Biomedical subjects

Monique Ernst

Publications and source records attributed to Monique Ernst.

At least 19 recordsLinked to original sources

PubMed2007

Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder.

CONTEXT: Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues. OBJECTIVE: To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents. DESIGN: Case-control study. SETTING: Government clinical research institute. PARTICIPANTS: Fifteen adolescents with generalized anxiety disorder and 20 controls. MAIN OUTCOME MEASURES: Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging. During imaging, participants completed a face-emotion rating task that systematically manipulated attention. RESULTS: While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful faces than to happy faces in a distributed network including the amygdala, ventral prefrontal cortex, and anterior cingulate cortex (P<.05, small-volume corrected, for all). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, ventral prefrontal cortex, and anterior cingulate cortex. CONCLUSIONS: This is the first evidence in juveniles that generalized anxiety disorder-associated patterns of pathologic fear circuit activation are particularly evident during certain attention states. Specifically, fear circuit hyperactivation occurred in an attention state involving focus on subjectively experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping the function of the adolescent human fear circuit.

Adolescent↗

PubMed2006

Effect of cigarette smoking on prefrontal cortical function in nondeprived smokers performing the Stroop Task.

Some reports indicate that cigarette smoking can help smokers focus attention, even when they have not abstained from smoking for a substantial period of time (eg, >1 h). Understanding the mechanisms by which smoking affects attention may help in designing smoking cessation treatments. Thirteen nonsmokers and nine smokers participated in two tests of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI). During fMRI, the participants performed the Stroop Task. There was a 15-min break between the two tests. During the break, each smoker smoked one cigarette. For smokers, the first test began 45-60 min after the last cigarette of ad libitum smoking. The differences in BOLD signal changes between Stroop conditions (ie, incongruent minus congruent) showed a group x test interaction in the right precentral sulcus, including the putative human frontal eye field (FEF). Smokers, but not nonsmokers, showed greater changes (relative to rest) in BOLD signal in the incongruent than in the congruent condition in the first fMRI test but not in the second. Even after brief abstinence from smoking, therefore, smokers exhibit compromised functional efficiency in the right FEF and adjacent precentral sulcus in a test of selective attention; and smoking ameliorates this condition.

Adolescent↗

PubMed2006

Neural substrates of choice selection in adults and adolescents: development of the ventrolateral prefrontal and anterior cingulate cortices.

A heightened propensity for risk-taking and poor decision-making underlies the peak morbidity and mortality rates reported during adolescence. Delayed maturation of cortical structures during the adolescent years has been proposed as a possible explanation for this observation. Here, we test the hypothesis of adolescent delayed maturation by using fMRI during a monetary decision-making task that directly examines risk-taking behavior during choice selection. Orbitofrontal/ventrolateral prefrontal cortex (OFC/VLPFC) and dorsal anterior cingulate cortex (ACC) were examined selectively since both have been implicated in reward-related processes, cognitive control, and resolution of conflicting decisions. Group comparisons revealed greater activation in the OFC/VLPFC (BA 47) and dorsal ACC (BA 32) in adults than adolescents when making risky selections. Furthermore, reduced activity in these areas correlated with greater risk-taking performance in adolescents and in the combined group. Consistent with predictions, these results suggest that adolescents engage prefrontal regulatory structures to a lesser extent than adults when making risky economic choices.

Adolescent↗

PubMed2006

Effects of acute smoking on brain activity vary with abstinence in smokers performing the N-Back task: a preliminary study.

We previously reported that compared with a non-deprivation state, overnight abstinence from cigarette smoking was associated with higher brain activity in the left dorsolateral prefrontal cortex (L-DLPFC) during a low demanding working memory challenge, and little increase beyond this activity level during more taxing working memory conditions. In the present study, we aimed to assess how recent smoking (overnight abstinence vs. smoking ad libitum) influenced the effect of smoking a cigarette on brain activity related to a working memory challenge. Six smokers performed the N-Back working memory task during functional magnetic resonance imaging (fMRI) both before and after smoking a cigarette in each of two test sessions: one following overnight abstinence from smoking ( approximately 13 h) and the other following ad libitum smoking. Task-related activity in L-DLPFC showed a significant interaction between the effects of acute smoking, test session, and task load. After overnight abstinence, post-smoking brain activity in L-DLPFC was lower than before smoking at low task load and higher at high task load; corresponding activity on a day of ad libitum smoking was higher at low load and lower at high task load after smoking during the session. These data suggest that the effect of acute smoking on working memory processing depends on recent prior smoking and task load. In particular, they provide preliminary evidence that functional efficiency of working memory is improved by smoking a cigarette during abstinence, while the effect of a cigarette in a non-deprived state varies with the nature and difficulty of the working memory challenge. This interaction merits further examination in larger studies specifically designed to consider this issue.

