Single trial fMRI reveals significant contralateral bias in responses to laser pain within thalamus and somatosensory cortices

Pain is processed in multiple brain areas, indicating the complexity of pain perception. The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. We used single-trial functional magnetic resonance imaging (fMRI) to assess hemodynamic responses to right and left painful stimulation. Thulium-YAG-(yttrium-aluminium-granate)-laser-evoked pain stimuli, without concomitant tactile component, were applied to either hand in a randomized order. A contralateral bias of the BOLD response was investigated to determine areas involved in the coding of the side of stimulation, which we observed in primary (SI) and secondary (SII) somatosensory cortex, insula, and the thalamus. This suggests that these structures provide spatial information of selective nociceptive stimuli. More importantly, this contralateral bias of activation allowed functionally segregated activations within the SII complex, the insula, and the thalamus. Only distinct subregions of the SII complex, the posterior insula and the lateral thalamus, but not the remaining SII complex, the anterior insula and the medial thalamus, showed a contralaterally biased representation of painful stimuli. This result supports the hypothesis that sensory-discriminative attributes of painful stimuli, such as those related to body side, are topospecifically represented within the forebrain projections of the nociceptive system and highlights the concept of functional segregation and specialization within these structures.

[1]  R. Coghill,et al.  Hemispheric lateralization of somatosensory processing. , 2001, Journal of neurophysiology.

[2]  H. Burton,et al.  Somatic submodality distribution within the second somatosensory (SII), 7b, retroinsular, postauditory, and granular insular cortical areas of M. fascicularis , 1980, The Journal of comparative neurology.

[3]  L. Krubitzer,et al.  Somatotopic organization of cortical fields in the lateral sulcus of Homo sapiens: Evidence for SII and PV , 2000, The Journal of comparative neurology.

[4]  J. Ochoa,et al.  Sensations evoked by intraneural microstimulation of C nociceptor fibres in human skin nerves. , 1989, The Journal of physiology.

[5]  Krish D. Singh,et al.  fMRI of Thermal Pain: Effects of Stimulus Laterality and Attention , 2002, NeuroImage.

[6]  M. Bushnell,et al.  Dissociation of sensory and affective dimensions of pain using hypnotic modulation , 1999, Pain.

[7]  Jen-Chuen Hsieh,et al.  Right-lateralised central processing for pain of nitroglycer-induced cluster headache , 1996, PAIN.

[8]  H Burton,et al.  Second somatic sensory cortical area (sii) in a prosimian primate, galago crassicaudatus , 1986, The Journal of comparative neurology.

[9]  R. Koeppe,et al.  Comparison of human cerebral activation pattern during cutaneous warmth, heat pain, and deep cold pain. , 1996, Journal of neurophysiology.

[10]  J. Maisog,et al.  Pain intensity processing within the human brain: a bilateral, distributed mechanism. , 1999, Journal of neurophysiology.

[11]  V. Jousmäki,et al.  Right-hemisphere preponderance of responses to painful CO2 stimulation of the human nasal mucosa , 1997, PAIN.

[12]  M. Bushnell,et al.  A thalamic nucleus specific for pain and temperature sensation , 1994, Nature.

[13]  P. Roland Cortical representation of pain , 1992, Trends in Neurosciences.

[14]  T. Mima,et al.  Functional localization of pain perception in the human brain studied by PET , 1997, Neuroreport.

[15]  Karl J. Friston,et al.  Cognitive Conjunction: A New Approach to Brain Activation Experiments , 1997, NeuroImage.

[16]  S. Derbyshire,et al.  Exploring the pain “neuromatrix” , 2000, Current review of pain.

[17]  B. Krauss,et al.  A Comparative fMRI Study of Cortical Representations for Thermal Painful, Vibrotactile, and Motor Performance Tasks , 1999, NeuroImage.

[18]  P Baraldi,et al.  Temporal and intensity coding of pain in human cortex. , 1998, Journal of neurophysiology.

[19]  Hiroshi Shibasaki,et al.  Primary somatosensory cortex is actively involved in pain processing in human , 2000, Brain Research.

[20]  Karl J. Friston,et al.  Spatial registration and normalization of images , 1995 .

[21]  Mara Fabri,et al.  Cortical areas within the lateral sulcus connected to cutaneous representations in areas 3b and 1: A revised interpretation of the second somatosensory area in macaque monkeys , 1995, The Journal of comparative neurology.

[22]  M. Bushnell,et al.  Pain perception: is there a role for primary somatosensory cortex? , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[23]  C. Büchel,et al.  Subcortical structures involved in pain processing: evidence from single-trial fMRI , 2002, PAIN.

