Biomedical subjects

Joel L Steinberg

Publications and source records attributed to Joel L Steinberg.

10 recordsLinked to original sources

PubMed2006

Response perseveration and adaptation in heavy marijuana-smoking adolescents.

The present study examined two behavioral processes - response perseveration and response adaptation - in adolescents who were heavy marijuana smokers and control adolescents. Testing took place in a controlled laboratory setting, using customized software and either a computer keyboard or a custom built response panel for response input. Adolescents age 14-18 were recruited into a heavy smoking (near daily) group (N=22) or a control group (N=31) with <15 lifetime uses of marijuana and no history of substance abuse or dependence. Marijuana use was verified by daily quantification of urinary cannabinoids and self-reports. Participants completed laboratory tasks designed to measure response perseveration (Wisconsin Card Sort Task, WCST) and response adaptation (concurrent variable-ratio reinforcement schedule with changing contingencies). Data were analyzed via ANOVA, controlling for multiple factors including: gender, age, nicotine use, presence of conduct disorder, and subscales of the Youth Self Report. After controlling for these compared to controls marijuana-using participants made significantly more perseverative and total errors on the WCST and showed significantly impaired (e.g., less adaptive) response allocation to the changing reinforcement contingencies on the concurrent-reinforcement task. Within the constraints of the study's limitations in controlling for alternative sources of between-subject variability, the data suggest that individuals who regularly smoke marijuana during adolescence show measurable perturbations in important basic behavioral processes. The data are also consistent with a previous laboratory study demonstrating reduced motivation in marijuana-smoking adolescents versus controls [Lane, S.D., Cherek, D.R., Pietras, C.J., and Steinberg, J.L. (2005). Performance of heavy marijuana-smoking adolescents on a laboratory measure of motivation. Addictive Behaviors, 30, 815-828].

Adaptation, Psychological↗

PubMed2006

Impulsivity and BOLD fMRI activation in MDMA users and healthy control subjects.

The correlation between scores on the Barratt Impulsiveness Scale (BIS) and activation measured by functional magnetic resonance imaging in a dorsolateral prefrontal cortical (DLPFC) activating task was examined in 15 MDMA-using subjects and 19 controls. A significant correlation between BIS scores and DLPFC activation was found, supporting a role for the DLPFC in BIS-measured impulsivity.

Adult↗

PubMed2005

Performance of heavy marijuana-smoking adolescents on a laboratory measure of motivation.

Marijuana smoking produces effects that may persist for hours or days beyond the period of acute intoxication. Despite evidence that adolescence represents a period of heightened exposure to marijuana, little research exists regarding possible impairment in adolescents who smoke marijuana regularly, and none exists regarding basic behavioral processes. In the present study, adolescents who smoked marijuana on a regular basis (near daily) were compared to a control group of adolescents on a two-option experimental task designed to measure motivation. The contingencies were arranged such that one option (work), which required systematically increasing response output, initially produced greater rates of monetary reinforcement than an alternative option (non-work) that required no response output to earn money. Switching to the non-work option was interpreted as a measure of reduced motivation. Significant differences were found between the groups: the marijuana-smoking participants switched earlier to the non-work option, and derived a greater percentage of their earnings from the non-work option. These differences existed when controlling for differences in cognitive aptitude, gender, and the presence of conduct disorder. A significant correlation between cannabinoid levels and percent of earnings derived from the non-work option suggests that these effects could be associated with the presence of cannabinoids in the marijuana-smoking group.

Adaptation, Psychological↗

PubMed2005

Reduced anterior corpus callosum white matter integrity is related to increased impulsivity and reduced discriminability in cocaine-dependent subjects: diffusion tensor imaging.

Brain imaging studies find evidence of prefrontal cortical dysfunction in cocaine-dependent subjects. Similarly, cocaine-dependent subjects have problems with behaviors related to executive function and impulsivity. Since prefrontal cortical axonal tracts cross between hemispheres in the corpus callosum, it is possible that white matter integrity in the corpus callosum could also be diminished in cocaine-dependent subjects. The purpose of this study was to compare corpus callosum white matter integrity as measured by the fractional anisotropy (FA) on diffusion tensor imaging (DTI) between 18 cocaine-dependent subjects and 18 healthy controls. The Barratt Impulsiveness Scale (BIS-11) and a continuous performance test: the Immediate and Delayed Memory Task (IMT/DMT) were also collected. Results of the DTI showed significantly reduced FA in the genu and rostral body of the anterior corpus callosum in cocaine-dependent subjects compared to controls. Cocaine-dependent subjects also had significantly higher BIS-11 scores, greater impulsive (commission) errors, and reduced ability to discriminate target from catch stimuli (discriminability) on the IMT/DMT. Within cocaine dependent subjects there was a significant negative correlation between FA in the anterior corpus callosum and behavioral laboratory measured impulsivity, and there was a positive correlation between FA and discriminability. The finding that reduced integrity of anterior corpus callosum white matter in cocaine users is related to impaired impulse control and reduced ability to discriminate between target and catch stimuli is consistent with prior theories regarding frontal cortical involvement in impaired inhibitory control in cocaine-dependent subjects.

