Long-term Memory Research Articles

The role of variable retrieval in effective learning

Current research on memory indicates that learning is most effective when it involves spaced retrieval practice of study materials. Here, we investigated whether the benefits of both retrieval practice and spacing can be further boosted when variability is introduced across practice sessions. Across six experiments, participants learned translations of foreign vocabulary, with foreign words embedded in contextual sentences hinting at the meaning of these words. These sentences were then either kept constant or varied from one learning cycle to another. Whenever repeated practice took the form of retrieval from long-term memory with contextual sentences serving as cues (with or without feedback after retrieval attempts), variable sentences led to better learning of the meanings of the embedded foreign words than constant sentences. The benefits of variable retrieval were observed both immediately after study and after a 24-h delay, and they were larger when retrieval practice was spaced rather than massed. However, these benefits were not appreciated by the learners who judged learning to be more effective with constant rather than variable cues. This metacognitive illusion, misaligning the effectiveness of learning and its appraisal by learners, was confirmed in the seventh experiment which focused on learning lecture content. Thus, while spaced retrieval practice employing variable cues clearly produces robust benefits for memory performance, such benefits may be severely underappreciated by the learners.

The Memory Abilities of the Elderly Horse.

Studies on short- and long-term memory and their decline with aging in horses are still limited. This research aimed to assess the learning and short- and long-term memory abilities of adult and senior horses. A total of 21 adult horses (5-15 years) and 23 senior horses (16 years and older) were subjected to a behavioral test (Target Touch Test), which was repeated three times each for the initial test (T1) and again after 10 days (T10). Statistical analysis revealed no significant differences between adult and senior horses in the three tests conducted at T1. However, a significant difference was observed at T10 (χ2 = 42.1; p < 0.001). In fact, senior horses took longer to complete the test than adults. A significant difference between males and females, adults and seniors, at T1 and T10 (χ2 = 56.3; p < 0.001) was found, but no difference between male and female adult and senior horses in completing the three single tests at T1 and T10 was evidenced. In conclusion, even senior horses are capable of associative learning, maintaining the memory of this learning even after 10 days. However, they show slower recovery times for recalling memorized information compared to animals under 16 years of age.

Optimal approximations for the free boundary problems of the space-time fractional Black-Scholes equations using a combined physics-informed neural network

The combined physics-informed neural network is employed to deal with the free boundary problems of fractional Black-Scholes equations. The solution assumption and the loss function are determined, the transfer learning is borrowed, the combined neural network with data enhancement layer is designed, then the classical Black-Scholes model is numerically solved and the comparative analysis of numerical results under different neural networks is made. For further insight into the long-term memory of fluctuation, the free boundary problems of the space-time Black-Scholes equations under Caputo, Caputo-Fabrizio and Atangana-Baleanu-Caputo fractional derivatives are studied. The corresponding empirical analyses are presented and the optimal exercise boundaries of American put option are simulated. The market analysis shows that introducing fractional calculus tools and neural network algorithms into American put option pricing can yield more realistic prediction results. The work provides a viable method for subsequent researchers to study American option pricing using fractional calculus and neural networks combined with true market data and to deal with the free boundary problems in other research fields.

The impact of salt consumption on cardiometabolic and cognitive health in aged female rats

Health concerns about excess dietary salt have traditionally focused on its relationship with hypertension and the increased risk of cognitive impairment. However, research has often overlooked the unique health concerns and physiological differences between men and women, leading to gaps in knowledge, particularly regarding disease prevention and treatment strategies for women. The present study examined aged female rats over 12 weeks, using control, low, and high salt diets to mimic the post-menopausal phase in human females when cardiovascular risks typically increase. Cardiometabolic parameters and cognition were monitored. The findings revealed the impact of varying salt diets on blood lipids, blood pressure (BP) and heart rate (HR) levels and variability, anxiety, and cognition. Specifically, intake of a low-salt diet led to a significant reduction in BP levels but an increase in BP variability starting from the eighth week of the diet onset. Moreover, HR levels and variability were notably higher with the low-salt diet. Aged female rats exhibited increased anxiety on the low-salt diet at the fourth week, but the anxiety began to improve starting from the eighth week. Additionally, a trend suggested that the low salt intake worsened short-term memory while improving long-term memory. Furthermore, plasma lipids decreased significantly in aged female rats on a high-salt diet compared to those on a low-salt diet. The study provides valuable insights into the effects of salt intake on cardiometabolic parameters and cognitive function in aged female rats, highlighting the importance of considering sex-specific dietary guidelines for cardiometabolic and cognitive health.

