Neuroimaging Evidence of Motor Control and Pain Processing in the Human Midcingulate Cortex.

Human neuroimaging and virus-tracing studies in monkey predict that motor control and pain processes should overlap in anterior midcingulate cortex (aMCC), but there is currently no direct evidence that this is the case. We used a novel functional magnetic resonance imaging paradigm to examine brain activity while subjects performed a motor control task, experienced a pain-eliciting stimulus on their hand, and performed the motor control task while also experiencing the pain-eliciting stimulus. Our experiment produced 3 novel results. First, group-level analyses showed that when separate trials of motor control and pain processing were performed, overlapping functional activity was found in the same regions of aMCC, supplementary motor area (SMA), anterior insula, and putamen. Secondly, increased activity was found in the aMCC and SMA when motor control and pain processing occurred simultaneously. Thirdly, individual-level analyses showed that 93% of subjects engaged the same region of aMCC during separate trials of motor control and pain processing irrespective of differences in the sulcal/gyral morphology of the cingulate cortex across individuals. These observations provide direct evidence in humans that the same region of aMCC is engaged for motor control and pain processing.

[1]  David E Vaillancourt,et al.  Selective regions of the visuomotor system are related to gain-induced changes in force error. , 2010, Journal of neurophysiology.

[2]  J. Krakauer,et al.  Differential cortical and subcortical activations in learning rotations and gains for reaching: a PET study. , 2004, Journal of neurophysiology.

[3]  C. A. Porro,et al.  Touch or pain? Spatio-temporal patterns of cortical fMRI activity following brief mechanical stimuli , 2008, PAIN.

[4]  L. McCracken,et al.  The pain anxiety symptoms scale: development and validation of a scale to measure fear of pain , 1992, Pain.

[5]  D Farina,et al.  Muscle pain induces task-dependent changes in cervical agonist/antagonist activity. , 2007, Journal of applied physiology.

[6]  C. Janelle,et al.  Emotional states alter force control during a feedback occluded motor task. , 2008, Emotion.

[7]  T. Ebner,et al.  Single trial coupling of Purkinje cell activity to speed and error signals during circular manual tracking , 2008, Experimental Brain Research.

[8]  Jonathan D. Cohen,et al.  Improved Assessment of Significant Activation in Functional Magnetic Resonance Imaging (fMRI): Use of a Cluster‐Size Threshold , 1995, Magnetic resonance in medicine.

[9]  F. Roux,et al.  Motor cortex stimulation for neuropathic pain. , 2007, Acta neurochirurgica. Supplement.

[10]  Christopher R. France,et al.  The relationship between pain-related fear and lumbar flexion during natural recovery from low back pain , 2007, European Spine Journal.

[11]  David Borsook,et al.  A key role of the basal ganglia in pain and analgesia - insights gained through human functional imaging , 2010, Molecular pain.

[12]  Brent A. Vogt,et al.  Cingulate Neurobiology and Disease , 2009 .

[13]  B. Vogt Pain and emotion interactions in subregions of the cingulate gyrus , 2005, Nature Reviews Neuroscience.

[14]  C. Spielberger,et al.  Manual for the State-Trait Anxiety Inventory , 1970 .

[15]  P. Strick,et al.  Activation of the supplementary motor area (SMA) during performance of visually guided movements. , 2003, Cerebral cortex.

[16]  RP Dum,et al.  The origin of corticospinal projections from the premotor areas in the frontal lobe , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[17]  R. Davidson,et al.  The integration of negative affect, pain and cognitive control in the cingulate cortex , 2011, Nature Reviews Neuroscience.

[18]  Derek B Archer,et al.  Effects of a force production task and a working memory task on pain perception. , 2013, The journal of pain : official journal of the American Pain Society.

[19]  Thomas Weiss,et al.  Perception to laser heat stimuli in depressed patients is reduced to Aδ- and selective C-fiber stimulation , 2011, Neuroscience Letters.

[20]  D. Vaillancourt,et al.  Neural Basis for the Processes That Underlie Visually-guided and Internally-guided Force Control in Humans , 2003 .

[21]  D. Farina,et al.  Low-frequency oscillations of the neural drive to the muscle are increased with experimental muscle pain. , 2012, Journal of neurophysiology.

