Biology subjects

Halgren, E.

Publications and source records attributed to Halgren, E..

At least 19 recordsLinked to original sources

bioRxiv2025

Stimulation with ECoG electrodes modulates cortical activity and sensory processing in the awake mouse brain

Electrical stimulation has been widely used to probe neural network properties and treat dysfunction. Electrocorticography (ECoG) electrodes, long used for activity monitoring, can also stimulate the brain in a minimally invasive and chronic manner. However, how cortical surface electrical stimulation impacts cortical network activity remains poorly understood. Using in vivo calcium imaging in the awake mouse brain with chronically implanted ECoG electrodes, we measured how electrical stimulation modulates the activity of visual cortical neurons, including during concurrent visual stimulation. We found that cortical surface electrical stimulation initially activates L2/3 neurons followed by prolonged inhibition lasting seconds after stimulation. Electrical stimulation suppresses the activity of neurons at their preferred grating orientation but enhances their responses to non-preferred visual stimuli, thereby reducing sensory feature selectivity. By measuring how electrical stimulation modulates the activity of inhibitory neuron subtypes including PV, SST, and NDNF interneurons, we propose a circuit model in which L1 NDNF interneurons are strongly activated by cortical electrical stimulation and, in turn, inhibit L2/3 excitatory neurons and PV interneurons through volume transmission of GABA.

neuroscience↗

bioRxiv2025

Cross-region neuron co-firing mediated by ripple oscillations supports distributed working memory representations.

High-frequency ([~]90Hz) ripple oscillations may promote integrative processing in mammalian brains. Previous work has demonstrated that the co-occurrence of these ripple oscillations is associated with enhanced temporal binding of neural activity between nearby human cortical neurons. However, it remains unclear whether such co-ripple facilitation of neuronal coupling supports cognitive processing, or if it occurs at greater distances. Here, we analyze intracranial recordings from patients implanted with microwire electrodes in the hippocampus, amygdala, ventromedial prefrontal cortex, anterior cingulate cortex, and pre-supplementary motor area, bilaterally, during a working memory task. We demonstrate that ripple oscillations significantly increase in all recorded regions, during encoding, maintenance and retrieval. Furthermore, co-occurrence of ripples increases between brain regions, associated with [~]30% increases in cross-region co-firing, both without decrement over distances up to 220 mm. These increases in cross-regional co-rippling and associated co-firing scale with memory load during maintenance and retrieval. During retrieval, co-ripples promote the reinstatement of the stimulus-specific long-distance co-firing patterns observed during encoding, especially during rapid recognition. Our findings reveal that co-occurring ripple oscillations orchestrate long-range neural communication that supports distributed neural representations during human cognition.

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bioRxiv2024

Modular Phoneme Processing in Human Superior Temporal Gyrus

Modular organization is fundamental to cortical processing, but its presence is human association cortex is unknown. We characterized phoneme processing with 128-1024 channel micro-arrays at 50-200m pitch on superior temporal gyrus of 7 patients. High gamma responses were highly correlated within [~]1.7mm diameter modules, sharply delineated from adjacent modules with distinct time-courses and phoneme-selectivity. We suggest that receptive language cortex may be organized in discrete processing modules.

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bioRxiv2023

Emergent effects of synaptic connectivity on cortical sleep slow wave amplitude, density and propagation in a large-scale thalamocortical network model of the human brain

