The experience of pain can be significantly influenced by expectancy (predictive cues). This ability to modulate pain has the potential to affect therapeutic analgesia substantially and constitutes a foundation for non-pharmacological pain relief. In this study, we investigated 1) brain regions involved in visual cue modulation of pain during anticipation of pain, pain administration, and pain rating; and 2) the association between pre-test resting-state functional connectivity and the magnitude of cue effects on pain ratings. We found that after cue conditioning, visual cues can significantly modulate subjective pain ratings. fMRI results suggested that brain regions pertaining to the frontoparietal network (prefrontal and parietal cortex) and a pain/emotion modulatory region (rostral anterior cingulate cortex, rACC) are involved in cue modulation during both pain anticipation and administration stage. Most interestingly, we found that pre-test resting state functional connectivity between the frontoparietal network (as identified by independent component analysis) and the rACC/MPFC was positively associated with cue effects on pain rating changes. We believe that these finding will shed new light on our understanding of variable cue/expectancy effects across individuals and how the intrinsic connectivity of the brain may influence expectancy induced modulation of pain.

BackgroundElectroacupuncture (EA) is currently one of the most popular acupuncture modalities. However, the continuous stimulation characteristic of EA treatment presents challenges to the use of conventional functional Magnetic Resonance Imaging (fMRI) approaches for the investigation of neural mechanisms mediating treatment response because of the requirement for brief and intermittent stimuli in event related or block designed task paradigms. A relatively new analysis method, functional connectivity fMRI (fcMRI), has great potential for studying continuous treatment modalities such as EA. In a previous study, we found that, compared with sham acupuncture, EA can significantly reduce Periaqueductal Gray (PAG) activity when subsequently evoked by experimental pain. Given the PAG's important role in mediating acupuncture analgesia, in this study we investigated functional connectivity with the area of the PAG we previously identified and how that connectivity was affected by genuine and sham EA.ResultsForty-eight subjects, who were randomly assigned to receive either genuine or sham EA paired with either a high or low expectancy manipulation, completed the study. Direct comparison of each treatment mode's functional connectivity revealed: significantly greater connectivity between the PAG, left posterior cingulate cortex (PCC), and precuneus for the contrast of genuine minus sham; significantly greater connectivity between the PAG and right anterior insula for the contrast of sham minus genuine; no significant differences in connectivity between different contrasts of the two expectancy levels.ConclusionsOur findings indicate the intrinsic functional connectivity changes among key brain regions in the pain matrix and default mode network during genuine EA compared with sham EA. We speculate that continuous genuine EA stimulation can modify the coupling of spontaneous activity in brain regions that play a role in modulating pain perception.

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Behavioral pattern separation (BPS) paradigms ask participants to discriminate previously encoded (old) stimuli from highly similar (lure) and categorically distinct (novel) stimuli. The lure-old discrimination, thought to uniquely reflect pattern separation in the hippocampal formation, is typically pitted against the traditional novel-old discrimination. However, BPS paradigms have measured lure-old discrimination neither consistently across studies nor in such a way that allows for accurate comparison to novel-old discrimination. Therefore, we advocate for signal detection theory (SDT) as a unified framework. Moreover, we compare SDT with previously used measures of lure-old discrimination, indicating how other formulas' inaccuracies can lead to erroneous conclusions.Tasks measuring behavioral pattern separation (BPS) are distinguished from standard tests of memory recognition by the inclusion of stimuli that are highly similar to those previously encoded. Because each of these "lure" stimuli differs only slightly from its corresponding previously encoded "old" stimulus, successful discrimination of old from lure stimuli is thought to denote particularly detailed memory representations of the old stimuli. In contrast, it has been suggested that successful discrimination of old from "novel" stimuli (i.e., categorically new, as commonly used in tests of recognition) need not rely on detailed representations of the old stimuli, but rather can be achieved even if the old stimuli have only gist-based representations. Consistent with this distinction, several studies imply a dissociation between novelold and lure-old discrimination. For example, using the BPS paradigm, researchers have argued that only detail-based lure-old discrimination is impaired in healthy aging (Stark et al. 2013) and enhanced by post-study caffeine (Borota et al. 2014). Claims from a more recent study (Reagh and Yassa 2014) support an even stronger, double dissociation: repeated-encoding benefits gist-based, novel-old discrimination (a finding known even to Ebbinghaus (1885)), but surprisingly impairs detail-based, lureold discrimination. One major concern-particularly with findings such as these, where there appear to be differences between novel-old and lure-old discrimination-is that the measures used for lure-old discrimination vary from each other and from those used for novel-old discrimination. A unified measurement approach is needed if one is to reliably characterize lure-old discrimination as well as properly compare it to novel-old discrimination.Here, we propose the use of signal detection theory (SDT) (Green and Swets 1966) for measuring lure-old discrimination. We reran the aforementioned BPS paradigm (Reagh and Yassa 2014), which tested effects of repeated encoding on both detail and gist-based memory representations. We demonstrate not only that SDT is an appropriate framework for measuring lure-old discrimination but that SDT formulas yield opposite results to those reported: lure-old discrimination, like novel-old discrimin...