Biology subjects

Forcato, C.

Publications and source records attributed to Forcato, C..

12 recordsLinked to original sources

bioRxiv2026

Closed-loop acoustic stimulation promotes local slow oscillation train initiation and persistence in elderly adults

Slow oscillations (SOs) during non-rapid eye movement (NREM) sleep support memory consolidation and metabolic waste clearance. Aging is associated with reduced SO amplitude and density and disrupted temporal organization, characterized by more isolated events and shorter SO trains. We investigated whether closed-loop acoustic stimulation (CLAS) could enhance the initiation and persistence of rhythmic SO activity in elderly adults. Twenty-seven participants underwent a baseline night followed by an experimental night, during which online-detected SOs were either stimulated using CLAS (STIM; n = 16) or left unstimulated (SHAM; n = 11). We quantified the proportions of isolated and consecutive SOs, train-initiation probability, and SO train length. Analyses assessed local effects around online-detected SOs and global effects across NREM sleep using offline detection. Locally, CLAS reduced the proportion of isolated SOs and increased the proportion of consecutive SOs, train-initiation probability, and mean train length. Global overnight effects were weaker but directionally consistent, primarily reflecting a shift toward longer SO trains. These changes occurred without a significant between-group difference in the change in SO density, and local effects remained significant after adjustment for SO density. Thus, CLAS promoted sustained rhythmic activity beyond changes in SO occurrence. These findings suggest that CLAS can modify the temporal organization of SOs in elderly adults, supporting its potential to mitigate age-related disruptions in SO dynamics. Temporal organization measures may complement conventional amplitude and density measures when evaluating CLAS effects. Further studies should establish whether these changes translate into cognitive benefits or improvements in other aspects of brain health.

neuroscience↗

bioRxiv2026

TARGETED MEMORY REACTIVATION DURING NON-RAPID EYE MOVEMENT SLEEP STRENGTHENS CONSOLIDATED DECLARATIVE MEMORIES

Targeted memory reactivation (TMR) during sleep can benefit recently acquired memories, but whether it can also influence memories after an initial period of consolidation remains unclear. Here, we tested whether auditory reactivation during non-rapid eye movement (NREM) sleep could strengthen declarative memories learned 24 h earlier. Twenty-six healthy young adults learned 30 sound word associations and returned the following day for a 90 min nap. During NREM sleep, participants in the Reactivation group received incomplete reminders consisting of the learned sound followed by the first syllable of the associated word, whereas the No-Reactivation group slept under the same conditions without memory related cues. Participants who received reminders showed significantly less forgetting, despite comparable training performance and sleep macroarchitecture. Across NREM sleep, reactivation was associated with greater slow oscillation and delta power, more slow oscillations and fast spindles, and greater slow oscillation spindle cooccurrence. The memory benefit remained significant after adjusting for NREM physiological measures and in sensitivity analyses restricted to overlapping physiological ranges between groups. Cue locked analyses revealed significant responses in the slow oscillation, delta, theta, and fast-spindle ranges, but the magnitude of these responses was not associated with memory change. These findings show that TMR during NREM sleep can benefit declarative memories after a 24 h consolidation interval and suggest that its effects extend beyond the immediate post-learning sleep period.

