Research Centers

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Sensorimotor Integration Lab

The Sensorimotor Integration Lab explores the influence of basal ganglia in adaptive learning and motor control in subjects undergoing surgery for movement disorders, such as Parkinson’s disease, while awake.

Overview

The basal ganglia play a critical but enigmatic role in many aspects of brain function including movement, motivation, reward and addiction. The vast number of neurologic disorders, such as Parkinson's disease, Huntington's disease, Tourette’s syndrome, Dystonia and Schizophrenia, which involve the basal ganglia are a testament to the importance of this role. However, precisely defining the purpose of the basal ganglia in the normal control of movement or motivation is surprisingly difficult. The goal of the experiments described here is to explore the influence of basal ganglia in adaptive learning and motor control in awake-behaving primates and in human subjects undergoing surgery. Our lab is uniquely positioned to investigate basal ganglia function in nonhuman primates and in humans undergoing surgery for movement disorders.

Areas of research focus:

  • Understanding the role of the anterior striatum in learning novel stimulus - response associations
  • Understanding the role nucleus accumbens in movtivation
  • Understanding the circuitry underlyling in Obsessive-compulsive disorder (OCD)
  • Investigating dopamine regulation in the striatum during 
behavior and learning
  • Investigating the role of deep brain stimulation in enhancing recovery after traumatic brain injury, stroke and other disorders
  • Investigating the role of the cingulate gyrus, nucleus accumbens, subthalamic nucleus and the globus pallidus internus in patients undergoing surgery for deep brain stimulation

Group Members

  • Emad N. Eskandar, MD
    Principal Investigator
, Director of Stereotactic and Functional Neurosurgery
, Department of Neurosurgery
  • Matthew Thombs
    Lab Manager, e-mail: mthombs@partners.org
  • Sameer Sheth, MD, PhD
    Resident Physician, PGY5 
Department of Neurosurgery
  • Clarissa Martinez-Rubio Fontané
    Post-Doctoral Research Fellow
, Department of Neurosurgery
  • Demetrio Sierra, PhD
    Post-Doctoral Research Fellow
, Department of Neurosurgery
  • Kaushik Ghose PhD
    Post-Doctoral Research Fellow
, Department of Neurosurgery
  • Churl-Su Kwon, MD
    Post-Doctoral Research Fellow
, Department of Neurosurgery
  • Fady Girgis, MD
    Post-Doctoral Research Fellow
, Department of Neurosurgery
  • Shaun Patel
    Graduate Student
, Department of Neurosurgery, 
Boston University School of Medicine
  • Matt Mian
    Medical Student, 
Department of Neurosurgery, 
Harvard Medical School
  • Christine Eckhardt
    Medical Student
, Department of Neurosurgery
, Harvard Medical School
  • Sarah Bourne
    Medical Student
, Department of Neurosurgery
, Vanderbilt University

Research Projects

Understanding the Role of the Anterior Striatum in Learning Novel Stimulus - Response Mappings

Most experimental paradigms in primates involve over-training the animals to perform a specific task. However, such an approach does not provide the opportunity to record while the animal is learning since the behavior is too variable. In these experiments the animal is explicitly forced to quickly learn new stimulus-response mappings. Our prediction is that successful stimulus - movement pairing will be associated with significantly different patterns of activity than unsuccessful pairings. Secondly, we predict that the dorsal (caudate nucleus) and ventral (nucleus accumbens) aspects of the anterior striatum will have dissociative roles in learning novel stimulus - response mappings.

Investigating Dopamine Regulation in the Striatum During Behavior and Learning

Dopamine is believed to play a significant role in learning new and performing behaviors already learned. Furthermore, dopamine depletion or dysfunction has been implicated in the underlying pathological mechanisms of a number of movement and psychological disorders. Using the electrochemical method of fixed-potential amperometry, we intend to examine the dynamic regulation of dopamine in the striatum during the execution of learned motor behaviors and during the learning of new motor behaviors.

Researching the Role of Subthalamic Nucleus and the Globus Pallidus Interna in Movement Control in Parkinsonian Patients Undergoing Surgery for Deep Brain Stimulation.

An intriguing manifestation of Parkinson's disease is the ability of patients to overcome their akinesia when presented with compelling visual cues. This suggests that sensory cues exert their effects by either transiently normalizing disordered basal ganglia activity or by employing different circuitry that bypasses the basal ganglia altogether. However, the basis for this observation is unknown. Comparing visually cued versus spontaneously generated movements is a potentially powerful method of exploring the functional derangements of Parkinson's disease.

Research Positions

Positions may be available at various times.  Please contact Dr. Eskandar for more information.

