How the Brain Wants What the Body Needs: The Neural Basis of Positive Alliesthesia

Abstract

Discontinuing unhealthy behaviors, such as overeating or drug use, depends upon an individual's ability to overcome the influence of environmental reward cues. The strength of that influence, however, varies greatly depending upon the internal state of the body. Characterizing the relationship between interoceptive signaling and shifting drug cue valuation provides an opportunity for understanding the neural bases of how changing internal states alter reward processing more generally. A total of 17 cigarette smokers rated the pleasantness of cigarette pictures when they were nicotine sated or nicotine abstinent. On both occasions, smokers also underwent functional magnetic resonance imaging (fMRI) scanning while performing a visceral interoceptive attention task and a resting-state functional connectivity scan. Hemodynamic, physiological, and behavioral parameters were compared between sated and abstinent scans. The relationships between changes in these parameters across scan sessions were also examined. Smokers rated cigarette pictures as significantly more pleasant while nicotine abstinent than while nicotine sated. Comparing abstinent with sated scans, smokers also exhibited significantly decreased mid-insula, amygdala, and orbitofrontal activity while attending to interoceptive signals from the body. Change in interoceptive activity within the left mid-insula predicted the increase in smoker's pleasantness ratings of cigarette cues. This increase in pleasantness ratings was also correlated with an increase in resting-state functional connectivity between the mid-insula and the ventral striatum and ventral pallidum. These findings support a model wherein interoceptive processing in the mid-insula of withdrawal signals from the body potentiates the motivational salience of reward cues through the recruitment of hedonic 'hot spots' within the brain's reward circuitry.

Figure 1

Nicotine abstinence decreases interoception-evoked brain activity within interoceptive and appetitive neurocircuitry. Daily cigarette smokers exhibit decreased hemodynamic activity during interoceptive (vs exteroceptive) attention while in a nicotine-abstinent state, compared with that in a nicotine-sated state, in multiple brain regions involved in appetitive and affective processing. Significantly decreased IA task activation was observed within a network of limbic and paralimbic brain regions including the bilateral dorsal mid-insula, amygdala, and orbitofrontal cortex, regions that have been previously identified as playing a key role in the experience of drug craving.

Figure 2

Decreased interoceptive mid-insula activity during nicotine abstinence is related to positive alliesthesia for smoking pictures. Of all of the brain regions identified in the IA task contrast (Figure 1), only the left dorsal mid-insula exhibited a significant relationship between the difference in BOLD response to interoceptive attention (ΔIA) between sated and abstinent scans and the difference in pleasantness ratings for smoking pictures (ΔSP). Notably, both ΔSP and ΔIA were also significantly related to the difference in exhaled carbon monoxide between scans (ΔCO). Importantly, ΔIA in the left dorsal mid-insula partially mediates the relationship between ΔCO, a biomarker of cigarette consumption, and the change in pleasantness ratings for smoking pictures. This indicates that, the greater the reduction in recent cigarette use, the greater the decrease in interoceptive insula activity, and the greater the increase in the perceived pleasantness of smoking pictures.

Figure 3

Increased interoceptive insula functional connectivity is related to positive alliesthesia for smoking pictures. The average time course from the left dorsal mid-insula ROI (Figure 1) was used to examine differences in subjects' resting-state functional connectivity between sated and abstinent scans, using the change in average pleasantness ratings from the SP task as a covariate. Abstinence-induced increase in the pleasantness ratings of smoking images is significantly related to increased dorsal mid-insula connectivity to the left ventral striatum and the right ventral pallidum. This suggests that processing in the mid-insula of afferent withdrawal signals from the body amplifies the perceived hedonic value of smoking cues through increased connectivity to the subcortical brain regions most directly implicated in the processing of salience and reward.