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Distinct RA- and PA-related connectivity patterns within cases. There was only one partly overlapping connectivity pattern related to both RA and PA for the seed in the left amygdala. The seed regions are depicted in the left panel, with corresponding projections shown in the right panel. The results are FWE-corrected, p < 0.008. The arrows reflect the effect direction (hyper- and hypo-connectivity)
Source publication
There is increasing evidence for altered brain resting state functional connectivity in adolescents with disruptive behavior. While a considerable body of behavioral research points to differences between reactive and proactive aggression, it remains unknown whether these two subtypes have dissociable effects on connectivity. Additionally, callous-...
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Evidence suggests that depressive symptomatology is a consequence of network dysfunction rather than lesion pathology. We studied whole-brain functional connectivity using a Minimum Spanning Tree as a graph-theoretical approach. Furthermore, we examined functional connectivity in the Default Mode Network, the Frontolimbic Network (FLN), the Salienc...
Citations
... This may result in an irritable child's own experiences of anger exerting a top-down influence on anger perception and leading to a greater tendency to interpret faces as angry. Similar increases in amygdala-precuneus functional connectivity have been associated with aggression in adolescents with disruptive behavior disorders (Werhahn et al., 2021), and have been observed in adolescents with mood disorders (Cullen et al., 2014;Singh et al., 2015). Task-based studies of attention bias using facial expression stimuli show altered function of the precuneus in irritable adolescents (Kryza-Lacombe et al., 2020;Naim et al., 2022), further highlighting the putative role of this region in pediatric irritability. ...
Neurocognitive models of pediatric irritability suggest a prominent role of anger; however, few studies have investigated anger-related biases and their neural correlates. Resting state functional connectivity (rsFC) of the amygdala was examined in relation to anger attribution bias (AAB) in a sample of young children (5–9 years old; N = 60; 55% White, 26.7% Hispanic) with clinically significant irritability characterized by impairing emotional outbursts (IEOs). Children completed a resting state functional magnetic resonance imaging scan as well as the assessment of children’s emotional skills (ACES), which yields three measures of AAB in the context of social situations, social behaviors, and facial expressions. ACES scores were entered into a general linear model to examine associations with rsFC of the bilateral amygdalae. Children with IEOs exhibited significant biases in attributing anger to others across all three ACES domains. Greater biases toward attributing anger in social situations were associated with reduced rsFC of the bilateral amygdalae with the fusiform/lingual gyri and lateral occipital cortex. Alternatively, greater biases toward attributing anger to facial expressions positively predicted right amygdala–precuneus rsFC. Greater bias toward attributing anger to others based on their behaviors was associated with heightened rsFC of the right amygdala with the left middle frontal gyrus. Findings extend previous work implicating functional connections among regions of default mode and frontoparietal networks in pediatric irritability. Longitudinal studies are needed to further investigate the putative role of AAB in the etiology and long-term outcomes of pediatric irritability.
... However, most of the studies they included were conducted in adults, and neural correlates of RA and PA in disruptive children and adolescents remain underexamined. To the best of our knowledge, only two previous studies have examined RA-and PA-related neural differences using functional connectivity in children and adolescents (Ibrahim et al., 2022;Werhahn et al., 2021). Ibrahim et al. (2022) employed connectome-based predictive modeling during an implicit face perception task and identified largely similar patterns of network connectivity for PA and RA in children (alongside with some distinct alterations). ...
... Ibrahim et al. (2022) employed connectome-based predictive modeling during an implicit face perception task and identified largely similar patterns of network connectivity for PA and RA in children (alongside with some distinct alterations). In our previous study, we had investigated rsFC differences related to PA and RA in children and adolescents with disruptive behavior disorder using a seed-based approach (Werhahn et al., 2021). Our results showed that both subdimensions were associated with overlapping as well as distinct effects on rsFC. ...
... Prior investigations showed that male adolescents with CU traits exhibited altered amygdala sub-regional rsFC (Aghajani et al., 2017(Aghajani et al., , 2016 and reduced amygdala efficiency (Jiang et al., 2021) compared to controls. Correlational studies conducted with large samples further demonstrated that CU traits were linked to rsFC abnormalities in the DMN and attention networks as well as disrupted connectivity between DMN (Umbach and Tottenham, 2021;Werhahn et al., 2021) and attention networks (Pu et al., 2017;Winters et al., 2023). However, these studies were also biased in terms of a priori selection of regions or parcellation maps. ...