Adult↗

PubMed2006

fMRI predictors of treatment outcome in pediatric anxiety disorders.

INTRODUCTION: A growing number of studies have found evidence that anxiety and depressive disorders are associated with atypical amygdala hyperactivation, which decreases with effective treatment. Interest has emerged in this phenomenon as a possible biological marker for individuals who are likely to benefit from tailored treatment approaches. OBJECTIVE: The present study was designed to examine relationships between pretreatment amygdala activity and treatment response in a sample of anxious children and adolescents. MATERIALS AND METHODS: Participants, who were diagnosed predominantly with generalized anxiety disorder (GAD), underwent functional magnetic resonance imaging (fMRI) scanning before treatment with fluoxetine or cognitive behavioral therapy (CBT). RESULTS: Results indicated significant negative associations between degree of left amygdala activation and measures of posttreatment symptom improvement in the group, as a whole. DISCUSSION: Taken together with research on associations between adult amygdala activation and treatment response, these findings suggest that patients whose pretreatment amygdala activity is the strongest may be particularly likely to respond well to such widely used treatments as selective serotonin reuptake inhibitor (SSRI) medications and CBT.

Adolescent↗

PubMed2006

Increased occupancy of dopamine receptors in human striatum during cue-elicited cocaine craving.

In all, 19 research subjects, with current histories of frequent cocaine use, were exposed to cocaine-related cues to elicit drug craving. We measured the change of occupancy of dopamine at D2-like receptors with positron emission tomography (PET) and inferred a change of intrasynaptic dopamine (endogenous dopamine release), based on the displacement of radiotracer [(11)C]raclopride. Receptor occupancy by dopamine increased significantly in putamen of participants who reported cue-elicited craving compared to those who did not. Further, the intensity of craving was positively correlated with the increase in dopamine receptor occupancy in the putamen. These results provide direct evidence that occupancy of dopamine receptors in human dorsal striatum increased in proportion to subjective craving, presumably because of increased release of intrasynaptic dopamine.

Adult↗

PubMed2006

Dose effects of triazolam on brain activity during episodic memory encoding: a PET study.

RATIONALE: Although it is well established that acute benzodiazepine administration impairs episodic memory encoding, little is known about the neuroanatomical substrates of this effect. OBJECTIVE: The objective was to examine the acute dose effects of the benzodiazepine hypnotic triazolam on brain activity during episodic memory encoding. METHODS: After oral capsule administration (placebo, 0.1, 0.2, and 0.4 mg/70 kg triazolam), regional cerebral blood flow (rCBF) was measured using positron emission tomography (PET) with 15O-H2O during performance of semantic categorization and orthographic categorization tasks in a double-blind, within-subject design in 12 healthy volunteers. The rCBF associated with episodic memory encoding was measured by subtracting the rCBF during orthographic categorization from that during semantic categorization and by examining correlations between brain activity during encoding and subsequent recognition memory performance. RESULTS: Results in the placebo condition replicated those of nonpharmacological encoding studies, including activation in left ventrolateral prefrontal cortex. Correlations between brain activity and subsequent memory performance additionally showed medial temporal activation. Triazolam produced dose-related impairment in memory performance and dose-related deactivation in encoding-associated areas including right prefrontal cortex, left parahippocampal gyrus, and left anterior cingulate cortex. CONCLUSIONS: Results are consistent with behavioral evidence that benzodiazepines impair prefrontal control processes as well as contextual memory and episodic binding processes thought to be controlled by the medial temporal lobe. In addition to elucidating the brain mechanisms underlying these benzodiazepine-induced behavioral deficits, results of this study also help validate hypotheses generated in nonpharmacological neuroimaging studies regarding the processes controlled by these brain regions.

Adult↗

PubMed2006

Striatal functional alteration in adolescents characterized by early childhood behavioral inhibition.

