Biology subjects

Schwabe, L.

Publications and source records attributed to Schwabe, L..

9 recordsLinked to original sources

bioRxiv2026

Glucocorticoids impair memory inference through noradrenergic disruption of GABAergic regulation in hippocampal CA3

The integration of separate memories sharing overlapping elements allows for inferring relationships between events that have never been experienced together. Recent findings indicate that stress impairs this process of mnemonic inference, which may have important implications for stress-related psychopathologies. However, the mechanisms underlying such impairments remain largely unknown. To elucidate the neuroendocrine mechanisms by which stress affects mnemonic inference, mice were first trained on two sets of auditory visual cue associations. Afterwards, one of the visual cues was paired with reward. Mnemonic inference was probed by examining reward seeking behavior in response to the auditory cues alone. Control mice successfully inferred the auditory cue outcome association, selectively seeking reward in response to the auditory cue associated with the rewarded visual cue. In contrast, systemic administration of the stress hormone corticosterone before testing impaired inference accuracy, leading mice to seek reward to both auditory cues. Corticosterone administration was accompanied by increased noradrenergic activity, and stimulation of noradrenergic signaling with yohimbine similarly disrupted inference accuracy. Conversely, the beta adrenoceptor antagonist propranolol prevented the corticosterone induced impairment, indicating that corticosterone effects depend on concurrent noradrenergic activation. At the neural level, the corticosterone induced mnemonic inference impairment was associated with enhanced GABAergic inhibition of pyramidal neurons in the hippocampal CA3 region. Furthermore, hippocampal administration of the GABAA receptor antagonist bicuculline prevented the corticosterone induced impairment in mnemonic inference. Together, these findings identify a glucocorticoid noradrenergic mechanism that disrupts mnemonic inference through enhanced GABAergic inhibition in hippocampal CA3, providing an account of how stress hormones impair inferential memory.

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bioRxiv2025

Task-irrelevant stimuli boost phasic pupil-linked arousal but not memory formation

AO_SCPLOWBSTRACTC_SCPLOWBrainstem arousal systems including the locus coeruleus noradrenaline system, respond transiently to behaviorally relevant events. Locus coeruleus activity also drives dilations of the pupil, which are often observed during cognitive tasks. The strength of pupil responses during encoding of stimulus material predicts the success of its later retrieval, which might reflect the impact of noradrenaline on synaptic plasticity and memory formation. The pupil also dilates in response to task-irrelevant sounds, which could therefore serve as a valuable tool for investigating causal effects of phasic, pupil-linked arousal on cognition. Here, we evaluated whether task-irrelevant white noise sounds affect memory formation and memory-based decisions. These sounds were played before, during or after the presentation of memoranda (images or spoken words). Memory success was measured in recognition and free recall tasks the day after. Trial-to-trial variations in the amplitude of pupil dilations during word encoding without task-irrelevant sounds predicted memory success. Task-irrelevant white-noise sounds also robustly dilated the pupil but did not improve memory formation for the words or the images. We conclude that pupil-linked arousal processes triggered by task-irrelevant sounds differ from those recruited endogenously during memory formation, for example in states of increased emotionality or attention.

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bioRxiv2025

Cortex-wide Dynamics of Internal Decisions About Behavioral Context

Many human decisions manifest in the outside world as motor actions. Correspondingly, neural signals reflecting decision formation are expressed in neural populations encoding the final action. Some decisions, however, are internal, shaping overt behavior indirectly through the selection of policies or rules that guide elementary sensory-motor decisions. We studied the human brain dynamics underlying internal decisions about the stimulus-response mapping rule for reporting visual orientation judgments. The rule changed unpredictably in a hidden fashion, and participants tracked it by accumulating ambiguous sensory cues. Computational model-based decoding of source-level magnetoencephalography data uncovered representations of the internal belief about the active rule in many areas, including occipital cortex. These representations exhibited profiles as predicted by normative models and as observed in action-related frontal areas during overt decisions. We conclude that a widely distributed network of cortical areas implements evidence accumulation for internal decisions, and that even visual cortex may represent high-level beliefs.

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bioRxiv2024

Post-retrieval noradrenergic activation impairs subsequent memory depending on cortico-hippocampal reactivation

When retrieved, seemingly stable memories can become sensitive to significant events, such as acute stress. The mechanisms underlying these memory dynamics remain poorly understood. Here we show that noradrenergic stimulation after memory retrieval impairs subsequent remembering, depending on hippocampal and cortical signals emerging during retrieval. In a three-day study, we measured brain activity using fMRI during initial encoding, 24h-delayed memory cueing followed by pharmacological elevations of glucocorticoid or noradrenergic activity, and final recall. While post-retrieval glucocorticoids did not affect subsequent memory, the impairing effect of noradrenergic arousal on final recall depended on hippocampal reactivation and category-level reinstatement in ventral temporal cortex during memory cueing. These effects did not require a reactivation of the original memory trace and did not interact with offline reinstatement during rest. Our findings demonstrate that, depending on the retrieval-related neural reactivation of memories, noradrenergic arousal after retrieval can alter the future accessibility of consolidated memories.

