This revised application for a Mentored Patient-Oriented Research (POR) Career Development Award (K23) is designed to provide and consolidate new research skills for the applicant to test programmatic treatment elements in behavioral treatments for schizophrenia (SCZ). The training and research plan coalesce the two scientific fields of motivational psychology and cognitive neuroscience to study intrinsic motivation (IM) and learning at the clinical and neural level. The career development plan will instruct the applicant in the (a) underlying neurobiological mechanisms of motivation and cognitive deficits in SCZ and neuroimaging methodology, and (b) motivational theories and instructional cues that inspire learning. The study has two general goals which are divided by studies: Study 1 is a clinical study that will attempt to determine the thresh- hold of motivational cues needed to enhance learning on an arithmetic learning task. Study 2 is a conceptual proposal to adapt a functional Magnetic Resonance Imaging (fMRI) learning paradigm to study the neural basis of the same motivational cues in Study 1 in regions associated with hedonia. Outcome measures for study 1 will assess self-reports of motivation and related psychological components associated with IM, working memory, executive ability, acquired knowledge in arithmetic, sustained and vigilant attention, and psychiatric symptomatology including anhedonia. Study 2 will use fMRI, self-reports of IM, psychiatric symptomatology, and performance on variations of a reinforcement learning paradigm. These studies will mutually provide empirical evidence to (a) explain what extent does hypothesized sensitivity thresholds in motivational cues relate to learning and anhedonia, a key feature of negative symptoms (b) establish an objective physiological measure of IM that correlates with a behavioral IM measure, and (c) lay the groundwork for understanding brain activation in healthy controls (HC) and SCZ in terms of intrinsically motivating experiences.
Aim 1 is to determine the thresh-hold of motivational cues needed to activate hedonia and enhance learning in SCZ. Hypothesis 1 is that the learning task incorporating more motivational cues will be associated with greater enjoyment for the task, greater direct learning, and greater cognitive benefit at post-treatment and 1-month follow-up (3 cues > 2 cues > 1 cue).
Aim 2 is to explore the neural correlates involved in the experience of IM through fMRI. Hypothesis 2 is that HC will show greater activity in the ventral striatum and orbitofrontal cortex on an IM learning paradigm compared to a mundane learning paradigm. Hypothesis 3 is that activations in the ventral striatum and orbitofrontal cortex will be correlated with subjective reports of IM in HC. Hypothesis 4 is that SCZ subjects will demonstrate better learning on the IM learning paradigm compared to the mundane learning paradigm. Hypothesis 5 is that compared to HC, SCZ will show reduced activity in ventral striatum and orbitofrontal cortex in relation to reduced subjective reports of IM on the mundane learning paradigm.
Many people with schizophrenia lack the basic motivation to engage in treatment and programs for cognitive training. This is due to the symptoms of the illness and the rigorous nature of the training exercises. Since cognitive ability plays a vital role in the ability to function independently, this study and career plan will identify methods to enhance motivation for cognitive training and explore brain mechanisms related to motivation and learning.
