close
Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2009 Feb;101(2):875-87.
doi: 10.1152/jn.91100.2008. Epub 2008 Dec 10.

Parsing pain perception between nociceptive representation and magnitude estimation

Affiliations

Parsing pain perception between nociceptive representation and magnitude estimation

M N Baliki et al. J Neurophysiol. 2009 Feb.

Abstract

Assessing the size of objects rapidly and accurately clearly has survival value. A central multisensory module for subjective magnitude assessment is therefore highly likely, suggested by psychophysical studies, and proposed on theoretical grounds. Given that pain perception is fundamentally an assessment of stimulus intensity, it must necessarily engage such a central module. Accordingly, we compared functional magnetic resonance imaging (fMRI) activity of pain magnitude ratings to matched visual magnitude ratings in 14 subjects. We show that brain activations segregate into two groups, one preferentially activated for pain and another equally activated for both visual and pain magnitude ratings. The properties of regions in the first group were consistent with encoding nociception, whereas those in the second group with attention and task control. Insular cortex responses similarly segregated to a pain-specific area and an area (extending to the lateral prefrontal cortex) conjointly representing perceived magnitudes for pain and vision. These two insular areas were differentiated by their relationship to task variance, ability to encode perceived magnitudes for each stimulus epoch, temporal delay differences, and brain intrinsic functional connectivity. In a second group of subjects (n=11) we contrasted diffusion tensor imaging-based white matter connectivity for these two insular areas and observed anatomical connectivity closely corresponding to the functional connectivity identified with fMRI. These results demonstrate that pain perception is due to the transformation of nociceptive representation into subjective magnitude assessment within the insula. Moreover, we argue that we have identified a multisensory cortical area for "how much" complementary and analogous to the "where" and "what" as described for central visual processing.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Brain activity maps for pain- and visual-rating tasks. A, top: average pain ratings for painful heat. Gray areas delineate epochs and intensities (in degrees Celsius for the thermal stimuli). Bottom: average rating for the visual task. The black trace is the visual stimulus, obtained from the subject's pain ratings. The red trace corresponds to the subject's rating (bars are SD). Scatterplots show the relationship between stimulus intensity and perceived magnitudes and follows a power function with exponent of 4.4 for pain and 1.0 for visual ratings. B: random-effects analysis for pain- and visual-rating tasks. Many cortical areas were commonly activated. Bilateral thalamus and basal ganglia (BG) were active only during pain. The conjunction map between pain and visual rating is shown in blue and represents voxels that were commonly activated for both tasks and highlight many cortical regions, including portions of the insula. The contrast map shows regions significantly more active for pain rating and include bilateral thalamus and BG and parts of insula and middle portions of the anterior cingulate cortex (mACc). There were no regions that were more active for the visual rating.
FIG. 2.
FIG. 2.
Individual pain and visual magnitude ratings. Left column shows individual on-line subjective pain ratings for the 14 healthy subjects included in the study on a scale of 0–100, where 0 is no pain and 100 is maximum imaginable pain. Right columns show the corresponding visual on-line ratings using the same scale. Variances for the pain and visual tasks are shown next to the time courses. Bottom left: the time course of the thermal stimulus, monitored on the skin and averaged across all participants. Bottom right: the highly significant correlation between the variance for pain- and visual-rating tasks across 14 subjects, which is the stimulus–response relationship for the visual task.
FIG. 3.
FIG. 3.
Brain regions encoding variance of pain- and visual-rating tasks. A: whole brain covariate analysis between variance and brain activity for pain- and for visual-rating tasks. B: conjunction analyses for the pain and visual covariate maps; multiple cortical areas encoded variance in both tasks including bilateral ventral premotor cortex (VPc), posterior parietal cortex (PPc), insula, in addition to right dorsal premotor cortex (DPc) and supplementary motor area (SMA). C: topological maps for insular activity and variance encoding in pain- and visual-rating tasks. Bottom right panels show spatial dissociation for pain-specific activation (region that is significantly more active during pain than the visual-rating task, nociceptive-specific [noci-INS], red contour) and magnitude encoding areas (regions that are commonly activated and equally encode magnitudes during pain- and visual-rating tasks, magnitude-related [mag-INS], blue contour). D: scatterplots depict the relationship between brain activity from mag-INS and noci-INS (mean z-score) and variance for pain (circle) and visual (triangle) tasks.