Background
Disruptive behavior in children and adolescents can manifest as reactive aggression and proactive aggression and is modulated by callous-unemotional traits and other comorbidities. Neural correlates of these aggression dimensions or subtypes and comorbid symptoms remain largely unknown. This multi-center study investigated the relationship between resting state functional connectivity (rsFC) and aggression subtypes considering comorbidities.
Methods
The large sample of children and adolescents aged 8–18 years (n = 207; mean age = 13.30±2.60 years, 150 males) included 118 cases with disruptive behavior (80 with Oppositional Defiant Disorder and/or Conduct Disorder) and 89 controls. Attention-deficit/hyperactivity disorder (ADHD) and anxiety symptom scores were analyzed as covariates when assessing group differences and dimensional aggression effects on hypothesis-free global and local voxel-to-voxel whole-brain rsFC based on functional magnetic resonance imaging at 3 Tesla.
Results
Compared to controls, the cases demonstrated altered rsFC in frontal areas, when anxiety but not ADHD symptoms were controlled for. For cases, reactive and proactive aggression scores were related to global and local rsFC in the central gyrus and precuneus, regions linked to aggression-related impairments. Callous-unemotional trait severity was correlated with ICC in the inferior and middle temporal regions implicated in empathy, emotion, and reward processing. Most observed aggression subtype-specific patterns could only be identified when ADHD and anxiety were controlled for.
Conclusions
This study clarifies that hypothesis-free brain connectivity measures can disentangle distinct though overlapping dimensions of aggression in youths. Moreover, our results highlight the importance of considering comorbid symptoms to detect aggression-related rsFC alterations in youths.
... The HBN adopted a community-referred recruitment model in which advertisements was provided to community members, educators, parents. Exclusion criteria were impairments that prevents full participation in the study (e.g., serious neurological disorders, between CU subconstructs (specifically callousness) and brain activity/functional connectivity measures (Lockwood et al., 2013;Werhahn et al., 2021;Yoder et al., 2016). ...
A large body of literature suggests that the primary (high callousness-unemotional traits [CU] and low anxiety) and secondary (high CU traits and anxiety) variants of psychopathy significantly differ in terms of their clinical profiles. However, little is known about their neurobiological differences. While few studies showed that variants differ in brain activity during fear processing, it remains unknown whether they also show atypical functioning in motivational and reward system. Latent Profile Analysis (LPA) was conducted on a large sample of adolescents (n = 1416) to identify variants based on their levels of callousness and anxiety. Seed-to-voxel connectivity analysis was subsequently performed on resting-state fMRI data to compare connectivity patterns of the nucleus accumbens across subgroups. LPA failed to identify the primary variant when using total score of CU traits. Using a family-wise cluster correction, groups did not differ on functional connectivity. However, at an uncorrected threshold the secondary variant showed distinct functional connectivity between the nucleus accumbens and posterior insula, lateral orbitofrontal cortex, supplementary motor area, and parietal regions. Secondary LPA analysis using only the callousness subscale successfully distinguish both variants. Group differences replicated results of deficits in functional connectivity between the nucleus accumbens and posterior insula and supplementary motor area, but additionally showed effect in the superior temporal gyrus which was specific to the primary variant. The current study supports the importance of examining the neurobiological markers across subgroups of adolescents at risk for conduct problems to precise our understanding of this heterogeneous population.
