Increased amygdala and decreased frontolimbic r esting- s tate functional connectivity in children with aggressive behavior.
ABSTRACT: Childhood maladaptive aggression is associated with disrupted functional connectivity within amygdala-prefrontal circuitry. In this study, neural correlates of childhood aggression were probed using the intrinsic connectivity distribution, a voxel-wise metric of global resting-state brain connectivity. This sample included 38 children with aggressive behavior (26 boys, 12 girls) ages 8-16 years and 21 healthy controls (14 boys, 6 girls) matched for age and IQ. Functional MRI data were acquired during resting state, and differential patterns of intrinsic functional connectivity were tested in a priori regions of interest implicated in the pathophysiology of aggressive behavior. Next, correlational analyses tested for associations between functional connectivity and severity of aggression measured by the Reactive-Proactive Aggression Questionnaire in children with aggression. Children with aggressive behavior showed increased global connectivity in the bilateral amygdala relative to controls. Greater severity of aggressive behavior was associated with decreasing global connectivity in the dorsal anterior cingulate and ventromedial prefrontal cortex. Follow-up seed analysis revealed that aggression was also positively correlated with left amygdala connectivity with the dorsal anterior cingulate, ventromedial and dorsolateral prefrontal cortical regions. These results highlight the potential role of connectivity of the amygdala and medial prefrontal and anterior cingulate cortices in modulating the severity of aggressive behavior in treatment-seeking children.
Project description:Impulsive aggression is common among military personnel after deployment and may arise because of impaired top-down regulation of the amygdala by prefrontal regions. This study sought to further explore this hypothesis via resting-state functional connectivity analyses in impulsively aggressive combat veterans. Male combat veterans with (n?=?28) and without (n?=?30) impulsive aggression problems underwent resting-state functional magnetic resonance imaging. Functional connectivity analyses were conducted with the following seed-regions: basolateral amygdala (BLA), centromedial amygdala, anterior cingulate cortex (ACC), and anterior insular cortex (AIC). Regions-of-interest analyses focused on the orbitofrontal cortex and periaqueductal gray, and yielded no significant results. In exploratory cluster analyses, we observed reduced functional connectivity between the (bilateral) BLA and left dorsolateral prefrontal cortex in the impulsive aggression group, relative to combat controls. This finding indicates that combat-related impulsive aggression may be marked by weakened functional connectivity between the amygdala and prefrontal regions, already in the absence of explicit emotional stimuli. Group differences in functional connectivity were also observed between the (bilateral) ACC and left cuneus, which may be related to heightened vigilance to potentially threatening visual cues, as well as between the left AIC and right temporal pole, possibly related to negative memory association in impulsive aggression.
Project description: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-unemotional traits are important specifiers in subtyping aggressive behavior along the affective dimension. Accordingly, we examined associations between two aggression subtypes along with callous-unemotional traits using a seed-to-voxel approach. Six functionally relevant seeds were selected to probe the salience and the default mode network, based on their presumed role in aggression. The resting state sequence was acquired from 207 children and adolescents of both sexes [mean age (standard deviation) = 13.30 (2.60); range = 8.02-18.35] as part of a Europe-based multi-center study. One hundred eighteen individuals exhibiting disruptive behavior (conduct disorder/oppositional defiant disorder) with varying comorbid attention-deficit/hyperactivity disorder (ADHD) symptoms were studied, together with 89 healthy controls. Proactive aggression was associated with increased left amygdala-precuneus coupling, while reactive aggression related to hyper-connectivities of the posterior cingulate cortex (PCC) to the parahippocampus, the left amygdala to the precuneus and to hypo-connectivity between the right anterior insula and the nucleus caudate. Callous-unemotional traits were linked to distinct hyper-connectivities to frontal, parietal, and cingulate areas. Additionally, compared to controls, cases demonstrated reduced connectivity of the PCC and left anterior insula to left frontal areas, the latter only when controlling for ADHD scores. Taken together, this study revealed aggression-subtype-specific patterns involving areas associated with emotion, empathy, morality, and cognitive control.
Project description:OBJECTIVE:Youths with disruptive behavior disorders (DBD) (conduct disorder and oppositional defiant disorder) have an elevated risk for maladaptive reactive aggression. Theory suggests that this is due to an elevated sensitivity of basic threat circuitry implicated in retaliation (amygdala/periaqueductal gray) in youths with DBD and low levels of callous-unemotional traits and dysfunctional regulatory activity in the ventromedial prefrontal cortex in youths with DBD irrespective of callous-unemotional traits. METHOD:A total of 56 youths 10-18 years of age (23 of them female) participated in the study: 30 youths with DBD, divided by median split into groups with high and low levels of callous-unemotional traits, and 26 healthy youths. All participants completed an ultimatum game task during functional MRI. RESULTS:Relative to the other groups, youths with DBD and low levels of callous-unemotional traits showed greater increases in activation of basic threat circuitry when punishing others and dysfunctional down-regulation of the ventromedial prefrontal cortex during retaliation. Relative to healthy youths, all youths with DBD showed reduced amygdala-ventromedial prefrontal cortex connectivity during high provocation. Ventromedial prefrontal cortex responsiveness and ventromedial prefrontal cortex-amygdala connectivity were related to patients' retaliatory propensity (behavioral responses during the task) and parent-reported reactive aggression. CONCLUSIONS:These data suggest differences in the underlying neurobiology of maladaptive reactive aggression in youths with DBD who have relatively low levels of callous-unemotional traits. Youths with DBD and low callous-unemotional traits alone showed significantly greater threat responses during retaliation relative to comparison subjects. These data also suggest that ventromedial prefrontal cortex-amygdala connectivity is critical for regulating retaliation/reactive aggression and, when dysfunctional, contributes to reactive aggression, independent of level of callous-unemotional traits.