FIG. 4.
FIG. 4.
Brain regions encoding magnitude for visual and pain perceived magnitudes. A: example of blood oxygenated level–dependent (BOLD) signal and rating in standard units from one subject. Peak BOLD and rating were extracted for each stimulation epoch (indicated by arrows) and submitted for correlational analyses. B: correlation of BOLD with magnitude for 2 regions derived from the conjunction of variance-related map (blue) and contrast map (red). Scatterplots depict the degree of association between individuals' region of interest (ROI) signal and magnitude for pain (circles) and visual (triangles) stimuli. The ordinate represents functional magnetic resonance imaging (fMRI) signal and the abscissa represents the magnitude rating for each stimulus epoch for each participant. C: correlation strengths between rated magnitude and BOLD for pain and visual stimuli across task (conjunction) and pain-specific (contrast) regions. *P < 0.01; **P < 0.001. R, right; L, left.
FIG. 5.
FIG. 5.
Timing of BOLD signals across brain regions during pain-rating task. A, top panels: the average time course of the stimulus and rating (convolved with hemodynamic function, shown twice to be compared with respective time courses below). Time course of average BOLD responses (bars are SE) for pain-specific areas (left column) and for brain regions derived from the conjunction of variance-related maps (right column). The ordinates represent the average BOLD signal for each area across 110 stimulation events and the abscissa represents the time from the start of the stimulus (time = 0 s). B, top: the stimulus-rating indices for mag-INS and noci-INS (correlation of signal of brain region with rating − correlation with stimulus) plotted as a function of the peak response latency for each cortical area from the start of application of the stimulus in each subject. The distributions of noci-INS and mag-INS show no overlap, as indicated by color markings. The mean (and SE) for stimulus-rating indices for each area across all subjects are shown in the bottom panel.
FIG. 6.
FIG. 6.
Functional and anatomical dissociation in the insula. A: functional connectivity maps for left noci-INS and mag-INS. noci-INS exhibits strong connectivity to pain-specific regions, including bilateral thalamus, putamen, caudate, and amygdala, in addition to ACc and ventral striatum. In contrast, mag-INS shows strong connectivity to task-related regions including bilateral PPc, DPc, SMA, and lateral frontal regions. B: probabilistic maps of white matter tracts for left mag-INS (blue) and noci-INS (right), determined in a separate group of subjects than the subjects studied with fMRI. Right graph shows the number of connections averaged across all subjects as a function of threshold of connectivity. C: right colored brain regions illustrate the targets used in connectivity. Bar graph displays the target connectivity (examined only ipsilateral to the seed) for mag-INS and noci-INS. Consistent with the functional connectivity maps, mag-INS (blue bars) had significantly higher connections with M1, S1, and S2, whereas noci-INS (red bars) had higher connections with amygdala, thalamus, and basal ganglia. Bars are median ± quartile range. *P < 0.01; **P < 0.01.

References

    1. AlexanderALAlexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics 4: 316–329, 2007. - PMC - PubMed
    1. ApkarianAVApkarian AV, Bushnell MC, Treede RD, Zubieta JK. Human brain mechanisms of pain perception and regulation in health and disease. Eur J Pain 9: 463–484, 2005. - PubMed
    1. ApkarianAVApkarian AV, Darbar A, Krauss BR, Gelnar PA, Szeverenyi NM. Differentiating cortical areas related to pain perception from stimulus identification: temporal analysis of fMRI activity. J Neurophysiol 81: 2956–2963, 1999. - PubMed
    1. ApkarianAVApkarian AV, Krauss BR, Fredrickson BE, Szeverenyi NM. Imaging the pain of low back pain: functional magnetic resonance imaging in combination with monitoring subjective pain perception allows the study of clinical pain states. Neurosci Lett 299: 57–60, 2001. - PubMed
    1. AugustineJRAugustine JR. Circuitry and functional aspects of the insular lobe in primates including humans. Brain Res Brain Res Rev 22: 229–244, 1996. - PubMed

MeSH terms

LinkOut - more resources