Episodic Memory Consolidation Research Articles

Spatial localization of hippocampal replay requires dopamine signaling.

Sequenced reactivations of hippocampal neurons called replays, concomitant with sharp-wave ripples in the local field potential, are critical for the consolidation of episodic memory, but whether replays depend on the brain's reward or novelty signals is unknown. Here we combined chemogenetic silencing of dopamine neurons in ventral tegmental area (VTA) and simultaneous electrophysiological recordings in dorsal hippocampal CA1, in freely behaving male rats experiencing changes to reward magnitude and environmental novelty. Surprisingly, VTA silencing did not prevent ripple increases where reward was increased, but caused dramatic, aberrant ripple increases where reward was unchanged. These increases were associated with increased reverse-ordered replays. On familiar tracks this effect disappeared, and ripples tracked reward prediction error, indicating that non-VTA reward signals were sufficient to direct replay. Our results reveal a novel dependence of hippocampal replay on dopamine, and a role for a VTA-independent reward prediction error signal that is reliable only in familiar environments.

How Psychedelics Modulate Multiple Memory Mechanisms in Posttraumatic Stress Disorder.

Posttraumatic stress disorder (PTSD) is a psychiatric disorder with defining abnormalities in memory, and psychedelics may be promising candidates for the treatment of PTSD given their effects on multiple memory systems. Most PTSD and psychedelic research has investigated memory with fear conditioning and extinction. While fruitful, conditioning and extinction provide a limited model of the complexity of PTSD and phenomenology of psychedelics, thereby limiting the refinement of therapies. In this review, we discuss abnormalities in fear conditioning and extinction in PTSD and review 25 studies testing psychedelics on these forms of memory. Perhaps the most reliable effect is that the acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD. However, the post-acute effects may also enhance extinction learning, and the acute effects can also enhance fear conditioning. We then discuss abnormalities in episodic and semantic memory in PTSD and review current knowledge on how psychedelics impact these memory systems. Although PTSD and psychedelics acutely impair the formation of hippocampal-dependent episodic memories, psychedelics may acutely enhance cortical-dependent learning of semantic memories that could facilitate the integration of trauma memories and disrupt maladaptive beliefs. More research is needed on the acute effects of psychedelics on episodic memory consolidation, retrieval, and reconsolidation and post-acute effects of psychedelics on all phases of episodic memory. We conclude by discussing how targeting multiple memory mechanisms could improve upon the current psychedelic therapy paradigm for PTSD, thereby necessitating a greater emphasis on assessing diverse measures of memory in translational PTSD and psychedelic research.

Sleep shapes the associative structure underlying pattern completion in multielement event memory

Sleep supports the consolidation of episodic memory. It is, however, a matter of ongoing debate how this effect is established, because, so far, it has been demonstrated almost exclusively for simple associations, which lack the complex associative structure of real-life events, typically comprising multiple elements with different association strengths. Because of this associative structure interlinking the individual elements, a partial cue (e.g., a single element) can recover an entire multielement event. This process, referred to as pattern completion, is a fundamental property of episodic memory. Yet, it is currently unknown how sleep affects the associative structure within multielement events and subsequent processes of pattern completion. Here, we investigated the effects of post-encoding sleep, compared with a period of nocturnal wakefulness (followed by a recovery night), on multielement associative structures in healthy humans using a verbal associative learning task including strongly, weakly, and not directly encoded associations. We demonstrate that sleep selectively benefits memory for weakly associated elements as well as for associations that were not directly encoded but not for strongly associated elements within a multielement event structure. Crucially, these effects were accompanied by a beneficial effect of sleep on the ability to recall multiple elements of an event based on a single common cue. In addition, retrieval performance was predicted by sleep spindle activity during post-encoding sleep. Together, these results indicate that sleep plays a fundamental role in shaping associative structures, thereby supporting pattern completion in complex multielement events.

