Derek G.V. Mitchell

Reduced Amygdala Response to Fearful Expressions in Children and Adolescents With Callous-Unemotional Traits and Disruptive Behavior Disorders

OBJECTIVE Extensive work implicates abnormal amygdala activation in emotional facial expression processing in adults with callous-unemotional traits. However, no research has examined amygdala response to emotional facial expressions in adolescents with disruptive behavior and callous-unemotional traits. Moreover, despite high comorbidity of callous-unemotional traits and attention deficit hyperactivity disorder (ADHD), no research has attempted to distinguish neural correlates of pediatric callous-unemotional traits and ADHD. METHOD Participants were 36 children and adolescents (ages 10-17 years); 12 had callous-unemotional traits and either conduct disorder or oppositional defiant disorder, 12 had ADHD, and 12 were healthy comparison subjects. Functional MRI was used to assess amygdala activation patterns during processing of fearful facial expressions. Patterns in the callous-unemotional traits group were compared with those in the ADHD and comparison groups. RESULTS In youths with callous-unemotional traits, amygdala activation was reduced relative to healthy comparison subjects and youths with ADHD while processing fearful expressions, but not neutral or angry expressions. Functional connectivity analyses demonstrated greater correlations between the amygdala and the ventromedial prefrontal cortex in comparison subjects and youths with ADHD relative to those with callous-unemotional traits. Symptom severity in the callous-unemotional traits groups was negatively correlated with connectivity between amygdala and ventromedial prefrontal cortex. CONCLUSIONS This is the first study to demonstrate reduced amygdala responsiveness in youths with callous-unemotional traits. These findings support the contention that callous and unemotional personality traits are associated with reduced amygdala response to distress-based social cues.

A selective impairment in the processing of sad and fearful expressions in children with psychopathic tendencies

The processing of emotional expressions is fundamental for normal socialisation and interaction. Reduced responsiveness to the expressions of sadness and fear has been implicated in the development of psychopathy (R. J. R. Blair, 1995). The current study investigates the sensitivity of children with psychopathic tendencies to facial expressions. Children with psychopathic tendencies and a comparison group, as defined by the Psychopathy Screening Device (PSD; P. J. Frick & R. D. Hare, in press), were presented with a cinematic display of a standardised set of facial expressions that depicted sadness, happiness, anger, disgust, fear, and surprise. Participants observed as these facial expressions slowly evolved through 20 successive frames of increasing intensity. The children with psychopathic tendencies presented with selective impairments; they needed significantly more stages before they could successfully recognise the sad expressions and even when the fearful expressions were at full intensity were significantly more likely to mistake them for another expression. These results are interpreted with reference to an amygdala and empathy impairment explanation of psychopathy.

Risky decisions and response reversal: is there evidence of orbitofrontal cortex dysfunction in psychopathic individuals?

This study investigates the performance of psychopathic individuals on tasks believed to be sensitive to dorsolateral prefrontal and orbitofrontal cortex (OFC) functioning. Psychopathic and non-psychopathic individuals, as defined by the Hare psychopathy checklist revised (PCL-R) [Hare, The Hare psychopathy checklist revised, Toronto, Ontario: Multi-Health Systems, 1991] completed a gambling task [Cognition 50 (1994) 7] and the intradimensional/extradimensional (ID/ED) shift task [Nature 380 (1996) 69]. On the gambling task, psychopathic participants showed a global tendency to choose disadvantageously. Specifically, they showed an impaired ability to show learning over the course of the task. On the ID/ED task, the performance of psychopathic individuals was not significantly different from incarcerated controls on attentional set-shifting, but significant impairments were found on response reversal. These results are interpreted with reference to an OFC and amygdala dysfunction explanation of psychopathy.

