Biology subjects

Mormann, F.

Publications and source records attributed to Mormann, F..

14 recordsLinked to original sources

bioRxiv2026

Human medial temporal lobe neurons link future reward coding with intertemporal choice and impulsivity

The ability to delay gratification emerges early in life and is linked to long-term health and economic success. Conversely, high impulsivity, marked by a preference for immediate rewards, can be associated with psychiatric disorders. Although processes underlying human delay discounting have been studied at behavioural and macroscopic neural levels, they remain elusive at the single-neuron level. Specifically, it remains unknown how human neurons encode extended reward delays, predict intertemporal choices, and how these processes vary with impulsivity. Here, we record single-neuron activity in the human medial temporal lobe (MTL) to explore decision and delay coding. We identify neurons that predict upcoming decisions in the amygdala and hippocampus. Neurons in the entorhinal cortex and hippocampus encode reward delays, with particularly hippocampal population activity coding prospective temporal periods. Importantly, neuronal activity in impulsive individuals shows diminished prospective temporal coding and predicts decisions only shortly before choices are reported. Our findings reveal how distinct MTL regions contribute to intertemporal decisions and provide insight into the neuronal signatures underlying impulsivity.

neuroscience↗

bioRxiv2026

Sleep ripples drive single-neuron reactivation for human memory consolidation

Sleep transforms fragile experiences into lasting memories, but the neuronal basis of this process in humans has remained elusive. In rodents, hippocampal ripples orchestrate the replay of place cell sequences, establishing a cellular mechanism for consolidation - though with limited generalizability to human memory. In humans, neuroimaging has revealed large-scale offline reactivation, but these coarse signals leave open whether individual neurons are reactivated and how ripples might mediate this process. Here, we bridge this gap by directly recording 1,466 medial temporal lobe (MTL) neurons and intracranial electroencephalography during learning, post-learning wakefulness, and sleep. We show that ripples robustly drive neuronal firing, with sleep ripples eliciting stronger activation than wake ripples. Critically, neurons tuned to items that were later remembered fired more strongly during ripples than those coding for forgotten items, and this memory-linked reactivation was selectively observed during sleep. Finally, ripple-associated neuronal MTL bursts were detectable across widespread cortical activity, pointing to a mechanism for systems-level consolidation. Together, these findings provide the first direct evidence that ripple-driven single-neuron reactivation supports human episodic memory consolidation and reveal why sleep -- compared to wakefulness -- offers a privileged window for stabilizing memories.

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bioRxiv2026

Sequential coupling of sleep oscillations enables concept-neuron reactivation and supports information flow across the human hippocampal-cortical circuit

Effective memory consolidation during sleep is thought to rely on the transfer of reactivated memory traces from the hippocampus to the cortex. However, the mechanisms supporting this essential dialogue across brain areas remain poorly understood. Here, we recorded single-neuron activity (n = 1097) in the medial temporal lobe (MTL) of 10 epilepsy patients across 21 nights of sleep. Before sleep, patients engaged in a memory task with stimuli eliciting concept-neuron responses. During non-rapid eye movement (NREM) sleep, neuronal firing locked to sharp wave-ripples (SWR) revealed a directed flow of information from the hippocampus to cortical targets. Notably, within SWR-driven activity, experience-dependent concept neurons exhibited elevated co-activation both within and across MTL regions, indicating selective reactivation of behaviorally relevant information. Cross-regional co-activation of concept cells was markedly enhanced when hippocampal SWRs coincided with cortical slow oscillation-spindle complexes, suggesting an active role of the cortex in shaping interregional communication. These findings provide evidence that SWRs in humans selectively reactivate experience-related neural ensembles across the hippocampal-cortical network, while synergistic interactions with cortical slow oscillation-spindle events might facilitate effective memory consolidation.

neuroscience↗

bioRxiv2026

Episodic memory consolidation by reactivation of human concept neurons during sleep reflects contents, not sequence of events

