Biology subjects

Brusco, L. I.

Publications and source records attributed to Brusco, L. I..

7 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

Distinct Multimodal Imaging Correlates of Depression in Middle-Aged Adults With and Without a Family History of Alzheimer Disease

BackgroundDepression is associated with risk for late-onset Alzheimers disease (LOAD), but its underlying pathogenesis in at-risk individuals remains unclear. We examined multimodal imaging correlates of depressive symptoms in cognitively normal middle-aged offspring of patients with LOAD (O-LOAD) compared with control individuals without LOAD history up to a 4th degree of kinship (HC). MethodsParticipants (n=58; 52{+/-}3 years; 74% female) underwent assessment with the Beck Depression Inventory-II (BDI), structural MRI, resting-state fMRI, FDG-PET, and PiB-PET. Resting-state fMRI data were available for 28 O-LOAD and 24 HC; PET data for 24 O-LOAD and 22 HC. General linear models tested associations between imaging measures and BDI, including group interactions. ResultsIn O-LOAD, higher BDI scores were associated with reduced cortical thickness in the left postcentral gyrus. Resting-state fMRI revealed significant group-by-BDI interactions involving cingulate and orbitofrontal networks. In O-LOAD, greater depressive symptom severity was associated with reduced cingulate connectivity across distributed corticolimbic, prefrontal, insular, occipital, and cerebellar regions ({beta} range -0.10 to -0.18). In HC, depressive symptoms were associated with reduced right orbitofrontal and somatosensory-medial orbitofrontal connectivity ({beta}=-0.13), with divergent patterns of cingulate connectivity. FDG-PET showed no significant associations with depressive symptoms. PiB-PET demonstrated regionally specific associations between amyloid signal and BDI in HC, involving an inverse pattern in anterior and posterior insular cortices. ConclusionsDepressive symptoms in middle-aged individuals at familial risk for LOAD are associated with distinct structural and functional alterations, involving circuitry subserving salience and reward, and suggesting early network-level mechanisms linking affective symptoms with vulnerability to neurodegeneration.

neuroscience↗

bioRxiv2025

Dysregulation of energy metabolism and calcium homeostasis in iPSC-derived neurons carrying Presenilin-1 M146L gene mutation

Impaired cellular activities, particularly in highly active cells such as neurons, are primarily supported by metabolic abnormalities and failures in Ca{superscript 2} homeostasis. Here, we provide an integrative analysis of human iPSC-derived neurons (iNs) carrying the Presenilin-1 M146L gene mutation (PS1M146L) and control cells (PS1control). PS1M146L iNs exhibited abnormal Ca{superscript 2} dynamics, a significant increase in key parameters of mitochondrial respiration, and higher intracellular ROS levels. KCl-evoked depolarisation was significantly lower in PS1M146L, suggesting a failure in maintaining the electrochemical gradient across the plasma membrane. Following thapsigargin stimulation, mitochondrial Ca{superscript 2} levels ([Ca{superscript 2}]m) were significantly reduced in PS1M146L, while [Ca{superscript 2}]m did not differ significantly between genotypes after treatment with bradykinin, suggesting that impairments in the [Ca{superscript 2}]m homeostasis are particularly evident under stress conditions and do not impact the 1,4,5-triphosphate (IP3) pathway. Since iNs of both genotypes were sensitive to the MCU-1 inhibitor, the deficits observed in PS1M146L could be the consequence of impairments in the ER-mitochondria contacts. Our results illustrate the utility of iNs carrying PS1 mutations in understanding how human neurons alter relevant pathways before neurodegeneration.

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↗