Cerebral Gray Matter May Not Explain Sleep Slow-Wave Characteristics after Severe Brain Injury.

Sleep slow waves are the hallmark of deeper non-rapid eye movement sleep. It is generally assumed that gray matter properties predict slow-wave density, morphology, and spectral power in healthy adults. Here, we tested the association between gray matter volume (GMV) and slow-wave characteristics in 27 patients with moderate-to-severe traumatic brain injury (TBI, 32.0 ± 12.2 years old, eight women) and compared that with 32 healthy controls (29.2 ± 11.5 years old, nine women). Participants underwent overnight polysomnography and cerebral MRI with a 3 Tesla scanner. A whole-brain voxel-wise analysis was performed to compare GMV between groups. Slow-wave density, morphology, and spectral power (0.4-6 Hz) were computed, and GMV was extracted from the thalamus, cingulate, insula, precuneus, and orbitofrontal cortex to test the relationship between slow waves and gray matter in regions implicated in the generation and/or propagation of slow waves. Compared with controls, TBI patients had significantly lower frontal and temporal GMV and exhibited a subtle decrease in slow-wave frequency. Moreover, higher GMV in the orbitofrontal cortex, insula, cingulate cortex, and precuneus was associated with higher slow-wave frequency and slope, but only in healthy controls. Higher orbitofrontal GMV was also associated with higher slow-wave density in healthy participants. While we observed the expected associations between GMV and slow-wave characteristics in healthy controls, no such associations were observed in the TBI group despite lower GMV. This finding challenges the presumed role of GMV in slow-wave generation and morphology.

Propagating population activity patterns during spontaneous slow waves in the thalamus of rodents.

Slow waves (SWs) represent the most prominent electrophysiological events in the thalamocortical system under anesthesia and during deep sleep. Recent studies have revealed that SWs have complex spatiotemporal dynamics and propagate across neocortical regions. However, it is still unclear whether neuronal activity in the thalamus exhibits similar propagation properties during SWs. Here, we report propagating population activity in the thalamus of ketamine/xylazine-anesthetized rats and mice visualized by high-density silicon probe recordings. In both rodent species, propagation of spontaneous thalamic activity during up-states was most frequently observed in dorsal thalamic nuclei such as the higher order posterior (Po), lateral posterior (LP) or laterodorsal (LD) nuclei. The preferred direction of thalamic activity spreading was along the dorsoventral axis, with over half of the up-states exhibiting a gradual propagation in the ventral-to-dorsal direction. Furthermore, simultaneous neocortical and thalamic recordings collected under anesthesia demonstrated that there is a weak but noticeable interrelation between propagation patterns observed during cortical up-states and those displayed by thalamic population activity. In addition, using chronically implanted silicon probes, we detected propagating activity patterns in the thalamus of naturally sleeping rats during slow-wave sleep. However, in comparison to propagating up-states observed under anesthesia, these propagating patterns were characterized by a reduced rate of occurrence and a faster propagation speed. Our findings suggest that the propagation of spontaneous population activity is an intrinsic property of the thalamocortical network during synchronized brain states such as deep sleep or anesthesia. Additionally, our data implies that the neocortex may have partial control over the formation of propagation patterns within the dorsal thalamus under anesthesia.

Whole-brain model replicates sleep-like slow-wave dynamics generated by stroke lesions.

Focal brain injuries, such as stroke, cause local structural damage as well as alteration of neuronal activity in distant brain regions. Experimental evidence suggests that one of these changes is the appearance of sleep-like slow waves in the otherwise awake individual. This pattern is prominent in areas surrounding the damaged region and can extend to connected brain regions in a way consistent with the individual's specific long-range connectivity patterns. In this paper we present a generative whole-brain model based on (f)MRI data that, in combination with the disconnection mask associated with a given patient, explains the effects of the sleep-like slow waves originated in the vicinity of the lesion area on the distant brain activity. Our model reveals new aspects of their interaction, being able to reproduce functional connectivity patterns of stroke patients and offering a detailed, causal understanding of how stroke-related effects, in particular slow waves, spread throughout the brain. The presented findings demonstrate that the model effectively captures the links between stroke occurrences, sleep-like slow waves, and their subsequent spread across the human brain.

