Memory circuits in dementia: The engram, hippocampal neurogenesis and Alzheimer's disease.

Here, we provide an in-depth consideration of our current understanding of engrams, spanning from molecular to network levels, and hippocampal neurogenesis, in health and Alzheimer's disease (AD). This review highlights novel findings in these emerging research fields and future research directions for novel therapeutic avenues for memory failure in dementia. Engrams, memory in AD, and hippocampal neurogenesis have each been extensively studied. The integration of these topics, however, has been relatively less deliberated, and is the focus of this review. We primarily focus on the dentate gyrus (DG) of the hippocampus, which is a key area of episodic memory formation. Episodic memory is significantly impaired in AD, and is also the site of adult hippocampal neurogenesis. Advancements in technology, especially opto- and chemogenetics, have made sophisticated manipulations of engram cells possible. Furthermore, innovative methods have emerged for monitoring neurons, even specific neuronal populations, in vivo while animals engage in tasks, such as calcium imaging. In vivo calcium imaging contributes to a more comprehensive understanding of engram cells. Critically, studies of the engram in the DG using these technologies have shown the important contribution of hippocampal neurogenesis for memory in both health and AD. Together, the discussion of these topics provides a holistic perspective that motivates questions for future research.

Lrp8 knockout mice fed a selenium-replete diet display subtle deficits in their spatial learning and memory function.

Selenium is an essential trace element that is delivered to the brain by the selenium transport protein selenoprotein P (SEPP1), primarily by binding to its receptor low-density lipoprotein receptor-related protein 8 (LRP8), also known as apolipoprotein E receptor 2 (ApoER2), at the blood-brain barrier. Selenium transport is required for several important brain functions, with transgenic deletion of either Sepp1 or Lrp8 resulting in severe neurological dysfunction and death in mice fed a selenium-deficient diet. Previous studies have reported that although feeding a standard chow diet can prevent these severe deficits, some motor coordination and cognitive dysfunction remain. Importantly, no single study has directly compared the motor and cognitive performance of the Sepp1 and Lrp8 knockout (KO) lines. Here, we report the results of a comprehensive parallel analysis of the motor and spatial learning and memory function of Sepp1 and Lrp8 knockout mice fed a standard mouse chow diet. Our results revealed that Sepp1 knockout mice raised on a selenium-replete diet displayed motor and cognitive function that was indistinguishable from their wild-type littermates. In contrast, we found that although Lrp8-knockout mice fed a selenium-replete diet had normal motor function, their spatial learning and memory showed subtle deficits. We also found that the deficit in baseline adult hippocampal neurogenesis exhibited by Lrp8-deficit mice could not be rescued by dietary selenium supplementation. Taken together, these findings further highlight the importance of selenium transport in maintaining healthy brain function. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Does context matter for memory? Testing the effectiveness of learning by imagining situated interactions with objects.

Mounting evidence supports the efficacy of mental imagery for verbal information retention. Motor imagery, imagining oneself interacting physically with the object to be learned, emerges as an optimal form compared to less physically engaging imagery. Yet, when engaging in mental imagery, it occurs within a specific context that may affect imagined actions and consequently impact the mnemonic benefits of mental imagery. In a first study, participants were given instructions for incidental learning: mental rehearsal, visual imagery, motor imagery or situated motor imagery. The latter, which involved imagining physical interaction with an item within a coherent situation, produced the highest proportion of correct recalls. This highlights memory's role in supporting situated actions and offers the possibility for further developing the mnemonic potential of embodied mental imagery. Furthermore, item-level analysis showed that individuals who engaged in situated motor imagery remembered words primarily due to the sensorimotor characteristics of the words' referent. A second study investigating the role of inter-item distinctiveness in this effect failed to determine the extent to which the situational and motor elements need to be distinctive in order to be considered useful retrieval cues and produce an optimal memory performance.

Predictors of post stroke cognitive impairment: VITATOPS cognition substudy.

INTRODUCTION: Post stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. METHODS: The Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups - visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function - that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. RESULTS: A total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. CONCLUSION: We identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.

