Hippocampal-occipital connectivity reflects autobiographical memory deficits in aphantasia.

Aphantasia refers to reduced or absent visual imagery. While most of us can readily recall decade-old personal experiences (autobiographical memories, AM) with vivid mental images, there is a dearth of information about whether the loss of visual imagery in aphantasics affects their AM retrieval. The hippocampus is thought to be a crucial hub in a brain-wide network underlying AM. One important question is whether this network, especially the connectivity of the hippocampus, is altered in aphantasia. In the current study, we tested 14 congenital aphantasics and 16 demographically matched controls in an AM fMRI task to investigate how key brain regions (i.e. hippocampus and visual-perceptual cortices) interact with each other during AM re-experiencing. All participants were interviewed regarding their autobiographical memory to examine their episodic and semantic recall of specific events. Aphantasics reported more difficulties in recalling AM, were less confident about their memories, and described less internal and emotional details than controls. Neurally, aphantasics displayed decreased hippocampal and increased visual-perceptual cortex activation during AM retrieval compared to controls. In addition, controls showed strong negative functional connectivity between the hippocampus and the visual cortex during AM and resting-state functional connectivity between these two brain structures predicted better visualization skills. Our results indicate that visual mental imagery plays an important role in detail-rich vivid AM, and that this type of cognitive function is supported by the functional connection between the hippocampus and the visual-perceptual cortex.

Impaired Dynamics of Positional and Contextual Neural Coding in an Alzheimer's Disease Rat Model.

Background: The hippocampal representation of space, formed by the collective activity of populations of place cells, is considered as a substrate of spatial memory. Alzheimer's disease (AD), a widespread severe neurodegenerative condition of multifactorial origin, typically exhibits spatial memory deficits among its early clinical signs before more severe cognitive impacts develop. Objective: To investigate mechanisms of spatial memory impairment in a double transgenic rat model of AD. Methods: In this study, we utilized 9-12-month-old double-transgenic TgF344-AD rats and age-matched controls to analyze the spatial coding properties of CA1 place cells. We characterized the spatial memory representation, assessed cells' spatial information content and direction-specific activity, and compared their population coding in familiar and novel conditions. Results: Our findings revealed that TgF344-AD animals exhibited lower precision in coding, as evidenced by reduced spatial information and larger receptive zones. This impairment was evident in maps representing novel environments. While controls instantly encoded directional context during their initial exposure to a novel environment, transgenics struggled to incorporate this information into the newly developed hippocampal spatial representation. This resulted in impairment in orthogonalization of stored activity patterns, an important feature directly related to episodic memory encoding capacity. Conclusions: Overall, the results shed light on the nature of impairment at both the single-cell and population levels in the transgenic AD model. In addition to the observed spatial coding inaccuracy, the findings reveal a significantly impaired ability to adaptively modify and refine newly stored hippocampal memory patterns.

The Association of Cerebral Autoregulation Dysfunction and Postoperative Memory Impairment in Cardiac Surgery Patients.

Background and Objectives: Cardiac surgery is associated with various durations of cerebral autoregulation (CA) impairment and can significantly impact cognitive function. Cognitive functions such as memory, psychomotor speed, and attention are significantly impacted after cardiac surgery, necessitating prioritization of these areas in cognitive function tests. There is a lack of research connecting cerebral autoregulation impairment to specific cognitive function domains after cardiac surgery. This study aimed to determine if impaired cerebral autoregulation is associated with postoperative memory impairment and to test the hypothesis that the duration of this impairment affects the development of postoperative memory issues. Materials and Methods: A prospective study was conducted in 2021-2023. After approval of the Ethics Committee and with patient's written consent, 83 adult patients undergoing elective on-pump coronary artery bypass graft (CABG) surgery were enrolled. All patients were assessed for cognitive function 1 day before surgery using the Mini-Mental state examination (MMSE-2) test as a screening tool and the Hopkins Verbal Learning Test-Revised (HVLT-R) to assess memory specifically. To diagnose possible memory impairment (IM), all patients underwent a repeat assessment of cognitive function on the 7th-10th postoperative day. Cerebral autoregulation monitoring using transcranial Doppler was performed. Cerebral autoregulation status index (Mx) was recorded using Intensive Care Brain Monitoring System software, 9.1.5.23 (Cambridge, UK). Results: According to our research, the incidence of postoperative memory impairment is 30.1%. Temporary cerebral autoregulation impairment occurs in all patients undergoing elective in-pump CABG surgery. The duration of the single longest CA impairment event in seconds (LCAI) and the LCAI dose were higher in patients with postoperative memory impairment, p = 0.006 and p < 0.007, respectively. Conclusions: Cerebral autoregulation impairment is important in developing memory loss after cardiac surgery. The duration and dose of the LCAI event are predictive of postoperative memory impairment.

