Preserved emotional awareness of pain in a patient with extensive bilateral damage to the insula, anterior cingulate, and amygdala

Abstract

Functional neuroimaging investigations of pain have discovered a reliable pattern of activation within limbic regions of a putative "pain matrix" that has been theorized to reflect the affective dimension of pain. To test this theory, we evaluated the experience of pain in a rare neurological patient with extensive bilateral lesions encompassing core limbic structures of the pain matrix, including the insula, anterior cingulate, and amygdala. Despite widespread damage to these regions, the patient's expression and experience of pain was intact, and at times excessive in nature. This finding was consistent across multiple pain measures including self-report, facial expression, vocalization, withdrawal reaction, and autonomic response. These results challenge the notion of a "pain matrix" and provide direct evidence that the insula, anterior cingulate, and amygdala are not necessary for feeling the suffering inherent to pain. The patient's heightened degree of pain affect further suggests that these regions may be more important for the regulation of pain rather than providing the decisive substrate for pain's conscious experience.

Keywords: Brain lesion; Consciousness; Emotion; Feeling; Limbic system.

Fig. 1

Roger’s brain. a Sagittal MRI slices showing bilateral lesions to the ACC (leftmost images) and insula (rightmost images). b Coronal MRI slices showing bilateral lesions to the amygdala (top) and right secondary somatosensory cortex (bottom). c 3D digital “dissection” of the insular cortex: top lateral view of the brain of a healthy non-brain damaged participant, revealing the gyrations of the insular cortex; bottom lateral view of Roger’s brain, highlighting the absence of an insular cortex; left axial MRI slices corresponding to the dashed lines on the 3D-images. All MRI slices are shown in radiological convention. Volumetric analyses (Philippi et al. 2012) reveal that his lesion encompasses 90 % of the insula, 99 % of the ACC, and 100 % of the amygdala. The lesion extends beyond these regions into other limbic territories with more extensive damage in the right hemisphere. The entire right insula is destroyed and the damage in the posterior sector extends into parietal operculum, secondary somatosensory cortex, and the underlying white matter. The vast majority of the left insula is also destroyed with the exception of a small island of tissue in the left dorsal anterior insula that appears to be functionally disconnected from the rest of the brain (Philippi et al. 2012). Although the ACC has been destroyed bilaterally, the more dorsal and posterior aspects of Brodmann area 32 appear to be spared in the left hemisphere; however, this remaining tissue is dorsal to the paracingulate sulcus, and is therefore considered part of the paracingulate cortex (and not the ACC proper). Of note, Roger’s lesion has largely spared the brainstem, thalamus, and primary and secondary somatosensory cortices. The only exception is the aforementioned damage to the right secondary somatosensory cortex, as well as some localized atrophy in the right thalamus and right pons. The reader is referred to Fig. 2 and Feinstein et al. and Philippi et al. for additional brain scans and a more detailed account of Roger’s damage

Fig. 2

Roger’s brain in comparison to the standard MNI brain. a Sagittal, b coronal, and c axial MRI slices through Roger’s brain placed next to the same slice from the standard MNI brain

Fig. 3

Self-ratings of pain. Roger’s real-time subjective ratings of pain using a 10-cm electronic visual analog scale. a Roger’s average level of pain across all four immersions for both the cold pressor and warm water trials. The black line represents the median cold pressor pain ratings in the healthy comparison sample and the shaded gray region represents the comparisons’ 25th–75th percentile. b Roger’s individual online ratings for each of the four cold pressor immersions. The ratings for the pain intensity trials range from “No Pain” (0) to “Worst Pain Imaginable” (10). The ratings for the pain affect trials range from “Not at all Unpleasant” (0) to “Extremely Unpleasant” (10). The closed circles represent the moment when Roger withdrew his hand from the water, thus terminating the trial

Fig. 4

Pain facial expressions. a Roger’s average pain face composite score during cold pressor trials (blue line) and warm water trials (orange line). b Average corrugator EMG responses (expressed in standard deviations of the power, with respect to baseline) during cold pressor trials (blue line) and warm water trials (orange line)

Fig. 5

Heart rate and skin conductance changes. Roger’s average autonomic response during cold pressor trials (blue line) and warm water trials (orange line). a Mean change from baseline in heart rate (beats per minute). b Mean skin conductance level (standard deviations from baseline). The gray dotted lines correspond to ±1SD across trials. The dip in average skin conductance around 37 s corresponds to the end of one of the trials when Roger withdrew his hand