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Journal of Neuroscience Research Sep 2023This study aimed to explore the alterations in gray matter volume (GMV) based on high-resolution structural data and the temporal precedence of structural alterations in...
This study aimed to explore the alterations in gray matter volume (GMV) based on high-resolution structural data and the temporal precedence of structural alterations in patients with sleep-related hypermotor epilepsy (SHE). After preprocessing of T1 structural images, the voxel-based morphometry and source-based morphometry (SBM) methods were applied in 60 SHE patients and 56 healthy controls to analyze the gray matter volumetric alterations. Furthermore, a causal network of structural covariance (CaSCN) was constructed using Granger causality analysis based on structural data of illness duration ordering to assess the causal impact of structural changes in abnormal gray matter regions. The GMVs of SHE patients were widely reduced, mainly in the bilateral cerebellums, fusiform gyri, the right angular gyrus, the right postcentral gyrus, and the left parahippocampal gyrus. In addition to those regions, the results of the SBM analysis also found decreased GMV in the bilateral frontal lobes, precuneus, and supramarginal gyri. The analysis of CaSCN showed that along with disease progression, the cerebellum was the prominent node that tended to affect other brain regions in SHE patients, while the frontal lobe was the transition node and the supramarginal gyrus was the prominent node that may be easily affected by other brain regions. Our study found widely affected regions of decreased GMVs in SHE patients; these regions underlie the morphological basis of epileptic networks, and there is a temporal precedence relationship between them.
Topics: Humans; China; Ethnicity; Brain; Gray Matter; Sleep
PubMed: 37183389
DOI: 10.1002/jnr.25203 -
Journal of Psychopharmacology (Oxford,... Nov 2023For many patients with major depressive disorder (MDD) adequate treatment remains elusive. Neuroimaging techniques received attention for their potential use in guiding...
BACKGROUND
For many patients with major depressive disorder (MDD) adequate treatment remains elusive. Neuroimaging techniques received attention for their potential use in guiding and predicting response, but were rarely investigated in real-world psychiatric settings.
AIMS
To identify structural and functional Magnetic Resonance Imaging (MRI) biomarkers associated with antidepressant response in a real-world clinical sample.
METHODS
We studied 100 MDD inpatients admitted to our psychiatric ward, treated with various antidepressants upon clinical need. Hamilton Depression Rating Scale percentage decrease from admission to discharge was used as a measure of response. All patients underwent 3.0 T MRI scanning. Grey matter (GM) volumes were investigated both in a voxel-based morphometry (VBM), and in a regions of interest (ROI) analysis. In a subsample of patients, functional resting-state connectivity patterns were also explored.
RESULTS
In the VBM analysis, worse response was associated to lower GM volumes in two clusters, encompassing the left hippocampus and parahippocampal gyrus, and the right superior and middle temporal gyrus. Investigating ROIs, lower bilateral hippocampi and amygdalae volumes predicted worse treatment outcomes. Functional connectivity in the right temporal and parahippocampal gyrus was also associated to response.
CONCLUSION
Our results expand existing literature on the relationship between the structure and function of several brain regions and treatment response in MDD. While we are still far from routine use of MRI biomarkers in clinical practice, we confirm a possible role of these techniques in guiding treatment choices and predicting their efficacy.
Topics: Humans; Depressive Disorder, Major; Depression; Brain; Antidepressive Agents; Neuroimaging; Hippocampus; Magnetic Resonance Imaging; Biomarkers
PubMed: 37589290
DOI: 10.1177/02698811231190859 -
Ageing Research Reviews Dec 2023In aging, olfactory deficits have been associated with lower cognition and motor function. Olfactory dysfunction is also one of the earliest features of... (Review)
Review
In aging, olfactory deficits have been associated with lower cognition and motor function. Olfactory dysfunction is also one of the earliest features of neurodegenerative disease. A comprehensive review of the neural correlates of olfactive function may reveal mechanisms underlying the associations among olfaction, cognition, motor function, and neurodegenerative diseases. Here, we summarize existing knowledge on the relationship between brain structural and functional measures and olfaction in older adults without and with cognitive impairment, including Alzheimer's disease. We identified 33 eligible studies (30 MRI/DTI,3 fMRI); 31 were cross-sectional, most assessed odor identification, and few examined multiple brain areas. Lower olfactory function was associated with smaller volumes in the temporal lobe (hippocampus,parahippocampal gyrus,fusiform gyrus), olfactory-related regions (piriform cortex,amygdala,entorhinal cortex), pre- and postcentral gyri, and globus pallidus. During aging, olfactory impairment may be associated with pathology in brain areas important for motor function and cognition, especially memory. Future longitudinal studies that include neuroimaging across different brain areas are warranted to determine the neurobiological changes underlying olfactory changes in the aging brain and the progression of neurodegeneration.
