Biology subjects

Schulze-Bonhage, A.

Publications and source records attributed to Schulze-Bonhage, A..

16 recordsLinked to original sources

bioRxiv2026

The human hippocampus retroactively binds experiences across time

Creating memories requires linking events across seconds and minutes, but canonical mechanisms of associative plasticity operate over much shorter timescales. This poses a fundamental problem: how can the brain bind information that arrives at different times? Computational model and animal studies implicate the hippocampus in associating events across time, but when the hippocampus becomes engaged and how it interacts with representations of preceding events are unknown. Here we show, using intracranial recordings in humans forming image-word associations across a ~2-s temporal gap, that hippocampal high-frequency activity predicts later memory when the second event arrives, but not during the initial image or intervening delay. At this moment, neurons tuned to the preceding image reinstate stimulus-specific firing despite its sensory absence. Across trials, hippocampal high-frequency activity was selectively coupled to this reinstatement during successful encoding and increased before spiking of image-tuned neurons. These findings reveal a retroactive mode of hippocampal binding, whereby representations of preceding events are recruited when new information arrives. This mechanism provides a neural solution for binding experiences across the temporal discontinuities that characterize everyday life.

neuroscience↗

bioRxiv2025

It's All In The Journey: Putative Strategies Extracted from Navigation Paths Predict Spatial Memory and Hippocampal Recruitment

Navigation in the real world may rely on a multitude of different strategies with distinct advantages and disadvantages. However, the characterization of spontaneous strategy use during wayfinding and underlying neural correlates are scarce. We explore data across three groups of participants who performed a virtual navigation task: (I) epilepsy patients undergoing invasive electrophysiological recordings of the hippocampus, and two groups who underwent fMRI scanning: (II) young adults at genetic risk for Alzheimers disease (APOE-e4 carriers) and (III) healthy controls. We establish three metrics by which to quantitatively characterize each taken path, with the aim of simultaneously reflecting the putative strategies used by humans to solve the task: 1. straightness of paths; 2. deviation towards the edge of the circular arena; and 3. overlap of individual paths leading to a specific object location, which putatively relate to reliance on allocentric (1) and egocentric reference frames (2 & 3). Extracted metrics were related to performance in the task and to hippocampal activity. We find that strategy use is variable within participant, changes across the experiment, and is adaptive in a group-dependent manner. While hippocampal BOLD activity and theta (gamma) power were generally inversely (positively) related, we found that the recruitment of the hippocampus was both group- and strategy- specific. Our results further our understanding of the heterogeneous and idiosyncratic nature of spatial navigation by revealing, how these behaviors are altered by disease and the subsequent compensatory neural dynamics, as well as the link between mesoscopic and macroscopic neural signals.

neuroscience↗

bioRxiv2025

Single-neuron encoding of rapidly learned visual information reshapes human perception

Humans can swiftly learn to recognize visual objects after minimal exposure. Integrating new information with existing knowledge requires forming enduring neuronal representations to enable future recognition. Yet, the neuronal mechanisms in the human brain underlying such rapid perceptual changes remain unclear. We recorded single-neuron activity in occipital (OC) and medial temporal lobe (MTL) regions as participants rapidly learned to recognize degraded images. OC and MTL neurons modulated their activity to encode newly learned visual information and reshape perception. Population decoding revealed that OC neurons required additional processing time to resolve the identity of learned images, delaying neuronal responses in the MTL. Our findings indicate that OC supports recognition after rapid learning via extensive recurrent processing, potentially involving higher-order neocortical areas, without relying on feedback from MTL. These results provide mechanistic constraints for biologically plausible models of visual recognition and few-shot visual learning.

neuroscience↗

bioRxiv2024

A preserved neural code for temporal order between memory formation and recall in the human medial temporal lobe

Temporal memory enables us to remember the temporal order of events happening in our life. The human medial temporal lobe (MTL) appears to contain neural representations supporting temporal memory formation, but the cellular mechanisms that preserve temporal order information for recall are largely unknown. Here, we examined whether human MTL neuronal activity represents the temporal position of events during memory formation and recall, using invasive single and multi-unit recordings in human epilepsy patients (n = 19). Participants freely navigated a virtual environment in order to explore and remember locations and temporal positions of objects. During each exploration period, they sequentially encountered two or three different objects, placed in different locations. This allowed us to examine single- and multi-unit neuronal firing rates (FR) as a function of the temporal position the objects were presented in. We found that a significant number of multi-units and single-units in various MTL regions including the hippocampus showed selectivity to the temporal position of objects during the exploration period. During recall, patients were asked to indicate which one of two objects from the same trial was found latter. Neural firing rates during recall showed a selectivity supporting recall of temporal positions. Interestingly, most of the selective single-units that stayed selective during encoding and recall preserved their temporal position preference. Our results thus suggest that neuronal activity in the human MTL contains a preserved neural code for temporal order in memory formation and recall.