Frontal midline theta transcranial alternating current stimulation enhances early consolidation of episodic memory

Evidence implicating theta rhythms in declarative memory encoding and retrieval, together with the notion that both retrieval and consolidation involve memory reinstatement or replay, suggests that post-learning theta rhythm modulation can promote early consolidation of newly formed memories. Building on earlier work employing theta neurofeedback, we examined whether theta-frequency transcranial alternating stimulation (tACS) can engender effective consolidation of newly formed episodic memories, compared with beta frequency stimulation or sham control conditions. We compared midline frontal and posterior parietal theta stimulation montages and examined whether benefits to memory of theta upregulation are attributable to consolidation rather than to retrieval processes by using a washout period to eliminate tACS after-effects between stimulation and memory assessment. Four groups of participants viewed object pictures followed by a free recall test during three study-test cycles. They then engaged in tACS (frontal theta montage/parietal theta montage/frontal beta montage/sham) for a period of 20 min, followed by a 2-h break. Free recall assessments were conducted after the break, 24 h later, and 7 days later. Frontal midline theta-tACS induced significant off-line retrieval gains at all assessment time points relative to all other conditions. This indicates that theta upregulation provides optimal conditions for the consolidation of episodic memory, independent of mental-state strategies.

Acoustic stimulation during slow wave sleep shows delayed effects on memory performance in older adults

IntroductionIn young healthy adults, phase-locked acoustic stimulation (PLAS) during slow wave sleep (SWS) can boost over-night episodic memory consolidation. In older adults, evidence is scarce and available results are inconsistent, pointing toward reduced PLAS-effectiveness. We argue that multiple stimulation nights are required for effects to unfold in older individuals to compensate for age-related reductions in both SWS and memory performance. We test this assumption in a longitudinal within-subject design.MethodsIn a larger previous project, older adults participated in a three-night intervention receiving either real-PLAS (STIM group) or sham-PLAS (SHAM group). Encoding and immediate recall of face-occupation pairs was administered on the evening of the first intervention night (session one), with feedback-based retrievals ensuing on all following mornings and evenings across the intervention. To test for the benefit of the real-PLAS over sham-PLAS intervention within participants, 16 older adults [agemean: 68.9 (SD: 3.7)] were re-invited receiving the real-PLAS intervention exclusively. This resulted in a SHAMSTIM group (n = 9; T1: sham-PLAS intervention, T2: real-PLAS intervention) and a STIMSTIM group (n = 7; T1 and T2: real-PLAS intervention).ResultsWhile the STIMSTIM group exhibited highly similar responses during T1 and T2, the SHAMSTIM group exhibited a significantly higher increase in memory performance at T2 (real-PLAS) compared to T1 (sham-PLAS). These gains can be attributed to the late stages of the experiment, after three nights of real-PLAS, and remained stable when correcting for changes in baseline sleep quality (PSQI) and baseline cognitive ability (Montreal Cognitive Assessment) between T1 and T2.ConclusionsWe show that in older adults, PLAS-induced memory effects are delayed and manifest over the course of a three-night-PLAS intervention. Our results might explain the lack of effects in previous PLAS studies, where memory performance was solely assessed after a single night of PLAS.

Entorhinal cortex-hippocampal circuit connectivity in health and disease.

The entorhinal cortex (EC) and hippocampal (HC) connectivity is the main source of episodic memory formation and consolidation. The entorhinal-hippocampal (EC-HC) connection is classified as canonically glutamatergic and, more recently, has been characterized as a non-canonical GABAergic connection. Recent evidence shows that both EC and HC receive inputs from dopaminergic, cholinergic, and noradrenergic projections that modulate the mnemonic processes linked to the encoding and consolidation of memories. In the present review, we address the latest findings on the EC-HC connectivity and the role of neuromodulations during the mnemonic mechanisms of encoding and consolidation of memories and highlight the value of the cross-species approach to unravel the underlying cellular mechanisms known. Furthermore, we discuss how EC-HC connectivity early neurodegeneration may contribute to the dysfunction of episodic memories observed in aging and Alzheimer's disease (AD). Finally, we described how exercise may be a fundamental tool to prevent or decrease neurodegeneration.

The neural replay mechanisms of episodic memory consolidation under stress in humans

The neural replay mechanisms of episodic memory consolidation under stress in humans

Let's Shape Learning Into Lasting Memories.

