The Hypothesis of Subliminal Cue Reactivity in Addiction Revisited: An fMRI Study

<b><i>Introduction:</i></b> Exposure to conditioned cues is a common trigger of relapse in addiction. It has been suggested that such cues can activate motivationally relevant neurocircuitry in individuals with substance use disorders even without being consciously perceived. We aimed to see if this could be replicated in a sample with severe amphetamine use disorder and a control group of healthy subjects. <b><i>Methods:</i></b> We used fMRI to test the hypothesis that individuals with amphetamine use disorder, but not healthy controls, exhibit a specific neural reactivity to subliminally presented pictures related to amphetamine use. Twenty-four amphetamine users and 25 healthy controls were recruited and left data of sufficient quality to be included in the final analysis. All subjects were exposed to drug-related and neutral pictures of short duration (13.3 ms), followed by a backward visual mask image. The contrast of interest was drug versus neutral subliminal pictures. <b><i>Results:</i></b> There were no statistically significant differences in BOLD signal between the drug and neutral cues, neither in the limbic regions of primary interest nor in exploratory whole-brain analyses. The same results were found both in amphetamine users and controls. <b><i>Discussion/Conclusion:</i></b> We found no evidence of neural reactivity to subliminally presented drug cues in this sample of subjects with severe amphetamine dependence. These results are discussed in relation to the earlier literature, and the evidence for subliminal drug cue reactivity in substance use disorders is questioned.

Event-Related Potentials in Women on the Pill: Neural Correlates of Positive and Erotic Stimulus Processing in Oral Contraceptive Users

Background/Aims: Exposure toward positive emotional cues with – and without – reproductive significance plays a crucial role in daily life and regarding well-being as well as mental health. While possible adverse effects of oral contraceptive (OC) use on female mental and sexual health are widely discussed, neural processing of positive emotional stimuli has not been systematically investigated in association with OC use. Considering reported effects on mood, well-being and sexual function, and proposed associations with depression, it was hypothesized that OC users showed reduced neural reactivity toward positive and erotic emotional stimuli during early as well as later stages of emotional processing and also rated these stimuli as less pleasant and less arousing compared to naturally cycling (NC) women.Method: Sixty-two female subjects (29 NC and 33 OC) were assessed at three time points across the natural menstrual cycle and corresponding time points of the OC regimen. Early (early posterior negativity, EPN) and late (late positive potential, LPP) event-related potentials in reaction to positive, erotic and neutral stimuli were collected during an Emotional Picture Stroop Paradigm (EPSP). At each appointment, subjects provided saliva samples for analysis of gonadal steroid concentration. Valence and arousal ratings were collected at the last appointment.Results: Oral contraceptive users had significantly lower endogenous estradiol and progesterone concentrations compared to NC women. No significant group differences in either subjective stimulus evaluations or neural reactivity toward positive and erotic emotional stimuli were observed. For the OC group, LPP amplitudes in reaction to erotic vs. neutral pictures differed significantly between measurement times across the OC regimen.Discussion: In this study, no evidence regarding alterations of neural reactivity toward positive and erotic stimuli in OC users compared to NC was found. Possible confounding factors and lines for future research are elaborated and discussed.

Oxytocin modulates neural reactivity in women to emotional stimuli of children depending on childhood emotional neglect

Sensitivity for rewarding cues and distress signals from children are fundamental to human caregiving, and modulated by the neuropeptide oxytocin. In a functional magnetic resonance imaging (fMRI) study we investigated whether oxytocin regulates neural responses to reward or distress cues form children. In a placebo controlled within-subject design we measured neural responses to positive, negative and neutral cues from children in 22 healthy female subjects who received oxytocin (24 IU) vs. placebo. Further, based on current literature, we hypothesized that oxytocin effects are modulated by experiences of childhood trauma. The task elicited valence specific effects, positive images activated the ventromedial prefrontal cortex, left anterior cingulate cortex and right putamen, and images of children in distress the bilateral amygdala, hippocampus and right medial superior frontal cortex. The effects of oxytocin depended on subjective reports of childhood emotional neglect. Self-reported neglect interacted with oxytocin administration in the amygdala, hippocampus and prefrontal areas. In individuals with higher scores of emotional neglect, oxytocin increased neural reactivity of limbic structures to positive and neutral images. Our findings need replication in larger samples but are in line with the recent literature on the modulating effect of childhood adversity on the sensitivity to OXT administration.