[22]  Hong Yu,et al.  Role of individual basal ganglia nuclei in force amplitude generation. , 2007, Journal of neurophysiology.

[23]  Alan C. Evans,et al.  Human cingulate and paracingulate sulci: pattern, variability, asymmetry, and probabilistic map. , 1996, Cerebral cortex.

[24]  M. Petrides,et al.  Neuroimaging evidence of the anatomo-functional organization of the human cingulate motor areas. , 2014, Cerebral cortex.

[25]  D. Vaillancourt,et al.  Maintaining Force Control Despite Changes in Emotional Context Engages Dorsomedial Prefrontal and Premotor Cortex , 2011, Cerebral cortex.

[26]  M. Lindquist,et al.  An fMRI-based neurologic signature of physical pain. , 2013, The New England journal of medicine.

[27]  Felipe Fregni,et al.  Motor cortex stimulation for chronic pain , 2008, Neurology.

[28]  Volkmar Glauche,et al.  Somatotopic organization of human somatosensory cortices for pain: a single trial fMRI study , 2004, NeuroImage.

[29]  G. Rizzolatti,et al.  Multiple representations of body movements in mesial area 6 and the adjacent cingulate cortex: An intracortical microstimulation study in the macaque monkey , 1991, The Journal of comparative neurology.

[30]  P. Strick,et al.  The Spinothalamic System Targets Motor and Sensory Areas in the Cerebral Cortex of Monkeys , 2009, The Journal of Neuroscience.

[31]  Alan C. Evans,et al.  In vivo morphometry of the intrasulcal gray matter in the human cingulate, paracingulate, and superior‐rostral sulci: Hemispheric asymmetries, gender differences and probability maps , 1996, The Journal of comparative neurology.

[32]  Sabine Kastner,et al.  Functional heterogeneity of conflict, error, task-switching, and unexpectedness effects within medial prefrontal cortex , 2011, NeuroImage.

[33]  S. Swinnen,et al.  Reduced basal ganglia function when elderly switch between coordinated movement patterns. , 2010, Cerebral cortex.

[34]  L. Becerra,et al.  Neural circuitry underlying pain modulation: expectation, hypnosis, placebo , 2003, Trends in Cognitive Sciences.

[35]  D. Borsook Pain and motor system plasticity , 2007, Pain.

[36]  M. Hallett,et al.  Mesial motor areas in self-initiated versus externally triggered movements examined with fMRI: effect of movement type and rate. , 1999, Journal of neurophysiology.

[37]  Felipe Fregni,et al.  Effects of motor cortex modulation and descending inhibitory systems on pain thresholds in healthy subjects. , 2012, The journal of pain : official journal of the American Pain Society.

[38]  C. Janelle,et al.  Emotional state and initiating cue alter central and peripheral motor processes. , 2007, Emotion.

[39]  S. Lev,et al.  Chronic pain-related remodeling of cerebral cortex - 'pain memory': a possible target for treatment of chronic pain. , 2013, Pain management.

[40]  P. van Donkelaar,et al.  The Human Dorsal Premotor Cortex Generates On-Line Error Corrections during Sensorimotor Adaptation , 2006, The Journal of Neuroscience.

[41]  Emma G Duerden,et al.  Localization of pain‐related brain activation: A meta‐analysis of neuroimaging data , 2013, Human brain mapping.

[42]  Klaus-Peter Hoffmann,et al.  Influence of visually guided tracking arm movements on single cell activity in area MT , 2009, Experimental Brain Research.

[43]  J. Cauraugh,et al.  Bimanual isometric force control: Asymmetry and coordination evidence post stroke , 2012, Clinical Neurophysiology.

[44]  K. Koltyn,et al.  Examination of the dose–response relationship between pain perception and blood pressure elevations induced by isometric exercise in men and women , 2010, Biological Psychology.

[45]  Daniel M. Corcos,et al.  Three-dimensional locations and boundaries of motor and premotor cortices as defined by functional brain imaging: A meta-analysis , 2006, NeuroImage.

[46]  Paul W. Hodges,et al.  Moving differently in pain: A new theory to explain the adaptation to pain , 2011, PAIN.

