6) were required to lift a reference weight with their non-dominant index, and then compare the target-weight with variable weights lifted by the dominant index. Two kinds of sequences were administered: (1) increasing, where the first weight was lighter than the reference weight and progressively increased in 20g steps, (2) decreasing, where trials started with a heavier weight and progressively decreased. We calculated the discrimination threshold (DT) across sequences as the weight for which the subject's response changed sign. The difference between the higher and the lower threshold was defined as "uncertain area". We predicted that controls should overestimate the reference weight lifted by their non-dominant hand because the same effort produces more force when applied to stronger muscles. If the basal ganglia mediates sensation of effort, patients' capability to discriminate weights should be degraded. As expected, normal subjects overestimated the reference weight lifted by their non-dominant index and showed a restricted uncertain area, thus, indicating that were able to discriminate minimal differences in generated forces. By contrast, patients with HD underestimated the reference weight lifted by their non-dominant hand and showed a broad uncertain area, thus, demonstrating that they could detect only important differences in the matched efforts. These results suggest that effort sensation critically involves the basal ganglia. In normal conditions, in parallel with the efferent command of force, an efferent copy reflecting the magnitude of the voluntary motor command is transmitted to sensory centres. This signal and/or the integration of sensory feedback which generates what is experienced as the sense of effort, would be altered in HD.