Chronic unpredictable stress induces autophagic death of adult hippocampal neural stem cells.

Chronic psychological stress is a critical factor for neurological complications like anxiety disorders, dementia, and depression. Our previous results show that chronic restraint stress causes cognitive deficits and mood dysregulation by inducing autophagic death of adult hippocampal neural stem cells (NSCs). However, it is unknown whether other models of psychological stress also induce autophagic death of adult hippocampal NSCs. Here, we show that chronic unpredictable stress (CUS) for 10 days impaired memory function and increased anxiety in mice. Immunohistochemical staining with SOX2 and KI67 revealed a significant reduction in the number of NSCs in the hippocampus following exposure to CUS. However, these deficits were prevented by NSC-specific, inducible conditional deletion of Atg7. These findings suggest that autophagic death of adult hippocampal NSCs is a critical pathogenic mechanism underlying stress-induced brain disorders.

Robust memory of face moral values is encoded in the human caudate tail: a simultaneous EEG-fMRI study.

Moral judgements about people based on their actions is a key component that guides social decision making. It is currently unknown how positive or negative moral judgments associated with a person's face are processed and stored in the brain for a long time. Here, we investigate the long-term memory of moral values associated with human faces using simultaneous EEG-fMRI data acquisition. Results show that only a few exposures to morally charged stories of people are enough to form long-term memories a day later for a relatively large number of new faces. Event related potentials (ERPs) showed a significant differentiation of remembered good vs bad faces over centerofrontal electrode sites (value ERP). EEG-informed fMRI analysis revealed a subcortical cluster centered on the left caudate tail (CDt) as a correlate of the face value ERP. Importantly neither this analysis nor a conventional whole-brain analysis revealed any significant coding of face values in cortical areas, in particular the fusiform face area (FFA). Conversely an fMRI-informed EEG source localization using accurate subject-specific EEG head models also revealed activation in the left caudate tail. Nevertheless, the detected caudate tail region was found to be functionally connected to the FFA, suggesting FFA to be the source of face-specific information to CDt. A further psycho-physiological interaction analysis also revealed task-dependent coupling between CDt and dorsomedial prefrontal cortex (dmPFC), a region previously identified as retaining emotional working memories. These results identify CDt as a main site for encoding the long-term value memories of faces in humans suggesting that moral value of faces activates the same subcortical basal ganglia circuitry involved in processing reward value memory for objects in primates.

Adult-born granule cells modulate CA2 network activity during retrieval of developmental memories of the mother.

Adult-born granule cells (abGCs) project to the CA2 region of the hippocampus, but it remains unknown how this circuit affects behavioral function. Here, we show that abGC input to the CA2 of adult mice is involved in the retrieval of remote developmental memories of the mother. Ablation of abGCs impaired the ability to discriminate between a caregiving mother and a novel mother, and this ability returned after abGCs were regenerated. Chemogenetic inhibition of projections from abGCs to the CA2 also temporarily prevented the retrieval of remote mother memories. These findings were observed when abGCs were inhibited at 4-6 weeks old, but not when they were inhibited at 10-12 weeks old. We also found that abGCs are necessary for differentiating features of CA2 network activity, including theta-gamma coupling and sharp wave ripples, in response to novel versus familiar social stimuli. Taken together, these findings suggest that abGCs are necessary for neuronal oscillations associated with discriminating between social stimuli, thus enabling retrieval of remote developmental memories of the mother by their adult offspring.

Post-retrieval stress impairs subsequent memory depending on hippocampal memory trace reinstatement during reactivation.

Upon retrieval, memories can become susceptible to meaningful events, such as stress. Post-retrieval memory changes may be attributed to an alteration of the original memory trace during reactivation-dependent reconsolidation or, alternatively, to the modification of retrieval-related memory traces that impact future remembering. Hence, how post-retrieval memory changes emerge in the human brain is unknown. In a 3-day functional magnetic resonance imaging study, we show that post-retrieval stress impairs subsequent memory depending on the strength of neural reinstatement of the original memory trace during reactivation, driven by the hippocampus and its cross-talk with neocortical representation areas. Comparison of neural patterns during immediate and final memory testing further revealed that successful retrieval was linked to pattern-dissimilarity in controls, suggesting the use of a different trace, whereas stressed participants relied on the original memory representation. These representation changes were again dependent on neocortical reinstatement during reactivation. Our findings show disruptive stress effects on the consolidation of retrieval-related memory traces that support future remembering.

