Catherine L. Sebastian

Social brain development and the affective consequences of ostracism in adolescence

Recent structural and functional imaging studies have provided evidence for continued development of brain regions involved in social cognition during adolescence. In this paper, we review this rapidly expanding area of neuroscience and describe models of neurocognitive development that have emerged recently. One implication of these models is that neural development underlies commonly observed adolescent phenomena such as susceptibility to peer influence and sensitivity to peer rejection. Experimental behavioural evidence of rejection sensitivity in adolescence is currently sparse. Here, we describe a study that directly compared the affective consequences of an experimental ostracism manipulation (Cyberball) in female adolescents and adults. The ostracism condition led to significantly greater affective consequences in the adolescents compared with adults. This suggests that the ability to regulate distress resulting from ostracism continues to develop between adolescence and adulthood. The results are discussed in the context of models of neurocognitive development.

Amygdala Response to Preattentive Masked Fear in Children With Conduct Problems: The Role of Callous-Unemotional Traits

OBJECTIVE In children with conduct problems, high levels of callous-unemotional traits are associated with amygdala hypoactivity to consciously perceived fear, while low levels of callous-unemotional traits may be associated with amygdala hyperactivity. Behavioral data suggest that fear processing deficits in children with high callous-unemotional traits may extend to stimuli presented below conscious awareness (preattentively). The authors investigated the neural basis of this effect. Amygdala involvement was predicted on the basis of its role in preattentive affective processing in healthy adults and its dysfunction in previous studies of conduct problems. METHOD Functional MRI was used to measure neural responses to fearful and calm faces presented preattentively (for 17 ms followed by backward masking) in boys with conduct problems and high callous-unemotional traits (N=15), conduct problems and low callous-unemotional traits (N=15), and typically developing comparison boys (N=16). Amygdala response to fearful and calm faces was predicted to differentiate groups, with the greatest response in boys with conduct problems and low callous-unemotional traits and the lowest in boys with conduct problems and high callous-unemotional traits. RESULTS In the right amygdala, a greater amygdala response was seen in boys with conduct problems and low callous-unemotional traits than in those with high callous-unemotional traits. The findings were not explained by symptom levels of conduct disorder, attention-deficit hyperactivity disorder, anxiety, or depression. CONCLUSIONS These data demonstrate differential amygdala activity to preattentively presented fear in children with conduct problems grouped by callous-unemotional traits, with high levels associated with lower amygdala reactivity. The studys findings complement increasing evidence suggesting that callous-unemotional traits are an important specifier in the classification of children with conduct problems.

Neural processing associated with cognitive and affective Theory of Mind in adolescents and adults

Theory of Mind (ToM) is the ability to attribute thoughts, intentions and beliefs to others. This involves component processes, including cognitive perspective taking (cognitive ToM) and understanding emotions (affective ToM). This study assessed the distinction and overlap of neural processes involved in these respective components, and also investigated their development between adolescence and adulthood. While data suggest that ToM develops between adolescence and adulthood, these populations have not been compared on cognitive and affective ToM domains. Using fMRI with 15 adolescent (aged 11-16 years) and 15 adult (aged 24-40 years) males, we assessed neural responses during cartoon vignettes requiring cognitive ToM, affective ToM or physical causality comprehension (control). An additional aim was to explore relationships between fMRI data and self-reported empathy. Both cognitive and affective ToM conditions were associated with neural responses in the classic ToM network across both groups, although only affective ToM recruited medial/ventromedial PFC (mPFC/vmPFC). Adolescents additionally activated vmPFC more than did adults during affective ToM. The specificity of the mPFC/vmPFC response during affective ToM supports evidence from lesion studies suggesting that vmPFC may integrate affective information during ToM. Furthermore, the differential neural response in vmPFC between adult and adolescent groups indicates developmental changes in affective ToM processing.

