Biology subjects

McKhann, G. M.

Publications and source records attributed to McKhann, G. M..

18 recordsLinked to original sources

bioRxiv2026

Electrophysiologically Targeted Biopsies Reveal the Transcriptional Landscape of Focal Epilepsy

Up to 30% of patients with epilepsy have intractable seizures, yet the mechanisms of focal ictogenesis remain unclear. Tissue involvement in ictal regions is heterogeneous, with different regions playing distinct roles in ictogenesis, seizure propagation, and resistance to spread. These roles are reflected in electrophysiologic differences between the seizure focus and the ictal penumbra, where evidence of synaptic spread is present but excitatory firing is constrained by largely intact inhibition. Investigation of the disruption of the normal interplay between excitatory and inhibitory activity, thought to underlie ictogenesis across a range of epilepsy etiologies, is limited by network complexity and cellular heterogeneity in human tissue samples. In this study, we relate cellular and molecular alterations to excitatory-inhibitory disruption in network dynamics defined by electrophysiologic features. This work may aid in the identification of clinically relevant tissue biomarkers and support novel preclinical therapeutic approaches for treatment-resistant focal epilepsy disorders. We developed a novel intracranial EEG guided, MRI-localized approach to sample paired biopsies from 11 patients with drug-resistant focal epilepsy with diverse etiologies, which were then studied using single-nucleus RNA sequencing (snRNAseq) and immunohistochemistry (IHC). EEG recorded from stereotactically implanted depth arrays (sEEG) was used to identify regions of epileptic involvement, based on findings from prior simultaneous clinical and microelectrode recordings. This approach addresses the intrinsic heterogeneity due to etiology and cortical architecture through paired, within-patient comparisons. We identified distinct cell-type specific transcriptional signatures that differentiate cellular populations in the seizure focus and ictal penumbra in intractable focal epilepsies. Our findings provide a link between tissue composition and gene expression that correlate with electrographic features in a heterogeneous seizure landscape. Our findings support common pathways of seizure generation and spread that are conserved across disease etiologies. Relative depletion of interneuron populations in the seizure focus supports the hypothesis of disrupted inhibition as a driver of epileptiform activity in the seizure focus. The enrichment of plasticity-associated gene signatures in the penumbra suggests a complex interaction of these regions with the seizure focus, as well as the role of the penumbra in enabling or limiting seizure expansion. This study provides a novel methodology for tissue sampling in epilepsy and uncovers biologically relevant tissue signatures that provide grounds for future work in targeting cellular and molecular alterations present in focal epilepsies.

neuroscience↗

bioRxiv2025

Speaker Identity is Robustly Encoded in Spatial Patterns of Intracranial EEG for Attention Decoding

The human auditory cortex robustly tracks attended speech, yet it remains unclear if speaker identity is encoded in spatial patterns of neural activity independent of temporal dynamics. Here, we demonstrate that the identity of an attended speaker is reliably reflected in distinct, time-invariant spatial activation maps in human intracranial EEG (iEEG). Leveraging these "neural fingerprints", we developed a novel framework for Auditory Attention Decoding (AAD) that shifts from traditional temporal envelope tracking to spatial speaker identification. By decoupling the decoding of "who" is speaking from "when" they are speaking, our modular system achieves state-of-the-art speech extraction, particularly in short time windows (<2 seconds) where temporal models typically fail. Furthermore, we observed a reciprocal shift in neural activity during attentional switches, confirming that these spatial codes dynamically track listener intent. These findings establish that speaker identity is a robust, spatially distributed feature in the auditory cortex, offering a high-speed, complementary mechanism for neuro-steered hearing technologies.

neuroscience↗

bioRxiv2025

Large Language Models Reveal the Neural Tracking of Linguistic Context in Attended and Unattended Multi-Talker Speech