Effect of electroacupuncture on proBDNF/mBDNF and synaptic plasticity in rats with learning and memory impairment after cerebral ischemia-reperfusion. / ç”µé’ˆå¯¹è„‘ç¼ºè¡€å†çŒæ³¨å­¦ä¹ è®°å¿†éšœç¢å¤§é¼ æµ·é©¬è„‘æºæ€§ç¥žç»è¥å »å› å­è½¬åŒ–å’Œçªè§¦å¯å¡‘æ€§çš„å½±å“.

OBJECTIVES: To observe the effect of electroacupuncture (EA) at "Baihui" (GV20) and "Shenting" (GV24) on the rats' behavior and the transforming precursor of brain-derived neurotrophic factor (proBDNF) into mature brain-derived neurotrophic factor (mBDNF) in the hippocampus of rats with learning and memory impairment induced by cerebral ischemia-reperfusion (IR), so as to explore its mechanisms underlying improvement of learning and memory ability. METHODS: SD rats were randomly divided into blank, sham operation, model, and EA groups, with 6 rats in each group. The model of IR was established by occlusion of the middle cerebral artery. EA (1 Hz/20 Hz) was applied to GV24 and GV20 for 30 min, once daily for 14 days. The neurological function was evaluated according to the Zea Longa's score criteria 24 h after modeling and after intervention. Morris water maze test was used to detect the learning and memory function of the rats. TTC staining was used to evaluate the cerebral infarction volume on the affected side. The protein expression levels of proBDNF, mBDNF, tissue plasminogen activator (tPA), tyrosine kinase receptor B (TrkB) and p75 neurotrophin receptor (p75NTR) in hippocampal tissue were detected by Western blot. RESULTS: Compared with the sham operation group, the neurological function score, the percentage of cerebral infarction volume and the expression levels of proBDNF and p75NTR protein in hippocampus were increased (P<0.01), while the times of crossing the original platform and the total distance in the target quadrant, the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were decreased (P<0.01, P<0.05) in the model group. Compared with the model group, the neurological function score, the percentage of cerebral infarction volume, and the expression levels of proBDNF and p75NTR protein in hippocampus were decreased (P<0.01, P<0.05), while the times of crossing the original platform, the total distance in the target quadrant, and the expression levels of mBDNF, TrkB and tPA protein and the ratio of mBDNF/proBDNF were increased (P<0.05, P<0.01) in the EA group. CONCLUSIONS: EA can alleviate learning and memory impairment in IR rats, which may be related to its function in up-regulating the expression of tPA protein and promoting the transformation of proBDNF to mBDNF, thus improving the synaptic plasticity.

Tenuifolin improves learning and memory by regulating long-term potentiation and dendritic structure of hippocampal CA1 area in healthy female mice but not male mice.

Polygala tenuifolia Wild is an ancient traditional Chinese medicine. Its main component, tenuifolin (TEN), has been proven to improve cognitive impairment caused by neurodegenerative diseases and ovariectomy. However, there was hardly any pharmacological research about TEN and its potential gender differences. Considering the reduction of TEN on learning and memory dysfunction in ovariectomized animals, therefore, we focused on the impact of TEN in different mice genders in the current study. Spontaneous alternation behavior (SAB), light-dark discrimination, and Morris water maze (MWM) tests were used to evaluate the mice's learning and memory abilities. The field excitatory postsynaptic potential (fEPSP) of the hippocampal CA1 region was recorded using an electrophysiological method, and the morphology of the dendritic structure was examined using Golgi staining. In the behavioral experiments, TEN improved the correct rate in female mice in the SAB test, the correct rate in the light-dark discrimination test, and the number of crossing platforms in the MWM test. Additionally, TEN reduced the latency of female mice rather than male mice in light-dark discrimination and MWM tests. Moreover, TEN could significantly increase the slope of fEPSP in hippocampal Schaffer-CA1 and enhance the total length and the number of intersections of dendrites in the hippocampal CA1 area in female mice but not in male mice. Collectively, the results of the current study showed that TEN improved learning and memory by regulating long-term potentiation (LTP) and dendritic structure of hippocampal CA1 area in female mice but not in males. These findings would help to explore the improvement mechanism of TEN on cognition and expand the knowledge of the potential therapeutic value of TEN in the treatment of cognitive impairment.

Lancao decoction alleviates cognitive dysfunction: A new therapeutic drug and its therapeutic mechanism.

