Mindfulness-based stress reduction for breast cancer survivors (MBSR(BC)): evaluating mediators of psychological and physical outcomes in a large randomized controlled trial.

MBSR(BC) is known to have a positive impact on psychological and physical symptoms among breast cancer survivors (BCS). The cognitive mechanisms of "how" MBSR(BC) works was addressed in a recent study that found that there was strong consistent evidence that reduced emotional reactivity is a mediator and moderate consistent evidence that mindfulness, rumination, and worry were mediators. The purpose of this study, as part of a larger R01 trial, was to test whether positive effects achieved from the MBSR(BC) program were mediated through changes in increased mindfulness, decreased fear of breast cancer recurrence, and perceived stress. Female BCS > 21 years diagnosed with Stage 0-III breast cancer were randomly assigned to a 6-week MBSR(BC) or a Usual Care (UC)regimen. Potential mediators of 6- and 12-week outcomes were identified by analysis of covariance (ANCOVA), followed by formal mediational analyses of main effects of MBSR(BC) on 6- and 12-week outcomes, including percentage of total effects explained. Among 322 BCS (167 MBSR(BC) and 155 UC), fear of recurrence and perceived stress, but not mindfulness, mediated reductions in anxiety and fatigue at weeks 6 and 12, partially supporting our hypothesis of cognitive mechanisms of MBSR(BC). TRIAL REGISTRATION: Registration Number: NCT01177124 http://www.ClinicalTrials.gov.

Sympathetic responding to unconditioned stimuli predicts subsequent threat expectancy, orienting, and visuocortical bias in human aversive Pavlovian conditioning.

Threat expectancy is the ability to predict an aversive outcome. What is not known is the influence of initial threat responding on the acquisition of verbal, attentional and perceptual biases towards conditioned threat cues. This study evaluated the extent to which initial unconditioned stimulus (UCS) responding was related to trial-by-trial self-reported expectancy, sensory processing (visuocortical EEG) and orienting (heart rate deceleration) to threat cues during extinction learning. Participants (n = 38) viewed oriented Gabor gratings, associated with the presence (CS+) or absence (CS-) of a 96 dB white noise (UCS), flickering at 12 Hz to elicit steady state visually evoked potentials (ssVEPs). Multivariate multiple regression revealed greater initial UCS skin conductance responding to predict extinction responding: enhanced visuocortical discrimination, greater heart rate deceleration to CS+, and greater threat expectancy endorsements. These results suggest that the motivational intensity of initial threat reactivity (sympathetic UCS responding) drives learning-induced defensive dispositions across multiple response systems.

How the visual brain detects emotional changes in facial expressions: Evidence from driven and intrinsic brain oscillations.

The processing of facial expressions is often studied using static pictorial cues. Recent work, however, suggests that viewing changing expressions more robustly evokes physiological responses. Here, we examined the sensitivity of steady-state visual evoked potentials and intrinsic oscillatory brain activity to transient emotional changes in facial expressions. Twenty-two participants viewed sequences of grayscale faces periodically turned on and off at a rate of 17.5 Hz, to evoke flicker steady-state visual evoked potentials (ssVEPs) in visual cortex. Each sequence began with a neutral face (flickering for 2290 msec), immediately followed by a face from the same actor (also flickering for 2290 msec) with one of four expressions (happy, angry, fearful, or another neutral expression), followed by the initially presented neutral face (flickering for 1140 msec). The amplitude of the ssVEP and the power of intrinsic brain oscillations were analyzed, comparing the four expression-change conditions. We found a transient perturbation (reduction) of the ssVEP that was more pronounced after the neutral-to-angry change compared to the other conditions, at right posterior sensors. Induced alpha-band (8-13 Hz) power was reduced compared to baseline after each change. This reduction showed a central-occipital topography and was strongest in the subtlest and rarest neutral-to-neutral condition. Thus, the ssVEP indexed involvement of face-sensitive cortical areas in decoding affective expressions, whereas mid-occipital alpha power reduction reflected condition frequency rather than expression-specific processing, consistent with the role of alpha power changes in selective attention.

What does the dot-probe task measure? A reverse correlation analysis of electrocortical activity.

