Chemogenetic activation or inhibition of histaminergic neurons bidirectionally modulates recognition memory formation and retrieval in male and female mice.

Several lines of evidence demonstrate that the brain histaminergic system is fundamental for cognitive processes and the expression of memories. Here, we investigated the effect of acute silencing or activation of histaminergic neurons in the hypothalamic tuberomamillary nucleus (TMNHA neurons) in vivo in both sexes in an attempt to provide direct and causal evidence of the necessary role of these neurons in recognition memory formation and retrieval. To this end, we compared the performance of mice in two non-aversive and non-rewarded memory tests, the social and object recognition memory tasks, which are known to recruit different brain circuitries. To directly establish the impact of inactivation or activation of TMNHA neurons, we examined the effect of specific chemogenetic manipulations during the formation (acquisition/consolidation) or retrieval of recognition memories. We consistently found that acute chemogenetic silencing of TMNHA neurons disrupts the formation or retrieval of both social and object recognition memory in males and females. Conversely, acute chemogenetic activation of TMNHA neurons during training or retrieval extended social memory in both sexes and object memory in a sex-specific fashion. These results suggest that the formation or retrieval of recognition memory requires the tonic activity of histaminergic neurons and strengthen the concept that boosting the brain histaminergic system can promote the retrieval of apparently lost memories.

Have you been there before? Decoding recognition of spatial scenes from fMRI signals in precuneus.

One potential application of forensic "brain reading" is to test whether a suspect has previously experienced a crime scene. Here, we investigated whether it is possible to decode real life autobiographic exposure to spatial locations using fMRI. In the first session, participants visited four out of eight possible rooms on a university campus. During a subsequent scanning session, subjects passively viewed pictures and videos from these eight possible rooms (four old, four novel) without giving any responses. A multivariate searchlight analysis was employed that trained a classifier to distinguish between "seen" versus "unseen" stimuli from a subset of six rooms. We found that bilateral precuneus encoded information that can be used to distinguish between previously seen and unseen rooms and that also generalized to the two stimuli left out from training. We conclude that activity in bilateral precuneus is associated with the memory of previously visited rooms, irrespective of the identity of the room, thus supporting a parietal contribution to episodic memory for spatial locations. Importantly, we could decode whether a room was visited in real life without the need of explicit judgments about the rooms. This suggests that recognition is an automatic response that can be decoded from fMRI data, thus potentially supporting forensic applications of concealed information tests for crime scene recognition.

Detecting recollection: Human evaluators can successfully assess the veracity of others' memories.

Humans have the highly adaptive ability to learn from others' memories. However, because memories are prone to errors, in order for others' memories to be a valuable source of information, we need to assess their veracity. Previous studies have shown that linguistic information conveyed in self-reported justifications can be used to train a machine-learner to distinguish true from false memories. But can humans also perform this task, and if so, do they do so in the same way the machine-learner does? Participants were presented with justifications corresponding to Hits and False Alarms and were asked to directly assess whether the witness's recognition was correct or incorrect. In addition, participants assessed justifications' recollective qualities: their vividness, specificity, and the degree of confidence they conveyed. Results show that human evaluators can discriminate Hits from False Alarms above chance levels, based on the justifications provided per item. Their performance was on par with the machine learner. Furthermore, through assessment of the perceived recollective qualities of justifications, participants were able to glean more information from the justifications than they used in their own direct decisions and than the machine learner did.

Recognizing ideas generated in a creative task: the roles of the hippocampus and medial prefrontal cortex in facilitating self-generated learning.

Creative idea generation plays an important role in promoting successful memory formation. Yet, its underlying neural correlates remain unclear. We investigated the self-generated learning of creative ideas motivated by the schema-linked interactions between medial prefrontal and medial temporal regions framework. This was achieved by having participants generate ideas in the alternative uses task, self-evaluating their ideas based on novelty and source (i.e. new or old), and then later being tested on the recognition performance of the generated ideas. At the behavioral level, our results indicated superior performances in discriminating novel ideas, highlighting the novelty effect on memory. At the neural level, the regions-of-interest analyses revealed that successful recognition of novel ideas was associated with greater activations in the hippocampus (HPC) and medial prefrontal cortex (mPFC) during ideation. However, only activation in the right HPC was positively related to the successful recognition of novel ideas. Importantly, the weaker the connection between the right HPC and left mPFC, the higher the recognition accuracy of novel ideas. Moreover, activations in the right HPC and left mPFC were both effective predictors of successful recognition of novel ideas. These findings uniquely highlight the role of novelty in promoting self-generated learning of creative ideas.