neuroscience↗

bioRxiv2024

Theta-phase locking of single neurons during human spatial memory

The precise timing of single-neuron activity in relation to local field potentials may support various cognitive functions. Extensive research in rodents, along with some evidence in humans, suggests that single-neuron activity at specific phases of theta oscillations plays a crucial role in memory processes. Our fundamental understanding of such theta-phase locking in humans and its dependency on basic electrophysiological properties of the local field potential is still limited, however. Here, using single-neuron recordings in epilepsy patients performing a spatial memory task, we thus aimed at improving our understanding of factors modulating theta-phase locking in the human brain. Combining a generalized-phase approach for frequency-adaptive theta-phase estimation with time-resolved spectral parameterization, our results show that theta-phase locking is a strong and prevalent phenomenon across human medial temporal lobe regions, both during spatial memory encoding and retrieval. Neuronal theta-phase locking increased during periods of elevated theta power, when clear theta oscillations were present, and when aperiodic activity exhibited steeper slopes. Theta-phase locking was similarly strong during successful and unsuccessful memory, and most neurons activated at similar theta phases between encoding and retrieval. Some neurons changed their preferred theta phases between encoding and retrieval, in line with the idea that different memory processes are separated within the theta cycle. Together, these results help disentangle how different properties of local field potentials and memory states influence theta-phase locking of human single neurons. This contributes to a better understanding of how interactions between single neurons and local field potentials may support human spatial memory.

neuroscience↗

bioRxiv2024

Focal cortical dysplasia type II-dependent maladaptive myelination in the human frontal lobe

Focal cortical dysplasias (FCDs) are local malformations of the human neocortex and a leading cause of intractable epilepsy. FCDs are classified into different subtypes including FCD IIa and IIb, characterized by a blurred gray-white matter boundary or a transmantle sign indicating abnormal white matter myelination. Recently, we have shown that myelination is also compromised in the gray matter of FCD IIa of the temporal lobe. Since myelination is key for brain function which is imbalanced in epilepsy, in the current study we investigated myelination in the gray matter of FCD IIa and IIb from the frontal lobe. We found that in particular FCD IIb showed myelination disturbances such as increased numbers of myelinating oligodendrocytes (OLs) and an irregular and disorganized myelination pattern covering an enlarged area in comparison to FCD IIa and controls. Interestingly, both FCD types presented with larger axon diameters when compared to controls. A significant correlation of axon diameter and myelin sheath thickness was found for FCD IIb and controls, whereas in FCD IIa large caliber axons were less myelinated. On the level of gene expression, FCD IIb presented with a significant up-regulation of myelin-associated mRNA synthesis in comparison to FCD IIa and by enhanced binding-capacities of the transcription factor MYRF to promoters of myelin-associated genes reflecting the need for more myelin due to increased axon diameters. These data show that FCD IIa and IIb are characterized by divergent signs of maladaptive myelination which may contribute to the epileptic phenotype. Main pointsO_LIIn the gray matter of the frontal lobe, FCD IIa and FCD IIb are characterized by divergent signs of maladaptive myelination. C_LIO_LIFCD IIa presents with an ordinary radial fiber pattern, but with a reduced thickness of the myelin sheath around large diameter axons and with an attenuation of the myelin synthesis machinery. C_LIO_LIFCD IIb is characterized by an irregular and disorganized myelin fiber pattern, a higher density of myelinating oligodendrocytes and an elevated transcriptional turnover of myelin-associated genes. C_LI

neuroscience↗

bioRxiv2023

Neurons in the human entorhinal cortex map abstract emotion space

When animals move through space, neurons in their entorhinal cortex activate periodically at multiple locations to form a map of the spatial environment. These grid cells may also map non-physical, conceptual spaces to support various other complex behaviors. Here, using intracranial recordings in neurosurgical patients performing an emotional memory task, we find that neurons in the human medial temporal lobe activate in a grid-like pattern across a two-dimensional feature space characterized by emotional valence and arousal. These neurons were different from cells tuned solely to valence or arousal, were preferentially located in the entorhinal cortex, and exhibited theta-phase locking. Our observation of grid-like neuronal activity during emotional processing in humans supports the idea that the neural structure of cognitive maps generalizes beyond spatial navigation.

