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Current Biology : CB Sep 2023Hippocampal sharp-wave ripples (SPW-Rs) are critical for memory consolidation and retrieval. The neuronal content of spiking during SPW-Rs is believed to be under the...
Hippocampal sharp-wave ripples (SPW-Rs) are critical for memory consolidation and retrieval. The neuronal content of spiking during SPW-Rs is believed to be under the influence of neocortical inputs via the entorhinal cortex (EC). Optogenetic silencing of the medial EC (mEC) reduced the incidence of SPW-Rs with minor impacts on their magnitude or duration, similar to local CA1 silencing. The effect of mEC silencing on CA1 firing and field potentials was comparable to the effect of transient cortex-wide DOWN states of non-REM (NREM) sleep, implying that decreased SPW-R incidence in both cases is due to tonic disfacilitation of hippocampal circuits. The neuronal composition of CA1 pyramidal neurons during SPW-Rs was altered by mEC silencing but was restored immediately after silencing. We suggest that the mEC provides both tonic and transient influences on hippocampal network states by timing the occurrence of SPW-Rs and altering their neuronal content.
Topics: Entorhinal Cortex; Hippocampus; Neurons; Pyramidal Cells; Memory Consolidation; Action Potentials
PubMed: 37572665
DOI: 10.1016/j.cub.2023.07.039 -
Acta Neuropathologica Communications May 2024Neuroinflammation and Alzheimer's disease (AD) co-pathology may contribute to disease progression and severity in dementia with Lewy bodies (DLB). This study aims to...
BACKGROUND
Neuroinflammation and Alzheimer's disease (AD) co-pathology may contribute to disease progression and severity in dementia with Lewy bodies (DLB). This study aims to clarify whether a different pattern of neuroinflammation, such as alteration in microglial and astroglial morphology and distribution, is present in DLB cases with and without AD co-pathology.
METHODS
The morphology and load (% area of immunopositivity) of total (Iba1) and reactive microglia (CD68 and HLA-DR), reactive astrocytes (GFAP) and proteinopathies of alpha-synuclein (KM51/pser129), amyloid-beta (6 F/3D) and p-tau (AT8) were assessed in a cohort of mixed DLB + AD (n = 35), pure DLB (n = 15), pure AD (n = 16) and control (n = 11) donors in limbic and neocortical brain regions using immunostaining, quantitative image analysis and confocal microscopy. Regional and group differences were estimated using a linear mixed model analysis.
RESULTS
Morphologically, reactive and amoeboid microglia were common in mixed DLB + AD, while homeostatic microglia with a small soma and thin processes were observed in pure DLB cases. A higher density of swollen astrocytes was observed in pure AD cases, but not in mixed DLB + AD or pure DLB cases. Mixed DLB + AD had higher CD68-loads in the amygdala and parahippocampal gyrus than pure DLB cases, but did not differ in astrocytic loads. Pure AD showed higher Iba1-loads in the CA1 and CA2, higher CD68-loads in the CA2 and subiculum, and a higher astrocytic load in the CA1-4 and subiculum than mixed DLB + AD cases. In mixed DLB + AD cases, microglial load associated strongly with amyloid-beta (Iba1, CD68 and HLA-DR), and p-tau (CD68 and HLA-DR), and minimally with alpha-synuclein load (CD68). In addition, the highest microglial activity was found in the amygdala and CA2, and astroglial load in the CA4. Confocal microscopy demonstrated co-localization of large amoeboid microglia with neuritic and classic-cored plaques of amyloid-beta and p-tau in mixed DLB + AD cases.
CONCLUSIONS
In conclusion, microglial activation in DLB was largely associated with AD co-pathology, while astrocytic response in DLB was not. In addition, microglial activity was high in limbic regions, with prevalent AD pathology. Our study provides novel insights into the molecular neuropathology of DLB, highlighting the importance of microglial activation in mixed DLB + AD.
