Biomedical subjects

Monique Ernst

Publications and source records attributed to Monique Ernst.

At least 37 records · Page 2Linked to original sources

PubMed2005

Brain activity in cigarette smokers performing a working memory task: effect of smoking abstinence.

BACKGROUND: When nicotine-dependent human subjects abstain from cigarette smoking, they exhibit deficits in working memory. An understanding of the neural substrates of such impairments may help to understand how nicotine affects cognition. Our aim, therefore, was to identify abnormalities in the circuitry that mediates working memory in nicotine-dependent subjects after they initiate abstinence from smoking. METHODS: We used blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study eight smokers while they performed a letter version of the N-Back working memory task under satiety (< or = 1.5 hours abstinence) and abstinence (> or = 14 hours abstinence) conditions. RESULTS: Task-related activity in the left dorsal lateral prefrontal cortex (DLPFC) showed a significant interaction between test session (satiety, abstinence) and task load (1-back, 2-back, and 3-back). This interaction reflected the fact that task-related activity in the satiety condition was relatively low during performance of the 1-back task but greater at the more difficult task levels, whereas task-related activity in the abstinence condition was relatively high at the 1-back level and did not increase at the more difficult task levels. CONCLUSIONS: We conclude that neural processing related to working memory in the left DLPFC is less efficient during acute abstinence from smoking than at smoking satiety.

Adult↗

PubMed2005

Cognitive control under contingencies in anxious and depressed adolescents: an antisaccade task.

BACKGROUND: Emotion-related perturbations in cognitive control characterize adult mood and anxiety disorders. Fewer data are available to confirm such deficits in youth. Studies of cognitive control and error processing can provide an ideal template to examine these perturbations. Antisaccade paradigms are particularly well suited for this endeavor because they provide exquisite behavioral measures of modulation of response errors. METHODS: A new monetary reward antisaccade task was used with 28 healthy, 11 anxious, and 12 depressed adolescents. Performance accuracy, saccade latency, and peak velocity of incorrect responses were analyzed. RESULTS: Performance accuracy across all groups was improved by incentives (obtain reward, avoid punishment). However, modulation of saccade errors by incentives differed by groups. In incentive trials relative to neutral trials, inhibitory efficiency (saccade latency) was enhanced in healthy, unaffected in depressed, and diminished in anxious adolescents. Modulation of errant actions (saccade peak velocity) was improved in the healthy group and unchanged in both the anxious and depressed groups. CONCLUSIONS: These findings provide grounds for testing hypotheses related to the impact of motivation deficits and emotional interference on directed action in adolescents with mood and anxiety disorders. Furthermore, neural mechanisms can now be examined by using this task paired with functional neuroimaging.

Adolescent↗

PubMed2005

Working memory in cigarette smokers: comparison to non-smokers and effects of abstinence.

The present study was designed to examine the effect of cigarette smoking and withdrawal on working memory. Participants included 15 smokers and 22 matched non-smokers. For both groups the N-Back Task (of working memory) was administered in two test blocks on each of two days. On one day, smokers were tested after >or=13 h abstinence; on the other day, testing began or=13 h but not <or=1 h abstinence was significantly less accurate than that of non-smokers. A within-subject comparison revealed that in the abstinence session, smokers had significantly longer response latencies (in the 2-back condition) and made more overall errors compared to the satiety session. Smoking between test blocks in the abstinence session did not significantly affect performance although it significantly reduced craving. These findings provide further evidence for a deficit in working memory associated with acute abstinence from smoking, which may contribute to the difficulty of smoking cessation.

Adult↗

PubMed2005

Selective reduction in amygdala volume in pediatric anxiety disorders: a voxel-based morphometry investigation.

BACKGROUND: Significant controversy has emerged concerning pediatric anxiety disorders. Some researchers question the justification for diagnosing and treating pediatric anxiety disorders, owing to concerns about the inappropriate medicalization of social problems. Others note the importance of diagnosis and treatment, given that pediatric anxiety disorders represent a strong risk factor for serious adult mental disorders. We examine the neural correlates of pediatric anxiety disorders, to consider the validity of the categorization scheme used in recent treatment studies. METHODS: Using inclusion criteria derived from recent treatment trials, we compared gray matter volume throughout the brain in children with and without anxiety. Morphometric analyses used optimized voxel-based morphometry, an automated method for examining structural changes throughout the brain. RESULTS: Reductions in left amygdala gray matter volume were noted for patients with anxiety disorders relative to comparison subjects. CONCLUSIONS: We discuss implications of these findings for current controversies.

