Biology subjects

Sarnthein, J.

Publications and source records attributed to Sarnthein, J..

13 recordsLinked to original sources

bioRxiv2026

Traveling brain waves support flexible storage of human working memory

Human working memory enables us to temporarily store and flexibly utilize information. It is thought that there are two distinct neural mechanisms by which information is retained in working memory: persistent firing of working memory-relevant neurons, or short-term synaptic plasticity in the absence of ongoing neuronal firing. However, both these mechanisms can lead to strong neural interference when working memory contents are updated with novel information. As an alternative, here we propose that information can be flexibly held in working memory in the form of traveling waves - spatiotemporal patterns of neural activity that propagate across brain tissue. In an artificial neural network, we simulated wave propagation by passing transient neural firing patterns representative of single-item information across different network layers. In comparison to sustained neural firing, we demonstrate that these transient traveling waves result in minimal synaptic plasticity, thereby facilitating working memory updating without significant neural interference. We then identified such traveling waves in intracranial recordings from the human temporal lobe. Traveling waves started precisely when information was being encoded and persisted uniformly throughout maintenance and recall, aligning with the activation pattern seen in the artificial neural network. In trials where participants committed memory errors, no such continuous traveling wave activity in the temporal lobe was observed. Our data from artificial neural networks and human intracranial brain recordings converge to indicate that neural traveling waves support information processing in working memory while minimizing interference during updating. This reported mechanism, together with the classical working memory models, serves as a mutually complementary, multi-mechanistic framework for working memory storage.

neuroscience↗

bioRxiv2026

Conjunctive coding of letter pairs emerges in segregated human medial temporal lobe neurons during working memory

Composing individual memory traces into unified representations is fundamental to encoding of structured relationships and flexible cognition. A central debate in neuroscience concerns the neural mechanisms of these compositions: are these compositions encoded through mixed selectivity, where the same neurons simultaneously represent individual and composed items, or through conjunctive coding within a distinct and specialized neuronal population? Here, we tested these competing hypotheses by recording 996 single units from the medial temporal lobe of 11 epilepsy patients performing a letter-string working memory task. We found neural encoding of both single letters and letter pairs during task related periods, with the latter peaking during the maintenance phase. Crucially, letter pairs were encoded by a sparse subset of neurons that did not show significant selectivity for their constituent letters. This suggests the existence of a segregated population of neurons recruited to compose items independently of single letter neural encoding. These findings provide evidence that the human medial temporal lobe separately encodes compositions within segregated neurons, offering direct neurophysiological support for conjunctive coding at the single-neuron level.

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bioRxiv2025

Emotional amnesia in humans with focal temporal pole lesions

Memory is typically better for emotional relative to neutral events, a process involving amygdala modulation of hippocampal activity1-6. These structures, however, form part of a larger emotional brain network, which in humans includes the temporal pole7, a cortical node whose functional role in emotional cognition remains poorly understood8-10. Here, we show, in pharmaco-resistant epilepsy patients performing verbal and visual emotional episodic memory tasks, a selective impairment in recalling verbal emotional memories in left ventral temporal pole (vTP) lesioned patients compared with control patients. Memory for neutral words, and verbal comprehension performance on standard neuropsychological testing, were intact in these patients, indicating absence of general episodic memory or semantic impairment. All patients underwent recordings with intracranial electrodes during memory task performance. Left vTP lesioned patients showed no differences in amygdala or hippocampal electrophysiological responses to emotional words, compared with control patients, putatively isolating a vTP role in emotional memory. Unlike verbal emotional recall, left vTP lesioned patients showed memory enhancement for emotional vs. neutral pictures, whereas two patients with right vTP lesions showed the opposite pattern: impaired memory for emotional pictures but intact verbal emotional memory. These observations establish a critical, lateralized, modality-specific role for human vTP in emotional memory, imply emotional memory deficits in neurological conditions affecting this region, and advance the vTP as a target for neuromodulation in diseases characterized by maladaptive emotional memories.

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bioRxiv2024

A hierarchical coordinate system for sequence memory in human entorhinal cortex.

