Skip to main content

Advertisement

SpringerLink
Log in

Measuring GABAergic Inhibitory Activity with TMS-EEG and Its Potential Clinical Application for Chronic Pain

  • INVITED REVIEW
  • Published:
Journal of Neuroimmune Pharmacology Aims and scope Submit manuscript

Abstract

Chronic pain is debilitating disorder in which the underlying pathophysiology is still unknown. Impaired cortical inhibition is one mechanism that is associated with chronic pain. Cortical inhibition refers to a neurophysiological process in which gamma-aminobutyric acid (GABA) inhibitory interneurons selectively attenuate the activity of pyramidal neurons in the cortex. Previous studies have capitalized on the ability of transcranial magnetic stimulation (TMS) to index cortical inhibition by stimulating the motor cortex and measuring the resulting peripheral motor evoked potentials with electromyography. Chronic pain has been shown to induce changes in cortical inhibition within the motor cortex using TMS. Electroencephalography (EEG) studies also demonstrate that gamma (30–50 Hz) oscillations in the prefrontal and somatosensory cortex are associated with the experience of pain. As gamma oscillations are mediated by GABA, the combination of TMS with EEG allows for the examination of the relationship between cortical inhibition, gamma and chronic pain. In this paper, we summarize the evidence of impaired GABAergic and gamma oscillations in chronic pain patients. We then demonstrate TMS-EEG as a reliable method in which to record cortical inhibition directly from the prefrontal cortex to examine the modulatory effect of GABAB receptor inhibition on cortical oscillations. Finally, the modulation of GABA and gamma oscillations with repetitive TMS will be suggested as the possible mechanism through which rTMS exerts its therapeutic effects in the treatment of pain. The aim of this paper, therefore, is to present the TMS-EEG as a potential method through which to better classify, diagnose and treat chronic pain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Akbarian S, Kim JJ, Potkin SG, Hagman JO, Tafazzoli A, Bunney WE Jr, Jones EG (1995) Gene expression for glutamic acid decarboxylase is reduced without loss of neurons in prefrontal cortex of schizophrenics [see comments]. Arch Gen Psychiatry 52(4):258–266, discussion 267-278

    Article  PubMed  CAS  Google Scholar 

  • Backonja MM (2003) Defining neuropathic pain. Anesth Analg 97(3):785–790

    Article  PubMed  Google Scholar 

  • Baron R (2006) Mechanisms of disease: neuropathic pain–a clinical perspective. Nat Clin Pract Neurol 2(2):95–106. doi:10.1038/ncpneuro0113

    Article  PubMed  Google Scholar 

  • Barr MS, Farzan F, Arenovich T, Chen R, Fitzgerald PB, Daskalakis ZJ (2011) The effect of repetitive transcranial magnetic stimulation on gamma oscillatory activity in schizophrenia. PLoS One 6(7):e22627. doi:10.1371/journal.pone.0022627

    Article  PubMed  CAS  Google Scholar 

  • Barr MS, Farzan F, Rusjan PM, Chen R, Fitzgerald PB, Daskalakis ZJ (2009) Potentiation of gamma oscillatory activity through repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex. Neuropsychopharmacology 34(11):2359–2367. doi:10.1038/npp.2009.79

    Article  PubMed  Google Scholar 

  • Bartos M, Vida I, Jonas P (2007) Synaptic mechanisms of synchronized gamma oscillations in inhibitory interneuron networks. Nat Rev Neurosci 8(1):45–56

    Article  PubMed  CAS  Google Scholar 

  • Basar-Eroglu C, Brand A, Hildebrandt H, Karolina Kedzior K, Mathes B, Schmiedt C (2007) Working memory related gamma oscillations in schizophrenia patients. Int J Psychophysiol 64(1):39–45

    Article  PubMed  Google Scholar 

  • Benes FM, McSparren J, Bird ED, SanGiovanni JP, Vincent SL (1991) Deficits in small interneurons in prefrontal and cingulate cortices of schizophrenic and schizoaffective patients. Arch Gen Psychiatry 48(11):996–1001

    Article  PubMed  CAS  Google Scholar 

  • Bonica JJ (1977) Basic principles in managing chronic pain. Arch Surg 112(6):783–788