No evidence that visual impulses enhance the readout of retrieved long-term memory contents from EEG activity

Abstract The application of multivariate pattern analysis (MVPA) to electroencephalography (EEG) data allows neuroscientists to track neural representations at temporally fine-grained scales. This approach has been leveraged to study the locus and evolution of long-term memory contents in the brain, but a limiting factor is that decoding performance remains low. A key reason for this is that processes such as encoding and retrieval are intrinsically dynamic across trials and participants, and this runs in tension with MVPA and other techniques that rely on consistently unfolding neural codes to generate predictions about memory contents. The presentation of visually perturbing stimuli may experimentally regularize brain dynamics, making neural codes more stable across measurements to enhance representational readouts. Such enhancements, which have repeatedly been demonstrated in working memory contexts, could offer a tool to improve decoding in long-term memory tasks. In this study, we evaluated whether visual perturbations—or pings—improve our ability to predict the category of retrieved images from EEG activity during cued recall. Overall, our findings suggest that while pings evoked a prominent neural response, they did not reliably produce improvements in MVPA-based classification across several analyses. We discuss possibilities that could explain these results, including the role of experimental and analysis parameter choices and mechanistic differences between working and long-term memory.

Study While You Sleep: Using Targeted Memory Reactivation as an Independent Research Project for Undergraduates.

Newly acquired information is stabilized into long-term memory through the process of consolidation. Memories are not static; rather, they are constantly updated via reactivation, and this reactivation occurs preferentially during Slow-Wave Sleep (SWS, also referred to as N3 in humans). Here we present a scalable neuroscience research investigation of memory reactivation using low-cost electroencephalogram (EEG) recording hardware and open-source software, for students and educators across the K-12 and higher education spectrum. The investigation uses a method called targeted memory reactivation (TMR), whereby auditory cues that were previously associated with learning are re-presented during sleep, triggering the recall of stored memories and (through this) strengthening these memories. We demonstrated the efficacy of this technique on seven healthy human subjects (ages 19-35). The subjects learned to play a spatial memory game on an app where they associated pictures (e.g., a clock) with locations on a grid while they listened to picture-appropriate sounds (e.g., "tic-toc"); next, they took a nap while undergoing EEG recordings. During SWS, half of the sounds from the game were replayed by the app, while half were substituted with non-learned sounds. Subjects then played the memory game again after waking. Results showed that spatial recall was improved more for cued than uncued memories, demonstrating the benefits of memory replay during sleep and suggesting that one may intervene in this process to boost recall of specific memories. This research investigation takes advantage of the importance of sleep for memory consolidation and demonstrates improved memory performance by cueing sounds during SWS.

Enhanced Tumor Immunotherapy by Triple Amplification Effects of Nanomedicine on the STING Signaling Pathway in Dendritic Cells.

Insufficient activation of stimulator of interferon genes (STING) signaling pathway in tumor-associated dendritic cells limits the efficiency of tumor immunotherapy. Herein, the "three-in-one" IAHA-LaP/siPTPN6 NPs containing lanthanum ions (La3+), cGAMP, and PTPN6 siRNA are developed for triple amplification of the STING pathway. In vitro results demonstrate that La3+ significantly promotes cGAMP-mediated activation of the STING pathway by enhancing the phosphorylation of STING, TBK1, IRF3, and NF-κB p65. Moreover, the IAHA-LaP/siPTPN6 NPs further significantly enhance the phosphorylation of STING and NF-κB p65 and augment K63-linked ubiquitination of STING protein via siPTPN6-mediated downregulation of SHP-1 protein. Furthermore, NPs improve the secretion of IFNβ (2.4-fold), IL-6 (1.5-fold), and TNF-α (1.4-fold), thereby promoting DCs maturation compared to the mixture of La3+ and cGAMP. In vivo results show that the IAHA-LaP/siPTPN6 NPs remarkably inhibit primary tumor growth by increasing the percentage of mature DCs in tumor-draining lymph nodes, polarizing M2/M1 phenotype in TME, and promoting the infiltration of CD8+T cells into tumors. Moreover, these NPs dramatically prevent the growth of distal tumor by inducing systemic anti-tumor immunity and generating a long-term anti-tumor memory for protection against tumor recurrence in mice bearing bilateral B16F10. These IAHA-LaP/siPTPN6 NPs may offer a promising platform for robust anti-tumor immune responses.