Aberrance in default mode and executive network activity underlie working memory deficits in addictive disorders: A preliminary, exploratory case-control study.

BACKGROUND: Addiction can alter neural processes during rest and cognitive performance. Subjects with addictive disorders exhibit preoccupation and anticipation for the psychoactive substance when idle and cognitive deficits, during tasks. METHODS: 128 channel EEG was recorded in sixty subjects (30, with alcohol, opioid and internet addiction; 30 controls) during rest and while performing working memory task to ascertain underlying differences in cortical activity between the groups while at rest and during performance of the task. Artifactually clean data was then subjected to source analysis using sLORETA software in both the groups. RESULTS: EEG cortical source analysis in subjects with addictive disorders showed significant activation of areas of Default Mode Network (DMN) and reduced activation in dorsolateral prefrontal cortices (DLPFC), an area known to be involved in executive function, during performance of task. However, control subjects demonstrated significantly reduced activation in areas of DMN; and increased activation of DLPFC during task performance. CONCLUSION: Inability to suppress DMN inhibits reallocation of neural resources to areas of executive functioning leading to working memory deficits in subjects with addictive disorder.

Hippocampal hub failure is linked to long-term memory impairment in anti-NMDA-receptor encephalitis: insights from structural connectome graph theoretical network analysis.

BACKGROUND: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is characterized by distinct structural and functional brain alterations, predominantly affecting the medial temporal lobes and the hippocampus. Structural connectome analysis with graph-based investigations of network properties allows for an in-depth characterization of global and local network changes and their relationship with clinical deficits in NMDAR encephalitis. METHODS: Structural networks from 61 NMDAR encephalitis patients in the post-acute stage (median time from acute hospital discharge: 18 months) and 61 age- and sex-matched healthy controls (HC) were analyzed using diffusion-weighted imaging (DWI)-based probabilistic anatomically constrained tractography and volumetry of a selection of subcortical and white matter brain volumes was performed. We calculated global, modular, and nodal graph measures with special focus on default-mode network, medial temporal lobe, and hippocampus. Pathologically altered metrics were investigated regarding their potential association with clinical course, disease severity, and cognitive outcome. RESULTS: Patients with NMDAR encephalitis showed regular global graph metrics, but bilateral reductions of hippocampal node strength (left: p = 0.049; right: p = 0.013) and increased node strength of right precuneus (p = 0.013) compared to HC. Betweenness centrality was decreased for left-sided entorhinal cortex (p = 0.042) and left caudal middle frontal gyrus (p = 0.037). Correlation analyses showed a significant association between reduced left hippocampal node strength and verbal long-term memory impairment (p = 0.021). We found decreased left (p = 0.013) and right (p = 0.001) hippocampal volumes that were associated with hippocampal node strength (left p = 0.009; right p < 0.001). CONCLUSIONS: Focal network property changes of the medial temporal lobes indicate hippocampal hub failure that is associated with memory impairment in NMDAR encephalitis at the post-acute stage, while global structural network properties remain unaltered. Graph theory analysis provides new pathophysiological insight into structural network changes and their association with persistent cognitive deficits in NMDAR encephalitis.