Effects of non-rapid eye movement sleep on the cortical synaptic expression of GluA1-containing AMPA receptors.

Converging electrophysiological, molecular and ultrastructural evidence supports the hypothesis that sleep promotes a net decrease in excitatory synaptic strength, counteracting the net synaptic potentiation caused by ongoing learning during waking. However, several outstanding questions about sleep-dependent synaptic weakening remain. Here, we address some of these questions by using two established molecular markers of synaptic strength, the levels of the AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors containing the GluA1 subunit and the phosphorylation of GluA1 at serine 845 (p-GluA1(845)). We previously found that, in the rat cortex and hippocampus, these markers are lower after 6-8 h of sleep than after the same time spent awake. Here, we measure GluA1 and p-GluA1(845) levels in synaptosomes of mouse cortex after 5 h of either sleep, sleep deprivation, recovery sleep after sleep deprivation or selective REM sleep deprivation (32 C57BL/B6 adult mice, 16 females). We find that relative to after sleep deprivation, these synaptic markers are lower after sleep independent of whether the mice were allowed to enter REM sleep. Moreover, 5 h of recovery sleep following acute sleep deprivation is enough to renormalize their expression. Thus, the renormalization of GluA1 and p-GluA1(845) expression crucially relies on NREM sleep and can occur in a few hours of sleep after acute sleep deprivation.

Maternal immune activation exerts long-term effects on activity and sleep in male offspring mice.

Exposure to infectious or non-infectious immune activation during early development is a serious risk factor for long-term behavioural dysfunctions. Mouse models of maternal immune activation (MIA) have increasingly been used to address neuronal and behavioural dysfunctions in response to prenatal infections. One commonly employed MIA model involves administering poly(I:C) (polyriboinosinic-polyribocytdilic acid), a synthetic analogue of double-stranded RNA, during gestation, which robustly induces an acute viral-like inflammatory response. Using electroencephalography (EEG) and infrared (IR) activity recordings, we explored alterations in sleep/wake, circadian and locomotor activity patterns on the adult male offspring of poly(I:C)-treated mothers. Our findings demonstrate that these offspring displayed reduced home cage activity during the (subjective) night under both light/dark or constant darkness conditions. In line with this finding, these mice exhibited an increase in non-rapid eye movement (NREM) sleep duration as well as an increase in sleep spindles density. Following sleep deprivation, poly(I:C)-exposed offspring extended NREM sleep duration and prolonged NREM sleep bouts during the dark phase as compared with non-exposed mice. Additionally, these mice exhibited a significant alteration in NREM sleep EEG spectral power under heightened sleep pressure. Together, our study highlights the lasting effects of infection and/or immune activation during pregnancy on circadian activity and sleep/wake patterns in the offspring.

Simultaneous Optical Imaging of Gastric Slow Waves and Contractions in the In Vivo Porcine Stomach.

