Early Life Adversity Predicts Reduced Hippocampal Volume in the Adolescent Brain Cognitive Development Study.

PURPOSE: Cross-sectional studies in adults have demonstrated associations between early life adversity (ELA) and reduced hippocampal volume, but the timing of these effects is not clear. The present study sought to examine whether ELA predicts changes in hippocampal volume over time in a large sample of early adolescents. METHODS: The Adolescent Brain Cognitive Development Study provides a large dataset of tabulated neuroimaging, youth-reported adverse experiences, and parent-reported financial adversity from a sample of children around the United States. Linear mixed effects modeling was used to determine the relationship between ELA and hippocampal volume change within youth (n = 7036) from ages 9-10 to 11-12 years. RESULTS: Results of the models indicated that the number of early adverse events predicted bilateral hippocampal volume change (ß = -0.02, t = -2.02, p < .05). Higher adversity was associated with lower hippocampal volume at Baseline (t = 5.55, p < .01) and at Year 2 (t = 6.14, p < .001). DISCUSSION: These findings suggest that ELA may affect hippocampal development during early adolescence. Prevention and early intervention are needed to alter the course of this trajectory. Future work should examine associations between ELA, hippocampal development, and educational and socioemotional outcomes.

Catalyzing communities of research rigour champions.

The biomedical sciences must maintain and enhance a research culture that prioritizes rigour and transparency. The US National Institute of Neurological Disorders and Stroke convened a workshop entitled 'Catalyzing Communities of Research Rigor Champions' that brought together a diverse group of leaders in promoting research rigour and transparency (identified as 'rigour champions') to discuss strategies, barriers and resources for catalyzing technical, cultural and educational changes in the biomedical sciences. This article summarizes 2 days of panels and discussions and provides an overview of critical barriers to research rigour, perspectives behind reform initiatives and considerations for stakeholders across science. Additionally, we describe applications of network science to foster, maintain and expand cultural changes related to scientific rigour and opportunities to embed rigourous practices into didactic courses, training experiences and degree programme requirements. We hope this piece provides a primer for the wider research community on current discussions and actions and inspires individuals to build, join or expand collaborative networks within their own institutions that prioritize rigourous research practices.

Aberrant gastric functioning in weight-restored but not acute restricting-type anorexia nervosa: An electrogastrography study.

OBJECTIVE: Individuals with anorexia nervosa (AN) have high levels of gastrointestinal (GI) symptoms, functional GI disorders, and alterations in interoception. The primary aims of the current study were to determine (1) whether individuals with AN differed in gastric physiology as measured by electrogastrography (EGG) as compared to healthy individuals and (2) whether their EGG activity changed from pre- to post-weight restoration. METHOD: Adolescent and young adult females receiving inpatient treatment for restricting-type AN (n = 20) and healthy control females (n = 21) completed two EGG sessions, with measurements taken in fasting state and after administration of a water load. Participants with AN completed the first session while underweight and the second session following weight restoration. Healthy control participants also completed two sessions matched for length of time between sessions. RESULTS: Participants with AN exhibited decreased normogastria post-water load when they were weight restored compared to when they were underweight. Healthy control participants' EGG measures were stable across sessions. DISCUSSION: Findings provide evidence for aberrant gastric physiology in individuals with AN who have been weight restored, but not those in the acute phase of the illness. This supports the need for further research on GI functioning in AN. PUBLIC SIGNIFICANCE: Anorexia nervosa (AN) is a highly debilitating eating disorder that is difficult to treat. The causes of AN are largely unknown, but some theories suggest problems in gastrointestinal functioning may contribute to the disorder. This study found aberrant gastric functioning in individuals diagnosed with AN after weight restoration treatment. These findings contribute to our understanding of the causes and maintenance of AN and may ultimately lead to better treatments.

Real-Time Functional Magnetic Resonance Imaging Dyadic Neurofeedback for Emotion Regulation: A Proof-of-Concept Study.

