Behaviorally-guided DBS may treat psychiatric conditions involving impaired decision-making

Emad N. Eskandar, M.D.

Massachusetts General Hospital

Department of Neurosurgery
Funded in December, 2012: $250000 for 3 years
LAY SUMMARY . ABSTRACT . BIOGRAPHY .

LAY SUMMARY

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Behaviorally-guided DBS may treat psychiatric conditions involving impaired decision-making

This neurosurgical research team will explore, at the neuronal level, how two brain networks normally drive the balance between safe and risky decision-making behaviors, and use the findings to design deep brain stimulation (DBS) strategies for modifying excessively risky or risk-adverse behaviors.
Ordinarily, people appropriately balance the drive between making a conservative and safe choices with making a risky but potentially rewarding choices, depending on the circumstances. However, a pathologic imbalance in these drives characterizes psychiatric conditions such as the risk-avoidance of obsessive compulsive disorder (OCD) and the excessive impulsivity and lack of control seen in addiction. Based on their prior research combining physiological of single neurons in brain circuits along with deep brain stimulation (DBS), the investigators hypothesize that two networks that connect the brain’s striatal and cortical areas explain the processes that drive balanced and imbalanced decision-making. Specifically, they anticipate that a dorsal compartment (composed of the cingulate cortex, caudate, and prefrontal cortex) is involved in driving decisions that are safe, with delayed gratification, while a ventral compartment (composed of the nucleus accumbens and orbital-frontal cortex) mediates reward-seeking and often risky or impulsive decisions.
This hypothesis arose from their pioneering efforts to study learning and its enhancement, using a combination of neurophysiological techniques such as electrical recordings from single neurons, functional imaging (fMRI), deep brain stimulation (DBS) to treat movement disorders, and behavioral assessments. Using these techniques, the investigators found that neurons in the nucleus accumbens encode decision-making signals involved in safe versus risky decisions. Moreover, when intermittent DBS stimulation was delivered at crucial time period, patients’ altered their decision-making processes toward more impulsive and risky decisions.  This finding suggests that DBS could also be used to promote more safe and deliberate decisions.
Now, the investigators will use these findings to guide DBS stimulation in the two networks at the critical time points in a total of about 60 patients who are undergoing DBS implantation for treatment of depression, OCD, and Parkinson’s disease. Patients will participate in decision-making tasks involving reward and delayed-gratification, during DBS surgery, and then again six-months following surgery. The neurosurgical researchers will determine whether DBS stimulation in the different compartments can be used to rectify the excessive risk-aversion seen in disorders such as OCD, or the excessive impulsivity, seen in addiction. If successful, this approach will pave the way for developing safe and reversible DBS treatment for a broad variety of disabling psychiatric conditions, similar to treatments in existence for movement disorders such as Parkinson Disease.
Significance: .If successful, these findings will pave the way for developing safe, adjustable,  and reversible DBS treatments for a broad variety of disabling psychiatric conditions characterized by impaired decision-making.

ABSTRACT

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The psychological tension between making a conservative safe choice, versus a risky but potentially rewarding choice, is familiar to all. A certain balance between these drives is necessary for success in science, business, and many other endeavors. An imbalance of these drives can lead to serious problems. For example, an excessive degree of risk aversion would limit exploration and innovation, and at the limit would be extremely crippling, for example in obsessive-compulsive disorder (OCD). Conversely, an excessive degree of reward seeking and risk taking would also be disabling, as in drug addiction or pathological gambling. These disorders have severe personal, public health, and societal consequences.
We propose to study two cortical-striatal networks to explain the processes that drive a balance in decision-making. We propose that a dorsal compartment, including the dorsal anterior cingulate cortex (dACC) caudate nucleus (Cd) and dorsal lateral prefrontal cortex (DLPFC), is involved in mediating safe and correct decisions and successfully delaying gratification. In contrast, we propose that a ventral compartment, including the nucleus accumbens core (NAcc) and orbital-frontal cortex (OFC), is involved in mediating immediate reward seeking, at the expense of increased risk and the potential loss of greater future reward. Our proposal has two main goals. First, we will use human single neuron data to compare the cortical-striatal networks implicated in decision-making to confirm the model. Second, we will utilize the neuronal data to devise rational neuromodulation therapies for these types of disorders.

INVESTIGATOR BIOGRAPHIES

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Emad N. Eskandar, M.D.

Dr. Emad Eskandar is a scientist and neurosurgeon at the Massachusetts General Hospital (MGH). He is also an Associate Professor of Surgery at Harvard Medical School (HMS). He obtained his MD at the University of Southern California, and completed his residency training at MGH and Harvard.  He was an Howard Hughes Medical Institute / National Institutes of Health (HHMI/NIH) research scholar for two years during medical school, received an NRSA award for an additional two years research fellowship at HMS during residency, and a K08 research award at the completion of residency with John Assad PhD as his mentor at Harvard Medical School.
Dr. Eskandar is now director of Functional Neurosurgery at MGH, treating disorders such as Parkinson Disease, Epilepsy, and chronic Pain. He also heads a large and active research laboratory investigating the cortex and basal ganglia (BG), a group of centrally located nuclei in the brain. The basal ganglia play a central role in theories of learning, motivation, and cognitive control. The laboratory uses microelectrode recordings and electrical micro-stimulation to evaluate the role of the BG in both primates and humans performing complex behavioral tasks. The laboratory is uniquely positioned in that ideas from the bench can quickly be tested in the clinical arena and vice-versa.
The Eskandar lab has made important scientific contributions in recent years. For example, one study, published in Nature Neuroscience, found that a part of the brain called the Cingulate Cortex plays an important role in linking reward information with action selection. Another study, also published in Nature Neuroscience, found that delivering micro-stimulation in a part of the basal ganglia, the caudate nucleus, significantly increases the rate of learning beyond baseline rates. These findings suggest that the caudate plays a critical role in learning, and that learning can be enhanced to promote recovery after brain injury.  One very recent study, published in Nature, found that the cingulate cortex plays an important role in adapting to varying degrees of cognitive difficulty. Dr. Eskandar has authored over 90 peer-reviewed papers, many in high impact journals such as Nature, Nature Neuroscience, PNAS, J. Neuroscience, Brain, and Cerebral Cortex. 
Dr. Eskandar has been the recipient of numerous honors and awards including the Grass Neuroscience Fellowship, National Research Service Award, the Excellence in Teaching Award at Harvard Medical School, and Excellence in Teaching Award from MGH Residents. He was also awarded the Howard Hughes Medical Institute Physician Scientist Early Career Award, an award from the Klingenstein Foundation, and a Harvard Catalyst Grant. In addition Dr. Eskandar has successfully obtained funding from the National Institutes of Health (NIH) and the National Science Foundation (NSF).