R. James R. Blair

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.

Disrupted Reinforcement Signaling in the Orbitofrontal Cortex and Caudate in Youths With Conduct Disorder or Oppositional Defiant Disorder and a High Level of Psychopathic Traits

OBJECTIVE Dysfunction in the amygdala and orbitofrontal cortex has been reported in youths and adults with psychopathic traits. The specific nature of the functional irregularities within these structures remains poorly understood. The authors used a passive avoidance task to examine the responsiveness of these systems to early stimulus-reinforcement exposure, when prediction errors are greatest and learning maximized, and to reward in youths with psychopathic traits and comparison youths. METHOD While performing the passive avoidance learning task, 15 youths with conduct disorder or oppositional defiant disorder plus a high level of psychopathic traits and 15 healthy subjects completed a 3.0-T fMRI scan. RESULTS Relative to the comparison youths, the youths with a disruptive behavior disorder plus psychopathic traits showed less orbitofrontal responsiveness both to early stimulus-reinforcement exposure and to rewards, as well as less caudate response to early stimulus-reinforcement exposure. There were no group differences in amygdala responsiveness to these two task measures, but amygdala responsiveness throughout the task was lower in the youths with psychopathic traits. CONCLUSIONS Compromised sensitivity to early reinforcement information in the orbitofrontal cortex and caudate and to reward outcome information in the orbitofrontal cortex of youths with conduct disorder or oppositional defiant disorder plus psychopathic traits suggests that the integrated functioning of the amygdala, caudate, and orbitofrontal cortex may be disrupted. This provides a functional neural basis for why such youths are more likely to repeat disadvantageous decisions. New treatment possibilities are raised, as pharmacologic modulations of serotonin and dopamine can affect this form of learning.

The neural basis of implicit moral attitude--an IAT study using event-related fMRI.

Recent models of morality have suggested the importance of affect-based automatic moral attitudes in moral reasoning. However, previous investigations of moral reasoning have frequently relied upon explicit measures that are susceptible to voluntary control. To investigate participants automatic moral attitudes, we used a morality Implicit Association Test (IAT). Participants rated the legality of visually depicted legal and illegal behaviors of two different intensity levels (e.g., high intensity illegal = interpersonal violence; low intensity illegal = vandalism) both when the target concept (e.g., illegal) was behaviorally paired with an associated attribute (e.g., bad; congruent condition) or an unassociated attribute (e.g., good; incongruent condition). Behaviorally, an IAT effect was shown; RTs were faster in the congruent rather than incongruent conditions. At the neural level, implicit moral attitude, as indexed by increased BOLD response as a function of stimulus intensity, was associated with increased activation in the right amygdala and the ventromedial orbitofrontal cortex. In addition, performance on incongruent trials relative to congruent trials was associated with increased activity in the right ventrolateral prefrontal cortex (BA 47), left subgenual cingulate gyrus (BA 25), bilateral premotor cortex (BA 6) and the left caudate. The functional contributions of these regions in moral reasoning are discussed.

Irritability in Pediatric Mania and Other Childhood Psychopathology

Abstract: Irritability is an important symptom in childhood psychopathology that has received relatively little research attention. Recent controversy concerning the diagnosis of mania in children has focused attention on how little is known about how to assess irritability in a systematic way, and about its diagnostic associations. For example, subtyping irritability according to course (chronic vs. episodic), precipitants, and family history may facilitate the identification of psychopathology and the study of pathophysiology. While normative and pathologic irritability can be differentiated reliably, the validity of the distinction is unclear. In addition, there is a need for scales designed to measure the severity of irritability in children with mood and anxiety disorders. In order to facilitate research, we propose a definition of irritability from the perspective of affective neuroscience. Because reactive aggression may be a helpful animal model for irritability, we review the neural circuitry mediating this behavior. Behavioral paradigms that evoke frustration, as well as those that assess the ability to inhibit a prepotent motor response, maintain attentional focus, execute response reversal, recognize angry faces, and regulate emotional responses, may be useful in the study of irritability. Examples of such paradigms are described, and the pharmacology of irritability is reviewed briefly.

Conduct Disorder and Callous–Unemotional Traits in Youth

Children with repetitive rule-breaking, aggression, and disregard for others are at increased risk for substance abuse, educational disruption, and criminal behavior. Progress is being made toward understanding the clinical and neurocognitive features of callous youth.

Impaired reversal but intact acquisition : Probabilistic response reversal deficits in adult individuals with psychopathy

The performance of adult psychopathic individuals on a novel response reversal task involving 2 reward-punishment contingencies (100-0 and 80-20) was investigated. In line with predictions, adults with psychopathy presented with impairment on the response reversal component but not on the acquisition component of this task. This selective impairment for response reversal was seen for both reward-punishment contingencies and was related to the tendency of individuals with psychopathy to be less likely to stay with a rewarded correct response to a stimulus on the subsequent presentation of that stimulus. Results are discussed with reference to current models of the development of psychopathy.