    Article  PubMed  CAS  Google Scholar 

  • Bouhassira D, Attal N, Alchaar H, Boureau F, Brochet B, Bruxelle J, Cunin G, Fermanian J, Ginies P, Grun-Overdyking A, Jafari-Schluep H, Lanteri-Minet M, Laurent B, Mick G, Serrie A, Valade D, Vicaut E (2005) Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4). Pain 114(1–2):29–36. doi:10.1016/j.pain.2004.12.010

    Article  PubMed  Google Scholar 

  • Bouhassira D, Attal N, Fermanian J, Alchaar H, Gautron M, Masquelier E, Rostaing S, Lanteri-Minet M, Collin E, Grisart J, Boureau F (2004) Development and validation of the neuropathic pain symptom inventory. Pain 108(3):248–257. doi:10.1016/j.pain.2003.12.024

    Article  PubMed  Google Scholar 

  • Bragin A, Jando G, Nadasdy Z, Hetke J, Wise K, Buzsaki G (1995) Gamma (40–100 Hz) oscillation in the hippocampus of the behaving rat. J Neurosci 15(1 Pt 1):47–60

    PubMed  CAS  Google Scholar 

  • Brown JT, Davies CH, Randall AD (2007) Synaptic activation of GABA(B) receptors regulates neuronal network activity and entrainment. Eur J Neurosci 25(10):2982–2990

    Article  PubMed  Google Scholar 

  • Burt T, Lisanby SH, Sackeim HA (2002) Neuropsychiatric applications of transcranial magnetic stimulation: a meta analysis. Int J Neuropsychopharmacol 5(1):73–103. doi:10.1017/S1461145702002791

    Article  PubMed  CAS  Google Scholar 

  • Buzsáki G (2006) Rhythms of the brain. Oxford University Press, New York

    Book  Google Scholar 

  • Casali AG, Casarotto S, Rosanova M, Mariotti M, Massimini M (2010) General indices to characterize the electrical response of the cerebral cortex to TMS. NeuroImage 49(2):1459–1468. doi:10.1016/j.neuroimage.2009.09.026

    Article  PubMed  Google Scholar 

  • Casarotto S, Romero Lauro LJ, Bellina V, Casali AG, Rosanova M, Pigorini A, Defendi S, Mariotti M, Massimini M (2010) EEG responses to TMS are sensitive to changes in the perturbation parameters and repeatable over time. PLoS One 5(4):e10281. doi:10.1371/journal.pone.0010281

    Article  PubMed  CAS  Google Scholar 

  • Chen R (2004) Interactions between inhibitory and excitatory circuits in the human motor cortex. Exp Brain Res 154(1):1–10

    Article  PubMed  Google Scholar 

  • Cho RY, Konecky RO, Carter CS (2006) Impairments in frontal cortical gamma synchrony and cognitive control in schizophrenia. Proc Natl Acad Sci U S A 103(52):19878–19883

    Article  PubMed  CAS  Google Scholar 

  • Cooper MS, Przebinda AS (2011) Synaptic conversion of chloride-dependent synapses in spinal nociceptive circuits: roles in neuropathic pain. Pain Res Treat 2011:738645. doi:10.1155/2011/738645

    PubMed  Google Scholar 

  • Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y (2005) BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438(7070):1017–1021. doi:10.1038/nature04223

    Article  PubMed  CAS  Google Scholar 

  • Crick F, Koch C (1990) Some reflections on visual awareness. Cold Spring Harb Symp Quant Biol 55:953–962

    Article  PubMed  CAS  Google Scholar 

  • Croft RJ, Williams JD, Haenschel C, Gruzelier JH (2002) Pain perception, hypnosis and 40 Hz oscillations. Int J Psychophysiol 46(2):101–108

    Article  PubMed  Google Scholar 

  • Cruccu G, Anand P, Attal N, Garcia-Larrea L, Haanpaa M, Jorum E, Serra J, Jensen TS (2004) EFNS guidelines on neuropathic pain assessment. Eur J Neurol 11(3):153–162

    Article  PubMed  CAS  Google Scholar 

  • Daskalakis ZJ, Farzan F, Barr MS, Maller JJ, Chen R, Fitzgerald PB (2008) Long-interval cortical inhibition from the dorsolateral prefrontal cortex: a TMS-EEG study. Neuropsychopharmacology 33(12):2860–2869