Recent experiments in rats and humans have indicated that the effects of non-invasive electrical stimulation are primarily due to transcutaneous stimulation of peripheral nerves, specifically the greater occipital nerve. This stimulation pathway activates communication gateways from the periphery to the brain, impacting memory consolidation. In this invited commentary, I delve into and offer additional insights concerning the enhancement of episodic memory through transcutaneous electrical stimulation of the greater occipital nerve, building upon the findings published by my laboratory in both Science Advances and Elife. Our research on non-invasive transcutaneous electrical stimulation of the greater occipital nerve (NITESGON) has shown to enhance episodic memory consolidation and promote communication between the locus coeruleus (LC) pathway and the hippocampus based on resting connectivity functional MRI. The LC, primarily responsible for releasing noradrenaline and dopamine, plays a crucial role in post-encoding memory stabilization. This suggests that NITESGON can improve memory but does not affect immediate learning. The concept of behavioural tagging, where weak memories can be stabilized through strong or novel events, and how NITESGON activates a memory consolidation through this mechanism are discussed. The role of NITESGON in enhancing memory stabilization is highlighted, providing a non-pharmaceutical solution with minimal side effects. The potential application of NITESGON in neurological conditions, including Alzheimer's disease, attention deficit hyperactivity disorder and post-traumatic stress disorder, is also discussed, emphasizing its promising therapeutic prospects.

Converging diencephalic and hippocampal supports for episodic memory

To understand the neural basis of episodic memory it is necessary to appreciate the significance of the fornix. This pathway creates a direct link between those temporal lobe and medial diencephalic sites responsible for anterograde amnesia. A collaboration with Andrew Mayes made it possible to recruit and scan 38 patients with colloid cysts in the third ventricle, a condition associated with variable fornix damage. Complete fornix loss was seen in three patients, who suffered chronic long-term memory problems. Volumetric analyses involving all 38 patients then revealed a highly consistent relationship between mammillary body volume and the recall of episodic memory. That relationship was not seen for working memory or tests of recognition memory. Three different methods all supported a dissociation between recollective-based recognition (impaired) and familiarity-based recognition (spared). This dissociation helped to show how the mammillary body-anterior thalamic nuclei axis, as well as the hippocampus, is vital for episodic memory yet is not required for familiarity-based recognition. These findings set the scene for a reformulation of temporal lobe and diencephalic amnesia. In this revised model, these two regions converge on overlapping cortical areas, including retrosplenial cortex. The united actions of the hippocampal formation and the anterior thalamic nuclei on these cortical areas enable episodic memory encoding and consolidation, impacting on subsequent recall.

5 Combining Neurophysiology and Behavioral Measures to Identify Biomarkers of Clinical and Preclinical Hippocampus-Dependent Memory Dysfunction

