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.

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).

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.

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.

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.

Bilateral eye movements disrupt the involuntary perceptual representation of trauma-related memories.

Bilateral eye movement (EM) is a critical component in eye movement desensitization and reprocessing (EMDR), an effective treatment for post-traumatic stress disorder. However, the role of bilateral EM in alleviating trauma-related symptoms is unclear. Here we hypothesize that bilateral EM selectively disrupts the perceptual representation of traumatic memories. We used the trauma film paradigm as an analog for trauma experience. Nonclinical participants viewed trauma films followed by a bilateral EM intervention or a static Fixation period as a control. Perceptual and semantic memories for the film were assessed with different measures. Results showed a significant decrease in perceptual memory recognition shortly after the EM intervention and subsequently in the frequency and vividness of film-related memory intrusions across one week, relative to the Fixation condition. The EM intervention did not affect the explicit recognition of semantic memories, suggesting a dissociation between perceptual and semantic memory disruption. Furthermore, the EM intervention effectively reduced psychophysiological affective responses, including the skin conductance response and pupil size, to film scenes and subjective affective ratings of film-related intrusions. Together, bilateral EMs effectively reduce the perceptual representation and affective response of trauma-related memories. Further theoretical developments are needed to elucidate the mechanism of bilateral EMs in trauma treatment.

Extracellular zinc regulates contextual fear memory formation in male rats through MMP-BDNF-TrkB pathway in dorsal hippocampus and basolateral amygdala.

Large amount of zinc (100 µM even up to 300 µM) is released from the nerve terminals in response to high frequency neuronal stimulation in certain brain regions including hippocampus and amygdala. However, its precise pharmacological effect is poorly understood. Here, we investigated the role of extracellular zinc (endogenous zinc) and exogenous zinc in memory formation using contextual fear conditioning (CFC) model. Male Sprague Dawley rats were trained for fear conditioning followed by in vivo microdialysis for collection of microdialysate samples from CA1 and CA3 regions of hippocampus and basolateral amygdala (BLA). Extracellular zinc chelator CaEDTA, BDNF scavenger TrkB-Fc, exogenous 7,8-DHF and matrix metalloproteinases (MMP) inhibitor were infused into the CA1 and CA3 regions of hippocampus and BLA after CFC. Different doses of exogenous zinc hydroaspartate were administered intraperitoneally immediately after CFC. We found that CFC increased the level of extracellular zinc in the hippocampus and BLA. Infusing the CaEDTA, TrkB-Fc and MMP inhibitor into the CA1 and CA3 regions of hippocampus and BLA disrupted the fear memory formation. Furthermore, administration of TrKB agonist 7,8-DHF reversed the inhibitory effect of CaEDTA on fear memory formation, suggesting that extracellular zinc may regulate fear memory formation via the BDNF-TrKB pathway. We also found that high dose of exogenous zinc hydroaspartate supplementation increased extracellular zinc levels in brain and enhanced fear memory formation. Altogether, these findings indicate that extracellular zinc may participate in formation of contextual fear memory through MMP-BDNF-TrkB pathway in the hippocampus and BLA.

"uma casa e uma sanfona para sonhar": grupo multifamiliar musicoterapêutico na comunidade / "una casa y un acordeón para soñar": grupo de musicoterapia multifamiliar en la comunidad / "a house and an accordion to dream": multifamily music therapy group in a community

RESUMO. Esta pesquisa tem por objetivo investigar o uso do Grupo Multifamiliar Musicoterapêutico (GMM) junto a famílias socialmente vulneráveis. Trata-se de uma pesquisa-intervenção realizada em uma região administrativa do Distrito Federal. Participaram do estudo 30 famílias inscritas no Cadastro Único do governo federal e atendidas no Centro de Referência em Assistência Social. Os instrumentos de coleta de dados foram as visitas domiciliares, as entrevistas semiestruturadas e os registros dos encontros e das supervisões. O GMM foi realizado em seis encontros, com duração de 03 horas cada, com periodicidade quinzenal, intercalados com as supervisões da equipe, formada por 15 profissionais das áreas de psicologia, pedagogia, assistência social e musicoterapia. Após a análise foram identificados dois temas: 1) música, afetos e reminiscências; 2) música e sonhos. Percebeu-se que as experiências musicais auxiliaram as famílias na conscientização das formas violentas de comunicação e na transformação por meio de expressões afetuosas mediadas pela música e seu potencial de evocar memórias e sonhos. A capacidade imaginativa das famílias foi uma estratégia de enfrentamento às adversidades e se constituiu como ponte entre o real e o imaginário, nutrindo a esperança de uma vida melhor. Destaca-se o valor da música que, com rapidez e emocionalidade, acessa e comunica com o tal público, por favorecer intervenções musicoterapêuticas comunitárias.