How do our brains manage to store our everyday experiences into memory? Neurons in the human temporal lobe that respond to the concept of an individual person or object have been shown to provide the semantic building blocks for episodic memory. Recording from 1433 neurons in neurosurgical patients who learned a story involving specific concepts, we found reactivation of neurons representing these concepts during slow-wave sleep after learning. Concept neurons were conjointly reactivated, particularly during sharp-wave ripples, with time lags suitable for synaptic modification. However, the temporal sequence of reactivation did not reflect the sequence of concepts in the learned story. Unlike rodent place cells, which can acquire preferred firing locations during exploration of new environments according to their pre-existing preferred sequence of activation, human concept neurons are tuned to specific semantic contents before learning starts. Consequently, pre-existing firing sequences correlate with consecutive place fields in rodents, but not with sequences of events in human experience. Thus, in contrast to reactivation of rodent place cells, reactivation of human concept cells does not reflect sequences of events in human experience.

neuroscience↗

bioRxiv2025

Attention modulates hippocampal sharp-wave ripples in humans

Hippocampal sharp-wave ripples (SWRs) are high-frequency events critical for memory consolidation, typically studied during sleep and quiet wakefulness. Emerging evidence suggests that SWRs also occur during active behavior, yet their role in awake cognition remains unclear. Here, we demonstrate that changes in sustained attention modulate both the occurrence of SWRs and their temporal alignment to ongoing hippocampal oscillations. Using intracranial EEG recordings from epilepsy patients performing a sustained attention to response task (SART), we first identified attentional states based on behavioral variability and subjective reports. Next, we observed that SWRs were more frequent during high-attention periods, despite the absence of memory demands. Importantly, SWRs during low-attention periods showed higher phase synchrony with low-frequency oscillations (theta to lower beta) indicating increased endogenous coordination of SWRs under low attentional focus. These findings show that SWRs are dynamically regulated by attentional engagement, supporting a broader role for ripples in active cognitive processing.

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bioRxiv2025

Semantic Tuning of Single Neurons in the Human Medial Temporal Lobe

The Medial Temporal Lobe (MTL) is key to human cognition, supporting memory, emotional processing, navigation, and semantic coding. Rare direct human MTL recordings revealed concept cells, which were proposed as episodic memory building blocks due to their context- and modality-invariant response. However, there is a long-standing debate whether concept cells encode information in a discrete, all-or-none fashion, or as a graded, continuous function of semantic dimensions. To resolve this, we developed a closed-loop protocol that analyzes neuronal spiking in real time and adaptively presents new stimuli based on semantic similarity to response-eliciting previous ones. We found that human concept cells show graded responses, following semantic tuning curves. Furthermore, the tuning width and steepness of MTL neurons vary, with the hippocampus exhibiting the steepest tuning. Regional analysis of these tuning curves yields region-specific categorical response profiles (e.g., food responses in the amygdala). Finally, we show that at the population level, MTL activity is best captured by continuous semantic vector models, which outperform categorical and network-based metrics. Together, these findings establish that concept cells exhibit semantic tuning curves, providing new mechanistic insights into the neural organization of semantic information in the human brain.

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bioRxiv2025

Gamma - Theta - Spike Coupling Coordinates Sequential Memory in Human MTL

It has been suggested that hierarchical synchronization of theta and gamma oscillations coordinates neural activity during sequence memory. Yet, the role of gamma oscillations and their interaction with theta and single-unit activity (SUA) has not been directly examined in humans. We analysed simultaneous micro wire recordings of single-unit activity (N = 1417) and local field potentials (N = 917 channels) from the medial temporal lobe (MTL) of epilepsy patients performing a visual multi-item sequence memory task. During encoding, both spiking activity and gamma power contained item-specific information and were temporally coupled. During memory maintenance, stimulus-specific gamma was characterized by recurring bursts during which spiking was tightly synchronized and both, gamma and spiking, were preferentially aligned to similar theta phases predictive of sequential stimulus position. These findings demonstrate that theta-gamma-spike interactions support a phase-based multiplexed code for sequential memories in the human MTL.