Topics: Humans; Aged; Neurodegenerative Diseases; Brain; Entorhinal Cortex; Hippocampus; Temporal Lobe; Magnetic Resonance Imaging; Cognitive Dysfunction
PubMed: 37913831
DOI: 10.1016/j.arr.2023.102095 -
Neuroscience and Biobehavioral Reviews Dec 2023The influence of Prediction Errors (PEs) on episodic memory has generated growing empirical and theoretical interest. This review explores how the relationship between... (Review)
Review
The influence of Prediction Errors (PEs) on episodic memory has generated growing empirical and theoretical interest. This review explores how the relationship between PE and memory may evolve throughout lifespan. Drawing upon the predictive processing framework and the Predictive, Interactive Multiple Memory System (PIMMS) model in particular, the paper highlights the hierarchical organization of memory systems and the interaction between top-down predictions and bottom-up sensory input, proposing that PEs promote synaptic change and improve encoding and consolidation processes. We discuss the neuroscientific mechanisms underlying PE-driven memory enhancement, focusing on the involvement of the hippocampus, the entorhinal cortex-hippocampus pathway, and the noradrenergic sympathetic system. Recognizing the divergent trajectories of episodic and semantic memory across the lifespan is crucial when examining the effects of PEs on memory. This review underscores the heterogeneity of memory processes and neurocognitive mechanisms underlying PE-driven memory enhancement across age. Future research is suggested to directly compare neural networks involved in learning from PEs across different age groups and to contribute to a deeper understanding of PE-driven learning across age.
Topics: Humans; Longevity; Memory, Episodic; Entorhinal Cortex; Hippocampus; Neural Networks, Computer
PubMed: 37951515
DOI: 10.1016/j.neubiorev.2023.105462 -
Alzheimer's & Dementia : the Journal of... Aug 2023Recent studies revealed the association of abnormal methylomic changes with Alzheimer's disease (AD) but there is a lack of systematic study of the impact of methylomic...
INTRODUCTION
Recent studies revealed the association of abnormal methylomic changes with Alzheimer's disease (AD) but there is a lack of systematic study of the impact of methylomic alterations over the molecular networks underlying AD.
METHODS
We profiled genome-wide methylomic variations in the parahippocampal gyrus from 201 post mortem control, mild cognitive impaired, and AD brains.
RESULTS
We identified 270 distinct differentially methylated regions (DMRs) associated with AD. We quantified the impact of these DMRs on each gene and each protein as well as gene and protein co-expression networks. DNA methylation had a profound impact on both AD-associated gene/protein modules and their key regulators. We further integrated the matched multi-omics data to show the impact of DNA methylation on chromatin accessibility, which further modulates gene and protein expression.
DISCUSSION
The quantified impact of DNA methylation on gene and protein networks underlying AD identified potential upstream epigenetic regulators of AD.
HIGHLIGHTS
A cohort of DNA methylation data in the parahippocampal gyrus was developed from 201 post mortem control, mild cognitive impaired, and Alzheimer's disease (AD) brains. Two hundred seventy distinct differentially methylated regions (DMRs) were found to be associated with AD compared to normal control. A metric was developed to quantify methylation impact on each gene and each protein. DNA methylation was found to have a profound impact on not only the AD-associated gene modules but also key regulators of the gene and protein networks. Key findings were validated in an independent multi-omics cohort in AD. The impact of DNA methylation on chromatin accessibility was also investigated by integrating the matched methylomic, epigenomic, transcriptomic, and proteomic data.
Topics: Humans; Alzheimer Disease; Epigenesis, Genetic; Gene Regulatory Networks; Proteomics; DNA Methylation
PubMed: 36811307
DOI: 10.1002/alz.12969 -
BMC Medicine Aug 2023Microglia are known to regulate stress and anxiety in both humans and animal models. Psychosocial stress is the most common risk factor for the development of...
BACKGROUND
Microglia are known to regulate stress and anxiety in both humans and animal models. Psychosocial stress is the most common risk factor for the development of schizophrenia. However, how microglia/brain macrophages contribute to schizophrenia is not well established. We hypothesized that effector molecules expressed in microglia/macrophages were involved in schizophrenia via regulating stress susceptibility.
METHODS
We recruited a cohort of first episode schizophrenia (FES) patients (n = 51) and age- and sex-paired healthy controls (HCs) (n = 46) with evaluated stress perception. We performed blood RNA-sequencing (RNA-seq) and brain magnetic resonance imaging, and measured plasma level of colony stimulating factor 1 receptor (CSF1R). Furthermore, we studied a mouse model of chronic unpredictable stress (CUS) combined with a CSF1R inhibitor (CSF1Ri) (n = 9 ~ 10/group) on anxiety behaviours and microglial biology.