neuroscience↗

bioRxiv2026

SLEEP CHANGES WHAT MEMORIES BECOME:DELAYED REACTIVATION REVEALS LATENT EFFECTS OF POST-LEARNING SLEEP

Sleep is thought to promote memory consolidation through the offline reactivation and reorganization of newly acquired information. However, most studies assess memory shortly after sleep, leaving unresolved whether an initial post-learning sleep episode produces enduring modifications that influence how memories respond to later reactivation. Importantly, the absence of behavioral differences after prolonged retention intervals does not necessarily imply that sleep failed to modify the original memory. Instead, sleep-dependent changes may persist in latent forms that are not readily captured by conventional memory assessments. Here, we investigated whether post-learning sleep produces lasting changes in declarative memories that influence their subsequent response to reactivation. In Study 1, participants learned a declarative memory task and were assigned to either a short nap, a wake condition, or an exploratory long-nap condition that included both NREM and REM sleep. Memory was assessed one week later. Despite substantial forgetting across the retention interval, no significant differences in memory performance were observed between groups. In Study 2, participants learned the same task and subsequently underwent either a short nap or wakefulness. Memory was reactivated six days after learning using an incomplete reminder previously shown to induce memory updating in human declarative memory, and memory was tested one day later. Under these conditions, participants who slept after learning showed better memory performance than wake controls. Moreover, sleep physiological measures predicted the magnitude of the post-reactivation memory benefit. These findings suggest that post-learning sleep induces enduring modifications in declarative memories that are not readily detectable through delayed memory testing alone. Instead, these sleep-dependent changes become evident when memories are challenged through subsequent reactivation. Our results indicate that sleep-dependent consolidation influences the future expression of memory, shaping how memories respond to later reactivation experiences and providing new insight into the relationship between consolidation and reconsolidation.

neuroscience↗

bioRxiv2026

Beyond Ground Truth in K-Complex Detection: A Waveform-Based SVM Classifier and the Limits of Expert Agreement

ObjectiveK-complexes (KCs) are large-amplitude EEG events that represent N2 sleep stage and have been linked to sensory gating, sleep protection, and memory consolidation. Their detection remains limited by inter-rater variability in visual scoring and by the reliance of detectors on features that discard temporal information. We propose a two-stage detector that combines a rule-based candidate localization algorithm with a Support Vector Machine (SVM) classifier operating directly on the raw 2-seconds waveform, and we evaluate it against an adjudicated expert consensus of two different datasets. MethodsPolysomnographic recordings from 10 healthy adults (Dataset 1) were independently annotated by two human scorers; discordant events were adjudicated by a senior expert, yielding 240 consensus KCs. The automatic classifier was evaluated using subject-level 10-fold Group K-Fold cross-validation and compared directly against the two human scorers under identical conditions. Cross-dataset generalization was further assessed on the public DREAMS database (Dataset 2) under both external and internal training criteria. ResultsThe SVM classifier achieved the highest F1-score (79.4%) and accuracy (78.8%) among all scorers, with balanced recall (81.7%) and specificity (75.8%). Of the 58 false positives, 42 originated from events both experts had rejected yet displayed canonical KC morphology and received high classifier confidence (P(KC)>0.7 in 45.2% of cases). This pattern was replicated on Dataset 2. ConclusionA waveform-based classifier matches expert performance and systematically flags morphologically valid KCs that fall outside conventional visual-scoring criteria. SignificanceThese findings question the existence of an unambiguous ground truth for KC detection and support a data-driven redefinition of the event boundary, with implications for sleep staging and memory-consolidation research.

bioengineering↗

bioRxiv2025

The hidden phase of memory: EEG signatures of reactivation during post-retrieval rest

AO_SCPLOWBSTRACTC_SCPLOWMemory retrieval reactivates previously encoded representations, allowing for their modification and strengthening. However, the neural processes that follow reactivation and contribute to long-term retention remain poorly understood. Here, we examined the post-retrieval resting period to identify neural markers of memory reactivation and their relation to subsequent memory performance. Participants learned pairs of nonsense syllables in multisensory contexts and, on the following day, received either a cue-syllable reminder (context + cue syllable; RX) or a context-only reminder (RCTX) while EEG activity was recorded before and after the reminder presentation. Both reminders elicited significant reductions in beta power (25-40 Hz) during the post-reminder rest, consistent with memory reactivation. The magnitude of beta decrement correlated with better long-term performance. Graph-theoretical analyses of phase synchronization networks in the beta band revealed that the RCTX reminder produced higher bilateral frontal betweenness centrality, suggesting greater engagement of frontal regions in mediating global information flow when retrieving only contextual cues. Moreover, frontal centrality and network density were predictive of subsequent memory accuracy. These findings demonstrate that memory reactivation extends beyond cue presentation into post-retrieval rest, leaving identifiable oscillatory and topological signatures that influence memory persistence. Our results underscore the crucial role of frontal network dynamics and beta-band activity in facilitating long-term memory.