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bioRxiv2024

Region-specific spreading depolarization drives aberrant post-ictal behavior

Confusion, aphasia, and unaware wandering are prominent post-ictal symptoms regularly observed in temporal lobe epilepsy (TLE)1. Despite the potentially life-threatening nature of the immediate post-ictal state2, its neurobiological underpinnings remain understudied3. We provide evidence in mice and humans that seizure-associated focal spreading depolarization (sSD) is a pathoclinical key factor in epilepsy. Using two-photon or widefield imaging (hippocampus, neocortex), field potential and single unit recordings, and behavioral assessment in mice, we first studied seizures during viral encephalitis, and subsequently established an optogenetic approach to dissociate hippocampal seizures and SD. We find region-specific occurrence of sSD that displays distinct spatial trajectories to preceding seizures, and show that seizure-related and isolated hippocampal SD prompt post-ictal wandering. This clinically relevant locomotor phenotype occurred in the absence of hippocampal SD progression to the neocortex. Finally, we confirm sSD existence in human epilepsy, in a patient cohort with refractory focal epilepsy, via Behnke-Fried electrode recordings. In this cohort, sSD displayed a similar temporomesial propensity as in mice. This work uncovers sSD as a previously underrecognized pathoclinical entity underlying postictal behavioral abnormalities in epilepsy. Our results carry wide-reaching ramifications for epilepsy research and neurology, and challenge current EEG-standards.

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bioRxiv2024

Decoding movie content from neuronal population activity in the human medial temporal lobe

The human medial temporal lobe (MTL), a region implicated in memory and high-level cognition, contains neurons that respond selectively to stimuli belonging to specific categories, such as individual people, landmarks, or objects. However, these neurons have been largely studied via static, isolated presentations of stimuli. Therefore, it is unclear how neurons in the MTL respond to rich stimuli such as movies, and which dynamical stimulus features can be retrieved from neuronal population spiking activity. We studied single-unit responses from 2286 neurons recorded from the amygdala, hippocampus, entorhinal cortex, and parahippocampal cortex of 29 intracranially implanted patients during the presentation of an 83-minute movie. We found only a few individual neurons that exhibited a classic selective response to semantic features. However, we successfully decoded the presence of characters, settings, and visual transitions from neuronal population activity. The information relevant for decoding varies across regions depending on the feature category, as visual transitions could be decoded from subsets of neurons with selective responses, whereas character and location features relied on distributed representations. Our results demonstrate an approach for reliably decoding movie features in the human MTL, and suggest that the brain uses a population code when representing character and location features.

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bioRxiv2023

How coupled slow oscillations, spindles and ripples control neuronal processing and communication during human sleep

Learning and plasticity rely on fine-tuned regulation of neuronal circuits during offline periods. An unresolved puzzle is how the sleeping brain - in the absence of external stimulation or conscious effort - controls neuronal firing rates (FRs) and communication within and across circuits, supporting synaptic and systems consolidation. Using intracranial Electroencephalography (iEEG) combined with multiunit activity (MUA) recordings from the human hippocampus and surrounding medial temporal lobe (MTL) areas, we here show that governed by slow oscillation (SO) up-states, sleep spindles set a timeframe for ripples to occur. This sequential coupling leads to a stepwise increase in (i) neuronal FRs, (ii) short-latency cross-correlations among local neuronal assemblies and (iii) cross-regional MTL interactions. Triggered by SOs and spindles, ripples thus establish optimal conditions for spike-timing dependent plasticity and systems consolidation. These results unveil how the coordinated coupling of specific sleep rhythms orchestrates neuronal processing and communication during human sleep.

