UC San Diego

Aims: Adolescents with substance use disorders (SUD) exhibit hyposensitivity to pleasant internally generated (interoceptive) stimuli and hypersensitivity to external rewarding stimuli. It is unclear whether similar patterns exist for aversive interoceptive stimuli. We compared activation in the insular cortex and other brain regions during the anticipation and experience of aversive stimuli between adolescents with SUD and those without. Design: Cross-sectional experimental study with two groups. Participants: Adolescents (ages 15-17years) with an alcohol or marijuana SUD (n=18) and healthy comparison subjects (CON, n=15).Participants were recruited by distributing flyers at local high schools. Setting: Keck Imaging Center, University of California San Diego, CA, USA. Measurements: Behavioral and neural responses to a continuous performance task with inspiratory breathing load recorded during an fMRI session. Questionnaires assessed life-time drug use, anxiety, sensation-seeking, impulsivity, affect and bodily awareness. Visual analog scales assessed drug craving and breathing load responses. Findings: Across subjects, experience of breathing load elicited greater bilateral anterior and posterior insula (AI and PI, respectively) activation than anticipation (F(1,31)=4.16, P<0.05). SUD exhibited greater left AI and bilateral PI activation during breathing load than anticipation, comparedwithCON (F(1,31)=4.16, P<0.05). In contrast, CON showed greater activation during anticipation than breathing load in left PI, comparedwithSUD (F(1,31)=4.16, P<0.05). Conclusions: Adolescents with alcohol and marijuana substance use disorders may be hypersensitive to aversive interoceptive stimuli.