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Studying task-related activity of individual neurons in the human brain


Single-neuronal studies remain the gold standard for studying brain function. Here we describe a protocol for studying task-related single-neuronal activity in human subjects during neurosurgical procedures involving microelectrode recordings. This protocol has two phases: a preoperative phase and an intraoperative phase. During the preoperative phase, we discuss informed consent, equipment setup and behavioral testing. During the intraoperative phase, we discuss the procedure for microelectrode recordings. Because patients are often awake during these procedures, this protocol can be performed in conjunction with behavioral tasks for studying a variety of cognitive functions. We describe the protocol in detail and provide two examples of expected results. In addition, we discuss the potential difficulties and pitfalls related to intraoperative studies. This protocol takes 1.5 h to complete.

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Figure 1: Photographs of intraoperative patient orientation and cannula placement.
Figure 2: Forward view of intraoperative physiology rig.
Figure 3: Composite image demonstrating electrode trajectory.
Figure 4: Top-down perspective of the operating room.
Figure 5: Representative neuronal data.
Figure 6: Individual and population neuronal responses of dorsal anterior cingulate cortex neurons during a cognitive interference task.
Figure 7: Population response of nucleus accumbens neurons predicting behavioral choice during a financial decision-making task.


  1. Hyde, I. A microelectrode and unicellular stimulation of single cells. Biol. Bull. 71, 130–133 (1921).

    Article  Google Scholar 

  2. Hodgkin, A.L. & Huxley, A.F. Action potentials recorded from inside a nerve fibre. Nature 144, 710–711 (1939).

    Article  Google Scholar 

  3. Eccles, J.C. & O'Connor, W.J. Responses which nerve impulses evoke in mammalian striated muscles. J. Physiol. 97, 44–102 (1939).

    Article  CAS  Google Scholar 

  4. Eccles, J.C. & Kuffler, S.W. The endplate potential during and after the muscle spike potential. J. Neurophysiol. 4, 486–506 (1941).

    Article  Google Scholar 

  5. Hubel, D. Tungsten microelectrode for recording from single units. Science 125, 549–550 (1957).

    Article  CAS  Google Scholar 

  6. Albe-Fessard, D., Dumont-TYC, S. & Jankowska, E. Somatotopic and associative neuron activities measured at the level of the primary somatic surface. J. Physiol. 53, 243–244 (1961).

    CAS  Google Scholar 

  7. Guiot, G., Hardy, J. & Albe-Fessard, D. Precise delimitation of the subcortical structures and identification of thalamic nuclei in man by stereotactic electrophysiology. Neurochirurgia 5, 1–18 (1962).

    CAS  PubMed  Google Scholar 

  8. Gaze, R.M. et al. Microelectrode recordings from the human thalamus. Brain 87, 691–706 (1964).

    Article  CAS  Google Scholar 

  9. Hardy, J. The development of the stereotaxic method in neurosurgery. Union Med. Can. 90, 969–971 (1961).

    CAS  PubMed  Google Scholar 

  10. Hamani, C. et al. Correspondence of microelectrode mapping with magnetic resonance imaging for subthalamic nucleus procedures. Surg. Neurol. 63, 249–253; discussion 253 (2005).

    Article  Google Scholar 

  11. Starr, P.A. et al. Implantation of deep brain stimulators into the subthalamic nucleus: technical approach and magnetic resonance imaging-verified lead locations. J. Neurosurg. 97, 370–387 (2002).

    Article  Google Scholar 

  12. Bakay, R.A.E. Movement Disorder Surgery. The Essentials (Thieme Medical Publishers, 2008).

  13. Hassler, R., Mundinger, F. & Riechert, T . Pathophysiology of tremor at rest derived from the correlation of anatomical and clinical data. Confin. Neurol. 32, 79–87 (1970).

    Article  CAS  Google Scholar 

  14. Wichmann, T. & DeLong, M.R. Pathophysiology of Parkinson's disease: the MPTP primate model of the human disorder. Ann. N Y Acad. Sci. 991, 199–213 (2003).

    Article  CAS  Google Scholar 

  15. Christine, C.W., Langston, J.W., Turner, R.S. & Starr, P.A. The neurophysiology and effect of deep brain stimulation in a patient with l-methyl-4-phenyl-l,2,3,6-tetrahydropyridine-induced parkinsonism. J. Neurosurg. 110, 234–238 (2009).

