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Altered Neurocognitive Processing of Tactile Stimuli in Patients with Complex Regional Pain Syndrome

  • Anoop Kuttikat
    Affiliations
    Department of Rheumatology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
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  • Valdas Noreika
    Affiliations
    Department of Psychology, University of Cambridge, Cambridge, United Kingdom

    Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, United Kingdom
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  • Srivas Chennu
    Affiliations
    School of Computing, University of Kent, Chatham Maritime, United Kingdom

    Department of Clinical Neurosciences, University of Cambridge, United Kingdom
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  • Nicholas Shenker
    Affiliations
    Department of Rheumatology, Addenbrooke's Hospital, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
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  • Tristan Bekinschtein
    Affiliations
    Department of Psychology, University of Cambridge, Cambridge, United Kingdom

    Medical Research Council, Cognition and Brain Sciences Unit, Cambridge, United Kingdom
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  • Christopher A. Brown
    Correspondence
    Address reprint requests to Christopher A. Brown, PhD, Department of Psychological Sciences, Faculty of Psychology, Health and Society, University of Liverpool, Liverpool, United Kingdom.
    Affiliations
    Department of Psychological Sciences, Faculty of Psychology, Health and Society, University of Liverpool, Liverpool, United Kingdom

    CamPAIN Group, Department of Anaesthesia, University of Cambridge, Cambridge, United Kingdom
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Published:December 08, 2017DOI:https://doi.org/10.1016/j.jpain.2017.11.008

      Highlights

      • Slower response times during digit discrimination in complex regional pain syndrome patients.
      • Response times correlated with late-latency tactile processing in supplementary motor area.
      • This P300-like activity was paradoxically related to better limb functioning.
      • Responses in parietal lobe were decreased in complex regional pain syndrome regardless of task demands.

      Abstract

      Chronic pain in complex regional pain syndrome (CRPS) has been linked to tactile misperceptions and deficits in somatotopic representation of the affected limb. In this study, we identify altered cognitive processing of tactile stimuli in CRPS patients that we propose marks heterogeneity in tactile decision-making mechanisms. In a case-control design, we compared middle- and late-latency somatosensory evoked potentials in response to pseudorandomized mechanical stimulation of the digits of both hands (including CRPS-affected and nonaffected sides) between 13 CRPS patients and 13 matched healthy controls. During a task to discriminate the digit simulated, patients (compared with controls) had significantly lower accuracy and slowed response times but with high between-subject variability. At middle latencies (124–132 ms), tactile processing in patients relative to controls showed decrements in superior parietal lobe and precuneus (that were independent of task demands) but enhanced activity in superior frontal lobe (that were task-dependent). At late latencies, patients showed an augmented P300-like response under task demands that localized to the supplementary motor area. Source activity in the supplementary motor area correlated with slowed response times, although its scalp representation intriguingly correlated with better functioning of the affected limb, suggesting a compensatory mechanism. Future research should investigate the clinical utility of these putative markers of tactile decision-making mechanisms in CRPS.

      Perspective

      We present evidence of altered but highly variable cognitive processing (124–268 ms latency) in response to mechanical tactile stimuli in patients with CRPS compared with healthy controls. Such mid- to late-latency responses could potentially provide convenient and robust biomarkers of abnormal perceptual decision-making mechanisms in CRPS to aid in clinical detection and treatment.