Large language models (LLMs) capture long-range contextual structure in natural language and have recently been shown to align with the human brains contextualized linguistic encoding. This makes them a promising computational probe for studying how context-dependent linguistic information is represented during natural speech perception. Speech perception often occurs in multi-talker environments, where attention must dynamically select among competing streams, yet how contextual information from attended and unattended speech is neurally encoded remains underexplored. Here, we investigate how auditory attention modulates neural tracking of context-dependent linguistic representations using electrocorticography (ECoG) and stereoelectroencephalography (sEEG) recordings from three epilepsy patients engaged in a two-conversation "cocktail party" paradigm. To model neural responses to attended and unattended speech streams, we used contextual word embeddings generated by large language models. We find that LLM-derived features reliably predict brain activity for the attended stream and that contextual information from the unattended stream also contributes to neural prediction. Importantly, these contributions extend beyond low-level acoustic features and shallow syntactic information, and depend on the surrounding linguistic context. Moreover, neural tracking of the unattended stream reflects shorter-range contextual integration than that of the attended stream. Together, these findings indicate that neural responses to speech reflect context-dependent linguistic representations from multiple concurrent speech streams, with attention modulating the depth and timescale of contextual integration. Our results highlight the utility of LLMs for probing higher-level linguistic representations in complex, naturalistic listening environments.

neuroscience↗

bioRxiv2024

An analysis of RNA quality metrics in human brain tissue

Human brain tissue studies have historically used a range of metrics to assess RNA quality. However, few large-scale cross-comparisons of pre-sequencing quality metrics with RNA-seq quality have been published. Here, we analyze how well metrics gathered before RNA sequencing (post-mortem interval (PMI) and RNA integrity number RIN) relate to analyses of RNA quality after sequencing (Percent of counts in Top Ten genes (PTT), 5 bias, and 3 bias) as well as with individual gene counts across the transcriptome. We conduct this analysis across four different human cortical brain tissue collections sequenced with varying library preparation protocols. PMI and RIN have a low inverse correlation, and both PMI and RIN show consistent and opposing correlations with PTT. Unlike PMI, RIN shows strong consistent correlations with measurements of 3 and 5 bias, and RIN also correlates with 3,933 genes across datasets, in comparison to 138 genes for PMI. Neuronal and immune response genes correlate positively and negatively with RIN respectively, suggesting that different gene sets have divergent relationships with RIN in brain tissue. In summary, these analyses suggest that conventional metrics of RNA quality have varying degrees of value, and that PMI has an overall minimal but reproducible effect on RNA quality.

neuroscience↗

bioRxiv2024

Temporal integration in human auditory cortex is predominantly yoked to absolute time, not structure duration

Sound structures such as phonemes and words have highly variable durations. Thus, there is a fundamental difference between integrating across absolute time (e.g., 100 ms) vs. sound structure (e.g., phonemes). Auditory and cognitive models have traditionally cast neural integration in terms of time and structure, respectively, but the extent to which cortical computations reflect time or structure remains unknown. To answer this question, we rescaled the duration of all speech structures using time stretching/compression and measured integration windows in the human auditory cortex using a new experimental/computational method applied to spatiotemporally precise intracranial recordings. We observed significantly longer integration windows for stretched speech, but this lengthening was very small ([~]5%) relative to the change in structure durations, even in non-primary regions strongly implicated in speech-specific processing. These findings demonstrate that time-yoked computations dominate throughout the human auditory cortex, placing important constraints on neurocomputational models of structure processing.

neuroscience↗

bioRxiv2024

Spectral-switching analysis reveals real-time neuronal network representations of concurrent spontaneous naturalistic behaviors in human brain

Despite abundant evidence of functional networks in the human brain, their neuronal underpinnings, and relationships to real-time behavior have been challenging to resolve. Analyzing brain-wide intracranial-EEG recordings with video monitoring, acquired in awake subjects during clinical epilepsy evaluation, we discovered the tendency of each brain region to switch back and forth between 2 distinct power spectral densities (PSDs 2-55Hz). We further recognized that this spectral switching occurs synchronously between distant sites, even between regions with differing baseline PSDs, revealing long-range functional networks that would be obscured in analysis of individual frequency bands. Moreover, the real-time PSD-switching dynamics of specific networks exhibited striking alignment with activities such as conversation and hand movements, revealing a multi-threaded functional network representation of concurrent naturalistic behaviors. Network structures and their relationships to behaviors were stable across days, but were altered during N3 sleep. Our results provide a new framework for understanding real-time, brain-wide neural-network dynamics.

neuroscience↗

bioRxiv2024

Brain-controlled augmented hearing for spatially moving conversations in multi-talker environments