BACKGROUND: Cognitive dysfunction (CD) is a neurodegenerative disease characterized primarily by the decline of learning and memory abilities. The physiological and pathological mechanisms of CD are very complex, which is mainly related to normal function of the hippocampus. Lancao decoction (LC) is a Chinese medicine formula, which has been used to treat neurodegenerative disorders. However, the potential of LC for the treatment of CD, as well as its underlying mechanisms, is unclear. PURPOSE: In the study, we aimed to reveal the functional and neuronal mechanisms of LC's treatments for CD in scopolamine-induced mice. METHODS: Gas chromatography (GC) was used to determine the stability of LC's extraction. CD model was established by the chronic induction of scopolamine (Scop, 1 mg/kg/day) for 1 week. Behavioral tests including morris water maze (MWM) and y-maze were used to evaluate learning and memory abilities of mice after LC's treatments. Immunofluorescence was used to detected the expressions of cFOS, Brdu and Ki67 after LC's treatments. Pharmacological blockade experiments explored the role of α-Amino-3­hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) in LC's treatments for CD and its relationships with regeneration, activities and differentiation of neurons. RESULTS: The results showed that LC was capable of improving spatial learning and memory and spontaneous alternating abilities in Scop-induced mice, which was similar to donepezil. LC could increase the number of cFOS positive cells, which was used as a marker of neuronal activity to upregulate by neuronal activities in hippocampus, but donepezil did not. Moreover, LC could strengthen neurogenesis and neuro-differentiation by increasing the number of Brdu and Ki67 positive cells in hippocampal dentate gyrus (DG), meanwhile, donepezil could only enhance the number of Ki67 positive cells. Transient inhibition of AMPAR by NBQX blunted the function of LC's treatment for CD and inhibited the enhanced effect of LC on Scop-induced hippocampal neuronal excitability and neurogenesis in mice. CONCLUSION: To sum up, our study demonstrated that LC had the function of treating CD by enhancing content of acetylcholine (ACh) to activate AMPAR, which further up-regulated neurogenesis and neuronal differentiation to strengthen neuroactivities in hippocampus.

Brain-wide neural activity underlying memory-guided movement.

Behavior relies on activity in structured neural circuits that are distributed across the brain, but most experiments probe neurons in a single area at a time. Using multiple Neuropixels probes, we recorded from multi-regional loops connected to the anterior lateral motor cortex (ALM), a circuit node mediating memory-guided directional licking. Neurons encoding sensory stimuli, choices, and actions were distributed across the brain. However, choice coding was concentrated in the ALM and subcortical areas receiving input from the ALM in an ALM-dependent manner. Diverse orofacial movements were encoded in the hindbrain; midbrain; and, to a lesser extent, forebrain. Choice signals were first detected in the ALM and the midbrain, followed by the thalamus and other brain areas. At movement initiation, choice-selective activity collapsed across the brain, followed by new activity patterns driving specific actions. Our experiments provide the foundation for neural circuit models of decision-making and movement initiation.

Effect of Polyphenol Supplementation on Memory Functioning in Overweight and Obese Adults: A Systematic Review and Meta-Analysis.

Negative health consequences of obesity include impaired neuronal functioning and cell death, thus bringing the risk of impaired cognitive functioning. Antioxidant properties of polyphenols offer a possible intervention for overweight people, but evidence for their effectiveness in supporting cognitive functioning is mixed. This review examined evidence from randomized controlled trials concerning the effect of polyphenols on tasks requiring either immediate or delayed retrieval of learned information, respectively, thus controlling for differences in cognitive processes and related neural substrates supporting respective task demands. Searches of the PubMed/Medline, PsycInfo, and Scopus databases identified 24 relevant primary studies with N = 2336 participants having a BMI ≥ 25.0 kg/m2. The participants' mean age for the 24 studies exceeded 60 years. Respective meta-analyses produced a significant summary effect for immediate retrieval but not for delayed retrieval. The present findings support a potential positive effect of chronic supplementation with polyphenols, most notably flavonoids, on immediate retrieval in participants aged over 60 years with obesity being a risk factor for cognitive impairment. We recommend further investigation of this potential positive effect in participants with such risk factors. Future research on all populations should report the phenolic content of the supplementation administered and be specific regarding the cognitive processes tested.