Reduced amygdala response in youths with disruptive behavior disorders and psychopathic traits: Decreased emotional response versus increased top-down attention to nonemotional features

OBJECTIVE Amygdala dysfunction has been reported to exist in youths and adults with psychopathic traits. However, there has been disagreement as to whether this dysfunction reflects a primary emotional deficit or is secondary to atypical attentional control. The authors examined the validity of the contrasting predictions. METHOD Participants were 15 children and adolescents (ages 10–17 years) with both disruptive behavior disorders and psychopathic traits and 17 healthy comparison youths. Functional MRI was used to assess the response of the amygdala and regions implicated in top-down attentional control (the dorsomedial and lateral frontal cortices) to emotional expression under conditions of high and low attentional load. RESULTS Relative to youths with disruptive behavior disorders and psychopathic traits, healthy comparison subjects showed a significantly greater increase in the typical amygdala response to fearful expressions under low relative to high attentional load conditions. There was also a selective inverse relationship between the response to fearful expressions under low attentional load and the callous-unemotional component (but not the narcissism or impulsivity component) of psychopathic traits. In contrast, the two groups did not differ in the significant recruitment of the dorsomedial and lateral frontal cortices as a function of attentional load. CONCLUSIONS Youths with disruptive behavior disorders and psychopathic traits showed reduced amygdala responses to fearful expressions under low attentional load but no indications of increased recruitment of regions implicated in top-down attentional control. These findings suggest that the emotional deficit observed in youths with disruptive behavior disorders and psychopathic traits is primary and not secondary to increased top-down attention to nonemotional stimulus features.

The impact of affect and frequency on lexical decision: the role of the amygdala and inferior frontal cortex.

The current study used event-related fMRI to examine BOLD responses associated with two factors that behaviorally determine speed of lexical decision: frequency and emotion. Thirteen healthy adults performed a visual lexical decision task, discriminating between words and orthographically and phonologically legal nonwords. The study involved a 2 (Frequency: high and low) x 3 (Emotional arousal: highly negative, mildly negative, and neutral words) design with word categories matched for number of letters and concreteness. There were significant main effects for both frequency and emotion in lexical decision reaction times but no significant interaction. Negative word lexical decisions were associated with increased activation in bilateral amygdala and middle temporal cortex as well as rostral anterior and posterior cingulate cortex. Low-frequency word lexical decisions, relative to high-frequency word lexical decisions, were associated with increased bilateral activity in inferior frontal cortex. Inferior frontal cortex activation was particularly low during lexical decision for high-frequency emotional words but significant for high-frequency neutral emotional words. We suggest that this is because the semantic representation of high-frequency emotional words may receive sufficient additional augmentation via the reciprocal activation from the amygdala such that selective augmentation by inferior frontal cortex to achieve lexical decision is unnecessary.

Emotion at the Expense of Cognition: Psychopathic Individuals Outperform Controls on an Operant Response Task

The impact of emotional stimuli on a simple motor response task in individuals with psychopathy and comparison individuals was investigated. Psychopathy was assessed using the Psychopathy Checklist Revised (Hare, 1991). Participants were presented with the Emotional Interrupt Task, in which they responded with left and right button presses to shapes that were temporally bracketed by positive, negative, and neutral visual images taken from the International Affective Picture System. The comparison group showed increased response latencies if the shape was temporally bracketed by either a positive or negative emotional stimulus relative to a neutral stimulus. Individuals with psychopathy did not show this modulation of reaction time for either positive or negative emotional stimuli. Results are discussed with reference to current models regarding the modulation of attention by emotion and the emotional impairment seen in individuals with psychopathy.

Disrupted Expected Value and Prediction Error Signaling in Youths With Disruptive Behavior Disorders During a Passive Avoidance Task

OBJECTIVE Youths with disruptive behavior disorders, including conduct disorder and oppositional defiant disorder, show major impairments in reinforcement-based decision making. However, the neural basis of these difficulties remains poorly understood. This partly reflects previous failures to differentiate responses during decision making and feedback processing and to take advantage of computational model-based functional MRI (fMRI). METHOD Participants were 38 community youths ages 10-18 (20 had disruptive behavior disorders, and 18 were healthy comparison youths). Model-based fMRI was used to assess the computational processes involved in decision making and feedback processing in the ventromedial prefrontal cortex, insula, and caudate. RESULTS Youths with disruptive behavior disorders showed reduced use of expected value information within the ventromedial prefrontal cortex when choosing to respond and within the anterior insula when choosing not to respond. In addition, they showed reduced responsiveness to positive prediction errors and increased responsiveness to negative prediction errors within the caudate during feedback. CONCLUSIONS This study is the first to determine impairments in the use of expected value within the ventromedial prefrontal cortex and insula during choice and in prediction error-signaling within the caudate during feedback in youths with disruptive behavior disorders.