Hippocampal Involvement in Safety Signal Learning Varies With Anxiety Among Healthy Adults.

Background: Safety signal learning (SSL), based on conditioned inhibition of fear in the presence of learned safety, can effectively attenuate threat responses in animal models and humans. Difficulty regulating threat responses is a core feature of anxiety disorders, suggesting that SSL may provide a novel mechanism for fear reduction. Cross-species evidence suggests that SSL involves functional connectivity between the anterior hippocampus and the dorsal anterior cingulate cortex. However, the neural mechanisms supporting SSL have not been examined in relation to trait anxiety or while controlling for the effect of novelty. Methods: Here, we investigated the neural mechanisms involved in SSL and associations with trait anxiety in a sample of 64 healthy (non-clinically anxious) adults (ages 18-30 years; 43 female, 21 male) using physiological, behavioral, and neuroimaging (functional magnetic resonance imaging) data collected during an SSL task. Results: During SSL, compared with individuals with lower trait anxiety, individuals with higher trait anxiety showed less fear reduction as well as altered hippocampal activation and hippocampal-dorsal anterior cingulate cortex functional connectivity, and lower inferior frontal gyrus and ventrolateral prefrontal cortex activation. Importantly, the findings show that SSL reduces threat responding, across learning and over and above the effect of novelty, and involves hippocampal activation. Conclusions: These findings provide new insights into the nature of SSL and suggest that there may be meaningful variation in SSL and related neural correlates as a function of trait anxiety, with implications for better understanding fear reduction and optimizing interventions for individuals with anxiety disorders.

Dispositional mindfulness: Dissociable affective and cognitive processes.

Mindfulness has been linked to a range of positive social-emotional and cognitive outcomes, but the underlying mechanisms are unclear. As one of the few traits or dispositions that are associated with both affective and cognitive benefits, we asked whether mindfulness is associated with affective and cognitive outcomes through a shared, unitary process or through two dissociable processes. We examined this in adolescents using behavioral measures and also reanalyzed previously reported neuroimaging findings relating mindfulness training to either affect (negative emotion, stress) or cognition (sustained attention). Using multivariate regression analyses, our findings suggest that the relationships between dispositional mindfulness and affective and cognitive processes are behaviorally dissociable and converge with neuroimaging data indicating that mindfulness modulates affect and cognition through separate neural pathways. These findings support the benefits of trait mindfulness on both affective and cognitive processes, and reveal that those benefits are at least partly dissociable in the mind and brain.

Multivariate links between the developmental timing of adversity exposure and white matter tract integrity in adulthood.

Early-life adversity is pervasive worldwide and represents a potent risk factor for increased mental health burden across the lifespan. However, there is substantial individual heterogeneity in associations between adversity exposure, neurobiological changes, and mental health problems. Accounting for key features of adversity such as the developmental timing of exposure may clarify associations between adversity, neurodevelopment, and mental health. The present study leverages sparse canonical correlation analysis to characterize modes of covariation between age of adversity exposure and the integrity of white matter tracts throughout the brain in a sample of 107 adults. We find that adversity exposure during middle childhood (ages 5-6 and 8-9 in particular) is consistently linked with alterations in white matter tract integrity, such that tracts supporting sensorimotor functions display higher integrity in relation to adversity exposure while tracts supporting cortico-cortical communication display lower integrity. Further, latent patterns of tract integrity linked with adversity experienced across preschool age and middle childhood (ages 4-9) were associated with trauma-related symptoms in adulthood. Our findings underscore that adversity exposure may differentially affect white matter in a function- and developmental-timing specific manner and suggest that adversity experienced between ages 4-9 may shape the development of global white matter tracts in ways that are relevant for adult mental health.

Neural effects of controllability as a key dimension of stress exposure.