Photo‐synaptic Memristor Devices from Solution‐processed Ga2O3 Thin Films

AbstractHardware integration with biological synaptic function is the key to realizing brain‐like computing. Resistive Random Access Memory (RRAM), with a similar structure to biological synapses, are important candidate for the simulation of biological synaptic function. In this work, Ga2O3 film as a functional layer of RRAM is prepared by the solution method, and an RRAM‐based photo‐synaptic device with an Ag/Ga2O3/Si structure is constructed subsequently. The device exhibits excellent bipolar resistive switching characteristics, with the merits of a large storage window and long retention time. Furthermore, the devices generated excitatory postsynaptic currents (EPSC) and paired‐pulse facilitation (PPF) behaviors under light pulse stimulation, enabling the simulation of synaptic plasticity. The transformation of synaptic behavior from short‐term memory (STM) to long‐term memory (LTM) is achieved by observing the spike‐duration dependent plasticity (SDDP), spike‐intensity dependent plasticity (SIDP), spike‐number dependent plasticity (SNDP) and spike‐rate dependent plasticity (SRDP) characteristics of photonic synapses under different conditions. The device also simulates the process of successive “learning‐forgotten‐remembering”, revealing that RRAM‐based photonic synapses have great potential in the fields of artificial visual perception and memory storage.

Theta-burst transcranial magnetic stimulation attenuates chronic ischemic demyelination and vascular cognitive impairment in mice

Vascular cognitive impairment and dementia (VCID) is mainly caused by chronic cerebral hypoperfusion and subsequent white matter lesions. Noninvasive transcranial magnetic stimulation has been utilized in treating various neurological disorders. However, the function of theta-burst transcranial magnetic stimulation on VCID remains to be defined. We utilized 4-week bilateral carotid artery stenosis model of male mice to mimic VCID. Intermittent theta-burst stimulation (iTBS) or consecutive theta-burst stimulation (cTBS) was administered for 14 consecutive days. Through luxol fast blue staining, electron microscopy and immunofluorescence, we found that iTBS, not cTBS, significantly improved demyelination, axonal damage and β-amyloid deposition, without affecting cerebral blood flow in VCID mice. At cellular levels, iTBS rescued the loss of mature oligodendrocytes, promoted precursor cell differentiation, and inhibited pro-inflammatory activation of astrocytes and microglia. Notably, iTBS attenuated cognitive deterioration in both short-term retention and long-term spatial memory of VCID mice as indicated by serial neurobehavioral tests. To explore the molecular involvement of iTBS, mRNA sequencing was carried out. By real-time PCR and combined RNA fluorescence in situ hybridization with immunofluorescence, iTBS was confirmed to increase Rxrg expression specifically in mature oligodendrocytes. Collectively, iTBS could ameliorate vascular cognitive dysfunction, probably via mitigating white matter lesions and neuroinflammation in the corpus callosum. Rxrg signaling in mature oligodendrocytes, which was increased by iTBS, might be a potential target for VCID treatment.

Executive control can query hidden human memories.

When we try to retrieve a representation from visual long-term memory there is a chance that we will fail to recall seeing it even though the memory is stored in our brain. Here we show that although mechanisms of explicit memory retrieval are sometimes unable to retrieve stored memories, that mechanisms of executive control can quickly query memory and determine if a representation is stored therein. Our findings suggest that the representations stored in human memory that cannot be accessed explicitly at that moment are nonetheless directly accessible by the brain's higher level control mechanisms.