... Some of these include parenting style, childhood trauma, environmental exposures, and genetic make-up (Fergusson et al., 2008;Krischer and Sevecke, 2008;Wright et al., 2008;Marcus et al., 2010;Waller et al., 2012;Beckley et al., 2018;Sampson and Winter, 2018;Reuben et al., 2019). Brain imaging has shown that these traits are associated with altered functioning, primarily in limbic and paralimbic regions (e.g., insulae, temporal poles, posterior and anterior cingulate cortex, ventral striatum, and amygdalae) but also across the default mode network more generally [DM: e.g., precuneus and medial prefrontal cortex (mPFC): Chen et al., 2015;Cohn et al., 2015;Thijssen and Kiehl, 2017;Dugré and Potvin, 2021;Thijssen et al., 2021;Umbach and Tottenham, 2021;Werhahn et al., 2021;Winters et al., 2021]. While the literature investigating the relationship between functional connectivity and antisocial traits in adolescents is growing, there is an absence of research focusing specifically on high-risk adolescent girls with established poor behavioral outcomes (i.e., arrests and convictions). ...
... We hypothesized that abnormalities in functional network connectivity related to psychopathic traits would occur primarily in limbic, paralimbic, and default mode network related regions of the brain (i.e., temporal poles, amygdalae, caudate/putamen, orbitofrontal cortex, dorsomedial prefrontal cortex, posterior cingulate cortex, and precunei). These regions span multiple cognitive domains, are involved in higher-order cognitive processes, such as emotion regulation, and are consistent with previously published studies in adolescent boys and adult men and women (Kiehl, 2006;Cope et al., 2014;Fairchild et al., 2014;Chen et al., 2015;Cohn et al., 2015;Philippi et al., 2015;Thijssen and Kiehl, 2017;Lindner et al., 2018;Dugré and Potvin, 2021;Thijssen et al., 2021;Umbach and Tottenham, 2021;Werhahn et al., 2021;Winters et al., 2021;Allen et al., 2022b). Parallel to analyses by our research group in incarcerated adult women and adolescent boys scoring high on psychopathic traits, this study serves an important role in assessing whether psychopathyrelated neural alterations are consistent from adolescence to adulthood, or rather, present differently in younger samples of women. ...
... Hz cutoffs. From the 39 extracted components, 10 components of interest were selected for the primary analyses based on relevant literature (see Figure 2 for a priori components of interest: Kiehl, 2006;Cope et al., 2014;Fairchild et al., 2014;Chen et al., 2015;Cohn et al., 2015;Philippi et al., 2015;Thijssen and Kiehl, 2017;Lindner et al., 2018;Dugré and Potvin, 2021;Thijssen et al., 2021;Umbach and Tottenham, 2021;Werhahn et al., 2021;Winters et al., 2021;Allen et al., 2022b). ...
Previous work in incarcerated boys and adult men and women suggest that individuals scoring high on psychopathic traits show altered resting-state limbic/paralimbic, and default mode functional network properties. However, it is unclear whether similar results extend to high-risk adolescent girls with elevated psychopathic traits. This study examined whether psychopathic traits [assessed via the Hare Psychopathy Checklist: Youth Version (PCL:YV)] were associated with altered inter-network connectivity, intra-network connectivity (i.e., functional coherence within a network), and amplitude of low-frequency fluctuations (ALFFs) across resting-state networks among high-risk incarcerated adolescent girls ( n = 40). Resting-state networks were identified by applying group independent component analysis (ICA) to resting-state fMRI scans, and a priori regions of interest included limbic, paralimbic, and default mode network components. We tested the association of psychopathic traits (PCL:YV Factor 1 measuring affective/interpersonal traits and PCL:YV Factor 2 assessing antisocial/lifestyle traits) to these three resting-state measures. PCL:YV Factor 1 scores were associated with increased low-frequency and decreased high-frequency fluctuations in components corresponding to the default mode network, as well as increased intra-network FNC in components corresponding to cognitive control networks. PCL:YV Factor 2 scores were associated with increased low-frequency fluctuations in sensorimotor networks and decreased high-frequency fluctuations in default mode, sensorimotor, and visual networks. Consistent with previous analyses in incarcerated adult women, our results suggest that psychopathic traits among incarcerated adolescent girls are associated with altered intra-network ALFFs—primarily that of increased low-frequency and decreased high-frequency fluctuations—and connectivity across multiple networks including paralimbic regions. These results suggest stable neurobiological correlates of psychopathic traits among women across development.
