BDNFval66met affects neural activation pattern during fear conditioning and 24 h delayed fear recall.

Brain-derived neurotrophic factor (BDNF), the most abundant neutrophin in the mammalian central nervous system, is critically involved in synaptic plasticity. In both rodents and humans, BDNF has been implicated in hippocampus- and amygdala-dependent learning and memory and has more recently been linked to fear extinction processes. Fifty-nine healthy participants, genotyped for the functional BDNFval66met polymorphism, underwent a fear conditioning and 24h-delayed extinction protocol while skin conductance and blood oxygenation level dependent (BOLD) responses (functional magnetic resonance imaging) were acquired. We present the first report of neural activation pattern during fear acquisition 'and' extinction for the BDNFval66met polymorphism using a differential conditioned stimulus (CS)+ > CS- comparison. During conditioning, we observed heightened allele dose-dependent responses in the amygdala and reduced responses in the subgenual anterior cingulate cortex in BDNFval66met met-carriers. During early extinction, 24h later, we again observed heightened responses in several regions ascribed to the fear network in met-carriers as opposed to val-carriers (insula, amygdala, hippocampus), which likely reflects fear memory recall. No differences were observed during late extinction, which likely reflects learned extinction. Our data thus support previous associations of the BDNFval66met polymorphism with neural activation in the fear and extinction network, but speak against a specific association with fear extinction processes.

Training-associated changes and stability of attention bias in youth: Implications for Attention Bias Modification Treatment for pediatric anxiety.

Attention Bias Modification Treatment (ABMT), an emerging treatment for anxiety disorders, is thought to modify underlying, stable patterns of attention. Therefore, ABMT research should take into account the impact of attention bias stability on attention training response, especially in pediatric populations. ABMT research typically relies on the dot-probe task, where individuals detect a probe following an emotional-neutral stimulus pair. The current research presents two dot-probe experiments relevant to ABMT and attention-bias stability. In Experiment 1, anxious youth receiving 8-weeks of cognitive-behavioral therapy (CBT) were randomly assigned to ABMT that trains attention towards happy faces (n=18) or placebo (n=18). Two additional comparison groups, anxious youth receiving only CBT (n=17) and healthy comparison youth (n=16), were studied. Active attention training towards happy faces did not augment clinician-rated response to CBT; however, individuals receiving training exhibited reductions on self-report measures of anxiety earlier than individuals receiving CBT only. In Experiment 2, healthy youth (n=12) completed a dot-probe task twice while undergoing functional magnetic resonance imaging. Intra-class correlation demonstrated stability of neural activation in response to attention bias in the ventrolateral prefrontal cortex and amygdala. Together, these two studies investigate the ways in which attention-bias stability may impact future work on ABMT.

Distinct contributions of the dorsolateral prefrontal and orbitofrontal cortex during emotion regulation.

The lateral prefrontal and orbitofrontal cortices have both been implicated in emotion regulation, but their distinct roles in regulation of negative emotion remain poorly understood. To address this issue we enrolled 58 participants in an fMRI study in which participants were instructed to reappraise both negative and neutral stimuli. This design allowed us to separately study activations reflecting cognitive processes associated with reappraisal in general and activations specifically related to reappraisal of negative emotion. Our results confirmed that both the dorsolateral prefrontal cortex (DLPFC) and the lateral orbitofrontal cortex (OFC) contribute to emotion regulation through reappraisal. However, activity in the DLPFC was related to reappraisal independently of whether negative or neutral stimuli were reappraised, whereas the lateral OFC was uniquely related to reappraisal of negative stimuli. We suggest that relative to the lateral OFC, the DLPFC serves a more general role in emotion regulation, perhaps by reflecting the cognitive demand that is inherent to the regulation task.

Nonconscious activation of placebo and nocebo pain responses.