Real-time fMRI (rt-fMRI) neurofeedback can be used to non-invasively modulate brain activity and has shown initial effectiveness in symptom reduction for psychiatric disorders. Neurofeedback paradigms often target the neurocircuitry underlying emotion regulation, as difficulties with emotion regulation are common across many psychiatric conditions. Adolescence is a key period for the development of emotion regulation, with the parent-adolescent relationship providing an important context for learning how to modulate one's emotions. Here, we present evidence for a novel extension of rt-fMRI neurofeedback wherein a second person (the parent) views neurofeedback from the focal participant (adolescent) and attempts to regulate the other person's brain activity. In this proof-of-concept study, mother-adolescent dyads (n = 6; all female) participated in a dyadic neurofeedback protocol, during which they communicated via active noise-canceling microphones and headphones. During the scan, adolescents described current emotionally upsetting situations in their lives, and their mothers responded while viewing neurofeedback from the adolescent's right anterior insular cortex (aIC)-a key hub for emotion-related processing. The mother was instructed to supportively respond to her daughter's negative emotions and attempt to downregulate the aIC activity. Mean right aIC activation during each run was calculated for each adolescent participant, and results revealed a downward trend across the session (ß = -0.17, SE ß = 0.19, Cohen's f 2 = 0.03). Results of this proof-of-concept study support further research using dyadic neurofeedback to target emotion-related processing. Future applications may include therapist-client dyads and continued research with parents and children. Clinical Trial Registration: [www.ClinicalTrials.gov], identifier [NCT03929263].

Effects of Parent Emotion Socialization on the Neurobiology Underlying Adolescent Emotion Processing: A Multimethod fMRI Study.

Parents' emotion socialization (ES) practices impact socioemotional development throughout adolescence. Little is known, however, regarding the neurobiology underlying these effects. This study used functional magnetic resonance imaging (fMRI) to examine how parent ES practices relate to adolescent brain function during emotion processing. Thirty-three adolescents (ages 14-16) reported on ES practices of a focal parent (primarily mothers) using the Emotions as a Child (EAC) Scale. Adolescents also completed a conflict discussion task with this parent, and parents' statements were coded for emotional valence. Adolescents performed two fMRI tasks: a standard emotion processing (EP) task (n = 32) and the Testing Emotional Attunement and Mutuality (TEAM) task (n = 27). The EP task consisted of viewing emotional pictures and either reacting naturally or using cognitive reappraisal to regulate emotional responses. The TEAM task was performed with the parent and included trials during which adolescents were shown that their parent made an error, costing the dyad $5. Parent negative verbalizations during the conflict discussion were associated with greater activity in the thalamus during the emotion reactivity condition of the EP task and in the thalamus, superior medial and superior frontal gyri, anterior insula, and dorsolateral prefrontal cortex during the costly error condition of the TEAM task. Unsupportive ES was associated with greater activity in the supplementary motor area and less activity in the paracentral gyrus and amygdala during the costly error condition of the TEAM task. This study supports the premise that ES influences adolescents' emotion-related neural processing, particularly when using ecologically valid tasks in social contexts.

The Role of Neurobiological Bases of Dyadic Emotion Regulation in the Development of Psychopathology: Cross-Brain Associations Between Parents and Children.

Daily interactions between parents and children play a large role in children's emotional development and mental health. Thus, it is important to investigate the neural mechanisms underlying this association within the context of these dyadic social interactions. We suggest that examining cross-brain associations, coordinated brain responses, among parents and children increases our understanding of patterns of social and emotion-related processes that occur during parent-child interactions, which may influence the development of child emotion regulation and psychopathology. Therefore, we extend the Parent-Child Emotion Regulation Dynamics Model (Morris et al., in: Cole and Hollenstein (eds) Dynamics of emotion regulation: A matter of time, Taylor & Francis, 2018) to include cross-brain associations involved in dyadic emotion regulation during parent-child social emotional interactions and discuss how this model can inform future research and its broader applications.

Into the Unknown: Examining Neural Representations of Parent-Adolescent Interactions.

The parent-adolescent relationship is important for adolescents' emotion regulation (ER), yet little is known regarding the neural patterns of dyadic ER that occur during parent-adolescent interactions. A novel measure that can be used to examine such patterns is cross-brain connectivity (CBC)-concurrent and time-lagged connectivity between two individuals' brain regions. This study sought to provide evidence of CBC and explore associations between CBC, parenting, and adolescent internalizing symptoms. Thirty-five adolescents (mean age = 15 years, 69% female, 72% Non-Hispanic White, 17% Black, 11% Hispanic or Latino) and one biological parent (94% female) completed an fMRI hyperscanning conflict discussion task. Results revealed CBC between emotion-related brain regions. Exploratory analyses indicated CBC is associated with parenting and adolescent depressive symptoms.