Gastric peristalsis is governed by electrical "slow waves" generally assumed to travel from proximal to distal stomach (antegrade propagation) in symmetric rings. While alternative slow wave patterns have been correlated with gastric disorders, their mechanisms and how they alter contractions remain understudied. Optical electromechanical mapping, a developing field in cardiac electrophysiology, images electrical and mechanical physiology simultaneously. Here, we translate this technology to the in-vivo porcine stomach. Stomachs were surgically exposed and a fluorescent dye (di-4-ANEQ(F)PTEA) that transduces the membrane potential (Vm) was injected through the right gastroepiploic artery. Fluorescence was excited by LEDs and imaged with one or two 256x256 pixel cameras. Motion artifact was corrected using a marker-based motion tracking method and excitation ratiometry, which cancels common-mode artifact. Tracking marker displacement also enabled gastric deformation to be measured. We validated detection of electrical activation and Vm morphology against alternative non-optical technologies. Non-antegrade slow waves and propagation direction differences between the anterior and posterior stomach were commonly present in our data. However, sham experiments suggest they were a feature of the animal preparation and not an artifact of optical mapping. In experiments to demonstrate the method's capabilities, we found that repolarization did not always follow at a fixed time behind activation "wavefronts," which could be a factor in dysrhythmia. Contraction strength and the latency between electrical activation and contraction differed between antegrade and non-antegrade propagation. In conclusion, optical electromechanical mapping, which simultaneously images electrical and mechanical activity, enables novel questions regarding normal and abnormal gastric physiology to be explored.

Electromechanical coupling and anatomy of the in vivo gastroduodenal junction.

Few biomarkers support the diagnosis and treatment of disorders of gut-brain interaction (DGBI), although gastroduodenal junction (GDJ) electromechanical coupling is a target for novel interventions. Rhythmic "slow waves," generated by interstitial cells of Cajal (ICC), and myogenic "spikes" are bioelectrical mechanisms underpinning motility. In this study, simultaneous in vivo high-resolution electrophysiological and impedance planimetry measurements were paired with immunohistochemistry to elucidate GDJ electromechanical coupling. Following ethical approval, the GDJ of anaesthetized pigs (n = 12) was exposed. Anatomically specific, high-resolution electrode arrays (256 electrodes) were applied to the serosa. EndoFLIP catheters (16 electrodes; Medtronic, MN) were positioned luminally to estimate diameter. Postmortem tissue samples were stained with Masson's trichrome and Ano1 to quantify musculature and ICC. Electrical mapping captured slow waves (n = 512) and spikes (n = 1,071). Contractions paralleled electrical patterns. Localized slow waves and spikes preceded rhythmic contractions of the antrum and nonrhythmic contractions of the duodenum. Slow-wave and spike amplitudes were correlated in the antrum (r = 0.74, P < 0.001) and duodenum (r = 0.42, P < 0.001). Slow-wave and contractile amplitudes were correlated in the antrum (r = 0.48, P < 0.001) and duodenum (r = 0.35, P < 0.001). Distinct longitudinal and circular muscle layers of the antrum and duodenum had a total thickness of (2.8 ± 0.9) mm and (0.4 ± 0.1) mm, respectively. At the pylorus, muscle layers merged and thickened to (3.5 ± 1.6) mm. Pyloric myenteric ICC covered less area (1.5 ± 1.1%) compared with the antrum (4.2 ± 3.0%) and duodenum (5.3 ± 2.8%). Further characterization of electromechanical coupling and ICC biopsies may generate DGBI biomarkers.NEW & NOTEWORTHY This study applies electrical mapping, impedance planimetry, and histological techniques to the gastroduodenal junction to elucidate electromechanical coupling in vivo. Contractions of the terminal antrum and pyloric sphincter were associated with gastric slow waves. In the duodenum, bursts of spike activity triggered oscillating contractions. The relative sparsity of myenteric interstitial cells of Cajal in the pylorus, compared with the adjacent antrum and duodenum, is hypothesized to prevent coupling between antral and duodenal slow waves.

Overnight Electroencephalogram to Forecast Epilepsy Development in Children with Autism Spectrum Disorders.

