Expert-level sleep staging using an electrocardiography-only feed-forward neural network.

Reliable classification of sleep stages is crucial in sleep medicine and neuroscience research for providing valuable insights, diagnoses, and understanding of brain states. The current gold standard method for sleep stage classification is polysomnography (PSG). Unfortunately, PSG is an expensive and cumbersome process involving numerous electrodes, often conducted in an unfamiliar clinic and annotated by a professional. Although commercial devices like smartwatches track sleep, their performance is well below PSG. To address these disadvantages, we present a feed-forward neural network that achieves gold-standard levels of agreement using only a single lead of electrocardiography (ECG) data. Specifically, the median five-stage Cohen's kappa is 0.725 on a large, diverse dataset of 5 to 90-year-old subjects. Comparisons with a comprehensive meta-analysis of between-human inter-rater agreement confirm the non-inferior performance of our model. Finally, we developed a novel loss function to align the training objective with Cohen's kappa. Our method offers an inexpensive, automated, and convenient alternative for sleep stage classification-further enhanced by a real-time scoring option. Cardiosomnography, or a sleep study conducted with ECG only, could take expert-level sleep studies outside the confines of clinics and laboratories and into realistic settings. This advancement democratizes access to high-quality sleep studies, considerably enhancing the field of sleep medicine and neuroscience. It makes less-expensive, higher-quality studies accessible to a broader community, enabling improved sleep research and more personalized, accessible sleep-related healthcare interventions.

Cellular composition and circuit organization of the locus coeruleus of adult mice.

The locus coeruleus (LC) houses the vast majority of noradrenergic neurons in the brain and regulates many fundamental functions, including fight and flight response, attention control, and sleep/wake cycles. While efferent projections of the LC have been extensively investigated, little is known about its local circuit organization. Here, we performed large-scale multipatch recordings of noradrenergic neurons in adult mouse LC to profile their morpho-electric properties while simultaneously examining their interactions. LC noradrenergic neurons are diverse and could be classified into two major morpho-electric types. While fast excitatory synaptic transmission among LC noradrenergic neurons was not observed in our preparation, these mature LC neurons connected via gap junction at a rate similar to their early developmental stage and comparable to other brain regions. Most electrical connections form between dendrites and are restricted to narrowly spaced pairs or small clusters of neurons of the same type. In addition, more than two electrically coupled cell pairs were often identified across a cohort of neurons from individual multicell recording sets that followed a chain-like organizational pattern. The assembly of LC noradrenergic neurons thus follows a spatial and cell-type-specific wiring principle that may be imposed by a unique chain-like rule.

What Makes an Image Interesting and How Can We Explain It.

Here, we explore the question: What makes a photograph interesting? Answering this question deepens our understanding of human visual cognition and knowledge gained can be leveraged to reliably and widely disseminate information. Observers viewed images belonging to different categories, which covered a wide, representative spectrum of real-world scenes, in a self-paced manner and, at trial's end, rated each image's interestingness. Our studies revealed the following: landscapes were the most interesting of all categories tested, followed by scenes with people and cityscapes, followed still by aerial scenes, with indoor scenes of homes and offices being least interesting. Judgments of relative interestingness of pairs of images, setting a fixed viewing duration, or changing viewing history - all of the above manipulations failed to alter the hierarchy of image category interestingness, indicating that interestingness is an intrinsic property of an image unaffected by external manipulation or agent. Contrary to popular belief, low-level accounts based on computational image complexity, color, or viewing time failed to explain image interestingness: more interesting images were not viewed for longer and were not more complex or colorful. On the other hand, a single higher-order variable, namely image uprightness, significantly improved models of average interest. Observers' eye movements partially predicted overall average interest: a regression model with number of fixations, mean fixation duration, and a custom measure of novel fixations explained >40% of variance. Our research revealed a clear category-based hierarchy of image interestingness, which appears to be a different dimension altogether from memorability or awe and is as yet unexplained by the dual appraisal hypothesis.

Orthopaedic and brain injuries over last 10 seasons in the National Football League (NFL): number and effect on missed playing time.