Topics: Humans; Lewy Body Disease; Alzheimer Disease; Female; Male; Aged; Aged, 80 and over; Neuroinflammatory Diseases; Microglia; Astrocytes; alpha-Synuclein; tau Proteins; Antigens, CD; Amyloid beta-Peptides; Middle Aged; Antigens, Differentiation, Myelomonocytic; Brain; CD68 Molecule
PubMed: 38715119
DOI: 10.1186/s40478-024-01786-z -
Neurological Research Aug 2023Previous functional magnetic resonance imaging (fMRI) studies reported inconsistent results for comparison in brain activation between migraine patients and healthy...
BACKGROUND
Previous functional magnetic resonance imaging (fMRI) studies reported inconsistent results for comparison in brain activation between migraine patients and healthy controls (HC). Thus, activation likelihood estimation (ALE) method, a powerful voxel-based technique, was used to explore the concordant functional brain changes in migraine patients.
METHODS
Studies published before October 2022 were searched in the following databases (PubMed, Web of Science and Google Scholar).
RESULTS
Migraine without aura (MWoA) patients showed reduced amplitude of low-frequency fluctuations (ALFF) in right lingual gyrus, the left posterior cingulate and the right precuneus (PCUN), compared to HC. Migraine patients showed increased ALFF in the right claustrum, the left caudate, the left insula and the right parahippocampal gyrus, compared to HC. MWoA patients showed reduced regional homogeneity (ReHo) in the right culmen, compared to HC. In addition, migraine patients showed increased ReHo in the bilateral thalamus, compared to HC. MWoA patients showed reduced whole-brain functional connectivity (FC) in the left middle occipital gyrus and the right superior parietal lobule, compared to HC. In addition, migraine patients showed increased whole-brain FC in the left middle temporal gyrus (MTG), the right inferior frontal gyrus, the right superior temporal gyrus (STG) and the left inferior temporal gyrus, compared to HC.
CONCLUSIONS
ALE analysis identified consistent functional changes in widespread regions, especially in cingulate gyrus, basal ganglia region and frontal cortex in migraine. These regions involve in pain processing, cognitive dysfunction and emotional problems. These results may provide important clues for clarifying the pathophysiology of migraine.
Topics: Humans; Likelihood Functions; Brain; Prefrontal Cortex; Brain Mapping; Magnetic Resonance Imaging; Migraine without Aura
PubMed: 37019685
DOI: 10.1080/01616412.2023.2199377 -
Brain : a Journal of Neurology Mar 2024Exposure to repetitive head impacts (RHIs) in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE) which...
Exposure to repetitive head impacts (RHIs) in contact sports is associated with neurodegenerative disorders including chronic traumatic encephalopathy (CTE) which currently can be diagnosed only at postmortem. American football players are at higher risk of developing CTE given their exposure to RHIs. One promising approach for diagnosing CTE in vivo is to explore known neuropathological abnormalities at postmortem in living individuals using structural magnetic resonance imaging (MRI). MRI brain morphometry was evaluated in 170 male former American football players ages 45-74 years (n = 114 professional; n = 56 college) and 54 same-age unexposed asymptomatic male controls (n = 58 age range 45-74). Cortical thickness and volume of regions of interest were selected based on established CTE pathology findings and were assessed using FreeSurfer. Group differences and interactions with age and exposure factors were evaluated using a generalized least squares model. A separate logistic regression and independent multinomial model were performed to predict each Traumatic Encephalopathy Syndrome (TES) diagnosis core clinical features and provisional level of certainty for CTE pathology using brain regions of interest. Former college and professional American football players (combined) showed significant cortical thickness and/or volume reductions compared to unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula temporal pole and superior frontal gyrus. Post-hoc analyses identified group-level differences between former professional players and unexposed asymptomatic controls in the hippocampus amygdala entorhinal cortex parahippocampal gyrus insula and superior frontal gyrus. Former college players showed significant volume reductions in the hippocampus amygdala and superior frontal gyrus compared to the unexposed asymptomatic controls. We did not observe age-by-group interactions for brain morphometric measures. Interactions between morphometry and exposure measures were limited to a single significant positive association between the age of first exposure to organized tackle football and right insular volume. We found no significant relationship between brain morphometric measures and the TES diagnosis core clinical features and provisional level of certainty for CTE pathology outcomes. These findings suggest that MRI morphometrics detects abnormalities in individuals with a history of RHI exposure that resemble the anatomic distribution of pathological findings from postmortem CTE studies. The lack of findings associating MRI measures with exposure metrics (except for one significant relationship) or TES diagnosis and core clinical features suggests that brain morphometry must be complemented by other types of measures to characterize individuals with RHIs.