Focusing on a specific conversation amidst multiple interfering talkers presents a significant challenge, especially for the hearing-impaired. Brain-controlled assistive hearing devices aim to alleviate this problem by separating complex auditory scenes into distinct speech streams and enhancing the attended speech based on the listeners neural signals using auditory attention decoding (AAD). Departing from conventional AAD studies that relied on oversimplified scenarios with stationary talkers, we present a realistic AAD task that mirrors the dynamic nature of acoustic settings. This task involves focusing on one of two concurrent conversations, with multiple talkers taking turns and moving continuously in space with background noise. Invasive electroencephalography (iEEG) data were collected from three neurosurgical patients as they focused on one of the two moving conversations. We propose an enhanced brain-controlled assistive hearing system that combines AAD and a binaural speaker-independent speech separation model. The separation model unmixes talkers while preserving their spatial location and provides talker trajectories to the neural decoder to improve auditory attention decoding accuracy. Our subjective and objective evaluations show that the proposed system enhances speech intelligibility and facilitates conversation tracking while maintaining spatial cues and voice quality in challenging acoustic environments. This research demonstrates the potential of our approach in real-world scenarios and marks a significant step towards developing assistive hearing technologies that adapt to the intricate dynamics of everyday auditory experiences. TAKEAWAYS- Brain-controlled hearing device for scenarios with moving conversations in multi-talker settings, closely mimicking real-world listening environments - Developed a binaural speech separation model that separates speech of moving talkers while retaining their spatial locations, enhancing auditory perception and auditory attention decoding - Proposed system enhances speech intelligibility and reduces listening effort in realistic acoustic scenes

neuroscience↗

bioRxiv2024

Glioma-Induced Alterations in Excitatory Neurons are Reversed by mTOR Inhibition

Gliomas are highly aggressive brain tumors characterized by poor prognosis and composed of diffusely infiltrating tumor cells that intermingle with non-neoplastic cells in the tumor microenvironment, including neurons. Neurons are increasingly appreciated as important reactive components of the glioma microenvironment, due to their role in causing hallmark glioma symptoms, such as cognitive deficits and seizures, as well as their potential ability to drive glioma progression. Separately, mTOR signaling has been shown to have pleiotropic effects in the brain tumor microenvironment, including regulation of neuronal hyperexcitability. However, the local cellular-level effects of mTOR inhibition on glioma-induced neuronal alterations are not well understood. Here we employed neuron-specific profiling of ribosome-bound mRNA via RiboTag, morphometric analysis of dendritic spines, and in vivo calcium imaging, along with pharmacological mTOR inhibition to investigate the impact of glioma burden and mTOR inhibition on these neuronal alterations. The RiboTag analysis of tumor-associated excitatory neurons showed a downregulation of transcripts encoding excitatory and inhibitory postsynaptic proteins and dendritic spine development, and an upregulation of transcripts encoding cytoskeletal proteins involved in dendritic spine turnover. Light and electron microscopy of tumor-associated excitatory neurons demonstrated marked decreases in dendritic spine density. In vivo two-photon calcium imaging in tumor-associated excitatory neurons revealed progressive alterations in neuronal activity, both at the population and single-neuron level, throughout tumor growth. This in vivo calcium imaging also revealed altered stimulus-evoked somatic calcium events, with changes in event rate, size, and temporal alignment to stimulus, which was most pronounced in neurons with high-tumor burden. A single acute dose of AZD8055, a combined mTORC1/2 inhibitor, reversed the glioma-induced alterations on the excitatory neurons, including the alterations in ribosome-bound transcripts, dendritic spine density, and stimulus evoked responses seen by calcium imaging. These results point to mTOR-driven pathological plasticity in neurons at the infiltrative margin of glioma - manifested by alterations in ribosome-bound mRNA, dendritic spine density, and stimulus-evoked neuronal activity. Collectively, our work identifies the pathological changes that tumor-associated excitatory neurons experience as both hyperlocal and reversible under the influence of mTOR inhibition, providing a foundation for developing therapies targeting neuronal signaling in glioma.

neuroscience↗

bioRxiv2021

The Spatial Reach of Neuronal Coherence and Spike-field Coupling across the Human Neocortex