RESUMEN. Este trabajo tiene como objetivo investigar el uso del Grupo Musicoterapéutico Multifamiliar (GMM) con familias socialmente vulnerables. Se trata de una intervención-investigación realizada en una Región Administrativa del Distrito Federal. Participaron del estudio 30 familias que se encuentran inscritas en el Registro Único del Gobierno Federal y que son atendidas en el Centro de Referencia de Asistencia Social. Los instrumentos de recolección de datos fueron: visitas domiciliarias, entrevistas semiestructuradas y registros de reuniones y supervisiones. El GMM fue realizado en seis encuentros, con una duración de tres horas cada uno. Los encuentros se realizaron cada dos semanas, intercalados con la supervisión del equipo, formado por 15 profesionales en las áreas de psicología, pedagogía, asistencia social y musicoterapia. Después del análisis temático, se identificaron dos temas: 1) música, afectos y reminiscencias; 2) y música y sueños. Se observó que las experiencias musicales ayudaron a las familias en la concientización de las formas violentas de comunicación y en la transformación por medio de expresiones afectuosas mediadas por la música y su potencial para evocar recuerdos y sueños. La capacidad imaginativa de las familias fue una estrategia para enfrentar las adversidades y se constituye como un puente entre lo real y lo imaginario, alimentando la esperanza de una vida mejor. Se destaca el valor de la música que, con rapidez y emotividad, accede en y se comunica con esa población, favoreciendo las intervenciones de musicoterapia comunitaria.

ABSTRACT: This research aims to investigate the use of Multi-family Music Therapy Group (MMG) with socially vulnerable families. This is an intervention research carried out in an Administrative Region in the Federal District of Brazil. The study included 30 families enrolled in the Federal Government's Single Registry and assisted at the Social Assistance Reference Center. The data collection instruments were: home visits, semi-structured interviews, and records of meetings and supervisions. The MMG was carried out in six meetings, lasting three hours each, every two weeks, interspersed with the supervision of the team, which was formed by 15 professionals from the fields of psychology, pedagogy, social assistance, and music therapy. After the thematic analysis, two themes were identified: 1) music, affections, and reminiscences; and 2) music and dreams. It was noticed that the musical experiences helped the families in the awareness of violent forms of communication and in the transformation through expressions of affection mediated by music and its potential to evoke memories and dreams. The families imaginative capacity was a strategy to face adversities and constitutes a bridge between the real and the imaginary, nurturing the hope of a better life. The value of music is highlighted, which quickly and emotionally accesses and communicates with that audience, favoring community music therapy interventions.

Guided reactivation of personal phobic memories prior to exposure exercises prevents the renewal of fear responses in subjects with claustrophobic fears.

BACKGROUND AND OBJECTIVES: Basic research suggest behavioral strategies for interferencing the reconsolidation of fear memories to be a promising approach in reducing clinical fears. However, first clinical studies revealed mixed results highlighting the need to identify boundary conditions. We experimentally tested the specific hypothesis that post-retrieval threat exposure prevents context renewal usually observed in protocols without fear memory reactivation. METHODS: In a preliminary investigation forty-three individuals with claustrophobic fears reactivated the individual phobic memory or not during a guided emotional imagery task and then performed standardized threat exposure to provide new information for updating the original memory. During retests seven and 28 days later, the context was different from that during treatment in half of the subjects. RESULTS: In those who were guided, the fear memory was successfully reactivated as indexed by increased skin conductance level (SCL) during the imagery of personal scenes relative to neutral scenes. During retests the subjects of the memory non-activation group showed a return of reported fear after context change that, however, was not observed after post-retrieval exposure. In line, autonomic arousal (SCL) decreased over time in the memory reactivation group only if the context changed during retest. LIMITATIONS: Limited sample size and the inclusion of an analog sample reduce the generalizability of the results. CONCLUSIONS: The reactivation of fear memory prior to treatment through guided imagery of past personal phobic situations prevented contextual renewal of phobic fears which was observed in those subjects without reactivation of memory.

