Research Supported by NIDA R01 DA016663-01

1. Striatal and Insular Hyperactivation during Pleasant Interoceptive Stimuli Characterizes the Transition to Problematic Stimulant Use in Young Adults April C. May1, Jennifer L. Stewart1, Jason M. Parnass1, Susan F. Tapert1,2& Martin P. Paulus1,2 1University of California San Diego, Department of Psychiatry 2Psychiatry Service, Veterans Affairs San Diego Health Care System Research Supported by NIDA R01 DA016663-01 • Interoceptiveprocessing has been hypothesized to be dysfunctional in substance using individuals (Naqvi & Bechara, 2010; Paulus et al., 2009). However, it is unclear whether this altered system is linked to a predisposition to use drugs in at-risk individuals, or a consequence of problem drug use. • Mechano-receptive C-fiber (MR-CF) stimulation via soft touch (Olausson et al., 2010) can be employed to (1) investigate interoceptive sensitivity to positively valenced stimuli, and (2) determine its relevance for addiction. • The present study examined whether brain and behavioral indices of interoception during MR-CF stimulation are altered as a consequence of problem drug use. • Do occasional stimulant users who transitioned to problem use differ in their interoceptive responses from occasional stimulant users who ceased use, as well as from stimulant-naïve comparison subjects? BACKGROUND PARTICIPANTS RESULTS PSU exhibited greater bilateral anterior insula than DSU and CTL across Anticipation and Soft Touch conditions (when compared to Baseline condition). Brain-Behavior Correlations In CTL, higher pleasantness VAS ratings were associated with greater left anterior insula activation. In contrast, DSU showed the opposite pattern and PSU exhibited no relationship. No significant correlations emerged between Verbal IQ/BDI-II and insula/striatum ROIs within PSU (all p > .14). Baseline PSU DSU Anticipation 32 28 6 sec • Groups did not differ in gender, ethnicity, impulsivity, sensation seeking, education, and age (p > .12). • However, verbal IQ was lower in PSU (M=108.1, SD=6.0) and DSU (M=110.3, SD=5.7) • than CTL (M=116.9, SD=7.8), F(2,41)=6.9, p=.01. • Moreover, PSU endorsed higher levels of depressive symptoms on the Beck Depression Inventory II (M=6.0, SD=7.1) than PSU (M=0.6, SD=0.7) and CTL (M=2.1, SD=2.1), F(2,45)=6.3, p=.01. Soft Touch R 2 sec 20 Groups did not differ in VAS ratings, Reaction Time, or Accuracy (>98.5%). During the Soft Touch Condition, PSU exhibited greater posterior insula and striatal activation than DSU and CTL. STATISTICAL ANALYSIS DISCUSSION Problem stimulant users relative to desisters and comparison subjects exhibited greater anterior/posterior insula and striatum activation during Soft Touch in the absence of behavioral differences between groups. Results suggest that neural differences in interoceptive sensitivity between groups are not due to a predisposition to use stimulants, but are instead a consequence of prolonged use. Findings indicate that the transition to stimulant dependence may be associated with exaggerated reward responsivity that may contribute to the propensity to increase use into adulthood. • Linear Mixed Effect Model • Dependent Variable: • - fMRI voxels, whole brain • Between Subjects Variable: • - Group (PSU, DSU, CTL) • Within Subjects Variables: • - Condition (Anticipation, Soft Touch) • - Stimulus Type (Palm, Forearm) • Univariate ANOVA • Dependent Variable: • - VAS pleasantness/intensity ratings • Between Subjects Variable: • - Group (PSU, DSU, CTL) • Repeated Measures ANOVA • Dependent Variable: • - Reaction Time, Accuracy • Between Subjects Variable: • - Group (PSU, DSU, CTL) • Within Subjects Variables: • - Condition (Anticipation, Soft Touch) • - Stimulus Type (Palm, Forearm) • Brain-Behavior Correlations • Within PSU only: Insula/striatum ROIs with: • - Verbal IQ • - BDI-II • - Lifetime Amphetamine Uses • Within each group: Insula/striatum ROIs with: • - VAS pleasantness SOFT TOUCH TASK • Continuous performance task with cued mechano-receptive C-fiber stimulation was administered during functional magnetic resonance imaging (fMRI; 3T UCSD Keck Center). • Participants responded to the orientation of arrows during three conditions: • Baseline – gray background • Anticipation- blue or yellow background signaling impending slow brush stroke to the left palm or forearm • Soft Touch – blue or yellow background; administered within the next 6 seconds using a soft brush at a velocity of 2 cm/sec • Interoceptive sensations (e.g., pleasantness, intensity) rated with visual analog scales (VAS) References Naqvi, N. H., & Bechara, A. (2010). The insula and drug addiction: an interoceptive view of pleasure, urges, and decision-making. Brain Structure and Function, 214(5), 435-450. Olausson, H., Wessberg, J., Morrison, I., McGlone, F., Vallbo, A. (2010). The neurophysiology of unmyelinated tactile afferents. Neurosci Biobehav Rev. 34(2), 185-191. Paulus, M. P., Tapert, S. F., & Schulteis, G. (2009). The role of interoception and alliesthesia in addiction. Pharmacology Biochemistry and Behavior, 94(1), 1-7. No touch R Palm Forearm