Adolescent↗

PubMed2005

Amygdala and nucleus accumbens in responses to receipt and omission of gains in adults and adolescents.

Adolescents' propensity for risk-taking and reward-seeking behaviors suggests a heightened sensitivity for reward, reflected by greater feedback-related activity changes in reward circuitry (e.g., nucleus accumbens), and/or a lower sensitivity to potential harm reflected by weaker feedback-related activity changes in avoidance circuitry (e.g., amygdala) relative to adults. Responses of nucleus accumbens and amygdala to valenced outcomes (reward receipt and reward omission) were assayed using an event-related functional magnetic resonance imaging procedure paired with a monetary reward task in 14 adults and 16 adolescents. Bilateral amygdala and nucleus accumbens showed significantly greater activation when winning than when failing to win in both groups. Group comparisons revealed stronger activation of left nucleus accumbens by adolescents, and of left amygdala by adults. When examining responses to reward receipts and to reward omissions separately, the most robust group difference was within the amygdala during reward omission. The reduction of the fMRI BOLD signal in the amygdala in response to reward omission was larger for adults than for adolescents. Correlations showed a close link between negative emotion and amygdala decreased BOLD signal in adults, and between positive emotion and nucleus accumbens activation in adolescents. Overall, these findings support the notion that the signal differences between positive and negative outcomes involve the nucleus accumbens more in adolescents than in adults, and the amygdala more in adults than in adolescents. These developmental differences, if replicated, may have important implications for the development of early-onset disorders of emotion and motivation.

Adolescent↗

PubMed2005

Cognitive performance and autonomic reactivity in abstinent drug abusers and nonusers.

In this study the authors compared the performance of abstinent drug abusers (n = 21) and nonuser control participants (n = 20) in neurocognitive and emotional functions by use of the Rogers Decision Making Task, Gambling Task, Emotional Stroop, impulsivity continuous performance task (CPT), and vigilance CPT. Skin conductance (SC) and heart rate (HR) monitoring was synchronized with task performance. Groups showed similar performance for vigilance, impulsivity, and emotional interference; however, drug abusers showed stronger SC responses. Drug abusers performed more poorly on the Gambling and Rogers Decision Making Tasks. When making risky decisions, drug abusers showed significantly less increase in SC activity than controls and exhibited lower HRs throughout performance on all tasks. In conclusion, complex tasks involving decision making, sensitivity to consequences, and emotional regulation discriminated between drug abusers and controls.

Adult↗

PubMed2005

Emotion recognition deficits in pediatric anxiety disorders: implications for amygdala research.

INTRODUCTION: Anxiety disorders in adults involve aberrant processing of emotional information that is hypothesized to reflect perturbations in the amygdala. This study examines the relationship between face-emotion recognition and anxiety in a sample of children and adolescents participating in a brain-imaging study of amygdala structure and function. METHODS: This study recruited 15 children and adolescents with ongoing anxiety disorders and 11 psychiatrically healthy comparisons group-matched on age, gender, and IQ. Face-emotion recognition was assessed using the Diagnostic Analysis of Nonverbal Accuracy Scale (DANVA). RESULTS: Children and adolescents with anxiety disorders exhibited significantly poorer performance on the face-emotion recognition task compared to healthy controls (z = 2.2; p < 0.05). This difference was found only for expressions posed by adults but not children. DISCUSSION: Reduced accuracy on a face-emotion recognition test is consistent with perturbed amygdala function in pediatric anxiety disorders. CONCLUSION: As this study was conducted in a sample undergoing a neuroimaging investigation of amygdala integrity, future analyses will examine associations among amygdala function, clinical anxiety, and face-recognition abilities.

Adolescent↗

PubMed2005

Evidence for a gene-environment interaction in predicting behavioral inhibition in middle childhood.

Gene-environment interactions are presumed to shape human behavior during early development. However, no human research has demonstrated that such interactions lead to stable individual differences in fear responses. We tested this possibility by focusing on a polymorphism in the promoter region of the gene for the serotonin transporter (5-HTT). This polymorphism has been linked to many indices of serotonin activity. Specifically, we tested the hypothesis that an interaction between children's 5-HTT status and maternal reports of social support predicts inhibited behavior with unfamiliar peers in middle childhood. Results were consistent with this hypothesis: Children with the combination of the short 5-HTT allele and low social support had increased risk for behavioral inhibition in middle childhood.

