Biology subjects

Ledergerber, D.

Publications and source records attributed to Ledergerber, D..

7 recordsLinked to original sources

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.

neuroscience↗

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.

neuroscience↗

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↗

bioRxiv2023

Bayesian inference of spike-time dependent learning rules from single neuron recordings in humans

Spike-timing dependent plasticity (STDP) learning rules are popular in both neuroscience and artificial neural networks due to their ability to capture the change in neural connections arising from the correlated activity of neurons. Recent technological advances have made large neural recordings common, substantially increasing the probability that two connected neurons are simultaneously observed, which we can use to infer functional connectivity and associated learning rules. We use a Bayesian framework and assume neural spike recordings follow a binary data model to infer the connections and their evolution over time from data using STDP rules. We test the resulting method on simulated and real data, where the real case study consists of human electrophysiological recordings. The simulated case study allows validation of the model, and the real case study shows that we are able to infer learning rules from awake human data.

neuroscience↗

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

Intrinsic neural timescales in the temporal lobe support an auditory processing hierarchy

During rest, intrinsic neural dynamics manifest at multiple timescales, which progressively increase along visual and somatosensory hierarchies. Theoretically, intrinsic timescales are thought to facilitate processing of external stimuli at multiple stages. However, direct links between timescales at rest and sensory processing, as well as translation to the auditory system are lacking. Here, we used intracranial electroencephalography in humans to show that in the auditory network, intrinsic neural timescales progressively increase, while the spectral slope flattens, from temporal to entorhinal cortex, hippocampus, and amygdala. Within the neocortex, intrinsic timescales exhibit spatial gradients that follow the temporal lobe anatomy. Crucially, intrinsic timescales at rest can explain the latency of auditory responses: as intrinsic timescales increase, so do the single-electrode response onset and peak latencies. Our results suggest that the human auditory network exhibits a repertoire of intrinsic neural dynamics, which manifest in cortical gradients with millimeter resolution and may provide a variety of temporal windows to support auditory processing.

neuroscience↗

bioRxiv2020

Task-dependent mixed selectivity in the subiculum

CA1 and subiculum (SUB) connect the hippocampus to numerous output regions. Cells in both areas have place-specific firing fields, although they are more dispersed in SUB. Weak responses to head direction and running speed have been reported in both regions. However, how such information is encoded in CA1 and SUB, and the resulting impact on downstream targets, is poorly understood. Here we estimate the tuning of simultaneously recorded CA1 and SUB cells to position, head direction, and speed. Individual neurons respond conjunctively to these covariates in both regions but the degree of mixed representation is stronger in SUB, and more so during goal-directed spatial navigation than free foraging. Each navigational variable could be decoded with higher precision, from a similar number of neurons, in SUB than CA1. The findings point to a possible contribution of mixed-selective coding in SUB to efficient transmission of hippocampal representations to widespread brain regions.

neuroscience↗