2011

Metaplastic bone in a cortical tuber of a young patient with tuberous sclerosis complex.
Gallagher A, Kovach A, Stemmer-Rachamimov A, Rosenberg AE, Eskandar E, Thiele EA.
Neurology.
2011 May 3;76(18):1602-4

Basal ganglia neurons dynamically facilitate exploration during associative learning.
Sheth SA, Abuelem T, Gale JT, Eskandar EN.
J Neurosci.
2011 Mar 30;31(13):4878-85

Single-neuron dynamics in human focal epilepsy.
Truccolo W, Donoghue JA, Hochberg LR, Eskandar EN, Madsen JR, Anderson WS, Brown EN, Halgren E, Cash SS.
Nat Neurosci.
2011 May;14(5):635-41. Epub 2011 Mar 27

AAV2-GAD gene therapy for advanced Parkinson's disease: a double-blind, sham-surgery controlled, randomised trial.
LeWitt PA, Rezai AR, Leehey MA, Ojemann SG, Flaherty AW, Eskandar EN, Kostyk SK, Thomas K, Sarkar A, Siddiqui MS, Tatter SB, Schwalb JM, Poston KL, Henderson JM, Kurlan RM, Richard IH, Van Meter L, Sapan CV, During MJ, Kaplitt MG, Feigin A.
Lancet Neurol.
2011 Apr;10(4):309-19

The variability of stimulus thresholds in electrophysiologic cortical language mapping.
Wang SG, Eskandar EN, Kilbride R, Chiappa KH, Curry WT, Williams Z, Simon MV.
J Clin Neurophysiol.
2011 Apr;28(2):210-6

VIM thalamic stimulation for monoclonal gammopathy-associated tremor.
Shields DC, Flaherty AW, Eskandar EN, Williams ZM.
Neurosurgery.
2011 Feb 9

Intra-operative behavioral tasks in awake humans undergoing deep brain stimulation surgery.
Gale JT, Martinez-Rubio C, Sheth SA, Eskandar EN.
J Vis Exp.
2011 Jan 6;(47). pii: 2156. doi: 10.3791/2156

 

2010

Facilitation of visuomotor associative learning by the basal ganglia.
Sheth SA, Mian MK, Abuelem T, Gale J, Eskandar EN.
Clin Neurosurg.
2010;57:145-50

Deep brain stimulation for obsessive-compulsive disorder: past, present, and future.
Mian MK, Campos M, Sheth SA, Eskandar EN.
Neurosurg Focus. 2010 Aug;29(2):E10. Review

Coalescence and fragmentation of cortical networks during focal seizures.
Kramer MA, Eden UT, Kolaczyk ED, Zepeda R, Eskandar EN, Cash SS.
J Neurosci.
2010 Jul 28;30(30):10076-85

Heterogeneous neuronal firing patterns during interictal epileptiform discharges in the human cortex.
Keller CJ, Truccolo W, Gale JT, Eskandar E, Thesen T, Carlson C, Devinsky O, Kuzniecky R, Doyle WK, Madsen JR, Schomer DL, Mehta AD, Brown EN, Hochberg LR, Ulbert I, Halgren E, Cash SS.
Brain.
2010 Jun;133(Pt 6):1668-81

Using point process models to compare neural spiking activity in the subthalamic nucleus of Parkinson's patients and a healthy primate.
Sarma SV, Eden UT, Cheng ML, Williams ZM, Hu R, Eskandar E, Brown EN.
IEEE Trans Biomed Eng.
 2010 Jun;57(6):1297-305. Epub 2010 Feb 17

The effects of EEG suppression and anesthetics on stimulus thresholds in functional cortical motor mapping.
Simon MV, Michaelides C, Wang S, Chiappa KH, Eskandar EN.
Clin Neurophysiol.
2010 May;121(5):784-92. Epub 2010 Feb 8

 

2009

Localization of seizure onset area from intracranial non-seizure EEG by exploiting locally enhanced synchrony.
Dauwels J, Eskandar E, Cash S.
Conf Proc IEEE Eng Med Biol Soc.
2009;2009:2180-3

Getting signals into the brain: visual prosthetics through thalamic microstimulation.
Pezaris JS, Eskandar EN.
Neurosurg Focus.
2009 Jul;27(1):E6. Review

Role of deep brain stimulation in modulating memory formation and recall.
Hu R, Eskandar E, Williams Z.
Neurosurg Focus.
2009 Jul;27(1):E3

Physiological responses to brain stimulation during limbic surgery: further evidence of anterior cingulate modulation of autonomic arousal.
Gentil AF, Eskandar EN, Marci CD, Evans KC, Dougherty DD.
Biol Psychiatry.
2009 Oct 1;66(7):695-701. Epub 2009 Jul 9

