Disentangling linear and nonlinear brain responses to evoked deep tissue pain

Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA
Pain (Impact Factor: 5.84). 08/2012; 153(10):2140-51. DOI: 10.1016/j.pain.2012.07.014
Source: PubMed

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.

Download full-text


Available from: Marco Loggia, Jul 03, 2015
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Imaging of the Human Brain in Health and Disease” examines the localization of neurotransmitter receptors in the nervous system of normal, healthy humans and compares that with humans who are suffering from various neurological diseases.
    Imaging of the human brain in health and disease, 10/2011: chapter Pain imaging in the human brain; Neuroscience Net.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Task-induced deactivation (TID) refers to a regional decrease in blood flow during an active task relative to a "resting" or "passive" baseline. We tested the hypothesis that TID results from a reallocation of processing resources by parametrically manipulating task difficulty within three factors: target discriminability, stimulus presentation rate, and short-term memory load. Subjects performed an auditory target detection task during functional magnetic resonance imaging (fMRI), responding to a single target tone or, in the short-term memory load conditions, to target sequences. Seven task conditions (a common version and two additional levels for each of the three factors) were each alternated with "rest" in a block design. Analysis of covariance identified brain regions in which TID occurred. Analyses of variance identified seven regions (left anterior cingulate/superior frontal gyrus, left middle frontal gyrus, right anterior cingulate gyrus, left and right posterior cingulate gyrus, left posterior parieto-occipital cortex, and right precuneus) in which TID magnitude varied across task levels within a factor. Follow-up tests indicated that for each of the three factors, TID magnitude increased with task difficulty. These results suggest that TID represents reallocation of processing resources from areas in which TID occurs to areas involved in task performance. Short-term memory load and stimulus rate also predict suppression of spontaneous thought, and many of the brain areas showing TID have been linked with semantic processing, supporting claims that TID may be due in part to suspension of spontaneous semantic processes that occur during "rest" (Binder et al., 1999). The concept that the typical "resting state" is actually a condition characterized by rich cognitive activity has important implications for the design and analysis of neuroimaging studies.
    Journal of Cognitive Neuroscience 05/2003; 15(3):394-408. DOI:10.1162/089892903321593117 · 4.69 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Recent functional brain connectivity studies have contributed to our understanding of the neurocircuitry supporting pain perception. However, evoked-pain connectivity studies have employed cutaneous and/or brief stimuli, which induce sensations that differ appreciably from the clinical pain experience. Sustained myofascial pain evoked by pressure cuff affords an excellent opportunity to evaluate functional connectivity change to more clinically relevant sustained deep-tissue pain. Connectivity in specific networks known to be modulated by evoked pain (sensorimotor, salience, dorsal attention, frontoparietal control, and default mode networks: SMN, SLN, DAN, FCN, and DMN) was evaluated with functional-connectivity magnetic resonance imaging, both at rest and during a sustained (6-minute) pain state in healthy adults. We found that pain was stable, with no significant changes of subjects' pain ratings over the stimulation period. Sustained pain reduced connectivity between the SMN and the contralateral leg primary sensorimotor (S1/M1) representation. Such SMN-S1/M1 connectivity decreases were also accompanied by and correlated with increased SLN-S1/M1 connectivity, suggesting recruitment of activated S1/M1 from SMN to SLN. Sustained pain also increased DAN connectivity to pain processing regions such as mid-cingulate cortex, posterior insula, and putamen. Moreover, greater connectivity during pain between contralateral S1/M1 and posterior insula, thalamus, putamen, and amygdala was associated with lower cuff pressures needed to reach the targeted pain sensation. These results demonstrate that sustained pain disrupts resting S1/M1 connectivity by shifting it to a network known to process stimulus salience. Furthermore, increased connectivity between S1/M1 and both sensory and affective processing areas may be an important contribution to interindividual differences in pain sensitivity.
    Pain 04/2013; 154(8). DOI:10.1016/j.pain.2013.04.016 · 5.84 Impact Factor