OBJECTIVE: To examine trends in number and seriousness of major injuries in the National Football League (NFL) over seasons 2010-2019 and the effect of rule changes to injuries to the leg, back, arm and head. METHODS: We calculated, from publicly available weekly injury reports, the number of players that were injured and playing time missed, that is, the number of weeks on average that an injured player had to sit out, as a function of injury to a specific body part. Using classical time series analysis techniques, we fitted injury data with linear and non-linear functions. RESULTS: The number of major injuries to the leg, back, arm and head has not declined over the last 10 years. During this time period, time missed because of injuries to the head has shown a significantly increasing trend. Rule changes designed specifically to protect arm or head have, respectively, succeeded in shortening the time that the injured player misses, but the impact lasts only over a single season. CONCLUSIONS: Overall, our data support the argument that new, well-intentioned rules adopted every season by the NFL have been proven to be too weak to make the NFL game safer. Broad-based management of brain and orthopaedic injuries and adoption of preventative measures to reduce the number of players injured and the seriousness of their injuries are required in the modern NFL.

What drives slow wave activity during early non-REM sleep: Learning during prior wake or effort?

What is the function of sleep in humans? One claim is that sleep consolidates learning. Slow wave activity (SWA), i.e. slow oscillations of frequency < 4 Hz, has been observed in electroencephalograms (EEG) during sleep; it increases with prior wakefulness and decreases with sleep. Studies have claimed that increase in SWA in specific regions of the sleeping brain is correlated with overnight improved performance, i.e. overnight consolidation, on a demanding motor learning task. We wondered if SWA change during sleep is attributable to overnight consolidation or to metabolic demand. Participants executed out-and-back movements to a target using a pen-like cursor with their dominant hand while the target and cursor position were displayed on a screen. They trained on three different conditions on separate nights, differing in the amount and degree of rotation between the actual hand movement direction and displayed cursor movement direction. In the no-rotation (NR) condition, there was no rotation. In the single rotation (SR) condition, the amount of rotation remained the same throughout, and performance improved both across pre-sleep training and after sleep, i.e. overnight consolidation occurred; in the random rotation (RR) condition, the amount of rotation varied randomly from trial to trial, and no overnight consolidation occurred; SR and RR were cognitively demanding. The average EEG power density of SWA for the first 30 min. of non-rapid eye movement sleep after training was computed. Both SR and RR elicited increase in SWA in the parietal region; furthermore, the topographic distribution of SWA in each was remarkably similar. No correlation was found between the overnight performance improvement on SR and the SWA change in the parietal region on measures of learning. Our results argue that regulation of SWA in early sleep is associated with high levels of cognitive effort during prior wakefulness, and not just overnight consolidation.

Two Visual Pathways in Primates Based on Sampling of Space: Exploitation and Exploration of Visual Information.

Evidence is strong that the visual pathway is segregated into two distinct streams-ventral and dorsal. Two proposals theorize that the pathways are segregated in function: The ventral stream processes information about object identity, whereas the dorsal stream, according to one model, processes information about either object location, and according to another, is responsible in executing movements under visual control. The models are influential; however recent experimental evidence challenges them, e.g., the ventral stream is not solely responsible for object recognition; conversely, its function is not strictly limited to object vision; the dorsal stream is not responsible by itself for spatial vision or visuomotor control; conversely, its function extends beyond vision or visuomotor control. In their place, we suggest a robust dichotomy consisting of a ventral stream selectively sampling high-resolution/focal spaces, and a dorsal stream sampling nearly all of space with reduced foveal bias. The proposal hews closely to the theme of embodied cognition: Function arises as a consequence of an extant sensory underpinning. A continuous, not sharp, segregation based on function emerges, and carries with it an undercurrent of an exploitation-exploration dichotomy. Under this interpretation, cells of the ventral stream, which individually have more punctate receptive fields that generally include the fovea or parafovea, provide detailed information about object shapes and features and lead to the systematic exploitation of said information; cells of the dorsal stream, which individually have large receptive fields, contribute to visuospatial perception, provide information about the presence/absence of salient objects and their locations for novel exploration and subsequent exploitation by the ventral stream or, under certain conditions, the dorsal stream. We leverage the dichotomy to unify neuropsychological cases under a common umbrella, account for the increased prevalence of multisensory integration in the dorsal stream under a Bayesian framework, predict conditions under which object recognition utilizes the ventral or dorsal stream, and explain why cells of the dorsal stream drive sensorimotor control and motion processing and have poorer feature selectivity. Finally, the model speculates on a dynamic interaction between the two streams that underscores a unified, seamless perception. Existing theories are subsumed under our proposal.

Interaction of finger representations in the cortex of individuals with autism: a functional window into cortical inhibition.

