To determine whether simultaneously recorded motor cortex neurons can be used for real-time device control, rats were trained to position a robot arm to obtain water by pressing a lever. Mathematical transformations, including neural networks, converted multineuron signals into 'neuronal population functions' that accurately predicted lever trajectory. Next, these functions were electronically converted into real-time signals for robot arm control. After switching to this 'neurorobotic' mode, 4 of 6 animals (those with > 25 task-related neurons) routinely used these brain-derived signals to position the robot arm and obtain water. With continued training in neurorobotic mode, the animals' lever movement diminished or stopped. These results suggest a possible means for movement restoration in paralysis patients.
Despite several studies and models, much remains unclear about how the human basal ganglia operate. Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective treatment for complicated Parkinson's disease, but how DBS acts also remains unknown. The clinical benefit of DBS at frequencies >100 Hz suggests the possible importance of neural rhythms operating at frequencies higher than the range normally considered for basal ganglia processing (<100 Hz). The electrodes implanted for DBS also offer the opportunity to record neural activity from the human basal ganglia. This study aimed to assess whether oscillations at frequencies >100 Hz operate in the human STN. While recording local field potentials from the STN of nine patients with Parkinson's disease through DBS electrodes, we found a dopamine- and movement-dependent 300-Hz rhythm. At rest, and in the absence of dopaminergic medication, in most cases (eight out of 11 nuclei) the 100-1000 Hz band showed no consistent rhythm. Levodopa administration elicited (or markedly increased) a 300-Hz rhythm at rest [(mean +/- SD) central frequency: 319 +/- 33 Hz; bandwidth: 72 +/- 21 Hz; power increase (after medication - before medication)/before medication: 1.30 +/- 1.25; n = 11, P = 0.00098]. The 300-Hz rhythm was also increased by apomorphine, but not by orphenadrine. The 300-Hz rhythm was modulated by voluntary movement. Before levodopa administration, movement-related power increase in the 300-Hz rhythm was variably present in different subjects, whereas after levodopa it became a robust phenomenon [before 0.014 +/- 0.014 arbitrary units (AU), after 0.178 +/- 0.339 AU; n = 8, P = 0.0078]. The dopamine-dependent 300-Hz rhythm probably reflects a bistable compound nuclear activity and supports high-resolution information processing in the basal ganglia circuit. An absent 300-Hz subthalamic rhythm could be a pathophysiological clue in Parkinson's disease. The 300-Hz rhythm also provides the rationale for an excitatory--and not only inhibitory--interpretation of DBS mechanism of action in humans.
Spinal cord injury can produce extensive long-term reorganization of the cerebral cortex. Little is known, however, about the sequence of cortical events starting immediately after the lesion. Here we show that a complete thoracic transection of the spinal cord produces immediate functional reorganization in the primary somatosensory cortex of anesthetized rats. Besides the obvious loss of cortical responses to hindpaw stimuli (below the level of the lesion), cortical responses evoked by forepaw stimuli (above the level of the lesion) markedly increase. Importantly, these increased responses correlate with a slower and overall more silent cortical spontaneous activity, representing a switch to a network state of slow-wave activity similar to that observed during slow-wave sleep. The same immediate cortical changes are observed after reversible pharmacological block of spinal cord conduction, but not after sham. We conclude that the deafferentation due to spinal cord injury can immediately (within minutes) change the state of large cortical networks, and that this state change plays a critical role in the early cortical reorganization after spinal cord injury.
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