Our
Research
Sleep is fascinating. We study brain activity during sleep, how it supports cognition and restorative functions, and how it affects sensation and consciousness.
Reseach themes:
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Sensory processing and sleep
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Sleep and memory
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Noradrenaline and arousal
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Basic sleep physiology
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Sleep and brain health
Sensory processing across low-arousal states of sleep,
anesthesia, and sleep-deprivation
Why are we disconnected from the environment during sleep? How does sensory processing change across sleep and other states with varying levels of arousal?
Reduced responsiveness is a defining property of sleep, but we do not understand yet the neuronal mechanisms that mediate such disconnection. Behavioral states of wakefulness, sleep, drowsiness, and anesthesia dramatically affect brain activity, and determine whether sensory stimuli will be perceived, induce plastic changes, and trigger behavior. More generally, sleep is a powerful model for how internal states of electrical activity and neuromodulation affect sensory processing. States of brain activity also dynamically change when we are awake and adapt to behavioral demands by tuning attention and expectation. We are investigating whether sleep/wake states and cognitive factors may modulate cortical responsiveness via shared mechanisms. We hope that our research may also help shed light on clinical conditions of unresponsiveness such as attention disorders, dementia, schizophrenia, autism, and vegetative states.
Sleep deprivation (SD) is commonplace in modern lifestyle and can lead to devastating outcomes, yet which aspects of cortical processing are affected by sleep deprivation (SD), and whether they also affect early sensory regions, remains unclear. we recorded spiking activity in rat auditory cortex along with polysomnography while presenting sounds during SD followed by recovery sleep. We found that frequency tuning, onset responses, and spontaneous firing rates were unaffected by SD. By contrast, SD decreased entrainment to rapid (≥20 Hz) click-trains, increased population synchrony, and increased the prevalence of stimulus-induced OFF states (silent periods not readily evident in ongoing activity) revealing latent neuronal bi-stability. Recovery NREM sleep was associated with similar effects as SD with even greater magnitude, while auditory processing during REM sleep was similar to vigilant wakefulness. Our results show that processes akin to those in NREM sleep invade the activity of cortical circuits during SD, already in early sensory cortex.
Sleep entails significant changes in neural activity and brain physiology. However, it is still unclear which neural changes underlie the accompanying dramatic behavioral and phenomenological changes. To focus on the minimal changes that accompany loss of consciousness and sensory disconnection during sleep we decided to examine the effects of falling asleep on neural processing in the rat auditory cortex. Our past work had demonstrated that there are specific features of auditory processing that are maximally sensitive to changes in arousal state. Will the same features be sensitive to the process of falling asleep, showing changes on a short timescale of seconds? Are some aspects of auditory processing especially modulated during the process of falling asleep? Are such changes in sensory processing occur gradually or in step-like manner? Such and more questions will shed light on the neural mechanisms of sleep.
Sleep and memory consolidation
How does sleep promote learning and memory consolidation of diverse memories?
Sleep is critical for long term memory consolidation – the transformation of unstable percepts to durable representations, but how brain activity during sleep supports this process is not fully understood. At the level of brain systems, this process likely involves coordinated interplay of slow waves, sleep spindles, and ripple oscillations along with reactivation of newly acquired information. For episodic hippocampal-dependent memory, a nocturnal ‘dialogue’ between hippocampus and neocortex may play a key role. We aim to bridge the gap between human cognitive research and mechanistic animal research of sleep and memory. We also wish to understand how sleep aids different forms of learning and memory (e.g. episodic, motor, emotional). We investigate how disrupted sleep may accelerate memory decline in aging and dementia, and seek to develop novel sleep interventions to improve memory.
Can we identify an abnormal semi epileptic activity in Alzheimer’s disease patients? Recent data implies there might be an Alzheimer’s subpopulation presenting Interictal spikes during sleep that may cause\contribute to memory decline. We are interested in whether those spikes, if appearing, might interfere with memory consolidation and learning at different sleep stages. We are using a multiple channel EEG recording during sleep and a passive eye tracking memory task in order to study this matter.
Perceptual generalization occurs when a new stimulus that resembles a familiar stimulus is perceived as the familiar stimulus. Generalization is an adaptive and delicate process that can easily go wrong and lead to overgeneralization around negative stimuli that might cause anxiety disorders. Patients that suffer from anxiety disorders usually also suffer from sleep difficulties and insomnia. We are interested in understanding the generalization processes that happen during sleep as they may be important for healthy and adaptive generalization. We use a triangular space of facial stimuli ranging from positive to negative to neutral associated to assess the generalization of these stimuli following wake and sleep intervals. Together with fMRI scans, EEG, actigraphy, and recordings from deep electrodes in human patients, we wish to understand the brain mechanisms underly this wake vs. sleep generalization.
Interictal epileptiform spikes (IESs) are brief paroxysmal electrographic events observed between spontaneous seizures in epilepsy patients. IESs occurring in the medial temporal lobe (MTL) during sleep may impair memory by inducing abnormal hippocampal-cortical coupling, and their reliable detection has clinical value in epilepsy and other neurological conditions. I am now working on incorporating machine learning tools to improve detection and test to what extent IEDs may be detected even in electrodes located further away from their physiological zone, using data of epilepsy patients implanted with clinical intracranial depth electrode in the MTL.
Sleep plays a key role in memory consolidation. Research studies focusing on sleep and declarative hippocampal-dependent memory typically use a paired association learning (PAL) task with word pairs as stimuli. We aim to develop and validate a paradigm appropriate for sleep and memory studies in heterogeneous clinical populations: a short (<30min) visual stimuli-based task, that has the potential to create a distinct brain activation signature that may be tracked during sleep.
