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Frontiers in Human Neuroscience 2021Although emerging evidence has implicated structural/functional abnormalities of patients with Autism Spectrum Disorder(ASD), definitive neuroimaging markers remain...
Although emerging evidence has implicated structural/functional abnormalities of patients with Autism Spectrum Disorder(ASD), definitive neuroimaging markers remain obscured due to inconsistent or incompatible findings, especially for structural imaging. Furthermore, brain differences defined by statistical analysis are difficult to implement individual prediction. The present study has employed the machine learning techniques under the unified framework in neuroimaging to identify the neuroimaging markers of patients with ASD and distinguish them from typically developing controls(TDC). To enhance the interpretability of the machine learning model, the study has processed three levels of assessments including model-level assessment, feature-level assessment, and biology-level assessment. According to these three levels assessment, the study has identified neuroimaging markers of ASD including the opercular part of bilateral inferior frontal gyrus, the orbital part of right inferior frontal gyrus, right rolandic operculum, right olfactory cortex, right gyrus rectus, right insula, left inferior parietal gyrus, bilateral supramarginal gyrus, bilateral angular gyrus, bilateral superior temporal gyrus, bilateral middle temporal gyrus, and left inferior temporal gyrus. In addition, negative correlations between the communication skill score in the Autism Diagnostic Observation Schedule (ADOS_G) and regional gray matter (GM) volume in the gyrus rectus, left middle temporal gyrus, and inferior temporal gyrus have been detected. A significant negative correlation has been found between the communication skill score in ADOS_G and the orbital part of the left inferior frontal gyrus. A negative correlation between verbal skill score and right angular gyrus and a significant negative correlation between non-verbal communication skill and right angular gyrus have been found. These findings in the study have suggested the GM alteration of ASD and correlated with the clinical severity of ASD disease symptoms. The interpretable machine learning framework gives sight to the pathophysiological mechanism of ASD but can also be extended to other diseases.
PubMed: 35273484
DOI: 10.3389/fnhum.2021.765517 -
Cell & Bioscience May 2023Where the gene is expressed determines the function of the gene. Neuregulin 1 (Nrg1) encodes a tropic factor and is genetically linked with several neuropsychiatry...
BACKGROUND
Where the gene is expressed determines the function of the gene. Neuregulin 1 (Nrg1) encodes a tropic factor and is genetically linked with several neuropsychiatry diseases such as schizophrenia, bipolar disorder and depression. Nrg1 has broad functions ranging from regulating neurodevelopment to neurotransmission in the nervous system. However, the expression pattern of Nrg1 at the cellular and circuit levels in rodent brain is not full addressed.
METHODS
Here we used CRISPR/Cas9 techniques to generate a knockin mouse line (Nrg1) that expresses a P2A-Cre cassette right before the stop codon of Nrg1 gene. Since Cre recombinase and Nrg1 are expressed in the same types of cells in Nrg1 mice, the Nrg1 expression pattern can be revealed through the Cre-reporting mice or adeno-associated virus (AAV) that express fluorescent proteins in a Cre-dependent way. Using unbiased stereology and fluorescence imaging, the cellular expression pattern of Nrg1 and axon projections of Nrg1-positive neurons were investigated.
RESULTS
In the olfactory bulb (OB), Nrg1 is expressed in GABAergic interneurons including periglomerular (PG) and granule cells. In the cerebral cortex, Nrg1 is mainly expressed in the pyramidal neurons of superficial layers that mediate intercortical communications. In the striatum, Nrg1 is highly expressed in the Drd1-positive medium spiny neurons (MSNs) in the shell of nucleus accumbens (NAc) that project to substantia nigra pars reticulata (SNr). In the hippocampus, Nrg1 is mainly expressed in granule neurons in the dentate gyrus and pyramidal neurons in the subiculum. The Nrg1-expressing neurons in the subiculum project to retrosplenial granular cortex (RSG) and mammillary nucleus (MM). Nrg1 is highly expressed in the median eminence (ME) of hypothalamus and Purkinje cells in the cerebellum.
CONCLUSIONS
Nrg1 is broadly expressed in mouse brain, mainly in neurons, but has unique expression patterns in different brain regions.
PubMed: 37147705
DOI: 10.1186/s13578-023-01032-4 -
Frontiers in Human Neuroscience 2022: It has been reported that type 2 diabetes (T2DM) is associated with olfactory identification (OI) impairments and cognitive decline. However, the relationship between...