OBJECTIVE: To establish the utility of long-term electroencephalogram (EEG) in forecasting epilepsy onset in children with autism spectrum disorder (ASD). STUDY DESIGN: A single-institution, retrospective analysis of children with ASD, examining long-term overnight EEG recordings collected over a period of 15 years, was conducted. Clinical EEG findings, patient demographics, medical histories, and additional Autism Diagnostic Observation Schedule data were examined. Predictors for the timing of epilepsy onset were evaluated using survival analysis and Cox regression. RESULTS: Among 151 patients, 17.2% (n = 26) developed unprovoked seizures (Sz group), while 82.8% (n = 125) did not (non-Sz group). The Sz group displayed a higher percentage of interictal epileptiform discharges (IEDs) in their initial EEGs compared with the non-Sz group (46.2% vs 20.0%, P = .01). The Sz group also exhibited a greater frequency of slowing (42.3% vs 13.6%, P < .01). The presence of IEDs or slowing predicted an earlier seizure onset, based on survival analysis. Multivariate Cox proportional hazards regression revealed that the presence of any IEDs (HR 3.83, 95% CI 1.38-10.65, P = .01) or any slowing (HR 2.78, 95% CI 1.02-7.58, P = .046 significantly increased the risk of developing unprovoked seizures. CONCLUSION: Long-term EEGs are valuable for predicting future epilepsy in children with ASD. These findings can guide clinicians in early education and potential interventions for epilepsy prevention.

Overnight changes in performance fatigability and their relationship to modulated deep sleep oscillations via auditory stimulation.

Deep sleep oscillations are proposed to be central in restoring brain function and to affect different aspects of motor performance such as facilitating the consolidation of motor sequences resulting in faster and more accurate sequence tapping. Yet, whether deep sleep modulates performance fatigability during fatiguing tasks remains unexplored. We investigated overnight changes in tapping speed and resistance against performance fatigability via a finger tapping task. During fast tapping, fatigability manifests as a reduction in speed (or "motor slowing") which affects all tapping tasks, including motor sequences used to study motor memory formation. We further tested whether overnight changes in performance fatigability are influenced by enhancing deep sleep oscillations using auditory stimulation. We found an overnight increase in tapping speed alongside a reduction in performance fatigability and perceived workload. Auditory stimulation led to a global enhancement of slow waves and both slow and fast spindles during the stimulation window and a local increase in slow spindles in motor areas across the night. However, overnight performance improvements were not significantly modulated by auditory stimulation and changes in tapping speed or performance fatigability were not predicted by individual changes in deep sleep oscillations. Our findings demonstrate overnight changes in fatigability but revealed no evidence suggesting that this effect is causally linked to temporary augmentation of slow waves or sleep spindles. Our results are important for future studies using tapping tasks to test the relationship between sleep and motor memory consolidation, as overnight changes in objectively measured and subjectively perceived fatigue likely impact behavioural outcomes.

Sleep and cardiac autonomic modulation in older adults: Insights from an at-home study with auditory deep sleep stimulation.

The autonomic nervous system regulates cardiovascular activity during sleep, likely impacting cardiovascular health. Aging, a primary cardiovascular risk factor, is associated with cardiac autonomic disbalance and diminished sleep slow waves. Therefore, slow waves may be linked to aging, autonomic activity and cardiovascular health. However, it is unclear how sleep and slow waves are linked to cardiac autonomic profiles across multiple nights in older adults. We conducted a randomized, crossover trial involving healthy adults aged 62-78 years. Across 2 weeks, we applied auditory stimulation to enhance slow waves and compared it with a SHAM period. We measured sleep parameters using polysomnography and derived heart rate, heart rate variability approximating parasympathetic activity, and blood pulse wave approximating sympathetic activity from a wearable. Here, we report the results of 14 out of 33 enrolled participants, and show that heart rate, heart rate variability and blood pulse wave within sleep stages differ between the first and second half of sleep. Furthermore, baseline slow-wave activity was related to cardiac autonomic activity profiles during sleep. Moreover, we found auditory stimulation to reduce heart rate variability, while heart rate and blood pulse wave remained unchanged. Lastly, within subjects, higher heart rate coincided with increased slow-wave activity, indicating enhanced autonomic activation when slow waves are pronounced. Our study shows the potential of cardiac autonomic markers to offer insights into participants' baseline slow-wave activity when recorded over multiple nights. Furthermore, we highlight that averaging cardiac autonomic parameters across a night may potentially mask dynamic effects of auditory stimulation, potentially playing a role in maintaining a healthy cardiovascular system.

