Background
Child maltreatment is common and has long‐term consequences for affective function. Investigations of neural consequences of maltreatment have focused on the amygdala. However, ...developmental neuroscience indicates that other brain regions are also likely to be affected by child maltreatment, particularly in the social information processing network (SIPN). We conducted a quantitative meta‐analysis to: confirm that maltreatment is related to greater bilateral amygdala activation in a large sample that was pooled across studies; investigate other SIPN structures that are likely candidates for altered function; and conduct a data‐driven examination to identify additional regions that show altered activation in maltreated children, teens, and adults.
Methods
We conducted an activation likelihood estimation analysis with 1,733 participants across 20 studies of emotion processing in maltreated individuals.
Results
Maltreatment is associated with increased bilateral amygdala activation to emotional faces. One SIPN structure is altered: superior temporal gyrus, of the detection node, is hyperactive in maltreated individuals. The results of the whole‐brain corrected analysis also show hyperactivation of the parahippocampal gyrus and insula in maltreated individuals.
Conclusions
The meta‐analysis confirms that maltreatment is related to increased bilateral amygdala reactivity and also shows that maltreatment affects multiple additional structures in the brain that have received little attention in the literature. Thus, although the majority of studies examining maltreatment and brain function have focused on the amygdala, these findings indicate that the neural consequences of child maltreatment involve a broader network of structures.
Autism spectrum disorders (ASD) impact social functioning and communication, and individuals with these disorders often have restrictive and repetitive behaviors. Accumulating data indicate that ASD ...is associated with alterations of neural circuitry. Functional MRI (FMRI) studies have focused on connectivity in the context of psychological tasks. However, even in the absence of a task, the brain exhibits a high degree of functional connectivity, known as intrinsic or resting connectivity. Notably, the default network, which includes the posterior cingulate cortex, retro-splenial, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus, is strongly active when there is no task. Altered intrinsic connectivity within the default network may underlie offline processing that may actuate ASD impairments. Using FMRI, we sought to evaluate intrinsic connectivity within the default network in ASD. Relative to controls, the ASD group showed weaker connectivity between the posterior cingulate cortex and superior frontal gyrus and stronger connectivity between the posterior cingulate cortex and both the right temporal lobe and right parahippocampal gyrus. Moreover, poorer social functioning in the ASD group was correlated with weaker connectivity between the posterior cingulate cortex and the superior frontal gyrus. In addition, more severe restricted and repetitive behaviors in ASD were correlated with stronger connectivity between the posterior cingulate cortex and right parahippocampal gyrus. These findings indicate that ASD subjects show altered intrinsic connectivity within the default network, and connectivity between these structures is associated with specific ASD symptoms.
Amygdala habituation, the rapid decrease in amygdala responsiveness to the repeated presentation of stimuli, is fundamental to the nervous system. Habituation is important for maintaining adaptive ...levels of arousal to predictable social stimuli and decreased habituation is associated with heightened anxiety. Input from the ventromedial prefrontal cortex (vmPFC) regulates amygdala activity. Although previous research has shown abnormal amygdala function in youth with autism spectrum disorders (ASD), no study has examined amygdala habituation in a young sample or whether habituation is related to amygdala connectivity with the vmPFC.
Data were analyzed from 32 children and adolescents with ASD and 56 typically developing controls who underwent functional magnetic resonance imaging while performing a gender identification task for faces that were fearful, happy, sad, or neutral. Habituation was tested by comparing amygdala activation to faces during the first half versus the second half of the session. VmPFC-amygdala connectivity was examined through psychophysiologic interaction analysis.
Youth with ASD had decreased amygdala habituation to sad and neutral faces compared with controls. Moreover, decreased amygdala habituation correlated with autism severity as measured by the Social Responsiveness Scale. There was a group difference in vmPFC-amygdala connectivity while viewing sad faces, and connectivity predicted amygdala habituation to sad faces in controls.
Sustained amygdala activation to faces suggests that repeated face presentations are processed differently in individuals with ASD, which could contribute to social impairments. Abnormal modulation of the amygdala by the vmPFC may play a role in decreased habituation.