Beyond hippocampus: Thalamic and prefrontal contributions to an evolving memory.

The hippocampus has long been at the center of memory research, and rightfully so. However, with emerging technological capabilities, we can increasingly appreciate memory as a more dynamic and brain-wide process. In this perspective, our goal is to begin developing models to understand the gradual evolution, reorganization, and stabilization of memories across the brain after their initial formation in the hippocampus. By synthesizing studies across the rodent and human literature, we suggest that as memory representations initially form in hippocampus, parallel traces emerge in frontal cortex that cue memory recall, and as they mature, with sustained support initially from limbic then diencephalic then cortical circuits, they become progressively independent of hippocampus and dependent on a mature cortical representation. A key feature of this model is that, as time progresses, memory representations are passed on to distinct circuits with progressively longer time constants, providing the opportunity to filter, forget, update, or reorganize memories in the process of committing to long-term storage.

Effect of Immersive Virtual Reality Reminiscence versus Traditional Reminiscence Therapy on Cognitive Function and Psychological Well-being among Older Adults in Assisted Living Facilities: A randomized controlled trial.

BACKGROUND: Virtual reality (VR) reminiscence is an innovative strategy that integrates technology into the care of older adults. Limited research was conducted to compare the role of VR reminiscence and traditional RT in improving older adults' cognitive and psychological well-being. AIM: Investigate the effect of virtual reality reminiscence versus traditional reminiscence therapy on cognitive function and psychological well-being among older adults in assisted living facilities. METHODS: A randomized controlled trial research design was followed. Sixty older adults were recruited and randomly assigned to three equal groups (20 older adults for each group). RESULTS: Post interventions, a significant increase in the mean scores of cognitive function and psychological well-being was evident among the VR and RT groups with statistically significant differences (P <0.05) compared with pre-intervention and the control group. CONCLUSION: Application of VR reminiscence or traditional RT is efficacious in improving cognitive function and psychological well-being among institutionalized older adults.

Probing the Neurophysiology of Temporal Sensitivity in the Somatosensory System Using the Mismatch Negativity (MMN) Sensory Memory Paradigm.

Duration is an amodal feature common to all sensory experiences, but low-level processing of the temporal qualities of somatosensation remains poorly understood. The goal of the present study was to evaluate electrophysiological discrimination of parametric somatosensory stimuli to better understand how the brain processes the duration of tactile information. This research used a somatosensory mismatch negativity (sMMN) paradigm to evaluate electrophysiological sensitivity to differences in the duration of vibrotactile stimuli in healthy young adults. Specifically, a 100 ms standard vibration was presented 80% of the time while the remaining 20% of presentations were made up of deviant stimuli with one of the following durations: 115, 130, 145, or 160 ms. When a deviation from the anticipated tactile input is detected, the distinct electrophysiological signature of the sMMN is present. A companion behavioral task assessed individual thresholds for cognizant awareness of the standard and deviant vibrotactile stimuli. The results of the present study demonstrated a sMMN response when deviant stimuli were 130, 145, and 160 ms, but not when they were 115 ms. This suggests that on average the participants did not electrophysiologically discriminate between the 100 and 115 ms. Future work may apply this paradigm to better understand atypical tactile sensitivity in various clinical conditions.

The effectiveness of two novel approaches to prevent intrusions: A pilot study comparing Tetris_dualtask and imagery rescripting to control.

BACKGROUND AND OBJECTIVES: Post-traumatic stress disorder (PTSD) is a global health problem. Although effective treatments for it exist, early interventions that prevent PTSD from developing are lacking. The aim of this pilot analogue trauma study was to compare the effects of two potential early intervention strategies, namely Tetris_dualtask and imagery rescripting (IR) to a no-intervention control group on intrusion frequency and the vividness and emotionality of aversive film memory. METHODS: Sixty healthy students were subjected to the trauma film paradigm and randomly allocated to either: Tetris_dualtask, IR or no-intervention. Main outcomes were the number of film-related intrusions at one week and vividness and emotionality ratings of the most aversive film memory. Secondary outcomes were PTSD-like symptoms, intrusion intensity, and explicit film memory. RESULTS: The Tetris_dualtask group reported significant fewer intrusions compared to the no-intervention group; whereas the IR group did not. No effect was found on vividness and emotionality ratings, PTSD-like symptoms, intrusion intensity, and explicit memory. LIMITATIONS: The sample size was small, and analogue trauma in healthy individuals was examined, thus generalizability may be limited. Also, to increase comparability between interventions, the duration of Tetris_dualtask and IR was standardized. As a result, the IR intervention was shorter compared to other studies, which might have decreased its efficacy. CONCLUSIONS: The results of this pilot study suggest that playing Tetris during retrieval of traumatic images, might hold potential as an early intervention strategy to reduce intrusions in the early aftermath of trauma and adversity. However, future large-scale replication research is needed.