The dot-probe task is considered a gold standard for assessing the intrinsic attentive selection of one of two lateralized visual cues, measured by the response time to a subsequent, lateralized response probe. However, this task has recently been associated with poor reliability and conflicting results. To resolve these discrepancies, we tested the underlying assumption of the dot-probe task-that fast probe responses index heightened cue selection-using an electrophysiological measure of selective attention. Specifically, we used a reverse correlation approach in combination with frequency-tagged steady-state visual potentials (ssVEPs). Twenty-one participants completed a modified dot-probe task in which each member of a pair of lateralized face cues, varying in emotional expression (angry-angry, neutral-angry, neutral-neutral), flickered at one of two frequencies (15 or 20 Hz), to evoke ssVEPs. One cue was then replaced by a response probe, and participants indicated the probe orientation (0° or 90°). We analyzed the ssVEP evoked by the cues as a function of response speed to the subsequent probe (i.e., a reverse correlation analysis). Electrophysiological measures of cue processing varied with probe hemifield location: Faster responses to left probes were associated with weak amplification of the preceding left cue, apparent only in a median split analysis. By contrast, faster responses to right probes were systematically and parametrically predicted by diminished visuocortical selection of the preceding right cue. Together, these findings highlight the poor validity of the dot-probe task, in terms of quantifying intrinsic, nondirected attentive selection irrespective of probe/cue location.

Disclosure of Diagnosis in Early Recognition of Psychosis.

There is a debate concerning risks and benefits of early intervention in psychosis, especially concerning diagnosis disclosure. The present study reports preliminary findings on self-reported locus of control and psychological distress after the disclosure of diagnosis in an early recognition center. We compared the ratings of the locus of control and psychological distress before and after communication of diagnosis. The study included individuals with an at-risk mental state (ARMS) (n = 10), schizophrenia (n = 9), and other psychiatric disorders (n = 11). Results indicate greater endorsement of the internal locus of control in individuals with ARMS after communication of diagnosis in contrast to the other groups. Our results suggest that disclosure of diagnosis in an early recognition center leads to a reduction of psychological distress and increased feelings of control over one's health. Persons with ARMS seem to particularly benefit from disclosure of diagnosis as part of early intervention.

Multimodal Imaging Evidence for a Frontoparietal Modulation of Visual Cortex during the Selective Processing of Conditioned Threat.

Emotionally salient cues are detected more readily, remembered better, and evoke greater visual cortical responses compared with neutral stimuli. The current study used concurrent EEG-fMRI recordings to identify large-scale network interactions involved in the amplification of visual cortical activity when viewing aversively conditioned cues. To generate a continuous neural signal from pericalcarine visual cortex, we presented rhythmic (10/sec) phase-reversing gratings, the orientation of which predicted the presence (CS+) or absence (CS-) of a cutaneous electric shock (i.e., the unconditioned stimulus). The resulting single trial steady-state visual evoked potential (ssVEP) amplitude was regressed against the whole-brain BOLD signal, resulting in a measure of ssVEP-BOLD coupling. Across all trial types, ssVEP-BOLD coupling was observed in both primary and extended visual cortical regions, the rolandic operculum, as well as the thalamus and bilateral hippocampus. For CS+ relative to CS- trials during the conditioning phase, BOLD-alone analyses showed CS+ enhancement at the occipital pole, superior temporal sulci, and the anterior insula bilaterally, whereas ssVEP-BOLD coupling was greater in the pericalcarine cortex, inferior parietal cortex, and middle frontal gyrus. Dynamic causal modeling analyses supported connectivity models in which heightened activity in pericalcarine cortex for threat (CS+) arises from cortico-cortical top-down modulation, specifically from the middle frontal gyrus. No evidence was observed for selective pericalcarine modulation by deep cortical structures such as the amygdala or anterior insula, suggesting that the heightened engagement of pericalcarine cortex for threat stimuli is mediated by cortical structures that constitute key nodes of canonical attention networks.

The role of the COMT val158met polymorphism in mediating aversive learning in visual cortex.