Early spatial recognition memory deficits in 5XFAD female mice are associated with disruption of prefrontal parvalbumin neurons.

Women have a two-fold increased risk of developing Alzheimer's disease (AD) than men, yet the underlying mechanisms of this sex-specific vulnerability remain unknown. Here, we aimed at determining in the 5XFAD mouse model whether deficits in prefrontal-dependent cognitive functions, which are impacted in the preclinical stages of AD, appear earlier in females, and whether these cognitive deficits are associated with alterations in the activity of prefrontal parvalbumin (PV)-neurons that regulate prefrontal circuits activity. We observed that 3.5-month-old 5XFAD females, but not males, display impairments in spatial short-term recognition memory, a function that relies on the integrity of the prefrontal cortex. Hippocampal-dependent cognitive functions were intact in both sexes. We then observed that 5XFAD females have more prefrontal PV neurons expressing the marker of chronic activity FosB; this was inversely correlated with prefrontal-dependent cognitive performances. Our findings show for the first time sex-specific, early deregulation of prefrontal PV neurons activity, which is associated with early appearance of prefrontal-dependent cognitive functions in 5XFAD females providing a potential novel mechanism to the increased risk to AD in females.

Memory Consolidation and Sleep in Children With Epilepsy: A Systematic Review.

BACKGROUND: Sleep is essential in the process of memory consolidation. Children and adolescents with epilepsy hold a significantly higher risk for memory impairment. Understanding the relationship between sleep and memory impairment in adolescents with epilepsy will help us to develop effective support services for this patient population. The present study provides a summary of the current research on the influence of epilepsy-related altered sleep patterns on memory consolidation in children and adolescents with epilepsy. The aim of this systematic review is to investigate the influence of epilepsy-related altered sleep conditions in children and adolescents and their impact on memory performance. MATERIALS: A systematic review was conducted according to the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses using the search terms "memory," "sleep," "epilepsy," "children," and "adolescents." A total of 4 studies met the inclusion criteria. The review focused on the association of sleep disorders and memory performance in children and adolescents aged up to 21 years without psychiatric comorbidities. RESULTS: The reviewed studies highlight a higher risk of sleep disturbance and lower sleep quality in children with epilepsy in comparison to control groups. Group differences in memory consolidation were found before, but not after one night of sleep. Three studies reported a significant association between sleep and memory performance. Two studies demonstrated an association between nocturnal interictal epileptiform discharges and memory performance in adolescents. CONCLUSION: Children and adolescents with epilepsy have a higher risk of sleep and memory disorders. Nocturnal interictal epileptiform discharges have been shown to interfere with memory consolidation. Conclusions on underlying mechanisms remain unclear. Further case-control studies addressing sleep and its influence on memory problems in pediatric epilepsy patients are needed.

Individual posterior alpha rhythms and cognitive reserve as possible early prognostic markers in people with subjective memory complaints.

Subjective memory complaints (SMCs) are a memory disorder that often precedes mild cognitive impairment (MCI) or Alzheimer's disease (AD). Both individual alpha rhythms and cognitive reserve (CR) represent key features of SMCs and provide useful tools to characterize and predict the course of the disorder. We studied whether older people with SMCs may also present some abnormal resting state electroencephalogram (rsEEG) alpha rhythms, and whether alpha rhythms are associated with CR. To do this, eyes-closed rsEEG were recorded in 68 older people with and without SMCs. The individual alpha indexes alpha/theta transition frequency (TF) and individual alpha frequency peak (IAFp) were computed. TF and IAFp were also used to determine the alpha1, alpha2, and alpha3 power frequency. Results indicated no differences in TF or IAFp between older people with SMCs and controls. The SMCs group showed a reduction in alpha3 power in comparison with controls. Specifically, women with SMCs were characterized by a significant decrease in alpha3 power compared to control women. Furthermore, only in SMCs group, greater CR was associated with slow IAFp. In sum, these results suggest that TF and IAFp are two stable indexes that are not influenced by the presence of SMCs. However, the reduction in alpha3, as observed in women with SMCs, shows an abnormal posterior rsEEG at alpha power. Finally, the compensatory mechanisms of CR appear to interact with the neurophysiological mechanisms that underlie the regulation of alpha rhythms.