: It has been reported that type 2 diabetes (T2DM) is associated with olfactory identification (OI) impairments and cognitive decline. However, the relationship between OI impairments and cognitive decline is largely unknown in T2DM patients. : Sixty-eight T2DM patients and 68 healthy controls underwent 3D-T1 MRI scans, olfactory and cognitive assessments. The cortical thickness of olfaction-related brain regions, olfactory and cognitive scores were compared between groups. Correlation analyses were carried out among cognition, olfaction, and cortical thickness of olfaction-related brain regions. : First, the cognitive and olfactory test scores of T2DM patients were lower than healthy subjects. Second, higher olfactory scores were associated with increased cortical thickness in the left parahippocampal gyrus and bilateral insula in T2DM. Third, higher olfactory scores were associated with higher cognitive performance in T2DM. Fourth, some cognitive performances were related to cortical thickness in the left parahippocampal gyrus and left insula in T2DM. : These findings indicated that olfactory dysfunction may be useful for future applications that attempt to predict cognitive decline or develop tailored therapies in T2DM patients.
PubMed: 35237139
DOI: 10.3389/fnhum.2022.773309 -
Frontiers in Aging Neuroscience 2022Central anosmia is a potential marker of the prodrome and progression of Parkinson's disease (PD). Resting-state functional magnetic resonance imaging studies have shown...
INTRODUCTION
Central anosmia is a potential marker of the prodrome and progression of Parkinson's disease (PD). Resting-state functional magnetic resonance imaging studies have shown that olfactory dysfunction is related to abnormal changes in central olfactory-related structures in patients with early PD.
METHODS
This study, which was conducted at Guanyun People's Hospital, analyzed the resting-state functional magnetic resonance data using the functional covariance connection strength method to decode the functional connectivity between the white-gray matter in a Chinese population comprising 14 patients with PD and 13 controls.
RESULTS
The following correlations were observed in patients with PD: specific gray matter areas related to smell (i.e., the brainstem, right cerebellum, right temporal fusiform cortex, bilateral superior temporal gyrus, right Insula, left frontal pole and right superior parietal lobule) had abnormal connections with white matter fiber bundles (i.e., the left posterior thalamic radiation, bilateral posterior corona radiata, bilateral superior corona radiata and right superior longitudinal fasciculus); the connection between the brainstem [region of interest (ROI) 1] and right cerebellum (ROI2) showed a strong correlation. Right posterior corona radiation (ROI11) showed a strong correlation with part 2 of the Unified Parkinson's Disease Rating Scale, and right superior longitudinal fasciculus (ROI14) showed a strong correlation with parts 1, 2, and 3 of the Unified Parkinson's Disease Rating Scale and Hoehn and Yahr Scale.
DISCUSSION
The characteristics of olfactory-related brain networks can be potentially used as neuroimaging biomarkers for characterizing PD states. In the future, dynamic testing of olfactory function may help improve the accuracy and specificity of olfactory dysfunction in the diagnosis of neurodegenerative diseases.
PubMed: 36688163
DOI: 10.3389/fnagi.2022.1071520 -
Cortex; a Journal Devoted To the Study... Aug 2023Lemon fragrance is known for its stimulating properties, but its mechanisms of action are not well known yet. This study aimed to examine the effect of lemon essential...
Lemon fragrance is known for its stimulating properties, but its mechanisms of action are not well known yet. This study aimed to examine the effect of lemon essential oil inhalation on healthy participants' alertness level and their neural correlates using magnetic resonance imaging (MRI). Twenty-one healthy men underwent functional MRI scans in different conditions: a resting state condition, a condition where they were exposed to passive lemon smelling (alternating exposure to lemon and breathing fresh air), and a control condition without lemon fragrance diffusion -the order of the last two conditions being randomized. Alertness levels were assessed immediately after each condition using the Karolinska Sleepiness Scale. Voxel-wise whole-brain global functional connectivity and graph theory analyses were computed to investigate brain functional connectivity and network topology alterations. After lemon fragrance inhalation, we observed a higher level of alertness as compared to resting state -but not compared to control condition. During lemon fragrance inhalation, we found increased global functional connectivity in the thalamus, paralleled by decreased global connectivity in several cortical regions such as precuneus, postcentral and precentral gyrus, lateral occipital cortex and paracingulate gyrus. Graph theory analysis revealed increased network integration in cortical regions typically involved in olfaction and emotion processing such as olfactory bulb, hypothalamus and thalamus, while decreased network segregation in several regions of the posterior part of the brain during olfaction as compared to resting state. The present findings suggest that lemon essential oil inhalation could increase the level of alertness.
Topics: Male; Humans; Brain; Brain Mapping; Magnetic Resonance Imaging; Attention; Thalamus
PubMed: 37285762
DOI: 10.1016/j.cortex.2023.04.012 -
Molecular Autism Apr 2024This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
This meta-analysis aimed to explore the most robust findings across numerous existing resting-state functional imaging and voxel-based morphometry (VBM) studies on the functional and structural brain alterations in individuals with autism spectrum disorder (ASD).