PubMed: 38533783
DOI: 10.1093/brain/awae098 -
The Journal of Neuroscience : the... Oct 2023Infant stimuli elicit widespread neural and behavioral response in human adults, and such massive allocation of resources attests to the evolutionary significance of the...
Infant stimuli elicit widespread neural and behavioral response in human adults, and such massive allocation of resources attests to the evolutionary significance of the primary attachment. Here, we examined whether attachment reminders also trigger cross-brain concordance and generate greater neural uniformity, as indicated by intersubject correlation. Human mothers were imaged twice in oxytocin/placebo administration design, and stimuli included four ecological videos of a standard unfamiliar mother and infant: two infant/mother alone () and two mother-infant dyadic contexts (). Theory-driven analysis measured cross-brain synchrony in preregistered nodes of the parental caregiving network (PCN), which integrates subcortical structures underpinning mammalian mothering with cortical areas implicated in simulation, mentalization, and emotion regulation, and data-driven analysis assessed brain-wide concordance using whole-brain parcellation. Results demonstrated widespread cross-brain synchrony in both the PCN and across the neuroaxis, from primary sensory/somatosensory areas, through insular-cingulate regions, to temporal and prefrontal cortices. The context yielded significantly more cross-brain concordance, with PCNs striatum, parahippocampal gyrus, superior temporal sulcus, ACC, and PFC displaying cross-brain synchrony only to mother-infant social cues. Moment-by-moment fluctuations in mother-infant social synchrony, ranging from episodes of low synchrony to tightly coordinated positive bouts, were tracked online by cross-brain concordance in the preregistered ACC. Findings indicate that social attachment stimuli, representing evolutionary-salient universal cues that require no verbal narrative, trigger substantial interbrain concordance and suggest that the mother-infant bond, an icon standing at the heart of human civilization, may function to glue brains into a unified experience and bind humans into social groups. Infant stimuli elicit widespread neural response in human adults, attesting to their evolutionary significance, but do they also trigger cross-brain concordance and induce neural uniformity among perceivers? We measured cross-brain synchrony to ecological mother-infant videos. We used theory-driven analysis, measuring cross-brain concordance in the parenting network, and data-driven analysis, assessing brain-wide concordance using whole-brain parcellation. Attachment cues triggered widespread cross-brain concordance in both the parenting network and across the neuroaxis. Moment-by-moment fluctuations in behavioral synchrony were tracked online by cross-brain variability in ACC. Attachment reminders bind humans' brains into a unitary experience and stimuli characterized by social synchrony enhance neural similarity among participants, describing one mechanism by which attachment bonds provide the neural template for the consolidation of social groups.
Topics: Infant; Adult; Animals; Humans; Female; Brain; Maternal Behavior; Temporal Lobe; Prefrontal Cortex; Mother-Child Relations; Mothers; Mammals
PubMed: 37813569
DOI: 10.1523/JNEUROSCI.0026-23.2023 -
Cortex; a Journal Devoted To the Study... Feb 2024Procrastination has adverse effects on personal growth and social development. Behavior research has found reward sensitivity is positively correlated with...
Procrastination has adverse effects on personal growth and social development. Behavior research has found reward sensitivity is positively correlated with procrastination. However, it remains unclear that the neural substrates underlie the relationship between reward sensitivity and procrastination. To address this issue, the present study used voxel-based morphometry (VBM) and resting-state functional connectivity (RSFC) analyses to investigate the neural substrates underlying the association with reward sensitivity and procrastination in two independent samples (N1 = 388, N2 = 330). In Sample 1, the behavioral result indicated reward sensitivity was positively correlated with procrastination. Moreover, the VBM analysis showed that reward sensitivity was positively associated with the gray matter volume (GMV) of the right parahippocampal gyrus. Furthermore, the RSFC result found reward sensitivity was negatively associated with the functional connectivity of the right parahippocampal gyrus-precuneus. Crucially, the mediation analysis revealed that functional connectivity of the right parahippocampal gyrus-precuneus mediated the relationship between reward sensitivity and procrastination. To verify the robustness of the results, confirmatory analysis was carried out in Sample 2. The results of Sample 1 (i.e., the behavioral, VBM, RSFC, and mediation results) can be verified in Sample 2. In brief, these findings suggested that the functional connectivity of the right parahippocampal gyrus-precuneus involved in reward impulsive control could modulate the relationship between reward sensitivity and procrastination, which is the first to reveal the neural underpinning of the association between reward sensitivity and procrastination.