... During resting-state, previous studies have shown that the severity of CU traits (and psychopathic traits in adults) is linked to altered connectivity between the amygdala and the dorsomedial prefrontal cortex (dmPFC), midcingulate cortex (MCC), precentral gyrus (Aghajani et al., 2017;Contreras-Rodríguez et al., 2015), and temporal regions such as the posterior superior temporal sulcus (pSTS) and the temporoparietal junction (TPJ) (Aghajani et al., 2017;Espinoza et al., 2019). However, some studies have found no significant association between callousness and amygdala connectivity in adolescents (Cohn et al., 2015;Werhahn et al., 2021). Methodological differences in resting-state connectivity analyses (e.g., ROI-to-ROI, seed-to-voxel, intrinsic networks), small sample sizes, and lack of consideration for confounders may partially explain these discrepant results. ...
Over the past years, research has shown that primary (high callousness and low anxiety) and secondary (high callousness and anxiety) variants of CU traits may be associated with opposite amygdala activity (hypo- and hyper-reactivity, respectively). However, their differences in amygdala functional connectivity remains largely unexplored. We conducted a Latent Profile Analysis on a large sample of adolescents (n = 1416) to identify homogeneous subgroups with different levels of callousness and anxiety. We then performed a seed-to-voxel connectivity analysis on resting-state fMRI data to compare subgroups on connectivity patterns of the amygdala. We examined the results in relation to conduct problems to identify potential neural risk factors. The Latent Profile Analysis revealed four subgroups, including primary and secondary variants of psychopathy, anxious adolescents, and typically developing adolescents. The seed-to-voxel analyses showed that the primary variant was mainly characterized by increased connectivity between the left amygdala, and left thalamus. The secondary variant exhibited deficient connectivity between the amygdala and the dorsomedial prefrontal cortex, temporo-parietal junction, premotor, and postcentral gyrus. Both variants showed increased connectivity with the right thalamus but exhibited opposite functional connectivity between the left amygdala and the parahippocampal gyrus. Dimensional analyses indicated that conduct problems may play a mediating role between callousness and amygdala-dmPFC functional connectivity across youths with already high levels of callousness. Our study highlights that both variants largely differ in the functional connectivity of the amygdala. The results support the importance of disentangling the heterogeneity of adolescents at risk for conduct problems.
... The precuneus, as part of the parietal lobe, is a brain area implied in a variety of complex functions and is part of the default mode network. Unsurprisingly, a recent metaanalysis of fMRI studies confirmed a significantly changed connectivity of the precuneus and frontal brain structures in aggression-prone individuals [47], as well as in juvenile violent offenders [97] and adolescents displaying disruptive behavior [98]. Additionally, increased neuronal reactivity to socio-emotional stimuli in the precuneus was linked to aggression [99,100]. ...
Aggression can be conceptualized as any behavior, physical or verbal, that involves attacking another person or animal with the intent of causing harm, pain or injury. Because of its high prevalence worldwide, aggression has remained a central clinical and public safety issue. Aggression can be caused by several risk factors, including biological and psychological, such as genetics and mental health disorders, and socioeconomic such as education, employment, financial status, and neighborhood. Research over the past few decades has also proposed a link between alcohol consumption and aggressive behaviors. Alcohol consumption can escalate aggressive behavior in humans, often leading to domestic violence or serious crimes. Converging lines of evidence have also shown that trauma and posttraumatic stress disorder (PTSD) could have a tremendous impact on behavior associated with both alcohol use problems and violence. However, although the link between trauma, alcohol, and aggression is well documented, the underlying neurobiological mechanisms and their impact on behavior have not been properly discussed. This article provides an overview of recent advances in understanding the translational neurobiological basis of aggression and its intricate links to alcoholism and trauma, focusing on behavior. It does so by shedding light from several perspectives, including in vivo imaging, genes, receptors, and neurotransmitters and their influence on human and animal behavior.
... Although some functional imaging studies revealed that emotional stimuli activate PCC (Maddock et al., 2003), its role in cognition, however, extends well beyond emotional processing (Leech & Sharp, 2014;Vogt, 2009). In term of aggression, PCC has been suggested to be implicated to both proactive-instrumental aggression-related moral cognition and emotion (Zhu et al., 2019) as well as reactive-impulsive aggression (Werhahn et al., 2021). ...
