The goal of our research program is to identify specific, low-level “building blocks” of cognition that are impaired in people with schizophrenia (PSZ), are linked with neurobiology, and can explain deficits in higher- level cognitive function. Our prior research has led to the hyperfocusing hypothesis, which proposes that many aspects of cognitive impairment in PSZ can be traced to overly narrow and intense focusing of processing resources on a subset of available inputs, and an inability to distribute resources among multiple sources of information. Hyperfocusing can explain reduced working memory capacity and impaired performance in a variety of attention tasks, and measures of hyperfocusing are strongly correlated with measures of broad cognitive function (e.g., IQ). We have also found that PSZ exhibit an aberrant working memory dynamics in tasks that require storing a single location or orientation in working memory on each trial. As the current-trial maintenance period increases, working memory representations in healthy control subjects (HCS) drift closer and closer toward the location or orientation of the previous-trial target (attraction), whereas working memory representations in PSZ drift farther and farther away (repulsion). Working with a computational neuroscientist, we have identified two potential neural mechanisms that could explain these aberrant working memory dynamics and may also explain our prior hyperfocusing results. One hypothesis is that short-term synaptic plasticity mechanisms are impaired in PSZ. The other hypothesis is that neuronal adaptation mechanisms are exaggerated in PSZ. The main goal of this project is to test these two hypotheses of microcircuit disfunction in schizophrenia and determine whether and how they are related to hyperfocusing and broad cognitive function. In Aim 1, we will use sophisticated behavioral tasks that can determine whether the aberrant working memory dynamics in PSZ are a result of impaired short-term synaptic plasticity or exaggerated neuronal adaptation. In Aim 2, we will provide converging evidence from other experimental paradigms, including both behavioral and neural measures. In Aim 3, we will determine whether the aberrant working memory dynamics and hyperfocusing reflect a common underlying mechanism, distinct from executive control. Aim 3a will address this statistically by obtaining multiple measures of working memory dynamics, hyperfocusing, executive control, and broad cognitive function in a relatively large sample of PSZ and HCS. Aim 3b will use neural network modeling to address the same issue by determining whether an alteration in a single component of the neural microcircuitry (e.g., reduced short-term synaptic plasticity) leads to patterns of aberrant behavior across models of different tasks that match the pattern of aberrant behavior exhibited by PSZ in these tasks. The results of the research will have important implications for efforts to develop new treatments...