METHODS
A whole-brain voxel-wise meta-analysis was conducted to compare the differences in the intrinsic functional activity and gray matter volume (GMV) between individuals with ASD and typically developing individuals (TDs) using Seed-based d Mapping software.
RESULTS
A total of 23 functional imaging studies (786 ASD, 710 TDs) and 52 VBM studies (1728 ASD, 1747 TDs) were included. Compared with TDs, individuals with ASD displayed resting-state functional decreases in the left insula (extending to left superior temporal gyrus [STG]), bilateral anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), left angular gyrus and right inferior temporal gyrus, as well as increases in the right supplementary motor area and precuneus. For VBM meta-analysis, individuals with ASD displayed decreased GMV in the ACC/mPFC and left cerebellum, and increased GMV in the left middle temporal gyrus (extending to the left insula and STG), bilateral olfactory cortex, and right precentral gyrus. Further, individuals with ASD displayed decreased resting-state functional activity and increased GMV in the left insula after overlapping the functional and structural differences.
CONCLUSIONS
The present multimodal meta-analysis demonstrated that ASD exhibited similar alterations in both function and structure of the insula and ACC/mPFC, and functional or structural alterations in the default mode network (DMN), primary motor and sensory regions. These findings contribute to further understanding of the pathophysiology of ASD.
Topics: Humans; Autism Spectrum Disorder; Brain; Cerebral Cortex; Gray Matter; Gyrus Cinguli; Magnetic Resonance Imaging
PubMed: 38576034
DOI: 10.1186/s13229-024-00593-6 -
Scientific Reports Sep 2020To investigate the changes and clinical significance of brain structural abnormalities in patients with Meige syndrome and related depressive symptoms. We...
To investigate the changes and clinical significance of brain structural abnormalities in patients with Meige syndrome and related depressive symptoms. We retrospectively analysed clinical data, imaging examinations, and Hamilton Depression Rating scale scores in 46 patients with Meige syndrome from January 2017 to January 2019. We compared the Meige syndrome group with the healthy control group, and the definite depression group with the non-definite depression group. Voxel-based morphometry (VBM) was used to compare grey matter (GM) volumes. We conducted two-sample t-tests corrected for subject age and gender. We tested at a level of significance of p < 0.001 with a false discovery rate (FDR) correction. VBM demonstrated decreased GM volume (p < 0.001 and cluster size > 50 voxels) in the left hemisphere in the middle frontal orbital gyrus, temporal pole (superior temporal gyrus) and insula and in the right hemisphere in the temporal pole (middle temporal gyrus), precuneus, inferior parietal, inferior temporal and olfactory cortices in the Meige syndrome group. Comparing VBM-MRI measures in Meige syndrome patients with and without depression, decreased GM volume was found in the left hemisphere in the cuneus and hippocampus and in the right hemisphere in the angular gyrus, middle frontal gyrus and middle occipital gyrus in the definite depression group. Unlike other dystonia studies that have suggested an involvement of the basal ganglia and motor cortex in the pathophysiology of the disorder , we believe that the precuneus is involved in the development of Meige syndrome. Additionally, our findings suggest that the hippocampus plays a role in the pathogenesis of depression in patients with Meige syndrome.
Topics: Aged; Female; Gray Matter; Humans; Magnetic Resonance Imaging; Male; Meige Syndrome; Middle Aged; Motor Cortex; Retrospective Studies
PubMed: 32884000
DOI: 10.1038/s41598-020-71479-9 -
Postepy Psychiatrii Neurologii Dec 2021Adult human brain neurogenesis is the process of cell division, differentiation, and integration of the new neurons in the brain. The neurons that arise in... (Review)
Review
PURPOSE
Adult human brain neurogenesis is the process of cell division, differentiation, and integration of the new neurons in the brain. The neurons that arise in subventricular zone migrate to the olfactory bulb, while the newly formed neurons in the dentate gyrus migrate locally. In adult neurogenesis starting from neural stem cells, in addition to glial neurons astrocytes and oligodendrocytes are also formed. Neurogenesis is regulated by endogenous and exogenous factors influencing the proliferation potential of progeni tor cells and accelerating the rate of development of the dendritic connections of newly formed neurons.
VIEWS
The slow, initial process of a developing neurodegenerative disease may have a stimulating effect on neurogenesis. Increased levels of pro-inflammatory factors may contribute to the formation of new neurons. A similar hypothesis seems to be confirmed by data in the literature. The importance of proneurogenic effects during inflammation is shown by proteins secreted by active microglia, mainly CD 47 and CD 55 and interleukin 4 and 10. On the other hand, the unfavorable effect of the inflammatory process in the brain is usually associated with chronic disease in it, when stimulated microglia increase the concentration of cytokines that have a negative effect on neurogenesis.
