Researcher’s Profile

Sameer Sheth, MD, PhD

Advisory Committee, CTNI
Unit Director, 8 Hudson North (Neurosurgery/Neurology)
Director, Psychiatric Neurosurgery Service
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Dr. Sheth graduated Summa Cum Laude from Harvard University with a degree in Physics and Astronomy. He then entered the Medical Scientist Training Program at the UCLA School of Medicine, where he received both his MD and PhD degrees. Dr. Sheth trained in Neurological Surgery at the Massachusetts General Hospital and Harvard Medical School.

Dr. Sheth specializes in the treatment of patients with Movement Disorders, Epilepsy, Brain Tumors, Trigeminal Neuralgia, Hydrocephalus, and certain Psychiatric Disorders. He enjoys bringing a personalized approach to each patient in order to arrive at an individually tailored treatment plan optimized for the patient and his or her family. He works with a world-class multi-disciplinary team of surgeons, neurologists, psychiatrists, radiologists, and others to provide compassionate, state-of-the-art care for his patients. Among the many techniques at his disposal are stereotactic neurosurgery, deep brain stimulation, ablative techniques, awake brain mapping, electrode recordings, computer-guided navigation, and microsurgery.

Dr. Sheth is also a neuroscientist, with PhD and post-doctoral training in neurophysiology. His research interests are centered on a desire to better understand brain function. Dr. Sheth’s research is motivated by the belief that if we can understand how the brain works at the level of individual neurons and circuits, we will be much better equipped to repair it. By understanding normal brain processes such as motor control, reward processing, and decision-making, we can understand disease processes such as movement disorders, addiction, and anxiety disorders. Dr. Sheth’s research has been funded by the NIH, the Harvard Catalyst, the MGH Cancer Center, and the American Association of Neurological Surgeons.

Dr. Sheth is Director and Founder of the Functional and Cognitive Neurophysiology laboratory, which focuses on the study of human decision-making, behavior, and cognitive processes.

Research Statement: 

The Functional and Cognitive Neurophysiology laboratory, led by Dr. Sameer Sheth, focuses on the study of human decision-making, behavior, and cognitive processes.  We use a combination of imaging and intracranial electrophysiology to investigate structural and functional relationships in the human brain. Neurosurgical procedures such as deep brain stimulation (DBS), epilepsy surgery, and brain tumor resection often require detailed imaging and electrophysiological recordings before, during, and after surgery. We utilize these unique opportunities to study the human brain and behavior in health and disease states.

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.

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 (rodent, nonhuman primate, human) 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.

Publications: 

Basic Science

Smith EH, Banks GP, Mikell CB, Cash SC, Patel SR, Eskandar EN, Sheth SA. “Frequency-dependent representation of reinforcement-related information in human medial and lateral prefrontal cortex.” Journal of Neuroscience (2015 in press).

Banks G, Mikell CB, Youngerman BE, Henriques B, Kelly KM, Chan AK, Herrera D, Dougherty DD, Eskandar EN, Sheth SA. “Neuroanatomical predictors of response to dorsal anterior cingulotomy for obsessive-compulsive disorder.” JAMA Psychiatry 72(2): 127-135 (2015).

McGovern, RA, Ratneswaren, T, Smith, EH, Russo, JF, Jongeling, AC, Bateman, LM, Schevon CA, Feldstein NF, McKhann GM, Sheth SA. Investigating the function of deep cortical and subcortical structures using stereotactic electroencephalography: lessons from the anterior cingulate cortex. Journal of Visualized Experiments : JoVE, (98). doi:10.3791/52773 (2015).

Patel SR, Sheth SA, Martinez-Rubio C, Mian MK, Asaad WF, Gerrard JL, Kwon CS, Dougherty DD, Flaherty AW, Greenberg BD, Gale JT, Williams ZM, Eskandar EN. “Studying task-related activity of individual neurons in the human brain.” Nature Protocols 8(5): 949-57 (2013).

Sheth SA, Mian MK, Patel SR, Asaad WF, Williams ZM, Dougherty DD, Bush G, Eskandar EN. “Human dorsal anterior cingulate neurons mediate ongoing behavioral adaptation.” Nature 488: 218-221 (2012).

Patel S*, Sheth SA*, Mian MK, Gale JT, Greenberg BD, Dougherty DD, Eskandar EN. “Single-neuronal responses during a financial decision making task in the human nucleus accumbens.” Journal of Neuroscience 32: 7311-7315 (2012). *Contributed equally.

Mian MK, Sheth SA, Patel SR, Spiliopoulos K, Eskandar EN, Williams ZW. “Encoding of rules by neurons in the human dorsolateral prefrontal cortex.” Cerebral Cortex Nov 21 (2012 Epub ahead of print).

Sheth SA, Abuelem T, Gale JT, Eskandar EN. “Basal Ganglia Neurons Dynamically Facilitate Exploration during Associative Learning.” Journal of Neuroscience 31(13): 4878-4885 (2011).

Clinical

Brown, LT, Mikell, CB, Youngerman, BE, Zhang, Y, McKhann, GM, Sheth, SA Dorsal anterior cingulotomy and anterior capsulotomy for severe, refractory obsessive-compulsive disorder: a systematic review of observational studies. Journal of Neurosurgery, 1–13. doi:10.3171/2015.1.JNS14681 (2015).

Russo JF, Sheth SA. “Deep brain stimulation of the dorsal anterior cingulate cortex for the treatment of chronic neuropathic pain.” Neurosurgical Focus (2015 in press).

Sinha S, McGovern RA, Sheth SA. “Deep brain stimulation for severe autism: from pathophysiology to procedure.” Neurosurgical Focus (2015 in press).

Sheth SA, Neal J, Tangherlini F, Mian MK, Dougherty D, Eskandar EN. “Limbic system surgery for treatment-refractory obsessive-compulsive disorder: five-year prospective follow-up in 64 patients.” Journal of Neurosurgery 118: 491-97 (2012).