Search Results (147)

Background/Objectives: Schizophrenia exhibits symptoms linked to the hippocampus and parahippocampal gyrus. This includes the entorhinal cortex (ERC) and perirhinal cortex (PRC) as anterior parts, along with the posterior segment known as the parahippocampal cortex (PHC). However, recent research has detailed atlases based on cytoarchitectural characteristics and the hippocampus divided into four subregions: cornu ammonis (CA), dentate gyrus (DG), subiculum (SUB), and hippocampal–amygdaloid transition (HATA). This study aimed to explore the functional connectivity (FC) changes between these hippocampal subregions and the parahippocampal gyrus structures (ERC, PRC, and PHC) as well as between hippocampal subregions and various functional brain networks in schizophrenia. Methods: In total, 50 individuals with schizophrenia and 50 matched healthy subjects were examined using resting state functional magnetic resonance imaging (rs-fMRI). Results: The results showed alterations characterized by increases and decreases in the strength of the positive connectivity between the parahippocampal gyrus structures and the four hippocampal subregions when comparing patients with schizophrenia with healthy subjects. Alterations were observed among the hippocampal subregions and functional brain networks, as well as the formation of new connections and absence of connections. Conclusions: There is strong evidence that the different subregions of the hippocampus have unique functions and their connectivity with the parahippocampal cortices and brain networks are affected by schizophrenia. Full article

Alzheimer’s dementia (AD) is a disease of the ageing brain. It begins in the hippocampal region with the epicentre in the entorhinal cortex, then gradually extends into adjacent brain areas involved in memory and cognition. The events which initiate the damage are unknown and under intense investigation. Localization to the hippocampus can now be explained by anatomical features of the blood vessels supplying this region. Blood supply and hence oxygen delivery to the area are jeopardized by poor flow through narrowed arteries. In genomic and metabolomic studies, the respiratory chain and mitochondrial pathways which generate ATP were leading pathways associated with AD. This review explores the notion that ATP depletion resulting from hippocampal hypoperfusion has a prime role in initiating damage. Sections cover sensing of ATP depletion and protective responses, vulnerable processes with very heavy ATP consumption (the malate shuttle, the glutamate/glutamine/GABA (γ-aminobutyric acid) cycle, and axonal transport), phospholipid disturbances and peroxidation by reactive oxygen species, hippocampal perfusion and the effects of hypertension, chronic hypoxia, and arterial vasospasm, and an overview of recent relevant genomic studies. The findings demonstrate strong scientific arguments for the proposal with increasing supportive evidence. These lines of enquiry should be pursued. Full article

Alzheimer’s disease (AD) and ischemic stroke (IS) are prevalent neurological disorders that frequently co-occur in the same individuals. Recent studies have demonstrated that AD and IS share several common risk factors and pathogenic elements, including an overlapping genomic architecture. However, the relationship between IS risk gene polymorphisms and AD has been less extensively studied. We aimed at determining whether IS risk gene polymorphisms were associated with the risk of AD and the severity of AD in AD patients. We utilized data of AD patients and normal controls (NCs) sourced from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. IS risk single nucleotide polymorphisms (SNPs) were identified through the most recent and largest IS genome-wide association study (GWAS) meta-analysis. Subsequently, we conducted SNP-based association analysis of IS-risk SNPs with the risk of AD, along with amyloid, tau, and neuroimaging for AD. The generalized multifactor dimensionality reduction (GMDR) model was used to assess the interactions among IS-risk SNPs and apolipoprotein E (ApoE) ε4. Protein–protein interactions (PPIs) of the IS-risk genes product and APOE were explored using the STRING database. Seven IS-risk SNPs were involved in the study. Five SNPs were found to be associated with at least one measurement of cerebrospinal fluid (CSF) levels of amyloid-beta 1–42 (Aβ₄₂), total tau (t-tau), and phosphorylated tau 181 (p-tau₁₈₁), as well as the volumes of the hippocampus, whole brain, entorhinal cortex, and mid-temporal regions. After multiple testing corrections, we found that T allele of rs1487504 contributed to an increased risk of AD in non-ApoE ε4 carriers. The combination of rs1487504 and ApoE ε4 emerged as the optimal two-factor model, and its interaction was significantly related to the risk of AD. Additionally, C allele of rs880315 was significantly associated with elevated levels of CSF Aβ₄₂ in AD patients, and A allele of rs10774625 was significantly related to a reduction in the volume of the entorhinal cortex in AD patients. This study found that IS risk SNPs were associated with both the risk of AD and AD major indicators in the ADNI cohort. These findings elucidated the role of IS in AD from a genetic perspective and provided an innovative approach to predict AD through IS-risk SNPs. Full article

