Eskandar Laboratory for Learning & Cognition Research
Overview
A key focus of our laboratory is studying the basal ganglia, a group of structures located in the center of the brain hemispheres (also known as the cerebral hemispheres), and their role in learning and motivation. We are also conducting research to better understand the transmission of signals that are involved in brain function. Our team utilizes multiple approaches to understand both the physiology and neuropharmacology (the study of drugs and their impact on the nervous system) of these circuits.
Neurophysiology of Addiction
There is extensive overlap between the neural circuits and physiological mechanisms underlying learning and addiction. Addictive substances have been shown to hijack the brain’s intrinsic reward systems, leading to an “artificial reward,” biasing individuals to addictive behaviors. We are investigating brain regions co-involved in learning and addiction, including the nucleus accumbens and dorsolateral prefrontal cortex, to elucidate the neurophysiology of addiction and derive deep brain stimulation paradigms to target addictive behavior.
Enhancement of Recovery from Stroke or Brain Injury
The nucleus basalis and medial forebrain bundle are key components of the brain circuitry of learning. The nucleus basalis provides cholinergic innervation to the entire cortex and can coordinate the cortex during cognitive processes. Degeneration of the nucleus basalis occurs early in neurodegenerative disorders, including Alzheimer’s disease and Parkinson’s disease, suggesting that its loss may play a significant role in the cognitive deficits seen in these disorders. The medial forebrain bundle carries projections from the nucleus accumbens to the prefrontal cortex and is thus an appealing target for neuromodulation, with early reports suggesting that deep brain stimulation (DBS) of the medial forebrain bundle is effective in modulating cognitive processes. By investigating the neurophysiology of these structures, we aim to design novel DBS treatment paradigms to enhance cognition.
Selected Publications
For a full list of publications, please visit: https://pubmed.ncbi.nlm.nih.gov/?term=Eskandar%20EN%5BAuthor%5D
Feigen CM, Eskandar EN. Responsive thalamic neurostimulation: A systematic review of a promising approach for refractory epilepsy. Front Hum Neurosci. 2022 Jul 5;16:910345. doi: 10.3389/fnhum.2022.910345. PMID: 35865353; PMCID: PMC9294465.
Aronson JP, Katnani HA, Huguenard A, Mulvaney G, Bader ER, Yang JC, Eskandar EN. Phasic Stimulation in the nucleus accumbens enhances learning after traumatic brain injury. Cereb Cortex Commun. 2022 Apr 9;3(2):tgac016. doi: 10.1093/texcom/tgac016. PMID: 35529519; PMCID: PMC9070350.
Bick SK, Patel SR, Katnani HA, Peled N, Widge A, Cash SS, Eskandar EN. Caudate stimulation enhances learning. Brain. 2019 Oct 1;142(10):2930-2937. doi: 10.1093/brain/awz254. Erratum in: Brain. 2019 Dec 1;142(12):e74. PMID: 31504220.
Bick SK, Dolatshahi MS, Grannan BL, Cole AJ, Hoch DB, Eskandar EN. Preoperative MRI findings and prediction of diagnostic utility of foramen ovale electrodes. J Neurosurg. 2019 Mar 8;132(3):692-699. doi: 10.3171/2018.12.JNS182093. PMID: 30849762.
Patel SR, Herrington TM, Sheth SA, Mian M, Bick SK, Yang JC, Flaherty AW, Frank MJ, Widge AS, Dougherty D, Eskandar EN. Intermittent subthalamic nucleus deep brain stimulation induces risk-aversive behavior in human subjects. Elife. 2018 Sep 10;7:e36460. doi: 10.7554/eLife.36460. PMID: 30198482; PMCID: PMC6130975.
Martinez-Rubio C, Paulk AC, McDonald EJ, Widge AS, Eskandar EN. Multimodal Encoding of Novelty, Reward, and Learning in the Primate Nucleus Basalis of Meynert. J Neurosci. 2018 Feb 21;38(8):1942-1958. doi: 10.1523/JNEUROSCI.2021-17.2017. Epub 2018 Jan 18. PMID: 29348191; PMCID: PMC5824738.
Asaad WF, Lauro PM, Perge JA, Eskandar EN. Prefrontal Neurons Encode a Solution to the Credit-Assignment Problem. J Neurosci. 2017 Jul 19;37(29):6995-7007. doi: 10.1523/JNEUROSCI.3311-16.2017. Epub 2017 Jun 20. PMID: 28634307; PMCID: PMC5518425.
Eskandar E. Editorial. Thalamic stimulation in vegetative or minimally conscious patients. J Neurosurg. 2018 Apr;128(4):1187-1188. doi: 10.3171/2017.3.JNS162558. Epub 2017 Jun 16. PMID: 28621625.
Widge AS, Ellard KK, Paulk AC, Basu I, Yousefi A, Zorowitz S, Gilmour A, Afzal A, Deckersbach T, Cash SS, Kramer MA, Eden UT, Dougherty DD, Eskandar EN. Treating refractory mental illness with closed-loop brain stimulation: Progress towards a patient-specific transdiagnostic approach. Exp Neurol. 2017 Jan;287(Pt 4):461-472. doi: 10.1016/j.expneurol.2016.07.021. Epub 2016 Jul 30. PMID: 27485972.
Lam AD, Deck G, Goldman A, Eskandar EN, Noebels J, Cole AJ. Silent hippocampal seizures and spikes identified by foramen ovale electrodes in Alzheimer's disease. Nat Med. 2017 Jun;23(6):678-680. doi: 10.1038/nm.4330. Epub 2017 May 1. PMID: 28459436; PMCID: PMC5461182.
