Biology subjects

Yuksel, C.

Publications and source records attributed to Yuksel, C..

6 recordsLinked to original sources

bioRxiv2026

Vagally Mediated Heart Rate Variability During REM Sleep is Associated with Retention of Fear Extinction in Generalized Anxiety Disorder

Fear extinction processes are central to the pathology and treatment of anxiety disorders. Emerging evidence implicates rapid eye movement (REM) sleep in the consolidation of extinction memory. Separately, converging theory and empirical work suggest that vagally mediated heart rate variability (VmHRV) serves as a peripheral index of cortico-subcortical regulatory capacity relevant to extinction circuitry. On this basis, we tested the hypothesis that VmHRV during REM sleep would be associated with the retention of extinction memory in individuals with generalized anxiety disorder (GAD). Participants underwent a validated two-day fear conditioning and extinction paradigm. Subjective extinction retention (sERI) was quantified during a recall test 24 hours after learning and ambulatory polysomnography was recorded on the intervening night. As hypothesized, higher REM VmHRV was significantly associated with better extinction retention. This association remained robust after controlling psychotropic medication use and REM density. In contrast, VmHRV during SWS or wakefulness, as well as other REM sleep measures, were not associated with extinction retention. These findings identify REM VmHRV as a significant predictor of extinction memory retention in GAD, extending prior findings in trauma-exposed individuals. We propose that reduced vagal tone indexes compromised prefrontal inhibitory control over amygdala and noradrenergic circuits, thereby impairing REM sleep-dependent consolidation. These results position VmHRV during REM sleep as a potential transdiagnostic biomarker of extinction memory processing and suggest that interventions enhancing vagal tone could improve treatment outcomes in anxiety disorders.

neuroscience↗

bioRxiv2025

Local and network neural activations and their associations with sleep parameters during threat conditioning and extinction in persons with Generalized Anxiety Disorder with and without Insomnia Disorder

Deficient extinction learning and memory are hypothesized mechanisms for pathological anxiety that are associated with sleep disturbance. fMRI neural activations to threat conditioning, extinction learning, and extinction recall were measured. Activations were compared, in persons with Generalized Anxiety Disorder (GAD), between those with moderate to severe Insomnia Disorder (ID) and those with absent or sub-threshold ID. Relationships of activations with measures of sleep quality and physiology were examined. Between-group comparisons and whole-sample correlation with sleep parameters were examined in relation to large-scale brain networks using a liberal cluster-determining threshold. Localized activations were then identified using family-wise error correction. Activations to the reinforced stimulus (CS+) that increased from the beginning to end ("across") threat conditioning were more extensive within the GAD+ID group. Increased activations to the CS+ across extinction learning were greater within the GAD-ID than the GAD+ID group, and delayed 24h in the latter. Greater sleep efficiency was associated with decreased activations across threat conditioning, but with increased activations across extinction learning. Better sleep quality promoted greater engagement of neural substrates of extinction learning. The GAD+ID group failed to engage brain areas supporting extinction learning immediately following threat conditioning, but did so when stimuli were again presented following a delay. HighlightsGeneralized Anxiety Disorder subjects with moderate/severe vs absent/mild insomnia compared Neural responses to threat conditioning, extinction learning/memory analyzed and sleep recorded Low and high thresholds identified large-scale networks and localized activations respectively Threat and regulatory activations at extinction learning in mild insomnia delayed when more severe Better sleep quality predicted greater activation of regulatory areas during extinction learning

neuroscience↗

bioRxiv2025

Slow oscillation-sleep spindle coupling is associated with fear extinction retention in trauma-exposed individuals

Posttraumatic stress disorder (PTSD) can be characterized as a disorder of fear learning and memory, in which there is a failure to retain memory for the extinction of conditioned fear. Sleep has been implicated in successful extinction retention. The coupling of sleep spindles to slow oscillations (SOs) during non-rapid eye movement sleep has been shown to broadly underpin sleeps beneficial effect on memory consolidation. However, the role of this oscillatory coupling in the retention of extinction memories is unknown. In a large sample of 124 trauma-exposed individuals, we investigated SO-spindle coupling in relation to fear extinction memory. We found that participants with a PTSD diagnosis, relative to trauma-exposed controls, showed significantly altered SO-spindle timing, such that PTSD participants exhibited spindle coupling further away from the peak of the SO. Across participants, the amount of coupling significantly predicted extinction retention, with coupled spindles uniquely predicting successful extinction retention compared to uncoupled spindles. These results suggest that SO-spindle coupling is critical for successful retention of extinguished fear, and that SO-spindle coupling dynamics are altered in PTSD. These alterations in the mechanics of sleep may have substantial clinical implications, meriting further investigation.