    Article  Google Scholar 

  16. Amirnovin, R., Williams, Z.M., Cosgrove, G.R. & Eskandar, E.N. Visually guided movements suppress subthalamic oscillations in Parkinson's disease patients. J. Neurosci. 24, 11302–11306 (2004).

    Article  CAS  Google Scholar 

  17. Zaghloul, K.A. et al. Human substantia nigra neurons encode unexpected financial rewards. Science 323, 1496–1499 (2009).

    Article  CAS  Google Scholar 

  18. Sheth, S.A. et al. Human dorsal anterior cingulate cortex neurons mediate ongoing behavioural adaptation. Nature 488, 218–221 (2012).

    Article  CAS  Google Scholar 

  19. Patel, S.R. et al. Single-neuron responses in the human nucleus accumbens during a financial decision-making task. J. Neurosci. 32, 7311–7315 (2012).

    Article  CAS  Google Scholar 

  20. Mian, M.K. et al. Encoding of rules by neurons in the human dorsolateral prefrontal cortex. Cereb. Cortex (21 November 2012).

  21. Starr, P.A., Barbaro, N.M. & Larson, P.S. Neurosurgical Operative Atlas. Functional Neurosurgery (Thieme Medical Publishers, 2008).

  22. Asaad, W.F. & Eskandar, E.A. A flexible software tool for temporally-precise behavioral control in MATLAB. J. Neurosci. Methods 174, 245–258 (2008).

    Article  Google Scholar 

  23. Asaad, W.F. & Eskandar, E.N. Achieving behavioral control with millisecond resolution in a high-level programming environment. J. Neurosci. Methods 173, 235–240 (2008).

    Article  Google Scholar 

  24. Williams, Z.M. & Eskandar, E.N. Human anterior cingulate neurons and the integration of monetary reward with motor responses. Nat. Neurosci. 7, 1370–1375 (2004).

    Article  CAS  Google Scholar 

  25. Weise, L., Eibach, S., Seifert, V. & Setzer, M. Intraoperative 3D fluoroscopy in stereotactic surgery. Acta Neurochir. 154, 815–821 (2012).

    Article  Google Scholar 

  26. Kramer, D.R. et al. Best surgical practices: a stepwise approach to the University of Pennsylvania deep brain stimulation protocol. Neurosurg. Focus 29, E3 (2010).

    Article  Google Scholar 

  27. Xie, K., Wang, S., Aziz, T.Z., Stein, J.F. & Liu, X. The physiologically modulated electrode potentials at the depth electrode-brain interface in humans. Neurosci. Lett. 402, 238–243 (2006).

    Article  CAS  Google Scholar 

  28. Maciver, M.B., Bronte-Stewart, H.M., Henderson, J.M., Jaffe, R.A. & Brock-Utne, J.G. Human subthalamic neuron spiking exhibits subtle responses to sedatives. Anesthesiology 115, 254–264 (2011).

    Article  Google Scholar 

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This work was supported by grants from the US National Institutes of Health (NIH) (National Institute on Drug Abuse (NIDA) no.R01DA026297). E.N.E. was supported by National Eye Institute (NEI) grant no. NEI 1R01EY017658-01A1, the National Institute of Mental Health (NIMH) Conte Award no. MH086400, the Klingenstein Foundation, the Howard Hughes Medical Institute and the Dana Foundation. S.R.P. was supported by the Sackler Programme in Psychobiology. S.A.S. was supported by National Institute of Neurological Disorders and Stroke (NINDS) grant no. R25 NS065743. We thank K. Finnis for providing the 3D reconstructions.

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S.R.P., S.A.S., C.M.-R., M.K.M., W.F.A., J.L.G., C.-S.K., J.T.G., Z.M.W. and E.N.E. designed, conducted or analyzed the data. D.D.D., A.W.F., B.D.G., Z.M.W. and E.N.E. evaluated the patients and provided clinical care. S.R.P. and S.A.S. wrote the manuscript. All the authors edited the manuscript.

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Correspondence to Shaun R Patel.

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Patel, S., Sheth, S., Martinez-Rubio, C. et al. Studying task-related activity of individual neurons in the human brain. Nat Protoc 8, 949–957 (2013).

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