Witnesses' susceptibility to misleading post-event information delivered in a social media-style video.

In many criminal cases, outcomes rely on eyewitness evidence. Exposure to misleading information after an event reduces the accuracy of witnesses' memories. In some circumstances, warnings about misinformation can protect witnesses. As social media is a growing source of misleading information, this study examined the effect of misleading post-event information delivered via a social media-style video, as well as the utility of a minimal versus detailed warning. Participants (N = 145) watched a video showing an electrician stealing items from a client's home. Next, they received one of three pre-warnings regarding forthcoming misleading information: a minimal warning indicating that caution should be taken, a detailed warning specifying the presence of misleading information, or no warning. Participants received the misleading information via a social media video or a standard text-based narrative. Finally, they completed a recognition test. Although delivery method did not affect errors for misleading items, detailed warnings were only effective against text-based misleading information. Participants were more confident about their correct than incorrect responses for misleading items; confidence was not affected by delivery method or warning. This experiment is the first to demonstrate people's susceptibility to misleading post-event information delivered in a social media-style video using an eyewitness paradigm.

Neuropsychological Consequences of Massive Trauma: Implications and Clinical Interventions.

Traumatic events, especially massive trauma resulting from catastrophic incidents, wars, or severe abuse can elicit significant neuropsychological alterations, with profound implications for cognitive, emotional, and behavioral functioning. This mini-review delineates the primary neural changes post-trauma and underscores the importance of timely neuropsychological and clinical interventions. Specific brain regions, including the amygdala and prefrontal cortex, undergo physiological changes that can lead to memory impairments, attention deficits, and emotional disturbances. PTSD, a commonly diagnosed condition post-trauma, exemplifies the intricate relationship between trauma and memory processing. Furthermore, the concept of neuroplasticity, the brain's inherent ability to adapt and rewire, offers hope for recovery. Current clinical interventions, such as cognitive behavioral therapy, mindfulness practices, and biofeedback, leverage this neuroplastic potential to foster healing. The review underscores the vital importance of early intervention to mitigate long-term neuropsychological impacts, emphasizing the role of timely and targeted clinical interventions. The synthesis of this knowledge is crucial for clinicians, allowing for informed therapeutic approaches that holistically address both the physiological and psychological dimensions of trauma.

The Role of Motor Representation in Enactment Effect of Action Memory.

Noun-verb phrases are more efficiently remembered when they are enacted during learning than when they are only verbally studied, a phenomenon known as the enactment effect. While studies have debated whether motor information is key to this effect, our study explores whether the organization of motor information can support the enactment effect. We used the retrieval-practice paradigm to induce retrieval-induced forgetting (RIF). In Experiment 1, we found an RIF effect of categorization into physical motor properties (e.g., rotation-motor category), which was significantly stronger during enactment learning. In Experiment 2, we also found an RIF effect of categorization into physical motor properties with additional imagery features (e.g., the hand-physical and round-object category), but there was no significant difference between enactment learning and verbal learning. These findings suggest that motor information is fundamental to the enactment effect, but it is not primarily assimilated, even in the presence of various types of information, in the processing of action memory. We discuss these findings in the context of multimodal theory and episodic integration theory.

Aphantasia within the framework of neurodivergence: Some preliminary data and the curse of the confidence gap.