CONCLUSIONS
Restoring the balance between dying and emerging neurons is important and offers hope for new therapy directions in the treatment of neurodegenerative diseases. We note common points that could become the target of further research. Attention should be paid to disorders of the calcium metabolism, so important in signal transduction, the state of mitochondria with enzymes involved in the formation of ATP, and the reduction of inflammation in neurogenic regions.
PubMed: 37082558
DOI: 10.5114/ppn.2021.111950 -
Frontiers in Neuroanatomy 2021Galectins are β-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system... (Review)
Review
Galectins are β-galactoside-binding lectins consisting of 15 members in mammals. Galectin-1,-3,-4,-8, and -9 are predominantly expressed in the central nervous system (CNS) and regulate various physiological and pathological events. This review summarizes the current knowledge of the cellular expression and role of galectins in the CNS, and discusses their functions in neurite outgrowth, myelination, and neural stem/progenitor cell niches, as well as in ischemic/hypoxic/traumatic injuries and neurodegenerative diseases such as multiple sclerosis. Galectins are expressed in both neurons and glial cells. Galectin-1 is mainly expressed in motoneurons, whereas galectin-3-positive neurons are broadly distributed throughout the brain, especially in the hypothalamus, indicating its function in the regulation of homeostasis, stress response, and the endocrine/autonomic system. Astrocytes predominantly contain galectin-1, and galectin-3 and-9 are upregulated along with its activation. Activated, but not resting, microglia contain galectin-3, supporting its phagocytic activity. Galectin-1,-3, and -4 are characteristically expressed during oligodendrocyte differentiation. Galectin-3 from microglia promotes oligodendrocyte differentiation and myelination, while galectin-1 and axonal galectin-4 suppress its differentiation and myelination. Galectin-1- and- 3-positive cells are involved in neural stem cell niche formation in the subventricular zone and hippocampal dentate gyrus, and the migration of newly generated neurons and glial cells to the olfactory bulb or damaged lesions. In neurodegenerative diseases, galectin-1,-8, and -9 have neuroprotective and anti-inflammatory activities. Galectin-3 facilitates pro-inflammatory action; however, it also plays an important role during the recovery period. Several ligand glycoconjugates have been identified so far such as laminin, integrins, neural cell adhesion molecule L1, sulfatide, neuropilin-1/plexinA4 receptor complex, triggering receptor on myeloid cells 2, and T cell immunoglobulin and mucin domain. -glycan branching on lymphocytes and oligodendroglial progenitors mediated by β1,6--acetylglucosaminyltransferase V (Mgat5/GnTV) influences galectin-binding, modulating inflammatory responses and remyelination in neurodegenerative diseases. De-sulfated galactosaminoglycans such as keratan sulfate are potential ligands for galectins, especially galectin-3, regulating neural regeneration. Galectins have multitudinous functions depending on cell type and context as well as post-translational modifications, including oxidization, phosphorylation, S-nitrosylation, and cleavage, but there should be certain rules in the expression patterns of galectins and their ligand glycoconjugates, possibly related to glucose metabolism in cells.
PubMed: 34720894
DOI: 10.3389/fnana.2021.767330 -
Neuropsychologia Nov 2022Olfaction, the sense of smell, provides important behavioral functions in many species. The hippocampus (HC) is critical for identifying odors, and hippocampal volume is...
Olfaction, the sense of smell, provides important behavioral functions in many species. The hippocampus (HC) is critical for identifying odors, and hippocampal volume is associated with odor identification ability. Impaired odor identification is often reported in old age and might provide an early marker of cognitive decline and dementia. Here, we explored cross-sectional (n = 225) and longitudinal (n = 118) associations between odor identification ability and hippocampal subfield volumes in a sample of middle-aged and older persons (25-80 years). In older participants, longitudinally decreasing volumes of the hippocampal tail, subiculum, CA4 and the dentate gyrus correlated with changes in odor identification. None of these correlations were observed in younger participants, but there was a significant correlation between longitudinal volume reduction in the tail subfield of the hippocampus and odor identification change across all participants. There were no significant cross-sectional associations between hippocampal subfields and odor identification. These exploratory results provide new information regarding precisely where and when declining HC subfield volumes might be associated with odor identification.
Topics: Middle Aged; Humans; Aged; Smell; Cross-Sectional Studies; Magnetic Resonance Imaging; Hippocampus; Organ Size
PubMed: 36210600
DOI: 10.1016/j.neuropsychologia.2022.108353