How adverse childhood experiences get under the skin: A systematic review, integration and methodological discussion on threat and reward learning mechanisms.

Adverse childhood experiences (ACEs) are a major risk factor for the development of multiple psychopathological conditions, but the mechanisms underlying this link are poorly understood. Associative learning encompasses key mechanisms through which individuals learn to link important environmental inputs to emotional and behavioral responses. ACEs may impact the normative maturation of associative learning processes, resulting in their enduring maladaptive expression manifesting in psychopathology. In this review, we lay out a systematic and methodological overview and integration of the available evidence of the proposed association between ACEs and threat and reward learning processes. We summarize results from a systematic literature search (following PRISMA guidelines) which yielded a total of 81 articles (threat: n=38, reward: n=43). Across the threat and reward learning fields, behaviorally, we observed a converging pattern of aberrant learning in individuals with a history of ACEs, independent of other sample characteristics, specific ACE types, and outcome measures. Specifically, blunted threat learning was reflected in reduced discrimination between threat and safety cues, primarily driven by diminished responding to conditioned threat cues. Furthermore, attenuated reward learning manifested in reduced accuracy and learning rate in tasks involving acquisition of reward contingencies. Importantly, this pattern emerged despite substantial heterogeneity in ACE assessment and operationalization across both fields. We conclude that blunted threat and reward learning may represent a mechanistic route by which ACEs may become physiologically and neurobiologically embedded and ultimately confer greater risk for psychopathology. In closing, we discuss potentially fruitful future directions for the research field, including methodological and ACE assessment considerations.

Decomposing Neural Representational Patterns of Discriminatory and Hedonic Information during Somatosensory Stimulation.

The ability to interrogate specific representations in the brain, determining how, and where, difference sources of information are instantiated can provide invaluable insight into neural functioning. Pattern component modeling (PCM) is a recent analytic technique for human neuroimaging that allows the decomposition of representational patterns in brain into contributing subcomponents. In the current study, we present a novel PCM variant that tracks the contribution of prespecified representational patterns to brain representation across areas, thus allowing hypothesis-guided employment of the technique. We apply this technique to investigate the contributions of hedonic and nonhedonic information to the neural representation of tactile experience. We applied aversive pressure (AP) and appetitive brush (AB) to stimulate distinct peripheral nerve pathways for tactile information (C-/CT-fibers, respectively) while patients underwent functional magnetic resonance imaging (fMRI) scanning. We performed representational similarity analyses (RSAs) with pattern component modeling to dissociate how discriminatory versus hedonic tactile information contributes to population code representations in the human brain. Results demonstrated that information about appetitive and aversive tactile sensation is represented separately from nonhedonic tactile information across cortical structures. This also demonstrates the potential of new hypothesis-guided PCM variants to help delineate how information is instantiated in the brain.

Data sharing in experimental fear and anxiety research: From challenges to a dynamically growing database in 10 simple steps.

Data sharing holds promise for advancing and accelerating science by facilitating and fostering collaboration, reproducibility and optimal use of sparse resources. We argue that despite the existence of general data sharing guidelines (e.g, FAIR-principles), their translation and implementation requires field-specific considerations. Here, we addressed this timely question for the field of experimental research on fear and anxiety and showcase the enormous prospects by illustrating the wealth and richness of a curated data collection of publicly available datasets using the fear conditioning paradigm based on 103 studies and 8839 participants. We highlight challenges encountered when aiming to reuse the available data corpus and derive 10 simple steps for making data sharing in the field more efficient and sustainable and hence facilitating collaboration, cumulative knowledge generation and large scale mega-, meta- and psychometric analyses. We share our vision and first steps towards transforming such curated data collections into a homogenized and dynamically growing database allowing for easy contributions and for living analysis tools for the collective benefit of the research community.

Robust group- but limited individual-level (longitudinal) reliability and insights into cross-phases response prediction of conditioned fear.

Here, we follow the call to target measurement reliability as a key prerequisite for individual-level predictions in translational neuroscience by investigating (1) longitudinal reliability at the individual and (2) group level, (3) internal consistency and (4) response predictability across experimental phases. One hundred and twenty individuals performed a fear conditioning paradigm twice 6 months apart. Analyses of skin conductance responses, fear ratings and blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) with different data transformations and included numbers of trials were conducted. While longitudinal reliability was rather limited at the individual level, it was comparatively higher for acquisition but not extinction at the group level. Internal consistency was satisfactory. Higher responding in preceding phases predicted higher responding in subsequent experimental phases at a weak to moderate level depending on data specifications. In sum, the results suggest that while individual-level predictions are meaningful for (very) short time frames, they also call for more attention to measurement properties in the field.

Revisiting potential associations between brain morphology, fear acquisition and extinction through new data and a literature review.