Adult↗

PubMed2005

Increased impulsivity associated with severity of suicide attempt history in patients with bipolar disorder.

BACKGROUND: Impulsivity is a prominent and measurable characteristic of bipolar disorder that can contribute to risk for suicidal behavior. The purpose of this study was to investigate the relationship between impulsivity and severity of past suicidal behavior, a potential predictor of eventual suicide, in patients with bipolar disorder. METHOD: In bipolar disorder subjects with either a definite history of attempted suicide or no such history, impulsivity was assessed with both a questionnaire (Barratt Impulsiveness Scale) and behavioral laboratory performance measures (immediate memory/delayed memory tasks). Diagnosis was determined with the Structured Clinical Interview for DSM-IV. Interviews of patients and review of records were used to determine the number of past suicide attempts and the medical severity of the most severe attempt. RESULTS: Subjects with a history of suicide attempts had more impulsive errors on the immediate memory task and had shorter response latencies, especially for impulsive responses. Impulsivity was highest in subjects with the most medically severe suicide attempts. Effects were not accounted for by presence of depression or mania at the time of testing. Barratt Impulsiveness Scale scores were numerically, but not significantly, higher in subjects with suicide attempts. A history of alcohol abuse was associated with greater probability of a suicide attempt. Multivariate analysis showed that ethanol abuse history and clinical state at the time of testing did not have a significant effect after impulsivity was taken into account. DISCUSSION: These results suggest that a history of severe suicidal behavior in patients with bipolar disorder is associated with impulsivity, manifested as a tendency toward rapid, unplanned responses.

Adult↗

PubMed2004

Functional MRI study of working memory in MDMA users.

RATIONALE: Methylene-dioxymethamphetamine (MDMA) is known to cause degeneration of serotonin nerve terminals after acute doses in animals. Similarly, behavioral studies in human MDMA users regularly find abnormalities in memory, mood, and impulse control. However, studies of brain function using brain imaging in MDMA users have been less consistent. OBJECTIVES: The purpose of this study was to determine, using functional magnetic resonance imaging (fMRI), whether individuals with a self-reported history of MDMA use would differ from non-MDMA using controls on activation while performing a working memory task. METHODS: Fifteen MDMA using subjects and 19 non-MDMA using controls underwent fMRI scanning while performing the immediate and delayed memory task (IMT/DMT). The study was based on a block design in which the delayed memory task (DMT) alternated with the immediate memory task (IMT), which served as a control condition. FMRI scans were acquired on a 1.5 T scanner, using a gradient echo echoplanar pulse sequence. RESULTS: Random effects SPM99 analysis showed significantly greater activation (whole volume corrected cluster P<0.05) during the DMT relative to the IMT in the MDMA subjects compared with the control subjects in the medial superior frontal gyrus, in the thalamus extending into putamen, and in the hippocampus. CONCLUSIONS: Although these effects could be due to other drugs used by MDMA users, these results are consistent with behavioral problems that are associated with MDMA use, and with animal studies on the effects of MDMA on brain function.

Adult↗

PubMed2003

Effects of methylphenidate on impulsive choice in adult humans.

RATIONALE: Several studies with nonhumans and humans have shown that stimulants decrease impulsive choices on delay-to-reinforcement (self-control) procedures. Little is known, however, about the effects of the stimulant methylphenidate on choice for delayed reinforcers in humans. OBJECTIVES: The present study was designed to investigate the effects of acute methylphenidate administrations on impulsive responding in adult humans on a delay-to-reinforcement task. METHODS: Eleven adult males with a history of criminal behavior but no history of attention-deficit hyperactivity disorder (ADHD) participated. Impulsive responding was measured using an adjusting-delay procedure in which subjects were presented with repeated choices between a small amount of money delivered after a short delay and a larger amount of money delivered after a delay that adjusted as a function of previous choices. Subjects were exposed to four experimental sessions each day of participation and 60 min prior to the first daily session received placebo or 0.15, 0.30, or 0.60 mg/kg methylphenidate. Stable choice patterns were re-established between each methylphenidate dose. RESULTS: Individuals differed in their sensitivity to methylphenidate, but in over half of the subjects methylphenidate decreased impulsive (i.e., increased the number of self-control choices) and increased the delay to the large reinforcer. The largest increases in self-control choices tended to occur at the 0.30-mg/kg and 0.60-mg/kg doses, and the effects often persisted across multiple daily sessions. In six subjects, under at least one methylphenidate dose, the number of impulsive choices decreased to zero. CONCLUSIONS: Acute methylphenidate administrations tended to decrease the number of impulsive choices in adult humans on an adjusting-delay procedure, although there were substantial individual differences in the sensitivity of choice to methylphenidate. In no case, however, did methylphenidate increase impulsive choices. These results are consistent with several recent laboratory studies with nonhumans and humans showing that stimulants increase preference for large, delayed reinforcers.