[47]  J. Summers,et al.  Emotion and motor preparation: A transcranial magnetic stimulation study of corticospinal motor tract excitability , 2009, Cognitive, affective & behavioral neuroscience.

[48]  David E Vaillancourt,et al.  Segregated and overlapping neural circuits exist for the production of static and dynamic precision grip force , 2011, Human brain mapping.

[49]  T. Ebner,et al.  What features of visually guided arm movements are encoded in the simple spike discharge of cerebellar Purkinje cells? , 1997, Progress in brain research.

[50]  B. Krauss,et al.  Cortical responses to thermal pain depend on stimulus size: a functional MRI study. , 2000, Journal of neurophysiology.

[51]  Stephen A. Coombes,et al.  Spatiotemporal tuning of brain activity and force performance , 2011, NeuroImage.

[52]  P. Strick,et al.  Motor areas of the medial wall: a review of their location and functional activation. , 1996, Cerebral cortex.

[53]  C. Spielberger Manual for the State-Trait Anxiety Inventory (STAI) (Form Y , 1983 .

[54]  Irene Tracey,et al.  The Cerebral Signature for Pain Perception and Its Modulation , 2007, Neuron.

[55]  Edward E. Smith,et al.  Placebo-Induced Changes in fMRI in the Anticipation and Experience of Pain , 2004, Science.

[56]  Stephan P. Swinnen,et al.  Specific cerebellar regions are related to force amplitude and rate of force development , 2012, NeuroImage.

[57]  Dennis Velakoulis,et al.  Variability of the paracingulate sulcus and morphometry of the medial frontal cortex: Associations with cortical thickness, surface area, volume, and sulcal depth , 2008, Human brain mapping.

[58]  J. Rhudy,et al.  Fear and anxiety: divergent effects on human pain thresholds , 2000, Pain.

[59]  J. Schmahmann,et al.  Aversion-Related Circuitry in the Cerebellum: Responses to Noxious Heat and Unpleasant Images , 2011, The Journal of Neuroscience.

[60]  M. Pessiglione,et al.  Get Aroused and Be Stronger: Emotional Facilitation of Physical Effort in the Human Brain , 2009, The Journal of Neuroscience.

[61]  David W. McNeal,et al.  Amygdala interconnections with the cingulate motor cortex in the rhesus monkey , 2007, The Journal of comparative neurology.

[62]  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.

[63]  P. Strick,et al.  Imaging the premotor areas , 2001, Current Opinion in Neurobiology.

[64]  C. Chapman,et al.  Predictability of painful stimulation modulates subjective and physiological responses. , 2010, The journal of pain : official journal of the American Pain Society.

[65]  Hilla Peretz,et al.  Ju n 20 03 Schrödinger ’ s Cat : The rules of engagement , 2003 .

[66]  B. Vogt,et al.  Pain Processing in Four Regions of Human Cingulate Cortex Localized with Co‐registered PET and MR Imaging , 1996, The European journal of neuroscience.

[67]  Janey Prodoehl,et al.  Basal ganglia mechanisms underlying precision grip force control , 2009, Neuroscience & Biobehavioral Reviews.

[68]  Roland Peyron,et al.  Motor cortex stimulation in neuropathic pain. Correlations between analgesic effect and hemodynamic changes in the brain. A PET study , 2007, NeuroImage.

[69]  Anders M. Dale,et al.  An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest , 2006, NeuroImage.

[70]  K. Zilles,et al.  A link between the systems: functional differentiation and integration within the human insula revealed by meta-analysis , 2010, Brain Structure and Function.

[71]  M. Knauf,et al.  Temporal summation of heat pain modulated by isometric exercise , 2013, European journal of pain.

[72]  Naomi Hasegawa,et al.  Thalamocortical and intracortical connections of monkey cingulate motor areas , 2003, The Journal of comparative neurology.

[73]  Elena Peltz,et al.  Functional connectivity of the human insular cortex during noxious and innocuous thermal stimulation , 2011, NeuroImage.

[74]  M. Inase,et al.  Neuronal activity in the primate premotor, supplementary, and precentral motor cortex during visually guided and internally determined sequential movements. , 1991, Journal of neurophysiology.