Inter-individual differences in defensive responding are widely established but their morphological correlates in humans have not been investigated exhaustively. Previous studies reported associations with cortical thickness of the dorsal anterior cingulate cortex, insula and medial orbitofrontal cortex as well as amygdala volume in fear conditioning studies. However, these associations are partly inconsistent and often derived from small samples. The current study aimed to replicate previously reported associations between physiological and subjective measures of fear acquisition and extinction and brain morphology. Structural magnetic resonance imaging was performed on 107 healthy adults who completed a differential cued fear conditioning paradigm with 24 h delayed extinction while skin conductance response (SCR) and fear ratings were recorded. Cortical thickness and subcortical volume were obtained using the software Freesurfer. Results obtained by traditional null hypothesis significance testing and Bayesians statistics do not support structural brain-behavior relationships: Neither differential SCR nor fear ratings during fear acquisition or extinction training could be predicted by cortical thickness or subcortical volume in regions previously reported. In summary, the current pre-registered study does not corroborate associations between brain morphology and inter-individual differences in defensive responding but differences in experimental design and analyses approaches compared to previous work should be acknowledged.

From Architecture to Evolution: Multisensory Evidence of Decentralized Emotion.

Emotional appraisal in humans is often considered a centrally mediated process by which sensory signals, void of emotional meaning, are assessed by integrative brain structures steps removed from raw sensation. We review emerging evidence that the emotional value of the environment is coded by nonvisual sensory systems as early as the sensory receptors and that these signals inform the emotional state of an organism independent of sensory cortical processes. We further present evidence for cross-species conservation of sensory projections to central emotion-processing brain regions. Based on this, we argue not only that emotional appraisal is a decentralized process, but that all human emotional experience may reflect the sensory experience of our ancestors.

Genesis and Maintenance of Attentional Biases: The Role of the Locus Coeruleus-Noradrenaline System.

Emotionally arousing events are typically better remembered than mundane ones, in part because emotionally relevant aspects of our environment are prioritized in attention. Such biased attentional tuning is itself the result of associative processes through which we learn affective and motivational relevance of cues. We propose that the locus coeruleus-noradrenaline (LC-NA) system plays an important role in the genesis of attentional biases through associative learning processes as well as their maintenance. We further propose that individual differences in and disruptions of the LC-NA system underlie the development of maladaptive biases linked to psychopathology. We provide support for the proposed role of the LC-NA system by first reviewing work on attentional biases in development and its link to psychopathology in relation to alterations and individual differences in NA availability. We focus on pharmacological manipulations to demonstrate the effect of a disrupted system as well as the ADRA2b polymorphism as a tool to investigate naturally occurring differences in NA availability. We next review associative learning processes that-modulated by the LC-NA system-result in such implicit attentional biases. Further, we demonstrate how NA may influence aversive and appetitive conditioning linked to anxiety disorders as well as addiction and depression.

What BANE can offer GANE: Individual differences in function of hotspot mechanisms.

In this commentary we focus on individual differences in proposed mechanisms underlying arousal-based enhancement of prioritized stimuli. We discuss the potential of genotyping studies for examining effects of noradrenergic processes on stimulus prioritization in humans and stress the importance of potential individual differences in the activity of specific receptor subtypes in hotspot processes proposed by the GANE model.

Neurogenetic variations in norepinephrine availability enhance perceptual vividness.

Emotionally salient aspects of the world are experienced with greater perceptual vividness than mundane ones; however, such emotionally enhanced vividness (EEV) may be experienced to different degrees for different people. We examined whether BOLD activity associated with a deletion variant of the ADRA2b gene coding for the α2b adrenoceptor modulates EEV in humans. Relative to noncarriers, ADRA2b deletion carriers showed higher levels of perceptual vividness, with the ventromedial prefrontal cortex (VMPFC) showing greater modulation by EEV. Deletion carriers were also more sensitive to the featural salience of the images, suggesting a more pervasive role of norepinephrine in perceptual encoding. Path analysis revealed that, whereas a simple model by which the amygdala modulated the lateral occipital complex best characterized EEV-related activity in noncarriers, contributions of an additional VMPFC pathway best characterized deletion carriers. Thus, common norepinephrine-related neurogenetic differences enhance the subjective vividness of perceptual experience and its emotional enhancement.

The P300 in middle cerebral artery strokes or hemorrhages: Outcome predictions and source localization.

OBJECTIVES: There are no reliable outcome predictors for severely impaired patients suffering from large infarctions or hemorrhages within the territory of the middle cerebral artery. This study investigated whether the amplitude of the event-related potential (ERP) component P300 predicts if a patient will be transferred to the next stage of rehabilitation (positive outcome) or to a nursing home (negative outcome). The second goal was to look for lesion locations determining the generation of the P300 amplitude. METHODS: Forty-seven patients performed an auditory oddball task to elicit the P300 and were assessed with different scores for activities of daily living (ADL). Patients were divided in two groups according to their outcome. P300 amplitudes were compared between these groups controlling for age and gender. Post-hoc analyses were performed to analyse the relationship between P300 amplitude and neurological outcome scores. In addition, lesion overlaps were created to detect which lesion pattern affects P300 generation. RESULTS: Patients with a positive outcome showed higher P300 amplitudes at frontal electrode sites than those with a negative outcome. P300 amplitude correlated with ADL score difference. Lesions in the superior temporal gyrus, middle and inferior frontal and prefrontal regions led to visibly diminished P300 amplitudes. CONCLUSIONS: The findings suggest that an impairment of attention (P300 amplitude reduction) negatively influences successful neurological rehabilitation. Left superior temporal lobe and the left premotor/prefrontal areas are essential brain areas for the generation of the P300. SIGNIFICANCE: P300 amplitude may be used as an outcome predictor for severely impaired patients suffering from middle cerebral artery strokes or hemorrhages.