Coupling between slow waves and sharp-wave ripples engages distributed neural activity during sleep in humans.

Hippocampal-dependent memory consolidation during sleep is hypothesized to depend on the synchronization of distributed neuronal ensembles, organized by the hippocampal sharp-wave ripples (SWRs, 80 to 150 Hz), subcortical/cortical slow-wave activity (SWA, 0.5 to 4 Hz), and sleep spindles (SP, 7 to 15 Hz). However, the precise role of these interactions in synchronizing subcortical/cortical neuronal activity is unclear. Here, we leverage intracranial electrophysiological recordings from the human hippocampus, amygdala, and temporal and frontal cortices to examine activity modulation and cross-regional coordination during SWRs. Hippocampal SWRs are associated with widespread modulation of high-frequency activity (HFA, 70 to 200 Hz), a measure of local neuronal activation. This peri-SWR HFA modulation is predicted by the coupling between hippocampal SWRs and local subcortical/cortical SWA or SP. Finally, local cortical SWA phase offsets and SWR amplitudes predicted functional connectivity between the frontal and temporal cortex during individual SWRs. These findings suggest a selection mechanism wherein hippocampal SWR and cortical slow-wave synchronization governs the transient engagement of distributed neuronal populations supporting hippocampal-dependent memory consolidation.

Transcutaneous Auricular Vagus Nerve Stimulation Normalizes Induced Gastric Myoelectrical Dysrhythmias in Controls Assessed by Body-Surface Gastric Mapping.

OBJECTIVES: Transcutaneous auricular vagus nerve stimulation (TaVNS) is a supplementary treatment for gastric symptoms resulting from dysrhythmias. The main objective of this study was to quantify the effects of 10, 40, and 80 Hz TaVNS and sham in healthy individuals in response to a 5-minute water-load (WL5) test. MATERIALS AND METHODS: Eighteen healthy volunteers aged between 21 and 55 years (body mass index: 27.1 ± 3.2) were recruited. Each subject fasted for up to eight hours and participated in four 95-minute sessions, which consisted of 30 fasted baseline, 30 minutes TaVNS, WL5, and 30 minutes post-WL5. Heart rate variability was assessed using sternal electrocardiogram. Body-surface gastric mapping and bloating (/10) were recorded. One-way ANOVA with post hoc Tukey test was performed to test the difference between TaVNS protocols in terms of frequency, amplitude, bloating scores, root mean square of the successive differences (RMSSD), and stress index (SI). RESULTS: On average, the subjects consumed 526 ± 160 mL of water, with volume ingested correlated to bloating (mean score 4.1 ± 1.8; r = 0.36, p = 0.029). In general, the reduction in frequency and rhythm stability during the post-WL5 period in sham was normalized by all three TaVNS protocols. Both 40- and 80-Hz protocols also caused increases in amplitude during the stim-only and/or post-WL5 periods. RMSSD increased during the 40-Hz protocol. SI increased during the 10-Hz protocol but decreased during the 40- and 80-Hz protocols. CONCLUSION: TaVNS proved effective in normalizing gastric dysrhythmias by WL5 in healthy subjects by altering both parasympathetic and sympathetic pathways.

Diverse nature of interictal oscillations: EEG-based biomarkers in epilepsy.

Interictal electroencephalogram (EEG) patterns, including high-frequency oscillations (HFOs), interictal spikes (ISs), and slow wave activities (SWAs), are defined as specific oscillations between seizure events. These interictal oscillations reflect specific dynamic changes in network excitability and play various roles in epilepsy. In this review, we briefly describe the electrographic characteristics of HFOs, ISs, and SWAs in the interictal state, and discuss the underlying cellular and network mechanisms. We also summarize representative evidence from experimental and clinical epilepsy to address their critical roles in ictogenesis and epileptogenesis, indicating their potential as electrophysiological biomarkers of epilepsy. Importantly, we put forwards some perspectives for further research in the field.