Project description:For some people facial expressions of aggression are intimidating, for others they are perceived as provocative, evoking an aggressive response. Identifying the key neurobiological factors that underlie this variation is fundamental to our understanding of aggressive behaviour. The amygdala and the ventral anterior cingulate cortex (ACC) have been implicated in aggression. Using functional magnetic resonance imaging (fMRI), we studied how the interaction between these regions is influenced by the drive to obtain reward (reward-drive or appetitive motivation), a personality trait consistently associated with aggression. Two distinct techniques showed that the connectivity between the ventral ACC and the amygdala was strongly correlated with personality, with high reward-drive participants displaying reduced negative connectivity. Furthermore, the direction of this effect was restricted from ventral ACC to the amygdala but not vice versa. The personality-mediated variation in the pathway from the ventral anterior cingulate cortex to the amygdala provides an account of why signals of aggression are interpreted as provocative by some individuals more than others.
Project description:Anxiety disorders are common in autism spectrum disorder (ASD) and associated with social-communication impairment and repetitive behavior symptoms. The neurobiology of anxiety in ASD is unknown, but amygdala dysfunction has been implicated in both ASD and anxiety disorders. Using resting-state functional magnetic resonance imaging, we compared amygdala-prefrontal and amygdala-striatal connections across three demographically matched groups studied in the Autism Brain Imaging Data Exchange (ABIDE): ASD with a comorbid anxiety disorder (N = 25; ASD + Anxiety), ASD without a comorbid disorder (N = 68; ASD-NoAnx), and typically developing controls (N = 139; TD). Relative to ASD-NoAnx and TD controls, ASD + Anxiety individuals had decreased connectivity between the amygdala and dorsal/rostral anterior cingulate cortex (dACC/rACC). The functional connectivity of these connections was not affected in ASD-NoAnx, and amygdala connectivity with ventral ACC/medial prefrontal cortex (mPFC) circuits was not different in ASD + Anxiety or ASD-NoAnx relative to TD. Decreased amygdala-dorsomedial prefrontal cortex (dmPFC)/rACC connectivity was associated with more severe social impairment in ASD + Anxiety; amygdala-striatal connectivity was associated with restricted, repetitive behavior (RRB) symptom severity in ASD-NoAnx individuals. These findings suggest comorbid anxiety in ASD is associated with disrupted emotion-monitoring processes supported by amygdala-dACC/mPFC pathways, whereas emotion regulation systems involving amygdala-ventromedial prefrontal cortex (vmPFC) are relatively spared. Our results highlight the importance of accounting for comorbid anxiety for parsing ASD neurobiological heterogeneity.
Project description:Individual differences in a person's ability to control fear have been linked to activation in the dorsal anterior cingulate cortex, the ventromedial prefrontal cortex, and the amygdala. This study investigated whether functional variance in this network can be predicted by resting metabolism in these same regions.The authors measured resting brain metabolism in healthy volunteers with positron emission tomography using [18F]fluorodeoxyglucose. This was followed by a 2-day fear conditioning and extinction training paradigm using functional MRI to measure brain activation during fear extinction and recall. The authors used skin conductance response to index conditioned responding, and they used resting metabolism in the amygdala, the dorsal anterior cingulate cortex, and the ventromedial prefrontal cortex to predict responses during fear extinction and extinction recall.During extinction training, resting amygdala metabolism positively predicted activation in the ventromedial prefrontal cortex and negatively predicted activation in the dorsal anterior cingulate cortex. In contrast, during extinction recall, resting amygdala metabolism negatively predicted activation in the ventromedial prefrontal cortex and positively predicted activation in the dorsal anterior cingulate cortex. In addition, resting metabolism in the dorsal anterior cingulate cortex predicted fear expression (as measured by skin conductance response) during extinction recall.Resting brain metabolism predicted neuronal reactivity and skin conductance changes associated with the recall of the fear extinction memory.