The temperamental style of behavioral inhibition has been characterized by exaggerated behavioral and neural responses to cues signaling threat. Virtually no work, however, has addressed whether behavioral inhibition may also confer heightened brain activation in response to positively valenced incentives. We used event-related functional MRI (fMRI) and a monetary incentive delay task to examine whether the neural response to incentives is also greater in adolescents characterized as behaviorally inhibited early in life compared with those characterized as non-inhibited. Whereas task performance did not differ between groups, fMRI revealed greater striatal activation to incentives in behaviorally inhibited adolescents than in non-inhibited adolescents. This was regardless of whether the incentive was an anticipated gain or loss. Alteration in neural systems underlying behavior modulated by both negative and positive contingencies may represent a correlate of behavioral inhibition that also underlies vulnerability to various forms of developmental psychopathology.

Adolescent↗

PubMed2006

Age-related influence of contingencies on a saccade task.

Adolescence is characterized by increased risk-taking and sensation-seeking, presumably brought about by developmental changes within reward-mediating brain circuits. A better understanding of the neural mechanisms underlying reward-seeking during adolescence can have critical implications for the development of strategies to enhance adolescent performance in potentially dangerous situations. Yet little research has investigated the influence of age on the modulation of behavior by incentives with neuroscience-based methods. A monetary reward antisaccade task (the RST) was used with 23 healthy adolescents and 30 healthy adults. Performance accuracy, latency and peak velocity of saccade responses (prosaccades and antisaccades) were analyzed. Performance accuracy across all groups was improved by incentives (obtain reward, avoid punishment) for both, prosaccades and antisaccades. However, modulation of antisaccade errors (direction errors) by incentives differed between groups: adolescents modulated saccade latency and peak velocity depending on contingencies, with incentives aligning their performance to that of adults; adults did not show a modulation by incentives. These findings suggest that incentives modulate a global measure of performance (percent direction errors) in adults and adolescents, and exert a more powerful influence on the control of incorrect motor responses in adolescents than in adults. These findings suggest that this task can be used in neuroimaging studies as a probe of the influence of incentives on cognitive control from a developmental perspective as well as in health and disease.

Adolescent↗

PubMed2006

Increased amygdala activity during successful memory encoding in adolescent major depressive disorder: An FMRI study.

BACKGROUND: Although major depressive disorder (MDD) represents one of the most serious psychiatric problems afflicting adolescents, efforts to understand the neural circuitry of adolescent MDD have lagged behind those of adult MDD. This study tests the hypothesis that adolescent MDD is associated with abnormal amygdala activity during evocative-face viewing. METHODS: Using functional magnetic resonance imaging (fMRI), between-group differences among MDD (n = 10), anxious (n = 11), and non-psychiatric comparisons (n = 23) were examined during successful vs. unsuccessful face encoding, with encoding success measured post-scan. RESULTS: Compared to healthy adolescents, MDD patients exhibited poorer memory for faces. fMRI analyses accounted for this performance difference through event-related methods. In an analysis comparing successful vs. unsuccessful face encoding, MDD patients exhibited greater left amygdala activation relative to healthy and anxious youth. CONCLUSIONS: Given prior findings among adults, this study suggests that adolescent and adult MDD may involve similar underlying abnormalities in amygdala functioning.

Adolescent↗

PubMed2006

Triadic model of the neurobiology of motivated behavior in adolescence.

BACKGROUND: Risk-taking behavior is a major cause of morbidity and mortality in adolescence. In the context of decision theory and motivated (goal-directed) behavior, risk-taking reflects a pattern of decision-making that favors the selection of courses of action with uncertain and possibly harmful consequences. We present a triadic, neuroscience systems-based model of adolescent decision-making. METHOD: We review the functional role and neurodevelopmental findings of three key structures in the control of motivated behavior, i.e. amygdala, nucleus accumbens, and medial/ventral prefrontal cortex. We adopt a cognitive neuroscience approach to motivated behavior that uses a temporal fragmentation of a generic motivated action. Predictions about the relative contributions of the triadic nodes to the three stages of a motivated action during adolescence are proposed. RESULTS: The propensity during adolescence for reward/novelty seeking in the face of uncertainty or potential harm might be explained by a strong reward system (nucleus accumbens), a weak harm-avoidant system (amygdala), and/or an inefficient supervisory system (medial/ventral prefrontal cortex). Perturbations in these systems may contribute to the expression of psychopathology, illustrated here with depression and anxiety. CONCLUSIONS: A triadic model, integrated in a temporally organized map of motivated behavior, can provide a helpful framework that suggests specific hypotheses of neural bases of typical and atypical adolescent behavior.