Psychological disorders co-occur often in children, but little has been done to document the types of conjoint pathways internalizing and externalizing symptoms may take from the crucial early period ...of toddlerhood or how harsh parenting may overlap with early symptom codevelopment. To examine symptom codevelopment trajectories, we identified latent classes of individuals based on internalizing and externalizing symptoms across ages 3-9 and found three symptom codevelopment classes: normative symptoms (low), severe-decreasing symptoms (initially high but rapidly declining), and severe symptoms (high) trajectories. Next, joint models examined how parenting trajectories overlapped with internalizing and externalizing symptom trajectories. These trajectory classes demonstrated that, normatively, harsh parenting increased after toddlerhood, but the severe symptoms class was characterized by a higher level and a steeper increase in harsh parenting and the severe-decreasing class by high, stable harsh parenting. In addition, a transactional model examined the bidirectional relationships among internalizing and externalizing symptoms and harsh parenting because they may cascade over time in this early period. Harsh parenting uniquely contributed to externalizing symptoms, controlling for internalizing symptoms, but not vice versa. In addition, internalizing symptoms appeared to be a mechanism by which externalizing symptoms increase. Results highlight the importance of accounting for both internalizing and externalizing symptoms from an early age to understand risk for developing psychopathology and the role harsh parenting plays in influencing these trajectories.
We describe an ecological approach to understanding the developing brain, with a focus on the effects of poverty-related adversity on brain function. We articulate how combining multilevel ecological ...models from developmental science and developmental psychopathology with human neuroscience can inform our approach to understanding the developmental neuroscience of risk and resilience. To illustrate this approach, we focus on associations between poverty and brain function, the roles parents and neighborhoods play in this context, and the potential impact of developmental timing. We also describe the major challenges and needed advances in these areas of research to better understand how and why poverty-related adversity may impact the developing brain, including the need for: a population neuroscience approach with greater attention to sampling and representation, genetically informed and causal designs, advances in assessing context and brain function, caution in interpretation of effects, and a focus on resilience. Work in this area has major implications for policy and prevention, which are discussed.
Public Significance Statement
Millions of youth grow up in poverty and are exposed to an unequal share of adversity which impacts brain and behavior development. An ecological approach to developmental neuroscience can help to articulate the active ingredients associated with poverty that impact brain development. Better understanding how and why various adversities, including harsh parenting and neighborhood poverty, impact brain development can inform policies to prevent negative outcomes.
Abstract Autism spectrum disorders (ASD) are associated with disturbances of neural connectivity. Functional connectivity between neural structures is typically examined within the context of a ...cognitive task, but also exists in the absence of a task (i.e., “rest”). Connectivity during rest is particularly active in a set of structures called the default network, which includes the posterior cingulate cortex (PCC), retrosplenial cortex, lateral parietal cortex/angular gyrus, medial prefrontal cortex, superior frontal gyrus, temporal lobe, and parahippocampal gyrus. We previously reported that adults with ASD relative to controls show areas of stronger and weaker connectivity within the default network. The objective of the present study was to examine the default network in adolescents with ASD. Sixteen adolescents with ASD and 15 controls participated in a functional MRI study. Functional connectivity was examined between a PCC seed and other areas of the default network. Both groups showed connectivity in the default network. Relative to controls, adolescents with ASD showed widespread weaker connectivity in nine of the eleven areas of the default network. Moreover, an analysis of symptom severity indicated that poorer social skills and increases in restricted and repetitive behaviors and interests correlated with weaker connectivity, whereas poorer verbal and non-verbal communication correlated with stronger connectivity in multiple areas of the default network. These findings indicate that adolescents with ASD show weaker connectivity in the default network than previously reported in adults with ASD. The findings also show that weaker connectivity within the default network is associated with specific impairments in ASD.
Characterizing the pathophysiology of irritability symptoms from a dimensional perspective above and beyond diagnostic boundaries is key to developing mechanism-based interventions that can be ...applied broadly. Face emotion processing deficits are present in youths with elevated levels of irritability. The present study aimed to identify the neural mechanisms of face emotion processing in a sample enriched for irritability by including youths with high-functioning autism spectrum disorder (HF-ASD).
Youths (N = 120, age = 8.3-19.2 years) completed an implicit face emotion task during functional magnetic resonance imaging. We evaluated how irritability, measured dimensionally, above and beyond diagnostic group, relates to whole-brain neural activation and amygdala connectivity in response to face emotions.
Both neural activation and amygdala connectivity differed as a function of irritability level and face emotion in the prefrontal cortex. Youths with higher irritability levels had decreased activation in response to both fearful and happy faces in the left middle frontal gyrus and to happy faces in the left inferior frontal gyrus. Furthermore, increased irritability levels were associated with altered right amygdala connectivity to the left superior frontal gyrus when viewing fearful and sad faces.