Child↗

PubMed2005

Attention bias to threat in maltreated children: implications for vulnerability to stress-related psychopathology.

OBJECTIVE: Previous research in adults implicates attention bias in posttraumatic stress disorder (PTSD). To study attention bias in children, the authors used picture-based versions of the visual-probe attention bias task previously used with adults. They tested the hypothesis that attention bias to threatening facial photographs is associated with maltreatment and PTSD. METHOD: A visual-probe task that manipulated threat levels was used to test 34 children who had been maltreated and 21 children who had not been maltreated. The visual-probe task involved showing photographs of actors with faces depicting neutral, angry/threatening, or happy expressions for 500 msec each. RESULTS: Attention bias away from threat was associated with severity of physical abuse and diagnosis of PTSD. This association reflected the tendency for high levels of abuse or PTSD to predict attention avoidance of threatening faces. CONCLUSIONS: Previous studies examined the engagement of specific brain regions associated with attention orientation to angry/threatening faces. The current study used similar methods to document associations between attention bias and maltreatment in children. This sets the stage for studies examining relationships in children among perturbed brain function, psychopathology, attention bias, and maltreatment.

Adolescent↗

PubMed2005

Safety and efficacy of the nicotine patch and gum for the treatment of adolescent tobacco addiction.

OBJECTIVES: To determine the safety and efficacy of the nicotine patch and gum for adolescents who want to quit smoking. DESIGN: Double-blind, double-dummy, randomized, 3-arm trial with a nicotine patch (21 mg), nicotine gum (2 and 4 mg), or a placebo patch and gum; all participants received cognitive-behavioral group therapy. SETTING: Inner-city, outpatient clinic on the East Coast. Subjects. Thirteen- to 17-year-old adolescents who smoked > or =10 cigarettes per day (CPD), scored > or =5 on the Fagerstrom Test of Nicotine Dependence, and were motivated to quit smoking. Intervention. Twelve weeks of nicotine patch or gum therapy with cognitive-behavioral therapy, with a follow-up visit at 6 months (3 months after the end of treatment). MAIN OUTCOME MEASURES: Safety assessed on the basis of adverse event reports for all 3 groups, prolonged abstinence, assessed through self-report and verified with exhaled carbon monoxide (CO) levels of < or =6 ppm, in intent-to-treat analyses, and smoking reduction (CPD and thiocyanate concentrations) among trial completers. RESULTS: A total of 120 participants were randomized (72% white, 70% female; age: 15.2 +/- 1.33 years; smoking: 18.8 +/- 8.56 CPD; Fagerstrom Test of Nicotine Dependence score: 7.04 +/- 1.29) from 1999 to 2003. Participants started smoking at 11.2 +/- 1.98 years of age and had been smoking daily for 2.66 +/- 1.56 years; 75% had at least 1 current psychiatric diagnosis. Mean compliance across groups was higher for the patch (mean: 78.4-82.8%) than for the gum (mean: 38.5-50.7%). Both the patch and gum were well tolerated, and adverse events were similar to those reported in adult trials. Changes in mean saliva cotinine concentrations throughout treatment were not statistically significant. Intent-to-treat analyses of all randomized participants showed CO-confirmed prolonged abstinence rates of 18% for the active-patch group, 6.5% for the active-gum group, and 2.5% for the placebo group; the difference between the active-patch and placebo arms was statistically significant. There was no significant effect of patch versus gum or gum versus placebo on cessation outcomes. Abstinence rates at the 3-month follow-up assessment were sustained but were not significantly associated with treatment group. Mean smoking rates, but not CO or thiocyanate concentrations, decreased significantly in all 3 arms but not as a function of treatment group. CONCLUSIONS: Nicotine patch therapy combined with cognitive-behavioral intervention was effective, compared with placebo, for treatment of tobacco dependence among adolescent smokers. Decreases in the numbers of cigarettes smoked appeared to be offset by compensatory smoking. Additional study of nicotine gum, with enhanced instructional support, is needed to assess its efficacy among adolescent smokers.

Administration, Cutaneous↗

PubMed2004

Experience-dependent plasticity for attention to threat: Behavioral and neurophysiological evidence in humans.