Neural correlates of individual differences in multimodal emotion recognition ability.

Studies have reported substantial variability in emotion recognition ability (ERA) - an important social skill - but possible neural underpinnings for such individual differences are not well understood. This functional magnetic resonance imaging (fMRI) study investigated neural responses during emotion recognition in young adults (N = 49) who were selected for inclusion based on their performance (high or low) during previous testing of ERA. Participants were asked to judge brief video recordings in a forced-choice emotion recognition task, wherein stimuli were presented in visual, auditory and multimodal (audiovisual) blocks. Emotion recognition rates during brain scanning confirmed that individuals with high (vs low) ERA received higher accuracy for all presentation blocks. fMRI-analyses focused on key regions of interest (ROIs) involved in the processing of multimodal emotion expressions, based on previous meta-analyses. In neural response to emotional stimuli contrasted with neutral stimuli, individuals with high (vs low) ERA showed higher activation in the following ROIs during the multimodal condition: right middle superior temporal gyrus (mSTG), right posterior superior temporal sulcus (PSTS), and right inferior frontal cortex (IFC). Overall, results suggest that individual variability in ERA may be reflected across several stages of decisional processing, including extraction (mSTG), integration (PSTS) and evaluation (IFC) of emotional information.

Neural mechanisms of Chinese character recognition, updating, and maintenance in the N-back task.

Using the N-back task, we investigated how memory load influences the neural activity of the Chinese character cognitive subprocess (recognition, updating, and maintenance) in Mainland Chinese speakers. Twenty-seven participants completed the Chinese character N-back paradigm while having their event-related potentials recorded. The study employed time and frequency domain analyses of EEG data. Results showed that accuracy decreased and response times increased with larger N values. For ERPs, N2pc and P300 amplitudes decreased and SW amplitude increased with larger N values. For time frequency analyses, the desynchronization of alpha oscillations decreased after stimulus onset, but the synchronization of alpha oscillations increased during the maintenance phase. The results suggest that greater memory load is related to a decrease in cognitive resources during updating and an increase in cognitive resources during information maintenance. The results of a behavioral-ERP data structural equation model analysis showed that the ERP indicators in the maintenance phase predicted behavioral performance.

Mesenchymal stem cell-derived exosomes improve neurogenesis and cognitive function of mice with methamphetamine addiction: A novel treatment approach.

BACKGROUND: Methamphetamine (METH) is a psychostimulant substance with highly addictive and neurotoxic effects, but no ideal treatment option exists to improve METH-induced neurocognitive deficits. Recently, mesenchymal stem cells (MSCs)-derived exosomes have raised many hopes for treating neurodegenerative sequela of brain disorders. This study aimed to determine the therapeutic potential of MSCs-derived exosomes on cognitive function and neurogenesis of METH-addicted rodents. METHODS: Male BALB/c mice were subjected to chronic METH addiction, followed by intravenous administration of bone marrow MSCs-derived exosomes. Then, the spatial memory and recognition memory of animals were assessed by the Barnes maze and the novel object recognition test (NORT). The neurogenesis-related factors, including NeuN and DCX, and the expression of Iba-1, a microglial activation marker, were assessed in the hippocampus by immunofluorescence staining. Also, the expression of inflammatory cytokines, including TNF-α and NF-κB, were evaluated by western blotting. RESULTS: The results showed that BMSCs-exosomes improved the time spent in the target quadrant and correct-to-wrong relative time in the Barnes maze. Also, NORT's discrimination index (DI) and recognition index (RI) were improved following exosome therapy. Additionally, exosome therapy significantly increased the expression of NeuN and DCX in the hippocampus while decreasing the expression of inflammatory cytokines, including TNF-α and NF-κB. Besides, BMSC-exosomes down-regulated the expression of Iba-1. CONCLUSION: Our findings indicate that BMSC-exosomes mitigated METH-caused cognitive dysfunction by improving neurogenesis and inhibiting neuroinflammation in the hippocampus.

