Activation of the anterior cingulate cortex by thalamic stimulation in patients with chronic pain: a positron emission tomography study

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  • 1 Departments of Surgery and Physiology, University of Toronto, Toronto, Ontario, Canada; The PET Centre, Clarke Institute of Psychiatry, Toronto, Ontario, Canada; and The Toronto Western Research Institute, Toronto, Ontario, Canada
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Object. Deep brain stimulation (DBS) of the sensory thalamus has been used to treat chronic, intractable pain. The goal of this study was to investigate the thalamocortical pathways activated during thalamic DBS.

Methods. The authors compared positron emission tomography (PET) images obtained before, during, and after DBS in five patients with chronic pain. Two of the five patients reported significant DBS-induced pain relief during PET scanning, and the remaining three patients did not report any analgesic effect of DBS during scanning. The most robust effect associated with DBS was activation of the anterior cingulate cortex (ACC). An anterior ACC activation was sustained throughout the 40 minutes of DBS, whereas a more posteriorly located ACC activation occurred at a delay after onset of DBS, although these activations were not dependent on the degree of pain relief reported during DBS. However, implications specific to the analgesic effect of DBS require further study of a larger, more homogeneous patient population. Additional effects of thalamic DBS were detected in motor-related regions (the globus pallidus, cortical area 4, and the cerebellum) and visual and association cortical areas.

Conclusions. The authors demonstrate that the ACC is activated during thalamic DBS in patients with chronic pain.

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Contributor Notes

Address reprint requests to: Karen D. Davis, Ph.D., Division of Neurosurgery, MP14-322, Toronto Western Hospital, 399 Bathurst Street, Toronto, Ontario, Canada M5T 2S8. kdavis@playfair.utoronto.ca.
  • 1.

    Besson JM, & Chaouch A: Peripheral and spinal mechanisms of nociception. Physiol Rev 67:67186, 1987 Besson JM, Chaouch A: Peripheral and spinal mechanisms of nociception. Physiol Rev 67:67–186, 1987

    • Search Google Scholar
    • Export Citation
  • 2.

    Bouckoms AF: Psychosurgery for pain, in Wall PD, & Melzack R (eds): Textbook of Pain, ed 2. Edinburgh: Churchill Livingstone, 1989, pp 868881 Bouckoms AF: Psychosurgery for pain, in Wall PD, Melzack R (eds): Textbook of Pain, ed 2. Edinburgh: Churchill Livingstone, 1989, pp 868–881

    • Search Google Scholar
    • Export Citation
  • 3.

    Casey KL, , Minoshima S, & Berger KL, et al: Positron emission tomographic analysis of cerebral structures activated specifically by repetitive noxious heat stimuli. J Neurophysiol 71:802807, 1994 Casey KL, Minoshima S, Berger KL, et al: Positron emission tomographic analysis of cerebral structures activated specifically by repetitive noxious heat stimuli. J Neurophysiol 71:802–807, 1994

    • Search Google Scholar
    • Export Citation
  • 4.

    Casey KL, , Minoshima S, & Morrow TJ, et al: Comparison of human cerebral activation patterns during cutaneous warmth, heat pain and deep cold pain. J Neurophysiol 76:571581, 1996 Casey KL, Minoshima S, Morrow TJ, et al: Comparison of human cerebral activation patterns during cutaneous warmth, heat pain and deep cold pain. J Neurophysiol 76:571–581, 1996

    • Search Google Scholar
    • Export Citation
  • 5.

    Chudler EH, & Dong WK: The role of the basal ganglia in nociception and pain. Pain 60:338, 1995 Chudler EH, Dong WK: The role of the basal ganglia in nociception and pain. Pain 60:3–38, 1995

    • Search Google Scholar
    • Export Citation
  • 6.

    Coghill RC, , Talbot JD, & Evans AC, et al: Distributed processing of pain and vibration by the human brain. J Neurosci 14:40954108, 1994 Coghill RC, Talbot JD, Evans AC, et al: Distributed processing of pain and vibration by the human brain. J Neurosci 14:4095–4108, 1994

    • Search Google Scholar
    • Export Citation
  • 7.

    Craig AD, , Reiman EM, & Evans A, et al: Functional imaging of an illusion of pain. Nature 384:258260, 1996 Craig AD, Reiman EM, Evans A, et al: Functional imaging of an illusion of pain. Nature 384:258–260, 1996

    • Search Google Scholar
    • Export Citation
  • 8.