The quality of life (QoL) perception has been studied in neurological diseases; however, there is limited information linking brain morphological characteristics, QoL, and cognition. Human behavior and perception are associated with specific brain areas that interact through diffuse electrochemical networking. We used magnetic resonance imaging (MRI) to analyze the brain region volume (BRV) correlation with the scores of Rand’s 36-item Short Form Survey (SF-36) and cognitive domains (memory and dementia status). We analyzed data from 420 adult participants in the Maracaibo Aging Study (MAS). Principal component analysis with oblimin axis rotation was used to gather redundant information from brain parcels and SF-36 domains. Canonical correlation was used to analyze the relationships between SF-36 domains and BRV (adjusted for intracranial cavity), as well as sex, age, education, obesity, and hypertension. The average age (±SD) of subjects was 56 ± 11.5 years; 71% were female; 39% were obese; 12% had diabetes, 52% hypertension, and 7% dementia. No sex-related differences were found in memory and orientation scores, but women had lower QoL scores. The 1st and 2nd canonical correlation roots support the association of SF-36 domains (except social functioning and role emotional) and total brain volume, frontal lobe volume, frontal pole, lateral orbital lobe, cerebellar, and entorhinal areas. Other variables, including age, dementia, memory score, and systolic blood pressure, had a significant influence. The results of this study demonstrate significant correlations between BRV and SF-36 components, adjusted for covariates. The frontal lobe and insula were associated with the mental health component; the lateral-orbital frontal lobe and entorhinal area were correlated with the physical component. Full article

The mechanisms of ictal discharge initiation remain incompletely understood, particularly the paradoxical role of inhibitory fast-spiking interneurons in seizure generation. Using simultaneous whole-cell recordings of interneurons and pyramidal neurons combined with extracellular [K⁺]_o monitoring in mouse entorhinal cortex-hippocampal slices (4-aminopyridine model of epileptiform activity), we identified a critical transition sequence: interneurons displayed high-frequency firing during the preictal phase before entering depolarization block (DB). DB onset coincided with the peak of rate of extracellular [K⁺] accumulation. Pyramidal cells remained largely silent during interneuronal hyperactivity but started firing within 1.1 ± 0.3 s after DB onset, marking the transition to ictal discharges. This consistent sequence (interneuron DB → [K⁺]_o rate peak → pyramidal cell firing) was observed in 100% of entorhinal cortex recordings. Importantly, while neurons across all entorhinal cortical layers synchronously fired during the first ictal discharge, hippocampal CA1 neurons showed fundamentally different activity: they generated high-frequency interictal bursts but did not participate in ictal events, indicating region-specific seizure initiation mechanisms. Our results demonstrate that interneuron depolarization block acts as a precise temporal switch for ictogenesis and suggest that the combined effect of disinhibition and K⁺-mediated depolarization triggers synchronous pyramidal neuron recruitment. These findings provide a mechanistic framework for seizure initiation in focal epilepsy, highlighting fast-spiking interneurons dysfunction as a potential therapeutic target. Full article