    Article  PubMed  Google Scholar 

  • Daskalakis ZJ, Moller B, Christensen BK, Fitzgerald PB, Gunraj C, Chen R (2006) The effects of repetitive transcranial magnetic stimulation on cortical inhibition in healthy human subjects. Exp Brain Res 174(3):403–412

    Article  PubMed  Google Scholar 

  • De Pascalis V, Cacace I (2005) Pain perception, obstructive imagery and phase-ordered gamma oscillations. Int J Psychophysiol 56(2):157–169. doi:10.1016/j.ijpsycho.2004.11.004

    Article  PubMed  Google Scholar 

  • Di Lazzaro V, Oliviero A, Mazzone P, Pilato F, Saturno E, Insola A, Visocchi M, Colosimo C, Tonali PA, Rothwell JC (2002) Direct demonstration of long latency cortico-cortical inhibition in normal subjects and in a patient with vascular parkinsonism. Clin Neurophysiol 113(11):1673–1679

    Article  PubMed  Google Scholar 

  • Di Lazzaro V, Oliviero A, Meglio M, Cioni B, Tamburrini G, Tonali P, Rothwell JC (2000) Direct demonstration of the effect of lorazepam on the excitability of the human motor cortex. Clin Neurophysiol 111(5):794–799

    Article  PubMed  Google Scholar 

  • Diamond A (1991) The future development of chronic pain relief. Anaesthesia 46(2):83–84

    Article  PubMed  CAS  Google Scholar 

  • Dworkin RH, Backonja M, Rowbotham MC, Allen RR, Argoff CR, Bennett GJ, Bushnell MC, Farrar JT, Galer BS, Haythornthwaite JA, Hewitt DJ, Loeser JD, Max MB, Saltarelli M, Schmader KE, Stein C, Thompson D, Turk DC, Wallace MS, Watkins LR, Weinstein SM (2003) Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol 60(11):1524–1534. doi:10.1001/archneur.60.11.1524

    Article  PubMed  Google Scholar 

  • Eisenberg E, Chistyakov AV, Yudashkin M, Kaplan B, Hafner H, Feinsod M (2005) Evidence for cortical hyperexcitability of the affected limb representation area in CRPS: a psychophysical and transcranial magnetic stimulation study. Pain 113(1–2):99–105. doi:10.1016/j.pain.2004.09.030

    Article  PubMed  Google Scholar 

  • Engel AK, Singer W (2001) Temporal binding and the neural correlates of sensory awareness. Trends Cogn Sci 5(1):16–25

    Article  PubMed  Google Scholar 

  • Farina S, Tinazzi M, Le Pera D, Valeriani M (2003) Pain-related modulation of the human motor cortex. Neurol Res 25(2):130–142

    Article  PubMed  Google Scholar 

  • Farzan F, Barr MS, Levinson AJ, Chen R, Wong W, Fitzgerald PB, Daskalakis ZJ (2010a) Evidence for gamma inhibition deficits in the dorsolateral prefrontal cortex of patients with schizophrenia. Brain 133(Pt 5):1505–1514. doi:10.1093/brain/awq046

    Article  PubMed  Google Scholar 

  • Farzan F, Barr MS, Levinson AJ, Chen R, Wong W, Fitzgerald PB, Daskalakis ZJ (2010b) Reliability of long-interval cortical inhibition in healthy human subjects: a TMS-EEG study. J Neurophysiol 104(3):1339–1346. doi:10.1152/jn.00279.2010

    Article  PubMed  Google Scholar 

  • Farzan F, Barr MS, Levinson AJ, Chen R, Wong W, Fitzgerald PB, Daskalakis ZJ (2010c) Reliability of long interval cortical inhibition in healthy human subjects: a TMS-EEG study. J Neurophysiol. doi:10.1152/jn.00279.2010

  • Farzan F, Barr MS, Wong W, Chen R, Fitzgerald PB, Daskalakis ZJ (2009) Suppression of gamma-oscillations in the dorsolateral prefrontal cortex following long interval cortical inhibition: a TMS-EEG study. Neuropsychopharmacology 34(6):1543–1551. doi:10.1038/npp.2008.211