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      References

        • Barrett L.F.
        • Simmons W.K.
        Interoceptive predictions in the brain.
        Nat Rev Neurosci. 2015; 16: 419-429
        • Bell A.J.
        • Sejnowski T.J.
        An information-maximization approach to blind separation and blind deconvolution.
        Neural Comput. 1995; 7: 1129-1159
        • Binkley J.M.
        • Stratford P.W.
        • Lott S.A.
        • Riddle D.L.
        The lower extremity functional scale (LEFS): Scale development, measurement properties, and clinical application.
        Phys Ther. 1999; 79: 371-383
        • Cavanna A.E.
        • Trimble M.R.
        The precuneus: A review of its functional anatomy and behavioural correlates.
        Brain. 2006; 129: 564-583
        • Chennu S.
        • Finoia P.
        • Kamau E.
        • Monti M.M.
        • Allanson J.
        • Pickard J.D.
        • Owen A.M.
        • Bekinschtein T.A.
        Dissociable endogenous and exogenous attention in disorders of consciousness.
        NeuroImage Clin. 2013; 3: 450-461
        • Chennu S.
        • Noreika V.
        • Gueorguiev D.
        • Blenkmann A.
        • Kochen S.
        • Ibáñez A.
        • Owen A.M.
        • Bekinschtein T.A.
        Expectation and attention in hierarchical auditory prediction.
        J Neurosci. 2013; 33: 11194-11205
        • Cleeland C.S.
        • Ryan K.M.
        Pain assessment: Global use of the Brief Pain Inventory.
        Ann Acad Med Singapore. 1994; 23: 129-138
        • Comerchero M.D.
        • Polich J.
        P3a, perceptual distinctiveness, and stimulus modality.
        Brain Res Cogn Brain Res. 1998; 7: 41-48
        • Delorme A.
        • Makeig S.
        EEGLAB: An open source toolbox for analysis of single-trial EEG dynamics including independent component analysis.
        J Neurosci Methods. 2004; 134: 9-21
        • DeMirci S.
        • Savas S.
        The auditory event related potentials in episodic and chronic pain sufferers.
        Eur J Pain. 2002; 6: 239-244
        • Di Pietro F.
        • McAuley J.H.
        • Parkitny L.
        • Lotze M.
        • Wand B.M.
        • Moseley G.L.
        • Stanton T.R.
        Primary somatosensory cortex function in complex regional pain syndrome: A systematic review and meta-analysis.
        J Pain. 2013; 14: 1001-1018
        • Di Pietro F.
        • Stanton T.R.
        • Moseley G.L.
        • Lotze M.
        • McAuley J.H.
        Interhemispheric somatosensory differences in chronic pain reflect abnormality of the Healthy side.
        Hum Brain Mapp. 2015; 36: 508-518
        • Duncan C.C.
        • Barry R.J.
        • Connolly J.F.
        • Fischer C.
        • Michie P.T.
        • Näätänen R.
        • Polich J.
        • Reinvang I.
        • Van Petten C.
        Event-related potentials in clinical research: Guidelines for eliciting, recording, and quantifying mismatch negativity, P300, and N400.
        Clin Neurophysiol. 2009; 120: 1883-1908
        • Förderreuther S.
        • Sailer U.
        • Straube A.
        Impaired self-perception of the hand in complex regional pain syndrome (CRPS).
        Pain. 2004; 110: 756-761
        • Galer B.
        • Jensen M.P.
        Neglect-like symptoms in CRPS. Results of a self-administered survey.
        J Pain Symptom Manage. 1999; 18: 213-217
        • Harden R.N.
        • Bruehl S.
        • Stanton-Hicks M.
        • Wilson P.R.
        Proposed new diagnostic criteria for complex regional pain syndrome.
        Pain Med. 2007; 8: 326-331
        • Hernández A.
        • Zainos A.
        • Romo R.
        Temporal evolution of a decision-making process in medial premotor cortex.
        Neuron. 2002; 33: 959-972
        • Hinds O.
        • Thompson T.W.
        • Ghosh S.
        • Yoo J.J.
        • Whitfield-Gabrieli S.
        • Triantafyllou C.
        • Gabrieli J.D.
        Roles of default-mode network and supplementary motor area in human vigilance performance: Evidence from real-time fMRI.
        J Neurophysiol. 2013; 109: 1250-1258
        • IBM
        IBM SPSS Statistics for Windows, Version 21.0.
        IBM Corp, Armonk, NY2012
        • Karl A.
        • Diers M.
        • Flor H.
        P300-amplitudes in upper limb amputees with and without phantom limb pain in a visual oddball paradigm.
        Pain. 2004; 110: 40-48
        • Kitada R.
        • Sasaki A.T.
        • Okamoto Y.
        • Kochiyama T.
        • Sadato N.
        Role of the precuneus in the detection of incongruency between tactile and visual texture information: A functional MRI study.
        Neuropsychologia. 2014; 64: 252-262
        • Kuttikat A.
        • Noreika V.
        • Shenker N.
        • Chennu S.
        • Bekinschtein T.
        • Brown C.A.
        Neurocognitive and neuroplastic mechanisms of novel clinical signs in CRPS.
        Front Hum Neurosci. 2016; 10: 16
        • Kuttikat A.
        • Shaikh M.
        • Oomatia A.
        • Parker R.
        • Shenker N.