The enactment effect: A systematic review and meta-analysis of behavioral, neuroimaging, and patient studies.

The enactment effect is the phenomenon that physically performing an action represented by a word or phrase (e.g., clap, clap your hands) results in better memory than does simply reading it. We examined data from three different methodological approaches to provide a comprehensive review of the enactment effect across 145 behavioral, 7 neuroimaging, and 31 neurological patient studies. Boosts in memory performance following execution of a physical action were compared to those produced by reading words or phrases, by watching an experimenter perform actions, or by engaging in self-generated imagery. Across the behavioral studies, we employed random-effects meta-regression with robust variance estimation (RVE) to reveal an average enactment effect size of g = 1.23. Further meta-analyses revealed that variations in study design and comparison task reliably influence the size of the enactment effect, whereas four other experiment factors-test format, learning instruction type, retention interval, and the presence of objects during encoding-likely do not influence the effect. Neuroimaging studies demonstrated enactment-related activation to be prevalent in the motor cortex and inferior parietal lobule. Patient studies indicated that, regardless of whether impairments of memory (e.g., Alzheimer's) or of motor capability (e.g., Parkinson's) were present, patients were able to benefit from enactment. The findings of this systematic review and meta-analysis highlight two components accounting for the memory benefit from enactment: a primary mental contribution relating to planning the action and a secondary physical contribution of the action itself. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Hypothalamic modulation of adult hippocampal neurogenesis in mice confers activity-dependent regulation of memory and anxiety-like behavior.

Adult hippocampal neurogenesis plays a critical role in memory and emotion processing, and this process is dynamically regulated by neural circuit activity. However, it remains unknown whether manipulation of neural circuit activity can achieve sufficient neurogenic effects to modulate behavior. Here we report that chronic patterned optogenetic stimulation of supramammillary nucleus (SuM) neurons in the mouse hypothalamus robustly promotes neurogenesis at multiple stages, leading to increased production of neural stem cells and behaviorally relevant adult-born neurons (ABNs) with enhanced maturity. Functionally, selective manipulation of the activity of these SuM-promoted ABNs modulates memory retrieval and anxiety-like behaviors. Furthermore, we show that SuM neurons are highly responsive to environmental novelty (EN) and are required for EN-induced enhancement of neurogenesis. Moreover, SuM is required for ABN activity-dependent behavioral modulation under a novel environment. Our study identifies a key hypothalamic circuit that couples novelty signals to the production and maturation of ABNs, and highlights the activity-dependent contribution of circuit-modified ABNs in behavioral regulation.

The "Sickness" Memory: Can Patients With Alzheimer Disease Remember the Diagnosis Announcement?

BACKGROUND: Diagnosis of Alzheimer disease (AD) can cause substantial psychological distress in patients. We thus assessed how patients with AD remember the announcement of diagnosis. METHODS: We recruited 47 participants with mild AD (26 women; M age=68.89 y, SD=7.37; M years of formal education=9.74, SD=3.00). We invited the participants to remember the moment when their clinicians announced their diagnosis, within 6 months of the event, as well as a control memory, over the same period. We analyzed memory retrieval regarding specificity, as well as the subjective experience of retrieval (ie, regarding mental time travel, visual imagery, emotion and importance). RESULTS: No significant differences were observed between memory of diagnosis and control memory regarding specificity, mental time travel and visual imagery. However, memory of diagnosis triggered a more intense emotional experience and feeling of importance than control memory. DISCUSSION: Retrieval of the diagnosis announcement can activate a strong emotional and personally important experience in patients with AD. When remembering the diagnosis announcement, patients with AD may re-experience some features of that turning point in which they shift from "person" to "patient."

Memory-directed acupuncture as a neuromodulatory treatment for PTSD: Theory, clinical model and case studies.