Neural dysfunction underlying working memory processing at different stages of the illness course in schizophrenia: a comparative meta-analysis.

Schizophrenia, as a chronic and persistent disorder, exhibits working memory deficits across various stages of the disorder, yet the neural mechanisms underlying these deficits remain elusive with inconsistent neuroimaging findings. We aimed to compare the brain functional changes of working memory in patients at different stages: clinical high risk, first-episode psychosis, and long-term schizophrenia, using meta-analyses of functional magnetic resonance imaging studies. Following a systematic literature search, 56 whole-brain task-based functional magnetic resonance imaging studies (15 for clinical high risk, 16 for first-episode psychosis, and 25 for long-term schizophrenia) were included. The separate and pooled neurofunctional mechanisms among clinical high risk, first-episode psychosis, and long-term schizophrenia were generated by Seed-based d Mapping toolbox. The clinical high risk and first-episode psychosis groups exhibited overlapping hypoactivation in the right inferior parietal lobule, right middle frontal gyrus, and left superior parietal lobule, indicating key lesion sites in the early phase of schizophrenia. Individuals with first-episode psychosis showed lower activation in left inferior parietal lobule than those with long-term schizophrenia, reflecting a possible recovery process or more neural inefficiency. We concluded that SCZ represent as a continuum in the early stage of illness progression, while the neural bases are inversely changed with the development of illness course to long-term course.

Treadmill exercise prevents recognition memory impairment in VD rat model and enhancement of hippocampal structural synaptic plasticity.

OBJECTIVE: In vascular dementia (VD), memory impairment caused by the damage of synaptic plasticity is the most prominent feature that afflicts patients and their families. Treadmill exercise has proven beneficial for memory by enhancing synaptic plasticity in animal models including stroke, dementia, and mental disorders. The aim of this study was to examine the effects of treadmill exercise on recognition memory and structural synaptic plasticity in VD rat model. METHODS: Male Sprague-Dawley rats were randomly assigned into four groups: control group (C group, n = 6), vascular dementia group (VD group, n = 6), treadmill exercise and vascular dementia group (Exe-VD group, n = 6), and treadmill exercise group (Exe group, n = 6). Four-week treadmill exercise was performed in the Exe-VD and Exe groups. Then, the common carotid arteries of rats in the VD and Exe-VD groups were identified to establish the VD model. Behavior tests (open-field test and novel recognition memory test) were adopted to evaluate anxiety-like behavior and recognition memory. Transmission electron microscopy and Golgi staining were performed to observe synaptic ultrastructure and spine density in the hippocampus. RESULTS: Our study demonstrated that VD rat exhibited significantly anxiety-like behavior and recognition impairment (p < .01), while treadmill exercise significantly alleviated anxiety-like behavior and improved recognition memory in VD rat (p < .01). Transmission electron microscopy revealed that hippocampal synapse numbers were significantly decreased in the VD group compared to the control group (p < .05). These alterations were reversed by treadmill exercise, and the rats exhibited healthier synaptic ultrastructure, including significantly increased synapse (p < .05). Meanwhile, golgi staining revealed that the spine numbers of the hippocampus were significantly decreased in the VD group compared to the control group (p < .05). When compared with the VD group, hippocampal spine numbers were significantly increased in the Exe-VD group (p < .05). CONCLUSION: The improvement of VD-associated recognition memory by treadmill exercises is associated with enhanced structural synaptic plasticity in VD rat model.

High-frequency repetitive transcranial magnetic stimulation ameliorates memory impairment by inhibiting neuroinflammation in the chronic cerebral hypoperfusion mice.

