Investigating the Physiology of Human Decision-Making

Sameer Sheth

Columbia University

Funded in September, 2013: $282000 for 3 years


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Deciphering the physiology of the human decision-making network

         Neurosurgical researchers will explore how a specific brain network functions as people make decisions.      

         We are constantly making decisions. Often we make them rapidly with nearly imperceptible effort. Other decisions require us to make a thorough but rapid examination of the circumstance, predict potential consequences and take action. Sometimes these actions are essential for survival and it is no surprise that the specialized networks for making decisions are located in the brain’s most evolutionarily advanced region, the pre-frontal cortex. Take, for example, deciding whether to stop at or drive through a yellow light. This situational context creates conflict between multiple simultaneous and mutually incompatible responses: depress the brake, step on the accelerator, or coast. The networks involved evaluate these options taking into account multiple factors, such as the car’s speed, distance to the intersection, and whether other cars (or police) are around. 

         Scientists have postulated that the decision process entails two functions. One function entails evaluating the situation by identifying the sources of conflict, while the other entails exerting control by initiating actions to resolve the conflict and execute the optimal response. Prior research suggests that an area in the middle of the pre-frontal cortex, called the dorsal anterior cingulate cortex (dACC), is primarily involved in monitoring conflicts while the dorsolateral pre-frontal cortex (DLPFC) exerts cognitive control to resolve conflict and optimize behavior. 

        Previous MRI studies suggest that the dACC monitors conflict and evaluates possible responses for their likely outcomes, and then sends signals to the DLPFC. When the demands are relatively stable, such as in deciding which suit to wear, this signal accelerates responses and promotes efficiency. In contrast, when demands are rapidly changing—as in the yellow light example—the signals retard responses and promote accuracy. In other words, in critical decision-making situations, accuracy trumps efficiency. 

         In this model, the dACC recruits the DLPFC to make adjustments in cognitive control. Investigation of the physiological process of cognitive control hinges on two behavioral observations. The first observation is that our reaction times are longer when there is incongruence (“cognitive interference”) between relevant and irrelevant stimuli, such as when the word “red” is written in green ink compared to when it is written in red ink. There is a tendency for the irrelevant green ink to impede our simultaneous processing of the relevant word “red”. The second observation is that we tend to adjust our current response based on recent past occurrences. 

         The Columbia University neurosurgical researchers are among the few groups in the country with the expertise and experience to study neural networks from the levels of individual cells and populations of cells. These investigators will extend prior research to answer key questions about the roles of dACC and DLPFC circuitry in cognitive control. They will study this decision-making network in participants as they make decisions on tasks that entail cognitive interference or recollection of recent prior experience. Investigators will compare the results from electrical recordings of single brain cells and of populations of cells to results obtained from fMRI imaging. The studies are designed to bridge the gap between findings from imaging and cellular recording and from human and non-human primates. 

           One study group will involve 30 patients with intractable epilepsy who will participate in the decision-making tasks prior to their surgical treatment. These patients ordinarily undergo electrode recordings prior to surgery so that the surgeons can identify brain areas that are critical for specific functions and need to be surgically sparred. As these patients participate in the two behavioral tasks, the surgeons will study the dACC to test three hypotheses: 1) The dACC, by weighing the most recent events most heavily, helps guides immediate decisions; but, by taking into account previous events, it remains sensitive to the historical context. 2) The dACC neurons encode possible responses that are activated by the amount of conflict. 3) The discrepancy in prior results from single cell responses and fMRI imaging will dissolve when the entire time-course of the trial is taken into account. 

         The other study group will consist of 30-45 patients with either intractable Parkinson’s disease or the related condition, “essential tremor.” The investigators will similarly undertake fMRI imaging and single and multiple cell electrode recordings in patients prior to undergoing deep brain stimulation (DBS) surgery. The neurosurgeons will first describe basic response properties of DLPFC neurons, and compare results to those previously obtained in non-human primates. Then they will test the hypothesis that the dACC signal recruits DLFPC control mechanisms to contend with conflict and optimize behavior. 