Spatiotemporal brain hierarchies of auditory memory recognition and predictive coding.

Our brain is constantly extracting, predicting, and recognising key spatiotemporal features of the physical world in order to survive. While neural processing of visuospatial patterns has been extensively studied, the hierarchical brain mechanisms underlying conscious recognition of auditory sequences and the associated prediction errors remain elusive. Using magnetoencephalography (MEG), we describe the brain functioning of 83 participants during recognition of previously memorised musical sequences and systematic variations. The results show feedforward connections originating from auditory cortices, and extending to the hippocampus, anterior cingulate gyrus, and medial cingulate gyrus. Simultaneously, we observe backward connections operating in the opposite direction. Throughout the sequences, the hippocampus and cingulate gyrus maintain the same hierarchical level, except for the final tone, where the cingulate gyrus assumes the top position within the hierarchy. The evoked responses of memorised sequences and variations engage the same hierarchical brain network but systematically differ in terms of temporal dynamics, strength, and polarity. Furthermore, induced-response analysis shows that alpha and beta power is stronger for the variations, while gamma power is enhanced for the memorised sequences. This study expands on the predictive coding theory by providing quantitative evidence of hierarchical brain mechanisms during conscious memory and predictive processing of auditory sequences.

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.

The effect of the apolipoprotein E ε4 allele and olfactory function on odor identification networks.

INTRODUCTION: The combination of apolipoprotein E ε4 (ApoE ε4) status, odor identification, and odor familiarity predicts conversion to mild cognitive impairment (MCI) and Alzheimer's disease (AD). METHODS: To further understand olfactory disturbances and AD risk, ApoE ε4 carrier (mean age 76.38 ± 5.21) and ε4 non-carrier (mean age 76.8 ± 3.35) adults were given odor familiarity and identification tests and performed an odor identification task during fMRI scanning. Five task-related functional networks were detected using independent components analysis. Main and interaction effects of mean odor familiarity ratings, odor identification scores, and ε4 status on network activation and task-modulation of network functional connectivity (FC) during correct and incorrect odor identification (hits and misses), controlling for age and sex, were explored using multiple linear regression. RESULTS: Findings suggested that sensory-olfactory network activation was positively associated with odor identification scores in ε4 carriers with intact odor familiarity. The FC of sensory-olfactory, multisensory-semantic integration, and occipitoparietal networks was altered in ε4 carriers with poorer odor familiarity and identification. In ε4 carriers with poorer familiarity, connectivity between superior frontal areas and the sensory-olfactory network was negatively associated with odor identification scores. CONCLUSIONS: The results contribute to the clarification of the neurocognitive structure of odor identification processing and suggest that poorer odor familiarity and identification in ε4 carriers may signal multi-network dysfunction. Odor familiarity and identification assessment in ε4 carriers may contribute to the predictive value of risk for MCI and AD due to the breakdown of sensory-cognitive network integration. Additional research on olfactory processing in those at risk for AD is warranted.

The Impact of Spectral and Temporal Degradation on Vocoded Speech Recognition in Early-Blind Individuals.