The neural mechanisms of face emotion processing differ in youths with higher irritability compared to their less irritable peers. The findings suggest that these irritability mechanisms may be common to both typically developing and HF-ASD youths. Understanding the neural mechanisms of pediatric irritability symptoms that cut across diagnostic boundaries may be leveraged for future intervention development.
The last decades of neuroscience research have produced immense progress in the methods available to understand brain structure and function. Social, cognitive, clinical, affective, economic, ...communication, and developmental neurosciences have begun to map the relationships between neuro-psychological processes and behavioral outcomes, yielding a new understanding of human behavior and promising interventions. However, a limitation of this fast moving research is that most findings are based on small samples of convenience. Furthermore, our understanding of individual differences may be distorted by unrepresentative samples, undermining findings regarding brain–behavior mechanisms. These limitations are issues that social demographers, epidemiologists, and other population scientists have tackled, with solutions that can be applied to neuroscience. By contrast, nearly all social science disciplines, including social demography, sociology, political science, economics, communication science, and psychology, make assumptions about processes that involve the brain, but have incorporated neural measures to differing, and often limited, degrees; many still treat the brain as a black box. In this article, we describe and promote a perspective—population neuroscience—that leverages interdisciplinary expertise to (i) emphasize the importance of sampling to more clearly define the relevant populations and sampling strategies needed when using neuroscience methods to address such questions; and (ii) deepen understanding of mechanisms within population science by providing insight regarding underlying neural mechanisms. Doing so will increase our confidence in the generalizability of the findings. We provide examples to illustrate the population neuroscience approach for specific types of research questions and discuss the potential for theoretical and applied advances from this approach across areas.
The uncinate fasciculus is a major white matter tract that provides a crucial link between areas of the human brain that underlie emotion processing and regulation. Specifically, the uncinate ...fasciculus is the major direct fiber tract that connects the prefrontal cortex and the amygdala. The aim of the present study was to use a multi-modal imaging approach in order to simultaneously examine the relation between structural connectivity of the uncinate fasciculus and functional activation of the amygdala in a youth sample (children and adolescents). Participants were 9 to 19years old and underwent diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI). Results indicate that greater structural connectivity of the uncinate fasciculus predicts reduced amygdala activation to sad and happy faces. This effect is moderated by age, with younger participants exhibiting a stronger relation. Further, decreased amygdala activation to sad faces predicts lower internalizing symptoms. These results provide important insights into brain structure–function relationships during adolescence, and suggest that greater structural connectivity of the uncinate fasciculus may facilitate regulation of the amygdala, particularly during early adolescence. These findings also have implications for understanding the relation between brain structure, function, and the development of emotion regulation difficulties, such as internalizing symptoms.
•We examined relation between frontolimbic white matter tract and amygdala activity.•Greater white matter connectivity predicts less amygdala activation in adolescents.•Moderation analysis shows that relation is strongest in youngest participants.•White matter connectivity may facilitate regulation of the amygdala.
The cerebellum plays a role in a wide variety of complex behaviors. In order to better understand the role of the cerebellum in human behavior, it is important to know how this structure interacts ...with cortical and other subcortical regions of the brain. To date, several studies have investigated the cerebellum using resting-state functional connectivity magnetic resonance imaging (fcMRI; Krienen and Buckner, 2009; O'Reilly et al., 2010; Buckner et al., 2011). However, none of this work has taken an anatomically-driven lobular approach. Furthermore, though detailed maps of cerebral cortex and cerebellum networks have been proposed using different network solutions based on the cerebral cortex (Buckner et al., 2011), it remains unknown whether or not an anatomical lobular breakdown best encompasses the networks of the cerebellum. Here, we used fcMRI to create an anatomically-driven connectivity atlas of the cerebellar lobules. Timecourses were extracted from the lobules of the right hemisphere and vermis. We found distinct networks for the individual lobules with a clear division into "motor" and "non-motor" regions. We also used a self-organizing map (SOM) algorithm to parcellate the cerebellum. This allowed us to investigate redundancy and independence of the anatomically identified cerebellar networks. We found that while anatomical boundaries in the anterior cerebellum provide functional subdivisions of a larger motor grouping defined using our SOM algorithm, in the posterior cerebellum, the lobules were made up of sub-regions associated with distinct functional networks. Together, our results indicate that the lobular boundaries of the human cerebellum are not necessarily indicative of functional boundaries, though anatomical divisions can be useful. Additionally, driving the analyses from the cerebellum is key to determining the complete picture of functional connectivity within the structure.