Cross-species evidence suggests that the ability to exert control over a stressor is a key dimension of stress exposure that may sensitize frontostriatal-amygdala circuitry to promote more adaptive responses to subsequent stressors. The present study examined neural correlates of stressor controllability in young adults. Participants (N = 56; Mage = 23.74, range = 18-30 years) completed either the controllable or uncontrollable stress condition of the first of two novel stressor controllability tasks during functional magnetic resonance imaging (fMRI) acquisition. Participants in the uncontrollable stress condition were yoked to age- and sex-matched participants in the controllable stress condition. All participants were subsequently exposed to uncontrollable stress in the second task, which is the focus of fMRI analyses reported here. A whole-brain searchlight classification analysis revealed that patterns of activity in the right dorsal anterior insula (dAI) during subsequent exposure to uncontrollable stress could be used to classify participants' initial exposure to either controllable or uncontrollable stress with a peak of 73% accuracy. Previous experience of exerting control over a stressor may change the computations performed within the right dAI during subsequent stress exposure, shedding further light on the neural underpinnings of stressor controllability.

Managing fear and anxiety in development: A framework for understanding the neurodevelopment of emotion regulation capacity and tendency.

How we manage emotional responses to environmental threats is central to mental health, as difficulties regulating threat-related distress can blossom into symptoms of anxiety disorders. Given that anxiety disorders emerge early in the lifespan, it is crucial we understand the multi-level processes that support effective regulation of distress. Scholars have given increased attention to behavioral and neural development of emotion regulation abilities, particularly cognitive reappraisal capacity (i.e., how strongly one can down-regulate negative affect by reinterpreting a situation to change one's emotions). However, this work has not been well integrated with research on regulatory tendency (i.e., how often one spontaneously regulates emotion in daily life). Here, we review research on the development of both emotion regulation capacity and tendency. We then propose a framework for testing hypotheses and eventually constructing a neurodevelopmental model of both dimensions of emotion regulation. Clarifying how the brain supports both effective and frequent regulation of threat-related distress across development is crucial to identifying multi-level signs of dysregulation and developing interventions that support youth mental health.

Decomposing complex links between the childhood environment and brain structure in school-aged youth.

Childhood experiences play a profound role in conferring risk and resilience for brain and behavioral development. However, how different facets of the environment shape neurodevelopment remains largely unknown. Here we sought to decompose heterogeneous relationships between environmental factors and brain structure in 989 school-aged children from the Adolescent Brain Cognitive Development Study. We applied a cross-modal integration and clustering approach called 'Similarity Network Fusion', which combined two brain morphometrics (i.e., cortical thickness and myelin-surrogate markers), and key environmental factors (i.e., trauma exposure, neighborhood safety, school environment, and family environment) to identify homogeneous subtypes. Depending on the subtyping resolution, results identified two or five subgroups, each characterized by distinct brain structure-environment profiles. Notably, more supportive caregiving and school environments were associated with greater myelination, whereas less supportive caregiving, higher family conflict and psychopathology, and higher perceived neighborhood safety were observed with greater cortical thickness. These subtypes were highly reproducible and predicted externalizing symptoms and overall mental health problems. Our findings support the theory that distinct environmental exposures are differentially associated with alterations in structural neurodevelopment. Delineating more precise associations between risk factors, protective factors, and brain development may inform approaches to enhance risk identification and optimize interventions targeting specific experiences.

Emotion and Emotion Preferences in Daily Life: The Role of Anxiety.

People vary in their emotion preferences (i.e., desired emotional states). No study, however, has examined the nature of emotion preferences in anxiety. The current study utilized a 14-day ecological momentary assessment (EMA) paradigm to investigate the daily dynamics of emotion preferences and state emotion as they relate to individual differences in trait anxiety and anxiety symptom severity. Individuals with higher levels of trait anxiety and with more severe anxiety symptoms report greater preferences for state anxiety compared to their low anxiety counterparts. Relations between anxiety preferences and subsequent anxiety vary as a function of trait anxiety and symptom severity, and different associations are observed between the two measures of anxiety. The current findings suggest that aberrant emotion preferences may contribute to emotion dysfunction in anxiety, and highlight emotion preferences as a novel treatment target for interventions that aim to improve emotion functioning among people with elevated levels of anxiety.

Mindfulness training preserves sustained attention and resting state anticorrelation between default-mode network and dorsolateral prefrontal cortex: A randomized controlled trial.