This study compared the impact of spectral and temporal degradation on vocoded speech recognition between early-blind and sighted subjects. The participants included 25 early-blind subjects (30.32 ± 4.88 years; male:female, 14:11) and 25 age- and sex-matched sighted subjects. Tests included monosyllable recognition in noise at various signal-to-noise ratios (-18 to -4 dB), matrix sentence-in-noise recognition, and vocoded speech recognition with different numbers of channels (4, 8, 16, and 32) and temporal envelope cutoff frequencies (50 vs 500 Hz). Cortical-evoked potentials (N2 and P3b) were measured in response to spectrally and temporally degraded stimuli. The early-blind subjects displayed superior monosyllable and sentence recognition than sighted subjects (all p < 0.01). In the vocoded speech recognition test, a three-way repeated-measure analysis of variance (two groups × four channels × two cutoff frequencies) revealed significant main effects of group, channel, and cutoff frequency (all p < 0.001). Early-blind subjects showed increased sensitivity to spectral degradation for speech recognition, evident in the significant interaction between group and channel (p = 0.007). N2 responses in early-blind subjects exhibited shorter latency and greater amplitude in the 8-channel (p = 0.022 and 0.034, respectively) and shorter latency in the 16-channel (p = 0.049) compared with sighted subjects. In conclusion, early-blind subjects demonstrated speech recognition advantages over sighted subjects, even in the presence of spectral and temporal degradation. Spectral degradation had a greater impact on speech recognition in early-blind subjects, while the effect of temporal degradation was similar in both groups.

Construction of a Chinese traditional instrumental music dataset: A validated set of naturalistic affective music excerpts.

Music is omnipresent among human cultures and moves us both physically and emotionally. The perception of emotions in music is influenced by both psychophysical and cultural factors. Chinese traditional instrumental music differs significantly from Western music in cultural origin and music elements. However, previous studies on music emotion perception are based almost exclusively on Western music. Therefore, the construction of a dataset of Chinese traditional instrumental music is important for exploring the perception of music emotions in the context of Chinese culture. The present dataset included 273 10-second naturalistic music excerpts. We provided rating data for each excerpt on ten variables: familiarity, dimensional emotions (valence and arousal), and discrete emotions (anger, gentleness, happiness, peacefulness, sadness, solemnness, and transcendence). The excerpts were rated by a total of 168 participants on a seven-point Likert scale for the ten variables. Three labels for the excerpts were obtained: familiarity, discrete emotion, and cluster. Our dataset demonstrates good reliability, and we believe it could contribute to cross-cultural studies on emotional responses to music.

From vector spaces to DRM lists: False Memory Generator, a software for automated generation of lists of stimuli inducing false memories.

The formation of false memories is one of the most widely studied topics in cognitive psychology. The Deese-Roediger-McDermott (DRM) paradigm is a powerful tool for investigating false memories and revealing the cognitive mechanisms subserving their formation. In this task, participants first memorize a list of words (encoding phase) and next have to indicate whether words presented in a new list were part of the initially memorized one (recognition phase). By employing DRM lists optimized to investigate semantic effects, previous studies highlighted a crucial role of semantic processes in false memory generation, showing that new words semantically related to the studied ones tend to be more erroneously recognized (compared to new words less semantically related). Despite the strengths of the DRM task, this paradigm faces a major limitation in list construction due to its reliance on human-based association norms, posing both practical and theoretical concerns. To address these issues, we developed the False Memory Generator (FMG), an automated and data-driven tool for generating DRM lists, which exploits similarity relationships between items populating a vector space. Here, we present FMG and demonstrate the validity of the lists generated in successfully replicating well-known semantic effects on false memory production. FMG potentially has broad applications by allowing for testing false memory production in domains that go well beyond the current possibilities, as it can be in principle applied to any vector space encoding properties related to word referents (e.g., lexical, orthographic, phonological, sensory, affective, etc.) or other type of stimuli (e.g., images, sounds, etc.).

The hippocampus supports the representation of abstract concepts: Implications for the study of recognition memory.

Words, unlike images, are symbolic representations. The associative details inherent within a word's meaning and the visual imagery it generates, are inextricably connected to the way words are processed and represented. It is well recognised that the hippocampus associatively binds components of a memory to form a lasting representation, and here we show that the hippocampus is especially sensitive to abstract word processing. Using fMRI during recognition, we found that the increased abstractness of words produced increased hippocampal activation regardless of memory outcome. Interestingly, word recollection produced hippocampal activation regardless of word content, while the parahippocampal cortex was sensitive to concreteness of word representations, regardless of memory outcome. We reason that the hippocampus has assumed a critical role in the representation of uncontextualized abstract word meaning, as its information-binding ability allows the retrieval of the semantic and visual associates that, when bound together, generate the abstract concept represented by word symbols. These insights have implications for research on word representation, memory, and hippocampal function, perhaps shedding light on how the human brain has adapted to encode and represent abstract concepts.