         Significance: This research is anticipated to provide a new understanding of the physiology of the network involved in normal decision-making. This understanding might then also shed light on disorders thought to arise from physiological malfunctioning of this network, such as obsessive-compulsive disorder, attention deficit hyperactivity disorder and schizophrenia


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Sameer Sheth

NAME SHETH, Sameer Anil POSITION TITLE Assistant Professor in Neurosurgery Columbia University Medical Center New York Presbyterian Hospital, New York, NY eRA COMMONS USER NAME (credential, e.g., agency login) SAMEER1 EDUCATION/TRAINING (Begin with baccalaureate or other initial professional education, such as nursing, include postdoctoral training and residency training if applicable.) INSTITUTION AND LOCATION DEGREE (if applicable) MM/YY FIELD OF STUDY Harvard University, Cambridge, MA B.A. 06/1998 Physics & Astronomy University of California, Los Angeles, LA, CA Ph.D. 12/2003 Neuroscience UCLA School of Medicine, Los Angeles, CA M.D. 06/2005 Medicine Massachusetts General Hospital Internship 06/2006 General Surgery Massachusetts General Hospital Postdoc 02/2011 Neurophysiology Massachusetts General Hospital Residency 06/2012 Neurosurgery A. Personal Statement Please see application. B. Positions and Honors 2012 Philip L. Gildenberg Resident Award, 2012 AANS annual meeting 2012 Plenary Session platform presentation, 2012 AANS annual meeting (“Cingulotomy for severe, treatment-refractory obsessive-compulsive disorder: a prospective long-term follow-up of 63 patients”) 2012 Plenary Session platform presentation, 2012 AANS annual meeting (“Reward Prediction Encoded by Single-Neuron Responses in the Human Nucleus Accumbens”) 2012 Harvard Medical School Resident Teaching Award 2011 Integra Foundation Award, 2011 AANS annual meeting 2011 Plenary Session platform presentation, 2011 AANS annual meeting (“Transsphenoidal surgery for Cushing's disease after non-diagnostic inferior petrosal sinus sampling”) 2010 Schmidek Fellowship to visit Professor Tipu Aziz in Oxford University Dept. of Neurosurgery 2010 CNS travel award for Neurological Society of India (NSI)-CNS meeting in Jaipur, India 2010 Best Paper, Neurology Category, 2010 Neurological Society of India (NSI)-CNS joint meeting 2010 Best Clinical Research Award for Residents/Fellows, 2010 ASSFN annual meeting 2010 Second Place, Stereotactic/Functional Award, 2010 AANS annual meeting 2009 Sherry Apple Resident Travel Scholarship, 2009 CNS annual meeting 2007 Stereotactic and Functional Neurosurgery Resident Award, 2007 CNS annual meeting 2002 Organization for Human Brain Mapping conference travel fellowship 2001 ARCS (Achievement Rewards for College Scientists) Foundation Scholarship 2001 UCLA Affiliates/Fishbaugh Scholarship 1998 Cumulative Group I Standing, Dean’s List every semester 1997 Harvard College Scholarship 1996 John Harvard Scholarship C. Selected Peer-reviewed Publications Most relevant to the current application 1. 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). 2. 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 (in press). 3. 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. 4. Mian MK, Sheth S, 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). 5. 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). 6. Sheth SA, Nemoto M, Guiou M, Walker M and Toga AW. “Spatiotemporal evolution of functional hemodynamic changes and their relationship to neuronal activity.” Journal of Cerebral Blood Flow and Metabolism March 2: 1-12 (2005). 