Adolescent↗

PubMed2006

Behavioral alterations in reward system function: the role of childhood maltreatment and psychopathology.

OBJECTIVE: To examine in children the influence of maltreatment and associated psychiatric sequelae on behavioral responses to reward stimuli. METHOD: A computerized two-choice decision-making task involving probabilistic monetary gains was used to probe elemental processes of goal-directed actions. Using different risk contingencies, the authors examined decision-making, expectations of outcomes, and affective responses to rewards in 38 maltreated children and 21 demographically matched controls (8-14 years old). RESULTS: Maltreated children selected risk options faster than controls; however, whereas controls responded more quickly as the chance of winning increased, maltreated children did not vary in response speed as a function of the likelihood of winning. When choosing between high- and low-risk options, maltreated children with depressive disorders more frequently selected safe over risky choices than did controls. No group differences emerged in self-report ratings of positive or negative reactions to winning or not winning, respectively. CONCLUSIONS: This initial experimental study of responses to reward lays the groundwork for subsequent research on neurodevelopmental aspects of reward processes in relationship to maltreatment and psychopathology. Clinical applications of these data may be relevant for developing treatment plans for maltreated children, particularly those with depression.

Adolescent↗

PubMed2006

An fMRI examination of developmental differences in the neural correlates of uncertainty and decision-making.

BACKGROUND: Maturation of prefrontal circuits during adolescence contributes to the development of cognitive processes such as decision-making. Recent theories suggest that these neural changes also play a role in the shift from generalized anxiety disorder (GAD) to depression that often occurs during this developmental period. Cognitive models of the development of GAD highlight the role of intolerance of uncertainty (IU), which can be characterized behaviorally by impairments in decision-making. The present study examines potential developmental differences in frontal regions associated with uncertain decision-making, and tests the impact of IU on these circuits. METHODS: Twelve healthy adults (ages 19-36) and 12 healthy adolescents (ages 13-17) completed a decision-making task with conditions of varied uncertainty while fMRI scans were acquired. They also completed measures of worry and IU, and a questionnaire about their levels of anxiety and certainty during the task. RESULTS: Combined group analyses demonstrated significant linear effects of uncertainty on activity within anterior cingulate cortex (ACC). Region of interest (ROI)-based analysis found a significant interaction of group and IU ratings in ACC. Increased IU was associated with robust linear increases in ACC activity only in adolescents. An ROI analysis of feedback-related processing found that adolescents demonstrated greater activation during incorrect trials relative to correct trials, while the adults showed no difference in neural activity associated with incorrect and correct feedback. CONCLUSIONS: This decision-making task was shown to be effective at eliciting uncertainty-related ACC activity in adults and adolescents. Further, IU impacts ACC activity in adolescents during uncertain decision-making, providing preliminary support for a developmental model of GAD.

Adolescent↗

PubMed2006

Ventrolateral prefrontal cortex activation and attentional bias in response to angry faces in adolescents with generalized anxiety disorder.

OBJECTIVE: While adolescent anxiety disorders represent prevalent, debilitating conditions, few studies have explored their brain physiology. Using event-related functional magnetic resonance imaging (fMRI) and a behavioral measure of attention to angry faces, the authors evaluated differences in response between healthy adolescents and adolescents with generalized anxiety disorder. METHOD: In the primary trials of interest, 18 adolescents with generalized anxiety disorder and 15 comparison subjects of equivalent age/gender/IQ viewed angry/neutral face pairs during fMRI acquisition. Following the presentation of each face pair, subjects pressed a button to indicate whether a subsequent asterisk appeared on the same (congruent) or opposite (incongruent) side as the angry face. Reaction time differences between congruent and incongruent face trials provided a measure of attention bias to angry faces. RESULTS: Relative to the comparison subjects, patients with generalized anxiety disorder manifested greater right ventrolateral prefrontal cortex activation to trials containing angry faces. Patients with generalized anxiety disorder also showed greater attention bias away from angry faces. Ventrolateral prefrontal cortex activation differences remained evident when differences in attention bias were covaried. Finally, in an examination among patients of the association between degree of anxiety and brain activation, the authors found that as ventrolateral prefrontal cortex activation increased, severity of anxiety symptoms diminished. CONCLUSIONS: Adolescents with generalized anxiety disorder show greater right ventrolateral prefrontal cortex activation and attentional bias away from angry faces than healthy adolescents. Among patients, increased ventrolateral prefrontal cortex activation is associated with less severe anxiety, suggesting that this activation may serve as a compensatory response.