The administration of a phentolamine infusion into the basolateral amygdala enhances long-term memory and diminishes anxiety-like behavior in stressed rats.

The basolateral amygdala (BLA) contains adrenergic receptors, which are known to be involved in stress, anxiety, and memory. The objective of this study was to explore whether inhibition of α-adrenergic receptors (by phentolamine, an α-adrenergic receptor antagonist) in the BLA can reduce foot-shock stress-induced anxiety-like behavior, memory deficits, and long-term potentiation (LTP) deficits within the CA1 region of the rat hippocampus. Forty male Wistar rats were assigned to the intact, control, stress (Str), Phent (phentolamine), and Phent + Str groups. Animals were subjected to six shocks on 4 consecutive days, and phentolamine was injected into BLA 20 min before the animals were placed in the foot-shock stress apparatus. Results from the elevated plus maze test (EPM) revealed a reduction in anxiety-like behaviors (by an increased number of entries into the open arm, percentage of time spent in the open arm, and rearing and freezing) among stressed animals upon receiving injections of phentolamine into the BLA. The open-field test results (increased rearing, grooming, and freezing behaviors) were consistent with the EPM test results. Phentolamine infusion into the BLA enhanced spatial memory, reducing errors in finding the target hole and decreasing latency time in the Barnes maze test for stress and nonstress conditions. Injecting phentolamine into the BLA on both sides effectively prevented LTP impairment in hippocampal CA1 neurons after being subjected to foot-shock stress. It has been suggested that phentolamine in the BLA can effectively improve anxiety-like behaviors and memory deficits induced by foot-shock stress.

Discrimination of mnemonic similarity is associated with short-term and long-term memory precision.

Remembering specific memories with precision relies on the differentiation of similar memory contents - a process commonly referred to as pattern separation and behaviorally operationalized as lure discrimination in the mnemonic similarity task. Although pattern separation is typically investigated in the context of long-term memory (LTM), recent research extends these findings to short-term memory (STM) within a mixture model framework, emphasizing the distinction between memory quality and quantity. According to this framework, pattern separation is associated with memory precision across STM and LTM, regardless of the overall memory likelihood. However, these associations among memory quality measures may persist without the mixture model assumption. In an alternative model, a unitary memory strength measure quantified as a discrimination score (d') may also capture the association between pattern separation and memory quality, as pattern separation has been previously linked with strength-based memory performance. We tested these possibilities based on individual differences among 132 participants who underwent tasks measuring mnemonic pattern separation and STM/LTM quality. We found that behavioral estimates of pattern separation are significantly correlated with STM and LTM precision, irrespective of the likelihood of STM/LTM recall success. However, these associations are absent when considering the correlation between pattern separation and memory strength under a unitary model framework. By leveraging individual differences to constrain our understanding of cognitive models, our data unravel the intricate relationship between pattern separation and memory quality across timescales. These findings may therefore contribute to identifying sensitive behavioral measures for detecting subtle memory deficits in older adults or clinical populations.

Application Research of Power Measurement Data Exchange Based on Uninterruptible Power Supply

With the maturity of the smart meter embedded system integration mode, the power consumption information can be fed back to the management center by the intelligent terminal through the power Internet of Things. The smart terminal adopts the narrowband data communication mode. However, the narrowband channel interval is hindered by interference signals, resulting in serious data packet loss. Therefore, a stable and efficient acquisition scheme is needed to ensure its smooth interaction. Based on the application of smart meter data communication, we analyze the power consumption optimization and carrier transmission optimization of the power Internet of Things and propose a data analysis method based on self-learning and external characteristics, which is used to calculate the offline execution strategy of smart meters when they encounter factors such as power outage or intrusion. A production task-driving rule is designed. The external characteristics of deep learning data of the power Internet of Things are collected. The accuracy of data classification is judged according to the parallel Internet of Things of a convolutional neural network and a long-term and short-term memory deep neural network. When dealing with high-dimensional original data, the data network is graded to reduce the work of feature selection and the difficulty of training. Moreover, we improve the autonomous execution ability of an embedded terminal device in an offline state. We also strengthen the ability of abnormal data detection and judgment learning to meet the requirements of efficient and stable operation of the power grid. Simulation results verify that compared with the current mainstream schemes, the performance of the proposed scheme is improved by more than 17%. Besides, the fault tolerance rate is enhanced by 29%, and the power consumption after optimization is reduced by 26.3% and 42.8%. These effects highlight the role of data processing in embedded systems. It solves the problem of abnormal data and energy loss affecting the accuracy of error estimation of electric energy meters, opens up a new way for data acquisition and processing of large-scale smart meters, and further improves the service level of information management of power systems.