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bioRxiv2024

Task-irrelevant stimuli reliably boost phasic pupil-linked arousal but do not affect decision formation

The arousal systems of the brainstem, specifically the locus coeruleus-noradrenaline system, respond "phasically" during decisions. These central arousal transients are accompanied by dilations of the pupil. Mechanistic attempts to understand the impact of phasic arousal on cognition would benefit from the ability to experimentally manipulate arousal in a temporally precise manner. Here, we evaluated a non-invasive candidate approach for such a manipulation in humans: presenting task-irrelevant auditory stimuli at different latencies during the execution of a challenging task. Task-irrelevant auditory stimuli drive responses of brainstem nuclei involved in the control of pupil size. But it is unknown whether such sound-evoked responses mimic the central arousal transients evoked during cognitive computations. A large body of evidence has implicated central arousal transients in a bias reduction during challenging perceptual decisions. We thus used challenging visual decisions as a testbed, combining them with task-irrelevant sounds of varying onset latency or duration. Across three experiments, the sounds consistently elicited well-controlled pupil responses that superimposed onto task-evoked responses. While we replicated a negative correlation between task-evoked pupil responses and bias established in previous work, the task-irrelevant sounds had no behavioral effect. This dissociation suggests that cognitive task engagement and task-irrelevant sounds may recruit distinct neural systems contributing to the control of pupil size.

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bioRxiv2023

Causal role of the angular gyrus in insight-driven memory reconfiguration

Maintaining an accurate model of the world relies on our ability to update memory representations in light of new information. Previous research on the integration of new information into memory mainly focused on the hippocampus. Here, we hypothesized that the angular gyrus, known to be involved in episodic memory and imagination, plays a pivotal role in the insight-driven reconfiguration of memory representations. To test this hypothesis, participants received continuous theta burst stimulation (cTBS) over the left angular gyrus or sham stimulation before gaining insight into the relationship between previously separate life-like animated events in a narrative-insight task. During this task, participants also underwent EEG recording and their memory for linked and non-linked events was assessed shortly thereafter. Our results show that cTBS to the angular gyrus decreased memory for the linking events and reduced the memory advantage for linked relative to non-linked events. At the neural level, cTBS targeting the angular gyrus reduced centro-temporal coupling with frontal regions and abolished insight-induced neural representational changes for events linked via imagination, indicating impaired memory reconfiguration. Further, the cTBS group showed representational changes for non-linked events that resembled the patterns observed in the sham group for the linked events, suggesting failed pruning of the narrative in memory. Together, our findings demonstrate a causal role of the left angular gyrus in insight-related memory reconfigurations.

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bioRxiv2021

Prediction errors for aversive events shape long-term memory formation through a distinct neural mechanism

Prediction errors (PEs) have been known for decades to guide associative learning, but their role in episodic memory formation has been discovered only recently. Using an encoding task in which participants learned to predict which stimuli are followed by aversive shocks, combined with univariate, multivoxel, and large-scale network analyses of fMRI data, we show that enhanced memory for events associated with negative PEs was linked to reduced hippocampal responses to PEs and increased crosstalk between the salience network and a frontoparietal network commonly implicated in memory formation for events that are in line with prior expectation. These PE-related effects could not be explained by mere changes in physiological arousal or the prediction itself. Our results suggest that superior memory for events associated with high PEs is driven by a distinct neural mechanism that might serve to set memories of high PE events apart from those with expected outcomes.

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bioRxiv2021

Stress diminishes outcome but enhances response representations during instrumental learning

Stress may shift behavioural control from a goal-directed system that encodes action-outcome relationships to a habit system that learns stimulus-response associations. Although this shift to habits is highly relevant for stress-related psychopathologies, limitations of existing behavioural paradigms hindered previous research to answer the fundamental question of whether the stress-induced bias to habits is due to impaired goal-directed or enhanced habitual processing (or both). Here, we leveraged EEG-based multivariate pattern analysis to decode neural outcome representations, crucial for goal-directed control, and response representations, essential for habitual responding, during instrumental learning. We show that stress reduces outcome representations but enhances response representations, both of which were directly associated with a behavioural index of habitual responding. Further, changes in outcome and response representations were uncorrelated, suggesting that these may reflect distinct processes. Our findings indicate that habit behaviour under stress is the result of both enhanced habitual and diminished goal-directed processing.

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bioRxiv2018

Reading memory formation from the eyes

At any time, we are processing thousands of stimuli, but only few of them will be remembered hours or days later. Is there any way to predict which ones? Here, we show that the pupil response to ongoing stimuli, an indicator of physiological arousal, is a reliable predictor of long-term memory for these stimuli, over at least one day. Pupil dilation was tracked while participants performed visual and auditory encoding tasks. Memory was tested immediately after encoding and 24 hours later. Irrespective of the encoding modality, trial-by-trial variations in pupil dilation predicted which stimuli were recalled in the immediate and 24 hours-delayed tests. These results show that our eyes may provide a window into the formation of long-term memories. Furthermore, our findings underline the important role of central arousal systems in the rapid formation of memories in the brain, possibly by gating synaptic plasticity mechanisms.

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