Neuronal coherence is thought to be a fundamental mechanism of communication in the brain, where synchronized field potentials coordinate synaptic and spiking events to support plasticity and learning. Although the spread of field potentials has garnered great interest, little is known about the spatial reach of phase synchronization, or neuronal coherence. Functional connectivity between different brain regions is known to occur across long distances, but the locality of coherence within a brain region is understudied. Here we used simultaneous recordings from electrocorticography (ECoG) grids and high-density microelectrode arrays to estimate the spatial reach of neuronal coherence and spike-field coherence (SFC) across frontal, temporal, and occipital cortices during cognitive tasks in humans. We observed the strongest coherence within a 2-3 cm distance from the microelectrode arrays, potentially defining an effective range for local communication. This range was relatively consistent across brain regions, spectral frequencies, and cognitive tasks. The magnitude of coherence showed power law decay with increasing distance from the microelectrode arrays, where the highest coherence occurred between ECoG contacts, followed by coherence between ECoG and deep cortical LFP, and then SFC (i.e., ECoG > LFP > SFC). The spectral frequency of coherence also affected its magnitude. Alpha coherence (8-14 Hz) was generally higher than other frequencies for signals nearest the microelectrode arrays, whereas delta coherence (1-3 Hz) was higher for signals that were farther away. Action potentials in all brain regions were most coherent with the phase of alpha oscillations, which suggests that alpha waves could play a larger, more spatially local role in spike timing than other frequencies. These findings provide a deeper understanding of the spatial and spectral dynamics of neuronal coherence, further advancing knowledge about how activity propagates across the human brain.

neuroscience↗

bioRxiv2021

Human interictal epileptiform discharges are traveling waves reflecting ictal self-organization

Interictal epileptiform discharges (IEDs), also known as interictal spikes, are large intermittent electrophysiological events observed between seizures in patients with epilepsy. Though they occur far more often than seizures, IEDs are less studied, and their relationship to seizures remains unclear. To better understand this relationship, we examined multi-day recordings of microelectrode arrays implanted in human epilepsy patients, allowing us to precisely observe the spatiotemporal propagation of IEDs, spontaneous seizures, and how they relate. These recordings showed that the majority of IEDs are traveling waves, traversing the same path as ictal discharges during seizures, and with a fixed direction relative to seizure propagation. Moreover, the majority of IEDs, like ictal discharges, were bidirectional, with one predominant and a second, less frequent antipodal direction. These results reveal a fundamental spatiotemporal similarity between IEDs and ictal discharges. These results also imply that most IEDs arise in brain tissue outside the site of seizure onset and propagate toward it, indicating that the propagation of IEDs provides useful information for localizing the seizure focus.

neuroscience↗

bioRxiv2021

Single Unit Analysis and Wide-Field Imaging Reveal Alterations in Excitatory andInhibitory Neurons in Glioma

Several studies have attributed the development of tumor-associated seizures to an excitatory-inhibitory imbalance, highlighting the importance of resolving the spatiotemporal interplay of different neuronal populations within the peritumoral microenvironment. We combined methods for microelectrode array recordings and single unit analysis during ictal events with wide-field optical mapping of pyramidal neurons in an ex vivo acute slice model of diffusely infiltrating glioma in Thy1-GCaMP6f mice. This approach allowed for characterization of excitatory and inhibitory populations across an extended peritumoral cortical region. As expected, measures of excitability were increased in tumor-bearing slices compared to control. This was accompanied by marked functional alterations in single units classified as fast-spiking interneurons, including reduced firing, altered timing with respect to excitatory firing, and deficits in surround inhibition. Inhibiting mTOR with AZD8055 reversed these glioma-induced changes to excitatory and inhibitory neuronal populations, suggesting a prominent role for functional mechanisms linked to mTOR activation.

cancer biology↗

bioRxiv2020

Neuroinflammation characterizes the earliest changes in Alzheimer's disease pathology and associated subjective cognitive impairment in adult hydrocephalus biopsies

In an effort to better characterize the transcriptomic changes that accompany early Alzheimers disease (AD) pathology in living patients and correlate with contemporaneous cognitive data, we performed RNA-seq on 106 cortical biopsies that were taken during shunt placement for adult onset hydrocephalus with varying degrees of comorbid AD pathology. A restricted set of genes correlate with AD pathology in these biopsies, and co-expression network analysis demonstrates an evolution from microglial homeostasis to a disease-associated microglial phenotype in conjunction with increasing AD pathologic burden, along with a subset of additional astrocytic and neuronal genes that accompany these changes. Further analysis demonstrates that these correlations are driven by patients that report mild cognitive symptoms, despite similar levels of {beta}-amyloid and tau pathology in comparison to patients who report no cognitive symptoms. Interestingly, downregulation of homeostatic genes and upregulation of disease-associated genes also correlate with microglial plaque invasion and an activated microglial morphology, and this change is not sensitive to cognitive status, suggesting that an initial microglial response to AD pathology is eventually maladaptive. Taken together, these findings highlight a restricted set of microglial and non-microglial genes and suggest that early AD pathology is largely characterized by a loss of homeostatic genes and an activated microglial phenotype that continues to evolve in conjunction with accumulating AD pathology in the setting of subjective cognitive decline.