Slow-wave sleep (SWS), characterized by slow oscillations (SO, <1Hz) of alternating active and silent states in the thalamocortical network, is a primary brain state during Non-Rapid Eye Movement (NREM) sleep. In the last two decades, the traditional view of SWS as a global and uniform whole-brain state has been challenged by a growing body of evidence indicating that SO can be local and can coexist with wake-like activity. However, the understanding of how global and local SO emerges from micro-scale neuron dynamics and network connectivity remains unclear. We developed a multi-scale, biophysically realistic human whole-brain thalamocortical network model capable of transitioning between the awake state and slow-wave sleep, and we investigated the role of connectivity in the spatio-temporal dynamics of sleep SO. We found that the overall strength and a relative balance between long and short-range synaptic connections determined the network state. Importantly, for a range of synaptic strengths, the model demonstrated complex mixed SO states, where periods of synchronized global slow-wave activity were intermittent with the periods of asynchronous local slow-waves. Increase of the overall synaptic strength led to synchronized global SO, while decrease of synaptic connectivity produced only local slow-waves that would not propagate beyond local area. These results were compared to human data to validate probable models of biophysically realistic SO. The model producing mixed states provided the best match to the spatial coherence profile and the functional connectivity estimated from human subjects. These findings shed light on how the spatio-temporal properties of SO emerge from local and global cortical connectivity and provide a framework for further exploring the mechanisms and functions of SWS in health and disease. Author SummarySlow Wave Sleep (SWS) is a primary brain state displayed during Non-Rapid Eye Movement (NREM) sleep. While previously thought of as homogenous waves of activity that sweep across the entire brain, modern research has suggested a more nuanced pattern of activity that can vary between local and global slow wave activity. However, understanding how these states emerge from small scale neuronal dynamics and network connectivity remains unclear. We developed a biophysically realistic model of the human brain capable of generating SWS-like behavior, and investigated the role of connectivity in the spatio-temporal dynamics of these slow waves. We found that the overall strength and a relative balance between long and short-range synaptic connections determined the network behavior - specifically, models with relatively weaker long-range connectivity resulted in mixed states of global and local slow waves. These results were compared to human data, and we found that models producing mixed states provided the best match to the network behavior and functional connectivity of human subject data. These findings shed light on how the spatio-temporal properties of SWS emerge from local and global cortical connectivity and provide a framework for further exploring the mechanisms and functions of SWS in health and disease.

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bioRxiv2023

The Brain Electroencephalogram Microdisplay for Precision Neurosurgery

Brain surgeries are among the most delicate clinical procedures and must be performed with the most technologically robust and advanced tools. When such surgical procedures are performed in functionally critical regions of the brain, functional mapping is applied as a standard practice that involves direct coordinated interactions between the neurosurgeon and the clinical neurology electrophysiology team. However, information flow during these interactions is commonly verbal as well as time consuming which in turn increases the duration and cost of the surgery, possibly compromising the patient outcomes. Additionally, the grids that measure brain activity and identify the boundaries of pathological versus functional brain regions suffer from low resolution (3-10 mm contact to contact spacing) with limited conformity to the brain surface. Here, we introduce a brain intracranial electroencephalogram microdisplay (Brain-iEEG-microdisplay) which conforms to the brain to measure the brain activity and display changes in near real-time (40 Hz refresh rate) on the surface of the brain in the surgical field. We used scalable engineered gallium nitride (GaN) substrates with 6" diameter to fabricate, encapsulate, and release free-standing arrays of up to 2048 GaN light emitting diodes (LEDs) in polyimide substrates. We then laminated the LED arrays on the back of micro-electrocorticography (ECoG) platinum nanorod grids (PtNRGrids) and developed hardware and software to perform near real-time intracranial EEG analysis and activation of light patterns that correspond to specific cortical activities. Using the Brain-iEEG-microdisplay, we precisely ideFSntified and displayed important cortical landmarks and pharmacologically induced pathological activities. In the rat model, we identified and displayed individual cortical columns corresponding to individual whiskers and the near real-time evolution of epileptic discharges. In the pig animal model, we demonstrated near real-time mapping and display of cortical functional boundaries using somatosensory evoked potentials (SSEP) and display of responses to direct electrical stimulation (DES) from the surface or within the brain tissue. Using a dual-color Brain-iEEG-microdisplay, we demonstrated co-registration of the functional cortical boundaries with one color and displayed the evolution of electrical potentials associated with epileptiform activity with another color. The Brain-iEEG-microdisplay holds the promise of increasing the efficiency of diagnosis and possibly surgical treatment, thereby reducing the cost and improving patient outcomes which would mark a major advancement in neurosurgery. These advances can also be translated to broader applications in neuro-oncology and neurophysiology. One Sentence SummaryA brain intracranial electroencephalogram microdisplay (Brain-iEEG-microdisplay) measures and displays real-time brain activity in the surgical field.

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bioRxiv2023

Human co-ripples facilitate neuronal interactions between cortical locations.

Synchronous bursts of high frequency oscillations ( ripples) are hypothesized to contribute to binding by facilitating integration of neuronal firing across cortical locations. We tested this hypothesis using local field-potentials and single-unit firing from four 96-channel microelectrode arrays in supragranular cortex of 3 patients. Neurons in co-rippling locations showed increased short-latency co-firing, prediction of each-others firing, and co-participation in neural assemblies. Effects were similar for putative pyramidal and interneurons, during NREM sleep and waking, in temporal and Rolandic cortices, and at distances up to 16mm. Increased co-prediction during co-ripples was maintained when firing-rate changes were equated, and were strongly modulated by ripple phase. Co-ripple enhanced prediction is reciprocal, synergistic with local upstates, and further enhanced when multiple sites co-ripple. Together, these results support the hypothesis that trans-cortical co-ripples increase the integration of neuronal firing of neurons in different cortical locations, and do so in part through phase-modulation rather than unstructured activation.

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bioRxiv2023

Do cortical co-ripples bind lines, letters, words, meanings, strategy and action in reading?

Whether high-frequency phase-locked oscillations facilitate integration ( binding) of information across widespread cortical areas is controversial. Here we show with intracranial EEG that cortico-cortical co-ripples ([~]100ms long [~]90Hz oscillations) increase during reading and semantic decisions, at the times and co-locations when and where binding should occur. Fusiform wordform areas co-ripple with virtually all language areas, maximally from 200-400ms post-word-onset. Semantically-specified target words evoke strong co-rippling between wordform, semantic, executive and response areas from 400-800ms, with increased co-rippling between semantic, executive and response areas prior to correct responses. Co-ripples were phase-locked at zero-lag over long distances (>12cm), especially when many areas were co-rippling. General co-activation, indexed by non-oscillatory high gamma, was mainly confined to early latencies in fusiform and earlier visual areas, preceding co-ripples. These findings suggest that widespread synchronous co-ripples may assist the integration of multiple cortical areas for sustained periods during cognition. One Sentence SummaryWidespread visual, wordform, semantic, executive and response areas phase-lock at 90Hz during integrative semantic processing.

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bioRxiv2022

Flexible, Scalable, High Channel Count Stereo-Electrode for Recording in the Human Brain

Over the past decade, stereotactically placed electrodes have become the gold standard for deep brain recording and stimulation for a wide variety of neurological and psychiatric diseases. Current electrodes, however, are limited in their spatial resolution and ability to record from small populations of neurons, let alone individual neurons. Here, we report on a novel, reconfigurable, monolithically integrated human-grade flexible depth electrode capable of recording from up to 128 channels and able to record at a depth of 10 cm in brain tissue. This thin, stylet-guided depth electrode is capable of recording local field potentials and single unit neuronal activity (action potentials), validated across species. This device represents a major new advance in manufacturing and design approaches which extends the capabilities of a mainstay technology in clinical neurology. One-Sentence SummaryA human-grade thin-film depth electrode offers new opportunities in spatial and temporal resolution for recording brain activity.

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bioRxiv2022

Cortico-cortical and hippocampo-cortical co-rippling are facilitated by thalamo-cortical spindles and upstates, but not by thalamic ripples

The co-occurrence of brief [~]90Hz oscillations (co-ripples) may be important for integrating information across the neocortex and hippocampus and, therefore, essential for sleep consolidation, and cognition in general. However, how such co-ripples are synchronized is unknown. We tested if cortico-cortical and hippocampal-cortical ripple co-occurrences are due to the simultaneous direct propagation of thalamic ripples, and/or if they are coordinated by lower frequency thalamic waves. Using human intracranial recordings, we found that ripples are generated in the anterior and posterior thalamus during local spindles on the down-to-upstate transition in non-rapid eye movement sleep, with similar characteristics as cortical and hippocampal ripples. However, thalamic ripples only infrequently co-occur or phase-lock, with cortical and hippocampal ripples. In contrast, thalamo-cortical spindles and upstates were strongly coordinated with cortico-cortical and hippocampo-cortical co-rippling. Thus, while thalamic ripples may not directly drive multiple cortical or hippocampal sites at ripple frequency, thalamo-cortical spindles and upstates may provide the input necessary for spatially distributed co-rippling to integrate information in the cortex. Significance StatementWidespread networks of [~]90 Hz oscillations, called "ripples," have recently been identified in humans and may help to bind information in the cortex and hippocampus for memory. However, it is not known whether the thalamus generates ripples, and if so whether they, or other thalamic waves, coordinate networks of co-occurring cortical and hippocampal ripples. Here, we show that the human thalamus generates [~]90 Hz ripples during NREM sleep. While thalamic ripples do not appear to directly synchronize ripple co-occurrence in the cortex and hippocampus, our data provide evidence that propagating thalamo-cortical spindles and upstates organize these networks. Thus, the thalamus projects slower frequency waves that modulate higher frequency hippocampo-cortical oscillatory networks for memory in humans.

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bioRxiv2021

Human spindle variability

In humans, sleep spindles are 10-16 Hz oscillations lasting approximately 0.5-2 s. Spindles, along with cortical slow oscillations, facilitate memory consolidation by enabling synaptic plasticity. Early recordings of spindles at the scalp found anterior channels had overall slower frequency than central-posterior channels. This robust, topographical finding led to dichotomizing spindles as slow versus fast, modelled as two distinct spindle generators in frontal versus posterior cortex. Using a large dataset of intracranial sEEG recordings (n=20, 365 bipolar recordings), we show that the difference in spindle frequency between frontal and parietal channels is comparable to the variability in spindle frequency within the course of individual spindles, across different spindles recorded by a given site, and across sites within a given region. Thus, fast and slow spindles only capture average differences that obscure a much larger underlying overlap in frequency. Furthermore, differences in mean frequency are only one of several ways that spindles differ. For example, compared to parietal, frontal spindles are smaller, tend to occur after parietal when both are engaged, and show a larger decrease in frequency within-spindles. However, frontal and parietal spindles are similar in being longer, less variable, and more widespread than occipital, temporal, and Rolandic spindles. These characteristics are accentuated in spindles which are highly phase-locked to posterior hippocampal spindles. We propose that rather than a strict parietal-fast/frontal-slow dichotomy, spindles differ continuously and quasi-independently in multiple dimensions, with variability due about equally to within-spindle, within-region and between-region factors. Significance StatementSleep spindles are 10-16 Hz neural oscillations generated by cortico-thalamic circuits that promote memory consolidation. Spindles are often dichotomized into slow-anterior and fast-posterior categories for cognitive and clinical studies. Here, we show that the anterior-posterior difference in spindle frequency is comparable to that observed between different cycles of individual spindles, between spindles from a given site, or from different sites within a region. Further, we show that spindles vary on other dimensions such as duration, amplitude, spread, primacy and consistency, and that these multiple dimensions vary continuously and largely independently across cortical regions. These findings suggest that multiple continuous variables rather than a strict frequency dichotomy may be more useful biomarkers for memory consolidation or psychiatric disorders.

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bioRxiv2021

The timescale and magnitude of aperiodic activity decreases with cortical depth in humans, macaques and mice

Cortical dynamics obey a 1/f power law, exhibiting an exponential decay of spectral power with increasing frequency. The slope and offset of this 1/f decay reflect the timescale and magnitude of aperiodic neural activity, respectively. These properties are tightly linked to cellular and circuit mechanisms (e.g. excitation:inhibition balance and firing rates) as well as cognitive processes (e.g. perception, memory, and state). However, the physiology underlying the 1/f power law in cortical dynamics is not well understood. Here, we compared laminar recordings from human, macaque and mouse cortex to evaluate how 1/f aperiodic dynamics vary across cortical layers and species. We report that 1/f slope is steepest in superficial layers and flattest in deep layers in each species. Additionally, the magnitude of this 1/f decay is greatest in superficial cortex and decreases with depth. We could account for both of these findings with a simple model in which superficial cortical transmembrane currents had longer time constants and greater densities than those in deeper layers. Together, our results provide novel insight into the organization of cortical dynamics, suggesting that the amplitude and time constant of local currents control circuit processing as a function of laminar depth. This may represent a general mechanism to facilitate appropriate integration of fast sensory inputs (infragranular) with slow feedback-type inputs (supragranular) across cortical areas and species.

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bioRxiv2021

Estimating the absolute number of axons connecting different cortical areas in humans with diffusion MRI

The tracts between cortical areas are conceived as playing a central role in cortical information processing, but their actual numbers have never been determined in humans. Here we estimate the absolute number of axons linking cortical areas from a whole-cortex diffusion-MRI (dMRI) connectome, calibrated using the histologically-measured callosal fiber density. Median connectivity is estimated as ~6200 axons between cortical areas within-hemisphere and ~1300 axons inter-hemispherically, with axons connecting functionally-related areas surprisingly sparse. For example, we estimate that <5% of the axons in the trunk of the arcuate and superior longitudinal fasciculi connect Wernickes and Brocas areas. These results suggest that detailed information is transmitted between cortical areas either via linkage of the dense local connections or via rare, extraordinarily privileged long-range connections.

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bioRxiv2021

Cortical ripples provide the conditions for consolidation during NREM sleep in humans

Hippocampal ripples index the reconstruction of spatiotemporal neuronal firing patterns essential for the consolidation of memories in the cortex during non-rapid eye movement sleep (NREM). Recently, cortical ripples in humans have been shown to enfold the replay of neuron firing patterns during cued recall. Here, using intracranial recordings from 18 patients (12 female), we show that cortical ripples also occur during NREM in humans, with similar density, oscillation frequency ([~]90 Hz), duration, and amplitude to waking. Ripples occurred in all cortical regions with similar characteristics, unrelated to putative hippocampal connectivity, and were less dense and robust in higher association areas. Putative pyramidal and interneuron spiking phase-locked to cortical ripples during NREM, with phase delays consistent with ripple generation through pyramidal-interneuron feedback. Cortical ripples were smaller in amplitude than hippocampal ripples, but were similar in density, frequency, and duration. Cortical ripples during NREM typically occurred just prior to the upstate peak, often during spindles. Upstates and spindles have previously been associated with memory consolidation, and we found that cortical ripples grouped co-firing between units within the window of spike-timing-dependent plasticity. Thus, human NREM cortical ripples are: ubiquitous and stereotyped with a tightly focused oscillation frequency; similar to hippocampal ripples; associated with upstates and spindles; and associated with unit co-firing. These properties are consistent with cortical ripples possibly contributing to memory consolidation and other functions during NREM in humans. Significance StatementIn rodents, hippocampal ripples organize replay during sleep to promote memory consolidation in the cortex, where ripples also occur. However, evidence for cortical ripples in human sleep is limited, and their anatomical distribution and physiological properties are unexplored. Here, using human intracranial recordings, we demonstrate that ripples occur throughout the cortex during waking and sleep with highly stereotyped characteristics. During sleep, cortical ripples tend to occur during spindles on the down-to-upstate transition, and thus participate in a sequence of sleep waves that is important for consolidation. Furthermore, cortical ripples organize single unit spiking with timing optimal to facilitate plasticity. Therefore, cortical ripples in humans possess essential physiological properties to support memory and other cognitive functions.

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bioRxiv2021

Widespread ripples synchronize human cortical activity

Declarative memory encoding, consolidation, and retrieval require the integration of elements encoded in widespread cortical locations. The mechanism whereby such binding of different components of mental events into unified representations occurs is unknown. The binding-bysynchrony theory proposes that distributed encoding areas are bound by synchronous oscillations enabling enhanced communication. However, evidence for such oscillations is sparse. Brief high-frequency oscillations ( ripples) occur in the hippocampus and cortex, and help organize memory recall and consolidation. Here, using intracranial recordings in humans, we report that these ~70ms duration 90Hz ripples often couple (within {+/-}500ms), co-occur ([≥]25ms overlap), and crucially, phase-lock (have consistent phase-lags) between widely distributed focal cortical locations during both sleep and waking, even between hemispheres. Cortical ripple co-occurrence is facilitated through activation across multiple sites, and phaselocking increases with more cortical sites co-rippling. Ripples in all cortical areas co-occur with hippocampal ripples but do not phase-lock with them, further suggesting that cortico-cortical synchrony is mediated by cortico-cortical connections. Ripple phase-lags vary across sleep nights, consistent with participation in different networks. During waking, we show that hippocampo-cortical and cortico-cortical co-ripples increase preceding successful delayed memory recall, when binding between the cue and response is essential. Ripples increase and phase-modulate unit firing, and co-ripples increase high-frequency correlations between areas, suggesting synchronized unit-spiking facilitating information exchange. Co-occurrence, phasesynchrony, and high-frequency correlation are maintained with little decrement over very long distances (25cm). Hippocampo-cortico-cortical co-ripples appear to possess the essential properties necessary to support binding-by-synchrony during memory retrieval, and perhaps generally in cognition. Significance StatementDifferent elements of a memory, or any mental event, are encoded in locations distributed across the cortex. A prominent hypothesis proposes that widespread networks are integrated with bursts of synchronized high-frequency oscillations called ripples, but evidence is limited. Here, using recordings inside the human brain, we show that ripples occur simultaneously in multiple lobes in both cortical hemispheres, and the hippocampus, generally during sleep and waking, and especially during memory recall. Ripples phase-lock local cell firing, and phase-synchronize with little decay between locations separated by up to 25cm, enabling long-distance integration. Indeed, co-rippling sites have increased correlation of very high-frequency activity which reflects cell firing. Thus, ripples may help bind information across the cortex in memory and other mental events.

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bioRxiv2020

A whole-cortex probabilistic diffusion tractography connectome

The WU-Minn Human Connectome Project (HCP) is a publicly-available dataset containing state-of-art structural, functional, and diffusion-MRI for over a thousand healthy subjects. While the planned scope of the HCP included an anatomical connectome, resting-state functional-MRI forms the bulk of the HCPs current connectomic output. We address this by presenting a full-cortex connectome derived from probabilistic diffusion tractography and organized into the HCP-MMP1.0 atlas. Probabilistic methods and large sample sizes are preferable for whole-connectome mapping as they increase the fidelity of traced low-probability connections. We find that overall, connection strengths are lognormally distributed and decay exponentially with tract length, that connectivity reasonably matches macaque histological tracing in homologous areas, that contralateral homologs and left-lateralized language areas are hyperconnected, and that hierarchical similarity influences connectivity. We compare the diffusion-MRI connectome to existing resting-state fMRI and cortico-cortico evoked potential connectivity matrices and find that it is more similar to the latter. This work helps fulfill the promise of the HCP and will make possible comparisons between the underlying structural connectome and functional connectomes of various modalities, brain states, and clinical conditions. Significance StatementThe tracts between cortical parcels can be estimated from diffusion MRI, but most studies concentrate on only the largest connections. Here we present an atlas, the largest and most detailed of its kind, showing connections among all cortical parcels. Connectivity is relatively enhanced between frontotemporal language areas and homologous contralateral locations. We find that connectivity decays with fiber tract distance more slowly than predicted by brain volume and that structural and stimulation-derived connectivity are more similar to each other than to resting-state functional MRI correlations. The connectome presented is publicly available and organized into a commonly used scheme for defining brain areas in order to enable ready comparison to other brain imaging datasets of various modalities.

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bioRxiv2020

Travelling spindles create necessary conditions for spike-timing-dependent plasticity in humans

Sleep spindles facilitate memory consolidation in the cortex during mammalian non-rapid eye movement (NREM) sleep. In rodents, phase-locked firing during spindles may facilitate spike-timing-dependent plasticity (STDP) by grouping pre- and post-synaptic cell firing within [~]25ms. Currently, microphysiological evidence in humans for conditions conducive for STDP during spindles is absent. We analyzed local field potentials and supragranular unit spiking during spindles from 10x10 arrays of microelectrodes at 400{micro}m pitch in humans. We found strong tonic and phase-locked increases in firing and co-firing within 25ms during spindles. Co-firing, spindle co-occurrence, and spindle coherence were greatest between sites within [~]2mm, and high co-firing of units on different electrodes was largely restricted to moments of high spindle coherence between those electrodes. Spindles propagated at [~]0.23m/s in distinct patterns, with correlated cell co-firing sequences. These results suggest that spindles may organize spatiotemporal patterns of neuronal co-firing which promote memory consolidation during NREM sleep.

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bioRxiv2019

Improved identification and differentiation from epileptiform activity of human hippocampal sharpwave-ripples during NREM sleep

In rodents, pyramidal cell firing patterns from waking may be replayed in NREM sleep during hippocampal sharpwave-ripples (HC-SWR). In humans, HC-SWR have only been recorded with electrodes implanted to localize epileptogenesis. Here, we characterize human HC-SWR with rigorous rejection of epileptiform activity, requiring multiple oscillations and coordinated sharpwaves. We demonstrated typical SWR in those rare HC recordings which lack interictal epileptiform spikes (IIS), and with no or minimal seizure involvement. These HC-SWR have a similar rate (~12/min) and apparent intra-HC topography (ripple maximum in putative stratum pyramidale, slow wave in radiatum) as rodents, though with lower frequency (~85Hz compared to ~140Hz in rodents). Similar SWR are found in HC with IIS, but no significant seizure involvement. These SWR were modulated by behavior, being largely absent (<2/min) except during NREM sleep in both stage 2 (~9/min) and stage 3 (~15/min), distinguishing them from IIS. This study quantifies the basic characteristics of a strictly selected sample of SWR recorded in relatively healthy human hippocampi.

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bioRxiv2019

Coordination of human hippocampal sharpwave-ripples during NREM sleep with cortical theta bursts, spindles, downstates and upstates

In rodents, waking firing patterns replay in NREM sleep during hippocampal sharpwave-ripples (HC-SWR), correlated with neocortical graphoelements (NC-GE). NC-GE include theta-bursts, spindles, downstates and upstates. In humans, consolidation during sleep is correlated with scalp-recorded spindles and down-upstates, but HC-SWR cannot be recorded non-invasively. Here we show in humans of both sexes that HC-SWR are highly correlated with NC-GE during NREM, with significantly more related HC-SWR/NC-GE for downstates or upstates than theta-bursts or spindles, in N2 than N3, in posterior than anterior HC, in frontal than occipital cortex, and ipsilaterally than contralaterally. The preferences interacted, e.g. frontal spindles co-occurred frequently with posterior HC-SWR in N2. These preferred GE, stages and locations for HC-SWR/NC-GE interactions may index selective consolidation activity, although that was not tested in this study. SWR recorded in different HC regions seldom co-occurred, and were related to GE in different cortical areas, showing that HC-NC interact in multiple transient, widespread but discrete, networks. NC-GE tend to occur with consistent temporal relationships to HC-SWR, and to each other. Cortical theta-bursts usually precede HC-SWR, where they may help define cortical input triggering HC-SWR firing. HC-SWR often follow cortical downstate onsets, surrounded by locally-decreased broadband power, suggesting a mechanism synchronizing cortical, thalamic and hippocampal activities. Widespread cortical upstates and spindles follow HC-SWR, consistent with the hypothesized contribution by hippocampal firing during HC-SWR to cortical firing-patterns during upstates and spindles. Overall, our results describe how hippocampal and cortical oscillations are coordinated in humans during events that are critical for memory consolidation in rodents.\n\nSignificance StatementHippocampal sharpwave-ripples, essential for memory consolidation, mark when hippocampal neurons replay waking firing patterns. In rodents, cortical sleep waves coordinate the transfer of temporary hippocampal to permanent cortical memories, but their relationship with human HC-SWR remains unclear. We show that human hippocampal sharpwave-ripples co-occur with all varieties of cortical sleep waves, in all cortical regions, and in all stages of Non-REM sleep but with overall preferences for each of these. We found that sharpwave-ripples in different parts of the hippocampus usually occurred independently of each other, and preferentially interacted with different cortical areas. We found that sharpwave-ripples typically occur after certain types of cortical waves, and before others, suggesting how the cortico-hippocampo-cortical interaction may be organized in time and space.

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