A sparse quantized hopfield network for online-continual memory.

An important difference between brains and deep neural networks is the way they learn. Nervous systems learn online where a stream of noisy data points are presented in a non-independent, identically distributed way. Further, synaptic plasticity in the brain depends only on information local to synapses. Deep networks, on the other hand, typically use non-local learning algorithms and are trained in an offline, non-noisy, independent, identically distributed setting. Understanding how neural networks learn under the same constraints as the brain is an open problem for neuroscience and neuromorphic computing. A standard approach to this problem has yet to be established. In this paper, we propose that discrete graphical models that learn via an online maximum a posteriori learning algorithm could provide such an approach. We implement this kind of model in a neural network called the Sparse Quantized Hopfield Network. We show our model outperforms state-of-the-art neural networks on associative memory tasks, outperforms these networks in online, continual settings, learns efficiently with noisy inputs, and is better than baselines on an episodic memory task.

Human intraparietal sulcal morphology relates to individual differences in language and memory performance.

The sulco-gyral pattern is a qualitative feature of the cortical anatomy that is determined in utero, stable throughout lifespan and linked to brain function. The intraparietal sulcus (IPS) is a nodal associative brain area, but the relation between its morphology and cognition is largely unknown. By labelling the left and right IPS of 390 healthy participants into two patterns, according to the presence or absence of a sulcus interruption, here we demonstrate a strong association between the morphology of the right IPS and performance on memory and language tasks. We interpret the results as a morphological advantage of a sulcus interruption, probably due to the underlying white matter organization. The right-hemisphere specificity of this effect emphasizes the neurodevelopmental and plastic role of sulcus morphology in cognition prior to lateralisation processes. The results highlight a promising area of investigation on the relationship between cognitive performance, sulco-gyral pattern and white matter bundles.

Eye movement intervention facilitates concurrent perception and memory processing.

A widely used psychotherapeutic treatment for post-traumatic stress disorder (PTSD) involves performing bilateral eye movement (EM) during trauma memory retrieval. However, how this treatment-described as eye movement desensitization and reprocessing (EMDR)-alleviates trauma-related symptoms is unclear. While conventional theories suggest that bilateral EM interferes with concurrently retrieved trauma memories by taxing the limited working memory resources, here, we propose that bilateral EM actually facilitates information processing. In two EEG experiments, we replicated the bilateral EM procedure of EMDR, having participants engaging in continuous bilateral EM or receiving bilateral sensory stimulation (BS) as a control while retrieving short- or long-term memory. During EM or BS, we presented bystander images or memory cues to probe neural representations of perceptual and memory information. Multivariate pattern analysis of the EEG signals revealed that bilateral EM enhanced neural representations of simultaneously processed perceptual and memory information. This enhancement was accompanied by heightened visual responses and increased neural excitability in the occipital region. Furthermore, bilateral EM increased information transmission from the occipital to the frontoparietal region, indicating facilitated information transition from low-level perceptual representation to high-level memory representation. These findings argue for theories that emphasize information facilitation rather than disruption in the EMDR treatment.

Effective modulation from the ventral medial to the dorsal medial portion of the prefrontal cortex in memory confidence-based behavioral control.

Metacognition includes the ability to refer to one's own cognitive states, such as confidence, and adaptively control behavior based on this information. This ability is thought to allow us to predictably control our behavior without external feedback, for example, even before we take action. Many studies have suggested that metacognition requires a brain-wide network of multiple brain regions. However, the modulation of effective connectivity within this network during metacognitive tasks remains unclear. This study focused on medial prefrontal regions, which have recently been suggested to be particularly involved in metacognition. We examined whether modulation of effective connectivity specific to metacognitive behavioral control is observed using model-based network analysis and dynamic causal modeling (DCM). The results showed that negative modulation from the ventral medial prefrontal cortex to the dorsal medial prefrontal cortex was observed in situations that required metacognitive behavioral control but not in situations that did not require such metacognitive control. Furthermore, this modulation was particularly pronounced in the group of participants who could better use metacognition for behavioral control. These results imply hierarchical properties of metacognition-related brain networks.