An established neural biomarker of autism spectrum disorder (ASD) has the potential to provide novel biological and pharmacological targets for treatment. Lower level of inhibition in brain circuits is a leading biomarker candidate. A physiological investigation of the functional levels of inhibition in the cortex of individuals with autism can provide a strong test of the hypothesis. The amplitude of cortical response to the stimulation of adjacent fingers is controlled by the level of cortical inhibition and provides just such a test. Using magnetoencephalography, we recorded the response of the somatosensory cortex to the passive tactile stimulation of the thumb (D1), and index finger (D2), and to the simultaneous stimulation of both fingers combined (D1,D2) of the dominant (right) hand of young subjects with and without autism. For each participant, we measured the response to the stimulation of both fingers combined (D1,D2) relative to the post hoc sum of the responses to the stimulation of each finger alone (D1+D2) in multiple different ways and linearly regressed the ASD and neurotypical (NT) groups' responses. The resulting slopes were then compared: Smaller slope values imply attenuated response to paired finger stimulation, and enhanced levels of inhibition. The short-latency M40 and mid-latency M80 response slopes of the group with autism obtained in different ways were either significantly smaller, or statistically indistinguishable from NT. The result does not support reduced inhibition in the somatosensory cortex of individuals with autism, contrary to the seminal hypothesis of reduced inhibition. Implications are discussed including refinements of current theory.

Functional assays of local connectivity in the somatosensory cortex of individuals with autism.

Emerging evidence for differences between individuals with autism spectrum disorder (ASD) and neurotypical (NT) individuals in somatic processing and brain response to touch suggests somatosensory cortex as a promising substrate for elucidating differences in functional brain connectivity between individuals with and without autism. Signals from adjacent digits project to neighboring locations or representations in somatosensory cortex. When a digit is stimulated, i.e. touched, its representation in cortex is directly activated; local intracortical connections indirectly activate nonprimary cortical representations corresponding to adjacent digits. The response of the nonprimary cortical representations is thus a proxy for connection strength. Local overconnectivity in autism implies that the nonprimary/primary response ratios of the ASD group will be higher than those of the NT group. D1 and D2 of the dominant hand of the participant were individually stimulated while we recorded neural responses using magnetoencephalography. The cortical representations of D1 and D2 (somatosensory-evoked fields) were computed from the ensemble-averaged data using (a) dipole model fits and (b) singular value decomposition. Individual adjacent/primary response ratios were measured, and group response ratio data were fitted with straight lines. Local overconnectivity in autism implies steeper ASD vs. NT group slopes. Our findings did not support local overconnectivity. Slopes were found to be significantly shallower for the ASD group than the NT group. Our findings support the idea of local underconnectivity in the somatosensory cortex of the brains of individuals with ASD.

Sound-induced perturbations of the brain network in non-REM sleep, and network oscillations in wake.

During sleep, the brain network processes sensory stimuli without awareness. Stimulation must affect differently brain networks in sleep versus wake, but these differences have yet to be quantified. We recorded cortical activity in stage 2 (SII) sleep and wake using EEG while a tone was intermittently played. Zero-lag correlation measured input to pairs of sensors in the network; cross-correlation and phase-lag index measured pairwise corticocortical connectivity. Our analysis revealed that under baseline conditions, the cortical network, in particular the central regions of the frontoparietal cortex, interact at a characteristic latency of 50 ms, but only during wake, not sleep. Nonsalient auditory stimulation causes far greater perturbation of connectivity from baseline in sleep than wake, both in the response to common input and corticocortical connectivity. The findings have key implications for sensory processing.

Dynamic multi-channel TMS with reconfigurable coil.

Investigations of the causal involvement of particular brain areas and interconnections in behavior require an external stimulation system with reasonable spatio-temporal resolution. Current transcranial magnetic stimulation (TMS) technology is limited to stimulating a single brain area once in a given trial. Here, we present a feasibility study for a novel TMS system based on multi-channel reconfigurable coils. With this hardware, researchers will be able to stimulate multiple brain sites in any temporal order in a trial. The system employs a wire-mesh coil, constructed using x- and y-directional wires. By varying the current direction and/or strength on each wire, we can configure the proposed mesh-wire coil into a standard loop coil and figure-eight coil of varying size. This provides maximum flexibility to the experimenter in that the location and extent of stimulation on the brain surface can be modified depending on experimental requirement. Moreover, one can dynamically and automatically modify the site(s) of stimulation several times within the span of seconds. By pre-storing various sequences of excitation patterns inside a control unit, one can explore the effect of dynamic TMS on behavior, in associative learning, and as rehabilitative therapy. Here, we present a computer simulation and bench experiments that show the feasibility of the dynamically-reconfigurable coil.

