Association Between Initial Age of Exposure to Childhood Abuse and Cognitive Control: Preliminary Evidence.

Cognitive control, which relies on the protracted development of frontal-parietal regions into adolescence, is a brain process that may be particularly vulnerable to the impact of childhood abuse. In this study, we used functional magnetic resonance imaging (fMRI) to examine associations between the age of onset of childhood abuse and alterations to the neural mechanisms supporting cognitive control in early adulthood, which have not been previously examined. During fMRI scanning, participants completed hybrid block/event-related versions of a classic color-word Stroop task as well as emotional Stroop tasks (threat and positive words). Participants were young adult women (N = 15; age range: 23-30 years) who had a history of childhood physical or sexual abuse that began prior to 13 years of age. Results indicated that earlier age of onset of childhood abuse was robustly associated with increased transient (i.e., event-related) recruitment of medial cognitive control regions in the classic color-word paradigm as well as with less suppression of medial frontal regions that are part of the default mode network, ßs = -.16 to -.87. In comparison, increased activation in dorsolateral prefrontal regions was associated with earlier age of abuse onset under conditions of sustained (i.e., blocked) cognitive control in the emotional Stroop task for blocks of positive distracting words versus fixation, ßs = -.50 to -.60. These results provide preliminary evidence that earlier age of exposure to childhood abuse impacts the functional activation of neural systems involved in cognitive control in adulthood.

Atypical spatial working memory and task-general brain activity in adolescents with a family history of alcoholism.

BACKGROUND: Altered behavioral performance and brain activation during spatial working memory (SWM) tasks have been demonstrated in individuals with an alcohol use disorder (AUD). It is possible that alterations in processing during SWM may be present prior to initiation of heavy alcohol use in adolescents with a family history of AUDs (family history positive [FHP]) and therefore represent a premorbid neural phenotype that could increase risk for developing an AUD. The goal of our study was to investigate group differences in brain activation during a SWM task between FHP adolescents and adolescents with no family history of AUDs (family history negative [FHN]), as well as examine the relationship between brain activation and individual differences in family history density (FHD) of AUDs. METHODS: Eighteen FHP and 16 gender and age-matched FHN participants completed a SWM and vigilance task while undergoing a functional magnetic resonance imaging (fMRI) scan. RESULTS: There were no group differences in task performance. The FHN group demonstrated expected greater activation during the SWM than vigilance condition in the right middle frontal gyrus and dorsolateral prefrontal cortex, whereas the FHP group demonstrated comparable brain activation for both the more demanding and simple task conditions. Additionally, FHD was associated with greater activation of the right superior parietal cortex and less activation of the right cerebellum during the SWM task, but not during the vigilance task. CONCLUSIONS: Results suggest FHP adolescents demonstrate alterations in activation of prefrontal regions that are related more generally to the maintenance of top-down cognitive control and alterations in parietal and cerebellar regions that are specific to SWM. Alterations in top-down cognitive control may be a general risk factor for FHP adolescents, whereas SWM-specific alterations are seen as a function of family history loading.

Time for a paradigm shift: The adolescent brain in addiction treatment.

OBJECTIVE: One route to improve adolescent addiction treatment outcomes is to use translational approaches to help identify developmental neuroscience mechanisms that undergird active treatment ingredients and advance adolescent behavior change. METHODS: This sample included 163 adolescents (ages 15-19) randomized to motivational interviewing (MI) vs. brief adolescent mindfulness (BAM). Youth completed an fMRI paradigm assessing adolescent brain response to therapist language (complex reflection vs. mindful; complex reflection vs. confront; mindful vs. confront) at pre- (prior to the completion of the full intervention) and post-treatment (at 3-month follow-up) and behavioral measures at 3, 6 and 12 months. RESULTS: Youth in both treatment groups showed significant problem drinking reductions at 3 and 6 months, but MI youth demonstrated significantly better treatment outcomes than BAM youth at 12 months. We observed several significant treatment group differences (MI > BAM) in neural response to therapist language, including at pre-treatment when examining complex reflection vs. mindful, and complex reflection vs. confront (e.g., superior temporal gyrus, lingual gyrus); and at post-treatment when examining mindful vs. confront (e.g., supplementary motor area; middle frontal gyrus). When collapsed across treatment groups (MI + BAM), we observed significant differences by time, with youth showing a pattern of brain change in response to complex reflection vs. mindful, and complex reflection vs. confront (e.g., precuneus; postcentral gyrus). There was no evidence of a significant group × time interaction. However, brain change in response to therapist language (complex reflection vs. confront) in regions such as middle frontal gyrus, was associated with reductions in problem drinking at 12 months. Yet, few treatment group differences were observed. CONCLUSIONS: These data underscore the need to better understand therapist language and it's impact on the developing brain, in order to inform and aggregate the most impactful elements of addiction treatment for future treatment development for adolescents.