Drift of neural ensembles driven by slow fluctuations of intrinsic excitability.

Representational drift refers to the dynamic nature of neural representations in the brain despite the behavior being seemingly stable. Although drift has been observed in many different brain regions, the mechanisms underlying it are not known. Since intrinsic neural excitability is suggested to play a key role in regulating memory allocation, fluctuations of excitability could bias the reactivation of previously stored memory ensembles and therefore act as a motor for drift. Here, we propose a rate-based plastic recurrent neural network with slow fluctuations of intrinsic excitability. We first show that subsequent reactivations of a neural ensemble can lead to drift of this ensemble. The model predicts that drift is induced by co-activation of previously active neurons along with neurons with high excitability which leads to remodeling of the recurrent weights. Consistent with previous experimental works, the drifting ensemble is informative about its temporal history. Crucially, we show that the gradual nature of the drift is necessary for decoding temporal information from the activity of the ensemble. Finally, we show that the memory is preserved and can be decoded by an output neuron having plastic synapses with the main region.

The effect of misophonia on cognitive and social judgments.

Misophonia, a heightened aversion to certain sounds, turns common cognitive and social exercises (e.g., paying attention during a lecture near a pen-clicking classmate, coexisting at the dinner table with a food-chomping relative) into challenging endeavors. How does exposure to triggering sounds impact cognitive and social judgments? We investigated this question in a sample of 65 participants (26 misophonia, 39 control) from the general population. In Phase 1, participants saw faces paired with auditory stimuli while completing a gender judgment task, then reported sound discomfort and identification. In Phase 2, participants saw these same faces with novel ones and reported face likeability and memory. For both oral and non-oral triggers, misophonic participants gave higher discomfort ratings than controls did-especially when identification was correct-and performed slower on the gender judgment. Misophonic participants rated lower likeability than controls did for faces they remembered with high discomfort sounds, and face memory was worse overall for faces originally paired with high discomfort sounds. Altogether, these results suggest that misophonic individuals show impairments on social and cognitive judgments if they must endure discomforting sounds. This experiment helps us better understand the day-to-day impact of misophonia and encourages usage of individualized triggers in future studies.

Eye tracking evidence for the reinstatement of emotionally negative and neutral memories.

Recent eye tracking studies have linked gaze reinstatement-when eye movements from encoding are reinstated during retrieval-with memory performance. In this study, we investigated whether gaze reinstatement is influenced by the affective salience of information stored in memory, using an adaptation of the emotion-induced memory trade-off paradigm. Participants learned word-scene pairs, where scenes were composed of negative or neutral objects located on the left or right side of neutral backgrounds. This allowed us to measure gaze reinstatement during scene memory tests based on whether people looked at the side of the screen where the object had been located. Across two experiments, we behaviorally replicated the emotion-induced memory trade-off effect, in that negative object memory was better than neutral object memory at the expense of background memory. Furthermore, we found evidence that gaze reinstatement was related to recognition memory for the object and background scene components. This effect was generally comparable for negative and neutral memories, although the effects of valence varied somewhat between the two experiments. Together, these findings suggest that gaze reinstatement occurs independently of the processes contributing to the emotion-induced memory trade-off effect.

Children exhibit superior memory for attended but outdated information compared to adults.

Research on the development of cognitive selectivity predominantly focuses on attentional selection. The present study explores another facet of cognitive selectivity-memory selection-by examining the ability to filter attended yet outdated information in young children and adults. Across five experiments involving 130 children and 130 adults, participants are instructed to use specific information to complete a task, and then unexpectedly asked to report this information in a surprise test. The results consistently demonstrate a developmental reversal-like phenomenon, with children outperforming adults in reporting this kind of attended yet outdated information. Furthermore, we provide evidence against the idea that the results are due to different processing strategies or attentional deployments between adults and children. These results suggest that the ability of memory selection is not fully developed in young children, resulting in their inefficient filtering of attended yet outdated information that is not required for memory retention.