BACKGROUND: High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been found to ameliorate cognitive impairment. However, the effects of HF-rTMS remain unknown in chronic cerebral hypoperfusion (CCH). AIM: To investigate the effects of HF-rTMS on cognitive improvement and its potential mechanisms in CCH mice. MATERIALS AND METHODS: Daily HF-rTMS therapy was delivered after bilateral carotid stenosis (BCAS) and continued for 14 days. The mice were randomly assigned to three groups: the sham group, the model group, and the HF-rTMS group. The Y maze and the new object recognition test were used to assess cognitive function. The expressions of MAP-2, synapsis, Myelin basic protein(MBP), and brain-derived growth factors (BDNF) were analyzed by immunofluorescence staining and western blot to evaluate neuronal plasticity and white matter myelin regeneration. Nissl staining and the expression of caspase-3, Bax, and Bcl-2 were used to observe neuronal apoptosis. In addition, the activation of microglia and astrocytes were evaluated by fluorescence staining. The inflammation levels of IL-1ß, IL-6, and Tumor Necrosis Factor(TNF)-α were detected by qPCR in the hippocampus of mice in each group. RESULTS: Via behavioral tests, the BCAS mice showed reduced a rate of new object preference and decreased a rate of spontaneous alternations, while HF-rTMS significantly improved hippocampal learning and memory deficits. In addition, the mice in the model group showed decreased levels of MAP-2, synapsis, MBP, and BDNF, while HF-rTMS treatment reversed these effects. As expected, activated microglia and astrocytes increased in the model group, but HF-rTMS treatment suppressed these changes. HF-rTMS decreased BCAS-induced neuronal apoptosis and the expression of pro-apoptotic protein (Caspase-3 and Bax) and increased the expression of anti-apoptotic protein (Bcl-2). In addition, HF-rTMS inhibited the expression of inflammatory cytokines (IL-1ß, IL-6, and TNF-α). CONCLUSIONS: HF-rTMS alleviates cognitive impairment in CCH mice by enhancing neuronal plasticity and inhibiting inflammation, thus serving as a potential method for vascular cognitive impairment.

Slow wave sleep is associated with forgetting in patients with temporal lobe epilepsy.

While time spent in slow wave sleep (SWS) after learning promotes memory consolidation in the healthy brain, it is unclear if the same benefit is obtained in patients with temporal lobe epilepsy (TLE). Interictal epileptiform discharges (IEDs) are potentiated during SWS and thus may disrupt memory consolidation processes thought to depend on hippocampal-neocortical interactions. Here, we explored the relationship between SWS, IEDs, and overnight forgetting in patients with TLE. Nineteen patients with TLE studied object-scene pairs and memory was tested across a day of wakefulness (6 hrs) and across a night of sleep (16 hrs) while undergoing continuous scalp EEG monitoring. We found that time spent in SWS after learning was related to greater forgetting overnight. Longer duration in SWS and number of IEDs were each associated with greater forgetting, although the number of IEDs did not mediate the relationship between SWS and memory. Further research, particularly with intracranial recordings, is required to identify the mechanisms by which SWS and IEDs can be pathological to sleep-dependent memory consolidation in patients with TLE.

Territory-Related Functional Connectivity Changes Associated with Verbal Memory Decline in Patients with Unilateral Asymptomatic Internal Carotid Stenosis.