Objective:Memory is a critical piece of the human experience and impairments in neural memory networks can have devastating consequences for the affected person. A subtype of memory, episodic memory generates context for the present based on past experience and allows us to make predictions about the future. Episodic memories become stable fixtures through long-term memory consolidation. It is believed that consolidation of episodic memory requires a dynamic interplay between connected hippocampal-cortical networks, mainly during sleep. Sleep oscillations, slow oscillations and thalamocortical spindles, coupled with hippocampal sharp wave ripples (SWR) is proposed to be mechanistically involved in establishing the crucial cortical-subcortical dialog. The current study aimed to determine alterations in typical sleep oscillations and oscillation coupling in patients with and without structural hippocampal damage and correlate them with neuropsychological measures believed to be sensitive to hippocampal dysfunction, i.e., Rey Auditory Verbal Learning Task (RAVLT) and Verbal Paired Associates (VPA-II).Participants and Methods:We used intracranial electroencephalography (iEEG) in 14 patients with epilepsy to directly record hippocampal and neocortical oscillations and neuropsychological measures obtained prior to implantation. Half of the participants were diagnosed with mesial temporal sclerosis (MTS) in the left hippocampus and healthy tissue in the right hippocampus. The other half did not have MTS and had either mesial temporal epilepsy without MTS or extra-temporal seizures. We analyzed hippocampal SWR output from both hippocampi and characterized neocortical slow oscillations and spindles and their coupling for each participant. We correlated electrophysiological data with behavioral results of neuropsychological testing in order to characterize the clinical relevance.Results:SWR analysis revealed significant differences in the frequency, t(7639) = 15.52, p>.001, p > .001), amplitude, t(7664) = -23.93, p > .001, and waveforms (p > .001) of SWR in the sclerotic versus healthy hippocampi. Patients with a sclerotic hippocampus but relatively preserved verbal memory scores (RAVLT, VPA-II) showed increased SWR amplitudes in the contralateral hippocampus compared to patients with low verbal memory scores. Additionally, we found differences between hemispheres in phase amplitude coupling of SWRs to spindles and SOs (p > 0.001). Results of our correlational analysis were variable and dependent upon additional factors, such as age of onset and diagnosis duration.Conclusions:Results from this work will aid in establishing a criterion for characterizing a relationship between subcortical and cortical oscillations as they relate to memory performance. Besides aiding our understanding of the neural mechanisms underpinning memory consolidation this will ideally help with developing neurophysiological biomarkers that may predict possible memory decline in resective or ablative neurosurgery absent of structural lesion. In addition, this work may potentially provide first evidence of a neurophysiological biomarker directly recorded from the human hippocampus to support possible reorganization of memory functioning in the non-sclerotic hippocampus.

Theta EEG neurofeedback promotes early consolidation of real life-like episodic memory.

Theta oscillations are believed to coordinate neuronal activity related to human cognition, especially for memory functions. Theta power during learning and retrieval has been found to correlate with memory performance success. Additionally, up-regulating theta oscillations during a post-encoding epoch crucial for memory consolidation was previously shown to benefit long-term memory for acquired motor sequences, pictures, and object-location associations. However, it remains to be determined whether such effects would be found for more ecological aspects of long-term episodic memory. Therefore, the current study assessed neurofeedback-based theta upregulation effects on movie memory. After viewing a 15-minute silent, narrative movie, participants engaged in neurofeedback-based theta/beta up-regulation, neurofeedback beta/theta up-regulation as an active control condition, or an unrelated passive control task. Memory was tested three times: once immediately after watching the movie (as baseline); 24 hours thereafter; and once again 1 week later. Memory performance 1 week after encoding was significantly enhanced in the theta/beta up-regulation group compared with the other groups. Additionally, changes in neurofeedback theta/beta ratio from baseline EEG recordings correlated with long-term memory gains in retrieving the movie's content. These findings highlight the relationship between post-learning theta oscillations and the consolidation of episodic memory for a naturalistic event.

0068 Effect of Duchenne muscular dystrophy on sleep-dependent consolidation of episodic memory: Pilot

Abstract Introduction About 50% of patients with Duchenne muscular dystrophy (DMD) exhibit learning and memory deficits. Sleep issues are also common in DMD, and their potential relevance to cognitive deficits is unexplored. In this pilot study, we investigate the effect of DMD on sleep-dependent consolidation of episodic memory, with a focus on the role of sleep-brain dynamics. Methods We studied boys aged 6–15 years who were typically developing (TD) or had DMD. First, we compared memory performance in an episodic memory task during a day of wake versus a night of sleep within subjects (Phase 1, n = 13), including a one-week sleep diary, and parent-rated, memory, and cognitive assessments. In Phase 2, we measured memory improvement in the same task across a night with polysomnography (24 head electrodes). Sleep was scored with AASM criteria. Slow oscillations (SO) (0.5-1.5 Hz) and spindles (10-16Hz) were detected algorithmically, assessing density, amplitude, and coordination. Results In Phase 1, data confirmed sleep-specific gains in memory performance when task difficulty was adjusted to our extended age range (mean accuracy change: 7% sleep, 0% wake). The DMD participant in Phase 1 exhibited worse immediate recall compared to TD peers (independent samples t-test; t(9) = -4.38, p =.02) and worse parent-rated sleep habits (t(9) = 4.01, p = .03 on Children Sleep Health Questionnaire). Phase 2 showed a physiological range of SOs and spindles density, amplitude, and duration in both groups, with potential differences in overall sleep quality. Conclusion This pilot study established the feasibility of a sleep-memory experiment including polysomnography in controls and DMD patients in the context of a pediatric research hospital. Data suggests the need for adaptive recruitment approaches for the DMD population in expanding the study. Sleep EEG analysis suggests the potential for subtle differences in DMD sleep brain dynamics that need to be investigated in a larger sample size. Support (if any) Center for Clinical and Translational Science voucher support to MW and Neurodevelopmental Research Affinity Group Pilot Award to PM

