Investigating the physiology of human decision-making in prefrontal cortex
Through our interactions with the environment, we are constantly faced with decisions. Although the majority of these decisions are made rapidly and with nearly imperceptible effort, some require a thorough but rapid examination of the circumstance, prediction of possible consequences, and execution of action: for example, whether to press the brake, accelerator, or neither when approaching a yellow traffic light. The behavioral output (action of the foot) must be delayed for a fraction of a second while this analysis is being performed. Our ability to efficiently evaluate the environmental cues, parse the likelihood of various outcomes for a narrow range of responses, and choose the most profitable action is essential for survival. The prefrontal cortex (PFC), the most evolutionarily advanced region of the human brain, has developed specialized networks for making these decisions.

Our previous results (Sheth et al. Nature 2012) demonstrated the critical role of the medial PFC, especially the dorsal anterior cingulate cortex (dACC), in optimizing performance in the face of conflicting contextual demands. Previous work from other groups has also described the importance of lateral PFC regions, especially dorsolateral PFC (dlPFC), in engaging control mechanisms to guide behavior in these circumstances.

We are currently using a combination of functional MRI (fMRI), single neuronal recordings, and local field potential recordings to investigate the interaction between lateral and medial PFC during decision-making.

Investigating cortical and basal ganglia networks involved in disorders of mental health
Patients with certain psychiatric disorders that are resistant to conventional treatment strategies may be candidates for surgical intervention. Studies over the past decade have shown extremely promising results for the surgical treatment of obsessive-compulsive disorder (OCD) and major depressive disorder (MDD), and many others are under investigation. The two types of surgical procedures currently available are targeted lesions and deep brain stimulation (DBS). By their stereotactic nature, both of these procedures target specific brain regions, putative nodes in a behavioral circuit whose function has gone awry.

We use imaging analysis techniques such as diffusion tensor imaging (DTI) and voxel-based morphometry (VBM) to study the structure of cortical and subcortical circuits in individuals with OCD, MDD, and other psychiatric conditions. We are interested in identifying structural or functional predictors of clinical response, as well as studying longitudinal changes over time.

Click here to listen to Dr. Sheth talk about neurosurgical options for severe, refractory OCD on the BlogTalk Radio Show.

Developing novel targets and indications for neuromodulation
The field of neuromodulation is undergoing a rapid expansion. Experimental studies and clinical trials are underway for a variety of neurological and psychiatric diseases. We collaborate closely with clinicians and scientists in the Departments of Psychiatry, Neurology, Neuroscience, Engineering, and others to develop new targets and indications for neuromodulation. Parallel investigations across species models and scale (synapses, cells, networks, behavior) allow information to flow back-and-forth between the lab and clinic, facilitating the advancement of our understanding of the system and how to therapeutically modulate it.

Investigating the coupling between neuronal activity and hemodynamics in human cortex
An increase in neuronal activity is associated with a spatially and temporally localized hemodynamic response. This hemodynamic response produces the changes in tissue oxygenation and blood volume that underlie the BOLD fMRI signal. If neurovascular coupling remains intact, the hemodynamic response can be a reliable indicator of neuronal activity. In collaboration with the Department of Biomedical Engineering, we use optical imaging techniques to visualize the hemodynamic response in patients undergoing neurosurgical procedures that require intraoperative functional mapping. We study basic questions about the origins of hemodynamic signals, as well as the clinical utility of these signals for mapping brain function.