Dr. Thakkar’s research program aims to understand the biological basis of psychotic disorders, namely schizophrenia. More specifically, she uses translational methods, largely grounded in animal neurophysiology, to examine the basic building blocks of impaired cognition, disrupted social abilities, and the core disturbances in the sense of self-purported to characterize psychosis. Understanding these most basic impairments that give rise to the profound cognitive, social, and psychotic symptoms of schizophrenia can help us pinpoint disturbances in specific functional circuitry. A deeper understanding of these symptoms and their mechanisms will eventually lead to more targeted behavioral and pharmacological treatment options. To explore the neurobiology of psychotic disorders, she uses a variety of approaches including eye tracking, functional magnetic resonance imaging (fMRI), diffusion tensor imaging (DTI), magnetic resonance spectroscopy (MRS), behavioral experiments, and first-person accounts of experience.
The ability to make rapid behavioral adjustments is critical in a dynamic environment, and impaired action control is associated with several neuropsychiatric disorders, including schizophrenia. Rapid action modification and cancellation has been investigated using the stop-signal task and related paradigms. These paradigms require a fast response to a movement cue unless a subsequent signal is presented that instructs participants to inhibit or change the planned movement. Performance on these tasks is modeled as a race between competing STOP and GO processes, which permits an estimation of the time it takes to stop a prepared action—stop-signal reaction time. Using oculomotor versions of such tasks, nonhuman primate studies have investigated the cellular basis of reactive action control and performance monitoring. This body of neurophysiology work provides a firm basis from which to understand the brain circuits supporting reactive action control in humans. In this talk, I will present work that uses fMRI to examine the network involved in rapid cancellation, modification, and monitoring of gaze in humans. In addition, I will present a series of studies indicating reduced efficiency of action cancellation in individuals with schizophrenia that are related to symptoms and functional outcomes and more recent work demonstrating altered activation in a frontobasal network in individuals with schizophrenia while performing a modified oculomotor stop-signal task. Combined, this work provides a link between mechanisms of action control in humans and non-human primates and insights into potential mechanisms of inefficient action control in individuals with schizophrenia.