Aggression is a complex social behavior that evolved in the context of defending a territory, fighting for limited resources, and competing for mates and protection. Although aggression considered as a negative or undesirable emotion is an essential part of many species' repertoire of social behaviors. For humans, the motivations, actions, and limits of aggressive acts are not always clear. However, uncontrolled aggression may have destructive consequences, and it develops inappropriately into violence. At the neural level, several studies demonstrated that aggression is related to cortical abnormalities, including the anterior cingulate cortex (ACC). This review summarizes the state of the literature regarding the involvement of ACC in the neurobiology of aggression and impulsivity. We will first review structural and neuroanatomical studies, including volumetric and functional investigations of aggression. Next, we will discuss the neurochemical and neuropharmacological studies of aggression related to the ACC. We will focus mainly on the gamma-aminobutyric acid/glutamate balance, as well as the serotoninergic system. Finally, we will try to integrate these results and reconcile discrepancies in the field and suggest recommendations for future studies. (PsycInfo Database Record (c) 2023 APA, all rights reserved).
... Head-to-head comparisons of proactively vs. reactively aggressive individuals or situations have found an assortment of differences in some neural structure volumes (Breitschuh et al., 2018;Naaijen et al., 2020;Yang et al., 2017b), resting state connectivity (Romero-Martínez et al., 2019;Werhahn et al., 2021) as well as ERP and EEG activity (Moran et al., 2014;Paiva et al., 2021). However, systematic patterns are not yet clear. ...
... For example, dorsal and posterior cingulate loci are activated in young adults playing proactively violent videogames (Mathiak and Weber, 2006). Posterior cingulate loci are also active during anger, which might involve their memory function, supporting recall of previous provoking events and grievances and outcomes of past hostile encounters at the early appraisal stage of emotion processing as well as during post-provocation angry rumination (Pelliccia et al., 2022;Werhahn et al., 2021). Hidden in the depths of the Sylvian fissure, the human insula, too, is activated in anger (Kim et al., 2021;Kirby and Robinson, 2017;Sorella et al., 2022). ...
Human aggression typologies largely correspond with those for other animals. While there may be no non-human equivalent of angry reactive aggression, we propose that human proactive aggression is similar to offense in other animals' dominance contests for territory or social status. Like predation/hunting, but unlike defense, offense and proactive aggression are positively reinforcing, involving dopamine release in accumbens. The drive these motivational states provide must suffice to overcome fear associated with initiating risky fights. We term the neural activity motivating proactive aggression "non-angry aggressive arousal", but use "angriffsberietschaft" for offense motivation in other animals to acknowledge possible differences. Temporal variation in angriffsberietschaft partitions fights into bouts; engendering reduced anti-predator vigilance, redirected aggression and motivational over-ride. Increased aggressive arousal drives threat-to-attack transitions, as in verbal-to-physical escalation and beyond that, into hyper-aggression. Proactive aggression and offense involve related neural activity states. Cingulate, insular and prefrontal cortices energize/modulate aggression through a subcortical core containing subnuclei for each aggression type. These proposals will deepen understanding of aggression across taxa, guiding prevention/intervention for human violence.
... Accordingly, most studies particularly distinguish between reactive aggression versus CU traits and proactive aggression with respect to emotion recognition abilities [6,7]. Yet, some recent studies point to distinct neural correlates for CU traits versus proactive aggression [8][9][10]. In addition, a person-oriented approach on clinic-referred youth with disruptive behavior resulted in different clusters with varying levels of CU traits and aggression, one of which exhibited high CU traits and reactive aggression yet low proactive aggression [11]. ...
