title: Attenuated Neural Processing of Risk in Young Adults at Risk for Stimulant Dependence.
abstract: OBJECTIVE
  Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate), which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing.
  
  
  METHODS
  158 occasional stimulants users (OSU) and 50 comparison subjects (CS) performed a "risky gains" decision making task during which they could select safe options (cash in 20 cents) or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, "risky decisions"). The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42), or <50 lifetime marijuana uses (n = 32), were compared to CS with <50 lifetime uses (n = 46) to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed.
  
  
  RESULTS
  There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC) and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options.
  
  
  CONCLUSIONS
  Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions critical for performance monitoring, reward processing and interoceptive awareness. Marijuana had additive effects by diminishing neural risk differentiation.
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, California, United States of America; Institute of Neuroscience and Medicine (INM-6), Computational and Systems Neuroscience and Institute for Advanced Simulation (IAS-6), Theoretical Neuroscience, Forschungszentrum Jülich GmbH, Jülich, Germany; JARA BRAIN Institute I, Jülich, Germany.
authors.forename: Martina
authors.initials: M
authors.lastname: Reske
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, California, United States of America; CUNY Queens College, Queens, New York, United States of America.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Stewart
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, California, United States of America; University of Texas, Austin, Texas, United States of America.
authors.forename: Taru M
authors.initials: TM
authors.lastname: Flagan
authors.affiliation: Department of Psychiatry, University of California San Diego, La Jolla, California, United States of America; Psychiatry Service, VA San Diego Healthcare System, La Jolla, California, United States of America; Laureate Institute for Brain Research, 6655 S Yale Ave, Tulsa, Oklahoma, United States of America.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Paulus
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000503:physiopathology*; D000697:Central Nervous System Stimulants / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D059906:Neuroimaging; D010641:Phenotype; D012307:Risk Factors; D012309:Risk-Taking; D019966:Substance-Related Disorders / Q000175:diagnosis* / Q000503:physiopathology*; D063189:Symptom Assessment; D055815:Young Adult
chemical_list: D000697:Central Nervous System Stimulants