neuroscience↗

bioRxiv2025

Caffeine increases false alarms in consolidation of face recognition memory

Numerous studies have shown that caffeine facilitates cognition, particularly memory, when consumed before learning and immediately tested. However, most of this evidence relates to its effects during encoding, and the role in memory consolidation remains unclear. A key study demonstrated that caffeine administered after learning can enhance object recognition memory consolidation by improving the discrimination between previously seen targets and similar lures. Here, we investigated the effects of post-encoding caffeine on the consolidation of face recognition memory using a randomized, double-blind design. Participants (N = 104) viewed ten artificially generated faces on Day 1 and then received 200 mg of caffeine or placebo. On Day 2, they completed a recognition task under two conditions: Present condition (original face with five similar distractors) and Absent condition (six similar distractors) adding a "none of the above" option. The results showed that, contrary to our expectation, caffeine consumption did not improve the consolidation of face recognition memory. Instead, it increased False alarm rate in both conditions, reducing the ability to discriminate between previously seen and similar faces. These findings discuss the idea of caffeine as a general cognition enhancer and aligned with studies suggesting it enhances global processing at the expense of detailed discrimination.

neuroscience↗

bioRxiv2025

Structural Connectivity Correlates of Response to Electroconvulsive Therapy in Treatment-Resistant Depression

BackgroundElectroconvulsive therapy (ECT) is the most effective option for treatment resistant depression (TRD). In this study, we sought to explore if structural connectivity of limbic networks has an association with response to ECT. MethodsWe studied 23 patients with TRD who underwent a course of bifrontal ECT, employing probabilistic tractography at baseline to assess structural connectivity between the thalamus (THA), posterior (PCC), subgenual cingulate cortices, anterior insula (aINS), amygdala and orbitofrontal and ventrolateral prefrontal cortices, hypothesizing that these hubs participate in the formation and refractoriness of depression symptoms. We also include 21 healthy subject as controls group (HC). ResultsConnectivity between left THA and left PCC was related to both baseline depression severity (R=0.504; p= 0.017) and clinical response (R=0.452; p=0.004). Right aINS-prefrontal connectivity was associated with less clinical response. Structural connectivity was globally higher in patients than in HC (F=2.488; p=0.007). ConclusionsThe association of ECT response with stronger structural connectivity between hubs supporting self-referential bodily experience as well as autobiographical memory encoding and retrieval deserves exploration as a predictor in persons with TRD. In turn, the right aINS is a major hub for the salience network and is involved in repetitive negative mentation. Stronger structural connectivity of this region may be a heuristically valid biomarker for refractory TRD. We discuss the potential of the present findings for the design of anatomically precise neuromodulation interventions that would be useful to treat TRD while circumventing cognitive side effects of ECT.

neuroscience↗

bioRxiv2025

ELECTROPHYSIOLOGICAL CORRELATES OF CONSCIOUS EXPERIENCES DURING SLEEP: LUCID DREAMS, SLEEP PARALYSIS, OUT-OF-BODY EXPERIENCES, AND FALSE AWAKENINGS

Consciousness does not always fade during sleep. Instead, it can re-emerge, giving rise to lucid dreams (LDs), sleep paralysis (SP), out-of-body experiences (OBEs), and false awakenings (FAs). While some of these states have been studied phenomenologically, their neurophysiological underpinnings remain unclear. Here, we investigate their electrophysiological correlates and distinguish them from standard sleep stages. We conducted overnight polysomnography in frequent experiencers, capturing 10 episodes (3 LDs, 2 SP, 2 OBEs, 3 FAs). Eye movement markers identified periods of lucidity. Relative spectral power was analyzed using principal component analysis (PCA) and permutation-based multivariate analysis of variance (PERMANOVA). Our results indicate that these conscious sleep states are distinct from wakefulness, yet share features with both stage 1 (S1) and rapid eye movement (REM) sleep. Notably, we provide the first documented eye movement markers during FAs and OBEs.

neuroscience↗

bioRxiv2023

Targeted memory reactivation is not more effective during slow wave sleep than sleep stage 2

