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Rapid and accurate detection of threat is adaptive. Yet, threat-related attentional biases, including hypervigilance, avoidance, and attentional disengagement delays, may contribute to the etiology and maintenance of anxiety disorders. Behavioral measures of attentional bias generally indicate that threat demands more attentional resources; however, indices exploring differential allocation of attention using reaction time fail to clarify the time course by which attention is deployed under threatening circumstances in healthy and anxious populations. In this review, we conduct an interpretive synthesis of 28 attentional bias studies focusing on event-related potentials (ERPs) as a primary outcome to inform an ERP model of the neural chronometry of attentional bias in healthy and anxious populations. The model posits that both healthy and anxious populations display modulations of early ERP components, including the P1, N170, P2, and N2pc, in response to threatening and emotional stimuli, suggesting that both typical and abnormal patterns of attentional bias are characterized by enhanced allocation of attention to threat and emotion at earlier stages of processing. Compared to anxious populations, healthy populations more clearly demonstrate modulations of later components, such as the P3, indexing conscious and evaluative processing of threat and emotion and disengagement difficulties at later stages of processing. Findings from the interpretive synthesis, existing bias models, and extant neural literature on attentional systems are then integrated to inform a conceptual model of the processes and substrates underlying threat appraisal and resource allocation in healthy and anxious populations. To conclude, we discuss therapeutic interventions for attentional bias and future directions.
Copyright © 2019 Elsevier B.V. All rights reserved.

This article reviews the interactions of estrogen changes and psychosocial stress in contributing to vulnerability to major depressive disorder (MDD) in women. Estrogen modulates brain networks and processes related to changes in stress response, cognition, and emotional dysregulation that are core characteristics of MDD. Synergistic effects of estrogen on cognitive and emotional function, particularly during psychosocial stress, may underlie the association of ovarian hormone fluctuation and depression in women. We propose a model of estrogen effects on multiple brain systems that interface with stress-related emotional and cognitive processes implicated in MDD and discuss possible mechanisms through which reproductive events and changes in estrogen may contribute to MDD risk in women with other concurrent risk factors.

Early institutional rearing is associated with increased risk for subsequent peer relationship difficulties, but the underlying mechanisms have not been identified. Friendship characteristics, social behaviors with peers, normed assessments of social problems, and social cue use were assessed in 142 children (mean age = 10.06, SD = 2.02; range 7-13 years), of whom 67 were previously institutionalized (PI), and 75 were raised by their biological families. Anxiety and attention-deficit/hyperactivity disorder (ADHD) symptoms, often elevated among PI children, were examined as potential mediators of PI status and baseline social functioning and longitudinal follow-ups (2 and 4 years later). Twenty-seven percent of PI children fell above the Child Behavior Checklist Social Problems cutoff. An examination of specific social behaviors with peers indicated that PI and comparison children did not differ in empathic concern or peer social approach, though parents were more likely to endorse aggression/overarousal as a reason that PI children might struggle with friendships. Comparison children outperformed PI children in computerized testing of social cue use learning. Finally, across these measures, social difficulties exhibited in the PI group were mediated by ADHD symptoms with predicted social problems assessed 4 years later. These findings show that, when PI children struggle with friendships, mechanisms involving attention and behavior regulation are likely contributors.

Frontal eye field (FEF) in macaque monkeys contributes to visual attention, visual-motor transformations and production of eye movements. Traditionally, neurons in FEF have been classified by the magnitude of increased discharge rates following visual stimulus presentation, during a waiting period, and associated with eye movement production. However, considerable heterogeneity remains within the traditional visual, visuomovement, and movement categories. Cluster analysis is a data-driven method of identifying self-segregating groups within a dataset. Because many cluster analysis techniques exist and outcomes vary with analysis assumptions, consensus clustering aggregates over multiple analyses, identifying robust groups. To describe more comprehensively the neuronal composition of FEF, we applied a consensus clustering technique for unsupervised categorization of patterns of spike rate modulation measured during a memory-guided saccade task. We report 10 functional categories, expanding on the traditional 3 categories. Categories were distinguished by latency, magnitude, and sign of visual response; the presence of sustained activity; and the dynamics, magnitude and sign of saccade-related modulation. Consensus clustering can include other metrics and can be applied to datasets from other brain regions to provide better information guiding microcircuit models of cortical function.