neuroscience↗

bioRxiv2023

Maintenance and transformation of representational formats during working memory prioritization

Visual working memory depends on both material-specific brain areas in the ventral visual stream (VVS) that support the maintenance of stimulus representations and on regions in prefrontal cortex (PFC) that control these representations. Recent studies identified stimulus-specific working memory contents via representational similarity analysis (RSA) and analyzed their representational format using deep neural networks (DNNs) as models of the multi-layered hierarchy of information processing. How executive control prioritizes relevant working memory contents and whether this affects their representational formats remains an open question, however. Here, we addressed this issue using a multi-item working memory task involving a retro-cue that prompted participants to maintain one particular item. We exploited the excellent spatiotemporal resolution of intracranial EEG (iEEG) recordings in epilepsy patients and analyzed activity at electrodes in VVS (n=28 patients) and PFC (n=16 patients). During encoding, we identified category-specific information in both VVS and PFC. During maintenance, this information re-occurred in VVS but not in the PFC - suggesting a transformation of PFC representations from encoding to maintenance which putatively reflects the prioritization process. We thus applied RSA in combination with different DNN architectures to investigate the representational format of prioritized working memory contents. Representations during the maintenance period matched representations in deep layers of recurrent but not feedforward DNNs, in both VVS and PFC. While recurrent DNN representations matched PFC representations in the beta band following the retro-cue, they corresponded to VVS representations in a lower theta-alpha frequency range (3-14Hz) towards the end of the maintenance period. Findings could be replicated in recurrent DNNs with two different architectures and using two different training sets. Together, these results demonstrate that VWM relies on representational transformations in VVS and PFC that give rise to distinct coding schemes of prioritized contents.

neuroscience↗

bioRxiv2022

Ripple-locked coactivity of stimulus-specific neurons supports human associative memory

Associative memory is the ability to encode and retrieve relations between different stimuli. To better understand its neural basis, we investigated whether associative memory involves precisely timed spiking of neurons in the medial temporal lobes that exhibit stimulus-specific tuning. Using single-neuron recordings from epilepsy patients performing an associative object-location memory task, we identified the object- and place-specific neurons that encoded the separate elements of each memory. When patients encoded and retrieved particular memories, the relevant object- and place-specific neurons activated synchronously during hippocampal ripples. This ripple-locked coactivity of stimulus-specific neurons emerged over time as the patients associative learning progressed. Our results suggest a cellular account of associative memory, in which hippocampal ripples coordinate the activity of specialized cellular populations to facilitate links between stimuli.

neuroscience↗

bioRxiv2022

Comprehensive multiomic profiling of somatic mutations in malformations of cortical development

Malformations of cortical development (MCD) are neurological conditions displaying focal disruption of cortical architecture and cellular organization arising during embryogenesis, largely from somatic mosaic mutations. Identifying the genetic causes of MCD has been a challenge, as mutations remain at low allelic fractions in brain tissue resected to treat epilepsy. Here, we report a genetic atlas from 317 brain resections, identifying 69 mutated genes through intensive profiling of somatic mutations, combining whole-exome and targeted-amplicon sequencing with functional validation and single-cell sequencing. Genotype-phenotype correlation analysis elucidated specific MCD gene sets associating distinct pathophysiological and clinical phenotypes. The unique spatiotemporal expression patterns identified by comparing single-nucleus transcriptional sequences of mutated genes in control and patient brains implicate critical roles in excitatory neurogenic pools during brain development, and in promoting neuronal hyperexcitability after birth.