Heightened neural reactivity to threat in child victims of family violence

Summary Exposure to family violence affects a significant minority of children: estimates of physical abuse range from 4 to 16%, while intimate partner violence affects between 8 and 25% of children [1]. These maltreatment experiences represent a form of environmental stress that significantly increases risk of later psychopathology, including anxiety [1,2]. To date, no functional magnetic resonance imaging (fMRI) studies have probed the neural correlates of emotional processing in children exposed to family violence. Previous psychological and electrophysiological studies indicate a selective hypervigilance to angry cues in physically abused children, which is in turn associated with elevated levels of anxiety [3]. Functional magnetic resonance imaging (fMRI) research has demonstrated increased reactivity of the anterior insula (AI) and amygdala to angry faces in individuals with anxiety disorder [4], and in psychiatrically healthy soldiers exposed to combat [5], making these regions plausible neural candidates for adaptation to threat. We demonstrated that children exposed to family violence (with normative levels of anxiety) show increased AI and amygdala reactivity in response to angry but not sad faces. While such enhanced reactivity to a biologically salient threat cue may represent an adaptive response to sustained environmental danger, it may also constitute a latent neurobiological risk factor increasing vulnerability to psychopathology.

Developmental influences on the neural bases of responses to social rejection: Implications of social neuroscience for education

Relational aggression such as social rejection is common within school peer groups. Converging evidence suggests that adolescent females are particularly sensitive to social rejection. We used a novel fMRI adaptation of the Cyberball social rejection paradigm to investigate the neural response to social rejection in 19 mid-adolescent (aged 14-16) and 16 adult female participants. Across all participants, social exclusion (relative to inclusion) elicited a response in bilateral medial prefrontal cortex (mPFC) extending into ventral and subgenual anterior cingulate cortex and medial orbitofrontal cortex; and the left ventrolateral PFC (vlPFC); regions that have been associated in previous studies with social evaluation, negative affective processing, and affect regulation respectively. However, the exclusion-related response in right vlPFC, a region associated in previous studies with the regulation of rejection-related distress, was attenuated in adolescents. Within mPFC, greater activation during exclusion vs. inclusion was associated with greater self-reported susceptibility to peer influence in adolescents but not in adults. This suggests that the brains response to experimentally-induced social rejection relates to adolescent behaviour in real-world social interactions. We speculate about the potential implications of these findings for educational settings. In particular, functional development of affective circuitry during adolescence may influence social interaction within the school peer group.

Functional specificity of human premotor-motor cortical interactions during action selection.

Functional connections between dorsal premotor cortex (PMd) and primary motor cortex (M1) have been revealed by paired‐pulse transcranial magnetic stimulation (TMS). We tested if such connections would be modulated during a cognitive process (response selection) known to rely on those circuits. PMd–M1 TMS applied 75 ms after a cue to select a manual response facilitated motor‐evoked potentials (MEPs). MEPs were facilitated at 50 ms in a control task of response execution, suggesting that PMd–M1 interactions at 75 ms are functionally specific to the process of response selection. At 100 ms, PMd–M1 TMS delayed choice reaction time (RT). Importantly, the MEP (at 75 ms) and the RT (at 100 ms) effects were correlated in a way that was hand‐specific. When the response was made with the M1‐contralateral hand, MEPs correlated with slower RTs. When the response was made with the M1‐ipsilateral hand, MEPs correlated with faster RTs. Paired‐pulse TMS confined to M1 did not produce these effects, confirming the causal influence of PMd inputs. This study shows that a response selection signal evolves in PMd early during the reaction period (75–100 ms), impacts on M1 and affects behaviour. Such interactions are temporally, anatomically and functionally specific, and have a causal role in choosing which movement to make.

Individual differences in white-matter microstructure reflect variation in functional connectivity during choice.

The relation between brain structure and function is of fundamental importance in neuroscience. Comparisons between behavioral and brain-imaging measures suggest that variation in brain structure correlates with the presence of specific skills. Behavioral measures, however, reflect the integrated function of multiple brain regions. Rather than behavior, a physiological index of function could be a more sensitive and informative measure with which to compare structural measures. Here, we test for a relationship between a physiological measure of functional connectivity between two brain areas during a simple decision-making task and a measure of structural connectivity. Paired-pulse transcranial magnetic stimulation indexed functional connectivity between two regions important for action choices: the premotor and motor cortex. Fractional anisotropy (FA), a marker of microstructural integrity, indexed structural connectivity. Individual differences in functional connectivity during action selection show highly specific correlations with FA in localized regions of white-matter interconnecting regions, including the premotor and motor cortex. Probabilistic tractography, a technique for identifying fiber pathways from diffusion-weighted imaging (DWI), was used to reconstruct the anatomical networks linking the component brain regions involved in making decisions. These findings demonstrate a relationship between individual differences in functional and structural connectivity within human brain networks central to action choice.