Modulation of emotion by cognition and cognition by emotion

In this study, we examined the impact of goal-directed processing on the response to emotional pictures and the impact of emotional pictures on goal-directed processing. Subjects (N=22) viewed neutral or emotional pictures in the presence or absence of a demanding cognitive task. Goal-directed processing disrupted the BOLD response to emotional pictures. In particular, the BOLD response within bilateral amygdala and inferior frontal gyrus decreased during concurrent task performance. Moreover, the presence of both positive and negative distractors disrupted task performance, with reaction times increasing for emotional relative to neutral distractors. Moreover, in line with the suggestion of the importance of lateral frontal regions in emotional regulation [Ochsner, K. N., Ray, R. D., Cooper, J. C., Robertson, E. R., Chopra, S., Gabrieli, J. D., et al. (2004). For better or for worse: neural systems supporting the cognitive down-and up-regulation of negative emotion. NeuroImage, 23(2), 483-499], connectivity analysis revealed positive connectivity between lateral superior frontal cortex and regions of middle frontal cortex previously implicated in emotional suppression [Beauregard, M., Levesque, J., and Bourgouin, P. (2001). Neural correlates of conscious self-regulation of emotion. J. Neurosci., 21 (18), RC165.; Levesque, J., Eugene, F., Joanette, Y., Paquette, V., Mensour, B., Beaudoin, G., et al. (2003). Neural circuitry underlying voluntary suppression of sadness. Biol. Psychiatry, 53 (6), 502-510.; Ohira, H., Nomura, M., Ichikawa, N., Isowa, T., Iidaka, T., Sato, A., et al. (2006). Association of neural and physiological responses during voluntary emotion suppression. NeuroImage, 29 (3), 721-733] and negative connectivity with bilateral amygdala. These data suggest that processes involved in emotional regulation are recruited during task performance in the context of emotional distractors.

Somatic markers and response reversal: Is there orbitofrontal cortex dysfunction in boys with psychopathic tendencies?

This study investigated the performance of boys with psychopathic tendencies and comparison boys, aged 9 to 17 years, on two tasks believed to be sensitive to amygdala and orbitofrontal cortex functioning. Fifty-one boys were divided into two groups according to the Psychopathy Screening Device (PSD, P. J. Frick & R. D. Hare, in press) and presented with two tasks. The tasks were the gambling task (A. Bechara, A. R. Damasio, H. Damasio, & S. W. Anderson, 1994) and the Intradimensional/Extradimensional (ID/ED) shift task (R. Dias, T. W. Robbins, & A. C. Roberts, 1996). The boys with psychopathic tendencies showed impaired performance on the gambling task. However, there were no group differences on the ID/ED task either for response reversal or extradimensional set shifting. The implications of these results for models of psychopathy are discussed.

Abnormal ventromedial prefrontal cortex function in children with psychopathic traits during reversal learning.

CONTEXT Children and adults with psychopathic traits and conduct or oppositional defiant disorder demonstrate poor decision making and are impaired in reversal learning. However, the neural basis of this impairment has not previously been investigated. Furthermore, despite high comorbidity of psychopathic traits and attention-deficit/hyperactivity disorder, to our knowledge, no research has attempted to distinguish neural correlates of childhood psychopathic traits and attention-deficit/hyperactivity disorder. OBJECTIVE To determine the neural regions that underlie the reversal learning impairments in children with psychopathic traits plus conduct or oppositional defiant disorder. DESIGN Case-control study. SETTING Government clinical research institute. PARTICIPANTS Forty-two adolescents aged 10 to 17 years: 14 with psychopathic traits and oppositional defiant disorder or conduct disorder, 14 with attention-deficit/hyperactivity disorder only, and 14 healthy controls. MAIN OUTCOME MEASURE Blood oxygenation level-dependent signal as measured via functional magnetic resonance imaging during a probabilistic reversal task. RESULTS Children with psychopathic traits showed abnormal responses within the ventromedial prefrontal cortex (Brodmann area 10) during punished reversal errors compared with children with attention-deficit/hyperactivity disorder and healthy children (P < .05 corrected for multiple comparisons). CONCLUSIONS To our knowledge, this study provides the first evidence of abnormal ventromedial prefrontal cortex responsiveness in children with psychopathic traits and demonstrates this dysfunction was not attributable to comorbid attention-deficit/hyperactivity disorder. These findings suggest that reversal learning impairments in patients with developmental psychopathic traits relate to abnormal processing of reinforcement information.