Adolescent↗

PubMed2002

Acute effects of baclofen, a gamma-aminobutyric acid-B agonist, on laboratory measures of aggressive and escape responses of adult male parolees with and without a history of conduct disorder.

RATIONALE: The possible role of gamma-aminobutyric acid (GABA) in human aggression was evaluated by administering baclofen, a GABA-B agonist and comparing the effects on laboratory measures of aggression and escape among subjects with and without a history of conduct disorder. METHODS: Twenty male subjects with a history of criminal behavior participated in experimental sessions, which measured aggressive and escape responses. Ten subjects had a history of childhood conduct disorder (CD+) and ten control subjects had no history of CD. Aggression was measured using the point subtraction aggression paradigm (PSAP), which provides subjects with aggressive, escape, and monetary-reinforced response options. RESULTS: Acute doses (0.07, 0.14 and 0.28 mg/kg) of baclofen had remarkably different effects on aggressive responses among CD+ subjects relative to control subjects. Aggressive responses of CD+ subjects decreased, while aggressive responses of control subjects increased following baclofen administration. Baclofen decreased escape responses for both CD+ and control subjects. No changes in monetary-reinforced responses were observed, indicative of no central nervous system stimulation or sedation. CONCLUSIONS: The GABA-B agonist baclofen suppressed aggressive responses in subjects with a history of childhood CD, while producing the opposite effect in control subjects. These suggest a possible unique role for GABA in the regulation of aggression in CD+ population.

Adult↗

PubMed2001

Effects of chronic paroxetine administration on measures of aggressive and impulsive responses of adult males with a history of conduct disorder.

RATIONALE: The role of serotonin in human aggression and impulsivity was evaluated by administering paroxetine or placebo for 3 weeks and comparing the effects on laboratory measures of aggression and impulsivity among male subjects with a history of conduct disorder. METHODS: Twelve male subjects with a history of criminal behavior participated in experimental sessions, which measured aggressive and impulsive responses. Six subjects were assigned to placebo treatment and six subjects to placebo and paroxetine treatment. Aggression was measured using the point subtraction aggression paradigm (PSAP), which provides subjects with an aggressive and monetary reinforced response options. Impulsive responses were measured using a paradigm that gives subjects choices between small rewards after short delays versus larger rewards after longer delays. RESULTS: Chronic administration of paroxetine (20 mg/day) for 21 days produced significant decreases in impulsive responses. Decreases in aggressive responses were evident only at the end of paroxetine treatment. Decreases in impulsive and aggressive responses could not be attributed to a non-specific sedative action because monetary reinforced responses were not decreased as has been observed following CNS sedation. CONCLUSIONS: Inhibition of serotonin reuptake by paroxetine is the possible mechanism for reductions in aggressive and impulsive responses. These results support other data linking serotonin function and aggression and impulsivity.

Administration, Oral↗

PubMedDate not supplied

Altered brain activation during cognitive control in patients with moderate to severe traumatic brain injury.

BACKGROUND: Persistent deficits in cognitive control have been documented following traumatic brain injury (TBI) but are inconsistently related to the presence and location of focal lesions. OBJECTIVE: Functional magnetic resonance imaging (fMRI) was used to examine brain activation during a cognitive control task in patients with moderate to severe TBI or orthopedic injury (OI). METHODS: Fourteen TBI patients and 10 OI patients underwent fMRI at 3 months postinjury using a stimulus-response compatibility task in which response accuracy and reaction time were measured. Performance between the groups was equated by individually adjusting the amount of training. Groups did not differ in age, gender, or education. RESULTS: Brain activation during stimulus-response incompatibility was greater in TBI patients than in OI patients within the cingulate, medial frontal, middle frontal, and superior frontal gyri. However, the positive regression of activation with response accuracy during stimulus-response incompatibility indicated a stronger relationship for OI patients than the TBI group within the anterior cingulate gyrus, medial frontal, and parietal regions, as well as deep brain structures (eg, brainstem). The number of focal lesions within either the whole brain or within prefrontal areas was not related to brain activation, but there was a relationship between activation and TBI severity. CONCLUSIONS: These findings suggest that neural networks mediating cognitive control are altered after moderate to severe TBI, possibly as a result of diffuse axonal injury, and that the typical relationship of brain activation to performance is disrupted.

Adolescent↗