Effects of Maternal Psychological Stress During Pregnancy on Offspring Brain Development: Considering the Role of Inflammation and Potential for Preventive Intervention.

Heightened psychological stress during pregnancy has repeatedly been associated with increased risk for development of behavior problems and psychiatric disorders in offspring. This review covers a rapidly growing body of research with the potential to advance a mechanistic understanding of these associations grounded in knowledge about maternal-placental-fetal stress biology and fetal brain development. Specifically, we highlight research employing magnetic resonance imaging to examine the infant brain soon after birth in relation to maternal psychological stress during pregnancy. This approach increases capacity to identify specific alterations in brain structure and function and to differentiate between effects of pre- versus postnatal exposures. We then focus on the extensive preclinical literature and emerging research in humans that have found that heightened maternal inflammation during pregnancy as a mechanism through which maternal stress influences the developing fetal brain. We place these findings in the context of recent work identifying psychotherapeutic interventions that have been found to be effective for reducing psychological stress among pregnant individuals and that also show promise for reducing inflammation. We argue that a focus on inflammation, among other mechanistic pathways, may lead to a productive and necessary integration of research focused on the effects of maternal psychological stress on offspring brain development and on prevention and intervention studies aimed at reducing maternal psychological stress during pregnancy. In addition to increasing capacity for common measurements and understanding potential mechanisms of action relevant to maternal mental health and fetal neurodevelopment, this focus may inform and broaden thinking about prevention and intervention strategies.

Cognitive-behavioral group therapy versus group psychotherapy for social anxiety disorder among college students: a randomized controlled trial.

OBJECTIVE: In this randomized controlled trial, cognitive-behavioral group therapy (CBGT) for social anxiety disorder (SAD) was compared to group psychotherapy (GPT), a credible, structurally equivalent control condition that included only nonspecific factors of group treatment (such as group dynamics). METHODS: Participants were 45 college students at the University of Colorado with a primary diagnosis of SAD. Each treatment condition comprised eight group sessions lasting 2 hr each. Independent assessors (blind to treatment assignment) assessed participants at baseline and posttreatment with the Clinical Global Impression Scale (CGI) and the Liebowitz Social Anxiety Scale (LSAS). RESULTS: Both treatments were found to be equally credible. There were five noncompleters in the CBGT condition (21.7%) and only one in the GPT condition (4.3%). There were no statistically significant differences posttreatment (controlling for pretreatment scores) between the two treatment conditions, and both treatments were found to be efficacious. Effect sizes for CBGT were similar to earlier studies, and adherence ratings revealed excellent adherence. CONCLUSIONS: Treatment of SAD appears to be moving toward individual CBT, partly because of high attrition rates and underutilization of group dynamics in group CBT. However, group therapy has unique therapeutic ingredients, and it may be too early to give up on group treatment altogether. Discussion of these findings included future directions with this treatment modality, especially whether these two types of group treatment could be combined and whether such combination might serve to decrease attrition, enhance efficacy, and facilitate dissemination.

Characterizing the impact of adversity, abuse, and neglect on adolescent amygdala resting-state functional connectivity.

Characterizing typologies of childhood adversity may inform the development of risk profiles and corresponding interventions aimed at mitigating its lifelong consequences. A neurobiological grounding of these typologies requires systematic comparisons of neural structure and function among individuals with different exposure histories. Using seed-to-whole brain analyses, this study examined associations between childhood adversity and amygdala resting-state functional connectivity (rs-fc) in adolescents aged 11-19 years across three independent studies (N = 223; 127 adversity group) in both general and dimensional models of adversity (comparing abuse and neglect). In a general model, adversity was associated with altered amygdala rs-fc with clusters within the left anterior lateral prefrontal cortex. In a dimensional model, abuse was associated with altered amygdala rs-fc within the orbitofrontal cortex, dorsal precuneus, posterior cingulate cortex, and dorsal anterior cingulate cortex/anterior mid-cingulate cortex, as well as within the dorsal attention, visual, and somatomotor networks. Neglect was associated with altered amygdala rs-fc with the hippocampus, supplementary motor cortex, temporoparietal junction, and regions within the dorsal attention network. Both general and dimensional models revealed unique regions, potentially reflecting pathways by which distinct histories of adversity may influence adolescent behavior, cognition, and psychopathology.

