EEG analysis reveals widespread directed functional interactions related to a painful cutaneous laser stimulus.

During attention to a painful cutaneous laser stimulus, event-related causality (ERC) has been detected in recordings from subdural electrodes implanted directly over cortical modules for the treatment of epilepsy. However, these studies afforded limited sampling of modules and did not examine interactions with a nonpainful stimulus as a control. We now sample scalp EEG to test the hypothesis that attention to the laser stimulus is associated with poststimulus ERC interactions that are different from those with attention to a nonpainful stimulus. Subjects attended to (counted) either a painful laser stimulus (laser attention task) or a nonpainful electrical cutaneous stimulus that produced distraction from the laser (laser distraction task). Both of these stimuli were presented in random order in a single train. The intensities of both stimuli were adjusted to produce similar baseline salience and sensations in the same cutaneous territory. The results demonstrated that EEG channels with poststimulus ERC interactions were consistently different during the laser stimulus versus the electric stimulus. Poststimulus ERC interactions for the laser attention task were different from the laser distraction task. Furthermore, scalp EEG frontal channels play a driver role while parietal temporal channels play a receiver role during both tasks, although this does not prove that these channels are connected. Sites at which large numbers of ERC interactions were found for both laser attention and distraction tasks (critical sites) were located at Cz, Pz, and C3. Stimulation leading to disruption of sites of these pain-related interactions may produce analgesia for acute pain.

[1]  J. Lefaucheur TMS and pain , 2008 .

[2]  S Seri,et al.  Quantitative EEG modifications during the Cold Water Pressor Test: hemispheric and hand differences. , 1994, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[3]  G H Duncan,et al.  Thalamic VPM nucleus in the behaving monkey. II. Response to air-puff stimulation during discrimination and attention tasks. , 1993, Journal of neurophysiology.

[4]  K L Casey,et al.  Concepts of pain mechanisms: the contribution of functional imaging of the human brain. , 2000, Progress in brain research.

[5]  Jejo D. Koola,et al.  Motor threshold in transcranial magnetic stimulation: The impact of white matter fiber orientation and skull‐to‐cortex distance , 2009, Human brain mapping.

[6]  A. Mouraux,et al.  Nociceptive laser-evoked brain potentials do not reflect nociceptive-specific neural activity. , 2009, Journal of neurophysiology.

[7]  W. Willis,et al.  The Human Pain System: Experimental and Clinical Perspectives , 2010 .

[8]  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.

[9]  Hiroyuki Oya,et al.  Functional connections between auditory cortical fields in humans revealed by Granger causality analysis of intra-cranial evoked potentials to sounds: Comparison of two methods , 2007, Biosyst..

[10]  Joachim Gross,et al.  Oscillatory activity reflects the excitability of the human somatosensory system , 2006 .

[11]  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.

[12]  J. Schoffelen,et al.  Functional integration within the human pain system as revealed by Granger causality , 2009, Human brain mapping.

[13]  Marshall Devor Pain networks , 1998 .

[14]  Piotr J. Franaszczuk,et al.  Quantifying Auditory Event-Related Responses in Multichannel Human Intracranial Recordings , 2009, Front. Comput. Neurosci..

[15]  Arnaud Delorme,et al.  EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis , 2004, Journal of Neuroscience Methods.

[16]  Ciprian M Crainiceanu,et al.  Dynamics of event‐related causality in brain electrical activity , 2008, Human brain mapping.

[17]  D. Yarnitsky,et al.  The P300 in pain evoked potentials , 1996, Pain.

[18]  A Mouraux,et al.  Non-phase locked electroencephalogram (EEG) responses to CO2 laser skin stimulations may reflect central interactions between A∂- and C-fibre afferent volleys , 2003, Clinical Neurophysiology.

[19]  A. Mouraux,et al.  The pain matrix reloaded A salience detection system for the body , 2011, Progress in Neurobiology.

[20]  M. Corbetta,et al.  Control of goal-directed and stimulus-driven attention in the brain , 2002, Nature Reviews Neuroscience.