Decoding familiar visual object categories in the mu rhythm oscillatory response.

Whilst previous research has linked attenuation of the mu rhythm to the observation of specific visual categories, and even to a potential role in action observation via a putative mirror neuron system, much of this work has not considered what specific type of information might be coded in this oscillatory response when triggered via vision. Here, we sought to determine whether the mu rhythm contains content-specific information about the identity of familiar (and also unfamiliar) graspable objects. In the present study, right-handed participants (N = 27) viewed images of both familiar (apple, wine glass) and unfamiliar (cubie, smoothie) graspable objects, whilst performing an orthogonal task at fixation. Multivariate pattern analysis (MVPA) revealed significant decoding of familiar, but not unfamiliar, visual object categories in the mu rhythm response. Thus, simply viewing familiar graspable objects may automatically trigger activation of associated tactile and/or motor properties in sensorimotor areas, reflected in the mu rhythm. In addition, we report significant attenuation in the central beta band for both familiar and unfamiliar visual objects, but not in the mu rhythm. Our findings highlight how analysing two different aspects of the oscillatory response - either attenuation or the representation of information content - provide complementary views on the role of the mu rhythm in response to viewing graspable object categories.

Temporal multiplexing of perception and memory codes in IT cortex.

A central assumption of neuroscience is that long-term memories are represented by the same brain areas that encode sensory stimuli1. Neurons in inferotemporal (IT) cortex represent the sensory percept of visual objects using a distributed axis code2-4. Whether and how the same IT neural population represents the long-term memory of visual objects remains unclear. Here we examined how familiar faces are encoded in the IT anterior medial face patch (AM), perirhinal face patch (PR) and temporal pole face patch (TP). In AM and PR we observed that the encoding axis for familiar faces is rotated relative to that for unfamiliar faces at long latency; in TP this memory-related rotation was much weaker. Contrary to previous claims, the relative response magnitude to familiar versus unfamiliar faces was not a stable indicator of familiarity in any patch5-11. The mechanism underlying the memory-related axis change is likely intrinsic to IT cortex, because inactivation of PR did not affect axis change dynamics in AM. Overall, our results suggest that memories of familiar faces are represented in AM and perirhinal cortex by a distinct long-latency code, explaining how the same cell population can encode both the percept and memory of faces.

Effects of unilateral hippocampal surgical procedures needed for calcium imaging on mouse behavior and adult hippocampal neurogenesis.

Hippocampus is essential for episodic memory formation, lesion studies demonstrating its role especially in processing spatial and temporal information. Further, adult hippocampal neurogenesis (AHN) in the dentate gyrus (DG) has also been linked to learning. To study hippocampal neuronal activity during events like learning, in vivo calcium imaging has become increasingly popular. It relies on the use of adeno-associated viral (AAV) vectors, which seem to lead to a decrease in AHN when applied on the DG. More notably, imaging requires the implantation of a relatively large lens into the tissue. Here, we examined how injection of an AAV vector and implantation of a 1-mm-diameter lens into the dorsal DG routinely used to image calcium activity impact the behavior of adult male C57BL/6 mice. To this aim, we conducted open-field, object-recognition and object-location tasks at baseline, after AAV vector injection, and after lens implantation. Finally, we determined AHN from hippocampal slices using a doublecortin-antibody. According to our results, the operations needed for in vivo imaging of the dorsal DG did not have adverse effects on behavior, although we noticed a decrease in AHN ipsilaterally to the operations. Thus, our results suggest that in vivo imaging can be safely used to, for example, correlate patterns of calcium activity with learned behavior. One should still keep in mind that the defects on the operated side might be functionally compensated by the (hippocampus in the) contralateral hemisphere.

The Costs (and Benefits?) of Effortful Listening for Older Adults: Insights from Simultaneous Electrophysiology, Pupillometry, and Memory.