neuroscience↗

bioRxiv2020

Dual mechanisms of ictal high frequency oscillations in human rhythmic onset seizures

High frequency oscillations (HFOs) recorded from intracranial electrodes during epileptiform discharges are a proposed biomarker of epileptic brain tissue and may also be useful for seizure forecasting, with mixed results. Despite such potential for HFOs, there is limited investigation into the spatial context of HFOs and their relationship to simultaneously recorded neuronal activity. We sought to further understand the biophysical underpinnings of ictal HFOs using unit recordings in the human neocortex and mesial temporal lobe during rhythmic onset seizures. We compare features of ictal discharges in both the seizure core and penumbra (spatial seizure domains defined by multiunit activity patterns). We report differences in spectral features, unit-local field potential coupling, and information theoretic characteristics of HFOs before and after local seizure invasion. Furthermore, we tie these timing-related differences to spatial domains of seizures, showing that penumbral discharges are widely distributed and less useful for seizure localization.

physiology↗

bioRxiv2020

Neuronal firing and waveform alterations through ictal recruitment in humans

AO_SCPLOWBSTRACTC_SCPLOWClinical analyses of neuronal activity during seizures, invariably using extracellular recordings, is greatly hindered by various phenomena that are well established in animal studies: changes in local ionic concentration, changes in ionic conductance, and intense, hypersynchronous firing. The first two alter the action potential waveform, whereas the third increases the "noise"; all three factors confound attempts to detect and classify single neurons (units). To address these analytical difficulties, we developed a novel template-matching based spike sorting method, which enabled identification of 1,239 single units in 27 patients with intractable focal epilepsy, that were tracked throughout multiple seizures. These new analyses showed continued neuronal firing through the ictal transition, which was defined as a transient period of intense tonic firing consistent with previous descriptions of the ictal wavefront. After the ictal transition, neurons displayed increased spike duration (p < 0.001) and reduced spike amplitude (p < 0.001), in keeping with prior animal studies; units in non-recruited territories, by contrast, showed more stable waveforms. All units returned to their pre-ictal waveforms after seizure termination. Waveshape changes were stereotyped across seizures within patients. Our analyses of single neuron firing patterns, at the ictal wavefront, showed widespread intense activation, and commonly involving marked waveshape alteration. We conclude that the distinction between tissue that has been recruited to the seizure versus non-recruited territories is evident at the level of single neurons, and that increased waveform duration and decreased waveform amplitude are hallmarks of seizure invasion that could be used as defining characteristics of local recruitment. SO_SCPLOWIGNIFICANCEC_SCPLOW SO_SCPLOWTATEMENTC_SCPLOWAnimal studies consistently show marked changes in action potential waveform during epileptic discharges, but acquiring similar evidence in humans has proved difficult. Assessing neuronal involvement in ictal events is pivotal to understanding seizure dynamics and in defining clinical localization of epileptic pathology. Using a novel method to track neuronal firing, we analyzed microelectrode array recordings of spontaneously occurring human seizures, and here report two dichotomous activity patterns. In cortex that is recruited to the seizure, neuronal firing rates increase and waveforms become longer in duration and shorter in amplitude, while penumbral tissue shows stable action potentials, in keeping with the "dual territory" model of seizure dynamics.

neuroscience↗

bioRxiv2019

A theoretical model for focal seizure initiation, propagation, termination, and progression

We developed a neural network model that can account for the major elements common to human focal seizures. These include the tonic-clonic transition, slow advance of clinical semiology and corresponding seizure territory expansion, widespread EEG synchronization, and slowing of the ictal rhythm as the seizure approaches termination. These were reproduced by incorporating usage-dependent exhaustion of inhibition in an adaptive neural network that receives global feedback inhibition in addition to local recurrent projections. Our model proposes mechanisms that may underline common EEG seizure onset patterns and status epilepticus and postulates a role for synaptic plasticity in emergence of epileptic foci. Complex patterns of seizure activity and bi-stable seizure evolution end-points arise when stochastic noise is included. With the rapid advancement of clinical and experimental tools, we believe that this can provide a roadmap and potentially a testbed for future explorations of seizure mechanisms and clinical therapies.