Posttraumatic stress disorder (PTSD) poses an ongoing challenge to society, to health systems, and to the trauma victims themselves. Today PTSD is often considered an incurable chronic problem that lacks effective treatment. While PTSD is closely related to memory, it also affects many physiological systems. PTSD is usually treated with medications and psychotherapy with moderate success, leaving a substantial proportion of patients with enduring distress and disability. Therefore, a search for better treatment options is vital. In this paper, we propose a model in which a conversation-based technique is integrated with bodily manipulation through acupuncture. This approach first emerged in clinical experience showing intriguing results from treating PTSD patients using acupuncture as a main strategy. Its theoretical foundations derive from the clinic and rely on contemporary neuroscience's understanding of memory consolidation and reconsolidation processes. Research shows that acupuncture can have potentially positive effects at three levels: (a) achieving a balance between sympathetic and parasympathetic neural activity; (b) reducing activation in the limbic system, hence inducing a calming effect; (c) reshaping the functional connectivity map within important and relevant cortical regions that encompass the default-mode network. We suggest that coupling traumatic memory retrieval leading to reconsolidation, combined with acupuncture, offers considerable potential for positive clinical improvement in patients with PTSD. This may explain the positive results of the described case studies and can pave the path for future advances in research and treatment in this field.

Potential improvements of the cognition of piglets through a synbiotic supplementation from 1 to 28 days via the gut microbiota.

The influence of feed supplements on behavior and memory has been recently studied in livestock. The objectives of the study were to evaluate the effects of a synbiotic on: an episodic-like (SOR: Spontaneous Object Recognition), a working (BARR: Fence barrier task), a long-term (TMAZE: Spatial T-maze task) memory test and on gut microbiota composition. Eighteen female piglets were supplemented from 1 to 28 days of age with a synbiotic (SYN), while 17 served as control (CTL). Feces were collected on days 16, 33 and 41 for 16S rRNA gene composition analyses. In the SOR, SYN piglets interacted more quickly with the novel object than CTL piglets. In the BARR, SYN piglets had shorter distances to finish the test in trial 3. In the TMAZE, SYN piglets were quicker to succeed on specific days and tended to try the new rewarded arm earlier during the reversal stage. Difference of microbiota composition between treatments was nonexistent on D16, a tendency on D33 and significant on D41. The synbiotic supplement may confer memory advantages in different cognitive tasks, regardless of the nature of the reward and the memory request. Difference in memory abilities can potentially be explained by differences in microbiota composition.

Progressive modulation of resting-state brain activity during neurofeedback of positive-social emotion regulation networks.

Neurofeedback allows for the self-regulation of brain circuits implicated in specific maladaptive behaviors, leading to persistent changes in brain activity and connectivity. Positive-social emotion regulation neurofeedback enhances emotion regulation capabilities, which is critical for reducing the severity of various psychiatric disorders. Training dorsomedial prefrontal cortex (dmPFC) to exert a top-down influence on bilateral amygdala during positive-social emotion regulation progressively (linearly) modulates connectivity within the trained network and induces positive mood. However, the processes during rest that interleave the neurofeedback training remain poorly understood. We hypothesized that short resting periods at the end of training sessions of positive-social emotion regulation neurofeedback would show alterations within emotion regulation and neurofeedback learning networks. We used complementary model-based and data-driven approaches to assess how resting-state connectivity relates to neurofeedback changes at the end of training sessions. In the experimental group, we found lower progressive dmPFC self-inhibition and an increase of connectivity in networks engaged in emotion regulation, neurofeedback learning, visuospatial processing, and memory. Our findings highlight a large-scale synergy between neurofeedback and resting-state brain activity and connectivity changes within the target network and beyond. This work contributes to our understanding of concomitant learning mechanisms post training and facilitates development of efficient neurofeedback training.

Independent dynamics of low, intermediate, and high frequency spectral intracranial EEG activities during human memory formation.

