Cerebral peak alpha frequency predicts individual differences in pain sensitivity

&NA; The identification of neurobiological markers that predict individual predisposition to pain are not only important for development of effective pain treatments, but would also yield a more complete understanding of how pain is implemented in the brain. In the current study using electroencephalography (EEG), we investigated the relationship between the peak frequency of alpha activity over sensorimotor cortex and pain intensity during capsaicin‐heat pain (C‐HP), a prolonged pain model known to induce spinal central sensitization in primates. We found that peak alpha frequency (PAF) recorded during a pain‐free period preceding the induction of prolonged pain correlated with subsequent pain intensity reports: slower peak frequency at pain‐free state was associated with higher pain during the prolonged pain condition. Moreover, the degree to which PAF decreased between pain‐free and prolonged pain states was correlated with pain intensity. These two metrics were statistically uncorrelated and in combination were able to account for 50% of the variability in pain intensity. Altogether, our findings suggest that pain‐free state PAF over relevant sensory systems could serve as a marker of individual predisposition to prolonged pain. Moreover, slowing of PAF in response to prolonged pain could represent an objective marker for subjective pain intensity. Our findings potentially lead the way for investigations in clinical populations in which alpha oscillations and the brain areas contributing to their generation are used in identifying and formulating treatment strategies for patients more likely to develop chronic pain. Graphical abstract Figure. No caption available. HighlightsRelationship between EEG peak alpha frequency and prolonged pain is examined.PAF during pain‐free state correlated with prolonged pain intensity 40 min later.PAF change from pain‐free to prolonged pain correlated with reported pain intensity.PAF and PAF changes could represent distinct mechanisms predicting pain sensitivity.

[1]  A. Kleinschmidt,et al.  Modulation of Visually Evoked Cortical fMRI Responses by Phase of Ongoing Occipital Alpha Oscillations , 2011, The Journal of Neuroscience.

[2]  Roshan Cools,et al.  Region-specific modulations in oscillatory alpha activity serve to facilitate processing in the visual and auditory modalities , 2014, NeuroImage.

[3]  Ulman Lindenberger,et al.  Peak individual alpha frequency qualifies as a stable neurophysiological trait marker in healthy younger and older adults. , 2013, Psychophysiology.

[4]  H. Aurlien,et al.  EEG background activity described by a large computerized database , 2004, Clinical Neurophysiology.

[5]  J. Gross,et al.  Brain Rhythms of Pain , 2017, Trends in Cognitive Sciences.

[6]  Claudia M. Campbell,et al.  207) Sex differences in the perception of pain from topical capsaicin , 2017 .

[7]  J. Ochoa,et al.  Heat and mechanical hyperalgesia induced by capsaicin. Cross modality threshold modulation in human C nociceptors. , 1989, Brain : a journal of neurology.

[8]  Robert Oostenveld,et al.  The five percent electrode system for high-resolution EEG and ERP measurements , 2001, Clinical Neurophysiology.

[9]  R. VanRullen,et al.  The Phase of Ongoing EEG Oscillations Predicts Visual Perception , 2009, The Journal of Neuroscience.

[10]  Harry van Goor,et al.  Altered resting state EEG in chronic pancreatitis patients: toward a marker for chronic pain , 2013, Journal of pain research.

[11]  Seppo P. Ahlfors,et al.  Parieto‐occipital ∼1 0Hz activity reflects anticipatory state of visual attention mechanisms , 1998 .

[12]  R. Llinás,et al.  Abnormal thalamocortical activity in patients with Complex Regional Pain Syndrome (CRPS) Type I , 2010, PAIN.

[13]  Badreddine Bencherif,et al.  Naloxone increases pain induced by topical capsaicin in healthy human volunteers , 2002, PAIN.

[14]  G. V. Simpson,et al.  Parieto‐occipital ∼1 0Hz activity reflects anticipatory state of visual attention mechanisms , 1998 .

[15]  Gregor Thut,et al.  Resting electroencephalogram alpha-power over posterior sites indexes baseline visual cortex excitability , 2008, Neuroreport.

[16]  Mark S. Cohen,et al.  Simultaneous EEG and fMRI of the alpha rhythm , 2002, Neuroreport.

[17]  J. Kim,et al.  Increased Low- and High-Frequency Oscillatory Activity in the Prefrontal Cortex of Fibromyalgia Patients , 2016, Front. Hum. Neurosci..

[18]  Michael X Cohen,et al.  Analyzing Neural Time Series Data: Theory and Practice , 2014 .

[19]  W. Klimesch.  EEG alpha and theta oscillations reflect cognitive and memory performance: a review and analysis , 1999, Brain Research Reviews.

[20]  B. Postle,et al.  Top-down control of the phase of alpha-band oscillations as a mechanism for temporal prediction , 2015, Proceedings of the National Academy of Sciences.

[21]  C. Babiloni,et al.  Subjective pain perception mediated by alpha rhythms , 2015, Biological Psychology.

[22]  Vincenzo Crunelli,et al.  Cellular Dynamics of Cholinergically Induced α (8–13 Hz) Rhythms in Sensory Thalamic Nuclei In Vitro , 2008, The Journal of Neuroscience.

[23]  Thomas Dierks,et al.  Association of individual resting state EEG alpha frequency and cerebral blood flow , 2010, NeuroImage.

[24]  S. Hughes,et al.  Temporal Framing of Thalamic Relay-Mode Firing by Phasic Inhibition during the Alpha Rhythm , 2009, Neuron.

[25]  Umesh Chand,et al.  Role of Al , 2018 .

[26]  G. Rees,et al.  Individual Differences in Alpha Frequency Drive Crossmodal Illusory Perception , 2015, Current Biology.