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bioRxiv2022

Phase of firing does not reflect temporal order in sequence memory of humans and recurrent neural networks

A prominent theory proposes that the temporal order of a sequence of items held in memory is reflected in ordered firing of neurons at different phases of theta oscillations 1. We probe this theory by directly measuring single neuron activity (1420 neurons) and local field potentials (LFP, 921 channels) in the medial temporal lobe of 16 epilepsy patients performing a working memory task for temporal order. We observe theta oscillations and preferential firing of single neurons at theta phase during memory maintenance. We find that - depending on memory performance - phase of firing is related to item position within a sequence. However, in contrast to the theory, phase order did not match item order. To investigate underlying mechanisms, we subsequently trained recurrent neural networks (RNNs) to perform an analogous task. Similar to recorded neural activity, we show that RNNs generate theta oscillations during memory maintenance. Importantly, model neurons exhibit theta phase-dependent firing related to item position, where phase of firing again did not match item order. Instead, we observed a mechanistic link between phase order, stimulus timing and oscillation frequency - a relationship we subsequently confirmed in our neural recordings. Taken together, in both biological and artificial neural networks we provide validating evidence for the role of phase-of-firing in memory processing while at the same time challenging a long-held theory about the functional role of spiking and oscillations in sequence memory.

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bioRxiv2022

A key role of the hippocampal P3 in the attentional blink

The attentional blink (AB) refers to an impaired identification of target stimuli (T2), which are presented shortly after a prior target (T1) within a rapid serial visual presentation (RSVP) stream. It has been suggested that the AB is related to a failed transfer of T2 into working memory and that hippocampus (HC) and entorhinal (EC) cortex are regions crucial for this transfer. Since the event-related P3 component has been linked to inhibitory processes, we hypothesized that the hippocampal P3 elicited by T1 may impact on T2 processing within HC and EC. To test this hypothesis, we reanalyzed microwire data from 21 patients, who performed an RSVP task, during intracranial recordings for epilepsy surgery assessment (Reber et al., 2017). We identified T1-related hippocampal P3 components in the local field potentials (LFPs) and determined the temporal onset of T2 processing in HC/EC based on single-unit response onset activity. In accordance with our hypothesis, T1-related single-trial P3 amplitudes at the onset of T2 processing were clearly larger for unseen compared to seen T2-stimuli. Moreover, increased T1-related single-trial P3 peak latencies were found for T2[unseen] versus T2[seen] trials in case of lags 1 to 3, which was in line with our predictions. In conclusion, our findings support inhibition models of the AB and indicate that the hippocampal P3 elicited by T1 plays a central role in the AB.

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bioRxiv2020

Auditory beat stimulation modulates memory-related single-neuron activity in the human medial temporal lobe

Auditory beats are composed of two sine waves using nearby frequencies, which can either be applied as a superposed signal to both ears or to each ear separately. In the first case, the beat sensation results from hearing an amplitude-modulated signal (monaural beat). In the second case, it is generated by phase-sensitive neurons in the brain stem (binaural beat). We investigated the effects of monaural and binaural 5 Hz beat stimulation on neural activity and memory performance in neurosurgical patients performing an associative recognition task. Previously, we had reported that these beat stimulation conditions modulated memory performance in opposite directions. Here, we analyzed data from a patient subgroup, in which microwires were implanted in the amygdala, hippocampus, entorhinal cortex and parahippocampal cortex. We identified neurons responding with firing rate changes to binaural versus monaural 5 Hz beat stimulation. In these neurons, we correlated the differences in firing rates for binaural versus monaural beats to the memory-related differences for remembered versus forgotten items and associations. In the left hemisphere for these neurons, we detected statistically significant negative correlations between firing rate differences for binaural versus monaural beats and remembered versus forgotten items/associations. Importantly, such negative correlations were also observed between beat stimulation-related firing rate differences in the baseline window and memory-related firing rate differences in the poststimulus windows. In line with concepts of homeostatic plasticity, we interpret our findings as indicating that beat stimulation is linked to memory performance via shifting baseline firing levels.

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bioRxiv2018

Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial EEG (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.

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