A wide spectrum of brain rhythms are engaged throughout the human cortex in cognitive functions. How the rhythms of various frequency ranges are coordinated across the space of the human cortex and time of memory processing is inconclusive. They can either be coordinated together across the frequency spectrum at the same cortical site and time or induced independently in particular bands. We used a large dataset of human intracranial electroencephalography (iEEG) to parse the spatiotemporal dynamics of spectral activities induced during formation of verbal memories. Encoding of words for subsequent free recall activated low frequency theta, intermediate frequency alpha and beta, and high frequency gamma power in a mosaic pattern of discrete cortical sites. A majority of the cortical sites recorded activity in only one of these frequencies, except for the visual cortex where spectral power was induced across multiple bands. Each frequency band showed characteristic dynamics of the induced power specific to cortical area and hemisphere. The power of the low, intermediate, and high frequency activities propagated in independent sequences across the visual, temporal and prefrontal cortical areas throughout subsequent phases of memory encoding. Our results provide a holistic, simplified model of the spectral activities engaged in the formation of human memory, suggesting an anatomically and temporally distributed mosaic of coordinated brain rhythms.

Aged Brains Express Less Melanocortin Receptors, Which Correlates with Age-Related Decline of Cognitive Functions.

Brain G-protein coupled receptors have been hypothesized to be potential targets for maintaining or restoring cognitive function in normal aged individuals or in patients with neurodegenerative disease. A number of recent reports suggest that activation of melanocortin receptors (MCRs) in the brain can significantly improve cognitive functions of normal rodents and of different rodent models of the Alzheimer's disease. However, the potential impact of normative aging on the expression of MCRs and their potential roles for modulating cognitive function remains to be elucidated. In the present study, we first investigated the expression of these receptors in six different brain regions of young (6 months) and aged (23 months) rats following assessment of their cognitive status. Correlation analysis was further performed to reveal potential contributions of MCR subtypes to spatial learning and memory. Our results revealed statistically significant correlations between the expression of several MCR subtypes in the frontal cortex/hypothalamus and the hippocampus regions and the rats' performance in spatial learning and memory only in the aged rats. These findings support the hypothesis that aging has a direct impact on the expression and function of MCRs, establishing MCRs as potential drug targets to alleviate aging-induced decline of cognitive function.

BACE inhibitor treatment of mice induces hyperactivity in a Seizure-related gene 6 family dependent manner without altering learning and memory.

BACE inhibitors, which decrease BACE1 (ß-secretase 1) cleavage of the amyloid precursor protein, are a potential treatment for Alzheimer's disease. Clinical trials using BACE inhibitors have reported a lack of positive effect on patient symptoms and, in some cases, have led to increased adverse events, cognitive worsening and hippocampal atrophy. A potential drawback of this strategy is the effect of BACE inhibition on other BACE1 substrates such as Seizure-related gene 6 (Sez6) family proteins which are known to have a role in neuronal function. Mice were treated with an in-diet BACE inhibitor for 4-8 weeks to achieve a clinically-relevant level of amyloid-ß40 reduction in the brain. Mice underwent behavioural testing and postmortem analysis of dendritic spine number and morphology with Golgi-Cox staining. Sez6 family triple knockout mice were tested alongside wild-type mice to identify whether any effects of the treatment were due to altered cleavage of Sez6 family proteins. Wild-type mice treated with BACE inhibitor displayed hyperactivity on the elevated open field, as indicated by greater distance travelled, but this effect was not observed in treated Sez6 triple knockout mice. BACE inhibitor treatment did not lead to significant changes in spatial or fear learning, reference memory, cognitive flexibility or anxiety in mice as assessed by the Morris water maze, context fear conditioning, or light-dark box tests. Chronic BACE inhibitor treatment reduced the density of mushroom-type spines in the somatosensory cortex, regardless of genotype, but did not affect steady-state dendritic spine density or morphology in the CA1 region of the hippocampus. Chronic BACE inhibition for 1-2 months in mice led to increased locomotor output but did not alter memory or cognitive flexibility. While the mechanism underlying the treatment-induced hyperactivity is unknown, the absence of this response in Sez6 triple knockout mice indicates that blocking ectodomain shedding of Sez6 family proteins is a contributing factor. In contrast, the decrease in mature spine density in cortical neurons was not attributable to lack of shed Sez6 family protein ectodomains. Therefore, other BACE1 substrates are implicated in this effect and, potentially, in the cognitive decline in longer-term chronically treated patients.