The catechol-O-methyltransferase (COMT) val158met single nucleotide polymorphism (SNP) alters metabolic activity of the COMT enzyme regulating catecholamines, with the Val (valine) allele resulting in 40% greater enzymatic activity than the Met (methionine) allele. Previous research has identified systematic inter-individual differences in cognitive and behavioral phenotypes related to this polymorphism, often attributed to the fact that extracellular dopamine in the prefrontal cortex is strongly affected by the COMT enzyme. The neurophysiological mechanisms mediating these inter-individual differences in specific brain systems and task contexts remain to be established however. In the current study, we examined the extent to which physio-mechanistic differences by COMT genotype affect somato-visceral and visual cortical responses to learned threat cues. Classical aversive differential conditioning was implemented using rapidly phase-reversing grating stimuli, previously shown to engage retinotopic visual cortex. Differential response patterns in sensory and autonomic systems were elicited by pairing one grating (CS+, conditioned stimulus), but not the other (CS-), with a noxious stimulus. Dense-array electroencephalography and somato-visceral measures of defensive reactivity were recorded in addition to self-report data. Individuals of the Val/Val genotype, compared to Met allele carriers, reliably showed greater initial enhancement in their visuocortical response to the CS+, accompanied by stronger defensive engagement, indexed by heart rate acceleration and startle potentiation. The finding that COMT polymorphism status affects threat cue reactivity at the visuocortical level is consistent with the notion that sensory processing of threat is facilitated by strong re-entrant bias signals from anterior areas, including the prefrontal cortex.

Aversive learning shapes neuronal orientation tuning in human visual cortex.

The responses of sensory cortical neurons are shaped by experience. As a result perceptual biases evolve, selectively facilitating the detection and identification of sensory events that are relevant for adaptive behaviour. Here we examine the involvement of human visual cortex in the formation of learned perceptual biases. We use classical aversive conditioning to associate one out of a series of oriented gratings with a noxious sound stimulus. After as few as two grating-sound pairings, visual cortical responses to the sound-paired grating show selective amplification. Furthermore, as learning progresses, responses to the orientations with greatest similarity to the sound-paired grating are increasingly suppressed, suggesting inhibitory interactions between orientation-selective neuronal populations. Changes in cortical connectivity between occipital and fronto-temporal regions mirror the changes in visuo-cortical response amplitudes. These findings suggest that short-term behaviourally driven retuning of human visual cortical neurons involves distal top-down projections as well as local inhibitory interactions.

Face-evoked steady-state visual potentials: effects of presentation rate and face inversion.

Face processing can be explored using electrophysiological methods. Research with event-related potentials has demonstrated the so-called face inversion effect, in which the N170 component is enhanced in amplitude and latency to inverted, compared to upright, faces. The present study explored the extent to which repetitive lower-level visual cortical engagement, reflected in flicker steady-state visual evoked potentials (ssVEPs), shows similar amplitude enhancement to face inversion. We also asked if inversion-related ssVEP modulation would be dependent on the stimulation rate at which upright and inverted faces were flickered. To this end, multiple tagging frequencies were used (5, 10, 15, and 20 Hz) across two studies (n = 21, n = 18). Results showed that amplitude enhancement of the ssVEP for inverted faces was found solely at higher stimulation frequencies (15 and 20 Hz). By contrast, lower frequency ssVEPs did not show this inversion effect. These findings suggest that stimulation frequency affects the sensitivity of ssVEPs to face inversion.

Affective learning and psychophysiological reactivity in dementia patients.

We examined the association of faces with biographical information that varied in emotional content in patients with Alzheimer's disease and a healthy control group. During two experimental sessions, participants rated neutral male faces on dimensions of hedonic valence and emotional arousal, later paired with fictitious biographical information. Both groups changed their ratings of the faces according to the biographical content. Free recall and recognition were tested in the second session. Patients neither recalled the biographical information nor recognized the faces, whereas the controls did. In addition, psychophysiological measures were taken in response to the face stimuli. Patients showed significant heart rate modulation as a function of their emotion ratings, whereas the controls did not. No correlation of rating changes with skin conductance was found in any group. Results suggest that psychophysiological reactions such as heart rate changes may indicate preserved affective associative learning in dementia patients despite impaired explicit memory.