Previous studies have largely overlooked cellular differential alterations across differentially affected brain regions in both disease mechanisms and therapeutic development of Alzheimer’s disease (AD). This study aimed to compare the differential cellular and transcriptional changes in the prefrontal cortex (PFC) and entorhinal cortex (EC) of AD patients through an integrated single-cell transcriptomic analysis. We integrated three single-cell RNA sequencing (scRNA-seq) datasets comprising PFC and EC samples from AD patients and age-matched healthy controls. A total of 124,658 nuclei and 31 cell clusters were obtained and classified into eight major cell types, with EC exhibiting much more pronounced transcriptional alterations than PFC. Through network analysis, we pinpointed hub regulatory genes that form interconnected networks driving AD pathogenesis, findings validated by RT-qPCR showing more pronounced expression changes in EC versus PFC of AD mice. Moreover, dysregulation of the LINC01099-associated regulatory networks in the PFC and EC, showing correlation with AD progression, may present new therapeutic targets for AD. Together, these results suggest that effective AD biomarkers and therapeutic strategies may require simultaneous, precise targeting of specific cell populations across multiple brain regions. Full article

Background: The gyrus rectus is a key brain region with neural connections to the entorhinal cortex and hippocampus, both of which are among the earliest areas affected in Alzheimer’s disease (AD). Investigating volumetric differences and asymmetry in this region may provide insights into disease progression. This study aimed to assess gyrus rectus volume and asymmetry in AD patients using an MRI-based parcellation method. Methods: This cross-sectional volumetric study included 25 cognitively healthy adults and 25 AD patients recruited from the Neurology Clinic of Balıkesir University Hospital. Brain MRI scans were obtained using a 1.5 Tesla MRI scanner. Volumetric measurements were computed using MRIStudio, an atlas-based image analysis program. Group differences in brain volume and asymmetry index were examined, and their correlations with Mini-Mental State Examination (MMSE) scores were evaluated. Results: AD patients exhibited significantly greater rightward volumetric asymmetry of the gyrus rectus volume than healthy controls (p < 0.05). Additionally, a positive correlation was observed between gyrus rectus volume and MMSE scores (p < 0.05). Conclusions: These results suggest that rightward volumetric asymmetry of the gyrus rectus may represent a promising biomarker for tracking the progression of Alzheimer’s disease. Detecting asymmetry in brain structures could improve understanding of AD pathology and aid clinical evaluation. Full article

Background: Apathy is almost ubiquitous across neurodegenerative diseases and can be a general model for understanding neuropsychiatric symptoms in dementia. Methods: We assessed apathy via Starkstein’s Apathy Scale—caregiver version (SAS-C) in patients with Alzheimer’s disease (AD) and behavioural variant frontotemporal dementia (bvFTD). Neuropsychological and structural neuroimaging data were also collected. Images were processed using the FreeSurfer program, and cortical thickness data were acquired for 68 brain regions. Results: Patients with bvFTD had statistically higher levels of apathy than those with AD. The multivariate linear regression model found that the left entorhinal cortex (lEC) was the only region statistically associated with apathy in the AD group (F(1,31) = 5.17; p = 0.030; R2 = 0.527), whereas, for bvFTD, the right lateral orbitofrontal cortex achieved significant association with apathy (F(1,30) = 5.69; p = 0.009; R2 = 0.804). Conclusions: These results demonstrate that apathy is associated with multiple brain regions, reinforcing its multidimensionality and specific profiles. Full article