The heart of the matter: Developing the whole child through community resources and caregiver relationships.

Numerous developmental scholars have been influenced by the research, policies, and thinking of the late Edward Zigler, who was instrumental in founding Head Start and Early Head Start. In line with the research and advocacy work of Zigler, we discuss two models that support the development of the whole child. We begin by reviewing how adverse and protective experiences "get under the skin" and affect developmental trajectories and risk and resilience processes. We then present research and examples of how experiences affect the whole child, the heart and the head (social, emotional, cognitive, and physical development), and consider development within context and across domains. We discuss examples of interventions that strengthen nurturing relationships as the mechanism of change. We offer a public health perspective on promoting optimal development through nurturing relationships and access to resources during early childhood. We end with a discussion of the myth that our current society is child-focused and argue for radical, essential change to make promoting optimal development for all children the cornerstone of our society.

Gastric symptoms and low perceived maternal warmth are associated with eating disorder symptoms in young adolescent girls.

OBJECTIVE: This study sought to determine whether gastric symptoms are associated with later eating disorder (ED) symptoms during early adolescence, and whether this relationship is moderated by parental warmth/acceptance and/or the child's sex. METHOD: Longitudinal data from the Adolescent Brain Cognitive DevelopmentSM Study were utilized. Participants ages 9-10 years old (N = 4,950; 2,370 female) completed measures at baseline and 1 year later (Y1). At baseline, gastric symptoms were measured by parent-reported items from the Child Behavior Checklist (CBCL), and perceived parental acceptance was measured by youth report on the Children's Report of Parent Behavior Inventory (CRPBI) Acceptance subscale separately for mothers and fathers. ED symptoms at Y1 were assessed by parent report on a computerized version of the Kiddie Schedule for Affective Disorders and Schizophrenia (K-SADS). Linear mixed-effects models were conducted separately for maternal and paternal acceptance to test relationships among variables. RESULTS: A three-way interaction between baseline gastric symptoms, sex, and maternal acceptance predicted Y1 ED symptoms (𝛽 = 0.08; p < .01). Post-hoc analyses revealed that the interaction between gastric symptoms and maternal acceptance was significant for girls only (𝛽 = -0.06, p < .01), such that low maternal acceptance was associated with a stronger relationship between baseline gastric symptoms and Y1 ED symptoms. No statistically significant main effects or interactions were found in the model for paternal acceptance. DISCUSSION: Gastric symptoms and low perceived maternal acceptance may interact to result in heightened risk for EDs in young adolescent girls.

Adverse and Protective Childhood Experiences and Parenting Attitudes: the Role of Cumulative Protection in Understanding Resilience.

Theory and research indicate that adverse childhood experiences (ACEs) are linked to negative parenting attitudes and behaviors. We posit that protective and compensatory experiences (PACEs) in childhood buffer the negative effects of ACEs on later parenting. To test this premise, the present study examined associations between ACEs, PACEs, and attitudes towards nurturing and harsh parenting in an ethnically diverse sample of parents with children of various ages (N = 109; 65% mothers, 35% fathers; M age = 38). Parents completed a widely used parenting attitudes questionnaire and the ACEs and PACEs surveys. PACEs were negatively correlated with ACEs and positively correlated with nurturing parenting attitudes and parent income and education levels. Linear regression models indicate that higher PACEs, ACEs, and family income and less harsh parenting attitudes predict nurturing parenting attitudes. In contrast, higher ACEs and less nurturing attitudes were correlated with harsh parenting attitudes. As expected, moderation analyses indicated that the association between ACEs and harsh parenting attitudes was conditional upon the level of PACEs. When PACE scores were low (M - 1 SD), but not when PACE scores were average or high (M + 1 SD), ACEs were associated with harsh parenting attitudes, suggesting a buffering effect of PACEs on negative parenting attitudes. These findings support the importance of including protective as well as adverse childhood experiences when assessing the role of childhood experiences on parenting attitudes and practices. Implications of these findings for researchers and practitioners are discussed, as well as new directions for PACEs research using a cumulative protection approach.