Mindfulness training can enhance cognitive control, but the neural mechanisms underlying such enhancement in children are unknown. Here, we conducted a randomized controlled trial (RCT) with sixth graders (mean age 11.76 years) to examine the impact of 8 weeks of school-based mindfulness training, relative to coding training as an active control, on sustained attention and associated resting-state functional brain connectivity. At baseline, better performance on a sustained-attention task correlated with greater anticorrelation between the default mode network (DMN) and right dorsolateral prefrontal cortex (DLPFC), a key node of the central executive network. Following the interventions, children in the mindfulness group preserved their sustained-attention performance (i.e., fewer lapses of attention) and preserved DMN-DLPFC anticorrelation compared to children in the active control group, who exhibited declines in both sustained attention and DMN-DLPFC anticorrelation. Further, change in sustained-attention performance correlated with change in DMN-DLPFC anticorrelation only within the mindfulness group. These findings provide the first causal link between mindfulness training and both sustained attention and associated neural plasticity. Administered as a part of sixth graders' school schedule, this RCT supports the beneficial effects of school-based mindfulness training on cognitive control.

Mindfulness training reduces stress and amygdala reactivity to fearful faces in middle-school children.

The impact of mindfulness training on stress and associated brain plasticity has been shown in adults, whereas the impact of such training in the developing brain remains unknown. To address this open question, 40 middle-school children were randomized to either mindfulness or coding training (active control) interventions during the school day for eight weeks. Outcome measures were ratings of self-perceived stress and right amygdala activation while viewing fearful, happy, and neutral facial expressions during functional MRI. Prior to intervention, greater stress correlated with greater right amygdala activation in response to fearful versus neutral facial expressions across all children. After intervention, children who received mindfulness training reported lower stress associated with reduced right amygdala activation to fearful faces relative to children in the control condition. Amygdala responses to happy faces were unrelated to either initial stress or mindfulness reduction of stress. Moreover, mindfulness training led to relatively stronger functional connectivity between the right amygdala and ventromedial prefrontal cortex during the viewing of fearful facial expressions. Changes in perceived stress and neuroplasticity occurred in nonmeditative states, indicating that the benefits of mindfulness training generalized beyond the active meditative state. This study provides initial evidence that mindfulness training in children reduces stress and promotes functional brain changes and that such training can be integrated into the school curriculum for entire classes. This study also reveals first evidence that a neurocognitive mechanism for both stress and its reduction by mindfulness training is related specifically to reduced amygdala responses to negative stimuli. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Evaluation of Visual-Evoked Cerebral Metabolic Rate of Oxygen as a Diagnostic Marker in Multiple Sclerosis.

A multiple sclerosis (MS) diagnosis often relies upon clinical presentation and qualitative analysis of standard, magnetic resonance brain images. However, the accuracy of MS diagnoses can be improved by utilizing advanced brain imaging methods. We assessed the accuracy of a new neuroimaging marker, visual-evoked cerebral metabolic rate of oxygen (veCMRO2), in classifying MS patients and closely age- and sex-matched healthy control (HC) participants. MS patients and HCs underwent calibrated functional magnetic resonance imaging (cfMRI) during a visual stimulation task, diffusion tensor imaging, T1- and T2-weighted imaging, neuropsychological testing, and completed self-report questionnaires. Using resampling techniques to avoid bias and increase the generalizability of the results, we assessed the accuracy of veCMRO2 in classifying MS patients and HCs. veCMRO2 classification accuracy was also examined in the context of other evoked visuofunctional measures, white matter microstructural integrity, lesion-based measures from T2-weighted imaging, atrophy measures from T1-weighted imaging, neuropsychological tests, and self-report assays of clinical symptomology. veCMRO2 was significant and within the top 16% of measures (43 total) in classifying MS status using both within-sample (82% accuracy) and out-of-sample (77% accuracy) observations. High accuracy of veCMRO2 in classifying MS demonstrated an encouraging first step toward establishing veCMRO2 as a neurodiagnostic marker of MS.