BACKGROUND AND PURPOSE: Verbal memory decline is a common complaint of patients with severe asymptomatic stenosis of the internal carotid artery (aICS). Previous publications explored the associations between verbal memory decline and altered functional connectivity (FC) after aICS. Patients with severe aICS may show reduced perfusion in the ipsilateral territory and redistribution of cerebral blood flow to compensate for the deficient regions, including expansion of the posterior and contralateral ICA territories via the circle of Willis. However, aICS-related FC changes in anterior and posterior territories and the impact of the sides of stenosis were less explored. This study aims to investigate the altered FC in anterior and posterior circulation territories of patients with left or right unilateral aICS and its association with verbal memory decline. MATERIALS AND METHODS: We enrolled 15 healthy controls (HCs), 22 patients with left aICS (aICSL), and 33 patients with right aICS (aICSR) to receive fMRI, Mini-Mental State Examination (MMSE), the Digit Span Test (DST), and the 12-item Chinese version of Verbal Learning Tests. We selected brain regions associated with verbal memory within anterior and posterior circulation territories. Territory-related FC alterations and verbal memory decline were identified by comparing the aICSL and aICSR groups with HC groups (P < .05, corrected for multiple comparisons), respectively. Furthermore, the association between altered FC and verbal memory decline was tested with the Pearson correlation analysis. RESULTS: Compared with HCs, patients with aICSL or aICSR had significant impairment in delayed recall of verbal memory. Decline in delayed recall of verbal memory was significantly associated with altered FC between the right cerebellum and right middle temporal pole in the posterior circulation territory (r = 0.40, P = .03) in the aICSR group and was significantly associated with altered FC between the right superior medial frontal gyrus and left lingual gyrus in the anterior circulation territory (r = 0.56, P = .01) in the aICSL group. CONCLUSIONS: Patients with aICSL and aICSR showed different patterns of FC alterations in both anterior and posterior circulation territories, which suggests that the side of aICS influences the compensatory mechanism for decline in delayed recall of verbal memory.

The neurophysiological mechanisms of medial prefrontal-perirhinal cortex circuit mediating temporal order memory decline in early stage of AD rats.

The temporal component of episodic memory has been recognized as a sensitive behavioral marker in early stage of Alzheimer's disease (AD) patients. However, parallel studies in AD animals are currently lacking, and the underlying neural circuit mechanisms remain poorly understood. Using a novel AppNL-G-F knock-in (APP-KI) rat model, the developmental changes of temporal order memory (TOM) and the relationship with medial prefrontal cortex and perirhinal cortex (mPFC-PRH) circuit were determined through in vivo electrophysiology and microimaging technique. We observed a deficit in TOM performance during the object temporal order memory task (OTOMT) in APP-KI rats at 6 month old, which was not evident at 3 or 4 months of age. Alongside behavioral changes, we identified a gradually extensive and aggravated regional activation and functional alterations in the mPFC and PRH during the performance of OTOMT, which occurred prior to the onset of TOM deficits. Moreover, coherence analysis showed that the functional connectivity between the mPFC and PRH could predict the extent of future behavioral performance. Further analysis revealed that the aberrant mPFC-PRH interaction mainly attributed to the progressive deterioration of synaptic transmission, information flow and network coordination from mPFC to PRH, suggesting the mPFC dysfunction maybe the key area of origin underlying the early changes of TOM. These findings identify a pivotal role of the mPFC-PRH circuit in mediating the TOM deficits in the early stage of AD, which holds promising clinical translational value and offers potential early biological markers for predicting AD memory progression.

Memory function in autoimmune encephalitis: a cross-sectional prospective study utilising multiple memory paradigms.

BACKGROUND AND OBJECTIVE: Autoimmune encephalitis (AE) is often associated with clinically significant memory impairment. This study aimed to evaluate memory in a cross-sectional prospective AE cohort using multiple memory paradigms. METHODS: 52 patients (50% seropositive) meeting Graus criteria for possible AE were prospectively recruited between October 2019 and August 202. A comprehensive examination of memory was performed, including tests of supraspan verbal memory (list learning), logicosemantic memory (story learning), figural memory (learning of geometric designs), and verbal associative learning (verbal paired associates). Memory scores were compared to demographically adjusted normative data. Pattern analysis was conducted to assist in the identification of patterns in memory performances. RESULTS: Mean memory scores were not significantly below the normative mean. At an individual patient level, over 20% of the cohort exhibited impaired delayed figural memory, supraspan verbal memory learning and recall. Observed performances were significantly below expected performance for story learning (p = 0.017) and recall (p = 0.003), figural recall (p < 0.0001), initial acquisition (p < 0.001) and final acquisition of a list (p < 0.001) and all delayed recall measures of the list (p < 0.00001). 54.76% of patients exhibited intact psychometrics, and 16 distinct patterns of impairment emerged, indicating variability in memory outcomes. DISCUSSION: While statistical evidence for memory impairment did not emerge at an aggregate level, a proportion of patients present with evidence of abnormal memory performance on psychometrics. Variability in impaired memory measures argues for an individualised patient-focused approach to clinical assessment in AE. Future research should validate these findings with a larger sample size and explore the relationships between memory profiles and other cognitive functions.

