Monoaminergic modulation of the relation between motor cortical activity and grip force

Our motor system can accurately control movement within both very low and very high force ranges, despite working through noisy cortical neurons, each with individually limited dynamic range. The visual system has peripheral gain mechanisms whereby neurons in the central nervous system see only a small fraction of the enormous range of luminance in the visual scene encountered throughout the day. The motor system might use an analogous system. One such mechanism could be mediated through monoaminergic input to the spinal cord and its modulation of the gain of motoneurons through its effect on persistent inward currents (PICs). To test this possibility, we measured the cortical activity of three monkeys during a power grasp task before and after giving them systemic serotonin agonist or antagonist drugs. We hypothesized that the drugs would alter the effect of serotonin on the PICs in motoneurons, thereby changing the relation between cortical activity and motor output. In two monkeys, this was largely the case, although in two conditions the results were not statistically significant. However, in a third monkey, the results were opposite to our hypothesis. These conflicting results raise further questions as to the roles monoamines may play in regulating motor excitability to maintain accurate force control across the wide range needed for grasping movements.NEW & NOTEWORTHY Monoamines have been suggested to act as force gain controllers through their action on persistent inward currents in motoneurons. We tested this idea by comparing the modulation of grasp-related M1 activity in monkeys before and after oral administration of various monoaminergic drugs. In two of the monkeys, effects were largely consistent with the model, but in a third, they were opposite. These results underscore the complex combination of peripheral and central effects of these drugs.