    Article  PubMed  CAS  Google Scholar 

  • Ferreri F, Pasqualetti P, Maatta S, Ponzo D, Ferrarelli F, Tononi G, Mervaala E, Miniussi C, Rossini PM (2011) Human brain connectivity during single and paired pulse transcranial magnetic stimulation. NeuroImage 54(1):90–102. doi:10.1016/j.neuroimage.2010.07.056

    Article  PubMed  Google Scholar 

  • Fisahn A, Pike FG, Buhl EH, Paulsen O (1998) Cholinergic induction of network oscillations at 40 Hz in the hippocampus in vitro. Nature 394(6689):186–189. doi:10.1038/28179

    Article  PubMed  CAS  Google Scholar 

  • Fitzgerald PB, Maller JJ, Hoy K, Farzan F, Daskalakis ZJ (2009) GABA and cortical inhibition in motor and non-motor regions using combined TMS-EEG: a time analysis. Clin Neurophysiol 120(9):1706–1710. doi:10.1016/j.clinph.2009.06.019

    Article  PubMed  CAS  Google Scholar 

  • Fries P, Reynolds JH, Rorie AE, Desimone R (2001) Modulation of oscillatory neuronal synchronization by selective visual attention. Science 291(5508):1560–1563. doi:10.1126/science.291.5508.1560

    Article  PubMed  CAS  Google Scholar 

  • Gross J, Schnitzler A, Timmermann L, Ploner M (2007) Gamma oscillations in human primary somatosensory cortex reflect pain perception. PLoS Biol 5(5):e133. doi:10.1371/journal.pbio.0050133

    Article  PubMed  CAS  Google Scholar 

  • Gupta A, Wang Y, Markram H (2000) Organizing principles for a diversity of GABAergic interneurons and synapses in the neocortex. Science 287(5451):273–278

    Article  PubMed  CAS  Google Scholar 

  • Hansson P (2002) Neuropathic pain: clinical characteristics and diagnostic workup. Eur J Pain 6(Suppl A):47–50. doi:10.1053/eujp.2001.0322

    Article  PubMed  Google Scholar 

  • Hansson PT, Dickenson AH (2005) Pharmacological treatment of peripheral neuropathic pain conditions based on shared commonalities despite multiple etiologies. Pain 113(3):251–254. doi:10.1016/j.pain.2004.10.007

    Article  PubMed  Google Scholar 

  • Hasenstaub A, Shu Y, Haider B, Kraushaar U, Duque A, McCormick DA (2005) Inhibitory postsynaptic potentials carry synchronized frequency information in active cortical networks. Neuron 47(3):423–435

    Article  PubMed  CAS  Google Scholar 

  • Hauck M, Lorenz J, Engel AK (2007) Attention to painful stimulation enhances gamma-band activity and synchronization in human sensorimotor cortex. J Neurosci 27(35):9270–9277. doi:10.1523/JNEUROSCI.2283-07.2007

    Article  PubMed  CAS  Google Scholar 

  • Herrmann CS, Munk MH, Engel AK (2004) Cognitive functions of gamma-band activity: memory match and utilization. Trends Cogn Sci 8(8):347–355. doi:10.1016/j.tics.2004.06.006

    Article  PubMed  Google Scholar 

  • Hershman KM, Freedman R, Bickford PC (1995) GABAB antagonists diminish the inhibitory gating of auditory response in the rat hippocampus. Neurosci Lett 190(2):133–136

    Article  PubMed  CAS  Google Scholar 

  • Hewitt SA, Wamsteeker JI, Kurz EU, Bains JS (2009) Altered chloride homeostasis removes synaptic inhibitory constraint of the stress axis. Nat Neurosci 12(4):438–443. doi:10.1038/nn.2274

    Article  PubMed  CAS  Google Scholar 

  • Howard MW, Rizzuto DS, Caplan JB, Madsen JR, Lisman J, Aschenbrenner-Scheibe R, Schulze-Bonhage A, Kahana MJ (2003) Gamma oscillations correlate with working memory load in humans. Cereb Cortex 13(12):1369–1374