Conditional knockout of Shank3 in the ventral CA1 by quantitative in vivo genome-editing impairs social memory in mice.

Individuals with autism spectrum disorder (ASD) have a higher prevalence of social memory impairment. A series of our previous studies revealed that hippocampal ventral CA1 (vCA1) neurons possess social memory engram and that the neurophysiological representation of social memory in the vCA1 neurons is disrupted in ASD-associated Shank3 knockout mice. However, whether the dysfunction of Shank3 in vCA1 causes the social memory impairment observed in ASD remains unclear. In this study, we found that vCA1-specific Shank3 conditional knockout (cKO) by the adeno-associated virus (AAV)- or specialized extracellular vesicle (EV)- mediated in vivo gene editing was sufficient to recapitulate the social memory impairment in male mice. Furthermore, the utilization of EV-mediated Shank3-cKO allowed us to quantitatively examine the role of Shank3 in social memory. Our results suggested that there is a certain threshold for the proportion of Shank3-cKO neurons required for social memory disruption. Thus, our study provides insight into the population coding of social memory in vCA1, as well as the pathological mechanisms underlying social memory impairment in ASD.

Developmental activity-based anorexia alters hippocampal non-genomic stress response and induces structural instability and spatial memory impairment in female rats.

OBJECTIVE: Anorexia nervosa (AN) is characterized by hyperactivation of the hypothalamic-pituitary-adrenal axis and cognitive deficits. However, little is known about the rapid non-genomic stress response involvement. This study investigates the molecular, structural and behavioral signatures of the anorexic phenotype induction in female rats on stress-related mechanisms in the hippocampus. METHOD: Female adolescent rats, exposed to the combination of food restriction and wheel access, i.e., the activity-based anorexia (ABA) protocol, were sacrificed in the acute phase of the pathology (postnatal day [P]42) or following a 7-day recovery period (P49). RESULTS: ABA rats, in addition to body weight loss and increased wheel activity, alter their pattern of activity over days, showing increased food anticipatory activity, a readout of their motivation to engage in intense physical activity. Corticosterone plasma levels were enhanced at P42 while reduced at P49 in ABA rats. In the membrane fraction of the hippocampus, we found reduced glucocorticoid receptor levels together with reduced expression of caldesmon, n-cadherin and neuroligin-1, molecular markers of cytoskeletal stability and glutamatergic homeostasis. Accordingly, structural analyses revealed reduced dendritic spine density, a reduced number of mushroom-shaped spines, together with an increased number of thin-shaped spines. These events are paralleled by impairment in spatial memory measured in the spatial order object recognition test. These effects persisted even when body weight of ABA rats was restored. DISCUSSION: Our findings indicate that ABA induction orchestrates hippocampal maladaptive structural and functional plasticity, contributing to cognitive deficits, providing a putative mechanism that could be targeted in AN patients.

Haploinsufficiency of GABAA Receptor-Associated Clptm1 Enhances Phasic and Tonic Inhibitory Neurotransmission, Suppresses Excitatory Synaptic Plasticity, and Impairs Memory.