Hippocampal sharp-wave ripples correlate with periods of naturally occurring self-generated thoughts in humans.

Core features of human cognition highlight the importance of the capacity to focus on information distinct from events in the here and now, such as mind wandering. However, the brain mechanisms that underpin these self-generated states remain unclear. An emerging hypothesis is that self-generated states depend on the process of memory replay, which is linked to sharp-wave ripples (SWRs), which are transient high-frequency oscillations originating in the hippocampus. Local field potentials were recorded from the hippocampus of 10 patients with epilepsy for up to 15 days, and experience sampling was used to describe their association with ongoing thought patterns. The SWR rates were higher during extended periods of time when participants' ongoing thoughts were more vivid, less desirable, had more imaginable properties, and exhibited fewer correlations with an external task. These data suggest a role for SWR in the patterns of ongoing thoughts that humans experience in daily life.

Electroacupuncture regulates Rab5a-mediating NGF transduction to improve learning and memory ability in the early stage of AD mice.

AIMS: Nerve growth factor (NGF) loss is a potential factor for the degeneration of basal forebrain cholinergic neurons (BFCNs) in Alzheimer's disease (AD), and Rab5a is a key regulatory molecule of NGF signaling transduction. Here, we investigated the changes of Rab5a in 5 × FAD mice and further explored the mechanism of Electroacupuncture (EA) treatment in improving cognition in the early stage of AD. METHODS: The total Rab5a and Rab5a-GTP in 5-month-old 5 × FAD mice and wild-type mice were detected using WB and IP technologies. 5 × FAD mice were treated with EA at the Bai hui (DU20) and Shen ting (DU24) acupoints for 4 weeks and CRE/LOXP technology was used to confirm the role of Rab5a in AD mediated by EA stimulation. The Novel Object Recognition and Morris water maze tests were used to evaluate the cognitive function of 5 × FAD mice. The Nissl, immunohistochemistry, and Thioflavin S staining were used to observe pathological morphological changes in the basal forebrain circuit. The Golgi staining was used to investigate the synaptic plasticity of the basal forebrain circuit and WB technology was used to detect the expression levels of cholinergic-related and NGF signal-related proteins. RESULTS: The total Rab5a was unaltered, but Rab5a-GTP increased and the rab5a-positive early endosomes appeared enlarged in the hippocampus of 5 × FAD mice. Notably, EA reduced Rab5a-GTP in the hippocampus in the early stage of 5 × FAD mice. EA could improve object recognition memory and spatial learning memory by reducing Rab5a activity in the early stage of 5 × FAD mice. Moreover, EA could reduce Rab5a activity to increase NGF transduction and increase the levels of phosphorylated TrkA, AKT, and ERK in the basal forebrain and hippocampus, and increase the expression of cholinergic-related proteins, such as ChAT, vAchT, ChT1, m1AchR, and m2AchR in the basal forebrain and ChAT, m1AchR, and m2AchR in the hippocampus, improving synaptic plasticity in the basal forebrain hippocampal circuit in the early stage of 5 × FAD mice. CONCLUSIONS: Rab5a hyperactivation is an early pathological manifestation of 5 × FAD mice. EA could suppress Rab5a-GTP to promote the transduction of NGF signaling, and enhance the synaptic plasticity of the basal forebrain hippocampal circuit improving cognitive impairment in the early stage of 5 × FAD mice.

Tactile memory impairments in younger and older adults.

Human tactile memory allows us to remember and retrieve the multitude of somatosensory experiences we undergo in everyday life. An unsolved question is how tactile memory mechanisms change with increasing age. We here use the ability to remember fine-grained tactile patterns passively presented to the fingertip to investigate age-related changes in tactile memory performance. In experiment 1, we varied the degree of similarity between one learned and several new tactile patterns to test on age-related changes in the "uniqueness" of a stored tactile memory trace. In experiment 2, we varied the degree of stimulus completeness of both known and new tactile patterns to test on age-related changes in the weighting between known and novel tactile information. Results reveal that older adults show only weak impairments in both precision and bias of tactile memories, however, they show specific deficits in reaching peak performance > 85% in both experiments. In addition, both younger and older adults show a pattern completion bias for touch, indicating a higher weighting of known compared to new information. These results allow us to develop new models on how younger and older adults store and recall tactile experiences of the past, and how this influences their everyday behavior.