    Davis KD, , Duffner F, & Houle S, et al: PET imaging during subthalamic nucleus stimulation in PD patients. Neuroimage 7 (Suppl):S997, 1998 (Abstract) Davis KD, Duffner F, Houle S, et al: PET imaging during subthalamic nucleus stimulation in PD patients. Neuroimage 7 (Suppl):S997, 1998 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 9.

    Davis KD, , Hutchison WD, & Lozano AM, et al: Altered pain and temperature perception following cingulotomy and capsulotomy in a patient with schizoaffective disorder. Pain 59:189199, 1994 Davis KD, Hutchison WD, Lozano AM, et al: Altered pain and temperature perception following cingulotomy and capsulotomy in a patient with schizoaffective disorder. Pain 59:189–199, 1994

    • Search Google Scholar
    • Export Citation
  • 10.

    Davis KD, , Kwan CL, & Crawley AP, et al: fMRI of the anterior cingulate cortex during painful, thermal and motor tasks in individual subjects. Neuroimage 7 (Suppl):S426, 1998 (Abstract) Davis KD, Kwan CL, Crawley AP, et al: fMRI of the anterior cingulate cortex during painful, thermal and motor tasks in individual subjects. Neuroimage 7 (Suppl):S426, 1998 (Abstract)

    • Search Google Scholar
    • Export Citation
  • 11.

    Davis KD, , Kwan CL, & Crawley AP, et al: Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold and tactile stimuli. J Neurophysiol 80:15331546, 1998 Davis KD, Kwan CL, Crawley AP, et al: Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold and tactile stimuli. J Neurophysiol 80:1533–1546, 1998

    • Search Google Scholar
    • Export Citation
  • 12.

    Davis KD, , Taub E, & Houle S, et al: Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms. Nature Med 3:671674, 1997 Davis KD, Taub E, Houle S, et al: Globus pallidus stimulation activates the cortical motor system during alleviation of parkinsonian symptoms. Nature Med 3:671–674, 1997

    • Search Google Scholar
    • Export Citation
  • 13.

    Davis KD, , Taylor SJ, & Crawley AP, et al: Functional MRI of pain- and attention-related activations in the human cingulate cortex. J Neurophysiol 77:33703380, 1997 Davis KD, Taylor SJ, Crawley AP, et al: Functional MRI of pain- and attention-related activations in the human cingulate cortex. J Neurophysiol 77:3370–3380, 1997

    • Search Google Scholar
    • Export Citation
  • 14.

    Davis KD, , Wood ML, & Crawley AP, et al: fMRI of human somatosensory and cingulate cortex during painful electrical nerve stimulation. Neuroreport 7:321325, 1995 Davis KD, Wood ML, Crawley AP, et al: fMRI of human somatosensory and cingulate cortex during painful electrical nerve stimulation. Neuroreport 7:321–325, 1995

    • Search Google Scholar
    • Export Citation
  • 15.

    Deiber MP, , Pollak P, & Passingham R, et al: Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography. Brain 116:267279, 1993 Deiber MP, Pollak P, Passingham R, et al: Thalamic stimulation and suppression of parkinsonian tremor. Evidence of a cerebellar deactivation using positron emission tomography. Brain 116:267–279, 1993

    • Search Google Scholar
    • Export Citation
  • 16.

    Derbyshire SWG, , Jones AKP, & Gyulai F, et al: Pain processing during three levels of noxious stimulation produces differential patterns of central activity. Pain 73:431445, 1997 Derbyshire SWG, Jones AKP, Gyulai F, et al: Pain processing during three levels of noxious stimulation produces differential patterns of central activity. Pain 73:431–445, 1997

    • Search Google Scholar
    • Export Citation
  • 17.

    Derbyshire SWG, , Vogt BA, & Jones AKP: Pain and Stroop interference tasks activate separate processing modules in anterior cingulate cortex. Exp Brain Res 118:5260, 1998 Derbyshire SWG, Vogt BA, Jones AKP: Pain and Stroop interference tasks activate separate processing modules in anterior cingulate cortex. Exp Brain Res 118:52–60, 1998

    • Search Google Scholar
    • Export Citation
  • 18.