Topics: Humans; Prefrontal Cortex; Brain Mapping; Procrastination; Magnetic Resonance Imaging; Parahippocampal Gyrus; Gray Matter; Parietal Lobe
PubMed: 38000138
DOI: 10.1016/j.cortex.2023.10.017 -
European Child & Adolescent Psychiatry Jan 2024The pathological mechanism of autism spectrum disorder (ASD) remains unclear. Nowadays, surface-based morphometry (SBM) based on structural magnetic resonance imaging... (Meta-Analysis)
Meta-Analysis
The pathological mechanism of autism spectrum disorder (ASD) remains unclear. Nowadays, surface-based morphometry (SBM) based on structural magnetic resonance imaging (sMRI) techniques have reported cortical thickness (CT) variations in ASD. However, the findings were inconsistent and heterogeneous. This current meta-analysis conducted a whole-brain vertex-wise coordinate-based meta-analysis (CBMA) on CT studies to explore the most noticeable and robust CT changes in ASD individuals by applying the seed-based d mapping (SDM) program. A total of 26 investigations comprised 27 datasets were included, containing 1,635 subjects with ASD and 1470 HC, along with 94 coordinates. Individuals with ASD exhibited significantly altered CT in several regions compared to HC, including four clusters with thicker CT in the right superior temporal gyrus (STG.R), the left middle temporal gyrus (MTG.L), the left anterior cingulate/paracingulate gyri, the right superior frontal gyrus (SFG.R, medial orbital parts), as well as three clusters with cortical thinning including the left parahippocampal gyrus (PHG.L), the right precentral gyrus (PCG.R) and the left middle frontal gyrus (MFG.L). Adults with ASD only demonstrated CT thinning in the right parahippocampal gyrus (PHG.R), revealed by subgroup meta-analyses. Meta-regression analyses found that CT in STG.R was positively correlated with age. Meanwhile, CT in MFG.L and PHG.L had negative correlations with the age of ASD individuals. These results suggested a complicated and atypical cortical development trajectory in ASD, and would provide a deeper understanding of the neural mechanism underlying the cortical morphology in ASD.
Topics: Adult; Humans; Autism Spectrum Disorder; Brain; Magnetic Resonance Imaging; Brain Mapping
PubMed: 36542200
DOI: 10.1007/s00787-022-02133-0 -
Journal of Neuro-oncology Sep 2023Glioblastoma (GBM) is the most common and aggressive malignant glioma, with an overall median survival of less than two years. The ability to predict survival before...
PURPOSE
Glioblastoma (GBM) is the most common and aggressive malignant glioma, with an overall median survival of less than two years. The ability to predict survival before treatment in GBM patients would lead to improved disease management, clinical trial enrollment, and patient care.
METHODS
GBM patients (N = 133, mean age 60.8 years, median survival 14.1 months, 57.9% male) were retrospectively recruited from the neurosurgery brain tumor service at Washington University Medical Center. All patients completed structural neuroimaging and resting state functional MRI (RS-fMRI) before surgery. Demographics, measures of cortical thickness (CT), and resting state functional network connectivity (FC) were used to train a deep neural network to classify patients based on survival (< 1y, 1-2y, >2y). Permutation feature importance identified the strongest predictors of survival based on the trained models.
RESULTS
The models achieved a combined cross-validation and hold out accuracy of 90.6% in classifying survival (< 1y, 1-2y, >2y). The strongest demographic predictors were age at diagnosis and sex. The strongest CT predictors of survival included the superior temporal sulcus, parahippocampal gyrus, pericalcarine, pars triangularis, and middle temporal regions. The strongest FC features primarily involved dorsal and inferior somatomotor, visual, and cingulo-opercular networks.