The entorhinal cortex (EC) supports a coordinate system for spatial memories, organised in a hierarchy along the EC dorso-ventral axis. Recent theories suggest that a similar coordinate system could scaffold non-spatial memories. Here we show that an abstract hierarchical coordinate system supports arbitrary sequence memories in the human medial temporal lobe (MTL). In single-unit recordings from MTL, we find abstract, coordinate-like coding in a simple sequential memory task. In fMRI we find that abstract coordinate representations are arranged hierarchically along the entorhinal cortex, mirroring the anatomical gradient of grid cells in the rodent EC but now for non-spatial sequences. We replicate this finding in an independent cohort of participants. These data suggest that memories are scaffolded on a hierarchical coordinate system aligned to preserved anatomy across domains and species.

neuroscience↗

bioRxiv2024

Encoding seizures with partial synchronization: A spiking neural network for biosignal monitoring on a mixed signal neuromorphic processor

Long-term monitoring of biomedical signals is essential for the modern clinical management of neurological conditions such as epilepsy. However, developing wearable systems that are able to monitor, analyze, and detect epileptic seizures with long-lasting operation times using current technologies is still an open challenge. Brain-inspired spiking neural networks (SNNs) represent a promising signal processing and computing framework as they can be deployed on ultra-low power neuromorphic computing systems, for this purpose. Here, we introduce a novel SNN architecture, co-designed and validated on a mixed-signal neuromorphic chip, that shows potential for always-on monitoring of epileptic activity. We demonstrate how the hardware implementation of this SNN captures the phenomenon of partial synchronization within neural activity during seizure periods. We assess the network using a full-custom asynchronous mixed-signal neuromorphic platform, processing analog signals in real-time from an Electroencephalographic (EEG) seizure dataset. The neuromorphic chip comprises an analog front-end (AFE) signal conditioning stage and an asynchronous delta modulation (ADM) circuit directly integrated on the same die, which can produce the stream of spikes as input to the SNN, directly from the analog EEG signals. We show a linear classifier in a post processing stage that is sufficient to reliably classify and detect seizures, from the local features extracted by the SNN, indicating the feasibility of full on-chip seizure monitoring in the future. This research marks a significant advancement toward developing embedded intelligent "wear and forget" units for resource-constrained environments. These units could autonomously detect and log relevant EEG events of interest in out-of-hospital environments, offering new possibilities for patient care and management of neurological disorders.

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bioRxiv2024

Retrieval of human aversive memories involves reactivation of gamma activity patterns in the hippocampus that originate in the amygdala during encoding

Emotional memories require coordinated activity of the amygdala and hippocampus. Human intracranial recordings have shown that formation of aversive memories involves an amygdala theta-hippocampal gamma phase code. Yet, the mechanisms engaged during translation of aversive experiences into memories and subsequent retrieval remain unclear. Directly recording from human amygdala and hippocampus, here we show that hippocampal gamma activity increases for correctly remembered aversive scenes, while exerting unidirectional oscillatory influence within the theta/beta frequency range on the amygdala for previously seen aversive scenes. Crucially, patterns of amygdala high amplitude gamma activity at encoding are reactivated in the hippocampus, but not amygdala, during both aversive encoding and retrieval. Trial-specific hippocampal gamma patterns showing highest representational similarity with amygdala activity at encoding are replayed in the hippocampus during aversive retrieval. This reactivation process occurs against a background of gamma activity that is otherwise decorrelated between encoding and retrieval. Thus, retrieval of aversive memories is hippocampal-centered, with hippocampal activity patterns apparently entrained by the amygdala during encoding.

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bioRxiv2023

Human hippocampal ripples tune cortical responses in uncertain visual contexts

To be able to encode information efficiently, our perceptual system should detect when situations are unpredictable (i.e., informative), and modulate brain dynamics to prepare for encoding. Here we show, with direct recordings from the human hippocampus and visual cortex, that after exposure to unpredictable visual stimulus streams, hippocampal ripple activity increases in frequency and duration prior to stimulus presentation, indicating context and experience-dependent prediction of predictability. Pre-stimulus hippocampal ripples suppress changes in visual (occipital) cortex gamma activity associated with uncertainty, and modulate post-stimulus prediction error gamma responses in higher-level visual (fusiform) cortex to surprising (i.e., unpredicted) stimuli. These results link hippocampal ripples with predictive coding accounts of neuronal message passing--and precision-weighted prediction errors--revealing a mechanism relevant for perceptual synthesis and subsequent memory encoding.