PFKFB3 ameliorates ischemia-induced neuronal damage by reducing reactive oxygen species and inhibiting nuclear translocation of Cdk5.

The enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB) plays an essential role in glycolysis and in the antioxidant pathway associated with glutathione. Therefore, we investigated the effects of PFKFB3 on oxidative and ischemic damage. We synthesized a fusion protein of transactivator of transcription (Tat)-PFKFB3 to facilitate its passage into the intracellular space and examine its effects against oxidative stress induced by hydrogen peroxide (H2O2) treatment and ischemic damage caused by occlusion of the common carotid arteries for 5min in gerbils. The Tat-PFKFB3 protein was efficiently delivered into HT22 cells in a concentration- and time-dependent manner, with higher levels observed 18h after treatment. Furthermore, treatment with 6 µM Tat-PFKFB3 demonstrated intracellular delivery into HT22 cells, as analyzed through immunocytochemical staining. Moreover, it significantly ameliorated the reduction of cell viability induced by 200 µM H2O2 treatment. Tat-PFKFB3 treatment also alleviated H2O2-induced DNA fragmentation and reactive oxygen species formation in HT22 cells. In gerbils, the intraperitoneal administration of 2mg/kg Tat-PFKFB3 efficiently delivered the substance to all hippocampal areas, including the hippocampal CA1 region. This administration significantly mitigated ischemia-induced hyperlocomotion, long-term memory deficits, and ischemic neuronal death in the hippocampal CA1 region after ischemia. Additionally, treatment with 2mg/kg Tat-PFKFB3 significantly ameliorated the translocation of Cdk5 from the cytosol to the nucleus in the hippocampal CA1 region 24h after ischemia, but not in other regions. The treatment also significantly reduced reactive oxygen species formation in the CA1 region. These findings suggest that Tat-PFKFB3 reduces neuronal damage in the hippocampal CA1 region after ischemia through the reduction of Cdk5 signaling and reactive oxygen species formation. Therefore, Tat-PFKFB3 may have potential applications in reducing ischemic damage.

The role of the claustrum in the acquisition, consolidation and reconsolidation of memories in mice

The claustrum is a brain structure that remains shrouded in mystery due to the limited understanding of its cellular structure, neural pathways, functionality and physiological aspects. Significant research has unveiled connections spanning from the claustrum to the entire cortex as well as subcortical areas. This widespread connectivity has led to speculations of its role in integrating information from different brain regions, possibly contributing to processes such as attention, consciousness, learning and memory. Our working hypothesis posits that claustrum neural activity contributes to the acquisition, consolidation and reconsolidation of long-term memories in mice. We found evidence in CF-1 mice of a decline in behavioral performance in an inhibitory avoidance task due to intra-claustral administration of 2% lidocaine immediately after a training session or memory recall. Nevertheless, this does not seem to be the case for the acquisition or retrieval of this type of memory, although its neural activity is significantly increased after training, evaluated through c-Fos expression. Moreover, inhibition of the claustrum’s synaptic activity appears to impair the consolidation but not acquisition or retrieval of an unconditioned memory formed in a nose-poke habituation task.

Diagnostic Accuracy of Neurocognitive and Executive Functions to Discriminate Women With and Without Fibromyalgia Syndrome: A Secondary Analysis.

