title: Behavioral and functional neuroimaging evidence for prefrontal dysfunction in methamphetamine-dependent subjects.
abstract: Stimulant-dependent subjects show dysfunctions in decision-making similar to those seen in subjects with ventromedial prefrontal cortex lesions. Studies of drug craving, reward association, and decision-making have implicated dysfunctions of the dorsolateral and orbitofrontal cortex as a key neural substrate in subjects with stimulant dependence. Here, a functional magnetic resonance imaging (fMRI) study was carried out to determine the relationship between decision-making dysfunction and neural activation in different prefrontal areas. This investigation tested the behavioral hypothesis that methamphetamine-dependent subjects in early sustained remission show decision-making dysfunctions that are consistent with an increased reliance on stimulus-contingent response selection. It was hypothesized that these decision-making dysfunctions are due to differences in task-related activation in the dorsolateral and ventromedial prefrontal cortex. Ten methamphetamine-dependent subjects were compared with ten age- and education-matched controls performing a two-choice prediction task and a two-choice response task during a fMRI session. Response bias, latency, and mutual information measures assessing the underlying strategies of the decision-making sequences were obtained. First, methamphetamine-dependent subjects were more influenced by the immediately preceding outcome during the two-choice prediction task relative to normal comparison subjects. Second, methamphetamine-dependent subjects activated less dorsolateral prefrontal cortex (BA 9) and failed to activate ventromedial cortex (BA 10,11) during the two-choice prediction task compared with the two-choice response task. These results support the basic hypothesis that stimulant-dependent subjects exhibit fundamental cognitive deficits during decision-making that are consistent with both orbitofrontal and dorsolateral prefrontal dysfunction.
authors.affiliation: Laboratory of Biological Dynamics and Theoretical Medicine, University of California San Diego, San Diego, CA 92093-0603, USA. martin@mag.ucsd.edu
authors.forename: Martin P
authors.initials: MP
authors.lastname: Paulus
authors.forename: Nikki E
authors.initials: NE
authors.lastname: Hozack
authors.forename: Blanca E
authors.initials: BE
authors.lastname: Zauscher
authors.forename: Lawrence
authors.initials: L
authors.lastname: Frank
authors.forename: Gregory G
authors.initials: GG
authors.lastname: Brown
authors.forename: David L
authors.initials: DL
authors.lastname: Braff
authors.forename: Marc A
authors.initials: MA
authors.lastname: Schuckit
mesh_terms: D000328:Adult; D019969:Amphetamine-Related Disorders / Q000473:pathology* / Q000523:psychology*; D001519:Behavior / Q000187:drug effects*; D005260:Female; D007839:Functional Laterality / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008694:Methamphetamine; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000473:pathology*; D011569:Psychiatric Status Rating Scales; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects
chemical_list: D008694:Methamphetamine