Sleep facilitates memory consolidation, which is assumed to rely on the reactivation of newly encoded memories orchestrated by the temporal interplay of slow oscillations (SO), fast spindles and ripples. SO as well as the number of spindles coupled to SO are more frequent during slow wave sleep (SWS) compared to lighter sleep stage 2 (S2). But, it is unclear whether memory reactivation is more effective during SWS than during S2. To test this question, we applied Targeted Memory Reactivation (TMR) by presenting learning-associated sound cues during SWS vs. S2 in a counterbalanced within-subject design. Contrary to our hypothesis, memory performance was not significantly better when cues were presented during SWS. Event-related potential (ERP) amplitudes were significantly higher for cues presented during SWS than S2, and the density of SO and SO-spindle complexes was generally higher during SWS than during S2. Whereas SO density increased during and after the TMR period, SO-spindle complexes decreased. None of the parameters were associated with memory performance. These findings suggest that the efficacy of TMR does not depend on whether it is administered during SWS or S2, despite differential processing of memory cues in these sleep stages.

neuroscience↗

bioRxiv2021

Impairment Of Aversive Episodic Memories During COVID-19 Pandemic: The Impact Of Emotional Context On Memory Processes

The threatening context of the COVID-19 pandemic provided a unique setting to study the effects of negative psychological symptoms on memory processes. Episodic memory is an essential function of the human being related to the ability to store and remember experiences and anticipate possible events in the future. Studying this function in this context is crucial to help understand what effects the pandemic will have on the formation of episodic memories. To study this, the formation of episodic memories was evaluated by free recall, recognition, and episode order tasks for an aversive and neutral content. The results indicated that aversive episodic memory is impaired both in the free recall task and in the recognition task. Even the beneficial effect that emotional memory usually has for the episodic order was undermined as there were no differences between the neutral and aversive condition. The present work adds to the evidence that indicates that the level of activation does not modify memory processes in a linear way, which also depends on the type of evocation that people are asked and the characteristics of the content to be encoded.

animal behavior and cognition↗

bioRxiv2021

NON-LINEAR SUSCEPTIBILITY TO INTERFERENCES IN DECLARATIVE MEMORY FORMATION

After encoding, memories go through a labile state followed by a stabilization process known as consolidation. Once consolidated they can enter a new labile state after the presentation of a reminder of the original memory, followed by a period of restabilization (reconsolidation). During these periods of lability the memory traces can be modified. Currently, there are studies that show a rapid stabilization after 30 min, while others show that stabilization occurs after longer periods (e.g. 6 h). Here we investigate the effect of an interference treatment on declarative memory consolidation, comparing distinct time intervals after acquisition. On day 1, participants learned a list of non-syllable pairs (List 1). Immediately after, 30 min, 3 h or 8 h later, they received an interference list (List 2) that acted as an amnesic agent. On day 2 (48 h after training) participants had to recall List 1 first, followed by List 2. We found that the List 1 memory was susceptible to interference when the List 2 was administered immediately or 3 h after learning; however, shortly after acquisition (e.g. 30 min) the List 1 memory becomes transiently protected against interference. We propose the possibility that this rapid memory protection could be induced by a fast and transient neocortical integration (where the memory is transiently protected) becoming partially independent from the hippocampus followed by a hippocampal re-engagement where the memory becomes susceptible to interferences again. Our results open a discussion about the contribution of molecular and systemic aspects to memory consolidation.

neuroscience↗

bioRxiv2021

Positive and Neutral Updating Reconsolidate Aversive Episodic Memories via Different Routes

Aversive memories are long-lasting and prone to have adverse effects on our emotional wellbeing and mental health. Yet, how to remedy the maladaptive effects of aversive memories remains elusive. Using memory reactivation and emotional updating manipulations, we investigated how positive and neutral emotion updates aversive memories for reconsolidation in humans. We found that positive updating after reactivation was equivalent to neutral updating in altering true memories of the aversive story, but introduced more false memory. Moreover, an additional 12 hours of sleep reconsolidation did not further enlarge true memory differences, but attenuated the effect of reactivation and updating on false memory. Interestingly, the neutral rather than the positive updating reduced the emotional arousal of the aversive memory 24 hours later. Our findings provide novel insights into real-world therapeutic applications regarding how updating with positive and neutral emotion may reshape aversive memories, especially when taking wake- and sleep-filled reconsolidation into account.

neuroscience↗