Stakeholder Perspectives on Advancing Understanding of Prenatal Opioid Exposure and Brain Development From the iOPEN Consortium of the Healthy Brain and Child Development Study.

Introduction: There is a dire need for research regarding the implications of opioid use during pregnancy on fetal and childhood development to better inform both medical practice and policy. The Healthy Brain and Child Development Study will examine brain and behavioral development from birth through the first decade of life. Due to large scope and anticipated complexity of this initiative, an 18-month planning phase was implemented across 28 sites across the nation. A core element of the Phase I initiative involved the development of Stakeholder Advisory Committees to inform the next phase of the initiative. Methods: Phase I stakeholder meetings were conducted at Oregon Health and Science University, New York University Langone Medical Center, the University of Pittsburgh, and the University of Vermont to better understand perspectives and inform upcoming research. Despite differences in the structure of the stakeholder meetings by site, the overarching goals for the meetings included establishing relationships, gathering input, and learning about research engagement. Documents from each meeting were reviewed for location, duration, attendees, common research themes, and pertinent suggestions for improving research approaches. Results: All stakeholders had high levels of interest in research for pregnant people with substance use disorders and agreed on research priorities including collaboration, connection, communication, and support. Different stakeholders offered unique perspectives on various aspects of study design and themes that emerged through meetings. Discussion: Overall, there was excitement about the research, especially the opportunity to include the voices of people with lived experience; collaboration between providers, peer support specialists, patients, and others; and excitement around contributing to research that could elucidate new and pertinent findings in the realm of addiction medicine and child development. Sites also found that there is mistrust between people with substance use disorder and the medical system, and this could be addressed by including people with lived experience on the research team, forming connections, communicating clearly, training the research team in implicit bias, and practicing trauma-informed care. In conclusion, these stakeholder meetings provided valuable information for structuring upcoming studies; however, researchers would have benefitted from more time and more opportunities for in-person connection.

Protocol for a mechanistic study of mindfulness based cognitive therapy during pregnancy.

OBJECTIVE: Preventive interventions for postpartum depression (PPD) are critical for women at elevated risk of PPD. Mindfulness based cognitive therapy - perinatal depression (MBCT-PD) is a preventive intervention that has been shown to reduce risk for PPD in women with a prior history of depression. The objective of this clinical trial is to examine two potential mechanisms of action of MBCT-PD, emotion regulation and cognitive control, using behavioral and neuroimaging methods. METHOD: This baseline protocol describes a randomized control trial (RCT) with two arms, MBCT-PD and treatment as usual (TAU). We plan on enrolling 74 females with a prior history of a major depressive episode, with 37 participants randomized to each arm. Participants in the MBCT-PD arm will receive MBCT-PD during pregnancy, and the TAU group will receive standard prenatal care. All participants will complete the Center for Epidemiological Studies Depression Scale - Revised (CESD-R), Emotion Regulation Questionnaire (ERQ), and classic Stroop task at multiple points from pregnancy through six months postpartum. Participants will also complete an fMRI scan at six weeks postpartum. RESULTS: All primary outcomes are collected at six weeks postpartum. Primary behavioral outcomes include: depressive symptoms on the CESD-R, cognitive reappraisal on the ERQ, and Stroop task performance. In parallel, the primary neurobiological outcomes include whole-brain activation during fMRI tasks when participants 1) regulate emotional responding and 2) engage cognitive control. CONCLUSIONS: This results of this innovative RCT will help identify potential behavioral and neurobiological mechanisms of action of preventive interventions for PPD for in-depth examination in larger scale RCTs. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Sex Differences in the Effect of Nucleus Accumbens Volume on Adolescent Drinking: The Mediating Role of Sensation Seeking in the NCANDA Sample.

OBJECTIVE: In adolescence, sensation seeking is associated with earlier onset of alcohol use, which is a risk factor for a variety of negative consequences later in life. Individual differences in sensation seeking are related to brain function in the nucleus accumbens (NAcc), a brain region that undergoes considerable structural development during adolescence. Therefore, the goal of this study was to determine whether NAcc volume in alcohol-naive adolescents was associated with future sensation seeking and alcohol use and whether these associations differed by sex. METHOD: High-resolution magnetic resonance imaging was used to measure NAcc volume at baseline in 514 alcohol-naive adolescents (50.2% female) from the National Consortium on Alcohol & Neurodevelopment in Adolescence study. Direct effects of NAcc volume on adolescent drinking 2 years after baseline, and indirect effects mediated through sensation seeking 1 year after baseline, were assessed. RESULTS: An indirect effect of NAcc volume on subsequent drinking through sensation seeking was significant for males, but not females. This effect was driven by a positive association between NAcc volume and sensation seeking observed in male, but not female, participants. A direct effect of NAcc volume on subsequent alcohol use was detected in females, but not males. In females, no association between NAcc volume and sensation seeking was detected, but NAcc volume was positively associated with future alcohol use. CONCLUSIONS: These findings suggest that delayed structural maturation of the NAcc may be a risk factor for alcohol use in adolescence; however, the mechanism by which the structure of the NAcc confers risk differs by sex.