    Dickenson A: The inhibitory effects of thalamic stimulation on the spinal transmission of nociceptive information in the rat. Pain 17:213224, 1983 Dickenson A: The inhibitory effects of thalamic stimulation on the spinal transmission of nociceptive information in the rat. Pain 17:213–224, 1983

    • Search Google Scholar
    • Export Citation
  • 19.

    Dostrovsky JO, , Hutchison WD, & Davis KD, et al: Potential role of orbital and cingulate cortices in nociception, in Besson JMR, , Guilbaud G, , Ollat H (eds): Forebrain Areas Involved in Pain Processing. Paris: John Libbey Eurotext, 1995, pp 171181 Dostrovsky JO, Hutchison WD, Davis KD, et al: Potential role of orbital and cingulate cortices in nociception, in Besson JMR, Guilbaud G, Ollat H (eds): Forebrain Areas Involved in Pain Processing. Paris: John Libbey Eurotext, 1995, pp 171–181

    • Search Google Scholar
    • Export Citation
  • 20.

    Duncan GH, , Bushnell MC, & Marchand S: Deep brain stimulation: a review of basic research and clinical studies. Pain 45:4959, 1991 Duncan GH, Bushnell MC, Marchand S: Deep brain stimulation: a review of basic research and clinical studies. Pain 45:49–59, 1991

    • Search Google Scholar
    • Export Citation
  • 21.

    Duncan GH, , Kupers RC, & Marchand S, et al: Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography. J Neurophysiol 80:33263330, 1998 Duncan GH, Kupers RC, Marchand S, et al: Stimulation of human thalamus for pain relief: possible modulatory circuits revealed by positron emission tomography. J Neurophysiol 80:3326–3330, 1998

    • Search Google Scholar
    • Export Citation
  • 22.

    Friston KJ, , Frith CD, & Liddle PF, et al: Comparing functional (PET) images: the assessment of significant change. J Cereb Blood Flow Metab 11:690699, 1991 Friston KJ, Frith CD, Liddle PF, et al: Comparing functional (PET) images: the assessment of significant change. J Cereb Blood Flow Metab 11:690–699, 1991

    • Search Google Scholar
    • Export Citation
  • 23.

    Fuchs PN, , Balinsky M, & Melzack R: Electrical stimulation of the cingulum bundle and surrounding cortical tissue reduces formalin-test pain in the rat. Brain Res 743:116123, 1996 Fuchs PN, Balinsky M, Melzack R: Electrical stimulation of the cingulum bundle and surrounding cortical tissue reduces formalin-test pain in the rat. Brain Res 743:116–123, 1996

    • Search Google Scholar
    • Export Citation
  • 24.

    Gerhart KD, , Yezierski RP, & Fang ZR, et al: Inhibition of primate spinothalamic tract neurons by stimulation in ventral posterior lateral (VPLc) thalamic nucleus: possible mechanisms. J Neurophysiol 49:406423, 1983 Gerhart KD, Yezierski RP, Fang ZR, et al: Inhibition of primate spinothalamic tract neurons by stimulation in ventral posterior lateral (VPLc) thalamic nucleus: possible mechanisms. J Neurophysiol 49:406–423, 1983

    • Search Google Scholar
    • Export Citation
  • 25.

    Hosobuchi Y: Combined electrical stimulation of the periaqueductal gray matter and sensory thalamus. Appl Neurophysiol 46:112115, 1983 Hosobuchi Y: Combined electrical stimulation of the periaqueductal gray matter and sensory thalamus. Appl Neurophysiol 46:112–115, 1983

    • Search Google Scholar
    • Export Citation
  • 26.

    Hosobuchi Y, , Adams JE, & Rutkin B: Chronic thalamic stimulation for the control of facial anesthesia dolorosa. Arch Neurol 29:158161, 1973 Hosobuchi Y, Adams JE, Rutkin B: Chronic thalamic stimulation for the control of facial anesthesia dolorosa. Arch Neurol 29:158–161, 1973

    • Search Google Scholar
    • Export Citation
  • 27.

    Hsu MM, & Shyu BC: Electrophysiological study of the connection between medial thalamus and anterior cingulate cortex in the rat. Neuroreport 8:27012707, 1997 Hsu MM, Shyu BC: Electrophysiological study of the connection between medial thalamus and anterior cingulate cortex in the rat. Neuroreport 8:2701–2707, 1997

    • Search Google Scholar
    • Export Citation
  • 28.