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bioRxiv2022

Auditory prediction hierarchy in the human hippocampus and amygdala

Our brains can extract structure from the environment and form predictions given past sensory experience. Predictive circuits have been identified in wide-spread cortical regions. However, the contribution of subcortical areas, such as the hippocampus and amygdala in the formation of predictions remains under-explored. Here, we hypothesized that the hippocampus would be sensitive to predictability in sound sequences, while the amygdala would be sensitive to unexpected violations of auditory rules. We presented epileptic patients undergoing presurgical monitoring with standard and deviant sounds, in a predictable or unpredictable context. Onsets of auditory responses and unpredictable deviance effects were detected at earlier latencies in the temporal cortex compared to the amygdala and hippocampus. Deviance effects in 1-20 Hz local field potentials were detected in the lateral temporal cortex, irrespective of predictability. The amygdala showed stronger deviance responses in the unpredictable context. Additionally, low frequency deviance responses in the hippocampus (1-8 Hz) were observed in the predictable but not in the unpredictable context. Our results reveal a distributed cortical-subcortical network underlying the generation of auditory predictions, comprising temporal cortex and the hippocampus and amygdala, and suggest that the neural basis of sensory predictions and prediction error signals needs to be extended to subcortical regions.

neuroscience↗

bioRxiv2022

Successful working memory linked to theta connectivity patterns in the hippocampal-entorhinal circuit

Working memory (WM) is the ability to actively maintain information for a short time and is central to human behavior. Rodent studies have proposed that hippocampal-entorhinal communication supports WM maintenance. However, the exact neural mechanisms of this interaction in WM remains unclear in humans. To address these questions, we combined machine learning analyses with intracranial electroencephalography (iEEG) recordings from the hippocampus and the entorhinal cortex (EC) in human participants, who maintained a set of letters in their WM. We found that WM maintenance was accompanied by elevated bidirectional hippocampal-EC information exchange via the theta band (2-8 Hz) and bidirectional cross-region theta-gamma phase-amplitude coupling (PAC). Further decoding analyses showed that the unidirectional inter-regional communication, with both theta oscillations in the hippocampus modulating EC gamma activity and theta band-coordinated information flow from the hippocampus, could decode correct performance at the level of participants. Taken together, our results demonstrate that theta functional coupling in the hippocampal-EC supports the maintenance of WM information via a specific pattern of frequency and direction. This connectivity-based coding could shed light on the neural mechanisms of WM processing. SignificanceRecent studies suggest a role for the hippocampus in working memory. How does the hippocampus coordinate with other brain regions to retain working memory information? The entorhinal cortex (EC) is the main gateway for information between the hippocampus and neocortex. To delineate whether (and how) the hippocampus and the entorhinal cortex interact during working memory and whether such interaction supports successful working memory, we used machine learning analyses of human intracranial EEG recordings while patients performed working memory tasks. Our results suggest that the human hippocampal-EC circuit supports working memory and is maintained in specific connectivity patterns, with a theta band (2-8 Hz)-coordinated unidirectional influence from the hippocampus to the EC. Our findings reveal that dynamic unidirectional interactions within the hippocampal-EC circuit underlie working memory and can contribute to a mechanistic circuit understanding of working memory.

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bioRxiv2021

Information flows from hippocampus to cortex during replay of verbal working memory items.

The maintenance of items in working memory relies on a widespread network of cortical areas and hippocampus where synchronization between electrophysiological recordings reflects functional coupling. We investigated the direction of information flow between auditory cortex and hippocampus while participants heard and then mentally replayed strings of letters in working memory by activating their phonological loop. We recorded LFP from the hippocampus, reconstructed beamforming sources of scalp EEG, and - additionally in 3 participants - recorded from subdural cortical electrodes. When analyzing Granger causality, the information flow was from auditory cortex to hippocampus with a peak in the 4-8 Hz range while participants heard the letters. This flow was subsequently reversed during maintenance while participants maintained the letters in memory. The functional interaction between hippocampus and the cortex and the reversal of information flow provide a physiological basis for the encoding of memory items and their active replay during maintenance.

neuroscience↗

bioRxiv2020

Neuronal firing in the medial temporal lobe reflects human working memory workload, performance and capacity.