Objective: The aim of the current study was to determine the capability of neurocognitive variables and executive functions to differentiate women with and without fibromyalgia syndrome (FMS). Methods: A secondary diagnostic accuracy analysis was conducted. A battery of neurocognitive and executive function tests (the D2 Attention test, the Rey-Osterrieth Complex Figure for visual perception, "Digits D/R/I" tests of the WAIS-IV battery for working memory, the 5-Digit test for mental inhibition, the Symbol Search for processing speed, and the Zoo Test for planning/decision-making) were collected in 129 women with FMS and 111 without FMS. The area under the receiver operating characteristic (ROC) curve, optimal cut-off point, sensitivity, specificity, and positive and negative likelihood ratios (LR) for each variable were calculated. Results: Between-group differences were identified in ROCF_Copy (p = 0.043), ROCF_Recall (p = 0.004), d2_TR (p = 0.019), d2_TA (p = 0.007), d2_TOT (p = 0.005), d2_CON (p = 0.004), d2_C (p = 0.042), Symbol Search (p = 0.008), Decoding _FDT (p = 0.001), Retrieving_FDT (p = 0.001), and Inhibiting_FDT (p = 0.024). The result showed that FDT-based outcomes (Retrieving_FDT: ROC 0.739, sensitivity 85.3%, specificity 48.6%; Decoding_FDT: ROC 0.724, sensitivity 50.4%, specificity 16.2%; Inhibiting_FDT: ROC 0.708, sensitivity 56.6%, specificity 22.5%) were the variables able to differentiate between women with and without FMS. Conclusions: Although women with FMS exhibited deficits in attention, long-term visual memory, processing speed, and mental inhibition when compared with women without FMS, only mental inhibition scores showed moderate diagnostic accuracy to discriminate between women with and without FMS. Future studies investigating these results in clinical settings are needed to identify the clinical relevance of these findings.

Cortical, striatal, and thalamic populations self-organize into a functionally connected circuit with long-term memory properties

The human brain is a complex organ with an intricate neuronal connectivity and diverse functional regions. Neurological disorders often disrupt the delicate balance among these anatomical compartments, resulting in severe impairments. The available therapeutic options constitute an incomplete solution as many patients respond partially, highlighting the need for continued research into causes and treatments. Bottom-up approaches, like in vitro models, offer insights into brain functions as they recreate the in vivo microenvironment that allows studying how specific features affect physiological and pathological conditions. In this work, we engineered the cortical-striatal-thalamic (CST) circuit, involved in many brain functions such as action initiation and selection, using a three-compartment polymeric device. We characterized the emerging spontaneous electrophysiological activity by using Micro-Electrode Arrays (MEAs). Cortical neurons exhibited complex bursting activity, which influenced the entire circuit. Striatal and thalamic neurons displayed predominantly tonic firing when isolated, while interconnections with the cortex synchronized and organized their neuronal activity, highlighting the cortical pivotal role in bursting activity and information processing. The CST circuit demonstrated self-organization abilities and displayed high entropy values, indicative of dynamic richness and information encoding potential. Furthermore, we proved the CST’s involvement in learning and memory. Our CST model provides a platform for further exploration into brain circuitry and potential therapeutic interventions, underscoring the necessity of realistic in vitro models to fully understand neurological diseases' pathophysiology.

Acute exercise performed during the late consolidation phase improves memory persistence by hippocampal protein synthesis and catecholamine modulation

Memory persistence is a crucial aspect of long-term memory (LTM) and involves late consolidation processes that modulate memory stability over time. Acute physical exercise (PE) has emerged as a potential strategy to modulate memory consolidation and enhance memory persistence. While its effects have been extensively explored in the early consolidation phase, its impact on the late phase remains unexplored. In this study, we investigated the effects and mechanisms of an acute PE on the late consolidation window of novel object recognition (NOR) memory in rats. A 30-minute running session applied 11 h after NOR memory acquisition significantly increased memory persistence for at least 7 days. The inhibition of hippocampal protein synthesis immediately after acute PE using anisomycin (a ribosomal inhibitor) or rapamycin (an mTOR pathway inhibitor) impaired the effect of PE on memory persistence. Animals only presented memory 1 day after acquisition. The same effect was observed with the inhibition of beta-adrenergic receptors by timolol. Although there were no differences between the groups' comparison, blocking D1/D5 receptors after acute PE resulted in a lack of memory persistence in the dichotomous testing (remember/non-remember). Therefore, our exploration of the mechanisms underlying this enhancement revealed the involvement of protein synthesis and the requirement of beta-adrenergic and dopaminergic D1/D5 receptors in the dorsal hippocampus. These findings provide valuable insights into PE as a potential memory modulator, contributing to expanding our understanding of memory consolidation dynamics and acute PE effects.

