The primary goals of this research are i) to establish how learning impacts the structure and function of the brain, and ii) to determine how learning can be modulated by factors such as feedback (positive or negative). Over the past year we have focused equally on both of these goals. 1) Impact of learning on brain structure and function (NCT00001360) Over the past few years, we have been conducting a long-term longitudinal study of participants learning different tasks (e.g. motor sequences, spatial layout) to determine how structural properties of the brain (gray matter, white matter) change over time. Over a period of four weeks, participants were trained in two different tasks and we collected extensive functional and structural MRI data over the course of training. While previous studies have identified structural changes associated with learning, even over the course of a couple of hours, our initial findings have highlighted a potential confound that needs to be accounted for in such studies. Specifically, we have found that the structural measures obtained with MRI fluctuate according to the time of day, with decreases in gray matter thickness and increases in ventricular volume. These fluctuations appear to be related to changes in cerebrospinal fluid in the brain and may reflect the impact of the daily circadian rhythm. Interestingly, these fluctuation appear to be modulated by training and we are trying to establish what additional structural and functional changes occur with training above and beyond these time-of-day effects. With the motor sequence task we find that, following training, sensorimotor networks show changes in their functional connectivity. In contrast, with the spatial layout task, hippocampal networks change. These findings suggest task-specific changes in particular networks underlie learning above and beyond any changes due to circadian fluctuations. 2) Impact of feedback on learning (NCT00001360) We are investigating the impact of feedback (positive, negative) on motor learning. Groups of participants were trained on one of two different motor tasks and either provided with positive, negative or neutral (uninformative) feedback. Training occurred in the MRI scanner and we measured fMRI activity before, during and after training. Behaviorally, we found that the impact of feedback is dependent on the task. While in a sequence learning task we find that punishment improves online performance, we observe the opposite effect in a purely motoric force-tracking task. In terms of brain activity, we found that punishment was more associated with changes in the medial temporal lobe and hippocampus, while reward was more associated with changes in the cerebellum. These findings suggest a dissociation of the neural mechanisms underlying the impact of reward and punishment that might be utilized to enhance training. Establishing the nature, degree and consequences of plasticity in the adult cortex provides important insights into the potential for rehabilitative brain therapies following injury or dysfunction in the nervous system.