BDNF Val66Met polymorphism is associated with consolidation of episodic memory during sleep

The brain-derived neurotrophic factor (BDNF) is an essential regulator of synaptic plasticity, a candidate neurobiological mechanism underlying learning and memory. A functional polymorphism in the BDNF gene, Val66Met (rs6265), has been linked to memory and cognition in healthy individuals and clinical populations. Sleep contributes to memory consolidation, yet information about the possible role of BDNF in this process is scarce. To address this question, we investigated the relationship between the BDNF Val66Met genotype and consolidation of episodic declarative and procedural (motor) non-declarative memories in healthy adults. The carriers of Met66 allele, as compared with Val66 homozygotes, showed stronger forgetting overnight (24 h after encoding), but not over shorter time (immediately or 20 min after word list presentation). There was no effect of Val66Met genotype on motor learning. These data suggest that BDNF plays a role in neuroplasticity underlying episodic memory consolidation during sleep.

Investigating the effects of sleep and sleep loss on the different stages of episodic emotional memory: A narrative review and guide to the future.

For two decades, sleep has been touted as one of the primary drivers for the encoding, consolidation, retention, and retrieval of episodic emotional memory. Recently, however, sleep’s role in emotional memory processing has received renewed scrutiny as meta-analyses and reviews have indicated that sleep may only contribute a small effect that hinges on the content or context of the learning and retrieval episodes. On the one hand, the strong perception of sleep’s importance in maintaining memory for emotional events may have been exacerbated by publication bias phenomena, such as the “winner’s curse” and “file drawer problem.” On the other hand, it is plausible that there are sets of circumstances that lead to consistent and reliable effects of sleep on emotional memory; these circumstances may depend on factors such as the placement and quality of sleep relative to the emotional experience, the content and context of the emotional experience, and the probes and strategies used to assess memory at retrieval. Here, we review the literature on how sleep (and sleep loss) influences each stage of emotional episodic memory. Specifically, we have separated previous work based on the placement of sleep and sleep loss in relation to the different stages of emotional memory processing: (1) prior to encoding, (2) immediately following encoding during early consolidation, (3) during extended consolidation, separated from initial learning, (4) just prior to retrieval, and (5) post-retrieval as memories may be restructured and reconsolidated. The goals of this review are three-fold: (1) examine phases of emotional memory that sleep may influence to a greater or lesser degree, (2) explicitly identify problematic overlaps in traditional sleep–wake study designs that are preventing the ability to better disentangle the potential role of sleep in the different stages of emotional memory processing, and (3) highlight areas for future research by identifying the stages of emotional memory processing in which the effect of sleep and sleep loss remains under-investigated. Here, we begin the task of better understanding the contexts and factors that influence the relationship between sleep and emotional memory processing and aim to be a valuable resource to facilitate hypothesis generation and promote important future research.

Post-learning caffeine administration improves ‘what-when’ and ‘what-where’ components of episodic-like memory in rats

Episodic-like memory (ELM) consists in the capacity of nonhuman animals to remember ‘where’ and ‘when’ a specific episode occurred (‘what’). Previous studies have showed that Wistar rats can form an ELM, but not after a 24 h retention delay. On the other hand, it has been demonstrated that caffeine can improve episodic memory consolidation in humans. Therefore, we verified whether acute post-sample caffeine administration could improve ELM consolidation in Wistar rats, as well if it could be related to neurochemical changes in the prefrontal cortex and hippocampus – regions related to episodic-like memory processing. 46 Male Wistar Rats, approximately 3 months-old, were divided into four groups as follows: untreated (n = 11), saline (n = 11), caffeine 10 mg ∕kg i.p (n = 12); caffeine 15 mg∕kgi.p (n = 12) and tested in WWWhen/ELM task. The animals treated with caffeine in different dosages (10 mg/kg and 15 mg/kg) discriminated temporally and spatially the objects, respectively. These groups also showed a dopamine renewal rate in the hippocampus, suggesting that there was an increase in the turnover compared with the groups with no caffeine administration. We can conclude that caffeine leads to an improvement in the consolidation of the temporal (‘what-when’) and spatial (‘what-where’) aspects of episodic-like memory.

