Elise E. DeVito

The Effects of Methylphenidate on Decision Making in Attention- Deficit/Hyperactivity Disorder

Background Children with attention-deficit/hyperactivity disorder (ADHD) frequently display poor judgment and risk taking in their everyday behavior, but there are little empirical data on decision-making cognition in this disorder. The objectives of the study were to assess the effects of stimulant medication on decision making in ADHD and compare performance on the Cambridge Gamble Task between boys with and without ADHD. Methods Twenty-one boys (aged 7–13) diagnosed with ADHD underwent a double-blind, placebo-controlled trial of methylphenidate (.5 mg/kg) during which they performed the Cambridge Gamble Task (CGT). A healthy age-matched control group was tested on two occasions off drug. Results The ADHD group bet more conservatively on the methylphenidate session than on the placebo session. In comparison with healthy control subjects, the ADHD group made more poor decisions, placed their bets more impulsively, and adjusted their bets less according to the chances of winning. Poor decision making was correlated with parent-reported symptoms and disruptive behavior in the ADHD group. Conclusions Methylphenidate reduced risk-prone betting behavior on the CGT. Compared with control subjects, children with ADHD display a number of decision-making deficits on the task, and the measure of rational decision making may serve as an ecologically valid neuropsychological marker of impairment.

A preliminary study of the neural effects of behavioral therapy for substance use disorders

BACKGROUND The mechanisms by which behavioral therapies for substance use disorders (SUDs) exert their effects and the components of treatment that contribute most to substance use outcome remain unclear. Disruptions to aspects of impulse control and attention have been hypothesized to contribute to the development and maintenance of addiction; moreover, alterations in these processes may underlie responses to treatment. METHODS Individuals participating in a randomized clinical trial evaluating computer-assisted cognitive behavioral therapy (CBT) for substance abuse participated in fMRI Stroop before and after treatment. A non-substance-using comparison group performed the same task under test-retest conditions. RESULTS The patient group demonstrated decreased Stroop-related BOLD signal in regions including the anterior cingulate, inferior frontal gyrus and midbrain at post-treatment relative to pre-treatment, and displayed a greater decrease in the subthalamic nucleus and surrounding regions compared to healthy controls following test-retest. CONCLUSIONS Behavioral therapies may be associated with reduction in substance use and effects on neural systems involved in cognitive control, impulsivity, motivation and attention.

Reliance on habits at the expense of goal-directed control following dopamine precursor depletion

RationaleDopamine is well known to play an important role in learning and motivation. Recent animal studies have implicated dopamine in the reinforcement of stimulus–response habits, as well as in flexible, goal-directed action. However, the role of dopamine in human action control is still not well understood.ObjectivesWe present the first investigation of the effect of reducing dopamine function in healthy volunteers on the balance between habitual and goal-directed action control.MethodsThe dietary intervention of acute dietary phenylalanine and tyrosine depletion (APTD) was adopted to study the effects of reduced global dopamine function on action control. Participants were randomly assigned to either the APTD or placebo group (ns = 14) to allow for a between-subjects comparison of performance on a novel three-stage experimental paradigm. In the initial learning phase, participants learned to respond to different stimuli in order to gain rewarding outcomes. Subsequently, an outcome-devaluation test and a slips-of-action test were conducted to assess whether participants were able to flexibly adjust their behaviour to changes in the desirability of the outcomes.ResultsAPTD did not prevent stimulus–response learning, nor did we find evidence for impaired response–outcome learning in the subsequent outcome-devaluation test. However, when goal-directed and habitual systems competed for control in the slips-of-action test, APTD tipped the balance towards habitual control. These findings were restricted to female volunteers.ConclusionsWe provide direct evidence that the balance between goal-directed and habitual control in humans is dopamine dependent. The results are discussed in light of gender differences in dopamine function and psychopathologies.