Association of Callous Traits with Reduced Neural Response to Others’ Pain in Children with Conduct Problems

Summary Children with conduct problems (CP) persistently violate others’ rights and represent a considerable societal cost [1]. These children also display atypical empathic responses to others’ distress [2], which may partly account for their violent and antisocial behavior. Callous traits index lack of empathy in these children and confer risk for adult psychopathy [3]. Investigating neural responses to others’ pain is an ecologically valid method to probe empathic processing [4], but studies in children with CP have been inconclusive [5, 6]. Using functional magnetic resonance imaging (fMRI), we measured neural responses to pictures of others in pain (versus no pain) in a large sample of children with CP and matched controls. Relative to controls, children with CP showed reduced blood oxygen level-dependent responses to others’ pain in bilateral anterior insula (AI), anterior cingulate cortex (ACC), and inferior frontal gyrus, regions associated with empathy for pain in previous studies [7, 8]. In the CP group, callous traits were negatively associated with responses to others’ pain in AI and ACC. We conclude that children with CP have atypical neural responses to others’ pain. The negative association between callous traits and AI/ACC response could reflect an early neurobiological marker indexing risk for empathic deficits seen in adult psychopathy.

Amygdala activation in maltreated children during pre-attentive emotional processing

BACKGROUND Childhood adversity is associated with significantly increased risk of psychiatric disorder. To date, functional magnetic resonance imaging (fMRI) studies of children have mainly focused on institutionalisation and investigated conscious processing of affect. AIMS To investigate neural response to pre-attentively presented affect cues in a community sample of children with documented experiences of maltreatment in the home. METHOD A masked dot-probe paradigm involving pre-attentive presentation of angry, happy and neutral facial expressions was employed. Eighteen maltreated children were compared with 23 carefully matched non-maltreated peers. RESULTS Increased neural response was observed in the right amygdala for pre-attentively presented angry and happy faces in maltreated v. non-maltreated children. Level of amygdala activation was negatively associated with age at onset for several abuse subtypes. CONCLUSIONS Maltreatment is associated with heightened neural response to positive and negative facial affect, even to stimuli outside awareness. This may represent a latent neural risk factor for future psychiatric disorder.

Reduced orbitofrontal and temporal grey matter in a community sample of maltreated children

BACKGROUND Childhood maltreatment is strongly associated with increased risk of psychiatric disorder. Previous neuroimaging studies have reported atypical neural structure in the orbitofrontal cortex, temporal lobe, amygdala, hippocampus and cerebellum in maltreated samples. It has been hypothesised that these structural differences may relate to increased psychiatric vulnerability. However, previous studies have typically recruited clinical samples with concurrent psychiatric disorders, or have poorly characterised the range of maltreatment experiences and levels of concurrent anxiety or depression, limiting the interpretation of the observed structural differences. METHODS We used voxel-based morphometry to compare grey matter volume in a group of 18 children (mean age 12.01 years, SD = 1.4), referred to community social services, with documented and well-characterised experiences of maltreatment at home and a group of 20 nonmaltreated children (mean age 12.6 years, SD = 1.3). Both groups were comparable on age, gender, cognitive ability, ethnicity and levels of anxiety, depression and posttraumatic stress symptoms. We examined five a priori regions of interest: the prefrontal cortex, temporal lobes, amygdala, hippocampus and cerebellum. RESULTS Maltreated children, compared to nonmaltreated peers, presented with reduced grey matter in the medial orbitofrontal cortex and the left middle temporal gyrus. CONCLUSIONS The medial orbitofrontal cortex and the middle temporal gyrus have been implicated in reinforcement-based decision-making, emotion regulation and autobiographical memory, processes that are impaired in a number of psychiatric disorders associated with maltreatment. We speculate that grey matter disturbance in these regions in a community sample of maltreated children may represent a latent neurobiological risk factor for later psychopathology and heightened risk taking.