        Novel signs and their clinical utility in diagnosing complex regional pain syndrome (CRPS)—a prospective observational cohort study.
        Clin J Pain. 2016; 1
        • Litvak V.
        • Friston K.
        Electromagnetic source reconstruction for group studies.
        Neuroimage. 2008; 42: 1490-1498
        • Litvak V.
        • Mattout J.
        • Kiebel S.
        • Phillips C.
        • Henson R.
        • Kilner J.
        • Barnes G.
        • Oostenveld R.
        • Daunizeau J.
        • Flandin G.
        • Penny W.
        • Friston K.
        EEG and MEG data analysis in SPM8.
        Comput Intell Neurosci. 2011; 2011: 852961
        • Marinus J.
        • Moseley G.L.
        • Birklein F.
        • Baron R.
        • Maihöfner C.
        • Kingery W.S.
        • van Hilten J.J.
        Clinical features and pathophysiology of CRPS.
        Lancet Neurol. 2011; 10: 637-648
        • Meehan S.K.
        • Staines W.R.
        The effect of task-relevance on primary somatosensory cortex during continuous sensory-guided movement in the presence of bimodal competition.
        Brain Res. 2007; 1138: 148-158
        • Moseley G.L.
        Why do people with complex regional pain syndrome take longer to recognize their affected hand?.
        Neurology. 2004; 62: 2182-2186
        • Parra M.A.
        • Ascencio L.L.
        • Urquina H.F.
        • Manes F.
        • Ibáñez A.M.
        P300 and neuropsychological assessment in mild cognitive impairment and Alzheimer dementia.
        Front Neurol. 2012; 3: 172
        • Pleger B.
        • Ragert P.
        • Schwenkreis P.
        • Förster A.F.
        • Wilimzig C.
        • Dinse H.
        • Nicolas V.
        • Maier C.
        • Tegenthoff M.
        Patterns of cortical reorganization parallel impaired tactile discrimination and pain intensity in complex regional pain syndrome.
        Neuroimage. 2006; 32: 503-510
        • Polich J.
        Updating P300: An integrative theory of P3a and P3b.
        Clin Neurophysiol. 2009; 118: 2128-2148
        • Preuschhof C.
        • Heekeren H.R.
        • Taskin B.
        • Schubert T.
        • Villringer A.
        Neural correlates of vibrotactile working memory in the human brain.
        J Neurosci. 2006; 26: 13231-13239
        • Ramchurn A.
        • de Fockert J.W.
        • Mason L.
        • Darling S.
        • Bunce D.
        Intraindividual reaction time variability affects P300 amplitude rather than latency.
        Front Hum Neurosci. 2014; 8: 557
        • Romo R.
        • Salinas E.
        Flutter discrimination: Neural codes, perception, memory and decision making.
        Nat Rev Neurosci. 2003; 4: 203-218
        • Zigmond A.S.
        • Snaith R.P.
        The hospital anxiety and depression scale.
        Acta Psychiatr Scand. 1983; 67: 361-370
        • Stratford P.W.
        • Binkley J.M.
        • Stratford D.
        Development and initial validation of the upper extremity functional index.
        Physiother Can. 2001; 53: 259-267
        • Tandon O.P.
        • Kumar A.
        • Dhar D.
        • Battacharya A.
        Event-related evoked potential responses (P 300) following epidural methylprednisolone therapy in chronic low back pain patients.
        Anaesthesia. 1997; 52: 1173-1176
        • Tarkka I.M.
        • Micheloyannis S.
        • Stoki D.S.
        Generators for human P300 elicited by somatosensory stimuli using multiple dipole source analysis.
        Neuroscience. 1996; 75: 275-287
        • Tomasevic-Todorovic S.
        • Boskovic K.
        • Filipovic D.
        • Milekic B.
        • Grajic M.
        • Hanna F.
        Auditory event-related p300 potentials in rheumatoid arthritis patients.
        Neurophysiology. 2015; 47: 138-143
        • Turetsky B.I.
        • Calkins M.E.
        • Light G.A.
        • Olincy A.
        • Radant A.D.
        • Swerdlow N.R.
        Neurophysiological endophenotypes of schizophrenia: The viability of selected candidate measures.
        Schizophr Bull. 2006; 33: 69-94
        • van Velzen G.A.
        • Rombouts S.A.
        • van Buchem M.A.
        • Marinus J.
        • van Hilten J.J.
        Is the brain of complex regional pain syndrome patients truly different?.
        Eur J Pain. 2016; 20: 1622-1633
        • Valeriani M.
        • Fraioli L.
        • Ranghi F.
        • Giaquinto S.
        Dipolar source modeling of the P300 event-related potential after somatosensory stimulation.
        Muscle Nerve. 2001; 24: 1677-1686
        • Kilner J.M.
        • Friston K.J.
        Topological inference for EEG and MEG.
        Ann Appl Stat. 2010; 4: 1272-1290
        • Phillips C.
        • Mattout J.
        • Friston K.
        Forward models for EEG.
        in: Friston K. Ashburner J. Kiebel S. Nichols T. Penny W. Statistical parametric mapping: The analysis of functional brain images. Academic Press, London, UK2007: 352-366
        • Mattout J.
        • Phillips C.
        • Penny W.D.
        • Rugg M.D.
        • Friston K.J.
        MEG source localization under multiple constraints: An extended Bayesian framework.
        Neuroimage. 2006; 30: 753-767