Background/Objectives: Olfaction is in many ways the least understood sensory modality. Its organization and connectivity are still under debate. The aim of this study was to investigate the anatomy of the olfactory system by using a cadaver fiber dissection technique and in vivo tractography to attain a deeper understanding of the subcortical connectivity and organization. Methods: Ten cerebral hemispheres were used in this study for white matter dissection according to Klingler’s technique. Measurements of different cortical structures and interhemispheric symmetry were compared. Diffusion tensor imaging sequences from twenty-five healthy individuals from the Human Connectome Project dataset were used to explore the connectivity of the olfactory system using DSI Studio. White matter connectivity between the following were reconstructed in vivo: (1) Olfactory bulb to primary olfactory cortices; (2) Olfactory bulb to secondary olfactory cortices; (3) Primary to secondary olfactory cortices. The DTI metrics of the identified major associative, projection and commissural pathways were subsequently correlated with olfactory function and cognition in seventy-five healthy individuals with Spearman’s rank correlation and the Benjamini–Hochberg method for false discoveries (CI 95%, p < 0.05) using R. Results: 1. The dissection showed that the lateral stria was significantly longer on the left side and projected towards the amygdala, the entorhinal and piriform cortex. 2. The medial stria was not evident as a consistent white matter structure. 3. Both dissection and tractography showed that major associative white matter pathways such as the uncinate fasciculus, the inferior fronto-occipital fasciculus and cingulum supported the connectivity between olfactory areas together with the anterior commissure. 4. No significant correlation was found between DTI metrics and sensory or cognition test results. Conclusions: We present the first combined fiber dissection analysis and tractography of the olfactory system. We propose a novel definition where the primary olfactory network is defined by the olfactory tract/bulb and primary olfactory cortices through the lateral stria only. The uncinate fasciculus, inferior fronto-occipital fasciculus and cingulum are the associative pathways supporting the connectivity between primary and secondary olfactory areas together with the anterior commissure. We suggest considering these structures as a secondary olfactory network. Further work is needed to attain a deeper understanding of the pathological and physiological implications of the olfactory system. Full article

An abnormal accumulation of misfolded proteins is a common feature shared by most neurodegenerative disorders. Olfactory dysfunction (OD) is common in the elderly population and is present in 90% of patients with Alzheimer’s or Parkinson’s disease, usually preceding the cognitive and motor symptoms onset by several years. Early Aβ, tau, and α-synuclein protein aggregates deposit in brain structures involved in odor processing (olfactory bulb and tract, piriform cortex, amygdala, entorhinal cortex, and hippocampus) and seem to underly OD. The glymphatic system is a glial-associated fluid transport system that facilitates the movement of brain fluids and removes brain waste during specific sleep stages. Notably, the glymphatic system became less functional in aging and it is impaired in several conditions, including neurodegenerative diseases. As the nasal pathway has been recently described as the main outflow exit of cerebrospinal fluid and solutes, we hypothesized that OD may indeed be a clinical marker of early glymphatic dysfunction through abnormal accumulation of pathological proteins in olfactory structures. This effect may be more pronounced in peri- and postmenopausal women due to the well-documented impact of estrogen loss on the locus coeruleus, which may disrupt multiple mechanisms involved in glymphatic clearance. If this hypothesis is confirmed, olfactory dysfunction might be considered as a clinical proxy of glymphatic failure in neurodegenerative diseases. Full article

Background: Childhood is a crucial period for brain development, and short-term juvenile stress has demonstrated long-lasting effects on cognitive and cellular functions in the hippocampus. However, the influence of such stress on the brain’s overall network remains unclear. Methods: In this study, we employed functional magnetic resonance imaging (fMRI) to explore the effects of transient wild stress on juvenile male rats. Pregnant rats were purchased and housed in a specific pathogen-free (SPF) environment, with pups separated by sex on postnatal day 21 (PD21). From PD27 to PD29, male rats were subjected to transient wild stress, which included forced swimming, elevated platform exposure, and restraint stress. Following stress exposure, all animals were carefully maintained and scanned at 42 days of age (PD42) using fMRI. Structural analysis was performed using voxel-based morphometry (VBM) to assess changes in gray matter volume, while functional activity was evaluated through regional homogeneity (ReHo) and voxel-wise functional connectivity. Results: The results showed significant reductions in gray matter volume in several brain regions in the stress group, including the periaqueductal gray (PAG), entorhinal cortex (Ent), and dentate gyrus (DG). In terms of functional activity, cortical regions, particularly the primary somatosensory areas, exhibited decreased activity, whereas increased activity was observed in the PAG, DG, and medulla. Furthermore, functional connectivity analysis revealed a significant reduction in connectivity between the DG and entorhinal cortex, while the DG-PAG connectivity was significantly enhanced. Conclusions: These findings suggest that juvenile stress leads to profound alterations in both brain structure and function, potentially disrupting emotional regulation and memory processing by affecting the development and connectivity of key brain regions. Full article