neuroscience↗

bioRxiv2019

Risk of Seizures Induced by Intracranial Research Stimulation: Analysis of 770 Stimulation Sessions

BackgroundPatients with medically refractory epilepsy often undergo intracranial electroencephalography (iEEG) monitoring to identify a seizure focus and determine their candidacy for surgical intervention. This clinically necessary monitoring period provides an increasingly utilized research opportunity to study human neurophysiology, however, ethical concerns demand a thorough appreciation of the associated risks.\n\nObjectiveWe measured the incidence of research stimulation-associated seizures in a large multi-institutional study on brain stimulations effect on memory in order to determine if brain stimulation was statistically associated with seizure incidence, and identify potential risk factors for stimulation-associated seizures.\n\nMethods188 subjects undergoing iEEG monitoring across 10 institutions participated in 770 research stimulation sessions over 3.5 years. Seizures within 30 minutes of a stimulation session were included in our retrospective analysis. We analyzed stimulation parameters, seizure incidence, and typical seizure patterns, to assess the likelihood that recorded seizures were stimulation-induced, rather than events that occurred by chance in epilepsy patients prone to seizing.\n\nResultsIn total, 14 seizures were included in our analysis. All events were single seizures, and no adverse events occurred. The mean amplitude of seizure-associated stimulation did not differ significantly from the mean amplitude delivered in sessions without seizures.\n\nIn order to determine the likelihood that seizures were stimulation induced, we used three sets of analyses: Visual iEEG analysis, statistical frequency, and power analyses. We determined that three of the 14 seizures were likely stimulation-induced, five were possibly stimulation-induced, and six were unlikely stimulation-induced. Overall, we estimate a rate of stimulation-induced seizures between 0.39% and 1.82% of sessions.\n\nConclusionsThe rarity of stimulation-associated seizures, and that none added morbidity or affected the clinical course of any patient, are important findings for understanding the feasibility and safety of intracranial stimulation for research purposes.

neuroscience↗

bioRxiv2018

Functionally distinct high and low theta oscillations in the human hippocampus

Based on rodent models, researchers have theorized that the hippocampus supports episodic memory and navigation via the theta oscillation, a ~4-10-Hz rhythm that coordinates brain-wide neural activity. However, recordings from humans have indicated that hippocampal theta oscillations are lower in frequency and less prevalent than in rodents, suggesting interspecies differences in thetas function. To characterize human hippocampal theta, we examined the properties of theta oscillations throughout the anterior-posterior length of the hippocampus as neurosurgical subjects performed a virtual spatial navigation task. During virtual movement, we observed hippocampal oscillations at multiple frequencies from 2 to 14 Hz. The posterior hippocampus prominently displayed oscillations at ~8-Hz and the precise frequency of these oscillations correlated with the speed of movement, implicating these signals in spatial navigation. We also observed slower ~3-Hz oscillations, but these signals were more prevalent in the anterior hippocampus and their frequency did not vary with movement speed. Our results converge with recent findings to suggest an updated view of human hippocampal electrophysiology. Rather than one hippocampal theta oscillation with a single general role, high-and low-theta oscillations, respectively, may reflect spatial and non-spatial cognitive processes.

neuroscience↗

bioRxiv2018

Single neurons in the human entorhinal cortex remap to distinguish individual spatial memories

The entorhinal cortex (EC) is known to play a key role in both memory and spatial navigation. Despite this overlap in spatial and mnemonic circuits, it is unknown how spatially responsive neurons contribute to our ability to represent and distinguish past experiences. Recording from medial temporal lobe (MTL) neurons in subjects performing cued recall of object-location memories in a virtual-reality environment, we identified \"trace cells\" in the EC that remap their spatial fields to locations subjects were cued to recall on each trial. In addition to shifting its firing field according to the memory cue, this neuronal activity exhibited a firing rate predictive of the cued memorys content. Critically, this memory-specific neuronal activity re-emerged when subjects were cued for recall without entering the environment, indicating that trace-cell memory representations generalized beyond navigation. These findings suggest a general mechanism for memory retrieval via trace-cell activity and remapping in the EC.

neuroscience↗