White Matter Integrity is Associated with Treatment Outcome Measures in Cocaine Dependence

Cocaine dependence is associated with white matter impairments that may compromise cognitive function and hence drug users’ abilities to engage in and benefit from treatment. The main aim of this study was to assess whether white matter integrity correlates with treatment outcome measures in cocaine dependence. Diffusion tensor imaging (DTI) was used to assess the white matter (WM) of 16 treatment-seeking cocaine-dependent patients before 8 weeks of therapy. The measures for treatment outcome were longest self-reported duration of continuous cocaine abstinence, percent of urine screens negative for cocaine, and duration (weeks) of treatment retention. Correlations between treatment outcome measures and DTI parameters (fractional anisotropy (FA), longitudinal eigenvalue (λ1), perpendicular eigenvalue (λT), and mean diffusivity (MD)) were analyzed. Longest self-reported abstinence from cocaine and percent of cocaine-negative urine samples during treatment positively correlated with FA values and negatively correlated with λ1, λT, and MD values across extensive brain regions including the corpus callosum, frontal, parietal, temporal, and occipital lobes, and cerebellum. The findings of an association between better WM integrity at treatment onset and longer abstinence suggest that strategies for improving WM integrity warrant consideration in developing new interventions for cocaine dependence.

The neuropsychology of normal pressure hydrocephalus (NPH).

Normal pressure hydrocephalus (NPH) accounts for one of the few known forms of reversible dementia. Varied aetiology and clinical presentation contribute to difficulties with early or differential diagnoses, and delayed surgical treatment may be less efficacious. Clinical neuropsychology provides a means of determining a cognitive profile for NPH, assisting in differential diagnosis, tracking the disorders progression and assessing the efficacy of treatment. This article will review possible applications of clinical neuropsychology and propose a clinical assessment protocol for NPH.

Neural Correlates of Impulsivity in Healthy Males and Females with Family Histories of Alcoholism

Individuals family-history positive (FHP) for alcoholism have increased risk for the disorder, which may be mediated by intermediate behavioral traits such as impulsivity. Given the sex differences in the risk for and clinical presentation of addictive disorders, risk for addiction may be differentially mediated by impulsivity within FHP males and females. FHP (N=28) and family-history negative (FHN, N=31) healthy, non-substance-abusing adults completed an fMRI Go/No-Go task and were assessed on impulsivity and alcohol use. Effects of family history and sex were investigated as were associations between neural correlates of impulse control and out-of-scanner measures of impulsivity and alcohol use. FHP individuals showed greater activation in the left anterior insula and inferior frontal gyrus during successful inhibitions, an effect that was driven primarily by FHP males. Higher self-reported impulsivity and behavioral discounting impulsivity, but not alcohol use measures, were associated with greater BOLD signal in the region that differentiated the FHP and FHN groups. Impulsivity factors were associated with alcohol use measures across the FHP and FHN groups. These findings are consistent with increased risk for addiction among FHP individuals being conferred through disrupted function within neural systems important for impulse control.

Gender differences in a clinical trial for prescription opioid dependence

Although gender differences in substance use disorders have been identified, few studies have examined gender differences in prescription drug dependence. The aim of this study was to examine gender differences in clinical characteristics and treatment outcomes in a large clinical trial for prescription opioid dependence. Despite no pre-treatment differences in opioid dependence severity, women reported significantly greater functional impairment, greater psychiatric severity, and higher likelihood of using opioids to cope with negative affect and pain than men. Women were also more likely than men to have first obtained opioids via a legitimate prescription and to use opioids via the intended route of administration. Men reported significantly more alcohol problems than women. There were no significant gender differences in medication dose, treatment retention, or opioid outcomes. Thus, despite the presence of pre-treatment gender differences in this population, once the study treatment was initiated, women and men exhibited similar opioid use outcomes.

