Author ManuscriptProg Neurobiol. Author Abamectin B1a custom synthesis manuscript; available in PMC 2016 April 01.Clauss et al.Pageof lifetime psychopathology (across both temperament groups) was associated with less dlPFC activation. Next, in a largely overlapping sample, Jarcho and colleagues (2014) examined attentional control using a variant of the Stroop task with emotional expressions and congruent or incongruent gender labels. When viewing fear faces with incongruent labels, inhibited individuals had greater activation of the dmPFC, dlPFC, ACC, suggesting that inhibited individuals need higher levels of PFC activation to enlist attentional control. In this task, brain function was not modulated by psychopathology. Together, these findings suggest that inhibited individuals engage the PFC in an attempt to dampen amygdala reactivity. These findings also highlight a role for PFC activation in the development of psychopathology. Inhibited subjects who are able to flexibly engage the prefrontal cortex during emotion regulation, have fewer anxiety symptoms or disorders, consistent with behavioral and EEG data in inhibited children that show that increased risk for anxiety is associated with stronger inhibitory control, heightened response monitoring, and deficits in attention shifting (Cavanagh and Shackman, 2014; McDermott et al., 2009; White et al., 2011). 2.1.3. Basal Ganglia–Although early studies provide compelling evidence that inhibited individuals have heightened neural reactivity to novel or threatening stimuli, several studies have also investigated the opposite side of the valence spectrum–response to positive stimuli which is mediated by the basal ganglia. In fMRI studies, the neural basis of response to reward and loss of potential reward is commonly investigated using the monetary incentive delay task. In this task, participants are taught to associate different cues with receiving money, losing money, or no effect. The outcome (receiving money or avoiding losing money) is contingent on pressing a button within a narrow time window when a target is detected. In an initial study, adolescents with a history of inhibited temperament had increased basal ganglia activity (caudate, putamen, and nucleus HIV-1 integrase inhibitor 2 web accumbens; Guyer et al., 2006), during anticipation of both loss and reward. A second study clarified that the observed increased basal ganglia activity was specific to conditions where loss or reward was contingent on the participant’s behavioral response (Bar-Haim et al., 2009). A third study found heightened caudate activation in inhibited individuals during notification of a “wrong” response and subsequent loss of reward (Helfinstein et al., 2011). Therefore, although these tasks were initially designed to probe reward processing, the observed basal ganglia hyperactivity in inhibited temperament more likely reflects performance monitoring and sensitivity to feedback. In support of this hypothesis, in a recent study, inhibited children had increased activation of the putamen after response selection and during anticipation of positive feedback from peers (Guyer et al., 2014). However, it should be noted that one recent study reported that basal ganglia (caudate, putamen, and nucleus accumbens) activation to reward cues moderated substance use, not abuse, in young adults with a history of inhibited temperament (Lahat et al., 2012). Additional studies will be needed to clarify the role of the basal ganglia in inhibited temperament and to determine whether t.Author ManuscriptProg Neurobiol. Author manuscript; available in PMC 2016 April 01.Clauss et al.Pageof lifetime psychopathology (across both temperament groups) was associated with less dlPFC activation. Next, in a largely overlapping sample, Jarcho and colleagues (2014) examined attentional control using a variant of the Stroop task with emotional expressions and congruent or incongruent gender labels. When viewing fear faces with incongruent labels, inhibited individuals had greater activation of the dmPFC, dlPFC, ACC, suggesting that inhibited individuals need higher levels of PFC activation to enlist attentional control. In this task, brain function was not modulated by psychopathology. Together, these findings suggest that inhibited individuals engage the PFC in an attempt to dampen amygdala reactivity. These findings also highlight a role for PFC activation in the development of psychopathology. Inhibited subjects who are able to flexibly engage the prefrontal cortex during emotion regulation, have fewer anxiety symptoms or disorders, consistent with behavioral and EEG data in inhibited children that show that increased risk for anxiety is associated with stronger inhibitory control, heightened response monitoring, and deficits in attention shifting (Cavanagh and Shackman, 2014; McDermott et al., 2009; White et al., 2011). 2.1.3. Basal Ganglia–Although early studies provide compelling evidence that inhibited individuals have heightened neural reactivity to novel or threatening stimuli, several studies have also investigated the opposite side of the valence spectrum–response to positive stimuli which is mediated by the basal ganglia. In fMRI studies, the neural basis of response to reward and loss of potential reward is commonly investigated using the monetary incentive delay task. In this task, participants are taught to associate different cues with receiving money, losing money, or no effect. The outcome (receiving money or avoiding losing money) is contingent on pressing a button within a narrow time window when a target is detected. In an initial study, adolescents with a history of inhibited temperament had increased basal ganglia activity (caudate, putamen, and nucleus accumbens; Guyer et al., 2006), during anticipation of both loss and reward. A second study clarified that the observed increased basal ganglia activity was specific to conditions where loss or reward was contingent on the participant’s behavioral response (Bar-Haim et al., 2009). A third study found heightened caudate activation in inhibited individuals during notification of a “wrong” response and subsequent loss of reward (Helfinstein et al., 2011). Therefore, although these tasks were initially designed to probe reward processing, the observed basal ganglia hyperactivity in inhibited temperament more likely reflects performance monitoring and sensitivity to feedback. In support of this hypothesis, in a recent study, inhibited children had increased activation of the putamen after response selection and during anticipation of positive feedback from peers (Guyer et al., 2014). However, it should be noted that one recent study reported that basal ganglia (caudate, putamen, and nucleus accumbens) activation to reward cues moderated substance use, not abuse, in young adults with a history of inhibited temperament (Lahat et al., 2012). Additional studies will be needed to clarify the role of the basal ganglia in inhibited temperament and to determine whether t.
