The direct cortico-motoneuronal connection is believed to be essential for the control of dexterous hand movements, such as precision grip in primates. It was reported, however, that even after lesion of the corticospinal tract (CST) at the C4-C5 segment, precision grip largely recovered within 1-3 mo, suggesting that the recovery depends on transmission through intercalated neurons rostral to the lesion, such as the propriospinal neurons (PNs) in the midcervical segments. To obtain direct evidence for the contribution of PNs to recovery after CST lesion, we applied a pathway-selective and reversible blocking method using double viral vectors to the PNs in six monkeys after CST lesions at C4-C5. In four monkeys that showed nearly full or partial recovery, transient blockade of PN transmission after recovery caused partial impairment of precision grip. In the other two monkeys, CST lesions were made under continuous blockade of PN transmission that outlasted the entire period of postoperative observation (3-4.5 mo). In these monkeys, precision grip recovery was not achieved. These results provide evidence for causal contribution of the PNs to recovery of hand dexterity after CST lesions; PN transmission is necessary for promoting the initial stage recovery; however, their contribution is only partial once the recovery is achieved.spinal cord injury | plasticity | neural circuit | nonhuman primates | viral vector A s a potential treatment for brain and spinal cord injury, regeneration of the injured axons has been attempted in animal models, often using rodents with corticospinal tract (CST) lesions. Regeneration of the injured CST fibers was facilitated by treatments such as peripheral nerve graft (1), application of an antibody against neurite growth inhibitors IN-1 (2), combined application of the antibody and neurotrophic factor NT-3 (3), and transplantation of neural stem cells derived from induced pluripotent stem cells (4). A more recent study showed that regenerated CST axons increased the connection to the spinal motoneurons (MNs) after spinal cord injury in monkeys (5). However, in these studies, the causal contribution of such regenerated fibers to the functional recovery was not directly demonstrated. Therefore, recent debates address the question whether these therapies should target repairing the injured CST fibers and/or facilitating compensation by indirect cortico-motoneuronal (CM) connections via other descending motor pathways (6-9).Traditionally, the neural control of dexterous hand movements in higher primates has primarily been associated with development of the direct pathway from the motor cortex to MNs, known as the CM pathway (10-12). Lesion of the CST at the brainstem level in nonhuman primates caused near-permanent loss of dexterous hand movements (13). The authors also argued for partial compensation of grasping movements by the brainstemmediated descending pathways such as the rubrospinal tract (14). More recent studies on the neural basis of functional recovery following CST lesions ...

Reaction time is accelerated if a loud (startling) sound accompanies the cue—the “StartReact” effect. Animal studies revealed a reticulospinal substrate for the startle reflex; StartReact may similarly involve the reticulospinal tract, but this is currently uncertain. Here we trained two female macaque monkeys to perform elbow flexion/extension movements following a visual cue. The cue was sometimes accompanied by a loud sound, generating a StartReact effect in electromyogram response latency, as seen in humans. Extracellular recordings were made from antidromically identified corticospinal neurons in primary motor cortex (M1), from the reticular formation (RF), and from the spinal cord (SC; C5–C8 segments). After loud sound, task-related activity was suppressed in M1 (latency, 70–200 ms after cue), but was initially enhanced (70–80 ms) and then suppressed (140–210 ms) in RF. SC activity was unchanged. In a computational model, we simulated a motoneuron pool receiving input from different proportions of the average M1 and RF activity recorded experimentally. Motoneuron firing generated simulated electromyogram, allowing reaction time measurements. Only if ≥60% of motoneuron drive came from RF (≤40% from M1) did loud sound shorten reaction time. The extent of shortening increased as more drive came from RF. If RF provided <60% of drive, loud sound lengthened the reaction time—the opposite of experimental findings. The majority of the drive for voluntary movements is thus likely to originate from the brainstem, not the cortex; changes in the magnitude of the StartReact effect can measure a shift in the relative importance of descending systems. SIGNIFICANCE STATEMENT Our results reveal that a loud sound has opposite effects on neural spiking in corticospinal cells from primary motor cortex, and in the reticular formation. We show that this fortuitously allows changes in reaction time produced by a loud sound to be used to assess the relative importance of reticulospinal versus corticospinal control of movement, validating previous noninvasive measurements in humans. Our findings suggest that the majority of the descending drive to motoneurons producing voluntary movement in primates comes from the reticulospinal tract, not the corticospinal tract.

Recently, surface electroencephalogram (EEG)-based brain-machine interfaces (BMI) have been usedfor people with disabilities. As a BMI signal source, event-related desynchronization of alpha-band EEG (8-13 Hz) during motor imagery (mu ERD), which is interpreted as desynchronized activities of the activated neurons, is commonly used. However, it is often difficult for patients with severe hemiparesis to produce mu ERD of sufficient strength to activate BMI. Therefore, whether it is possible to modulate mu ERD during motor imagery with anodal transcranial direct-current stimulation (tDCS) was assessed in a severe left hemiparetic stroke patient. EEG was recorded over the primary motor cortex (M1), and mu ERD during finger flexion imagery was measured before and after a 5-day course of tDCS applied to M1. The ERD recorded over the affected M1 increased significantly after tDCS intervention. Anodal tDCS may increase motor cortex excitability and potentiate ERD during motor imagery in patients with severe hemiparetic stroke. (Keio J Med 60 (4) : 114-118, December 2011)