Should brain chip implants for memory and cognitive enhancement be banned in competitive national examinations?

In a recent medical breakthrough, Elon Musk's startup company Neuralink implanted the first brain chip in a human patient, purportedly for aiding paralysis. While certainly representing a significant medical milestone for many patients afflicted with debilitating brain and spinal cord injuries, as well as devastating neurodegenerative diseases such as Parkinson's and Alzheimer's, it must be noted that this very same technology can also be manipulated for human memory or cognitive enhancement. What happens if a brain chip were to be developed that can significantly improve either IQ (intelligence quotient) or memory, and these were then implanted in people to enhance their performance in highly competitive national examinations for college entrance or gaining employment in civil service positions? This article therefore discusses the ethical implications of this nascent technology platform, and whether its use in competitive national examinations should be banned.

Computational models of intrinsic motivation for curiosity and creativity.

We link Ivancovsky et al.'s novelty-seeking model (NSM) to computational models of intrinsically motivated behavior and learning. We argue that dissociating different forms of curiosity, creativity, and memory based on the involvement of distinct intrinsic motivations (e.g., surprise and novelty) is essential to empirically test the conceptual claims of the NSM.

An extension of the novelty-seeking model: Considering the plurality of novelty types and their differential interactions with memory.

The novelty-seeking model suggests that curiosity and creativity originate from novelty processes. However, different types of novelty exist, each with distinctive relationships with memory, which potentially influence curiosity and creativity in distinct ways. We thus propose expanding the NSM model to consider these different novelty types and their specific involvement in creativity.

Tai Chi Chuan evidence related to impulsivity and impulse related disorders: A scoping review.

BACKGROUND: The purpose of this study was to review the evidence for the potential of Tai Chi Chuan (TCC) as a model of meditative movement in benefiting people with impulsivity related disorders and provide guidance for future research. METHODS: A scoping review of the literature was conducted in five databases. Eligibility criteria were original articles reporting TCC based interventions or included TCC techniques and provided any assessment on impulsivity or related measures, impulse control disorders, or other psychiatric disorders related to impulsivity (e.g., addictive disorders, ADHD, and other conduct disorders). Twenty-eight out of 304 studies initially retrieved were reviewed. The reports concentrated mostly on neurodegenerative conditions, cognitive decline, and substance use disorders (SUD). RESULTS: TCC had several positive effects in cognitive domains resulting in improvements in memory, executive functions, inhibitory control, attention, and verbal fluency. These improvements in memory, executive function, including inhibitory control and attention, and verbal fluency were associated with changes in the brain plasticity, resting activity, and other neurobiological markers. CONCLUSION: Albeit no study was found on the use of TCC in impulse control disorders or impulse related conditions, other than SUD, the findings suggest that considering the behavioral impact of TCC, especially the improvement of executive functions, it could be a valuable therapeutic tool for approaching impulse control related disorders.

Infralimbic activity during REM sleep facilitates fear extinction memory.

Rapid eye movement (REM) sleep is known to facilitate fear extinction and play a protective role against fearful memories.1,2 Consequently, disruption of REM sleep after a traumatic event may increase the risk for developing PTSD.3,4 However, the underlying mechanisms by which REM sleep promotes extinction of aversive memories remain largely unknown. The infralimbic cortex (IL) is a key brain structure for the consolidation of extinction memory.5 Using calcium imaging, we found in mice that most IL pyramidal neurons are intensively activated during REM sleep. Optogenetically suppressing the IL specifically during REM sleep within a 4-h window after auditory-cued fear conditioning impaired extinction memory consolidation. In contrast, REM-specific IL inhibition after extinction learning did not affect the extinction memory. Whole-cell patch-clamp recordings demonstrated that inactivating IL neurons during REM sleep depresses their excitability. Together, our findings suggest that REM sleep after fear conditioning facilitates fear extinction by enhancing IL excitability and highlight the importance of REM sleep in the aftermath of traumatic events for protecting against traumatic memories.