Herrington TM, Cheng JJ, Eskandar EN. Mechanisms of deep brain stimulation. J Neurophysiol. 2016 Jan 1;115(1):19-38. doi: 10.1152/jn.00281.2015. Epub 2015 Oct 28. Erratum in: J Neurophysiol. 2020 Mar 1;123(3):1277. PMID: 26510756; PMCID: PMC4760496.
Ishizawa Y, Ahmed OJ, Patel SR, Gale JT, Sierra-Mercado D, Brown EN, Eskandar EN. Dynamics of propofol-induced loss of consciousness across primate neocortex. J Neurosci. 2016 Jul 20;36(29):7718-26. doi: 10.1523/JNEUROSCI.4577-15.2016. PMID: 27445148; PMCID: PMC4951576.
Katnani HA, Patel SR, Kwon C-S, Abdel-Aziz S, Gale JT, Eskandar EN. Temporally coordinated deep brain stimulation in the dorsal and ventral striatum synergistically enhances associative learning. Sci Rep. 2016 Jan 4;6:18806. doi: 10.1038/srep18806. PMID: 26725509; PMCID: PMC4698744.
Smith EH, Banks GP, Mikell CB, Cash SS, Patel SR, Eskandar EN, Sheth SA. Frequency-dependent representation of reinforcement-related information in the human medial and lateral prefrontal cortex. J Neurosci. 2015 Dec 2;35(48):15827-36. doi: 10.1523/JNEUROSCI.1864-15.2015. PMID: 26631465; PMCID: PMC4666912.
Gale JTPD, Shields DC, Ishizawa Y, Eskandar EN. Reward and reinforcement activity in the nucleus accumbens during learning. Front Behav Neurosci. 2014 Apr 3;8:114. doi: 10.3389/fnbeh.2014.00114. PMID: 24765069; PMCID: PMC3982058.
Mian MK, Sheth SA, Patel SR, Spiliopoulos K, Eskandar EN, Williams ZM. Encoding of rules by neurons in the human dorsolateral prefrontal cortex. Cereb Cortex. 2014 Mar;24(3):807-16. doi: 10.1093/cercor/bhs361. Epub 2012 Nov 21. PMID: 23172774; PMCID: PMC3920771.
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. Nat Protoc. 2013 May;8(5):949-57. doi: 10.1038/nprot.2013.050. Epub 2013 Apr 18. PMID: 23598445.
Sheth SA, Mian MK, Patel SR, Asaad WF, Williams ZM, Dougherty DD, Bush G, Eskandar EN. Human dorsal anterior cingulate cortex neurons mediate ongoing behavioural adaptation. Nature. 2012 Aug 9;488(7410):218-21. doi: 10.1038/nature11239. PMID: 22722841; PMCID: PMC3416924.
Patel SR, Sheth SA, Mian MK, Gale JT, Greenberg BD, Dougherty DD, Eskandar EN. Single-neuron responses in the human nucleus accumbens during a financial decision-making task. J Neurosci. 2012 May 23;32(21):7311-5. doi: 10.1523/JNEUROSCI.0027-12.2012. PMID: 22623676; PMCID: PMC3486634.
Asaad WF, Eskandar EN. Encoding of both positive and negative reward prediction errors by neurons of the primate lateral prefrontal cortex and caudate nucleus. J Neurosci. 2011 Dec 7;31(49):17772-87. doi: 10.1523/JNEUROSCI.3793-11.2011. PMID: 22159094; PMCID: PMC3266530.
Sheth SA, Abuelem T, Gale JT, Eskandar EN. Basal ganglia neurons dynamically facilitate exploration during associative learning. J Neurosci. 2011 Mar 30;31(13):4878-85. doi: 10.1523/JNEUROSCI.3658-10.2011. PMID: 21451026; PMCID: PMC3486636.
Williams ZM, Eskandar EN. Selective enhancement of associative learning by microstimulation of the anterior caudate. Nat Neurosci. 2006 Apr;9(4):562-8. doi: 10.1038/nn1662. Epub 2006 Feb 26. PMID: 16501567.
Amirnovin R, Williams ZM, Cosgrove GR, Eskandar EN. Visually guided movements suppress subthalamic oscillations in Parkinson's disease patients. J Neurosci. 2004 Dec 15;24(50):11302-6. doi: 10.1523/JNEUROSCI.3242-04.2004. PMID: 15601936; PMCID: PMC6730370.
Williams ZM, Bush G, Rauch SL, Cosgrove GR, Eskandar EN. Human anterior cingulate neurons and the integration of monetary reward with motor responses. Nat Neurosci. 2004 Dec;7(12):1370-5. doi: 10.1038/nn1354. Epub 2004 Nov 21. Erratum in: Nat Neurosci. 2005 Jan;8(1):121. PMID: 15558064.
Emad N. Eskandar, MD
About Emad Eskandar MD, MBA
Dr. Emad Eskandar received a bachelor of arts degree in chemistry from the University of Nebraska. He earned a medical degree at the University of Southern California, Los Angeles, and a master of business administration degree at the Sloan School of Management at the Massachusetts Institute of Technology. He was a neurological surgery resident at Massachusetts General Hospital in Boston, MA, and a neurophysiology fellow at Harvard Medical School. He previously held the Charles Anthony Pappas endowed chair of neurosurgery at Harvard Medical School, where he also served as professor of neurosciences. Dr. Eskandar is board-certified by the American Board of Neurological Surgery. He is a member of the American Association of Neurological Surgeons and the American Academy of Neurological Surgeons. He is a past president of the American Society for Stereotactic and Functional Neurosurgery.