7. Sheth SA, Nemoto M, Guiou M, Walker M, Pouratian N and Toga AW. “Linear and nonlinear relationships between neuronal activity, oxygen metabolism, and hemodynamic responses.” Neuron 42(2): 347-355 (2004). Cover article. 8. Nemoto M, Sheth S, Guiou M, Pouratian N, Chen JWY and Toga AW. “Functional signal and paradigm dependent linear relationships between synaptic activity and hemodynamic responses in rat somatosensory cortex.” Journal of Neuroscience 24(15): 3850-3863 (2004). Cover article. 9. Sheth SA, Nemoto M, Guiou M, Walker M, Pouratian N, Hageman N and Toga AW. “Columnar specificity of microvascular oxygenation and volume responses: Implications for functional brain mapping.” Journal of Neuroscience 24(3): 634-641 (2004). Other publications 1. 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 (in press). 2. Snuderl M, Wirth D, Sheth SA, Bourne SK, Kwon CS, Ancukiewicz M, Curry WT, Frosch MP, Yaroslavsky AN. “Dye-enhanced multimodal confocal imaging as a novel approach to intraoperative diagnosis of brain tumors.” Brain Pathology Aug 6 (2012). 3. Bourne SK, Eckhardt CA, Sheth SA, Eskandar EN. “Mechanisms of deep brain stimulation for obsessive compulsive disorder: effects upon cells and circuits.” Frontiers in Integrated Neuroscience 6(29): 1-14 (2012). 4. Sheth SA, Mian MK, Neal J, Tritos NA, Nachtigall L, Klibanski A, Biller BMK, Swearingen B. “Transsphenoidal surgery for Cushing's disease after non-diagnostic inferior petrosal sinus sampling.” Neurosurgery 71: 14-22 (2012). 5. Walcott BP, Nahed BV, Sheth SA, Caracci JR, Asaad WF. “Bilateral hemicraniectomy in non-penetrating traumatic brain injury.” Journal of Neurotrauma 29: 1879-1885 (2012). 6. Wirth D, Snuderl M, Sheth SA, Kwon CS, Frosch M, Curry WT, Yaroslavsky A. “Identifying brain neoplasms using dye-enhanced multimodal confocal imaging.” Journal of Biomedical Optics 17(2): 026012:1-7 (2012). 7. Patel SR, Aronson JP, Sheth SA, Eskandar EN. “Lesion procedures in psychiatric neurosurgery.” World Neurosurgery (in press). 8. Karakis I, Velez-Ruiz N, Pathmanathan J, Sheth SA, Eskandar EN, Cole AJ. “Foramen ovale electrodes in the evaluation of epilepsy surgery: conventional and unconventional uses.” Epilepsy and Behavior 22(2): 247-54 (2011). 9. Gale JT, Martinez-Rubio C, Sheth SA, Eskandar EN. “Intra-operative behavioral tasks in awake humans undergoing deep brain stimulation surgery.” Journal of Visualized Experiments 47 (2011). 10. Sheth SA, Mian M, Abuelem T, Gale JT, Eskandar, EN. “Facilitation of visuomotor associative motor learning by the basal ganglia.” Clinical Neurosurgery 57: 145-150 (2010). 11. Mian M, Campos M, Sheth SA, Eskandar EN. “Deep brain stimulation for obsessive-compulsive disorder: past, present, and future.” Neurosurgical Focus 29(2): E10 (2010). 12. Sheth SA, McGirt M, Woodworth G, Wang P, Rigamonti D. “Ultrasound guidance for distal insertion of ventriculo-atrial shunt catheters: technical note.” Neurology Research 31(3): 280-2 (2009). 13. Sheth SA, Prakash N, Guiou M and Toga AW. “Validation and visualization of two-dimensional optical spectroscopic imaging of cerebral hemodynamics.” NeuroImage (Suppl 2): T36-43 (2009). 14. Prakash N, Uhlemann F, Sheth SA, Bookheimer S, Martin N and Toga AW. “Current trends in intraoperative optical imaging for functional brain mapping and delineation of lesions of language cortex.” NeuroImage (Suppl 2): T116-26 (2009). 15. Harris S, Sheth S and Cohen MS. “Functional neuroimaging of belief, disbelief, and uncertainty.” Annals of Neurology 63(2): 141-7 (2008). 