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Objectives: Functional reorganisation of the motor or sensory cortex has been demonstrated in animals after section of mixed peripheral nerves. Here functional changes in the motor cortex specifically after peripheral motor denervation in humans are investigated. Methods: Functional MRI (fMRI) was used to study brain activation during a finger flexion-extension task in patients with a late onset, acquired pure motor neuropathy (n=6), contrasting results with those from patients with pure sensory neuropathies (n=4) or healthy controls (n=7). Results: Increases in the extent of activation in the motor cortex both ipsilateral and contralateral to the hand moved were found in the patients with motor neuropathy. The neuroanatomical localisation of the mixed contralateral sensorimotor cortex activation volume was more posterior for the patients with motor neuropathy than for the healthy controls (mean difference, 12 mm, p<0.05). The pure sensory neuropathy group by contrast showed no change in the extent of activation relative to healthy controls and a trend for more anterior primary sensorimotor cortex activation (p<0.06). To test whether the increased activation volumes found in patients with motor neuropathy were a result simply of factors such as increased effort with movement rather than the motor denervation, patients with hand weakness from inclusion body myositis (n=4) were studied while making similar hand movements. No differences in either the numbers of significantly activated voxels or in their localisation were found relative to healthy controls (n=10). Conclusions: These results provide a novel demonstration that peripheral denervation (as distinguished from factors related to weakness) leads to functional reorganisation of the sensorimotor cortex in the adult brain. This suggests that adaptive responses to motor denervation involve the central as well as the peripheral nervous system.

We have performed self-consistent Monte Carlo simulations on repeated velocity overshoot structures. From our calculations, we may assess the potential of such structures to enhance the average drift velocity of electrons. We find that there is no enhancement for uniformly doped structures. For spike-doped structures there is a small enhancement, but this is gained at the expense of a drop in current density. In both structures the velocity enhancement is limited by intervalley scattering.

We performed a short-term, double-blind, placebo-controlled, crossover trial of sodium dichloroacetate (DCA) therapy in 11 patients affected by various primary mitochondrial disorders. Independent measures of oxidative metabolism (venous blood metabolites, exercise testing, phosphorus magnetic resonance [MR] spectroscopy of muscle, and proton MR spectroscopy of brain) were used in order to monitor metabolic responses to the drug. One week of DCA treatment produced significant decreases (p less than 0.05) in blood lactate, pyruvate, and alanine at rest and after bicycle exercise. Proton MR spectra collected from a supraventricular volume of interest in brain of seven of 11 patients also showed significant changes. Brain lactate/creatine ratio decreased by 42% during DCA treatment (p less than 0.05). Brain choline/creatine ratio (which is low in patients with myelinopathies) increased by 18% (p less than 0.01) after therapy. N-Acetylaspartate/creatine ratio (an index of neuronal damage or loss) increased by 8% after treatment (p less than 0.05). Proton MR spectra collected in two of 11 patients from a volume of interest including the basal ganglia showed similar results (decrease of 36.6% in lactate/creatine; increases of 16% in choline/creatine and 4.5% in N-acetylaspartate/creatine). Phosphorus MR spectroscopy of muscle and self-assessed clinical disability were unchanged. Our study indicates that short-term DCA treatment not only lowers blood lactate but also improves indices of both brain oxidative metabolism and neuronal and glial density or function.