Beyond synchrony: the capacity of fMRI hyperscanning for the study of human social interaction.

Hyperscanning-simultaneous brain scanning of two or more individuals-holds great promise in elucidating the neurobiological underpinnings of social cognitive functions. This article focuses on functional magnetic resonance imaging (fMRI) hyperscanning and identifies promising targets for studying the neuroscience of social interaction with fMRI hyperscanning. Specifically, we present applications of fMRI hyperscanning in the study of social interaction along with promising analysis approaches for fMRI hyperscanning, with its high spatial and low temporal resolution. We first review fMRI hyperscanning studies in social neuroscience and evaluate the premise of using this costly neuroimaging paradigm. Many second-person social neuroscience studies are possible without fMRI hyperscanning. However, certain fundamental aspects of social cognition in real-life social interactions, including different roles of interactors, shared intention emerging through interaction and history of interaction, can be addressed only with hyperscanning. We argue that these fundamental aspects have not often been investigated in fMRI hyperscanning studies. We then discuss the implication of the signal coupling found in fMRI hyperscanning and consider analysis approaches that make fair use of it. With fMRI hyperscanning, we can explore not only synchronous brain activations but whole-brain asymmetric activation patterns with a lagged association between interacting individuals.

TEAMwork: Testing Emotional Attunement and Mutuality During Parent-Adolescent fMRI.

The parent-child relationship and family context influence the development of emotion regulation (ER) brain circuitry and related skills in children and adolescents. Although both parents' and children's ER neurocircuitry simultaneously affect how they interact with one another, neuroimaging studies of parent-child relationships typically include only one member of the dyad in brain imaging procedures. The current study examined brain activation related to parenting and ER in parent-adolescent dyads during concurrent fMRI scanning with a novel task - the Testing Emotional Attunement and Mutuality (TEAM) task. The TEAM task includes feedback trials indicating the other dyad member made an error, resulting in a monetary loss for both participants. Results indicate that positive parenting practices as reported by the adolescent were positively correlated with parents' hemodynamic activation of the ventromedial prefrontal cortex, a region related to empathy, during these error trials. Additionally, during feedback conditions both parents and adolescents exhibited fMRI activation in ER-related regions, including the dorsolateral prefrontal cortex, anterior insula, fusiform gyrus, thalamus, caudate, precuneus, and superior parietal lobule. Adolescents had higher left amygdala activation than parents during the feedback condition. These findings demonstrate the utility of dyadic fMRI scanning for investigating relational processes, particularly in the parent-child relationship.

Appetite changes reveal depression subgroups with distinct endocrine, metabolic, and immune states.

There exists little human neuroscience research to explain why some individuals lose their appetite when they become depressed, while others eat more. Answering this question may reveal much about the various pathophysiologies underlying depression. The present study combined neuroimaging, salivary cortisol, and blood markers of inflammation and metabolism collected prior to scanning. We compared the relationships between peripheral endocrine, metabolic, and immune signaling and brain activity to food cues between depressed participants experiencing increased (N = 23) or decreased (N = 31) appetite and weight in their current depressive episode and healthy control participants (N = 42). The two depression subgroups were unmedicated and did not differ in depression severity, anxiety, anhedonia, or body mass index. Depressed participants experiencing decreased appetite had higher cortisol levels than subjects in the other two groups, and their cortisol values correlated inversely with the ventral striatal response to food cues. In contrast, depressed participants experiencing increased appetite exhibited marked immunometabolic dysregulation, with higher insulin, insulin resistance, leptin, CRP, IL-1RA, and IL-6, and lower ghrelin than subjects in other groups, and the magnitude of their insulin resistance correlated positively with the insula response to food cues. These findings provide novel evidence linking aberrations in homeostatic signaling pathways within depression subtypes to the activity of neural systems that respond to food cues and select when, what, and how much to eat. In conjunction with prior work, the present findings strongly support the existence of pathophysiologically distinct depression subtypes for which the direction of appetite change may be an easily measured behavioral marker.

Appetite change profiles in depression exhibit differential relationships between systemic inflammation and activity in reward and interoceptive neurocircuitry.