The emotional attentional blink (EAB) refers to a temporary impairment in the ability to identify a target when it is preceded by an emotional distractor. It is thought to occur because the emotional salience of the distractor exogenously captures attention for a brief duration, rendering the target unattended and preventing it from reaching awareness. Here we tested the extent to which the EAB can be attenuated by inducing a diffuse top-down attentional state, which has been shown to improve target identification in an analogous attentional phenomenon, the attentional blink. Rapid sequences of landscape images were presented centrally, and participants reported the orientation of a ± 90° rotation of a landscape target. To induce a diffuse state of attention, participants were given a secondary task of monitoring for the appearance of a colored dot in the periphery. We found that emotional distractors impaired target recognition performance to comparable extents, regardless of whether or not participants concurrently performed the peripheral-monitoring task. Moreover, we found that performance of the secondary task led to an impaired ability to ignore neutral distractors. Subjective ratings of target vividness mirrored the behavioral accuracy, with frequent reports of intermediate levels of vividness suggesting that the EAB might impair target visibility in a graded manner. Our results demonstrate that the EAB is robust to manipulations of top-down attention, suggesting that the temporary capture of attention by emotionally salient stimuli involves processes that are distinct from those that produce the attentional blink.

Despite a growing understanding that early adversity in childhood broadly affects risk for psychopathology, the contribution of stressful life events to the development of symptoms of attention-deficit/hyperactivity disorder (ADHD) is not clear. In the present study, we examined the association between number of stressful life events experienced and ADHD symptoms, assessed using the Attention Problems subscale of the Child Behavior Checklist, in a sample of 214 children (43% male) ages 9.11-13.98 years (M = 11.38, SD = 1.05). In addition, we examined whether the timing of the events (i.e., onset through age 5 years or after age 6 years) was associated with ADHD symptoms. Finally, we examined variation in brain structure to determine whether stressful life events were associated with volume in brain regions that were found to vary as a function of symptoms of ADHD. We found a small to moderate association between number of stressful life events and ADHD symptoms. Although the strength of the associations between number of events and ADHD symptoms did not differ as a function of the age of occurrence of stressful experiences, different brain regions were implicated in the association between stressors and ADHD symptoms in the two age periods during which stressful life events occurred. These findings support the hypothesis that early adversity is associated with ADHD symptoms, and provide insight into possible brain-based mediators of this association.

Avoiding distraction by conspicuous but irrelevant stimuli is critical to accomplishing daily tasks. Regions of prefrontal cortex control attention by enhancing the representation of task-relevant information in sensory cortex, which can be measured in modulation of both single neurons and event-related electrical potentials (ERPs) on the cranial surface [1, 2]. When irrelevant information is particularly conspicuous, it can distract attention and interfere with the selection of behaviorally relevant information. Such distraction can be minimized via top-down control [3-5], but the cognitive and neural mechanisms giving rise to this control over distraction remain uncertain and debated [6-9]. Bridging neurophysiology to electrophysiology, we simultaneously recorded neurons in prefrontal cortex and ERPs over extrastriate visual cortex to track the processing of salient distractors during a visual search task. Critically, when the salient distractor was successfully ignored, but not otherwise, we observed robust suppression of salient distractor representations. Like target selection, the distractor suppression was observed in prefrontal cortex before it appeared over extrastriate cortical areas. Furthermore, all prefrontal neurons that showed suppression of the task-irrelevant distractor also contributed to selecting the target. This suggests a common prefrontal mechanism is responsible for both selecting task-relevant and suppressing task-irrelevant information in sensory cortex. Taken together, our results resolve a long-standing debate over the mechanisms that prevent distraction, and provide the first evidence directly linking suppressed neural firing in prefrontal cortex with surface ERP measures of distractor suppression.
Copyright © 2017 Elsevier Ltd. All rights reserved.