Slow oscillations promote long-range effective communication: The key for memory consolidation in a broken-down network.

A prominent and robust finding in cognitive neuroscience is the strengthening of memories during nonrapid eye movement (NREM) sleep, with slow oscillations (SOs;<1Hz) playing a critical role in systems-level consolidation. However, NREM generally shows a breakdown in connectivity and reduction of synaptic plasticity with increasing depth: a brain state seemingly unfavorable to memory consolidation. Here, we present an approach to address this apparent paradox that leverages an event-related causality measure to estimate directional information flow during NREM in epochs with and without SOs. Our results confirm that NREM is generally a state of dampened neural communication but reveals that SOs provide two windows of enhanced large-scale communication before and after the SO trough. These peaks in communication are significantly higher when SOs are coupled with sleep spindles compared with uncoupled SOs. To probe the functional relevance of these SO-selective peaks of information flow, we tested the temporal and topographic conditions that predict overnight episodic memory improvement. Our results show that global, long-range communication during SOs promotes sleep-dependent systems consolidation of episodic memories. A significant correlation between peaks of information flow and memory improvement lends predictive validity to our measurements of effective connectivity. In other words, we were able to predict memory improvement based on independent electrophysiological observations during sleep. This work introduces a noninvasive approach to understanding information processing during sleep and provides a mechanism for how systems-level brain communication can occur during an otherwise low connectivity sleep state. In short, SOs are a gating mechanism for large-scale neural communication, a necessary substrate for systems consolidation and long-term memory formation.

Acquisition and consolidation of verbal learning and episodic memory as predictors of the conversion from mild cognitive impairment to probable Alzheimer’s disease

ABSTRACT Verbal episodic memory tests assess memory performance using total learning scores. The analysis of inter-trial indices such as gained (GA) and lost (LA) access can provide additional information on the acquisition and consolidation processes. The main objetive was to determine whether the GA and LA indices, derived from a word-list verbal episodic memory test are useful for predicting cognitive impairment in aging. 60 older people aged was divided into 3 groups: cognitively healthy, stable Mild Cognitive Impairment (MCI) and MCI converting to probable Alzheimer's disease (MCI-conv). The results showed that GA and LA measures are independent from the traditional measures -total score of correct answers-. Logistic regression showed that these values are predictive of the conversion over time and could be a cognitive marker of conversion from MCI to AD. This suggests that the GA index, which shows acquisition processes in word-list tests, may be a marker of cognitive impairment.

The role of sleep for episodic memory consolidation: Stabilizing or rescuing?

Prior studies suggest a role for sleep in memory consolidation, with specific contributions from slow oscillations and sleep spindles (Rasch & Born, 2013). However, recent studies failed to replicate sleep’s superiority over wake in strengthening memory against interference (Cordi & Rasch, 2021). The goal of the current study is to investigate whether sleep protects newly formed memory from unspecific interference induced by daytime experiences over 24 h, as well as to elucidate the sleep features that are involved. 56 healthy adults were randomly assigned to either the Sleep First or Wake First group. The Sleep First group encoded word pairs at night before sleep, while the Wake First group encoded word pairs in the morning before a day of wakefulness. Memory was tested 30 min, 12 h, and 24 h after encoding for both groups. The Sleep First group performed significantly better 12 h after encoding, replicating prior findings that memory is better after a period of sleep compared to wake. However, after 24 h, the two groups performed similarly. The Wake First group showed a positive correlation between overnight memory improvement and the theta and delta band power during slow wave sleep, an effect not found in the Sleep First group. These correlations suggest the possibility that after a day of waking interference, the brain recruits extra sleep resources to rescue memories from further forgetting. Our results are not consistent with prior studies showing a significant role for sleep in stabilizing memory from future interference, but they may suggest that sleep rescues memories after interference has occurred.