Project description:BACKGROUND:Connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC) is compromised in multiple psychiatric disorders, many of which emerge during adolescence. To identify to what extent the deviations in amygdala-vmPFC maturation contribute to the onset of psychiatric disorders, it is essential to characterize amygdala-vmPFC connectivity changes during typical development. METHODS:Using an accelerated cohort longitudinal design (1-3 time points, 10-25 years old, n = 246), we characterized developmental changes of the amygdala-vmPFC subregion functional and structural connectivity using resting-state functional magnetic resonance imaging and diffusion-weighted imaging. RESULTS:Functional connectivity between the centromedial amygdala and rostral anterior cingulate cortex (rACC), anterior vmPFC, and subgenual cingulate significantly decreased from late childhood to early adulthood in male and female subjects. Age-associated decreases were also observed between the basolateral amygdala and the rACC. Importantly, these findings were replicated in a separate cohort (10-22 years old, n = 327). Similarly, structural connectivity, as measured by quantitative anisotropy, significantly decreased with age in the same regions. Functional connectivity between the centromedial amygdala and the rACC was associated with structural connectivity in these same regions during early adulthood (22-25 years old). Finally, a novel time-varying coefficient analysis showed that increased centromedial amygdala-rACC functional connectivity was associated with greater anxiety and depression symptoms during early adulthood, while increased structural connectivity in centromedial amygdala-anterior vmPFC white matter was associated with greater anxiety/depression during late childhood. CONCLUSIONS:Specific developmental periods of functional and structural connectivity between the amygdala and the prefrontal systems may contribute to the emergence of anxiety and depressive symptoms and may play a critical role in the emergence of psychiatric disorders in adolescence.
Project description:The ability to voluntarily regulate our emotional response to threatening and highly arousing stimuli by using cognitive reappraisal strategies is essential for our mental and physical well-being. This might be achieved by prefrontal brain regions (e.g. inferior frontal gyrus, IFG) down-regulating activity in the amygdala. It is unknown, to which degree effective connectivity within the emotion-regulation network is linked to individual differences in reappraisal skills. Using psychophysiological interaction analyses of functional magnetic resonance imaging data, we examined changes in inter-regional connectivity between the amygdala and IFG with other brain regions during reappraisal of emotional responses and used emotion regulation success as an explicit regressor. During down-regulation of emotion, reappraisal success correlated with effective connectivity between IFG with dorsolateral, dorsomedial and ventromedial prefrontal cortex (PFC). During up-regulation of emotion, effective coupling between IFG with anterior cingulate cortex, dorsomedial and ventromedial PFC as well as the amygdala correlated with reappraisal success. Activity in the amygdala covaried with activity in lateral and medial prefrontal regions during the up-regulation of emotion and correlated with reappraisal success. These results suggest that successful reappraisal is linked to changes in effective connectivity between two systems, prefrontal cognitive control regions and regions crucially involved in emotional evaluation.
Project description:The ability to successfully suppress impulses and angry affect is fundamental to control aggressive reactions following provocations. The aim of this study was to examine neural responses to provocations and aggression using a laboratory model of reactive aggression. We used a novel functional magnetic resonance imaging point-subtraction aggression paradigm in 44 men, of whom 18 were incarcerated violent offenders and 26 were control non-offenders. We measured brain activation following provocations (monetary subtractions), while the subjects had the possibility to behave aggressively or pursue monetary rewards. The violent offenders behaved more aggressively than controls (aggression frequency 150 vs 84, P?=?0.03) and showed significantly higher brain reactivity to provocations within the amygdala and striatum, as well as reduced amygdala-prefrontal and striato-prefrontal connectivity. Amygdala reactivity to provocations was positively correlated with task-related behavior in the violent offenders. Across groups, striatal and prefrontal reactivity to provocations was positively associated with trait anger and trait aggression. These results suggest that violent individuals display abnormally high neural sensitivity to social provocations, a sensitivity related to aggressive behavior. These findings provide novel insight into the neural pathways that are sensitive to provocations, which is critical to more effectively shaped interventions that aim to reduce pathological aggressive behavior.
Project description:Early life trauma exposure represents a potent risk factor for the development of mental illnesses such as anxiety, depression and post-traumatic stress disorder. Moreover, deleterious consequences of trauma are exacerbated in youth living in impoverished, urban environments. A priori probability maps were used to examine resting-state functional connectivity (FC) of the amygdala in 21 trauma-exposed, and 21 age- and sex-matched urban children and adolescents (youth) without histories of trauma. Intrinsic FC analyses focused on amygdala-medial prefrontal circuitry, a key emotion regulatory pathway in the brain. We discovered reduced negative amygdala-subgenual cingulate connectivity in trauma-exposed youth. Differences between groups were also identified in anterior insula and dorsal anterior cingulate to amygdala connectivity. Overall, results suggest a model in which urban-dwelling trauma-exposed youth lack negative prefrontal to amygdala connectivity that may be critical for regulation of emotional responses. Functional changes in amygdala circuitry might reflect the biological embedding of stress reactivity in early life and mediate enhanced vulnerability to stress-related psychopathology.