Sleep shelters verbal memory from different kinds of interference.

STUDY OBJECTIVES: Studies have shown that sleep shelters old verbal memories from associative interference arising from new, more recently acquired memories. Our objective is to extend the forms of interference for which sleep provides a sheltering benefit to non-associative and prospective interference, and to examine experimental conditions and memory strengths for which sleep before or after learning particularly affects verbal memory consolidation. DESIGN: Acquiring paired word associates, retention across intervening sleep and wake, training on new, interfering word associates, and test recall of both sets. SETTING: University laboratory. PARTICIPANTS: Healthy volunteers. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Comparing recall before and after intervening periods of sleep versus wake, we found that: (i) Sleep preferentially shields weakly encoded verbal memories from retroactive interference. (ii) Sleep immediately following learning helps shelter memory from associative and non-associative forms of retroactive interference. (iii) Sleep protects new verbal memories from prospective interference. (iv) Word associations acquired for the first time in the evening after a day spent in the wake state are encoded more strongly than word associations acquired in the morning following a night of sleep. CONCLUSIONS: The findings extend the known sleep protection from interference to non-associative as well as prospective interference, and limit the protection to weakly encoded word associations. Combined, our results suggest that sleep immediately after verbal learning isolates newly formed memory traces and renders them inaccessible, except by specific contextual cues. Memory isolation in sleep is a passive mechanism that can reasonably account for several experimental findings.

Sleep's influence on a reflexive form of memory that does not require voluntary attention.

STUDY OBJECTIVES: Studies to date have examined the influence of sleep on forms of memory that require voluntary attention. The authors examine the influence of sleep on a form of memory that is acquired by passive viewing. DESIGN: Induction of the McCollough effect, and measurement of perceptual color bias before and after induction, and before and after intervening sleep, wake, or visual deprivation. SETTING: Sound-attenuated sleep research room. PARTICIPANTS: 13 healthy volunteers (mean age = 23 years; age range = 18-31 years) with normal or corrected-to-normal vision. INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: ) ENCODING: sleep preceded adaptation. On separate nights, each participant slept for an average of 0 (wake), 1, 2, 4, or 7 hr (complete sleep). Upon awakening, the participant's baseline perceptual color bias was measured. Then, he or she viewed an adapter consisting of alternating red/horizontal and green/vertical gratings for 5 min. Color bias was remeasured. The strength of the aftereffect is the postadaptation color bias relative to baseline. A strong orientation contingent color aftereffect was observed in all participants, but total sleep duration (TSD) prior to the adaptation did not modulate aftereffect strength. Further, prior sleep provided no benefit over prior wake. Retention: sleep followed adaptation. The procedure was similar except that adaptation preceded sleep. Postadaptation sleep, irrespective of its duration (1, 3, 5, or 7 hr), arrested aftereffect decay. By contrast, aftereffect decay was arrested during subsequent wake only if the adapted eye was visually deprived. CONCLUSIONS: Sleep as well as passive sensory deprivation enables the retention of a color aftereffect. Sleep shelters this reflexive form of memory in a manner akin to preventing sensory interference.

Extracting biomarkers of autism from MEG resting-state functional connectivity networks.

The present study is a preliminary attempt to use graph theory for deriving distinct features of resting-state functional networks in young adults with autism spectrum disorder (ASD). Networks modeled neuromagnetic signal interactions between sensors using three alternative interdependence measures: (a) a non-linear measure of generalized synchronization (robust interdependence measure [RIM]), (b) mutual information (MI), and (c) partial directed coherence (PDC). To summarize the information contained in each network model we employed well-established global graph measures (average strength, assortativity, clustering, and efficiency) as well as graph measures (average strength of edges) tailored to specific hypotheses concerning the spatial distribution of abnormalities in connectivity among individuals with ASD. Graph measures then served as features in leave-one-out classification analyses contrasting control and ASD participants. We found that combinations of regionally constrained graph measures, derived from RIM, performed best, discriminating between the two groups with 93.75% accuracy. Network visualization revealed that ASD participants displayed significantly reduced interdependence strength, both within bilateral frontal and temporal sensors, as well as between temporal sensors and the remaining recording sites, in agreement with previous studies of functional connectivity in this disorder.

Phantom flashes caused by interactions across visual space.