Dose-dependent effect of acute THC on extinction memory recall and fear renewal: a randomized, double-blind, placebo-controlled study.

Prior work from our lab and others demonstrates that the endocannabinoid system is a promising avenue for improving fear memory deficits in posttraumatic stress disorder (PTSD). Specifically, 7.5mg of delta-9-tetrahydrocannabinol (THC) decreases fear responding in healthy adults and increases prefrontal cortex activation during extinction learning and fear renewal in adults with PTSD. The present study will determine whether there is a dose-dependent effect of THC on short-term (24h) and long-term (one week) fear learning and memory in adults with PTSD. Using a randomized, double-blind, placebo-controlled design, N = 36 adults with PTSD completed the study and were randomized to receive placebo (PBO, n = 11), 5mg of THC (n = 11), or 10mg of THC (n = 14) prior to fear extinction learning. Participants completed a Pavlovian conditioning paradigm with extinction recall and fear renewal occurring 24h and one week later, where we measured concurrent functional imaging and behavioral responses. Twenty-four hours after drug administration, individuals with PTSD given 5mg of THC exhibited greater anterior cingulate cortex and prefrontal cortex activation during early fear renewal. One week later, individuals given 10mg of THC exhibited greater hippocampus activation during extinction recall and prefrontal cortex activation during fear renewal. These data suggest that dosing and timing are critical for facilitating fear memory processes in PTSD, and that low-dose oral THC prior to extinction learning can affect brain indices of fear learning and memory both acutely and one week after administration.

Functional connectivity in resting-state networks relates to short-term global cognitive functioning in cardiac arrest survivors.

Long-term cognitive impairment is common in cardiac arrest survivors. Screening to identify patients at risk is recommended. Functional magnetic resonance brain imaging (fMRI) holds potential to contribute to prediction of cognitive outcomes. In this study, we investigated the possible value of early changes in resting-state networks for predicting short and long-term cognitive functioning of cardiac arrest survivors. We performed a prospective multicenter cohort study in cardiac arrest survivors in three Dutch hospitals. Resting-state fMRI scans were acquired within a month after cardiac arrest. We primarily focused on functional connectivity within the default-mode network (DMN) and salience network (SN), and additionally explored functional connectivity in seven other networks. Cognitive outcome was measured using the Montreal Cognitive Assessment (MoCA) during hospital admission and at 3 and 12 months, and by neuropsychological examination (NPE) at 12 months. We tested mixed effects models to evaluate the value of connectivity within the networks for predicting global cognitive outcomes at the three time points, and long-term cognitive outcomes in the memory, attention, and executive functioning domains. We included 80 patients (age 60 ± 11 years, 72 (90%) male). MoCA scores increased significantly between hospital admission and 3 months (ΔMoCAhospital-3M = 2.89, p < 0.01), but not between 3 and 12 months (ΔMoCA3M-12M = 0.38, p = 0.52). Connectivity within the DMN, SN, and dorsal attention network (DAN) was positively related to global cognitive functioning during hospital admission (βDMN = 0.85, p = 0.03; βSN = 1.48, p < 0.01; βDAN = 0.96, p = 0.01), but not at 3 and 12 months. Network connectivity was also unrelated to long-term memory, attention, or executive functioning. Resting-state functional connectivity in the DMN, SN, and DAN measured in the first month after cardiac arrest is related to short-term global, but not long-term global or domain-specific cognitive performance of survivors. These results do not support the value of functional connectivity within these RSNs for prediction of long-term cognitive performance after cardiac arrest.