[21]  R. Melzack Pain and the neuromatrix in the brain. , 2001, Journal of dental education.

[22]  H. Karnath,et al.  Comment on “Movement Intention After Parietal Cortex Stimulation in Humans” , 2010, Science.

[23]  A. Apkarian,et al.  Segregation of nociceptive and non-nociceptive networks in the squirrel monkey somatosensory thalamus. , 2000, Journal of neurophysiology.

[24]  N. Crone,et al.  Fear conditioning is associated with dynamic directed functional interactions between and within the human amygdala, hippocampus, and frontal lobe , 2011, Neuroscience.

[25]  N. Crone,et al.  Attention to a painful cutaneous laser stimulus modulates electrocorticographic event-related desynchronization in humans , 2004, Clinical Neurophysiology.

[26]  Jian Kong,et al.  Using fMRI to dissociate sensory encoding from cognitive evaluation of heat pain intensity , 2006, Human brain mapping.

[27]  N. Crone,et al.  Painful laser stimuli induce directed functional interactions within and between the human amygdala and hippocampus , 2011, Neuroscience.

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

[29]  Karl J. Friston,et al.  Cortical and subcortical localization of response to pain in man using positron emission tomography , 1991, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[30]  R. Treede,et al.  Human brain mechanisms of pain perception and regulation in health and disease , 2005, European journal of pain.

[31]  F. L. D. Silva,et al.  Event-related EEG/MEG synchronization and desynchronization: basic principles , 1999, Clinical Neurophysiology.

[32]  Simon J. Sheather,et al.  Confidence intervals based on interpolated order statistics , 1986 .

[33]  M. Kaminski,et al.  Determination of information flow direction among brain structures by a modified directed transfer function (dDTF) method , 2003, Journal of Neuroscience Methods.

[34]  P. Franaszczuk,et al.  Attention to painful cutaneous laser stimuli evokes directed functional connectivity between activity recorded directly from human pain-related cortical structures , 2011, PAIN®.

[35]  Lars Arendt-Nielsen,et al.  Anticipatory electroencephalography alpha rhythm predicts subjective perception of pain intensity. , 2006, The journal of pain : official journal of the American Pain Society.

[36]  H. Jasper,et al.  The ten-twenty electrode system of the International Federation. The International Federation of Clinical Neurophysiology. , 1999, Electroencephalography and clinical neurophysiology. Supplement.

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

[38]  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.

[39]  Randy L. Gollub,et al.  Exploring the brain in pain: Activations, deactivations and their relation , 2010, PAIN.

[40]  J. Downar,et al.  A cortical network sensitive to stimulus salience in a neutral behavioral context across multiple sensory modalities. , 2002, Journal of neurophysiology.

[41]  A. Mouraux,et al.  Determinants of laser-evoked EEG responses: pain perception or stimulus saliency? , 2008, Journal of neurophysiology.

[42]  G. Pfurtscheller,et al.  Event-related cortical desynchronization detected by power measurements of scalp EEG. , 1977, Electroencephalography and clinical neurophysiology.

[43]  Thomas Weiss,et al.  How do brain areas communicate during the processing of noxious stimuli? An analysis of laser-evoked event-related potentials using the Granger causality index. , 2008, Journal of neurophysiology.

[44]  S. Bressler,et al.  Trial-to-trial variability of cortical evoked responses: implications for the analysis of functional connectivity , 2002, Clinical Neurophysiology.

[45]  H. Akaike A new look at the statistical model identification , 1974 .

[46]  D. Price Psychological and neural mechanisms of the affective dimension of pain. , 2000, Science.

[47]  M. Desmurget,et al.  Response to Comment on “Movement Intention After Parietal Cortex Stimulation in Humans” , 2010, Science.

[48]  C. Granger Investigating causal relations by econometric models and cross-spectral methods , 1969 .

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

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

[51]  M. Desmurget,et al.  Movement Intention After Parietal Cortex Stimulation in Humans , 2009, Science.

[52]  Katja Wiech,et al.  Flexible cerebral connectivity patterns subserve contextual modulations of pain. , 2011, Cerebral cortex.