Neural Mechanisms of Intimate Partner Aggression

People sometimes hurt those they profess to love; yet our understanding of intimate partner aggression (IPA) and its causes remains incomplete. We examined brain activity using functional magnetic resonance imaging (fMRI) in an ethnically and racially diverse sample of 50 female-male, monogamous romantic couples as they completed an aggression task against their intimate partner, a close friend, and a different-sex stranger. Laboratory and real-world IPA were uniquely associated with altered activity within and connectivity between cortical midline structures that subserve social cognition and the computation of value. Men’s IPA most corresponded to lower posterior cingulate reactivity during provocation and women’s IPA most corresponded to lower ventromedial prefrontal cortex activity during IPA itself. Actor-partner independence modeling suggested women’s IPA may correspond to their male partner’s neural reactivity to provocation. Broadly, these findings highlight the importance of self-regulatory functions of the medial cortex and away from effortful inhibition subserved by dorsolateral cortices.

Healthcare experience disrupts representational similarity between one's and others' pain in anterior insula

Medical students and professional healthcare providers often underestimate patients' pain, an effect associated with decreased neural response of the anterior insula to pain information. However, the functional significance of these neural modulations is still debated. We recruited university medical students and emergency caregivers to test the role of healthcare experience on the behavioral/neural reactivity to other's pain, emotions, and beliefs. We confirmed that healthcare experience decreased the sensitivity to others' suffering, as measured by subjective ratings and insular response. This effect was independent from stimulus modality (pictures, texts), but specific for pain, as it did not generalize to emotions or beliefs. Critically, multivariate pattern analysis revealed that healthcare experience impacted specifically a component of the neural representation of others' pain shared with that of first-hand nociception. This suggests a reduced likelihood of appraising others' sufferance as one's own, and might offer a mechanistic explanation for pain underestimation in clinical settings.

Effects of Cognitive Reappraisal on Subjective and Neural Reactivity to Angry Faces in Children with Social Anxiety Disorder, Clinical Controls with Mixed Anxiety Disorders and Healthy Children

Cognitive models of social anxiety suggest that social anxiety disorder (SAD) is characterized by both enhanced emotional reactivity and deficits in emotion regulation. Emotional reactivity to socially threatening children’s faces and their modulation through reappraisal were measured via subjective ratings and electrocortical responses in children (age 10–13) with SAD (n = 28), clinical controls with mixed anxiety disorders (n = 28), and healthy controls (n = 29). Children with SAD showed higher subjective reactivity to the images of angry children’s faces while all children reported reduced reactivity in their subjective ratings following reappraisal. Reduced electrocortical reactivity after reappraisal was only evident in older children and boys and was unrelated to anxiety. The present study indicates that cognitive reappraisal may be beneficial in reducing subjective reactivity in children with anxiety disorders, while neural effects of reappraisal may emerge at older ages.

Anxiolytic effects of chronic intranasal oxytocin on neural responses to threat are dose-frequency dependent

Anxiety disorders are prevalent psychiatric conditions characterized by exaggerated anxious arousal and threat reactivity. Animal and human studies suggest an anxiolytic potential of the neuropeptide oxytocin (OT), yet, while a clinical application will require chronic administration protocols previous studies in humans have exclusively focused on single-dose (acute) intranasal OT effects. We aimed at determining whether the anxiolytic effects of OT are maintained with repeated (chronic) administration or are influenced by dose frequency and trait anxiety. A double-blind randomized, placebo-controlled pharmaco-fMRI trial (n=147) determined acute (single-dose) as well as chronic effects of two different dose frequencies of OT (OT administered daily for 5 days or every other day) on emotional reactivity in healthy subjects with high versus low trait anxiety. OT produced valence, dose frequency and trait anxiety specific effects, such that the low-frequency (intermittand) chronic dosage specifically attenuated neural reactivity in amygdala-insula-prefrontal regions in high anxious subjects in response to threatening but not positive stimuli. The present trial provides evidence that low dose frequency chronic oxytocin nasal spray has the potential to alleviate exaggerated neural threat reactivity in subjects with elevated anxiety levels underscoring a treatment potential for anxiety disorders.