Stress dynamically reduces sleep depth: temporal proximity to the stressor is crucial.

The anticipation of a future stressor can increase worry and cognitive arousal and has a detrimental effect on sleep. Similarly, experiencing a stressful event directly before sleep increases physiological and cognitive arousal and impairs subsequent sleep. However, the effects of post- vs. pre-sleep stress on sleep and their temporal dynamics have never been directly compared. Here, we examined the effect of an anticipated psychosocial stressor on sleep and arousal in a 90-min daytime nap, in 33 healthy female participants compared to an anticipated within-subject relaxation task. We compared the results to an additional group (n = 34) performing the same tasks directly before sleep. Anticipating stress after sleep reduced slow-wave activity/beta power ratio, slow-wave sleep, sleep spindles, and slow-wave parameters, in particular during late sleep, without a concomitant increase in physiological arousal. In contrast, pre-sleep psychosocial stress deteriorated the same parameters during early sleep with a concomitant increase in physiological arousal. Our results show that presleep cognitions directly affect sleep in temporal proximity to the stressor. While physiological arousal mediates the effects of presleep stress on early sleep, we suggest that effects during late sleep originate from a repeated reactivation of mental concepts associated with the stressful event during sleep.

Noninvasive Transcutaneous Auricular Vagal Nerve Stimulation Improves Gastric Slow Waves Impaired by Cold Stress in Healthy Subjects.

BACKGROUND/AIMS: Stress is known to inhibit gastric motility. The aim of this study was to investigate the effects and autonomic mechanisms of transcutaneous auricular vagal nerve stimulation (taVNS) on cold stress (CS)-induced impairment in gastric motility that are relevant to the brain-gut interactions in healthy volunteers. MATERIALS AND METHODS: Healthy volunteers (eight women; age 28.2 ± 1.8 years) were studied in four randomized sessions (control, CS, CS + taVNS, and CS + sham-electrical stimulation [sham-ES]). Each session was composed of 30 minutes in the fasting state and 30 minutes after a standard test meal. CS was induced during minutes 10 to 30 after the meal, whereas taVNS or sham-ES was performed during minutes 0 to 30 after the meal. The electrogastrogram and electrocardiogram were recorded for assessing gastric slow waves and autonomic functions, respectively. RESULTS: First, CS decreased the percentage of normal gastric slow waves (59.7% ± 9.8% vs 85.4% ± 4.5%, p < 0.001 vs control); this impairment was dramatically improved by taVNS (75.5% ± 6.3% vs 58.4% ± 12.5%, p < 0.001 vs sham-ES). Second, CS increased the symptom score (22.0 ± 12.1 vs 39.3 ± 11.5, p = 0.001 vs control); taVNS, but not sham-ES, reduced the symptom score (26.0 ± 12.2 vs 38.3 ± 21.6, p = 0.026 vs sham-ES). Third, CS decreased vagal activity assessed from the spectral analysis of heart rate variability (0.21 ± 0.10 vs 0.26 ± 0.11, p < 0.05 vs control) and increased the sympathovagal ratio (4.89 ± 1.94 vs 3.74 ± 1.32, p = 0.048 vs control); taVNS normalized CS-induced suppression in vagal activity (0.27 ± 0.13 vs 0.22 ± 0.10, p = 0.049 vs sham-ES; p > 0.05 vs control) and CS-induced increase in the sympathovagal ratio (3.28 ± 1.61 vs 4.28 ± 2.10, p = 0.042 vs sham-ES; p > 0.05 vs control). CONCLUSION: The noninvasive taVNS improves the CS-induced impairment in gastric pace-making activity, possibly by reversing the detrimental effect of CS on autonomic functions. taVNS may have a therapeutic potential for stress-induced gastric dysmotility.