neuroscience↗

bioRxiv2024

Poor Self-Reported Sleep is Associated with Prolonged White Matter T2 Relaxation in Psychotic Disorders

BackgroundSchizophrenia (SZ) and bipolar disorder (BD) are characterized by white matter (WM) abnormalities, however, their relationship with illness presentation is not clear. Sleep disturbances are common in both disorders, and recent evidence suggests that sleep plays a critical role in WM physiology. Therefore, it is plausible that sleep disturbances are associated with impaired WM integrity in these disorders. To test this hypothesis, we examined the association of self-reported sleep disturbances with WM transverse (T2) relaxation times in patients with SZ spectrum disorders and BD with psychotic features. Methods28 patients with psychosis (17 BD-I, with psychotic features and 11 SZ spectrum disorders) were included. Metabolite and water T2 relaxation times were measured in the anterior corona radiata at 4T. Sleep was evaluated using the Pittsburgh Sleep Quality Index. ResultsPSQI total score showed a moderate to strong positive correlation with water T2 (r = 0.64, p<0.001). Linear regressions showed that this association was specific to sleep disturbance but was not a byproduct of exacerbation in depressive, manic, or psychotic symptoms. In our exploratory analysis, sleep disturbance was correlated with free water percentage, suggesting that increased extracellular water may be a mechanism underlying the association of disturbed sleep and prolonged water T2 relaxation. ConclusionOur results highlight the connection between poor sleep and WM abnormalities in psychotic disorders. Future research using objective sleep measures and neuroimaging techniques suitable to probe free water is needed to further our insight into this relationship.

neuroscience↗

bioRxiv2023

REM Sleep Measures and REM Vagal Activity Predict Extinction Recall in Trauma-Exposed Individuals

Accumulating evidence suggests that rapid eye movement sleep (REM) supports the consolidation of extinction memory. REM is disrupted in PTSD, and REM abnormalities after traumatic events increase the risk of developing PTSD. Therefore, it was hypothesized that abnormal REM in trauma-exposed individuals may pave the way for PTSD by interfering with the processing of extinction memory. In addition, PTSD patients display reduced vagal activity. Vagal activity contributes to the strengthening of memories, including fear extinction memory, and recent studies show that the role of vagus in memory processing extends to memory consolidation during sleep. Therefore, it is plausible that reduced vagal activity during sleep in trauma-exposed individuals may be an additional mechanism that impairs extinction memory consolidation. However, to date, the contribution of sleep vagal activity to the consolidation of extinction memory or any emotional memory has not been investigated. To test these hypotheses, we examined the association of extinction memory with REM characteristics and REM vagal activity (indexed as heart rate variability) in a large sample of trauma-exposed individuals (n=113). Consistent with our hypotheses, REM disruption was associated with poorer physiological and explicit extinction memory. Furthermore, higher vagal activity during REM was associated with better explicit extinction memory, and physiological extinction memory in males. These findings support the notion that abnormal REM may contribute to PTSD by impairing the consolidation of extinction memory and indicate the potential utility of interventions that target REM sleep characteristics and REM vagal activity in fear-related disorders.

neuroscience↗

bioRxiv2023

Emotional memories are enhanced when reactivated in slow wave sleep, but impaired when reactivated in REM

Sleep supports memory consolidation. However, it is not completely clear how different sleep stages contribute to this process. While rapid eye movement sleep (REM) has traditionally been implicated in the processing of emotionally charged material, recent studies indicate a role for slow wave sleep (SWS) in strengthening emotional memories. Here, to directly examine which sleep stage is primarily involved in emotional memory consolidation, we used targeted memory reactivation (TMR) in REM and SWS during a daytime nap. Contrary to our hypothesis, reactivation of emotional stimuli during REM led to impaired memory. Consistent with this, REM% was correlated with worse recall in the group that took a nap without TMR. Meanwhile, cueing benefit in SWS was strongly correlated with the product of times spent in REM and SWS (SWS-REM product), and reactivation significantly enhanced memory in those with high SWS-REM product. Surprisingly, SWS-REM product was associated with better memory for reactivated items and poorer memory for non-reactivated items, suggesting that sleep both preserved and eliminated emotional memories, depending on whether they were reactivated. Notably, the emotional valence of cued items modulated both sleep spindles and delta/theta power. Finally, we found that emotional memories benefited from TMR more than did neutral ones. Our results suggest that emotional memories decay during REM, unless they are reactivated during prior SWS. Furthermore, we show that active forgetting complements memory consolidation, and both take place across SWS and REM. In addition, our findings expand upon recent evidence indicating a link between sleep spindles and emotional processing.

neuroscience↗