The ability to make accurate movements in response to environmental stimuli is integral to the survival and well-being of many animal species. To that end, many of the movements we make on a daily basis have been practiced to the point of near-automatic accuracy. Even with intensive practice, however, repeated attempts at the same movement goal are inevitably variable at a fine scale. Traditional theories of motor control have attributed trial-by-trial variability in motor output to the failure of peripheral effectors, such as muscles and joints, to perfectly execute the motor command specified by the brain. More recent evidence suggests that at least some variability in motor output is correlated with variable neural responses in certain areas of the brain. This has led to the emerging view that trial-by-trial neural variability, rather than representing "noise" may be inherent to the "signal" that the brain uses to control motor output.

In this thesis, we used visually guided reaching as a model to study the relationship of neural variability in the dorsal premotor cortex (PMd) to movement variability. As described in Chapter 1, we found that for some PMd neurons, variability in planning-related activity, preceding movement onset, is correlated with trial-by-trial fluctuations in reach direction. We exploited these correlations to distinguish target- and movement-related neurons; our results suggest that PMd activity preceding movement is related to both the movement goal and the intended action. In Chapter 2, we quantified the fraction of movement direction variability predicted by planning-related activity of individual PMd neurons as well as of ensembles of 19-115 simultaneously recorded neurons. We found that preparatory activity of individual neurons typically predicted less than 1% of movement direction variability, while ensemble activity could predict up to 30-40%. Our results suggest that the movement planning process may be variable even under nominally identical task conditions, and that variability in the motor plan could give rise to measurable changes in movement direction across repeated trials.