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.

VRAG-R Documentation

The VRAG-R is designed to assess the likelihood of violent or sexual reoffending among male offenders. The data set comprises demographic, criminal history, psychological assessment, and psychiatric information about the offenders gathered from institutional files together with post-release recidivism information. The VRAG-R is a twelve-item actuarial instrument and the scores on these items form part of the data set. Because one of the goals of the VRAG-R development project was to compare the VRAG-R to the VRAG, subjects' VRAG scores are included in this data set. Access to the VRAG-R dataset is restricted. Contact Data Services, Queen's University Library (academic.services@queensu.ca) for access.

Coding Manuals

The VRAG-R is designed to assess the likelihood of violent or sexual reoffending among male offenders. The data set comprises demographic, criminal history, psychological assessment, and psychiatric information about the offenders gathered from institutional files together with post-release recidivism information. The VRAG-R is a twelve-item actuarial instrument and the scores on these items form part of the data set. Because one of the goals of the VRAG-R development project was to compare the VRAG-R to the VRAG, subjects' VRAG scores are included in this data set. Access to the VRAG-R dataset is restricted. Contact Data Services, Queen's University Library (academic.services@queensu.ca) for access.