Parallel versus serial processing dependencies in the perisylvian speech network: a Granger analysis of intracranial EEG data.
Gow DW Jr, Keller CJ, Eskandar E, Meng N, Cash SS.
Brain Lang .
2009 Jul;110(1):43-8. Epub 2009 Apr 7

Risk factors for hemorrhage during microelectrode-guided deep brain stimulation and the introduction of an improved microelectrode design.
Ben-Haim S, Asaad WF, Gale JT, Eskandar EN.
Neurosurgery .
2009 Apr;64(4):754-62; discussion 762-3

Entrapment of the glossopharyngeal nerve in patients with Eagle syndrome: surgical technique and outcomes in a series of 5 patients.
Shin JH, Herrera SR, Eboli P, Aydin S, Eskandar EH, Slavin KV.
J Neurosurg .
2009 Dec;111(6):1226-30

Subthalamic nucleus discharge patterns during movement in the normal monkey and Parkinsonian patient.
Gale JT, Shields DC, Jain FA, Amirnovin R, Eskandar EN.
Brain Res .
2009 Mar 13;1260:15-23. Epub 2009 Jan 7

Are cortical tubers epileptogenic? Evidence from electrocorticography.
Major P, Rakowski S, Simon MV, Cheng ML, Eskandar E, Baron J, Leeman BA, Frosch MP, Thiele EA.
Epilepsia.
2009 Jan;50(1):147-54

Consideration of epilepsy surgery in adults should be independent of age.
Costello DJ, Shields DC, Cash SS, Eskandar EN, Cosgrove GR, Cole AJ.
Clin Neurol Neurosurg.
2009 Apr;111(3):240-5. Epub 2008 Nov 22

Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression.
Malone DA Jr, Dougherty DD, Rezai AR, Carpenter LL, Friehs GM, Eskandar EN, Rauch SL, Rasmussen SA, Machado AG, Kubu CS, Tyrka AR, Price LH, Stypulkowski PH, Giftakis JE, Rise MT, Malloy PF, Salloway SP, Greenberg BD.
Biol Psychiatry.
2009 Feb 15;65(4):267-75. Epub 2008 Oct 8

 

2008

A flexible software tool for temporally-precise behavioral control in Matlab.
Asaad WF, Eskandar EN.
J Neurosci Methods.
2008 Sep 30;174(2):245-58. Epub 2008 Jul 25

Achieving behavioral control with millisecond resolution in a high-level programming environment.
Asaad WF, Eskandar EN.
J Neurosci Methods.
2008 Aug 30;173(2):235-40. Epub 2008 Jun 17

Increased prevalence of obesity and obesity-related postoperative complications in male meningioma patients.
Aghi MK, Eskandar EN, Carter BS, Curry WT Jr, Barker FG 2nd.
Clin Neurosurg .
2007;54:236-40

Prospective assessment of stereotactic ablative surgery for intractable major depression.
Shields DC, Asaad W, Eskandar EN, Jain FA, Cosgrove GR, Flaherty AW, Cassem EH, Price BH, Rauch SL, Dougherty DD.
Biol Psychiatry .
2008 Sep 15;64(6):449-54. Epub 2008 May 16

The movers and shakers of deep brain stimulation.
Asaad W, Eskandar E.
Nat Med.
2008 Jan;14(1):17-9


2007


Microelectrode-guided deep brain stimulation for Tourette syndrome: within-subject comparison of different stimulation sites.

Shields DC, Cheng ML, Flaherty AW, Gale JT, Eskandar EN.
Stereotact Funct Neurosurg.
2008;86(2):87-91. Epub 2007 Dec 12

From symphony to cacophony: pathophysiology of the human basal ganglia in Parkinson disease.
Gale JT, Amirnovin R, Williams ZM, Flaherty AW, Eskandar EN.
Neurosci Biobehav Rev .
2008;32(3):378-87. Epub 2007 Apr 26. Review

Pallidal stimulation for dystonia in pantothenate kinase-associated neurodegeneration.
Shields DC, Sharma N, Gale JT, Eskandar EN.
Pediatr Neurol.
2007 Dec;37(6):442-5

Increased prevalence of obesity and obesity-related postoperative complications in male patients with meningiomas.
Aghi MK, Eskandar EN, Carter BS, Curry WT Jr, Barker FG 2nd.
Neurosurgery.
2007 Oct;61(4):754-60; discussion 760-1

Stereotactic cortical resection in non-lesional extra-temporal partial epilepsy.
Shields DC, Costello DJ, Gale JT, Hoch DB, Eskandar EN.
Eur J Neurol .
2007 Oct;14(10):1186-8. Epub 2007 Aug 15

 

 

 

Sensorimotor Integration Lab

Edwards Research Building
50 Blossom Street
Room 410
Boston, MA 02114

Phone: 617-726-5754
Fax: 617-726-3210

Public Transportation Access: yes