    Hutchison WD, , Davis KD, & Lozano AM, et al: Pain-related neurons in the human cingulate cortex. Nat Neurosci 2:403405, 1999 Hutchison WD, Davis KD, Lozano AM, et al: Pain-related neurons in the human cingulate cortex. Nat Neurosci 2:403–405, 1999

    • Search Google Scholar
    • Export Citation
  • 29.

    Jones AKP, , Brown WD, & Friston KJ, et al: Cortical and subcortical localization of response to pain in man using positron emission tomography. Proc R Soc Lond (B) 244:3944, 1991 Jones AKP, Brown WD, Friston KJ, et al: Cortical and subcortical localization of response to pain in man using positron emission tomography. Proc R Soc Lond (B) 244:39–44, 1991

    • Search Google Scholar
    • Export Citation
  • 30.

    Katayama Y, , Tsubokawa T, & Hirayama T, et al: Response of regional cerebral blood flow and oxygen metabolism to thalamic stimulation in humans as revealed by positron emission tomography. J Cereb Blood Flow Metab 6:637641, 1986 Katayama Y, Tsubokawa T, Hirayama T, et al: Response of regional cerebral blood flow and oxygen metabolism to thalamic stimulation in humans as revealed by positron emission tomography. J Cereb Blood Flow Metab 6:637–641, 1986

    • Search Google Scholar
    • Export Citation
  • 31.

    Kumar K, , Toth C, & Nath RK: Deep brain stimulation for intractable pain: a 15-year experience. Neurosurgery 40:736747, 1997 Kumar K, Toth C, Nath RK: Deep brain stimulation for intractable pain: a 15-year experience. Neurosurgery 40:736–747, 1997

    • Search Google Scholar
    • Export Citation
  • 32.

    Marini G, , Pianca L, & Tredici G: Thalamocortical projection from the parafascicular nucleus to layer V pyramidal cells in frontal and cingulate areas of the rat. Neurosci Lett 203:8184, 1996 Marini G, Pianca L, Tredici G: Thalamocortical projection from the parafascicular nucleus to layer V pyramidal cells in frontal and cingulate areas of the rat. Neurosci Lett 203:81–84, 1996

    • Search Google Scholar
    • Export Citation
  • 33.

    Musil SY, & Olson CR: Organization of cortical and subcortical projections to anterior cingulate cortex in the cat. J Comp Neurol 272:203218, 1988 Musil SY, Olson CR: Organization of cortical and subcortical projections to anterior cingulate cortex in the cat. J Comp Neurol 272:203–218, 1988

    • Search Google Scholar
    • Export Citation
  • 34.

    Phelps ME, & Mazziotta JC: Positron emission tomography: human brain function and biochemistry. Science 228:799809, 1985 Phelps ME, Mazziotta JC: Positron emission tomography: human brain function and biochemistry. Science 228:799–809, 1985

    • Search Google Scholar
    • Export Citation
  • 35.

    Pillay PK, & Hassenbusch SJ: Bilateral MRI-guided stereotactic cingulotomy for intractable pain. Stereotact Funct Neurosurg 59:3338, 1992 Pillay PK, Hassenbusch SJ: Bilateral MRI-guided stereotactic cingulotomy for intractable pain. Stereotact Funct Neurosurg 59:33–38, 1992

    • Search Google Scholar
    • Export Citation
  • 36.

    Rainville P, , Duncan GH, & Price DD, et al: Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 277:968971, 1997 Rainville P, Duncan GH, Price DD, et al: Pain affect encoded in human anterior cingulate but not somatosensory cortex. Science 277:968–971, 1997

    • Search Google Scholar
    • Export Citation
  • 37.

    Robertson RT, & Kaitz SS: Thalamic connections with limbic cortex. I. Thalamocortical projections. J Comp Neurol 195:501525, 1981 Robertson RT, Kaitz SS: Thalamic connections with limbic cortex. I. Thalamocortical projections. J Comp Neurol 195:501–525, 1981

    • Search Google Scholar
    • Export Citation
  • 38.

    Sikes RW, & Vogt BA: Nociceptive neurons in area 24 of rabbit cingulate cortex. J Neurophysiol 68:17201732, 1992 Sikes RW, Vogt BA: Nociceptive neurons in area 24 of rabbit cingulate cortex. J Neurophysiol 68:1720–1732, 1992

    • Search Google Scholar
    • Export Citation
  • 39.