The mechanisms utilized by neurons to regulate the efficacy of phasic and tonic inhibition and their impacts on synaptic plasticity and behavior are incompletely understood. Cleft lip and palate transmembrane protein 1 (Clptm1) is a membrane-spanning protein that interacts with multiple γ-aminobutyric acid type A receptor (GABAAR) subunits, trapping them in the endoplasmic reticulum and Golgi network. Overexpression and knock-down studies suggest that Clptm1 modulates GABAAR-mediated phasic inhibition and tonic inhibition as well as activity-induced inhibitory synaptic homeostasis in cultured hippocampal neurons. To investigate the role of Clptm1 in the modulation of GABAARs in vivo, we generated Clptm1 knock-out (KO) mice. Here, we show that genetic KO of Clptm1 elevated phasic and tonic inhibitory transmission in both male and female heterozygous mice. Although basal excitatory synaptic transmission was not affected, Clptm1 haploinsufficiency significantly blocked high-frequency stimulation-induced long-term potentiation (LTP) in hippocampal CA3→CA1 synapses. In the hippocampus-dependent contextual fear-conditioning behavior task, both male and female Clptm1 heterozygous KO mice exhibited impairment in contextual fear memory. In addition, LTP and contextual fear memory were rescued by application of L-655,708, a negative allosteric modulator of the extrasynaptic GABAAR α5 subunit. These results suggest that haploinsufficiency of Clptm1 contributes to cognitive deficits through altered synaptic transmission and plasticity by elevation of inhibitory neurotransmission, with tonic inhibition playing a major role.

fNIRS as a biomarker for individuals with subjective memory complaints and MCI.

INTRODUCTION: Identifying individuals at risk of developing dementia is crucial for early intervention. Mild cognitive impairment (MCI) and subjective memory complaints (SMCs) are considered its preceding stages. This study aimed to assess the utility of functional near-infrared spectroscopy (fNIRS) in identifying individuals with MCI and SMC. METHODS: One hundred fifty-one participants were categorized into normal cognition (NC); amnestic MCI (aMCI); non-amnestic MCI (naMCI); and mild, moderate, and severe SMC groups. Task-related prefrontal hemodynamics were measured using fNIRS during a visual memory span task. RESULTS: Results showed significantly lower oxyhemoglobin (HbO) levels in aMCI, but not in naMCI, compared to the NC. In addition, severe SMC had lower HbO levels than the NC, mild, and moderate SMC. Receiver operating characteristic analysis demonstrated 69.23% and 69.70% accuracy in differentiating aMCI and severe SMC from NC, respectively. DISCUSSION: FNIRS may serve as a potential non-invasive biomarker for early detection of dementia. HIGHLIGHTS: Only amnestic mild cognitive impairment (aMCI), but not non-amnestic MCI, showed lower oxyhemoglobin (HbO) than normal individuals. Reduced HbO was observed in those with severe subjective memory complaints (SMCs) compared to normal cognition (NC), mild, and moderate SMCs. Functional near-infrared spectroscopy measures were associated with performance in memory assessments. Prefrontal hemodynamics could distinguish aMCI and severe SMC from NC.

Ethanol's impact on the brain: a neurobiological perspective on the mechanisms of memory impairment.

Alcohol consumption is known to have detrimental effects on memory function, with various studies implicating ethanol in the impairment of cognitive processes related to memory retention and retrieval. This review aims to elucidate the complex neurobiological mechanisms underlying ethanol-induced memory impairment. Through a thorough search of existing literature using electronic databases, relevant articles focusing on the neurobiological mechanisms of ethanol on memory were identified and critically evaluated. This review focuses on the molecular and neural pathways through which ethanol exerts its effects on memory formation, consolidation, and recall processes. Key findings from the included studies shed light on the impact of ethanol on neurotransmitter systems, synaptic plasticity, and neuroinflammation in relation to memory impairment. This review contributes to a better understanding of the intricate mechanisms by which alcohol impairs memory function, offering insights for future research directions and the development of targeted interventions to alleviate these cognitive impairments.