Biased attention to threat represents a key feature of anxiety disorders. This bias is altered by therapeutic or stressful experiences, suggesting that the bias is plastic. Charting on-line behavioral and neurophysiological changes in attention bias may generate insights on the nature of such plasticity. We used an attention-orientation task with threat cues to examine how healthy individuals alter their response over time to such cues. In Experiments 1 through 3, we established that healthy individuals demonstrate an increased attention bias away from threat over time. For Experiment 3, we used functional magnetic resonance imaging to determine the neural bases for this phenomenon. Gradually increasing attention bias away from threat is associated with increased activation in the occipitotemporal cortex. Examination of plasticity of attention bias with individuals at risk for anxiety disorders may reveal how threatening stimuli come to be categorized differently in this population over time.

Adolescent↗

PubMed2004

A developmental examination of gender differences in brain engagement during evaluation of threat.

BACKGROUND: Females appear to be more sensitive and responsive to social cues, including threat signals, than are males. Recent theoretical models suggest that developmental changes in brain functioning play important roles in the emergence of such gender differences. METHODS: We used functional magnetic resonance imaging to examine developmental and gender differences in activation of neural structures thought to mediate attention to emotional faces depicting varying degrees of threat. Analyses focused on the orbitofrontal cortex, amygdala, and anterior cingulate cortex during the evaluation of threat conveyed by faces. Healthy adolescents (n = 17; 53% male) and adults (n = 17; 53% male) were scanned while they rated how threatening pictures of neutral and emotional (angry, fearful, or happy) faces appeared. RESULTS: Results indicate significant interactions among age, gender, and face type for activation during explicit threat monitoring. In particular, adult women activated orbitofrontal cortex and amygdala selectively to unambiguous threat (angry) cues, while adult men showed a less discriminating pattern of activation. No gender differences were evident for adolescents, who as a group resembled adult males. CONCLUSIONS: These findings suggest that there are gender differences in patterns of neural responses to emotional faces that are not fully apparent until adulthood.

Adolescent↗

PubMed2004

Reward-related processes in pediatric bipolar disorder: a pilot study.

BACKGROUND: Neuropsychological research on children with bipolar disorder (BPD) is scarce. Here, we examine reward-related behaviors in children with BPD using a Wheel of Fortune task in which subjects could win or lose money depending on their decisions. The intent of this work was to investigate performance differences between BPD and healthy children on a task that could be used in an fMRI environment to inform the neural substrates of reward processes in BPD. This study has no direct clinical implications. We hypothesized that relative to healthy children, children with BPD would select risky options more frequently, be less confident in a favorable outcome, and report stronger emotional responses to outcomes. METHODS: Forty-four children (22 BPD; 22 control) were compared on (i) decision-making with varying levels of risk, (ii) level of confidence in favorable outcomes, and (iii) responses to feedback. The task included a win-no win version and a lose-no lose version. RESULTS: Patterns of selection did not differ between groups. In the lose-no lose task, BPD patients were less confident than controls in favorable outcomes. BPD patients expressed greater dissatisfaction than controls at not winning in win-no win, and greater satisfaction than controls at not losing in lose-no lose. LIMITATIONS: Limitations of this study included that the children with BPD were mostly in a depressed state, were medicated, and had co-morbid disorders. CONCLUSIONS: This is the first experimental study to examine associations between pediatric BPD and reward-related behaviors. Although we failed to detect abnormalities in risky decision-making in children with BPD, we found significant differences between groups in both confidence ratings and response to feedback, consistent with our predictions. Our ultimate goal is to use this task in the fMRI environment to gain a better understanding of the neural correlates of reward-related processes in pediatric BPD.

Adolescent↗

PubMed2004

Choice selection and reward anticipation: an fMRI study.

We examined neural activations during decision-making using fMRI paired with the wheel of fortune task, a newly developed two-choice decision-making task with probabilistic monetary gains. In particular, we assessed the impact of high-reward/risk events relative to low-reward/risk events on neural activations during choice selection and during reward anticipation. Seventeen healthy adults completed the study. We found, in line with predictions, that (i) the selection phase predominantly recruited regions involved in visuo-spatial attention (occipito-parietal pathway), conflict (anterior cingulate), manipulation of quantities (parietal cortex), and preparation for action (premotor area), whereas the anticipation phase prominently recruited regions engaged in reward processes (ventral striatum); and (ii) high-reward/risk conditions relative to low-reward/risk conditions were associated with a greater neural response in ventral striatum during selection, though not during anticipation. Following an a priori ROI analysis focused on orbitofrontal cortex, we observed orbitofrontal cortex activation (BA 11 and 47) during selection (particularly to high-risk/reward options), and to a more limited degree, during anticipation. These findings support the notion that (1) distinct, although overlapping, pathways subserve the processes of selection and anticipation in a two-choice task of probabilistic monetary reward; (2) taking a risk and awaiting the consequence of a risky decision seem to affect neural activity differently in selection and anticipation; and thus (3) common structures, including the ventral striatum, are modulated differently by risk/reward during selection and anticipation.