Youth with disruptive behavior showing high callous-unemotional (CU) traits and proactive aggression are often assumed to exhibit distinct impairments in emotion recognition from those showing mainly reactive aggression. Yet, reactive and proactive aggression and CU traits may co-occur to varying degrees across individuals. We aimed to investigate emotion recognition in more homogeneous clusters based on these three dimensions. In a sample of 243 youth (149 with disruptive behavior problems and 94 controls) aged 8–18 years, we used model-based clustering on self-report measures of CU traits and reactive and proactive aggression and compared the resulting clusters on emotion recognition (accuracy and response bias) and working memory. In addition to a Low and Low-Moderate symptom cluster, we identified two high CU clusters. The CU-Reactive cluster showed high reactive and low-to-medium proactive aggression; the CU-Mixed cluster showed high reactive and proactive aggression. Both CU clusters showed impaired fear recognition and working memory, whereas the CU-Reactive cluster also showed impaired recognition of disgust and sadness, partly explained by poor working memory, as well as a response bias for anger and happiness. Our results confirm the importance of CU traits as a core dimension along which youth with disruptive behavior may be characterized, yet challenge the view that high CU traits are closely linked to high proactive aggression per se. Notably, distinct neurocognitive processes may play a role in youth with high CU traits and reactive aggression with lower versus higher proactive aggression.
... For example, those with higher CU traits demonstrate reduced connectivity within the DMN (Umbach and Tottenham, 2020) and SAL, (Yoder et al., 2016) as well as aberrant connectivity within the FPN (Pu et al., 2017), which are inverse to the associations reported for empathy above. Similarly, although in normative samples we expect anticorrelation in functional coupling between task positive and task negative networks (for review see: Menon, 2015), that is suggested to support empathy , those with higher CU traits demonstrate with less anticorrelation between DMN-FPN (Pu et al., 2017;Werhahn et al., 2020;Winters et al., 2021b) and DMN-SAL (Werhahn et al., 2020). Together these findings suggest reduced efficiency of network function in those with higher CU traits that also support empathy. ...
... For example, those with higher CU traits demonstrate reduced connectivity within the DMN (Umbach and Tottenham, 2020) and SAL, (Yoder et al., 2016) as well as aberrant connectivity within the FPN (Pu et al., 2017), which are inverse to the associations reported for empathy above. Similarly, although in normative samples we expect anticorrelation in functional coupling between task positive and task negative networks (for review see: Menon, 2015), that is suggested to support empathy , those with higher CU traits demonstrate with less anticorrelation between DMN-FPN (Pu et al., 2017;Werhahn et al., 2020;Winters et al., 2021b) and DMN-SAL (Werhahn et al., 2020). Together these findings suggest reduced efficiency of network function in those with higher CU traits that also support empathy. ...
... Between DMN-SAL connectivity was higher with higher CU traits, whereas between DMN-SAL connectivity was lower at higher levels of both cognitive and affective empathy. This finding extends the extant literature on CU traits (Werhahn et al., 2020) and both cognitive and affective empathy (Winters et al., 2021a) by demonstrating their similar, and inverse, associations with between DMN-SAL connectivity among the same sample of adolescents. ...
Background
Low empathy is one component of affective impairments defining the antisocial youth phenotype callous-unemotional (CU) traits. Research suggests CU traits may be negatively associated with neural networks that are positively associated with cognitive and affective empathy – specifically the default mode (DMN), frontoparietal (FPN), and salience (SAL) networks. Determining which functional network connections are shared between CU traits and empathy could elucidate the extent to which CU traits shares neural substrates with cognitive versus affective empathy. The present study tested whether CU traits and both cognitive and affective empathy share network connections within and between the DMN, FPN, and SAL.
Methods
Participants (n = 112, aged 13–17, 43 % female) completed resting-state functional magnetic resonance imaging and self-reports for CU traits and empathy as part of a Nathan-Kline Institute study.
Results
Analyses revealed inverse associations with shared network connections between CU traits and both cognitive and affective empathy. Specifically, within-DMN connectivity negatively associated with CU traits, but positively associated with cognitive empathy; and between DMN-SAL connectivity positively associated with CU traits, but negatively associated with both cognitive and affective empathy. However, joint models revealed little variance explained by CU traits and empathy overlapped.
Limitations
The sample was cross-sectional collection with limited participants (n = 112) from the community that may not generalize to incarcerated adolescents.
Conclusions
Results demonstrate CU traits inversely associated with similar connectivity patterns as cognitive and affective empathy though prediction among constructs did not significantly overlap. Further investigation of these connections can inform a mechanistic understanding of empathy impairments in CU traits.