Adolescent↗

PubMed2006

Imaging genomics applied to anxiety, stress response, and resiliency.

Anxiety and stress response/resiliency are heritable traits central to the etiology of multiple psychiatric diseases, but efforts to identify genetic variation influencing this broad domain of neurobiological function are hampered by the coarseness of the phenotypic measures and the effects of environmental factors. Neuroimaging offers a powerful approach for assessing functional neuronal activity. Neurophysiological measures can serve as intermediate phenotypes more directly linked to small gene effects, compared with behavioral end points of neural dysfunction. Imaging genomics is a relatively new research area that is concerned with linking functional gene variants and brain information processing. Here, we will focus on processes affected by anxiety and stress. Neuroimaging has been combined with genetic analysis to reveal genetic effects of functional variants of the serotonin transporter (5-HTT) and catechol-O-methyltransferase (COMT) genes on brain response to stressful stimuli. The low-expressing allele of the 5-HTT promoter polymorphism (HTTLPR) is associated with anxiety and with greater amygdala and other regional responses to emotional. The COMT Met158 allele leads to lower COMT activity and has also been associated with anxiety, and the effect of this gene is apparently additive with HTTLPR. Individuals with Met158 genotypes are more sensitive to pain stress and, as shown by C11 Carfentanil imaging, have diminished ability to upregulate opioid release after pain/stress. These results suggest that functional variants of 5-HTT and COMT impact brain functions involved in stress and anxiety.

Adaptation, Psychological↗

PubMed2006

Behavioral predictors of substance-use initiation in adolescents with and without attention-deficit/hyperactivity disorder.

OBJECTIVE: Our goal was to examine substance-use initiation in healthy adolescents and in adolescents who have been diagnosed with attention-deficit/hyperactivity disorder. METHODS: Seventy-eight adolescents (28 healthy and 50 with attention-deficit/hyperactivity disorder) participated in an ongoing longitudinal study of predictors of substance use. The substances most commonly reported were tobacco, alcohol, and marijuana. Aggression, conduct problems, hyperactivity, impulsivity, inattention, anxiety/depression, social difficulties, and somatic complaints were assessed at study entry and tested as predictors for later substance use. RESULTS: With an average of 4 years into the study, 37 adolescents had not used any substances, 41 had experimented with at least 1 substance, and 29 experimented with >1 substance. Psychiatric diagnoses (attention-deficit/hyperactivity disorder, attention-deficit/hyperactivity disorder and conduct disorder, and attention-deficit/hyperactivity disorder and depression/anxiety) did not influence reports of substance use. Distinct behavioral measures collected at study entry predicted use of different substances. In a multivariate analysis, aggression had the greatest association with tobacco smoking and marijuana use. Impulsivity was associated with alcohol use. Severity of drug exposure, indexed by the number of substances used, was predicted by aggression. CONCLUSIONS: This 4-year longitudinal study captured the onset of substance use, not abuse. Behavioral predictors differed with the type of substance used. These behavioral characteristics may raise suspicion among pediatricians for enhanced risk for substance-use initiation.

Adolescent↗

PubMed2006

The role of functional neuroimaging in pediatric brain injury.

The aim of this article is to review empirical studies published in the last 10 years that used various functional neuroimaging techniques to assess pediatric patients with brain injury. Overall, these studies have demonstrated the ability of functional neuroimaging to offer unique information concerning the diagnosis, clinical outcome, and recovery mechanisms after pediatric brain injury. Future research using functional neuroimaging is recommended to better understand the functional reorganization and neurodevelopmental consequences resulting from brain injury. Such research might allow clinicians to design tailored early-intervention and rehabilitation programs to maximize the recovery process for pediatric patients. Limitations and advantages associated with the use of functional neuroimaging in pediatric populations are discussed.

Brain Injuries↗

PubMed2005

Neurobiology of decision making: a selective review from a neurocognitive and clinical perspective.

We present a temporal map of key processes that occur during decision making, which consists of three stages: 1) formation of preferences among options, 2) selection and execution of an action, and 3) experience or evaluation of an outcome. This framework can be used to integrate findings of traditional choice psychology, neuropsychology, brain lesion studies, and functional neuroimaging. Decision making is distributed across various brain centers, which are differentially active across these stages of decision making. This approach can be used to follow developmental trajectories of the different stages of decision making and to identify unique deficits associated with distinct psychiatric disorders.

Animals↗