Revisiting Sex Differences in the Acquisition and Extinction of Threat Conditioning in Humans

Findings pertaining to sex differences in the acquisition and extinction of threat conditioning, a paradigm widely used to study emotional homeostasis, remain inconsistent, particularly in humans. This inconsistency is likely due to multiple factors, one of which is sample size. Here, we pooled functional magnetic resonance imaging (fMRI) and skin conductance response (SCR) data from multiple studies in healthy humans to examine sex differences during threat conditioning, extinction learning, and extinction memory recall. We observed increased functional activation in males, relative to females, in multiple parietal and frontal (medial and lateral) cortical regions during acquisition of threat conditioning and extinction learning. Females mainly exhibited higher amygdala activation during extinction memory recall to the extinguished conditioned stimulus and also while responding to the unconditioned stimulus (presentation of the shock) during threat conditioning. Whole-brain functional connectivity analyses revealed that females showed increased connectivity across multiple networks including visual, ventral attention, and somatomotor networks during late extinction learning. At the psychophysiological level, a sex difference was only observed during shock delivery, with males exhibiting higher unconditioned responses relative to females. Our findings point to minimal to no sex differences in the expression of conditioned responses during acquisition and extinction of such responses. Functional MRI findings, however, show some distinct functional activations and connectivities between the sexes. These data suggest that males and females might use different neural mechanisms, mainly related to cognitive processing, to achieve comparable levels of acquired conditioned responses to threating cues

Assessing the Dream-Lag Effect for REM and NREM Stage 2 Dreams

This study investigates evidence, from dream reports, for memory consolidation during sleep. It is well-known that events andmemories from waking life can be incorporated into dreams. These incorporations can be a literal replication of what occurredin waking life, or, more often, they can be partial or indirect. Two types of temporal relationship have been found tocharacterize the time of occurrence of a daytime event and the reappearance or incorporation of its features in a dream. Thesetemporal relationships are referred to as the day-residue or immediate incorporation effect, where there is the reappearance offeatures from events occurring on the immediately preceding day, and the dream-lag effect, where there is the reappearanceof features from events occurring 5–7 days prior to the dream. Previous work on the dream-lag effect has used spontaneoushome recalled dream reports, which can be from Rapid Eye Movement Sleep (REM) and from non-Rapid Eye Movement Sleep(NREM). This study addresses whether the dream-lag effect occurs only for REM sleep dreams, or for both REM and NREM stage2 (N2) dreams. 20 participants kept a daily diary for over a week before sleeping in the sleep laboratory for 2 nights. REM andN2 dreams collected in the laboratory were transcribed and each participant rated the level of correspondence between everydream report and every diary record. The dream-lag effect was found for REM but not N2 dreams. Further analysis indicatedthat this result was not due to N2 dream reports being shorter, in terms of number of words, than the REM dream reports.These results provide evidence for a 7-day sleep-dependent non-linear memory consolidation process that is specific to REMsleep, and accord with proposals for the importance of REM sleep to emotional memory consolidation

Distributed Neural Representations of Conditioned Threat in the Human Brain

Detecting and responding to threat engages several neural nodes including the amygdala, hippocampus, insular cortex, and medial prefrontal cortices. Recent propositions call for the integration of more distributed neural nodes that process sensory and cognitive facets related to threat. Integrative, sensitive, and reproducible distributed neural decoders for the detection and response to threat and safety have yet to be established. We combine functional MRI data across varying threat conditioning and negative affect paradigms from 1465 participants with multivariate pattern analysis to investigate distributed neural representations of threat and safety. The trained decoders sensitively and specifically distinguish between threat and safety cues across multiple datasets. We further show that many neural nodes dynamically shift representations between threat and safety. Our results establish reproducible decoders that integrate neural circuits, merging the well-characterized \u27threat circuit\u27 with sensory and cognitive nodes, discriminating threat from safety regardless of experimental designs or data acquisition parameters

Sleep Power Spectral Density and Spindles in PTSD and Their Relationship to Symptom Severity

Sleep disturbances are common in post-traumatic stress disorder (PTSD), although which sleep microarchitectural characteristics reliably classify those with and without PTSD remains equivocal. Here, we investigated sleep microarchitectural differences (i.e., spectral power, spindle activity) in trauma-exposed individuals that met ( n = 45) or did not meet ( n = 52) criteria for PTSD and how these differences relate to post-traumatic and related psychopathological symptoms. Using ecologically-relevant home sleep polysomnography recordings, we show that individuals with PTSD exhibit decreased beta spectral power during NREM sleep and increased fast sleep spindle peak frequencies. Contrary to prior reports, spectral power in the beta frequency range (20.31-29.88 Hz) was associated with reduced PTSD symptoms, reduced depression, anxiety and stress and greater subjective ability to regulate emotions. Increased fast frequency spindle activity was not associated with individual differences in psychopathology. Our findings may suggest an adaptive role for beta power during sleep in individuals exposed to a trauma, potentially conferring resilience. Further, we add to a growing body of evidence that spindle activity may be an important biomarker for studying PTSD pathophysiology

Sleep and REM sleep disturbance in the pathophysiology of PTSD: the role of extinction memory

Post-traumatic stress disorder (PTSD) is accompanied by disturbed sleep and an impaired ability to learn and remember extinction of conditioned fear. Following a traumatic event, the full spectrum of PTSD symptoms typically requires several months to develop. During this time, sleep disturbances such as insomnia, nightmares, and fragmented rapid eye movement sleep predict later development of PTSD symptoms. Only a minority of individuals exposed to trauma go on to develop PTSD. We hypothesize that sleep disturbance resulting from an acute trauma, or predating the traumatic experience, may contribute to the etiology of PTSD. Because symptoms can worsen over time, we suggest that continued sleep disturbances can also maintain and exacerbate PTSD. Sleep disturbance may result in failure of extinction memory to persist and generalize, and we suggest that this constitutes one, non-exclusive mechanism by which poor sleep contributes to the development and perpetuation of PTSD. Also reviewed are neuroendocrine systems that show abnormalities in PTSD, and in which stress responses and sleep disturbance potentially produce synergistic effects that interfere with extinction learning and memory. Preliminary evidence that insomnia alone can disrupt sleep-dependent emotional processes including consolidation of extinction memory is also discussed. We suggest that optimizing sleep quality following trauma, and even strategically timing sleep to strengthen extinction memories therapeutically instantiated during exposure therapy, may allow sleep itself to be recruited in the treatment of PTSD and other trauma and stress-related disorders