Subjective, Physiological, and Cognitive Responses to Intravenous Nicotine: Effects of Sex and Menstrual Cycle Phase

Nicotine dependence is a serious public health concern. Optimal treatment of nicotine dependence will require greater understanding of the mechanisms that contribute to the maintenance of smoking behaviors. A growing literature indicates sex and menstrual phase differences in responses to nicotine. The aim of this study was to assess sex and menstrual phase influences on a broad range of measures of nicotine response including subjective drug effects, cognition, physiological responses, and symptoms of withdrawal, craving, and affect. Using a well-established intravenous nicotine paradigm and biochemical confirmation of overnight abstinence and menstrual cycle phase, analyses were performed to compare sex (age 18–50 years; 115 male and 45 female) and menstrual cycle phase (29 follicular and 16 luteal) effects. Females had diminished subjective drug effects of, but greater physiological responses to, nicotine administration. Luteal-phase females showed diminished subjective drug effects and better cognition relative to follicular-phase women. These findings offer candidate mechanisms through which the luteal phase, wherein progesterone is dominant relative to estradiol, may be protective against vulnerability to smoking.

Toward empirical identification of a clinically meaningful indicator of treatment outcome: features of candidate indicators and evaluation of sensitivity to treatment effects and relationship to one year follow up cocaine use outcomes.

BACKGROUND Selection of an appropriate indictor of treatment response in clinical trials is complex, particularly for the various illicit drugs of abuse. Most widely used indicators have been selected based on expert group recommendation or convention rather than systematic empirical evaluation. Absence of an evidence-based, clinically meaningful index of treatment outcome hinders cross-study evaluations necessary for progress in addiction treatment science. METHOD Fifteen candidate indicators used in multiple clinical trials as well as some proposed recently are identified and discussed in terms of relative strengths and weaknesses (practicality, cost, verifiability, sensitivity to missing data). Using pooled data from five randomized controlled trials of cocaine dependence (N=434), the indicators were compared in terms of sensitivity to the effects of treatment and relationship to cocaine use and general functioning during follow-up. RESULTS Commonly used outcome measures (percent negative urine screens; percent days of abstinence) performed relatively well in that they were sensitive to the effects of the therapies evaluated. Others, including complete abstinence and reduction in frequency of use, were less sensitive to effects of specific therapies and were very weakly related to cocaine use or functioning during follow-up. Indicators more strongly related to cocaine use during follow-up were those that reflected achievement of sustained periods of abstinence, particularly at the end of treatment. CONCLUSIONS These analyses did not demonstrate overwhelming superiority of any single indicator, but did identify several that performed particularly poorly. Candidates for elimination included retention, complete abstinence, and indicators of reduced frequency of cocaine use.

A preliminary investigation of Stroop-related intrinsic connectivity in cocaine dependence: associations with treatment outcomes.

Abstract Background: Cocaine-dependent individuals demonstrate neural and behavioral differences compared to healthy comparison subjects when performing the Stroop color-word interference test. Stroop measures also relate to treatment outcome for cocaine dependence. Intrinsic connectivity analyses assess the extent to which task-related regional brain activations are related to each other in the absence of defining a priori regions of interest. Objective: This study examined 1) the extent to which cocaine-dependent and non-addicted individuals differed on measures of intrinsic connectivity during fMRI Stroop performance; and 2) the relationships between fMRI Stroop intrinsic connectivity and treatment outcome in cocaine dependence. Methods: Sixteen treatment-seeking cocaine-dependent patients and matched non-addicted comparison subjects completed an fMRI Stroop task. Between-group differences in intrinsic connectivity were assessed and related to self-reported and urine-toxicology-based cocaine-abstinence measures. Results: Cocaine-dependent patients vs. comparison subjects showed less intrinsic connectivity in cortical and subcortical regions. When adjusting for individual degree of intrinsic connectivity, cocaine-dependent vs. comparison subjects showed relatively greater intrinsic connectivity in the ventral striatum, putamen, inferior frontal gyrus, anterior insula, thalamus and substantia nigra. Non-mean-adjusted intrinsic-connectivity measures in the midbrain, thalamus, ventral striatum, substantia nigra, insula and hippocampus negatively correlated with measures of cocaine abstinence. Conclusion: The diminished intrinsic connectivity in cocaine-dependent vs. comparison subjects suggests poorer communication across brain regions during cognitive-control processes. In mean-adjusted analyses, the cocaine-dependent group displayed relatively greater Stroop-related connectivity in regions implicated in motivational processes in addictions. The relationships between treatment outcomes and connectivity in the midbrain and basal ganglia suggest that connectivity represents a potential treatment target.