This study examined sequential associations between pairs of caregiver talk and caregiver-child joint engagement categories. Sequential associations quantify the extent to which one event (such as a particular type of caregiver talk) follows another event (such as a particular type of joint engagement) in a pre-specified time window, while controlling for the chance occurrence of the sequence. Although unable to support strong conclusions about causality, the requirement of sequential analysis that key events occur within a close temporal sequence rules out alternative explanation for associations that summary-level correlations cannot. We applied sequential analysis to observational data on 98 caregiver-child dyads, fifty of which included a child with autism spectrum disorder (ASD). Groups were matched on mental age, and all were just beginning to develop spoken vocabulary. Sequential associations between supported joint engagement and caregiver follow-in utterances were stronger in ASD dyads as compared to dyads with typically developing children. Further, sequential associations between utterances related to the child's focus of attention followed by higher order supported joint engagement (HSJE) were stronger than between utterances that related to the caregiver's focus of attention and HSJE, across both groups. Finally, sequential associations between follow-in directives followed by HSJE were stronger than between follow-in comments followed by HSJE, again across both groups of children. Autism Res 2018, 11: 755-765. © 2018 International Society for Autism Research, Wiley Periodicals, Inc.
LAY SUMMARY - Our findings suggest that caregivers of children with autism spectrum disorder (ASD) may be particularly adept at timing their talk to follow moments of high-level joint engagement, and that follow-in directives are particularly facilitative of high-level joint engagement. Future intervention work can capitalize on these findings to support high level caregiver-child engagement around toys, which may promote development in children with ASD.
© 2018 International Society for Autism Research, Wiley Periodicals, Inc.

BACKGROUND - Dopamine (DA) is a critical neuromodulator in the retina. Disruption of retinal DA synthesis and signaling significantly attenuates light-adapted, electroretinogram (ERG) responses, as well as contrast sensitivity and acuity. As these measures can be detected noninvasively, they may provide opportunities to detect disease processes linked to perturbed DA signaling. Recently, we identified a rare, functional DA transporter (DAT, SLC6A3) coding substitution, Ala559Val, in subjects with attention-deficit/hyperactivity disorder (ADHD), demonstrating that DAT Val559 imparts anomalous DA efflux (ADE) with attendant physiological, pharmacological, and behavioral phenotypes. To understand the broader impact of ADE on ADHD, noninvasive measures sensitive to DAT reversal are needed.
METHODS - Here, we explored this question through ERG-based analysis of retinal light responses, as well as HPLC measurements of retinal DA in DAT Val559 mice.
RESULTS - Male mice homozygous (HOM) for the DAT Val559 variant demonstrated increased, light-adapted ERG b-wave amplitudes compared to wild type (WT) and heterozygous (HET) mice, whereas dark-adapted responses were indistinguishable across genotypes. The elevated amplitude of the photopic light responses in HOM mice could be mimicked in WT mice by applying D and D DA receptor agonists and suppressed in HOM mice by introducing D antagonist, supporting elevated retinal DA signaling arising from ADE. Following the challenge with amphetamine, WT exhibited an increase in light-adapted response amplitudes, while HOM did not. Total retinal DA content was similar across genotypes. Interestingly, female DAT Val559 HOM animals revealed no significant difference in photopic ERG responses when compared with WT and HET littermates.
CONCLUSIONS - These data reveal that noninvasive, in vivo evaluation of retinal responses to light can reveal physiological signatures of ADE, suggesting a possible approach to the segregation of neurobehavioral disorders based on the DAT-dependent control of DA signaling.

Attending to a visual stimulus increases its detectability, even if gaze is directed elsewhere. This covert attentional selection is known to enhance spiking across many brain areas, including the primary visual cortex (V1). Here we investigate the temporal dynamics of attention-related spiking changes in V1 of macaques performing a task that separates attentional selection from the onset of visual stimulation. We found that preceding attentional enhancement there was a sharp, transient decline in spiking following presentation of an attention-guiding cue. This disruption of V1 spiking was not observed in a task-naïve subject that passively observed the same stimulus sequence, suggesting that sensory activation is insufficient to cause suppression. Following this suppression, attended stimuli evoked more spiking than unattended stimuli, matching previous reports of attention-related activity in V1. Laminar analyses revealed a distinct pattern of activation in feedback-associated layers during both the cue-induced suppression and subsequent attentional enhancement. These findings suggest that top-down modulation of V1 spiking can be bidirectional and result in either suppression or enhancement of spiking responses.