Brain mechanisms supporting spatial discrimination of pain

Abstract

Pain is a uniquely individual experience that is heavily shaped by evaluation and judgments about afferent sensory information. In visual, auditory, and tactile sensory modalities, evaluation of afferent information engages brain regions outside of the primary sensory cortices. In contrast, evaluation of sensory features of noxious information has long been thought to be accomplished by the primary somatosensory cortex and other structures associated with the lateral pain system. Using functional magnetic resonance imaging and a delayed match-to-sample task, we show that the prefrontal cortex, anterior cingulate cortex, posterior parietal cortex, thalamus, and caudate are engaged during evaluation of the spatial locations of noxious stimuli. Thus, brain mechanisms supporting discrimination of sensory features of pain extend far beyond the somatosensory cortices and involve frontal regions traditionally associated with affective processing and the medial pain system. These frontoparietal interactions are similar to those involved in the processing of innocuous information and may be critically involved in placing afferent sensory information into a personal historical context.

Figures

Figure 1.

The temporal sequence of the discrimination task. Noxious heat (or innocuous cool) stimuli were delivered sequentially to the back of the lower leg via two thermal probes separated by varying distances. Before the end of T2, subjects had to indicate whether T2 was in a different (or same) spatial location as T1. Discrimination-related brain activity was identified using regressors determined by response latencies in each individual discrimination trial. Additional regressors were used to identify brain activation that was related to spatial memory and to perceived pain (or cool).

Figure 2.

Behavioral responses during spatial discrimination (means ± SEM). Discrimination of noxious heat became progressively more difficult with increasing probe proximity (16, 8, 4 cm). Response latencies, error rates, and subjective ratings of perceived difficulty increased monotonically as stimuli were delivered closer together. In contrast, perceived pain intensity exhibited a trend toward decreasing with increasing stimulus proximity. At 4 cm separation distances, cool discrimination was performed more rapidly than noxious heat discrimination but was nearly equally difficult. VAS, Visual analog scale.

Figure 3.

Brain activation related to spatial discrimination of noxious stimuli is distinct from that related to perceived pain. These images are located at x = 0 mm, x = 30 mm, z = 5 mm, and y = −30 mm in standard stereotaxic space. IPL/SPL, Inferior parietal lobule/superior parietal lobule; GP/PT, globus pallidus/putamen; M1, primary motor cortex; DISCRIM., discrimination.

Figure 4.

Brain activation during spatial discrimination of innocuous cool stimuli. These images are located at x = 0 mm, x = 30 mm, z = 5 mm, and y = −30 mm in standard stereotaxic space. IPL/SPL, Inferior parietal lobule/superior parietal lobule; GP/PT, globus pallidus/putamen; M1, primary motor cortex, DISCRIM., discrimination.

Figure 5.

Brain activation during the memory period is related to the use of verbal mnemonic strategies. In >80% of discrimination trials, subjects used verbal strategies to remember the spatial location of the T1 stimulus. Consistent with such a verbal strategy, memory-related brain activation was lateralized to the left hemisphere in regions involved in verbal processing such as Broca's area on the inferior frontal gyrus. Activation during the memory period overlapped with activation during the discrimination period only in areas associated with motor planning. The left side of each brain image corresponds to the right side of the brain. IPL, Inferior parietal lobule; M1, primary motor cortex; DISCRIM., discrimination.