    Article  PubMed  Google Scholar 

  • IASP (2011) Classification of chronic pain. In: Merskey H, Bogduk N (eds) Descriptions of chronic pain syndromes and definitions of pain terms. 2nd ed. Seattle: ISAP Press

  • Janssen SP, Truin M, Van Kleef M, Joosten EA (2011) Differential GABAergic disinhibition during the development of painful peripheral neuropathy. Neuroscience 184:183–194. doi:10.1016/j.neuroscience.2011.03.060

    Article  PubMed  CAS  Google Scholar 

  • Ji G, Neugebauer V (2011) Pain-related deactivation of medial prefrontal cortical neurons involves mGluR1 and GABA(A) receptors. J Neurophysiol 106(5):2642–2652. doi:10.1152/jn.00461.2011

    Article  PubMed  CAS  Google Scholar 

  • Jones EG (1993) GABAergic neurons and their role in cortical plasticity in primates. Cereb Cortex 3(5):361–372

    Article  PubMed  CAS  Google Scholar 

  • Kahle KT, Staley KJ, Nahed BV, Gamba G, Hebert SC, Lifton RP, Mount DB (2008) Roles of the cation-chloride cotransporters in neurological disease. Nat Clin Pract Neurol 4(9):490–503. doi:10.1038/ncpneuro0883

    Article  PubMed  CAS  Google Scholar 

  • Kujirai T, Caramia MD, Rothwell JC, Day BL, Thompson PD, Ferbert A, Wroe S, Asselman P, Marsden CD (1993) Corticocortical inhibition in human motor cortex. J Physiol 471:501–519

    PubMed  CAS  Google Scholar 

  • Lee J, Back SK, Lim EJ, Cho GC, Kim MA, Kim HJ, Lee MH, Na HS (2010) Are spinal GABAergic elements related to the manifestation of neuropathic pain in rat? Korean J Physiol Pharmacol 14(2):59–69. doi:10.4196/kjpp.2010.14.2.59

    Article  PubMed  CAS  Google Scholar 

  • Lefaucheur JP (2006) The use of repetitive transcranial magnetic stimulation (rTMS) in chronic neuropathic pain. Neurophysiol Clin 36(3):117–124. doi:10.1016/j.neucli.2006.08.002

    Article  PubMed  CAS  Google Scholar 

  • Lefaucheur JP, Drouot X, Menard-Lefaucheur I, Keravel Y, Nguyen JP (2006) Motor cortex rTMS restores defective intracortical inhibition in chronic neuropathic pain. Neurology 67(9):1568–1574. doi:10.1212/01.wnl.0000242731.10074.3c

    Article  PubMed  CAS  Google Scholar 

  • Leung LS, Shen B (2007) GABAB receptor blockade enhances theta and gamma rhythms in the hippocampus of behaving rats. Hippocampus 17(4):281–291

    Article  PubMed  CAS  Google Scholar 

  • Lewis DA, Pierri JN, Volk DW, Melchitzky DS, Woo TU (1999) Altered GABA neurotransmission and prefrontal cortical dysfunction in schizophrenia. Biol Psychiatry 46(5):616–626

    Article  PubMed  CAS  Google Scholar 

  • Lioumis P, Kicic D, Savolainen P, Makela JP, Kahkonen S (2009) Reproducibility of TMS-Evoked EEG responses. Hum Brain Mapp 30(4):1387–1396. doi:10.1002/hbm.20608

    Article  PubMed  Google Scholar 

  • Llinas RR, Ribary U, Jeanmonod D, Kronberg E, Mitra PP (1999) Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc Natl Acad Sci U S A 96(26):15222–15227

    Article  PubMed  CAS  Google Scholar 

  • Malan TP, Mata HP, Porreca F (2002) Spinal GABA(A) and GABA(B) receptor pharmacology in a rat model of neuropathic pain. Anesthesiology 96(5):1161–1167

    Article  PubMed  CAS  Google Scholar 

  • Mann EO, Radcliffe CA, Paulsen O (2005) Hippocampal gamma-frequency oscillations: from interneurones to pyramidal cells, and back. J Physiol 562(Pt 1):55–63

    PubMed  CAS  Google Scholar 

  • Mannaioni G, Marino MJ, Valenti O, Traynelis SF, Conn PJ (2001) Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function. J Neurosci 21(16):5925–5934