Appetite change is a defining feature of major depressive disorder (MDD), yet little neuroscientific evidence exists to explain why some individuals experience increased appetite when they become depressed while others experience decreased appetite. Previous research suggests depression-related appetite changes can be indicative of underlying neural and inflammatory differences among MDD subtypes. The present study explores the relationship between systemic inflammation and brain circuitry supporting food hedonics for individuals with MDD. Sixty-four participants (31 current, unmedicated MDD and 33 healthy controls [HC]) provided blood samples for analysis of an inflammatory marker, C-reactive protein (CRP), and completed a functional magnetic resonance imaging (fMRI) scan in which they rated the perceived pleasantness of various food stimuli. Random-effects multivariate modeling was used to explore group differences in the relationship between CRP and the coupling between brain activity and inferred food pleasantness (i.e., strength of the relationship between activity and pleasantness ratings). Results revealed that for MDD with increased appetite, higher CRP in blood related to greater coupling between orbitofrontal cortex and anterior insula activity and inferred food pleasantness. Compared to HC, all MDD exhibited a stronger positive association between CRP and coupling between activity in striatum and inferred food pleasantness. These findings suggest that for individuals with MDD, systemic low-grade inflammation is associated with differences in reward and interoceptive-related neural circuitry when making hedonic inferences about food stimuli. In sum, altered immunologic states may affect appetite and inferences about food reward in individuals with MDD and provide evidence for physiological subtypes of MDD.

Always on my mind: Cross-brain associations of mental health symptoms during simultaneous parent-child scanning.

How parents manifest symptoms of anxiety or depression may affect how children learn to modulate their own distress, thereby influencing the children's risk for developing an anxiety or mood disorder. Conversely, children's mental health symptoms may impact parents' experiences of negative emotions. Therefore, mental health symptoms can have bidirectional effects in parent-child relationships, particularly during moments of distress or frustration (e.g., when a parent or child makes a costly mistake). The present study used simultaneous functional magnetic resonance imaging (fMRI) of parent-adolescent dyads to examine how brain activity when responding to each other's costly errors (i.e., dyadic error processing) may be associated with symptoms of anxiety and depression. While undergoing simultaneous fMRI scans, healthy dyads completed a task involving feigned errors that indicated their family member made a costly mistake. Inter-brain, random-effects multivariate modeling revealed that parents who exhibited decreased medial prefrontal cortex and posterior cingulate cortex activation when viewing their child's costly error response had children with more symptoms of depression and anxiety. Adolescents with increased anterior insula activation when viewing a costly error made by their parent had more anxious parents. These results reveal cross-brain associations between mental health symptomatology and brain activity during parent-child dyadic error processing.

Parental influences on neural mechanisms underlying emotion regulation.

Emotional intelligence allows for the recognition and regulation of emotions in the self and others, making it critical for healthy social and emotional development. Research has shown that the parent-child relationship and family environment are influential in the development of emotion regulation, one key component of emotional intelligence. However, the neurobiological processes underlying this relationship have yet to be fully explored. This review examines perspectives from several disciplines to further understand the influence of parent-child interactions on the neurocircuitry shaping emotion regulation. Our proposed model demonstrates how parent-child interactions and parents' emotion regulation neurocircuitry may influence the development of children's own emotion regulation neurocircuitry, with a specific focus on associations among prefrontal regions, the anterior insula, and the amygdala.

Impairment of Inhibition of Trigeminal Nociception via Conditioned Pain Modulation in Persons with Migraine Headaches.