[24]  A. Schnitzler,et al.  Differential coding of pain intensity in the human primary and secondary somatosensory cortex. , 2001, Journal of neurophysiology.

[25]  de Carvalho La Modeling the thalamocortical loop. , 1994 .

[26]  Alan C. Evans,et al.  Multiple representations of pain in human cerebral cortex. , 1991, Science.

[27]  Anthony K. P. Jones,et al.  Pain processing during three levels of noxious stimulation produces differential patterns of central activity , 1997, Pain.

[28]  R. Dubner,et al.  The detection and perceived intensity of noxious thermal stimuli in monkey and in human. , 1989, Journal of neurophysiology.

[29]  C. L. Kwan,et al.  Functional MRI study of thalamic and cortical activations evoked by cutaneous heat, cold, and tactile stimuli. , 1998, Journal of neurophysiology.

[30]  R. Peyron,et al.  Functional imaging of brain responses to pain. A review and meta-analysis (2000) , 2000, Neurophysiologie Clinique/Clinical Neurophysiology.

[31]  C Büchel,et al.  Painful stimuli evoke different stimulus-response functions in the amygdala, prefrontal, insula and somatosensory cortex: a single-trial fMRI study. , 2002, Brain : a journal of neurology.

[32]  H. Freund,et al.  Parallel activation of primary and secondary somatosensory cortices in human pain processing. , 1999, Journal of neurophysiology.

[33]  Alan C. Evans,et al.  Distributed processing of pain and vibration by the human brain , 1994, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[34]  B. Bromm,et al.  Responses of human cutaneous afferents to CO2 laser stimuli causing pain , 2004, Experimental Brain Research.

[35]  A Villringer,et al.  Somatotopic organization of human secondary somatosensory cortex. , 2001, Cerebral cortex.

[36]  Richard F. Martin,et al.  Nociceptive responses of trigeminal neurons in SII-7b cortex of awake monkeys , 1989, Brain Research.

[37]  K. Worsley,et al.  Local Maxima and the Expected Euler Characteristic of Excursion Sets of χ 2, F and t Fields , 1994, Advances in Applied Probability.

[38]  N. Costes,et al.  Haemodynamic brain responses to acute pain in humans: sensory and attentional networks. , 1999, Brain : a journal of neurology.

[39]  C. Büchel,et al.  Dissociable Neural Responses Related to Pain Intensity, Stimulus Intensity, and Stimulus Awareness within the Anterior Cingulate Cortex: A Parametric Single-Trial Laser Functional Magnetic Resonance Imaging Study , 2002, The Journal of Neuroscience.

[40]  M. Mesulam,et al.  Insula of the old world monkey. III: Efferent cortical output and comments on function , 1982, The Journal of comparative neurology.

[41]  M. Bushnell,et al.  Pain affect encoded in human anterior cingulate but not somatosensory cortex. , 1997, Science.

[42]  Bengt Långström,et al.  Somatotopic organization along the central sulcus, for pain localization in humans, as revealed by positron emission tomography , 1997, Experimental Brain Research.

[43]  E. Reiman,et al.  Thermosensory activation of insular cortex , 2000, Nature Neuroscience.

[44]  P. Fox,et al.  Computational approaches to network analysis in functional brain imaging , 1994 .

[45]  Karl J. Friston,et al.  Statistical parametric maps in functional imaging: A general linear approach , 1994 .

[46]  A. Apkarian,et al.  Cortical representation of pain: functional characterization of nociceptive areas near the lateral sulcus , 2000, Pain.

[47]  W D Willis,et al.  Responses of neurons in primate ventral posterior lateral nucleus to noxious stimuli. , 1980, Journal of neurophysiology.

[48]  Stuart W. G. Derbyshire,et al.  Meta-Analysis of thirty-four independent samples studied using PET reveals a significantly attenuated central response to noxious stimulation in clinical pain patients , 1999, Current review of pain.

[49]  H. Breiter,et al.  Human brain activation under controlled thermal stimulation and habituation to noxious heat: An fMRI study , 1999, Magnetic resonance in medicine.

[50]  S Minoshima,et al.  Temporal and spatial dynamics of human forebrain activity during heat pain: analysis by positron emission tomography. , 2001, Journal of neurophysiology.

[51]  J. Spiegel,et al.  Clinical evaluation criteria for the assessment of impaired pain sensitivity by thulium-laser evoked potentials , 2000, Clinical Neurophysiology.