[53]  J. Smith,et al.  Tonic changes in alpha power during immersion of the hand in cold water. , 1991, Electroencephalography and clinical neurophysiology.

[54]  Hermann Haken,et al.  Exploring the Brain , 2013 .

[55]  Riitta Hari,et al.  Modulation of motor-cortex oscillatory activity by painful Aδ- and C-fiber stimuli , 2004, NeuroImage.

[56]  Rolf-Detlef Treede,et al.  Attention to pain is processed at multiple cortical sites in man , 2004, Experimental Brain Research.

[57]  V. Legrain,et al.  Involuntary orientation of attention to unattended deviant nociceptive stimuli is modulated by concomitant visual task difficulty. Evidence from laser evoked potentials , 2005, Clinical Neurophysiology.

[58]  Hualou Liang,et al.  Short-window spectral analysis of cortical event-related potentials by adaptive multivariate autoregressive modeling: data preprocessing, model validation, and variability assessment , 2000, Biological Cybernetics.

[59]  Heidi Johansen-Berg,et al.  Counter-stimulatory effects on pain perception and processing are significantly altered by attention: an fMRI study , 2001, NeuroImage.

[60]  M. Bushnell,et al.  Effects of attention on the intensity and unpleasantness of thermal pain , 1989, Pain.

[61]  R Kakigi,et al.  Effects of distraction on pain perception: magneto- and electro-encephalographic studies. , 1999, Brain research. Cognitive brain research.

[62]  David E. Cummings,et al.  Response to Comment on: Cohen et al. Effects of Gastric Bypass Surgery in Patients With Type 2 Diabetes and Only Mild Obesity. Diabetes Care 2012;35:1420–1428 , 2013, Diabetes Care.

[63]  Piotr J. Franaszczuk,et al.  Attention to painful cutaneous laser stimuli evokes directed functional interactions between human sensory and modulatory pain-related cortical areas , 2011, PAIN.

[64]  S. Bressler,et al.  Beta oscillations in a large-scale sensorimotor cortical network: directional influences revealed by Granger causality. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[65]  L. Garcia-Larrea,et al.  Contribution of attentional and cognitive factors to laser evoked brain potentials , 2003, Neurophysiologie Clinique/Clinical Neurophysiology.

[66]  N. Crone,et al.  Analysis of synchrony demonstrates ‘pain networks’ defined by rapidly switching, task-specific, functional connectivity between pain-related cortical structures , 2006, PAIN.

[67]  M. Boly,et al.  Baseline brain activity fluctuations predict somatosensory perception in humans , 2007, Proceedings of the National Academy of Sciences.

[68]  T. Sejnowski,et al.  Network Oscillations: Emerging Computational Principles , 2006, The Journal of Neuroscience.

[69]  J. Kimura Handbook of transcranial stimulation , 2002 .

[70]  Jonathan Downar,et al.  Neural correlates of the prolonged salience of painful stimulation , 2003, NeuroImage.

[71]  C. Gilbert,et al.  Brain States: Top-Down Influences in Sensory Processing , 2007, Neuron.

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

[73]  M. Bushnell,et al.  Sensory and affective aspects of pain perception: is medial thalamus restricted to emotional issues? , 2004, Experimental Brain Research.

[74]  N. Crone,et al.  Analysis of synchrony demonstrates that the presence of “pain networks” prior to a noxious stimulus can enable the perception of pain in response to that stimulus , 2008, Experimental Brain Research.

[75]  M. Bushnell,et al.  Attentional influences on noxious and innocuous cutaneous heat detection in humans and monkeys , 1985 .

[76]  Katja Wiech,et al.  Prestimulus functional connectivity determines pain perception in humans , 2009, Proceedings of the National Academy of Sciences.

[77]  V. Walsh,et al.  Diffusion tensor MRI-based estimation of the influence of brain tissue anisotropy on the effects of transcranial magnetic stimulation , 2007, NeuroImage.

[78]  Ana-Maria Staicu,et al.  Generalized Multilevel Functional Regression , 2009, Journal of the American Statistical Association.