Adult↗

PubMed2004

Prefrontal cortical dysfunction in abstinent cocaine abusers.

The anterior cingulate cortex (ACC) and lateral prefrontal (LPFC) cortex are brain regions important to executive cognitive functions (ECF). We determined ACC and LPFC function in 23-day abstinent cocaine abusers using positron emission tomography (PET H(2)(15)O) during performance of a modified version of the Stroop Task. Cocaine abusers showed less activation than non-drug-using comparison subjects in the left ACC and the right LPFC and greater activation in the right ACC. Average amount of cocaine used per week was negatively correlated with activity in the rostral ACC and right LPFC. Disruption of ECF in substance abusers could interfere with attempts to stop drug use and undermine treatment. Since impairment in ECF may be a common feature of various neuropsychiatric disorders, these findings have applicability beyond the neurobiology of addiction.

Adult↗

PubMed2003

2-[18F]F-A-85380: PET imaging of brain nicotinic acetylcholine receptors and whole body distribution in humans.

Noninvasive imaging of nicotinic acetylcholine receptors (nAChRs) in the human brain in vivo is critical for elucidating the role of these receptors in normal brain function and in the pathogenesis of brain disorders. Here we report the first in vivo visualization of human brain areas containing nAChRs by using PET and 2-[18F]fluoro-3-(2(S)azetidinylmethoxy)pyridine (2-[18F]FA). We acquired scans from six healthy non-smoking volunteers after i.v. bolus administration of 2-[18F]FA (1.6 MBq/kg or 0.043 +/- 0.002 mCi/kg). This dose was sufficient for visualizing nAChRs in the thalamus up to 5 h after injection. There were no adverse effects associated with administration of no-carrier-added 2-[18F]FA (1.3-10 pmol/kg). Consistent with the distribution of nAChRs in human brain, accumulated radioactivity was greatest in thalamus, intermediate in the midbrain, pons, cerebellum, and cortex; and least in white matter. As approximately 90% of the injected radioactivity was eliminated via the urine (biological half-life ca. 4 h), the urinary bladder wall received the highest radiation dose. The estimate of radiation dose equivalent to the urinary bladder wall (ca. 180 +/- 30 mSv/MBq or 0.7 rem/mCi with a 2.4 h void interval) suggests that multiple studies could be performed in a single subject. The results predict that quantitative PET imaging of nAChRs in human brain with 2-[18F]FA is feasible.

Azetidines↗

PubMed2003

A neuroimaging method for the study of threat in adolescents.

Little is understood about the brain basis of anxiety, particularly among youth. However, threat paradigms with animals are delineating the relationship between anxietylike behaviors and brain function. We adapted a threat paradigm for adolescents using functional magnetic resonance imaging. The aim was to examine amygdala activation to fear. The threat was an aversive air blast directed to the larynx. Participants were explicitly informed that they might receive the air blast when viewing one stimulus (threat condition) and would not receive the blast when viewing the other stimulus (safe condition). Participants provided fear ratings immediately after each trial. Based on the relatively mild nature of the air blast, we expected participants to report varying degrees of fear. Those who reported increased fear showed right amygdala activation during the threat condition and left amygdala activation in the safe condition. These procedures offer a promising tool for studying youth with anxiety disorders.

Adolescent↗

PubMed2003

Neuroimaging and mechanisms of drug abuse: interface of molecular imaging and molecular genetics.

Whereas ligand studies can inform the end-products of dysregulation of genetic expression, reporter gene imaging can provide the means to understand the genetic origin of these end-products. As with radioligand studies, in vivo direct measurement of gene expression will allow genetic processes to be monitored over time in the same subject, use of a subject as his/her own control in intervention studies (i.e., measurement before and after an intervention), and monitoring the spatial distribution of molecular events in the whole brain. Furthermore, reporter gene imaging, by advancing knowledge of the biologic mechanisms of disease states, has important clinical implications, particularly in the development and monitoring of treatments. We expect PET to play a prominent role in the elucidation of substance abuse mechanisms and contribute significantly to the development of innovative treatment strategies.

Brain↗