    PubMed  CAS  Google Scholar 

  • Markram H, Toledo-Rodriguez M, Wang Y, Gupta A, Silberberg G, Wu C (2004) Interneurons of the neocortical inhibitory system. Nat Rev Neurosci 5(10):793–807. doi:10.1038/nrn1519

    Article  PubMed  CAS  Google Scholar 

  • Max MB (2002) Clarifying the definition of neuropathic pain. Pain 96(3):406–407, author reply 407–408

    Article  PubMed  Google Scholar 

  • McCormick DA (1989) GABA as an inhibitory neurotransmitter in human cerebral cortex. J Neurophysiol 62(5):1018–1027

    PubMed  CAS  Google Scholar 

  • McDonnell MN, Orekhov Y, Ziemann U (2006) The role of GABA(B) receptors in intracortical inhibition in the human motor cortex. Exp Brain Res 173(1):86–93

    Article  PubMed  CAS  Google Scholar 

  • Metz AE, Yau HJ, Centeno MV, Apkarian AV, Martina M (2009) Morphological and functional reorganization of rat medial prefrontal cortex in neuropathic pain. Proc Natl Acad Sci U S A 106(7):2423–2428. doi:10.1073/pnas.0809897106

    Article  PubMed  CAS  Google Scholar 

  • Mhalla A, de Andrade DC, Baudic S, Perrot S, Bouhassira D (2010) Alteration of cortical excitability in patients with fibromyalgia. Pain 149(3):495–500. doi:10.1016/j.pain.2010.03.009

    Article  PubMed  Google Scholar 

  • Moore KA, Kohno T, Karchewski LA, Scholz J, Baba H, Woolf CJ (2002) Partial peripheral nerve injury promotes a selective loss of GABAergic inhibition in the superficial dorsal horn of the spinal cord. J Neurosci 22(15):6724–6731

    PubMed  CAS  Google Scholar 

  • Niebur E, Koch C (1994) A model for the neuronal implementation of selective visual attention based on temporal correlation among neurons. J Comput Neurosci 1(1–2):141–158

    Article  PubMed  CAS  Google Scholar 

  • Oren I, Hajos N, Paulsen O (2010) Identification of the current generator underlying cholinergically induced gamma frequency field potential oscillations in the hippocampal CA3 region. J Physiol 588(Pt 5):785–797. doi:10.1113/jphysiol.2009.180851

    Article  PubMed  CAS  Google Scholar 

  • Paus T, Sipila PK, Strafella AP (2001) Synchronization of neuronal activity in the human primary motor cortex by transcranial magnetic stimulation: an EEG study. J Neurophysiol 86(4):1983–1990

    PubMed  CAS  Google Scholar 

  • Picarelli H, Teixeira MJ, de Andrade DC, Myczkowski ML, Luvisotto TB, Yeng LT, Fonoff ET, Pridmore S, Marcolin MA (2010) Repetitive transcranial magnetic stimulation is efficacious as an add-on to pharmacological therapy in complex regional pain syndrome (CRPS) type I. J Pain 11(11):1203–1210. doi:10.1016/j.jpain.2010.02.006

    Article  PubMed  Google Scholar 

  • Pleger B, Janssen F, Schwenkreis P, Volker B, Maier C, Tegenthoff M (2004) Repetitive transcranial magnetic stimulation of the motor cortex attenuates pain perception in complex regional pain syndrome type I. Neurosci Lett 356(2):87–90

    Article  PubMed  CAS  Google Scholar 

  • Rogasch NC, Fitzgerald PB (2012) Assessing cortical network properties using TMS-EEG. Hum Brain Mapp. doi:10.1002/hbm.22016

  • Rosanova M, Casali A, Bellina V, Resta F, Mariotti M, Massimini M (2009) Natural frequencies of human corticothalamic circuits. J Neurosci 29(24):7679–7685. doi:10.1523/JNEUROSCI.0445-09.2009

    Article  PubMed  CAS  Google Scholar 

  • Sailer A, Molnar GF, Paradiso G, Gunraj CA, Lang AE, Chen R (2003) Short and long latency afferent inhibition in Parkinson’s disease. Brain 126(Pt 8):1883–1894. doi:10.1093/brain/awg183