RESULTS
FES patients showed higher scores of perceived stress scale (PSS, p < 0.05), lower blood CSF1R mRNA (FDR = 0.003) and protein (p < 0.05) levels, and smaller volumes of the superior frontal gyrus and parahippocampal gyrus (both FDR < 0.05) than HCs. In blood RNA-seq, CSF1R-associated differentially expressed blood genes were related to brain development. Importantly, CSF1R facilitated a negative association of the superior frontal gyrus with PSS (p < 0.01) in HCs but not FES patients. In mouse CUS+CSF1Ri model, similarly as CUS, CSF1Ri enhanced anxiety (both p < 0.001). Genes for brain angiogenesis and intensity of CD31-blood vessels were dampened after CUS-CSF1Ri treatment. Furthermore, CSF1Ri preferentially diminished juxta-vascular microglia/macrophages and induced microglia/macrophages morphological changes (all p < 0.05).
CONCLUSION
Microglial/macrophagic CSF1R regulated schizophrenia-associated stress and brain angiogenesis.
Topics: Animals; Humans; Mice; Brain; Disease Models, Animal; Macrophages; Microglia; Receptors, Granulocyte-Macrophage Colony-Stimulating Factor; Schizophrenia
PubMed: 37542262
DOI: 10.1186/s12916-023-02959-8 -
Scientific Data Sep 2023Alzheimer's disease (AD) is the most common form of dementia worldwide, with a projection of 151 million cases by 2050. Previous genetic studies have identified three...
Alzheimer's disease (AD) is the most common form of dementia worldwide, with a projection of 151 million cases by 2050. Previous genetic studies have identified three main genes associated with early-onset familial Alzheimer's disease, however this subtype accounts for less than 5% of total cases. Next-generation sequencing has been well established and holds great promise to assist in the development of novel therapeutics as well as biomarkers to prevent or slow the progression of this devastating disease. Here we present a public resource of functional genomic data from the parahippocampal gyrus of 201 postmortem control, mild cognitively impaired (MCI) and AD individuals from the Mount Sinai brain bank, of which whole-genome sequencing (WGS), and bulk RNA sequencing (RNA-seq) were previously published. The genomic data include bulk proteomics and DNA methylation, as well as cell-type-specific RNA-seq and assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) data. We have performed extensive preprocessing and quality control, allowing the research community to access and utilize this public resource available on the Synapse platform at https://doi.org/10.7303/syn51180043.2 .
Topics: Humans; Alzheimer Disease; Biological Assay; Multiomics; Parahippocampal Gyrus
PubMed: 37684260
DOI: 10.1038/s41597-023-02507-2 -
Neural Computation Sep 2023Grid cells play a principal role in enabling cognitive representations of ambient environments. The key property of these cells-the regular arrangement of their firing...
Grid cells play a principal role in enabling cognitive representations of ambient environments. The key property of these cells-the regular arrangement of their firing fields-is commonly viewed as a means for establishing spatial scales or encoding specific locations. However, using grid cells' spiking outputs for deducing geometric orderliness proves to be a strenuous task due to fairly irregular activation patterns triggered by the animal's sporadic visits to the grid fields. This article addresses statistical mechanisms enabling emergent regularity of grid cell firing activity from the perspective of percolation theory. Using percolation phenomena for modeling the effect of the rat's moves through the lattices of firing fields sheds new light on the mechanisms of spatial information processing, spatial learning, path integration, and establishing spatial metrics. It is also shown that physiological parameters required for spiking percolation match the experimental range, including the characteristic 2/3 ratio between the grid fields' size and the grid spacing, pointing at a biological viability of the approach.
Topics: Rats; Animals; Grid Cells; Entorhinal Cortex; Models, Neurological; Action Potentials; Neurons; Space Perception
PubMed: 37523457
DOI: 10.1162/neco_a_01606 -
Epilepsy & Behavior : E&B Jul 2024In this paper we look at non-pharmaceutical treatments for intractable epilepsy based on neurophysiological methods especially with EEG analysis. In summary, there are a... (Review)
Review
In this paper we look at non-pharmaceutical treatments for intractable epilepsy based on neurophysiological methods especially with EEG analysis. In summary, there are a number of limbic and thalamo-cortical related structures involved in the processing of musical emotion (exposure), including the amygdala (arousal, expression of mood, fear), hippocampus (memory, regulation of HPA axis, stress), parahippocampal gyrus (recognition, memory retrieval), insula (valence), temporal poles (connectivity), ventral striatum (expectation and experience of reward), orbitofrontal cortex (valence) and cingulate cortex (autonomic regulation). One method is to audify (a form of sonification) EEG activity to find music by feedback to entrain abnormal EEG activity. We discuss various methods and our use of X-System (https://www.x-system.co.uk/) which is a computational model of the musical brain capable of predicting the neurophysiological effects of music. It models structures and pathways related to responses to music, including the cochlea, brain stem, auditory and motor cortex, as well as basal ganglia, cerebellum and limbic structures. It can predict autonomic and endocrine activity as well as the substrates of electrical activity to select music which can regularise EEG abnormalities to decrease epileptic activity and seizures, especially in those unresponsive to antiepileptic medication or invasive treatments.
Topics: Humans; Epilepsy; Music Therapy; Music; Electroencephalography; Brain; Auditory Perception; Precision Medicine
PubMed: 38761451
DOI: 10.1016/j.yebeh.2024.109829