genetics↗

bioRxiv2020

A learned map for places and concepts in the human MTL

Distinct lines of research in both humans and animals point to a specific role of the hippocampus in both spatial and episodic memory function. The discovery of concept cells in the hippocampus and surrounding medial-temporal lobe (MTL) regions suggests that the MTL maps physical and semantic spaces with a similar neural architecture. Here, we studied the emergence of such maps using MTL micro-wire recordings from 20 patients navigating a virtual environment featuring salient landmarks with established semantic meaning. We present several key findings: The array of local field potentials in the MTL contains sufficient information to decode subjects instantaneous location in the environment. Closer examination revealed that the field potentials represent both the subjects locations in virtual space and in high-dimensional semantic space. We further show that both spatial and semantic representations strengthen over time. This learning effect appears as subjects increase their knowledge of the environments spatial and semantic layout. Similarly, we observe a learning effect on temporal sequence coding. Over time, field potentials come to represent future locations, even after controlling for spatial proximity. This predictive coding of future states, more so than the strength of spatial representations per se, explains variability in subjects navigation performance. Our results thus support the conceptualization of the MTL as a memory space, building semantic knowledge, spatial and non-spatial, from episodic experience to plan future actions and predict their outcomes. Significance statementUsing rare micro-wire recordings, we studied the representation of spatial, semantic and temporal information in the human MTL. Our findings demonstrate that subjects acquire a cognitive map that simultaneously represents the spatial and semantic relations between landmarks. We further show that the same learned representation is used to predict future states, implicating MTL cell assemblies as the building blocks of prospective memory functions.

neuroscience↗

bioRxiv2020

A neural code of egocentric spatial information in human medial temporal lobe

Spatial navigation relies on neural systems that encode information about places, distances, and directions in relation to the external world or relative to the navigating organism. Since the proposal of cognitive maps, the neuroscience of navigation has focused on allocentric (world-referenced) neural representations including place, grid, and head-direction cells. Here, using single-neuron recordings during virtual navigation, we identify "anchor cells" in the human brain as a neural code for egocentric (self-centered) spatial maps: Anchor cells represent egocentric directions towards "anchor points" located in the environmental center or periphery. Anchor cells were abundant in parahippocampal cortex, supported full vectorial representations of egocentric space, and were integrated into a neural memory network. Neurons encoding allocentric direction complemented anchor-cell activity, potentially assisting anchor cells in transforming percepts into allocentric representations. Anchor cells may facilitate egocentric navigation strategies, may support route planning from egocentric viewpoints, and may underlie the first-person perspective in episodic memories.

neuroscience↗

bioRxiv2020

Epidynamics characterize and navigate the map of seizure dynamics

Seizures are a disruption of normal brain activity present across a vast range of species, diseases, and conditions. Here we introduce an organizing principle that leads to the first objective Taxonomy of Seizure Dynamics (TSD) based on bifurcation theory, and applied it to the analysis of EEG data. The "dynamotype" of a seizure is the part of its dynamic composition that defines its observable characteristics, including how it starts, evolves and terminates. Analyzing over 2000 focal-onset seizures recorded from 7 epilepsy centers on five continents, we find evidence of all 16 dynamotypes predicted in TSD. We demonstrate that patients dynamotypes evolve during their lifetime and display complex but systematic variations including hierarchy (certain dynamotypes are more common), non-bijectivity (a patient may display multiple dynamotypes) and pairing preference (multiple dynamotypes may occur during one seizure). TSD not only provides a way to stratify patients in complement to present practical classifications but also guides biophysically based mechanistic approaches and provides a language to describe the most critical features of seizure dynamics. Impact statementTaxonomy of Seizure Dynamics (TSD) provides a rigorous method for classifying and quantifying seizures and a principled framework for understanding seizure initiation and propagation.

bioinformatics↗

bioRxiv2019

Topography, Spectral Characteristics, and Extra-to-Intracranial Propagation Pathways of EMG