Ongoing neural oscillations predict the post-stimulus outcome of closed loop auditory stimulation during slow-wave sleep.

Large slow oscillations (SO, 0.5-2 Hz) characterise slow-wave sleep and are crucial to memory consolidation and other physiological functions. Manipulating slow oscillations may enhance sleep and memory, as well as benefitting the immune system. Closed-loop auditory stimulation (CLAS) has been demonstrated to increase the SO amplitude and to boost fast sleep spindle activity (11-16 Hz). Nevertheless, not all such stimuli are effective in evoking SOs, even when they are precisely phase locked. Here, we studied what factors of the ongoing activity patterns may help to determine what oscillations to stimulate to effectively enhance SOs or SO-locked spindle activity. Hence, we trained classifiers using the morphological characteristics of the ongoing SO, as measured by electroencephalography (EEG), to predict whether stimulation would lead to a benefit in terms of the resulting SO and spindle amplitude. Separate classifiers were trained using trials from spontaneous control and stimulated datasets, and we evaluated their performance by applying them to held-out data both within and across conditions. We were able to predict both when large SOs occurred spontaneously, and whether a phase-locked auditory click effectively enlarged them with good accuracy for predicting the SO trough (∼70%) and SO peak values (∼80%). Also, we were able to predict when stimulation would elicit spindle activity with an accuracy of ∼60%. Finally, we evaluate the importance of the various SO features used to make these predictions. Our results offer new insight into SO and spindle dynamics and may suggest techniques for developing future methods for online optimization of stimulation.

Slow oscillation-spindle coupling is negatively associated with emotional memory formation following stress.

Both stress and sleep enhance emotional memory. They also interact, with the largest effect of sleep on emotional memory being seen when stress occurs shortly before or after encoding. Slow wave sleep (SWS) is critical for long-term episodic memory, facilitated by the temporal coupling of slow oscillations and sleep spindles. Prior work in humans has shown these associations for neutral information in non-stressed participants. Whether coupling interacts with stress to facilitate emotional memory formation is unknown. Here, we addressed this question by reanalyzing an existing dataset of 64 individuals. Participants underwent a psychosocial stressor (32) or comparable control (32) prior to the encoding of 150-line drawings of neutral, positive, and negative images. All participants slept overnight with polysomnography, before being given a surprise memory test the following day. In the stress group, time spent in SWS was positively correlated with memory for images of all valences. Results were driven by those who showed a high cortisol response to the stressor, compared to low responders. The amount of slow oscillation-spindle coupling during SWS was negatively associated with neutral and emotional memory in the stress group only. The association with emotional memory was significantly stronger than for neutral memory within the stress group. These results suggest that stress around the time of initial memory formation impacts the relationship between slow wave sleep and memory.

Validation of noninvasive body-surface gastric mapping for detecting gastric slow-wave spatiotemporal features by simultaneous serosal mapping in porcine.

