Memory traces of pain in human cortex

Abstract

Distinct brain regions process sensory discriminative and affective components of pain; however, the role of these areas in pain memory is unknown. This event-related study investigated the short-term memory for sensory features of cutaneous heat pain using a delayed-discrimination paradigm and functional magnetic resonance imaging. During memory trials, subjects discriminated the location and intensity of two painful stimuli presented sequentially to the right hand. Control trials comprised the same sequence of stimuli and motor responses but required no delayed discrimination. Stimulus-evoked activity for memory and control trials was generally indistinguishable within the network of regions normally responsive to experimental pain [i.e., the primary somatosensory cortex/posterior parietal cortex (SI/PPC), secondary somatosensory cortex (SII), and anterior insular cortex (aIC)]; these data confirm the painful nature of the stimuli and the similar levels of attention and stimulus encoding engaged during the two randomly presented trial types. Memory-specific activity, assessed by contrasting the interstimulus interval in memory and control trials, was observed in SI/PPC and aIC but not in SII. We propose that SI/PPC plays a role in the short-term retention of spatial and intensity aspects of noxious stimuli and that aIC activation during memory trials is consistent with the integration of sensory and cognitive (attention, awareness, salience, and memory) components of pain perception. The absence of memory-specific anterior cingulate cortex activation, generally associated with pain unpleasantness, suggests that remembering affective aspects of the stimuli was not required during performance of the sensory delayed-discrimination task.

Figure 1.

Schematic representation of the stimulation protocol with an 8 s ISI; the memory and control trials were presented in a pseudo-randomized order. See Materials and Methods, Experimental paradigm, for a description of each time period for both trial types.

Figure 2.

Cortical regions significantly activated during the ISI between the pairs of stimuli in both the memory and control trials and memory-specific activation observed within pain-related sites. Delay-related activation, assessed by contrasting the BOLD responses associated with the delay and the baseline, was similar for both experimental and control trials in bilateral SI/PPC, SII, and aIC (illustrations are focused on BOLD responses exceeding a significance level of p < 0.001, corrected for multiple comparisons). Memory-specific activation observed within these pain-related areas, resulting from a contrast of experimental and control trials, was observed in contralateral SI/PPC and bilateral aIC (data illustrated with a threshold of p < 0.05, corrected for multiple comparisons). No trends toward memory-specific activation were seen within SII.

Figure 3.

Mean time course of the memory-specific percentage BOLD signal from the group average observed during the course of experimental and control trials, synchronized on the start of each trial. In all cases illustrated, the BOLD signal increase observed during the ISI is significantly higher during experimental memory trials compared with that observed during the same interval of the control trials. Time 0 is the onset of the trial; the red box illustrates the expected time period of peak BOLD responses associated with the ISI, after taking into consideration the delay of the hemodynamic response function.