16. Prakash N, Biag J, Sheth SA, Mitsuyama S, Theriot J, Ramachandra C and Toga AW. “Temporal profiles and 2-dimensional oxy-, deoxy-, and total-hemoglobin somatosensory maps in rat versus mouse cortex.” NeuroImage 37(Suppl 1): S27-36 (2007). 17. Fuster J, Guiou M, Ardestani A, Cannestra A, Sheth S, Zhou Y-D, Toga AW and Bodner M. “Near-infrared spectroscopy (NIRS) in cognitive neuroscience of the primate brain.” NeuroImage 26(1):215-20 (2005). 18. Guiou M, Sheth S, Nemoto M, Walker M, Pouratian N, Ba A and Toga AW. “Cortical spreading depression produces long-term disruption of activity-related changes in cerebral blood volume and neurovascular coupling.” Journal of Biomedical Optics 10(1): 011004:1-7 (2005). 19. Sheth S, Nemoto M, Guiou M, Walker M, Pouratian N and Toga AW. “Evaluation of coupling between optical intrinsic signals and neuronal activity in rat somatosensory cortex.” NeuroImage 19(3):884-94 (2003). 20. Pouratian N, Sheth SA, Bookheimer SY, Martin NA and Toga AW. “Applications and limitations of perfusion-dependent functional brain mapping for neurosurgical guidance.” Neurosurgical Focus 15(1), Article 2: 1-8 (2003). 21. Pouratian N, Sheth SA, Martin NA and Toga AW. “Shedding light on brain mapping: advances in human optical imaging.” Trends in Neurosciences 26(5):277-82 (2003). 22. Mair RW, Hoffmann D, Sheth SA, Wong GP, Butler JP, Patz S, Topulos GP and Walsworth RL. “Reduced xenon diffusion for quantitative lung study – The Role of SF6.” NMR in Biomedicine, 13(4):229-33 (2000). 23. Sheth S, Liang E, Luo C and Murakami T. “ASCA Measurement of the Hydrogen Column Density to 1E 1740.7–2942.” Astrophysical Journal 468 (no.2, pt. 1):755-760 (2000). D. Research Support Ongoing research support K12 NS080223 Eskandar (PI) 07/01/12-06/30/14 NIH Neurosurgeon Research Career Development Program The goal of this project is to study human cognitive function using intra- and peri-operative electrode recordings Role: Fellow Completed research support most relevant to current application R25 NS065743 Young (PI) 03/01/09-02/28/11 Neuroscience Resident Research Program The goal of the project was to investigate the cortical and sub-cortical circuitry involved in the pathophysiology of OCD Role: Fellow NREF Sheth (PI) 03/01/10-02/28/11 Intraoperative Functional Brain Mapping with Optical Polarization Imaging The goal of the project was to use optical imaging techniques for intraoperative brain mapping during neurosurgical procedures near eloquent cortex Role: PI F30 MH67432 Sheth (PI) 07/01/02-06/30/04 Assessing Neurovascular Coupling with Functional Mapping The goal of the project was to study neurovascular coupling using high-resolution imaging techniques Role: PI Other completed research support MGH Cancer Center Curry (PI) 01/01/09-12/31/09 Identifying Boundaries of Infiltrative Brain Tumors with Wide-Field High-Resolution Optical Polarization Imaging The goal of the project was to initiate a clinical trial to study dye-enhanced multimodal imaging techniques for intraoperative distinction between tumor and brain Role: Fellow Harvard Catalyst Eskandar (PI) 01/01/09-12/31/10 Intraoperative Functional Brain Mapping The goal of the project was to develop dye-enhanced imaging techniques for distinguishing tumor from brain Role: Fellow T32 MH19950 Toga (PI) 07/01/01-06/30/03 Training Grant in Neuroimaging The goal of the project was to investigate neurovascular coupling in the rat somatosensory cortex using optical imaging and electrophysiology Role: Trainee T32 GM08042 Korenman (PI) 07/01/98-06/01/05 Medical Scientist Training Program Role: Trainee