The dominant theories of human placebo effects rely on a notion that consciously perceptible cues, such as verbal information or distinct stimuli in classical conditioning, provide signals that activate placebo effects. However, growing evidence suggest that behavior can be triggered by stimuli presented outside of conscious awareness. Here, we performed two experiments in which the responses to thermal pain stimuli were assessed. The first experiment assessed whether a conditioning paradigm, using clearly visible cues for high and low pain, could induce placebo and nocebo responses. The second experiment, in a separate group of subjects, assessed whether conditioned placebo and nocebo responses could be triggered in response to nonconscious (masked) exposures to the same cues. A total of 40 healthy volunteers (24 female, mean age 23 y) were investigated in a laboratory setting. Participants rated each pain stimulus on a numeric response scale, ranging from 0 = no pain to 100 = worst imaginable pain. Significant placebo and nocebo effects were found in both experiment 1 (using clearly visible stimuli) and experiment 2 (using nonconscious stimuli), indicating that the mechanisms responsible for placebo and nocebo effects can operate without conscious awareness of the triggering cues. This is a unique experimental verification of the influence of nonconscious conditioned stimuli on placebo/nocebo effects and the results challenge the exclusive role of awareness and conscious cognitions in placebo responses.

Attention orientation in parents exposed to the 9/11 terrorist attacks and their children.

While trauma affects both parents and their children, minimal research examines the role of information-processing perturbations in shaping reactions to trauma experienced by parents and, in turn, the effect this trauma has on their children. This study examines familial associations among trauma, psychopathology, and attention bias. Specifically, group differences in psychopathology and attention bias were examined in both adults and their children based on trauma exposure. In addition, the association between attention bias in parents and attention bias in their children was examined. Parents exposed to the 9/11 World Trade Center attacks and their children were recruited from the New York City Metropolitan area. Levels of trauma exposure, psychiatric symptoms, and attention bias to threat, as measured with the dot-probe task, were each assessed in 90 subjects, comprising of 45 parents and one of their children. These measures were examined in parents and their children separately; each parent and child was categorized on the presence of high or low levels of trauma exposure. Although trauma exposure did not relate to psychopathology, parents who were highly exposed to trauma showed greater attention bias towards threat than parents with low trauma exposure. However, the children of high trauma-exposed parents did not show enhanced attention bias towards threat, though threat bias in the high trauma-exposed parents did negatively correlate with threat bias in their children. This association between trauma and attention bias in parents was found four-to-five years after 9/11, suggesting that trauma has enduring influences on threat processing. Larger, prospective studies might examine relationships within families among traumatic exposures, psychopathology, and information-processing functions.

Neural and behavioral responses to threatening emotion faces in children as a function of the short allele of the serotonin transporter gene.

Recent evidence suggests that a genetic polymorphism in the promoter region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) mediates stress reactivity in adults. Little is known, however, about this gene-brain association in childhood and adolescence, generally conceptualized as a time of heightened stress reactivity. The present study examines the association between 5-HTTLPR allelic variation and responses to fearful and angry faces presented both sub- and supraliminally in participants, ages 9-17. Behaviorally, carriers of the 5-HTTLPR short (s) allele exhibited significantly greater attentional bias to subliminally presented fear faces than did their long (l)-allele homozygous counterparts. Moreover, s-allele carriers showed greater neural activations to fearful and angry faces than did l-allele homozygotes in various regions of association cortex previously linked to attention control in adults. These results indicate that in children and adolescents, s-allele carriers can be distinguished from l-allele homozygotes on the basis of hypervigilant behavioral and neural processing of negative material.

Normative data on development of neural and behavioral mechanisms underlying attention orienting toward social-emotional stimuli: an exploratory study.

The ability of positive and negative facial signals to influence attention orienting is crucial to social functioning. Given the dramatic developmental change in neural architecture supporting social function, positive and negative facial cues may influence attention orienting differently in relatively young or old individuals. However, virtually no research examines such age-related differences in the neural circuitry supporting attention orienting to emotional faces. We examined age-related correlations in attention-orienting biases to positive and negative face emotions in a healthy sample (N=37; 9-40 years old) using functional magnetic resonance imaging and a dot-probe task. The dot-probe task in an fMRI setting yields both behavioral and neural indices of attention biases towards or away from an emotional cue (happy or angry face). In the full sample, angry-face attention bias scores did not correlate with age, and age did not correlate with brain activation to angry faces. However, age did positively correlate with attention bias towards happy faces; age also negatively correlated with left cuneus and left caudate activation to a happy bias fMRI contrast. Secondary analyses suggested age-related changes in attention bias to happy faces. The tendency in younger children to direct attention away from happy faces (relative to neutral faces) was diminished in the older age groups, in tandem with increasing neural deactivation. Implications for future work on developmental changes in attention-emotion processing are discussed.