[75]  C. Vierck,et al.  Attenuation of pain reactivity by caudate nucleus stimulation in monkeys , 1975, Brain Research.

[76]  A. Prochazka,et al.  Voluntary and reflex control of human back muscles during induced pain , 1999, The Journal of physiology.

[77]  A. Schulze-Bonhage,et al.  Functional organization of the human anterior insular cortex , 2009, Neuroscience Letters.

[78]  Marta Ghisi,et al.  Beck Depression Inventory-Second Edition. Adattamento italiano: Manuale , 2006 .

[79]  Katiuscia Sacco,et al.  Functional connectivity of the insula in the resting brain , 2011, NeuroImage.

[80]  Lumy Sawaki,et al.  The contribution of the putamen to sensory aspects of pain: insights from structural connectivity and brain lesions. , 2011, Brain : a journal of neurology.

[81]  Stephen A. Coombes,et al.  Force control and degree of motor impairments in chronic stroke , 2010, Clinical Neurophysiology.

[82]  A. Craig,et al.  How do you feel — now? The anterior insula and human awareness , 2009, Nature Reviews Neuroscience.

[83]  Raphael J Leo,et al.  Repetitive transcranial magnetic stimulation (rTMS) in experimentally induced and chronic neuropathic pain: a review. , 2007, The journal of pain : official journal of the American Pain Society.

[84]  M. Posner,et al.  Cognitive and emotional influences in anterior cingulate cortex , 2000, Trends in Cognitive Sciences.

[85]  Paul Van Hecke,et al.  Internal vs external generation of movements: differential neural pathways involved in bimanual coordination performed in the presence or absence of augmented visual feedback , 2003, NeuroImage.

[86]  B. Vogt,et al.  Human cingulate cortex: Surface features, flat maps, and cytoarchitecture , 1995, The Journal of comparative neurology.

[87]  Karen D Davis,et al.  Interactions of pain intensity and cognitive load: the brain stays on task. , 2007, Cerebral cortex.

[88]  J. Dostrovsky,et al.  Human anterior cingulate cortex neurons modulated by attention-demanding tasks. , 2000, Journal of neurophysiology.

[89]  Jun Tanji,et al.  Cingulofrontal Interactions and the Cingulate Motor Areas , 2009 .

[90]  K. Zilles,et al.  The "what" and "when" of self-initiated movements. , 2013, Cerebral cortex.

[91]  L. Pessoa,et al.  Emotion affects action: Midcingulate cortex as a pivotal node of interaction between negative emotion and motor signals , 2010, Cognitive, affective & behavioral neuroscience.

[92]  C. L. Kwan,et al.  An fMRI study of the anterior cingulate cortex and surrounding medial wall activations evoked by noxious cutaneous heat and cold stimuli , 2000, Pain.

[93]  J. Taha,et al.  Outcome of unilateral and bilateral pallidotomy for Parkinson's disease: patient assessment. , 2000, Neurosurgery.

[94]  P. Strick,et al.  Frontal Lobe Inputs to the Digit Representations of the Motor Areas on the Lateral Surface of the Hemisphere , 2005, The Journal of Neuroscience.

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

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

[97]  Paulina J. M. Bank,et al.  Motor consequences of experimentally induced limb pain: A systematic review , 2013, European journal of pain.

[98]  Zara M. Bergström,et al.  A Specific Brain Structural Basis for Individual Differences in Reality Monitoring , 2011, The Journal of Neuroscience.

[99]  C. Janelle,et al.  Dissociating Motivational Direction and Affective Valence , 2007, Psychological science.

[100]  Lisa Feldman Barrett,et al.  Functional grouping and cortical–subcortical interactions in emotion: A meta-analysis of neuroimaging studies , 2008, NeuroImage.

[101]  M. Mesulam,et al.  Insula of the old world monkey. Architectonics in the insulo‐orbito‐temporal component of the paralimbic brain , 1982, The Journal of comparative neurology.

[102]  P. Strick,et al.  Spinal Cord Terminations of the Medial Wall Motor Areas in Macaque Monkeys , 1996, The Journal of Neuroscience.

[103]  Kelly M. Naugle,et al.  A meta-analytic review of the hypoalgesic effects of exercise. , 2012, The journal of pain : official journal of the American Pain Society.