title: You are the danger: attenuated insula response in methamphetamine users during aversive interoceptive decision-making.
abstract: BACKGROUND
  Drug dependent individuals often make drug-taking decisions when they do not feel well. Yet, few studies have examined the influence of an aversive state on decision-making related neural processing.
  
  
  METHODS
  We investigate brain activation to decision-making during an aversive interoceptive challenge in methamphetamine users using functional magnetic resonance imaging (fMRI). Recently abstinent inpatients with methamphetamine use disorder (METH; n=20) and healthy comparison subjects (CTL; n=22) performed a two-choice prediction task at three fixed error rates (ER; 20%=reward, 50%=uncertainty, 80%=punishment) while anticipating and experiencing episodes of inspiratory breathing load during fMRI.
  
  
  RESULTS
  METH exhibited higher trait anxiety in conjunction with lower anterior insula (AI) and inferior frontal gyrus (IFG) activation than CTL across trials. METH also showed lower posterior insula (PI) and anterior cingulate cortex (ACC) activation than CTL during breathing load independent of ER. For the crucial ER by interoception interaction, METH displayed lower ACC activation to punishment/loss than CTL during breathing load. Within METH, lower trait anxiety was linked to AI/IFG attenuation across trials.
  
  
  CONCLUSIONS
  AI/IFG attenuations in METH are suggestive of an executive functioning deficit, particularly in users with low anxiety, reflecting reduced resources allocated to choice selection. In contrast, PI/ACC reductions in METH appear specific to impairments in registering and evaluating interoceptive experiences. Taken together, inadequate activation of brain areas that are important for regulating when one does not feel well may be the neural basis for poor decision-making by METH.
authors.affiliation: Department of Psychiatry, University of California, San Diego, 8939 Villa La Jolla Drive, Suite 200, La Jolla, San Diego, CA 92037-0855, USA. Electronic address: j6stewart@ucsd.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Stewart
authors.affiliation: Department of Psychiatry, University of California, San Diego, 8939 Villa La Jolla Drive, Suite 200, La Jolla, San Diego, CA 92037-0855, USA.
authors.forename: April C
authors.initials: AC
authors.lastname: May
authors.affiliation: Department of Psychiatry, University of California, San Diego, 8939 Villa La Jolla Drive, Suite 200, La Jolla, San Diego, CA 92037-0855, USA.
authors.forename: Tasha
authors.initials: T
authors.lastname: Poppa
authors.affiliation: Department of Physiological Sciences, University of Florida, Box 100144, 1333 Center Drive, Gainesville, FL 32610-0144, USA.
authors.forename: Paul W
authors.initials: PW
authors.lastname: Davenport
authors.affiliation: Department of Psychiatry, University of California, San Diego, 8939 Villa La Jolla Drive, Suite 200, La Jolla, San Diego, CA 92037-0855, USA; Psychiatry Service, Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
authors.forename: Susan F
authors.initials: SF
authors.lastname: Tapert
authors.affiliation: Department of Psychiatry, University of California, San Diego, 8939 Villa La Jolla Drive, Suite 200, La Jolla, San Diego, CA 92037-0855, USA; Psychiatry Service, Veterans Affairs San Diego Healthcare System, 3350 La Jolla Village Drive, San Diego, CA 92161, USA.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Paulus
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000503:physiopathology* / Q000523:psychology; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology; D001931:Brain Mapping; D002540:Cerebral Cortex / Q000503:physiopathology*; D003657:Decision Making / Q000502:physiology*; D055030:Drug Users / Q000523:psychology*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008694:Methamphetamine; D008875:Middle Aged; D009483:Neuropsychological Tests; D011597:Psychomotor Performance / Q000502:physiology; D056152:Respiratory Rate / Q000502:physiology; D012201:Reward; D035501:Uncertainty
chemical_list: D008694:Methamphetamine
keywords: Breathing load; Decision-making; Error processing; Functional magnetic resonance imaging (fMRI); Interoception; Methamphetamine