The nexus between decision making and emotion regulation: A review of convergent neurocognitive substrates

Emotional information, such as reward or punishment, gains rapid and often preferential access to neurocognitive resources. This ability to quickly evaluate and integrate emotion-related information is thought to benefit a range of behaviours critical for survival. Conversely, the improper use of, or preoccupation with, emotional information is associated with disruptions in functioning and psychiatric disorders. Optimally, an organism utilizes emotional information when it is significant, and minimizes its influence when it is not. Recently, similar regions of prefrontal cortex have been identified that are associated with regulating both behavioural conflict (motor response selection or inhibition) and affective conflict (emotional representation and awareness). In this review, data will be examined that concerns this convergence between decision making (modulating what we do) and emotion regulation (modulating how we feel) and an informal model will be proposed linking these processes at a neurocognitive level. The studies reviewed collectively support the conclusion that overlapping areas of prefrontal cortex perform similar computations whether the functional objective is to modulate an operant response, or an emotional one. Specifically, the idea is raised that key aspects of decision making and emotion regulation are bound by a common functional objective in which internal representations of conditioned stimuli and reinforcers are modulated to facilitate optimal behaviour or states. Emphasis is placed on dorsomedial, dorsolateral, ventrolateral, and ventromedial regions of prefrontal cortex.

The impact of processing load on emotion

This event-related fMRI study examined the impact of processing load on the BOLD response to emotional expressions. Participants were presented with composite stimuli consisting of neutral and fearful faces upon which semi-transparent words were superimposed. This manipulation held stimulus-driven features constant across multiple levels of processing load. Participants made either (1) gender discriminations based on the face; (2) case judgments based on the words; or (3) syllable number judgments based on the words. A significant main effect for processing load was revealed in prefrontal cortex, parietal cortex, visual processing areas, and amygdala. Critically, enhanced activity in the amygdala and medial prefrontal cortex seen during gender discriminations was significantly reduced during the linguistic task conditions. A connectivity analysis conducted to investigate theories of cognitive modulation of emotion showed that activity in dorsolateral prefrontal cortex was inversely related to activity in the ventromedial prefrontal cortex. Together, the data suggest that the processing of task-irrelevant emotional information, like neutral information, is subject to the effects of processing load and is under top-down control.

Neural Substrates of Reward Magnitude, Probability, and Risk During a Wheel of Fortune Decision-Making Task

Economic decision-making involves the weighting of magnitude and probability of potential gains/losses. While previous work has examined the neural systems involved in decision-making, there is a need to understand how the parameters associated with decision-making (e.g., magnitude of expected reward, probability of expected reward and risk) modulate activation within these neural systems. In the current fMRI study, we modified the monetary wheel of fortune (WOF) task [Ernst, M., Nelson, E.E., McClure, E.B., Monk, C.S., Munson, S., Eshel, N., et al. (2004). Choice selection and reward anticipation: an fMRI study. Neuropsychologia 42(12), 1585-1597.] to examine in 25 healthy young adults the neural responses to selections of different reward magnitudes, probabilities, or risks. Selection of high, relative to low, reward magnitude increased activity in insula, amygdala, middle and posterior cingulate cortex, and basal ganglia. Selection of low-probability, as opposed to high-probability reward, increased activity in anterior cingulate cortex, as did selection of risky, relative to safe reward. In summary, decision-making that did not involve conflict, as in the magnitude contrast, recruited structures known to support the coding of reward values, and those that integrate motivational and perceptual information for behavioral responses. In contrast, decision-making under conflict, as in the probability and risk contrasts, engaged the dorsal anterior cingulate cortex whose role in conflict monitoring is well established. However, decision-making under conflict failed to activate the structures that track reward values per se. Thus, the presence of conflict in decision-making seemed to significantly alter the pattern of neural responses to simple rewards. In addition, this paradigm further clarifies the functional specialization of the cingulate cortex in processes of decision-making.

Differentiating among prefrontal substrates in psychopathy: Neuropsychological test findings

Frontal lobe and consequent executive dysfunction have long been related to psychopathy. More recently, there have been suggestions that specific regions of frontal cortex, rather than all of frontal cortex, may be implicated in psychopathy. To examine this issue, the authors presented 25 individuals with psychopathy and 30 comparison individuals with measures preferentially indexing the orbitofrontal cortex (OFC; object alternation task), dorsolateral prefrontal cortex (DLPFC; spatial alternation task), and anterior cingulate cortex (ACC; number-Stroop reading and counting tasks). The individuals with psychopathy showed significant impairment on the measure preferentially sensitive to OFC functioning. In contrast, the 2 groups did not show impairment on the measures preferentially sensitive to the functioning of the DLPFC or ACC. These results are interpreted with reference to executive dysfunction accounts of the disorder.