A hippocampus dependent neural circuit loop underlying the generation of auditory mismatch negativity

Extracting relevant information and transforming it into appropriate behavior, is a fundamental brain function, and requires the coordination between the sensory and cognitive systems, however, the underlying mechanisms of interplay between sensory and cognition systems remain largely unknown. Here, we developed a mouse model for mimicking human auditory mismatch negativity (MMN), a well-characterized translational biomarker for schizophrenia, and an index of early auditory information processing. We found that a subanesthetic dose of ketamine decreased the amplitude of MMN in adult mice. Using pharmacological and chemogenetic approaches, we identified an auditory cortex–entorhinal cortex–hippocampus neural circuit loop that is required for the generation of MMN. In addition, we found that inhibition of dCA1→MEC circuit impaired the auditory related fear discrimination. Moreover, we found that ketamine induced MMN deficiency by inhibition of long-range GABAergic projection from the CA1 region of the dorsal hippocampus to the medial entorhinal cortex. These results provided circuit insights for ketamine effects and early auditory information processing. As the entorhinal cortex is the interface between the neocortex and hippocampus, and the hippocampus is critical for the formation, consolidation, and retrieval of episodic memories and other cognition, our results provide a neural mechanism for the interplay between the sensory and cognition systems.

Lower regional cerebrovascular reactivity relates to worse episodic memory among older adults

AbstractBackgroundCerebrovascular reactivity (CVR) measures the ability of the cerebrovasculature to respond to vasoactive stimuli. Decreased CVR in the default mode network (DMN) has been associated with increased vascular risk factor burden. DMN connectivity is fundamentally dependent on vascular compliance, which can be altered in MCI, and may impact episodic memory consolidation. This study cross‐sectionally evaluated whether the topography of CVR is associated with episodic memory performance.MethodVanderbilt Memory &amp; Aging Project participants free of stroke were included (n=117, 76.0±7.3 years, 46% female). Participants underwent neuropsychological assessment and multimodal 3T brain MRI, including T1‐weighted imaging and T2*‐weighted blood‐oxygenation level‐dependent (BOLD‐fMRI) for quantifying CVR. During the BOLD‐fMRI acquisition, a hypercapnic normoxic respiratory challenge was administered by alternating normocapnic normoxia and hypercapnic normoxia (5% CO2/95%‐air) in 90s blocks. BOLD‐fMRI data were time‐delay processed, yielding whole‐brain mapping of the maximum correlation with the gas stimulus (CVRMAX) and time‐to‐max CVR (CVRDELAY). Mean CVR metrics were calculated in atlas‐derived DMN regions. Ordinary least squares regression models related DMN‐CVR to episodic memory performance adjusting for demographics, Framingham Stroke Risk Profile, and apolipoprotein E‐e4 status. Clusters were corrected using family‐wise‐error rate p&lt;0.05.ResultDMN‐CVRMAX was related to episodic memory performance (b=1.0x10‐3, p=0.03) but DMN‐CVRDELAY was not (p=0.09). In voxelwise analysis relating CVRMAX to memory, seven clusters surviving correction were identified, all suggesting lower CVRMAX related to worse memory performance. The peak value of the top cluster was located in the middle temporal gyrus. In voxelwise analysis relating CVRDELAY to memory, 11 clusters surviving correction were identified, all indicating longer CVRDELAY related to worse memory performance. The peak value of the top cluster was located in postcentral gyrus.ConclusionAmong older adults, lower DMN‐CVRMAX is associated with worse episodic memory performance and this association is not confined to the DMN. Associations between regionally reduced vascular compliance and episodic memory may result from vascular impairment of large‐scale brain networks such as the DMN, though these associations should be further explored. T32‐AG058524, IIRG‐08‐88733, R01‐AG034962, R01‐NS100980, K24‐AG046373, P20‐AG068082