    Article  PubMed  Google Scholar 

  • Sanger TD, Garg RR, Chen R (2001) Interactions between two different inhibitory systems in the human motor cortex. J Physiol 530(Pt 2):307–317

    Article  PubMed  CAS  Google Scholar 

  • Schwenkreis P, Janssen F, Rommel O, Pleger B, Volker B, Hosbach I, Dertwinkel R, Maier C, Tegenthoff M (2003) Bilateral motor cortex disinhibition in complex regional pain syndrome (CRPS) type I of the hand. Neurology 61(4):515–519

    Article  PubMed  CAS  Google Scholar 

  • Schwenkreis P, Scherens A, Ronnau AK, Hoffken O, Tegenthoff M, Maier C (2010) Cortical disinhibition occurs in chronic neuropathic, but not in chronic nociceptive pain. BMC Neurosci 11:73. doi:10.1186/1471-2202-11-73

    Article  PubMed  Google Scholar 

  • Siebner HR, Dressnandt J, Auer C, Conrad B (1998) Continuous intrathecal baclofen infusions induced a marked increase of the transcranially evoked silent period in a patient with generalized dystonia. Muscle Nerve 21(9):1209–1212

    Article  PubMed  CAS  Google Scholar 

  • Singer W (1999) Neuronal synchrony: a versatile code for the definition of relations? Neuron 24(1):49–65, 111-125

    Article  PubMed  CAS  Google Scholar 

  • Sohal VS, Zhang F, Yizhar O, Deisseroth K (2009) Parvalbumin neurons and gamma rhythms enhance cortical circuit performance. Nature 459(7247):698–702. doi:10.1038/nature07991

    Article  PubMed  CAS  Google Scholar 

  • Steinmetz PN, Roy A, Fitzgerald PJ, Hsiao SS, Johnson KO, Niebur E (2000) Attention modulates synchronized neuronal firing in primate somatosensory cortex. Nature 404(6774):187–190. doi:10.1038/35004588

    Article  PubMed  CAS  Google Scholar 

  • Tallon-Baudry C, Bertrand O, Henaff MA, Isnard J, Fischer C (2005) Attention modulates gamma-band oscillations differently in the human lateral occipital cortex and fusiform gyrus. Cereb Cortex 15(5):654–662. doi:10.1093/cercor/bhh167

    Article  PubMed  Google Scholar 

  • Thomson AM (2000) Neurotransmission: chemical and electrical interneuron coupling. Curr Biol 10(3):R110–R112

    Article  PubMed  CAS  Google Scholar 

  • Treede RD, Jensen TS, Campbell JN, Cruccu G, Dostrovsky JO, Griffin JW, Hansson P, Hughes R, Nurmikko T, Serra J (2008) Neuropathic pain: redefinition and a grading system for clinical and research purposes. Neurology 70(18):1630–1635. doi:10.1212/01.wnl.0000282763.29778.59

    Article  PubMed  CAS  Google Scholar 

  • Tsubokawa T, Katayama Y, Yamamoto T, Hirayama T, Koyama S (1991) Chronic motor cortex stimulation for the treatment of central pain. Acta Neurochir Suppl (Wien) 52:137–139

    Article  CAS  Google Scholar 

  • Turgut N, Altun BU (2009) Cortical disinhibition in diabetic patients with neuropathic pain. Acta Neurol Scand 120(6):383–388. doi:10.1111/j.1600-0404.2009.01235.x

    Article  PubMed  CAS  Google Scholar 

  • Turton AJ, McCabe CS, Harris N, Filipovic SR (2007) Sensorimotor integration in Complex Regional Pain Syndrome: a transcranial magnetic stimulation study. Pain 127(3):270–275. doi:10.1016/j.pain.2006.08.021

    Article  PubMed  Google Scholar 

  • Valls-Sole J, Pascual-Leone A, Wassermann EM, Hallett M (1992) Human motor evoked responses to paired transcranial magnetic stimuli. Electroencephalogr Clin Neurophysiol 85(6):355–364