General and emotion-specific alterations to cognitive control in women with a history of childhood abuse.

BACKGROUND: Although limited, the literature suggests alterations in activation of cognitive control regions in adults and adolescents with a history of childhood abuse. The current study examined whether such alterations are increased in the face of emotionally-distracting as compared to emotionally neutral information, and whether such alterations occur in brain regions that exert cognitive control in a more top-down sustained manner or a more bottom-up transient manner. METHODS: Participants were young adult women (ages 23-30): one group with a history of childhood physical or sexual abuse (N = 15) and one with no trauma exposure (N = 17), as assessed through the Trauma History Questionnaire and a two-stage interview adapted from the National Crime Victims Survey. Participants underwent fMRI scanning while completing hybrid block/event-related versions of a classic color-word and an emotional Stroop paradigm (threat and positive words). This paradigm allowed us to examine both sustained (activation persisting across blocks) and transient (event-specific activation) aspects of cognitive control. RESULTS: Women with a history of childhood abuse demonstrated decreased recruitment of frontal-parietal regions involved in cognitive control and enhanced recruitment of a ventral attention surveillance network during blocks of both versions of the Stroop task. Additionally, they had less suppression of brain regions involved in self-referential processes for threat blocks, but greater suppression of these regions for positive blocks. Severity of avoidance symptoms was associated with sustained activation in lateral prefrontal regions, whereas hyperarousal/re-experiencing symptoms were associated with sustained activity in temporal regions. No differential effects were observed for transient control. CONCLUSIONS: Results suggest exposure to childhood abuse is associated with blunted recruitment of brain regions supporting task-set maintenance but hypervigilance for task-irrelevant information, regardless of whether distractors are emotionally neutral or emotional. Exposure to childhood abuse is also associated with less suppression of default mode brain regions associated with self-referential processing in the face of irrelevant threat information, but heightened ability to suppress similar processing for irrelevant positive information.

Multiple modes of clearing one's mind of current thoughts: overlapping and distinct neural systems.

This study used the power of neuroimaging to identify the neural systems that remove information from working memory, a thorny issue to examine because it is difficult to confirm that individuals have actually modified their thoughts. To overcome this problem, brain activation as measured via fMRI was assessed when individuals had to clear their mind of all thought (global clear), clear their mind of a particular thought (targeted clear), or replace the current thought (replace), relative to maintaining an item in working memory. The pattern of activity in posterior sensory regions across these conditions confirmed compliance with task demands. A hierarchy of brain regions involved in cognitive control, including parietal, dorsolateral prefrontal and frontopolar regions, were engaged to varying degrees depending on the manner in which information was removed from working memory. In addition, individuals with greater difficulty in controlling internal thoughts exhibited greater activity in prefrontal brain regions associated with cognitive control, as well as in left lateral prefrontal areas including Broca's area, which is associated with inner speech.

Cognitive control in adolescence: neural underpinnings and relation to self-report behaviors.

BACKGROUND: Adolescence is commonly characterized by impulsivity, poor decision-making, and lack of foresight. However, the developmental neural underpinnings of these characteristics are not well established. METHODOLOGY/PRINCIPAL FINDINGS: To test the hypothesis that these adolescent behaviors are linked to under-developed proactive control mechanisms, the present study employed a hybrid block/event-related functional Magnetic Resonance Imaging (fMRI) Stroop paradigm combined with self-report questionnaires in a large sample of adolescents and adults, ranging in age from 14 to 25. Compared to adults, adolescents under-activated a set of brain regions implicated in proactive top-down control across task blocks comprised of difficult and easy trials. Moreover, the magnitude of lateral prefrontal activity in adolescents predicted self-report measures of impulse control, foresight, and resistance to peer pressure. Consistent with reactive compensatory mechanisms to reduced proactive control, older adolescents exhibited elevated transient activity in regions implicated in response-related interference resolution. CONCLUSIONS/SIGNIFICANCE: Collectively, these results suggest that maturation of cognitive control may be partly mediated by earlier development of neural systems supporting reactive control and delayed development of systems supporting proactive control. Importantly, the development of these mechanisms is associated with cognitive control in real-life behaviors.