Although the impact of acoustic challenge on speech processing and memory increases as a person ages, older adults may engage in strategies that help them compensate for these demands. In the current preregistered study, older adults (n = 48) listened to sentences-presented in quiet or in noise-that were high constraint with either expected or unexpected endings or were low constraint with unexpected endings. Pupillometry and EEG were simultaneously recorded, and subsequent sentence recognition and word recall were measured. Like young adults in prior work, we found that noise led to increases in pupil size, delayed and reduced ERP responses, and decreased recall for unexpected words. However, in contrast to prior work in young adults where a larger pupillary response predicted a recovery of the N400 at the cost of poorer memory performance in noise, older adults did not show an associated recovery of the N400 despite decreased memory performance. Instead, we found that in quiet, increases in pupil size were associated with delays in N400 onset latencies and increased recognition memory performance. In conclusion, we found that transient variation in pupil-linked arousal predicted trade-offs between real-time lexical processing and memory that emerged at lower levels of task demand in aging. Moreover, with increased acoustic challenge, older adults still exhibited costs associated with transient increases in arousal without the corresponding benefits.

Manipulation of α4ßδ GABAA receptors alters synaptic pruning in layer 3 prelimbic prefrontal cortex and impairs temporal order recognition: Implications for schizophrenia and autism.

Temporal order memory is impaired in autism spectrum disorder (ASD) and schizophrenia (SCZ). These disorders, more prevalent in males, result in abnormal dendritic spine pruning during adolescence in layer 3 (L3) medial prefrontal cortex (mPFC), yielding either too many (ASD) or too few (SCZ) spines. Here we tested whether altering spine density in neural circuits including the mPFC could be associated with impaired temporal order memory in male mice. We have shown that α4ßδ GABAA receptors (GABARs) emerge at puberty on spines of L5 prelimbic mPFC (PL) where they trigger pruning. We show here that α4ßδ receptors also increase at puberty in L3 PL (P < 0.0001) and used these receptors as a target to manipulate spine density here. Pubertal injection (14 d) of the GABA agonist gaboxadol, at a dose (3 mg/kg) selective for α4ßδ, reduced L3 spine density by half (P < 0.0001), while α4 knock-out increased spine density âˆ¼ 40 % (P < 0.0001), mimicking spine densities in SCZ and ASD, respectively. In both cases, performance on the mPFC-dependent temporal order recognition task was impaired, resulting in decreases in the discrimination ratio which assesses preference for the novel object: -0.39 ± 0.15, gaboxadol versus 0.52 ± 0.09, vehicle; P = 0.0002; -0.048 ± 0.10, α4 KO versus 0.49 ± 0.04, wild-type; P < 0.0001. In contrast, the number of approaches was unaltered, reflecting unchanged locomotion. These data suggest that altering α4ßδ GABAR expression/activity alters spine density in L3 mPFC and impairs temporal order memory to mimic changes in ASD and SCZ. These findings may provide insight into these disorders.

Remembering what we imagine: the role of event schemas in shaping how imagined autobiographical events are recalled.

Much like recalling autobiographical memories, constructing imagined autobiographical events depends on episodic memory processes. The ability to imagine events contributes to several future-oriented behaviors (e.g., decision-making, problem solving), which relies, in part, on the ability to remember the imagined events. A factor affecting the memorability of such events is their adherence to event schemas-conceptualizations of how events generally unfold. In the current study, we examined how two aspects of event schemas-event expectancy and familiarity-affect the ability to recall imagined events. Participants first imagined and described in detail autobiographical events that either aligned with or deviated from an event, expected to occur in a context (e.g., a kitchen) that was either familiar or unfamiliar. This resulted in imaginations ranging from maximally schema-congruent (expected events in a familiar context) to maximally novel (unexpected events in an unfamiliar context). Twenty-four hours later, participants recalled these imagined events. Recollections were scored for the number of reinstated details from the imaginations and the number of newly added details. We found greater reinstatement of details for both the maximally congruent and maximally novel events, while maximally novel events were recalled more precisely than other events (i.e., fewer added details). Our results indicate a complementary benefit to remembering schematic and novel imagined events, which may guide equally important but distinct future-oriented behaviors.