OBJECTIVE: To assess conditioned pain modulation efficiency in persons with and without migraine headaches. DESIGN: Cross-sectional assessment of experimental pain. SETTING: University campus and surrounding community in a large Midwestern US city. SUBJECTS: Twenty-three adults with and 32 without a history of migraine headaches participated in the study. Participants were mostly female (N = 40) with an average age of 23 years. METHODS: Four electrocutaneous stimulations of the supraorbital branch of the left trigeminal nerve were delivered at 150% of an individually determined pain threshold. Conditioned pain modulation was assessed by applying a noxious counterstimulus (forearm ischemia) and delivering four more electrocutaneous stimulations. After each stimulation, pain and the nociceptive blink reflex were assessed. Depression and pain catastrophizing were assessed to control for the potential influence of these variables on pain modulation. RESULTS: Participants with and without migraine headaches had similar baseline pain responsivity, without significant differences in pain report or nociceptive blink reflexes. Pain report was inhibited by conditioned pain modulation in both the migraine and control groups. However, unlike nonmigraine controls, participants with migraines did not exhibit an inhibition of nociceptive blink reflexes during the ischemia task. This pattern persisted after controlling for level of pain catastrophizing and depression. CONCLUSIONS: Migraine sufferers exhibited impaired conditioned pain modulation of the nociceptive blink reflex, suggesting a deficiency in inhibition of trigeminal nociception, which may contribute to the development of migraine headaches.

The Neural Bases of Interoceptive Encoding and Recall in Healthy Adults and Adults With Depression.

BACKGROUND: Theoretical models assert that the brain's interoceptive network links external stimuli with their interoceptive consequences, thereby supporting later recall of these associations to guide the selection of healthy behaviors. If these accounts are correct, previously reported interoceptive abnormalities in major depressive disorder (MDD) should lead to altered recall of associations between external stimuli and their interoceptive (somatic) consequences. To date, the processes underlying interoceptive recall have never been experimentally investigated. METHODS: We designed and implemented the Interoceptive Encoding and Recall task to compare interoceptive and exteroceptive recall among subjects with MDD (n = 24) and healthy comparison subjects (n = 21). During the encoding phase, subjects learned to pair neutral visual cues (geometric shapes) with aversive interoceptive and exteroceptive stimuli. Later, while undergoing functional magnetic resonance imaging, subjects were prompted to recall the stimulus associated with each shape. RESULTS: Interoceptive recall, relative to exteroceptive recall, was associated with bilateral mid-to-posterior insula activation. Relative to the healthy control participants, participants with depression exhibited marked hypoactivation of the right dorsal mid-insula during interoceptive recall. CONCLUSIONS: In healthy control subjects, simply recalling a stimulus associated with a previous interoceptive challenge activated a key region in the brain's interoceptive network. Although previous research has linked MDD with aberrant processing of interoceptive stimuli, the current study is the first to demonstrate that individuals with MDD exhibit decreased insula activity while recalling interoceptive memories. It is possible that insula hypoactivation during interoceptive recall may affect the representation of prior interoceptive experiences in ways that contribute to depressive symptomology and the relationship between depression and systemic health.

Influence of Visceral Interoceptive Experience on the Brain's Response to Food Images in Anorexia Nervosa.

OBJECTIVE: The aim of the study was to determine how visceral sensations affect responses to food stimuli in anorexia nervosa (AN). METHODS: Twenty weight-restored, unmedicated adolescent and young adult women with AN and twenty healthy control participants completed an interoceptive attention task during which they focused on sensations from the heart, stomach, and bladder and made ratings of these sensations. They then underwent functional magnetic resonance imaging scanning while viewing pictures of food and nonfood objects. Between-groups t tests were employed to investigate group differences in the relationship between interoceptive sensation ratings and brain hemodynamic response to food pictures and, specifically, to highly palatable foods. RESULTS: In response to food pictures, AN participants exhibited a positive relationship between stomach sensation ratings and posterior insula activation (peak t = 4.30). AN participants displayed negative relationships between stomach sensation ratings and amygdala activation (peak t = -4.05) and heart sensation ratings and ventromedial prefrontal cortex activation (peak t = -3.52). In response to highly palatable foods, AN was associated with positive relationships between stomach sensation ratings and activity in the subgenual anterior cingulate (peak t = 3.88) and amygdala (peak t = 4.83), and negative relationships in the ventral pallidum (peak t = -3.99) and ventral tegmental area (peak t = -4.03). AN participants also exhibited negative relationships between cardiac sensations and activation in response to highly palatable foods in the putamen (peak t = -3.41) and ventromedial prefrontal cortex (peak t = -3.61). Healthy participants exhibited the opposite pattern in all of these regions. CONCLUSIONS: Hedonic and interoceptive inferences made by individuals with AN at the sight of food may be influenced by atypical visceral interoceptive experience, which could contribute to restrictive eating.