[27]  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.

[28]  John J. Foxe,et al.  The Role of Alpha-Band Brain Oscillations as a Sensory Suppression Mechanism during Selective Attention , 2011, Front. Psychology.

[29]  Wolfgang Klimesch,et al.  Resting state alpha frequency is associated with menstrual cycle phase, estradiol and use of oral contraceptives , 2014, Brain Research.

[30]  G. Pfurtscheller,et al.  Event-related synchronization (ERS) in the alpha band--an electrophysiological correlate of cortical idling: a review. , 1996, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[31]  Jörn Lötsch,et al.  Pattern of neuropathic pain induced by topical capsaicin application in healthy subjects , 2015, Pain.

[32]  Ralf Baron,et al.  Neuropathic pain: a clinical perspective. , 2009, Handbook of experimental pharmacology.

[33]  M. Neale,et al.  Are Smarter Brains Running Faster? Heritability of Alpha Peak Frequency, IQ, and Their Interrelation , 2001, Behavior genetics.

[34]  Thomas J. Schnitzer,et al.  Corticostriatal functional connectivity predicts transition to chronic back pain , 2012, Nature Neuroscience.

[35]  R. Meyer,et al.  Secondary hyperalgesia to mechanical but not heat stimuli following a capsaicin injection in hairy skin , 1996, Pain.

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

[37]  R. Oostenveld,et al.  Neuronal Dynamics Underlying High- and Low-Frequency EEG Oscillations Contribute Independently to the Human BOLD Signal , 2011, Neuron.

[38]  D. Lindsley,et al.  A Longitudinal Study of the Occipital Alpha Rhythm in Normal Children: Frequency and Amplitude Standards , 1939 .

[39]  Ali Hashemi,et al.  Characterizing Population EEG Dynamics throughout Adulthood , 2016, eNeuro.

[40]  W. Klimesch.  Alpha-band oscillations, attention, and controlled access to stored information , 2012, Trends in Cognitive Sciences.

[41]  Thomas Dierks,et al.  Linking Brain Connectivity Across Different Time Scales with Electroencephalogram, Functional Magnetic Resonance Imaging, and Diffusion Tensor Imaging , 2012, Brain Connect..

[42]  G. Pfurtscheller,et al.  Alpha frequency, cognitive load and memory performance , 1993, Brain Topography.

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

[44]  A. Moritz,et al.  Studies of Thermal Injury: II. The Relative Importance of Time and Surface Temperature in the Causation of Cutaneous Burns. , 1947, The American journal of pathology.

[45]  Diane M. Beck,et al.  To See or Not to See: Prestimulus α Phase Predicts Visual Awareness , 2009, The Journal of Neuroscience.

[46]  G. Mangun,et al.  Functional Disconnection of Frontal Cortex and Visual Cortex in Attention-Deficit/Hyperactivity Disorder , 2010, Biological Psychiatry.

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

[48]  B. Kavanagh,et al.  Acute pain after thoracic surgery predicts long-term post-thoracotomy pain. , 1996, The Clinical journal of pain.

[49]  Ali Mazaheri,et al.  Cross‐sensory modulation of alpha oscillatory activity: suppression, idling, and default resource allocation , 2017, The European journal of neuroscience.

[50]  W. Klimesch,et al.  EEG alpha oscillations: The inhibition–timing hypothesis , 2007, Brain Research Reviews.

[51]  Nicholas G Martin,et al.  Genetic variation of individual alpha frequency (IAF) and alpha power in a large adolescent twin sample. , 2006, International journal of psychophysiology : official journal of the International Organization of Psychophysiology.

[52]  J. Sarnthein,et al.  Increased EEG power and slowed dominant frequency in patients with neurogenic pain. , 2006, Brain : a journal of neurology.

[53]  S. Hughes,et al.  Thalamic Mechanisms of EEG Alpha Rhythms and Their Pathological Implications , 2005, The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry.

[54]  O. Jensen,et al.  Prestimulus alpha and mu activity predicts failure to inhibit motor responses , 2009, Human brain mapping.

[55]  R. Llinás,et al.  Rhythmic and dysrhythmic thalamocortical dynamics: GABA systems and the edge effect , 2005, Trends in Neurosciences.

[56]  Alon Sinai,et al.  Pain assessment by continuous EEG: Association between subjective perception of tonic pain and peak frequency of alpha oscillations during stimulation and at rest , 2010, Brain Research.

[57]  D. Vernon,et al.  Interpreting EEG alpha activity , 2014, Neuroscience & Biobehavioral Reviews.

[58]  R H LaMotte,et al.  Pain, hyperalgesia and activity in nociceptive C units in humans after intradermal injection of capsaicin. , 1992, The Journal of physiology.

[59]  Alon Sinai,et al.  Tonic pain and continuous EEG: Prediction of subjective pain perception by alpha-1 power during stimulation and at rest , 2012, Clinical Neurophysiology.

[60]  Gerome Breen,et al.  Genetic Variation , 2020, Population Genetics with R.

[61]  R. LaMotte,et al.  Neurogenic hyperalgesia: the search for the primary cutaneous afferent fibers that contribute to capsaicin-induced pain and hyperalgesia. , 1991, Journal of neurophysiology.

[62]  O. Jensen,et al.  Shaping Functional Architecture by Oscillatory Alpha Activity: Gating by Inhibition , 2010, Front. Hum. Neurosci..

[63]  Terrence J. Sejnowski,et al.  An Information-Maximization Approach to Blind Separation and Blind Deconvolution , 1995, Neural Computation.

[64]  R. Gracely,et al.  The human capsaicin model of allodynia and hyperalgesia: sources of variability and methods for reduction. , 1998, Journal of pain and symptom management.