Studies regarding the effects of context on the perception of a visual target's temporal properties have generally addressed the cross-modal integration of auditory context, within a functional or ecological (e.g., Bayesian) framework. A deeper understanding of contextual effects in temporal vision may be gained by drawing connections with the rich models of signal processing developed in the field of spatial vision. To bridge this gap, we investigate a purely visual version of the cross-modal "double-flash" illusion (L. Shams, Y. Kamitani, & S. Shimojo, 2000; J. T. Wilson & W. Singer, 1981). Here, a single target flash can be perceived as several flashes if it is presented in the context of multiple visual inducers. This effect is robust across conditions where the target and inducers are of opposite contrast polarity, in different hemifields, are non-collinear, are presented dichoptically, or are high-frequency Gabor patches. The effect diminishes when target-inducer distance is increased or when the target is moved toward the fovea. When the target is foveated, the effect can still be recovered if the inducers are placed at 3° distance. Finally, we find that multiple target flashes are not "merged" into a smaller number of perceived flashes when presented with singular inducers. These results suggest a cortical mechanism based on isotropic propagation of transient signals or possibly based on higher level event detection. Finally, we find that multiple target flashes are not "merged" into a smaller number of perceived flashes when presented with singular inducers. These results suggest a mechanism based on the propagation of transient signals and argue against the relevance of the cue integration model developed for the cross-modal version of the effect.

Detecting social and non-social changes in natural scenes: performance of children with and without autism spectrum disorders and typical adults.

We probed differences in the ability to detect and interpret social cues in adults and in children and young adolescents with and without autism spectrum disorders (ASD) by investigating the effect of various social and non-social contexts on the visual exploration of pictures of natural scenes. Children and adolescents relied more on social referencing cues in the scene as compared to adults, and in the presence of such cues, were less able to use other kinds of cues. Typically developing children and adolescents were no better than those with ASD at detecting changes within the various social contexts. Results suggest children and adolescents with ASD use relevant social cues while searching a scene just as typical children do.

Perceiving a discontinuity in motion.

Studies have shown that the position of a target stimulus is misperceived owing to ongoing motion. Although static forces (fixation, landmarks) affect perceived position, motion remains the overwhelming force driving estimates of position. Motion endpoint estimates biased in the direction of motion are perceptual signatures of motion's dominant role in localization. We sought conditions in which static forces exert the predominant influence over perceived position: stimulus displays for which target position is perceived backward relative to motion. We used a target that moved diagonally with constant speed, abruptly turned 90° and continued at constant speed; observers localized the discontinuity. This yielded a previously undescribed effect, "turn-point shift," the tendency of observers to estimate the position of orthogonal direction change backward relative to subsequent motion direction. Display and mislocalization direction differ from past studies. Static forces (foveal attraction, repulsion by subsequently occupied spatial positions) were found to be responsible. Delayed turn-point estimates, reconstructed from probing the entire trajectory, shifted the horizontal coordinate forward in the direction of motion. This implies more than one percept of turn-point position. As various estimates of turn-point position arise at different times, under different task demands, the perceptual system does not necessarily resolve conflicts between them.

Increased response variability in autistic brains?

One of the key ideas regarding atypical connectivity in autistic brains is the hypothesis of noisier networks. The systems level version of this hypothesis predicts reduced reliability or increased variability in the evoked responses of individuals with autism. Using magnetoencephalography, we examined the response of individuals with autism spectrum disorder versus matched typically developing persons to passive tactile stimulation of the thumb and index finger of the dominant (right) hand. A number of different analyses failed to show higher variability in the evoked response to the thumb or to the index finger in the autism group as compared with typicals. Our results argue against the hypothesis that the brain networks in autism are noisier than normal.

Does sleep really influence face recognition memory?

Mounting evidence implicates sleep in the consolidation of various kinds of memories. We investigated the effect of sleep on memory for face identity, a declarative form of memory that is indispensable for nearly all social interaction. In the acquisition phase, observers viewed faces that they were required to remember over a variable retention period (0-36 hours). In the test phase, observers viewed intermixed old and new faces and judged seeing each before. Participants were classified according to acquisition and test times into seven groups. Memory strength (d') and response bias (c) were evaluated. Substantial time spent awake (12 hours or more) during the retention period impaired face recognition memory evaluated at test, whereas sleep per se during the retention period did little to enhance the memory. Wakefulness during retention also led to a tightening of the decision criterion. Our findings suggest that sleep passively and transiently shelters face recognition memory from waking interference (exposure) but does not actively aid in its long-term consolidation.