Aphantasia is a neurocognitive phenomenon affecting voluntary visual imagery, such that it is either entirely absent, or markedly impaired. Using both the social and medical models of disability, this article discusses the extent to which aphantasia can be understood as a disorder or just a form of neutral neurodivergence, given that imagery plays a central role in thinking and memory for most other people. Preliminary school performance data are presented, showing that low imagery does not necessarily complicate life, especially given compensatory strategies and low societal barriers. In addition, we discuss the consequences of labelling aphantasia a disorder with regard to self- and public stigma, and we provide further data regarding a confidence gap, by which aphantasics perceive themselves as performing worse than they objectively do. We conclude that aphantasia should be understood as neutral neurodivergence and that labelling it a disorder is not only wrong, but potentially harmful.

40 Hz Electroacupuncture relieves the memory dysfunction of 5xFAD mice by regulating neuronal electrical activity.

In this investigation, we probed the impacts of 40 Hz Electroacupuncture (EA) on the cognitive function and brain activity in 5xFAD mice. Three groups of mice were constituted: the Model group of 5xFAD mice, the Wild Type (WT) group of littermate controls, and the EA group of 5xFAD mice subjected to EA treatment. Behavioral tests were conducted to evaluate memory function and anxiety levels, while the presence of Aß plaques were detected via immunostaining, and neuronal activity was measured using multichannel recordings. Our results indicated that EA therapy enhanced memory function and anxiety-like behavior in 5xFAD mice, as well as diminishing the abundance and dimensions of Aß plaques in the hippocampus and mPFC regions. Notably, the suppression of astrocyte activation was observed, which was potentially associated with alterations in gamma oscillation. Furthermore, the synaptic transmission of neurons was amplified, suggesting a possible modulation in neural activity. These findings indicate that 40 Hz EA could influence cognitive performance and potentially affect neuronal activity in 5xFAD mice, while the direct connection between EA and neuronal electrical activity regulation requires further exploration. The potential frequency-specific effects of EA on protective mechanisms in the brain was not addressed in this study and thus presents a direction for future research.

The effects of closed-loop auditory stimulation on sleep oscillatory dynamics in relation to motor procedural memory consolidation.

STUDY OBJECTIVES: Healthy aging and many disorders show reduced sleep-dependent memory consolidation and corresponding alterations in non-rapid eye movement sleep oscillations. Yet sleep physiology remains a relatively neglected target for improving memory. We evaluated the effects of closed-loop auditory stimulation during sleep (CLASS) on slow oscillations (SOs), sleep spindles, and their coupling, all in relation to motor procedural memory consolidation. METHODS: Twenty healthy young adults had two afternoon naps: one with auditory stimulation during SO upstates and another with no stimulation. Twelve returned for a third nap with stimulation at variable times in relation to SO upstates. In all sessions, participants trained on the motor sequence task prior to napping and were tested afterward. RESULTS: Relative to epochs with no stimulation, upstate stimuli disrupted sleep and evoked SOs, spindles, and SO-coupled spindles. Stimuli that successfully evoked oscillations were delivered closer to the peak of the SO upstate and when spindle power was lower than stimuli that failed to evoke oscillations. Across conditions, participants showed similar significant post-nap performance improvement that correlated with the density of SO-coupled spindles. CONCLUSIONS: Despite its strong effects on sleep physiology, CLASS failed to enhance motor procedural memory. Our findings suggest methods to overcome this failure, including better sound calibration to preserve sleep continuity and the use of real-time predictive algorithms to more precisely target SO upstates and to avoid disrupting endogenous SO-coupled spindles and their mnemonic function. They motivate continued development of CLASS as an intervention to manipulate sleep oscillatory dynamics and improve memory.

Phytotherapy of abnormality of fear memory: A narrative review of mechanisms.

It is generally believed that in post-traumatic stress disorder (PTSD), the high expression of fear memory is mainly determined by amygdala hyperactivity and hippocampus hypoactivity. In this review, we firstly updated the mechanisms of fear memory, and then searched the experimental evidence of phytotherapy for fear memory in the past five years. Based on the summary of those experimental studies, we further discussed the future research strategies of plant medicines, including the study of the mechanism of specific brain regions, the optimal time for the prevention and treatment of fear memory-related diseases such as PTSD, and the development of new drugs with active components of plant medicines. Accordingly, plant medicines play a clear role in improving fear memory abnormalities and have the drug development potential in the treatment of fear-related disorders.