2The involvement of the medial temporal lobe (MTL) in working memory is controversially discussed. Critically, it is unclear whether and how the MTL supports performance of working memory. We recorded single neuron firing in 13 epilepsy patients while they performed a visual working memory task. The number of colored squares in the stimulus set determined the workload of the trial. We used the subjects memory capacity (Cowans K) to split them into a low and high capacity group. We found MTL neurons that showed persistent firing during the maintenance period. Firing was higher in the hippocampus for trials with correct compared to incorrect performance. Population firing predicted workload particularly during the maintenance period. Prediction accuracy of single trial activity was strongest for neurons in the entorhinal cortex of low capacity subjects. We provide evidence that low capacity subjects recruit their MTL to cope with an overload of working memory task demands. 1 SignificanceHumans are highly limited in processing multiple objects over a short period of time. The capacity to retain multiple objects in working memory is typically associated with frontal and parietal lobe functioning, even though medial temporal lobe (MTL) neural architecture seems capable to process such information. However, there are conflicting findings from patient, electrophysiological and neuroimaging studies. Here we show for the first time that correct performance, workload and individual performance differences are reflected in separate mechanisms of neural activity within the MTL during maintenance of visual information in working memory. The data suggest that low capacity subjects use the MTL to process the overload of information.

neuroscience↗

bioRxiv2020

Functional synchronization between hippocampal sEEG, parietal ECoG and scalp EEG during a verbal working memory task.

BackgroundThe maintenance of items in working memory (WM) relies on a widespread network of brain areas where synchronization between electrophysiological recordings may reflect functional coupling. While the coupling from hippocampus to scalp EEG is well established, we provide here direct cortical recordings for a fine-grained analysis. MethodsA patient performed a WM task where a string of letters was presented all at once, thus separating the encoding period from the maintenance period. We recorded sEEG from the hippocampus, temporo-parietal ECoG from a 64-contact grid electrode, and scalp EEG. ResultsPower spectral density (PSD) showed a clear task dependence: PSD in the posterior parietal lobe (10 Hz) and in the hippocampus (20 Hz) peaked towards the end of the maintenance period. Inter-area synchronization was characterized by the phase locking value (PLV). WM maintenance enhanced PLV between hippocampal sEEG and scalp EEG specifically in the theta range [6 7] Hz. PLV from hippocampus to parietal cortex increased during maintenance in the [9 10] Hz alpha and the 20 Hz range. When analyzing the information flow to and from auditory cortex by Granger causality, the flow was from auditory cortex to hippocampus with a peak in the [8 18] Hz range while letters were presented, and this flow was subsequently reversed during maintenance, while letters were maintained in memory. ConclusionsThe increased functional interaction between hippocampus and cortex through synchronized oscillatory activity and the directed information flow provide physiological basis for reverberation of memory items during maintenance. This points to a network for working memory that is bound by coherent oscillations involving cortical areas and hippocampus. SIGNIFICANCE STATEMENTHippocampal activity is known for its role in cognitive tasks involving episodic memory or spatial navigation, but its role in working memory and its sensitivity to workload is still under debate. Here, we investigated hippocampal and cortical activity while a subject maintained sets of letters in verbal working memory for a few seconds to guide action. After confirming the coupling between hippocampal oscillations and oscillations on the scalp, we found during maintenance that hippocampal oscillations increased coupling differentially to several areas of cortex by recording directly from the cortex.. During encoding of the letters, information flow was from auditory cortex to hippocampus and subsequently reversed during maintenance, thus providing a physiological basis for memory encoding and maintenance. This demonstrates a network for working memory that is bound by coherent oscillations that underlie the functional connectivity between cortical areas and hippocampus.

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bioRxiv2018

Power spectrum slope and motor function recovery after focal cerebral ischemia in the rat

EEG changes across vigilance states have been observed after ischemic stroke in patients and experimental stroke models, but their relation to functional recovery remains unclear. Here, we evaluate motor function, as measured by single pellet reaching (SPR), as well as local EEG changes in NREM, REM and wakefulness during a 30-day recovery period after middle cerebral artery occlusion (MCAO) or sham surgery in rats. Small cortical infarcts resulted in poor SPR performance and induced widespread changes in EEG spectra in the ipsilesional hemisphere in all vigilance states, without causing major changes in sleep-wake architecture. Ipsilesional 1-4 Hz power was increased after stroke, whereas power in higher frequencies was reduced, resulting in a steeper slope of the power spectrum. Multielectrode array analysis of ipsilesional M1 showed that these spectral changes were present on the microelectrode level throughout M1 and were not related to increased synchronization between electrodes. Spectrum slope was significantly correlated with post-stroke motor function.

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