CONCLUSION
We demonstrate that machine learning can accurately classify survival in GBM patients based on multimodal neuroimaging before any surgical or medical intervention. These results were achieved without information regarding presentation symptoms, treatments, postsurgical outcomes, or tumor genomic information. Our results suggest GBMs have a global effect on the brain's structural and functional organization, which is predictive of survival.
Topics: Humans; Male; Middle Aged; Female; Glioblastoma; Retrospective Studies; Magnetic Resonance Imaging; Neuroimaging; Machine Learning
PubMed: 37668941
DOI: 10.1007/s11060-023-04439-8 -
Scientific Reports Oct 2023The pathological features of Alzheimer's disease are the formation of amyloid plaques and entanglement of nerve fibers. Studies have shown that Cu may be involved in the...
The pathological features of Alzheimer's disease are the formation of amyloid plaques and entanglement of nerve fibers. Studies have shown that Cu may be involved in the formation of amyloid plaques. However, their role has been controversial. The aim of this study was to explore the role of Cu in AD. We applied the "R" software for our differential analysis. Differentially expressed genes were screened using the limma package. Copper metabolism-related genes and the intersection set of differential genes with GSE5281 were searched; functional annotation was performed. The protein-protein interaction network was constructed using several modules to analyse the most significant hub genes. The hub genes were then qualified, and a database was used to screen for small-molecule AD drugs. We identified 87 DEGs. gene ontology analysis focused on homeostatic processes, response to toxic substances, positive regulation of transport, and secretion. The enriched molecular functions are mainly related to copper ion binding, molecular function regulators, protein-containing complex binding, identical protein binding and signalling receptor binding. The KEGG database is mainly involved in central carbon metabolism in various cancers, Parkinson's disease and melanoma. We identified five hub genes, FGF2, B2M, PTPRC, CD44 and SPP1, and identified the corresponding small molecule drugs. Our study identified key genes possibly related to energy metabolism in the pathological mechanism of AD and explored potential targets for AD treatment by establishing interaction networks.
Topics: Humans; Gene Expression Profiling; Entorhinal Cortex; Copper; Alzheimer Disease; Plaque, Amyloid
PubMed: 37838728
DOI: 10.1038/s41598-023-44656-9 -
Frontiers in Aging Neuroscience 2023The correlation between gut microbiota and Alzheimer's disease (AD) is increasingly being recognized by clinicians. However, knowledge about the gut-brain-cognition...
BACKGROUND
The correlation between gut microbiota and Alzheimer's disease (AD) is increasingly being recognized by clinicians. However, knowledge about the gut-brain-cognition interaction remains largely unknown.
METHODS
One hundred and twenty-seven participants, including 35 normal controls (NCs), 62 with subjective cognitive decline (SCD), and 30 with cognitive impairment (CI), were included in this study. The participants underwent neuropsychological assessments and fecal microbiota analysis through 16S ribosomal RNA (rRNA) Illumina Miseq sequencing technique. Structural MRI data were analyzed for cortical anatomical features, including thickness, sulcus depth, fractal dimension, and Toro's gyrification index using the SBM method. The association of altered gut microbiota among the three groups with structural MRI metrics and cognitive function was evaluated. Furthermore, co-expression network analysis was conducted to investigate the gut-brain-cognition interactions.
RESULTS
The abundance of , and decreased with cognitive ability. , and were specifically enriched in the CI group. abundance was correlated with changes in brain gray matter and cerebrospinal fluid volume ( = 0.0214, = 0.0162) and significantly with changes in cortical structures in brain regions, such as the internal olfactory area and the parahippocampal gyrus. The three colonies enriched in the CI group were positively correlated with cognitive function and significantly associated with changes in cortical structure related to cognitive function, such as the precuneus and syrinx gyrus.
CONCLUSION
This study provided evidence that there was an inner relationship among the altered gut microbiota, brain atrophy, and cognitive decline. Targeting the gut microbiota may be a novel therapeutic strategy for early AD.
PubMed: 37520126
DOI: 10.3389/fnagi.2023.1216509