LEARNING IMPULSE CONTROL IN A NOVEL ANIMAL MODEL: SYNAPTIC, CELLULAR, AND PHARMACOLOGICAL SUBSTRATES

Impulse control, an executive process that restrains inappropriate actions, is impaired in numerous psychiatric conditions. This thesis reports three experiments that utilized a novel animal model of impulse control, the response inhibition (RI) task, to examine the substrates that underlie learning this task. In the first experiment, rats were trained to withhold responding on the RI task, and then euthanized for electrophysiological testing. Training in the RI task increased the AMPA/NMDA ratio at the synapses of pyramidal neurons in the prelimbic, but not infralimbic, region of the medial prefrontal cortex. This enhancement paralleled performance as subjects underwent acquisition and extinction of the inhibitory response. AMPA/NMDA was elevated only in neurons that project to the ventral striatum. Thus, this experiment identified a synaptic correlate of impulse control. In the second experiment, a separate group of rats were trained in the RI task prior to electrophysiological testing. Training in the RI task produced a decrease in membrane excitability in prelimbic, but not infralimbic, neurons as measured by maximal spiking evoked in response to increasing current injection. Importantly, this decrease was strongly correlated with successful inhibition in the task. Fortuitously, subjects trained in an operant control condition showed elevated infralimbic, but not prelimbic, excitability, which was produced by learning an anticipatory signal that predicted imminent reward availability. These experiments revealed two cellular correlates of performance, corresponding to learning two different associations under distinct task conditions. In the final experiment, rats were trained on the RI task under three conditions: Short (4-s), long (60-s), or unpredictable (1-s to 60-s) premature phases. These conditions produced distinct errors on the RI task. Interestingly, amphetamine increased premature responding in the short and long conditions, but decreased premature responding in the unpredictable condition. This dissociation may arise from interactions between amphetamine and underlying cognitive processes, such as attention, timing, and conditioned avoidance. In summary, this thesis showed that learning to inhibit a response produces distinct synaptic, cellular, and pharmacological changes. It is hoped that these advances will provide a starting point for future therapeutic interventions of disorders of impulse control.

Vibrational Feedback Training System for Use with SEMG Controlled Powered Prostheses

Loss of limb results in loss of function and a partial loss of freedom. A powered prosthetic device can partially assist an individual with everyday tasks and therefore return some level of independence. Powered upper limb prostheses are often controlled by the user generating surface electromyographic (SEMG) signals. The goal of this thesis is to develop a virtual environment in which a user can control a virtual hand to safely grasp representations of everyday objects using EMG signals from his/her forearm muscles, and experience visual and vibrotactile feedback relevant to the grasping force in the process. This can then be used to train potential wearers of real EMG controlled prostheses, with or without vibrotactile feedback. To test this system an experiment was designed and executed involving ten subjects, twelve objects, and three feedback conditions. The tested feedback conditions were visual, vibrotactile, and both visual and vibrotactile. In each experimental exercise the subject attempted to grasp a virtual object on the screen using the virtual hand controlled by EMG electrodes placed on his/her forearm. Two metrics were used: score, and time to task completion, where score measured grasp dexterity. It was hypothesized that with the introduction of vibrotactile feedback, dexterity, and therefore score, would improve and time to task completion would decrease. Results showed that time to task completion increased, and score did not improve with vibrotactile feedback. Details on the developed system, the experiment, and the results are presented in this thesis.