Interoceptive attention in opioid and stimulant use disorder

Abstract

Blunted anterior insula activation during interoceptive perturbations has been associated with stimulant (cocaine and amphetamine) use disorder (SUD) and is related to risk for and prognosis of SUD. However, little is known whether these interoceptive alterations extend to opioid use disorder (OUD). This exploratory study used the same experimental probe during functional magnetic resonance imaging (fMRI) to test the hypothesis that SUD and OUD exhibit interoceptive discrepancies characterized by subjective ratings and activation within the insula. Recently, abstinent individuals diagnosed with current SUD (n = 40) or current OUD (n = 20) were compared with healthy individuals (CTL; n = 30) on brain and self-report responses during an interoceptive attention task known to elicit insula activation. Participants selectively attended to interoceptive (heartbeat and stomach) and exteroceptive signals during blood-oxygen-level-dependent fMRI recording. Groups and conditions were compared on (a) activation within probabilistic cytoarchitectonic segmentations of the insula and (b) self-reported stimulus intensity. First, SUD showed amplified ratings of heart-related sensations but attenuation of dorsal dysgranular insula activity relative to CTL. Amplified ratings were linked to drug use recency, while attenuation was normalized with greater past-year stimulant use. Second, SUD and OUD showed attenuation of dorsal dysgranular insula activity during attention to stomach sensations relative to CTL. Taken together, these results are consistent with altered neural processing of interoceptive signals in drug addiction, particularly as a function of SUD. Future studies will need to determine whether interoceptive metrics help to explain substance use disorder pathophysiology and are useful for predicting outcomes.

Keywords: cytoarchitecture; insula; interoception; opioid use disorder; stimulant use disorder.

Figure 1.

Diagram highlighting participant inclusion and exclusion into three groups for statistical analysis: Current stimulant use disorder (SUD; n = 40), current opioid use disorder (OUD, n = 20), and healthy comparison subjects (CTL, n = 30). MINI = MINI international neuropsychiatric interview. CDDR = Customary Drinking and Drug Use Record. MRI = magnetic resonance imaging.

Figure 2.

Six insular cortex regions of interest (ROIs) extracted from the Brainnetome Atlas.

Figure 3.

(A) Group*condition interaction results for stimulus intensity ratings. Intensity ratings could range from 0 = no sensation to 6 = extreme sensation. SUD = current stimulant use disorder. OUD = current opioid use disorder. CTL = healthy comparisons. The blue star indicates a significant difference for SUD versus CTL. Error bars reflect +/− 1 standard error. (B) Within SUD, more recent illicit drug use was associated with greater reported intensity of heartbeat sensations, sharing 15% of the variance.

Figure 4.

(A) Group*region*condition interaction results for insular blood-oxygen-level dependent (BOLD) percent signal change (PSC) from baseline. SUD = current stimulant use disorder. OUD = current opioid use disorder. CTL = healthy comparisons. The blue stars indicates a significant difference for SUD versus CTL, whereas the red star indicates a significant difference for OUD versus CTL. Error bars reflect +/− 1 standard error. (B) Within SUD, greater past-year stimulant use was associated with higher dorsal dysgranular insula BOLD signal during the heart condition, sharing 11% of the variance.