title: Disentangling linear and nonlinear brain responses to evoked deep tissue pain.
abstract: Pain stimuli evoke widespread responses in the brain. However, our understanding of the physiological significance underlying heterogeneous response within different pain-activated and -deactivated regions is still limited. Using functional magnetic resonance imaging, we evaluated brain responses to a wide range of stimulus intensity levels (1 innocuous, 7 painful) in order to estimate region-specific stimulus-response functions, which we hypothesized could illuminate that region's functional relationship to pain. Linear and nonlinear brain responses to pain were estimated through independent Legendre polynomial transformations of pain ratings within a general linear model. This approach identified at least 5 different, regionally specific activity profiles in the brain. Linearly increasing (eg, primary somatosensory/motor cortex, insulae) and intensity-independent (eg, secondary somatosensory cortex) activation was noted in traditional pain-processing areas, potentially reflecting sensory encoding and all-or-none salience responses, respectively. Multiple activity profiles were seen in areas of the default mode network (DMN): intensity-independent deactivation (eg, posterior cingulate cortex), linearly decreasing (eg, contralateral inferior parietal lobule), and quadratic (U-shaped; eg, medial prefrontal cortex). The latter observation suggests that: (1) different DMN subregions exhibit functional heterogeneity and (2) some DMN subregions respond in a percept-related manner to pain, suggesting closer linkage between the DMN and pain processing than previously thought. Future studies should apply a similar approach using innocuous stimuli of multiple intensities to evaluate whether the response profiles reported here can also be generalized to nonpainful somatosensory processing.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Psychiatry, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA MGH/MIT/HMS Athinoula A. Martinos Center for Biomedical Imaging, Charlestown, MA, USA Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Chronic Pain and Fatigue Research Center, Department of Anesthesiology, University of Michigan, Ann Arbor, MI, USA Department of Biomedical Engineering, Kyunghee University, Yongin, Republic of Korea Department of Radiology, Logan College of Chiropractic, Chesterfield, MO, USA.
authors.forename: Marco L
authors.initials: ML
authors.lastname: Loggia
authors.forename: Robert R
authors.initials: RR
authors.lastname: Edwards
authors.forename: Jieun
authors.initials: J
authors.lastname: Kim
authors.forename: Mark G
authors.initials: MG
authors.lastname: Vangel
authors.forename: Ajay D
authors.initials: AD
authors.lastname: Wasan
authors.forename: Randy L
authors.initials: RL
authors.lastname: Gollub
authors.forename: Richard E
authors.initials: RE
authors.lastname: Harris
authors.forename: Kyungmo
authors.initials: K
authors.lastname: Park
authors.forename: Vitaly
authors.initials: V
authors.lastname: Napadow
mesh_terms: D001921:Brain / Q000503:physiopathology*; D005073:Evoked Potentials, Somatosensory; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008959:Models, Neurological; D017711:Nonlinear Dynamics; D010146:Pain / Q000503:physiopathology*; D017288:Pain Threshold / Q000502:physiology*; D055815:Young Adult