ObjectiveIntracranial EEG (iEEG) plays an increasingly important role in neuroscientific research and can provide informative control signal for brain-machine interfaces (BMI). While it is clear that electromyographic (EMG) activity of extracranial origin reaches intracranial recordings, the topographic and spectral characteristics of intracranial EMG have been scarcely investigated. It is currently unclear how these characteristics compare to those of physiological brain activity. Little is also known about the exact pathways of extra- to intracranial volume conduction, including the role of craniotomy defects.\n\nMethodsIn 5 epilepsy patients under invasive pre-neurosurgical EEG monitoring, we examined chewing-related effects (ChREs) as a source of intracranial EMG activity and compared those effects with physiological brain activity of 9 patients during several behavioural tasks. These included speech production, finger movements, and music perception. Further, we analyzed the association of craniotomy defects (burr-holes and saw-lines) and the intracranial EMG-effects based on the individual post-operative images.\n\nResultsChRE presented with a spatially smooth distribution across almost all intracranial electrodes with the maximum below the temporal muscle. In contrast, the responses of neural origin were spatially more focalized. ChREs were broad-banded and had a higher spectral power and affected higher frequencies than event-related neural activity. ChRE were largely independent of the individual configuration of craniotomy defects. However, we found indications that the silicone sheet, in which electrocorticography (ECoG) electrodes are embedded, attenuates EMG influences, when sufficiently large.\n\nConclusionThe present work is the first comprehensive evaluation of topographic and spectral characteristics of EMG effects in iEEG based on a large sample of subjects. It shows that chewing-related EMG can affect iEEG recordings with higher power than typical physiological brain activity, especially in higher spectral frequencies. As the topographic pattern of ChRE is largely independent of the individual position of craniotomy defects, a direct pathway of volume conduction through the intact skull plays an important role for extra- to-intracranial signal propagation. Intracranial EMG activity related to natural behavior should be accounted for in neuroscientific and BMI applications, especially when based on high-frequency iEEG components. A detailed knowledge of EMG properties may help to design both EMG-reducing algorithms and ECoG grids with a high shielding factor.\n\nHighlightsO_LIFirst comprehensive description of chewing-related EMG artifacts in iEEG recordings\nC_LIO_LIEMG artifacts and brain activity have distinct topographic and spectral iEEG characteristics\nC_LIO_LIChewing EMG reaches the brain with higher spectral power than task-related brain activity\nC_LIO_LIChewing-related EMG artifacts are largely independent of the the position of craniotomy defects\nC_LI

neuroscience↗

bioRxiv2018

Reactivated spatial context guides episodic recall

The medial temporal lobe (MTL) is known as the locus of spatial coding and episodic memory, but the interaction between these cognitive domains, as well as the extent to which they rely on common neurophysiological mechanisms is poorly understood. Here, we use a hybrid spatial-episodic memory task to determine how spatial information is dynamically reactivated in sub-regions of the MTL and how this reactivation guides recall of episodic information. Our results implicate theta oscillations across the MTL as a common neurophysiological substrate for spatial coding in navigation and episodic recall. We further show that spatial context information is initially retrieved in the hippocampus (HC) and subsequently emerges in the parahippocampal gyrus (PHG). Finally, we demonstrate that hippocampal theta phase modulates parahippocampal gamma amplitude during retrieval of spatial context, suggesting a role for cross frequency coupling in coding and transmitting retrieved spatial information.

neuroscience↗

bioRxiv2017

Global and Local Dynamics of High-Gamma Activity Underlying Error Processing in the Human Brain Revealed by Noninvasive and Intracranial EEG

Error detection in motor behavior is a fundamental cognitive function heavily relying on cortical information processing. Neural activity in the high-gamma frequency band (HGB) closely reflects such local cortical processing, but little is known about its role in error processing, particularly in the healthy human brain. Here we characterize the error-related response of the human brain based on data obtained with noninvasive EEG optimized for HGB mapping in 31 healthy subjects (15 females, 16 males), and additional intracranial EEG data from 9 epilepsy patients (4 females, 5 males). Our findings reveal a comprehensive picture of the global and local dynamics of error-related HGB activity in the human brain. On the global level as reflected in the noninvasive EEG, the error-related response started with an early component dominated by anterior brain regions, followed by a shift to parietal regions, and a subsequent phase characterized by sustained parietal HGB activity. This phase lasted for more than 1 s after the error onset. On the local level reflected in the intracranial EEG, a cascade of both transient and sustained error-related responses involved an even more extended network, spanning beyond frontal and parietal regions to the insula and the hippocampus. HGB mapping appeared especially well suited to investigate late, sustained components of the error response, possibly linked to downstream functional stages such as error-related learning and behavioral adaptation. Our findings establish the basic spatio-temporal properties of HGB activity as a neural correlate of error processing, complementing traditional error-related potential studies.\n\nSignificance StatementThere is great interest to understand how the human brain reacts to errors in goal-directed behavior. An important index of cortical and subcortical information processing is fast oscillatory brain activity, particularly in the high-gamma band (above 50 Hz). Here we show that it is possible to detect signatures of errors in event-related high-gamma responses with noninvasive techniques, characterize these responses comprehensively, and validate the EEG procedure for the detection of such signals. In addition, we demonstrate the added value of intracranial recordings pinpointing the fine-grained spatio-temporal patterns in error-related brain networks. We anticipate that the optimized noninvasive EEG techniques as described here will be helpful in many areas of cognitive neuroscience where fast oscillatory brain activity is of interest.

neuroscience↗