Gastric disorders are increasingly prevalent, but reliable noninvasive tools to objectively assess gastric function are lacking. Body-surface gastric mapping (BSGM) is a noninvasive method for the detection of gastric electrophysiological features, which are correlated with symptoms in patients with gastroparesis and functional dyspepsia. Previous studies have validated the relationship between serosal and cutaneous recordings from limited number of channels. This study aimed to comprehensively evaluate the basis of BSGM from 64 cutaneous channels and reliably identify spatial biomarkers associated with slow-wave dysrhythmias. High-resolution electrode arrays were placed to simultaneously capture slow waves from the gastric serosa (32 × 6 electrodes at 4 mm spacing) and epigastrium (8 × 8 electrodes at 20 mm spacing) in 14 porcine subjects. BSGM signals were processed based on a combination of wavelet and phase information analyses. A total of 1,185 individual cycles of slow waves were assessed, out of which 897 (76%) were classified as normal antegrade waves, occurring in 10 (71%) subjects studied. BSGM accurately detected the underlying slow wave in terms of frequency (r = 0.99, P = 0.43) as well as the direction of propagation (P = 0.41, F-measure: 0.92). In addition, the cycle-by-cycle match between BSGM and transitions of gastric slow wave dysrhythmias was demonstrated. These results validate BSGM as a suitable method for noninvasively and accurately detecting gastric slow-wave spatiotemporal profiles from the body surface.NEW & NOTEWORTHY Gastric dysfunctions are associated with abnormalities in the gastric bioelectrical slow waves. Noninvasive detection of gastric slow waves from the body surface can be achieved through multichannel, high-resolution, body-surface gastric mapping (BSGM). BSGM matched the spatiotemporal characteristics of gastric slow waves recorded directly and simultaneously from the serosal surface of the stomach. Abnormal gastric slow waves, such as retrograde propagation, ectopic pacemaker, and colliding wavefronts can be detected by changes in the phase of BSGM.

No difference between slow oscillation up- and down-state cueing for memory consolidation during sleep.

The beneficial effects of sleep for memory consolidation are assumed to rely on the reactivation of memories in conjunction with the coordinated interplay of sleep rhythms like slow oscillations and spindles. Specifically, slow oscillations are assumed to provide the temporal frame for spindles to occur in the slow oscillations up-states, enabling a redistribution of reactivated information within hippocampal-neocortical networks for long-term storage. Memory reactivation can also be triggered externally by presenting learning-associated cues (like odours or sounds) during sleep, but it is presently unclear whether there is an optimal time-window for the presentation of such cues in relation to the phase of the slow oscillations. In the present within-subject comparison, participants (n = 16) learnt word-pairs visually presented with auditory cues of the first syllable. These syllables were subsequently used for real-time cueing either in the up- or down-state of endogenous slow oscillations. Contrary to our hypothesis, we found differences in memory performance neither between up- and down-state cueing, nor between word-pairs that were cued versus uncued. In the up-state cueing condition, higher amounts of rapid eye movement sleep were associated with better memory for cued contents, whereas higher amounts of slow-wave sleep were associated with better memory for uncued contents. Evoked response analyses revealed signs of cue processing in both conditions. Interestingly, both up- and down-state cueing evoked a similar spindle response with the induced slow oscillations up-state at ~1000 ms post-cue. We speculate that our cueing procedure triggered generalised reactivation processes that facilitated the consolidation of both cued and uncued memories irrespective of the slow oscillation phase.

Down-phase auditory stimulation is not able to counteract pharmacologically or physiologically increased sleep depth in traumatic brain injury rats.

Modulation of slow-wave activity, either via pharmacological sleep induction by administering sodium oxybate or sleep restriction followed by a strong dissipation of sleep pressure, has been associated with preserved posttraumatic cognition and reduced diffuse axonal injury in traumatic brain injury rats. Although these classical strategies provided promising preclinical results, they lacked the specificity and/or translatability needed to move forward into clinical applications. Therefore, we recently developed and implemented a rodent auditory stimulation method that is a scalable, less invasive and clinically meaningful approach to modulate slow-wave activity by targeting a particular phase of slow waves. Here, we assessed the feasibility of down-phase targeted auditory stimulation of slow waves and evaluated its comparative modulatory strength in relation to the previously employed slow-wave activity modulators in our rat model of traumatic brain injury. Our results indicate that, in spite of effectively reducing slow-wave activity in both healthy and traumatic brain injury rats via down-phase targeted stimulation, this method was not sufficiently strong to counteract the boost in slow-wave activity associated with classical modulators, nor to alter concomitant posttraumatic outcomes. Therefore, the usefulness and effectiveness of auditory stimulation as potential standalone therapeutic strategy in the context of traumatic brain injury warrants further exploration.