    Svensson P, , Minoshima S, & Beydoun A, et al: Cerebral processing of acute skin and muscle pain in humans. J Neurophysiol 78:450460, 1997 Svensson P, Minoshima S, Beydoun A, et al: Cerebral processing of acute skin and muscle pain in humans. J Neurophysiol 78:450–460, 1997

    • Search Google Scholar
    • Export Citation
  • 40.

    Talairach J, & Tournoux P: Co-Planar Stereotaxic Atlas of the Human Brain. New York: Thieme, 1988, pp 1122 Talairach J, Tournoux P: Co-Planar Stereotaxic Atlas of the Human Brain. New York: Thieme, 1988, pp 1–122

    • Search Google Scholar
    • Export Citation
  • 41.

    Talbot JD, , Marrett S, & Evans AC, et al: Multiple representations of pain in human cerebral cortex. Science 251:13551358, 1991 Talbot JD, Marrett S, Evans AC, et al: Multiple representations of pain in human cerebral cortex. Science 251:1355–1358, 1991

    • Search Google Scholar
    • Export Citation
  • 42.

    Tsubokawa T, , Yamamoto T, & Katayama Y, et al: Thalamic relay nucleus stimulation for relief of intractable pain. Clinical results and β-endorphin immunoreactivity in the cerebrospinal fluid. Pain 18:115126, 1984 Tsubokawa T, Yamamoto T, Katayama Y, et al: Thalamic relay nucleus stimulation for relief of intractable pain. Clinical results and β-endorphin immunoreactivity in the cerebrospinal fluid. Pain 18:115–126, 1984

    • Search Google Scholar
    • Export Citation
  • 43.

    Vaccarino AL, & Melzack R: Analgesia produced by injection of lidocaine into the anterior cingulum bundle of the rat. Pain 39:213219, 1989 Vaccarino AL, Melzack R: Analgesia produced by injection of lidocaine into the anterior cingulum bundle of the rat. Pain 39:213–219, 1989

    • Search Google Scholar
    • Export Citation
  • 44.

    Vogt BA, , Derbyshire S, & Jones AKP: Pain processing in four regions of human cingulate cortex localized with co-registered PET and MR imaging. Eur J Neurosci 8:14611473, 1996 Vogt BA, Derbyshire S, Jones AKP: Pain processing in four regions of human cingulate cortex localized with co-registered PET and MR imaging. Eur J Neurosci 8:1461–1473, 1996

    • Search Google Scholar
    • Export Citation
  • 45.

    Vogt BA, , Pandya DN, & Rosene DL: Cingulate cortex of the rhesus monkey: I. Cytoarchitecture and thalamic afferents. J Comp Neurol 262:256270, 1987 Vogt BA, Pandya DN, Rosene DL: Cingulate cortex of the rhesus monkey: I. Cytoarchitecture and thalamic afferents. J Comp Neurol 262:256–270, 1987

    • Search Google Scholar
    • Export Citation
  • 46.

    Vogt BA, , Rosene DL, & Pandya DN: Thalamic and cortical afferents differentiate anterior from posterior cingulate cortex in the monkey. Science 204:205207, 1979 Vogt BA, Rosene DL, Pandya DN: Thalamic and cortical afferents differentiate anterior from posterior cingulate cortex in the monkey. Science 204:205–207, 1979

    • Search Google Scholar
    • Export Citation
  • 47.

    Willis WD, & Westlund KN: Neuroanatomy of the pain system and of the pathways that modulate pain. J Clin Neurophysiol 14:231, 1997 Willis WD, Westlund KN: Neuroanatomy of the pain system and of the pathways that modulate pain. J Clin Neurophysiol 14:2–31, 1997

    • Search Google Scholar
    • Export Citation
  • 48.

    Yasui Y, , Itoh K, & Kamiya H, et al: Cingulate gyrus of the cat receives projection fibers from the thalamic region ventral to the ventral border of the ventrobasal complex. J Comp Neurol 274:91100, 1988 Yasui Y, Itoh K, Kamiya H, et al: Cingulate gyrus of the cat receives projection fibers from the thalamic region ventral to the ventral border of the ventrobasal complex. J Comp Neurol 274:91–100, 1988

    • Search Google Scholar
    • Export Citation

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