    Article  PubMed  CAS  Google Scholar 

  • Volk DW, Pierri JN, Fritschy JM, Auh S, Sampson AR, Lewis DA (2002) Reciprocal alterations in pre- and postsynaptic inhibitory markers at chandelier cell inputs to pyramidal neurons in schizophrenia. Cereb Cortex 12(10):1063–1070

    Article  PubMed  Google Scholar 

  • Wang XJ, Buzsaki G (1996) Gamma oscillation by synaptic inhibition in a hippocampal interneuronal network model. J Neurosci 16(20):6402–6413

    PubMed  CAS  Google Scholar 

  • Werhahn KJ, Kunesch E, Noachtar S, Benecke R, Classen J (1999) Differential effects on motorcortical inhibition induced by blockade of GABA uptake in humans. J Physiol (Lond) 517(Pt 2):591–597

    Article  CAS  Google Scholar 

  • Whittington MA, Traub RD, Jefferys JG (1995) Synchronized oscillations in interneuron networks driven by metabotropic glutamate receptor activation. Nature 373(6515):612–615

    Article  PubMed  CAS  Google Scholar 

  • Woolf CJ (2004) Dissecting out mechanisms responsible for peripheral neuropathic pain: implications for diagnosis and therapy. Life Sci 74(21):2605–2610. doi:10.1016/j.lfs.2004.01.003

    Article  PubMed  CAS  Google Scholar 

  • Yaksh TL (1989) Behavioral and autonomic correlates of the tactile evoked allodynia produced by spinal glycine inhibition: effects of modulatory receptor systems and excitatory amino acid antagonists. Pain 37(1):111–123

    Article  PubMed  CAS  Google Scholar 

  • Ziemann U, Lonnecker S, Steinhoff BJ, Paulus W (1996) The effect of lorazepam on the motor cortical excitability in man. Exp Brain Res 109(1):127–135

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The authors gratefully acknowledge Anosha Zanjani for her creation of Figure One for this review paper.

The authors alone are responsible for the content and the writing of the paper. PBF is supported by a NHMRC Practitioner Fellowship and has received equipment for research from Medtronic, MagVenture A/S and Brainsway Ltd and research funding from Cervil Neurotech. ZJD has received research funding from Aspect Medical Inc, Brainsway Inc and Neuronetics Inc; he has also received a travel allowance from Pfizer and Merck. This work was funded, in part, by the Ontario Mental Health Foundation (OMHF, ZFD, MB), Canadian Institutes of Health Research (CIHR) doctoral award (FF), Clinician Scientist Award (ZJD), and by a National Health and Medical Research Council (NHMRC) Practitioner Fellowship (PBF) and by Constance and Stephen Lieber through a National Alliance for Research on Schizophrenia and Depression (NARSAD) Lieber Young Investigator award (ZJD). The authors report no conflicts of interest.

Author information

Authors and Affiliations

  1. Schizophrenia Program; Mood and Anxiety Program, Centre for Addiction and Mental Health, 250 College Street, Toronto, Ontario, Canada, M5T 1R8

    Mera S. Barr

  2. Harvard Medical School, Boston, MA, USA

    Faranak Farzan

  3. Berenson–Allen Center for Noninvasive Brain Stimulation, Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA, USA

    Faranak Farzan

  4. Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada

    Karen D. Davis

  5. Department of Surgery, University of Toronto, Toronto, Ontario, Canada

    Karen D. Davis

  6. Division of Brain, Imaging and Behaviour-Systems Neuroscience; Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada

    Karen D. Davis

  7. Monash Alfred Psychiatry Research Centre, The Alfred and Monash University Central Clinical School, Melbourne, Victoria, Australia

    Paul B. Fitzgerald

  8. Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada

    Zafiris J. Daskalakis

Authors
  1. Mera S. Barr
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Faranak Farzan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Karen D. Davis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Paul B. Fitzgerald
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zafiris J. Daskalakis
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mera S. Barr.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barr, M.S., Farzan, F., Davis, K.D. et al. Measuring GABAergic Inhibitory Activity with TMS-EEG and Its Potential Clinical Application for Chronic Pain. J Neuroimmune Pharmacol 8, 535–546 (2013). https://doi.org/10.1007/s11481-012-9383-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11481-012-9383-y

Keywords

Search

Navigation