Sleep and memory research typically uses presentation of long lists of word pairs in laboratory settings. This approach is suboptimal for research in elderly and demented individuals. We are using eye tracking to develop ecological paradigms to study memory, and its consolidation during sleep.
The locus-coeruleus noradrenaline system and arousal
How does LC-NE and other wake-promoting systems affect arousal and brain function?
Wake-promoting neuromodulatory systems such as those secreting noradrenaline, acetylcholine, serotonin, histamine, and hypocretin (orexin) support different aspects of arousal. Neuromodulation affects awakenings from sleep, cortical desynchronization, sensory perception, orienting to salient stimuli, plasticity, autonomic arousal (e.g. pupil dilation), and motor behaviors. We focus on noradrenaline, secreted in the forebrain by brainstem neurons in the locus coeruleus. We investigate the functional organization of the LC-NE system, how it supports different aspects of arousal, sensory processing and perception, and how its (in)activity contributes to the functional benefits of sleep.
We are interested in the impact noradrenaline can have on wake, sleep and disengagement from the environment. To address this research question we set up a fiber photometry recording system in our lab. This method allows bulk calcium recording from a neuronal population in a genetically based manor. This allowed us to target and record solely from noradrenergic neurons during long hours of natural behavior and sleep. Our results confirm former electrophysiological recordings from the LC and demonstrate higher LC activation during wake, in response to nociceptive stimuli and in correlation with pupil dilation and diminished sigma power during NREM sleep. This tool will allow us in the future to target subpopulations of the LC and examine differences between neurons that project onto distinct brain regions.
Opto-fMRI, a technique that combines the relatively high spatial resolution of high-field fMRI with the precision of optogenetic stimulation allows the research of the functional connectivity of precise neural circuits across the entire intact brain. Defining the large-scale behavior of brain circuits with cell type specificity is a major goal of neuroscience and our lab focuses on LC-NE activity to characterize functional LC brain networks and delineate whole-brain functional networks associated with LC subpopulations.
Brain activity in sleep, anesthesia, and sleep deprivation
What happens in our brain during sleep and what are the functional consequences?
For many years, brain activity during sleep was assumed to be relatively uniform. For example, sleep stages regard activity as homogenous across the entire brain, and consider activity in 30sec intervals as belonging to the same category. We seek to advance a more detailed understanding of brain activity during sleep in specific regions and circuits, and reveal how such activity patterns relate to cognition and behavior.
People: Yael Gat
Can we identify an abnormal semi epileptic activity in Alzheimer’s disease patients? Recent data implies there might be an Alzheimer’s subpopulation presenting Interictal spikes during sleep that may cause\contribute to memory decline. We are interested in whether those spikes, if appearing, might interfere with memory consolidation and learning at different sleep stages. We are using a multiple channel EEG recording during sleep and a passive eye tracking memory task in order to study this matter.
Interictal epileptiform spikes (IESs) are brief paroxysmal electrographic events observed between spontaneous seizures in epilepsy patients. IESs occurring in the medial temporal lobe (MTL) during sleep may impair memory by inducing abnormal hippocampal-cortical coupling, and their reliable detection has clinical value in epilepsy and other neurological conditions. I am now working on incorporating machine learning tools to improve detection and test to what extent IEDs may be detected even in electrodes located further away from their physiological zone, using data of epilepsy patients implanted with clinical intracranial depth electrode in the MTL.
Sleep as a window into brain function in health and disease
Can we use sleep to advance understanding, improve early diagnosis, and offer novel treatments in neuropsychiatric disorders?
Nearly all neurological and psychiatric disorders (and many other medical disorders) affect sleep. Through a tight collaboration with the sleep lab at the Tel Aviv Sourasky Medical Center (‘Ichilov’), we are investigating sleep in healthy individuals, in neurodegeneration, and in other patient populations. We aim to reveal specific biomarkers of disease status by going beyond sleep stages, and using advanced data analysis tools to focus on sleep oscillations occurring at specific times, frequencies, and locations. We study whether subtle changes in sleep EEG may serve as markers and aid in diagnosis of underlying neuropsychiatric conditions, or help predict neurodegenerative disease prior to manifestation of overt clinical symptoms. We are also developing and testing novel sleep technologies and devices for interventions that may improve sleep and its benefits.
Can we identify an abnormal semi epileptic activity in Alzheimer’s disease patients? Recent data implies there might be an Alzheimer’s subpopulation presenting Interictal spikes during sleep that may cause\contribute to memory decline. We are interested in whether those spikes, if appearing, might interfere with memory consolidation and learning at different sleep stages. We are using a multiple channel EEG recording during sleep and a passive eye tracking memory task in order to study this matter.
Interictal epileptiform spikes (IESs) are brief paroxysmal electrographic events observed between spontaneous seizures in epilepsy patients. IESs occurring in the medial temporal lobe (MTL) during sleep may impair memory by inducing abnormal hippocampal-cortical coupling, and their reliable detection has clinical value in epilepsy and other neurological conditions. I am now working on incorporating machine learning tools to improve detection and test to what extent IEDs may be detected even in electrodes located further away from their physiological zone, using data of epilepsy patients implanted with clinical intracranial depth electrode in the MTL.
Experimental setups:
Research is conducted in behaving rodents and in human studies, using a combination of multiple techniques:
