Biology subjects

Ulbert, I.

Publications and source records attributed to Ulbert, I..

At least 19 recordsLinked to original sources

bioRxiv2026

Thermoplastic polyurethane as a base material for soft, high-density neural interfaces

Polymers used as substrate and encapsulation for implantable devices are typically deposited layer-by-layer, leaving polymer-polymer interfaces that adhere poorly and become a critical failure point. Thermoplastic polyurethane (TPU) elastomers combine four properties not found together in any other candidate: decades of clinical use in long-term implants and availability in medical grade, a stiffness well below that of polyimide and parylene C, compatibility with microfabrication, and thermoplastic self-fusion, which removes the polymer-polymer interface entirely. This work introduces TPU as a base material for soft, high-density neural interfaces and demonstrates one route to realizing them. Gold is patterned on a sacrificial copper sheet by maskless lithography and transferred into TPU by vacuum lamination, giving conformally coated tracks down to 15 um at 30 um pitch within a single, merged polymer body. An additional electroplating step produces a nanostructured pinecone gold surface that increases the electrochemically active area of the electrodes, approximately doubling the charge injection capacity. Daisy-chain silicon chips were also embedded within the soft polymer body. The films transmit up to 88% at 470 nm, a wavelength commonly used for optogenetics. TPU showed no cytotoxicity towards differentiated SH-SY5Y cells and only a mild tissue response after 9.5 months of subcutaneous implantation in rats.

bioengineering↗

bioRxiv2026

Cortical isolation separates rhythmic synchrony from network integration in the human neocortex.

Human cortical activity reflects interactions between local recurrent circuits and distributed brain-wide inputs, but how these contributions shape cortical dynamics remains unclear. We compared oscillatory and single unit activity in laminar recordings from the same human cortical regions in eight patients across wakefulness, NREM sleep, and acute slices after surgical isolation. Gamma-band spike-field synchronization increased from wakefulness to sleep and isolated cortex, whereas population coupling, putative connectivity, network integration, and dynamical dimensionality declined. Laminar gamma sink-source organization persisted in isolation, indicating the presence of local gamma-generating mechanisms. Integration with histological data showed preserved tissue architecture, while neuronal density predicted population integration in vivo but not after isolation. Removing long-range inputs thus did not suppress cortical activity but shifted its organization toward stronger rhythmic coordination and reduced integration. Our findings suggest that neocortical microcircuits intrinsically generate coherent gamma activity, whereas network embedding supports the diverse, high-dimensional dynamics of the intact cortex.

neuroscience↗

bioRxiv2026

Preserved functions with profound morphological reorganization in human organotypic cultures

Human organotypic slice cultures provide experimental access to adult human neuronal circuits ex vivo, yet it remains unclear whether these networks preserve function or undergo fundamental reorganization following the profound perturbation of slice preparation. Here, we combined extracellular population and single-unit electrophysiology, longitudinal calcium imaging, and quantitative histology to track the changes of human cortical slice cultures over several weeks in vitro. Early phases were marked by pronounced variability and instability, with reduced firing rates, increased burst propensity in principal cells, elevated discharge irregularity, and heterogeneous recruitment during population activity. These functional changes coincided with substantial structural remodeling, including considerable neuronal loss, disruption of laminar architecture, reactive gliosis, and selective vulnerability of inhibitory interneurons. Strikingly, despite this progressive structural degradation, neuronal activity did not diverge but instead converged. By the fourth week in culture, electrophysiological properties, cell-type-specific firing patterns, and population-event recruitment became stable and highly consistent across patients. Calcium imaging revealed persistent, spatially confined regions of synchronous activity, indicating the preservation of structured network dynamics. These events remained within physiological regimes and lacked features of epileptiform discharges. Thus, human neuronal circuits exhibit a robust capacity for self-organization, transitioning from heterogeneous, injury-driven dynamics to stable and homogeneous functional states. This dissociation between structural deterioration and functional convergence establishes human organotypic slice cultures as a reproducible and translationally relevant platform for studying human brain network dynamics ex vivo.

neuroscience↗

bioRxiv2026

Polymer-based flexible multi-shank probes for simultaneous intracortical microstimulation and two-photon calcium imaging

Intracortical microstimulation is an essential tool for basic neuroscience and sensory restoration, yet the spatiotemporal effects of advanced multielectrode stimulation strategies on cortical networks remain poorly understood. This study presents a versatile experimental platform featuring polymer-based, flexible multi-shank electrode arrays integrated with a custom high-density neurostimulator. The polyimide penetrating probes contain densely spaced iridium oxide microelectrodes on thin, flexible shanks with sharp tips designed to minimize mechanical mismatch, tissue damage, and brain dimpling. The system was validated in transgenic GCaMP6 mice through simultaneous two-photon calcium imaging and electrical stimulation in layer 2/3 of the visual cortex. Monopolar stimulation reliably evoked robust, parameter-dependent neuronal activation, with neuronal recruitment increasing as a function of current intensity and pulse duration. Bipolar stimulation produced activation patterns distinct from monopolar stimulation, with neuronal responses that were more spatially confined when bipolar electrodes were positioned in close proximity. Furthermore, static current steering--implemented by varying the current ratio between the selected electrode pair--successfully shifted the centroid of activated neuronal populations, enabling fine spatial control over the site of activation. The developed platform provides a flexible framework for investigating local neuronal responses to complex electrical stimulation paradigms, facilitating the development of neural prostheses with higher spatial precision.

neuroscience↗

bioRxiv2025

Local infrared stimulation modulates spontaneous cortical slow wave dynamics in anesthetized rats

Cortical slow waves are hallmark oscillations of deep sleep and certain anesthetic conditions, yet the neurobiological mechanisms controlling their dynamics remain incompletely understood. Here, we investigated the effects of local near-infrared (NIR) stimulation on slow-wave activity in ketamine/xylazine-anesthetized rats. Using a silicon-based multimodal optrode, we simultaneously delivered NIR light and recorded local field potentials (LFPs) and multi-unit activity (MUA) across cortical layers in the primary somatosensory (S1Tr) and parietal association (PtA) cortices. NIR stimulation induced local tissue heating, resulting in reproducible and reversible changes in the properties of slow waves. Specifically, up-state durations were shortened, down-states prolonged, and MUA amplitudes during up-states increased, with steeper slopes at state transitions, indicative of enhanced neuronal synchronization. LFP amplitude and spectral changes varied across cortical regions: PtA exhibited increased slow wave (0.5 - 2 Hz) and high delta (2 - 4 Hz) band activity, while S1Tr showed a trend toward reduction. Our findings demonstrate that local infrared stimulation can reliably modulate cortical slow-wave dynamics, likely through temperature-mediated changes in neuronal excitability. This approach provides a minimally invasive method for precise, local manipulation of cortical network activity and offers new insights into the biophysical regulation of slow oscillations.

neuroscience↗

bioRxiv2025

CoreTIA: a modular, statistically robust transduction inhibition assay for AAV neutralization

Adeno-associated virus (AAV) gene therapy is often limited by pre-existing neutralizing antibodies (NAbs), yet current assays for NAb detection lack standardization and rarely quantify uncertainty, complicating cross-study comparisons. We present coreTIA (core Transduction Inhibition Assay), a modular experimental protocol combined with a statistically robust analysis pipeline that delivers precise, reproducible NAb titers with quantified uncertainty for every result. coreTIAs statistical framework enables robust estimation of neutralization even when dilution series are incomplete, helping to reduce repeat testing and minimizing sample volume requirements. Evaluation and refinement of key assay parameters support consistent performance across AAV serotypes. By providing a protocol and analysis suite as an open resource, coreTIA facilitates more consistent and transparent NAb measurement, potentially aiding assay harmonization and regulatory assessment, addressing a key barrier to progress in gene therapy research and development.

immunology↗

bioRxiv2024

TRPV3 channel activity helps cortical neurons stay active during fever

Fever raises body temperature (Tb) from [~]37 {degrees}C to beyond 38.4 {degrees}C to combat pathogens. While generally well tolerated below 40 {degrees}C, in rare cases fever can abnormally elevate neural activity and induce seizures in neurotypical children aged 2-5 years. This study investigates the mechanisms by which neuronal activity is maintained and stabilized during exposure to fever-range temperatures. Recordings of layer (L)4-evoked spiking in L2/3 pyramidal neurons (PNs) of mouse somatosensory cortex revealed four outcomes as temperature increased from 30{degrees}C to 36 {degrees}C and 39 {degrees}C (fever-range): neurons remained inactive, stayed active, ceased activity, or initiated activity. Roughly equal proportions of neurons ceased or initiated spiking, making the subset of "STAY" PNs, those that remain active across temperatures, crucial for maintaining stable cortical output. STAY PNs were more prevalent at younger postnatal ages. Their firing stability was supported by a distinct ion channel composition, including the thermosensitive channel TRPV3, which enables continued spiking by adjusting depolarization to meet spike threshold. Intracellular blockade of TRPV3, but not TRPV4, significantly reduced the proportion of STAY PNs and suppressed spiking at 39 {degrees}C. Moreover, in Trpv3-/-mice, temperature increases to 39 {degrees}C reduced both spiking and postsynaptic potential amplitude, and these mice exhibited a delayed seizure onset. Together, these findings suggest that TRPV3 contributes to the preservation of cortical activity during fever.

neuroscience↗

bioRxiv2024

Longevity of Implantable Silicon-ICs for Emerging Neural Applications: Evaluation of Bare Die and PDMS-Coated ICs After Accelerated Aging and Implantation Studies

Silicon integrated circuits (ICs) are central to the next-generation miniature active neural implants, whether packaged in soft polymers for flexible bioelectronics or implanted as bare die for neural probes. These emerging applications bring the IC closer to the corrosive body environment, raising reliability concerns, particularly for long-term clinical use. Here, we evaluated the long-term electrical and material stability of silicon-ICs from two foundries, after one-year accelerated in vitro and in vivo animal studies. The ICs featured various custom-designed test structures and were partially PDMS coated, creating two regions on each chip, uncoated "bare die" and "PDMS-coated". During the accelerated in vitro study, ICs were electrically biased and periodically monitored. Results demonstrated stable electrical performance for at least a year, suggesting that bare die ICs can function in the body for months. Despite electrical stability, material analysis revealed chemical and electrically driven degradation of the IC passivation in the bare die regions. In contrast, PDMS-coated regions revealed no such degradation, making PDMS a highly suitable encapsulant for ICs intended for years-long implantation. Based on the new insights, guidelines are proposed that may enhance the longevity of implantable ICs, significantly broadening their applications in the biomedical field.

neuroscience↗

bioRxiv2023

DREDge: robust motion correction for high-density extracellular recordings across species

High-density microelectrode arrays (MEAs) have opened new possibilities for systems neuroscience in human and non-human animals, but brain tissue motion relative to the array poses a challenge for downstream analyses, particularly in human recordings. We introduce DREDge (Decentralized Registration of Electrophysiology Data), a robust algorithm which is well suited for the registration of noisy, nonstationary extracellular electrophysiology recordings. In addition to estimating motion from spikes in the action potential (AP) frequency band, DREDge enables automated tracking of motion at high temporal resolution in the local field potential (LFP) frequency band. In human intraoperative recordings, which often feature fast (period <1s) motion, DREDge correction in the LFP band enabled reliable recovery of evoked potentials, and significantly reduced single-unit spike shape variability and spike sorting error. Applying DREDge to recordings made during deep probe insertions in nonhuman primates demonstrated the possibility of tracking probe motion of centimeters across several brain regions while simultaneously mapping single unit electrophysiological features. DREDge reliably delivered improved motion correction in acute mouse recordings, especially in those made with an recent ultra-high density probe. We also implemented a procedure for applying DREDge to recordings made across tens of days in chronic implantations in mice, reliably yielding stable motion tracking despite changes in neural activity across experimental sessions. Together, these advances enable automated, scalable registration of electrophysiological data across multiple species, probe types, and drift cases, providing a stable foundation for downstream scientific analyses of these rich datasets.

neuroscience↗

bioRxiv2023

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 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.

neuroscience↗

bioRxiv2021

The sleep EEG envelope: a novel, neuronal firing-based human biomarker

Sleep EEG reflects instantaneous voltage differences relative to a reference, while its spectrum reflects the degree to which it is comprised of oscillations at various frequencies. In contrast, the envelope of the sleep EEG reflects the instantaneous amplitude of oscillations at specific frequencies, and its spectrum reflects the rhythmicity of the occurrence of these oscillations. The ordinary sleep EEG and its spectrum have been extensively studied and its individual stability and relationship to various demographic characteristics, psychological traits and pathologies is well known. In contrast, the envelope spectrum has not been extensively studied before. In two studies, we explored the generating mechanisms and utility of studying the envelope of the sleep EEG. First, we used human invasive data from cortex-penetrating microelectrodes and subdural grids to demonstrate that the sleep EEG envelope spectrum reflects local neuronal firing. Second, we used a large database of healthy volunteers to demonstrate that the scalp EEG envelope spectrum is highly stable within individuals, especially in NREM sleep, and that it is affected by age and sex. Multivariate models based on a learning algorithm could predict both age (r=0.6) and sex (r=0.5) with considerable accuracy from the EEG envelope spectrum. With age, oscillations characteristically shifted from a 4-5 second rhythm to higher rhythms. The envelope spectrum was not associated with general cognitive ability (IQ). Our results demonstrate that the sleep envelope spectrum is a promising, neuronal firing-based biomarker of various demographic and disease-related phenotypes.

neuroscience↗

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.

neuroscience↗

bioRxiv2021

Huygens synchronization of medial septal pacemaker neurons generates hippocampal theta oscillation

Episodic learning and memory retrieval are critically dependent on a hippocampal 4-12 Hz oscillatory clock signal, the theta oscillation. This clock is largely externally paced, by a network of GABAergic neurons in the medial septum (MS). Theoretical studies suggested a range of hypotheses how this network may achieve theta synchrony; however, experimental evidence is still lacking. By recording multiple single MS neurons and hippocampal local field potential oscillations simultaneously, with both acute and chronically implanted silicon probes, we show that MS pacemaker units oscillate at individual frequencies within the theta range in rodents. Synchronization of MS neuron frequencies, accompanied by an elevation of firing rates, was found to parallel hippocampal theta formation in multiple rodent model systems. This suggests a general mechanism for theta synchronization, akin to the synchronization of weakly coupled pendulum clocks observed by Huygens in the 17th century. We optogenetically identified the MS pacemaker units as parvalbumin-expressing GABAergic neurons, while the previously enigmatic MS glutamatergic neurons were mostly theta-activated non-rhythmic cells. Our data were consistent with a network model of partially connected single-compartment inhibitory pacemaker neurons, in which synchronization and de-synchronization in the frequency domain upon waxing and waning tonic excitatory drive was sufficient to toggle MS network output between theta and non-theta states. These results provide experimental and theoretical support to a frequency-synchronization mechanism for pacing hippocampal theta, which may serve as an inspirational prototype for the countless examples of synchronization processes in the central nervous system from Nematoda to Anthropoda to Chordate and Vertebrate phyla.

neuroscience↗

bioRxiv2020

Recording site placement on planar silicon-based probes affects neural signal quality: edge sites enhance acute recording performance

ObjectiveMultisite, silicon-based probes are widely used tools to record the electrical activity of neuronal populations. Several physical features of these devices (e.g. shank thickness, tip geometry) are designed to improve their recording performance. Here, our goal was to investigate whether the position of recording sites on the silicon shank might affect the quality of the recorded neural signal in acute experiments. ApproachNeural recordings obtained with five different types of high-density, single-shank, planar silicon probes from anesthetized rats were analyzed. Wideband data were filtered (500 - 5000 Hz) to extract spiking activity, then various quantitative properties (e.g. amplitude distribution of the filtered potential, single unit yield) of the recorded cortical and thalamic activity were compared between sites located at different positions of the silicon shank, focusing particularly on edge and center sites. Main resultsEdge sites outperformed center sites: mean values of the examined properties of the spiking activity were in most cases higher for edge sites (~94%, 33/35) and a large fraction of these differences were also statistically significant (~45%, 15/33) with effect sizes ranging from small to large. Although the single unit yield was similar between site positions, the difference in signal quality was remarkable in the range corresponding to high-amplitude spikes. Furthermore, the advantage of edge sites slightly decreased for probes having a narrower shank. SignificanceThe better signal quality on edge sites might be the result of the reduced shielding effect of the silicon shank providing a larger field of view for edge sites to detect spikes, or the less tissue damage caused near the edges of the shank. Our results might aid the design of novel neural implants in enhancing their recording performance by identifying more efficient recording site placements.

neuroscience↗

bioRxiv2019

The laminar profile of sleep spindles in humans

Sleep spindles are generated in thalamocortical, corticothalamic and possibly cortico-cortical circuits. Previous hypotheses suggested that slow and fast spindles or spindles with various spatial extent may be generated in different circuits with various cortical laminar innervation patterns. We used NREM sleep EEG data recorded from four human epileptic patients undergoing presurgical electrophysiological monitoring with subdural electrocorticographic grids (ECoG) and implanted laminar microelectrodes penetrating the cortex (IME). The position of IME electrodes within cortical layers was confirmed using postsurgical histological reconstructions. Many micro-domain spindles detected on the IME occurred only in one layer and were absent from the ECoG, but with increasing amplitude simultaneous detection in other layers and on the ECoG became more likely. Macro-domain spindles sufficiently large to be detected on the ECoG were in contrast usually accompanied by IME spindles. Neither micro-domain nor macro-domain spindle cortical profiles were strongly associated with sleep spindle frequency or globality. Multiple-unit and single-unit activity during spindles, however, was heterogeneous across spindle types, but also across layers and subjects. Our results indicate that extremely local spindles may occur in any cortical layer, but co-occurrence at other locations becomes likelier with increasing amplitude and the relatively large spindles detected on ECoG channels have a stereotypical laminar profile. We found no compelling evidence that different spindle types are associated with different laminar profiles, suggesting that they are generated in cortical and thalamic circuits with similar cortical innervation patterns. Local neuronal activity is a stronger candidate mechanism for driving functional differences between spindles subtypes.

neuroscience↗

bioRxiv2019

Dissociation of broadband high-frequency activity and neuronal firing in the neocortex

Broadband High-frequency Activity (BHA; 70-150 Hz), also known as \"high gamma,\" a key analytic signal in human intracranial recordings is often assumed to reflect local neural firing (multiunit activity; MUA). Accordingly, BHA has been used to study neuronal population responses in auditory (1,2), visual (3,4), language (5), mnemonic processes (6-9) and cognitive control (10,11). BHA is arguably the electrophysiological measure best correlated with the Blood Oxygenation Level Dependent (BOLD) signal in fMRI (12-13). However, beyond the fact that BHA correlates with neuronal spiking (12, 14-16), the neuronal populations and physiological processes generating BHA are not precisely defined. Although critical for interpreting intracranial signals in human and non-human primates, the precise physiology of BHA remains unknown. Here, we show that BHA dissociates from MUA in primary visual and auditory cortex. Using laminar multielectrode data in monkeys, we found a bimodal distribution of stimulus-evoked BHA across depth of a cortical column: an early-deep, followed by a later-superficial layer response. Only, the early-deep layer BHA had a clear local MUA correlate, while the more prominent superficial layer BHA had a weak or undetectable MUA correlate. In many cases, particularly in V1 (70%), supragranular sites showed strong BHA in lieu of any detectable increase in MUA. Due to volume conduction, BHA from both the early-deep and the later-supragranular generators contribute to the field potential at the pial surface, though the contribution may be weighted towards the late-supragranular BHA. Our results demonstrate that the strongest generators of BHA are in the superficial cortical layers and show that the origins of BHA include a mixture of the neuronal action potential firing and dendritic processes separable from this firing. It is likely that the typically-recorded BHA signal emphasizes the latter processes to a greater extent than previously recognized.

neuroscience↗

bioRxiv2018

Why not record from every channel with a CMOS scanning probe?

It is an uninformative truism to state that the brain operates at multiple spatial and temporal scales, each with each own set of emergent phenomena. More worthy of attention is the point that our current understanding of it cannot clearly indicate which of these phenomenological scales are the significant contributors to the brains function and primary output (i.e. behaviour). Apart from the sheer complexity of the problem, a major contributing factor to this state of affairs is the lack of instrumentation that can simultaneously address these multiple scales without causing function altering damages to the underlying tissue. One important facet of this problem is that standard neural recording devices normally require one output connection per electrode. This limits the number of electrodes that can fit along the thin shafts of implantable probes generating a limiting balance between density and spread. Sharing a single output connection between multiple electrodes relaxes this constraint and permits designs of ultra-high density probes. Here we report the design and in-vivo validation of such a device, a complementary metal-oxide-semiconductor (CMOS) scanning probe with 1344 electrodes; the outcome of the European research project NeuroSeeker. We show that this design targets both local and global spatial scales by allowing the simultaneous recording of more than 1000 neurons spanning 7 functional regions with a single shaft. The neurons show similar recording longevity and signal to noise ratio to passive probes of comparable size and no adverse effects in awake or anesthetized animals. Addressing the data management of this device we also present novel visualization and monitoring methods. Using the probe with freely moving animals we show how accessing a number of cortical and subcortical brain regions offers a novel perspective on how the brain operates around salient behavioural events. Finally, we compare this probe with lower density, non CMOS designs (which have to adhere to the one electrode per output line rule). We show that an increase in density results in capturing neural firing patterns, undetectable by lower density devices, which correlate to self-similar structures inherent in complex naturalistic behaviour. To help design electrode configurations for future, even higher density, CMOS probes, recordings from many different brain regions were obtained with an ultra-dense passive probe.

neuroscience↗

bioRxiv2017

Superficial Slow Rhythms Integrate Cortical Processing in Humans

The neocortex is composed of six anatomically and physiologically specialized layers. It has been proposed that integration of activity across cortical areas is mediated anatomically by associative connections terminating in superficial layers, and physiologically by slow cortical rhythms. However, the means through which neocortical anatomy and physiology interact to coordinate neural activity remains obscure. Using laminar microelectrode arrays in 19 human participants, we found that most EEG activity is below 10-Hz (delta/theta) and generated by superficial cortical layers during both wakefulness and sleep. Cortical surface grid, grid-laminar, and dual-laminar recordings demonstrate that these slow rhythms are synchronous within upper layers across broad cortical areas. The phase of this superficial slow activity is reset by infrequent stimuli and coupled to the amplitude of faster oscillations and neuronal firing across all layers. These findings support a primary role of superficial slow rhythms in generating the EEG and integrating cortical activity.

neuroscience↗