Grid cells in the brain’s entorhinal cortex are essential for spatial navigation and have inspired advancements in robotic navigation systems. This paper first provides an overview of recent research on grid cell-based navigation in robotics, focusing on deep learning models and algorithms capable of handling uncertainty and dynamic environments. We then present experimental results where a grid cell network was trained using trajectories from a mobile unmanned ground vehicle (UGV) robot. After training, the network’s units exhibited spatially periodic and hexagonal activation patterns characteristic of biological grid cells, as well as responses resembling border cells and head-direction cells. These findings demonstrate that grid cell networks can effectively learn spatial representations from robot trajectories, providing a foundation for developing advanced navigation algorithms for mobile robots. We conclude by discussing current challenges and future research directions in this field. Full article

We describe GridMet as open-source software that automatically measures the spatial tuning parameters of grid cells, such as firing field size, spacing, and orientation angles. Applying these metrics to experimental data can help quantify changes in the geometric characteristics of grid cell firing across experimental conditions. GridMet uses clustering and other advanced methods to detect and characterize fields, increasing accuracy compared to alternative methods such as those based on peak firing. Novel contributions of this work include an effective approach for automated field size estimation and an original method for estimating field spacing that can overcome challenges encountered in other software. The user-friendly yet flexible design of GridMet aims to facilitate widespread community adoption. Specifically, GridMet allows basic usage with default parameter settings while also enabling the expert configuration of many parameter values for more advanced applications. Free release of the MATLAB source code will encourage the development of custom variations or integration with other software packages. At the same time, we also provide a runtime version of GridMet, thus avoiding the requirement to purchase any separate licenses. We have optimized GridMet for batch scripting workflows to aid investigations of multi-trial data on multiple grid cells. Full article

Objectives: The purpose was to quantitatively examine brain structures using 7 Tesla MRI in the presence of visual loss caused by retinitis pigmentosa (RP) related to retinitis pigmentosa GTPase regulator (RPGR) gene pathogenic variants. Methods: Twelve male patients with RP (mean visual acuity 0.4) related to confirmed RPGR pathogenic variants and fifteen healthy volunteers were examined with 7 Tesla MRI of the brain. Measures of the lateral geniculate nucleus (LGN) volume were performed manually by three independent investigators (radiologists) using ITK-SNAP (Insight Segmentation and Registration Toolkit) software. Other brain structures were evaluated using the open-source automated software package FreeSurfer. Prior to the 7 Tesla MRI, patients underwent an ophthalmic examination and a 1.5 Tesla MRI. Results: The mean LGN volume (right—100 mm³, left—96 mm³) and left lingual gyrus volume (6162 mm³) were significantly lower in RPGR patients in comparison to the control group (129 mm³, 125 mm³, and 7310 mm³, respectively), whilst some brain regions related to other sensory information such as the left isthmus cingulate (3690 mm³) and entorhinal cortex (right—1564 mm³, left 1734 mm³) were significantly or almost significantly higher in the RPGR group than in the control group (2682 mm³, 960 mm³, and 1030 mm³, respectively). Moreover, compared to the control group, the RPGR group’s thalamus-to-LGN ratio was substantially higher. Conclusions: The use of the 7 Tesla MRI revealed numerous structural abnormalities of the visual pathway in patients with RPGR-related RP. The reorganization of the structures of the brain demonstrated in patients with RPGR-related RP reveals a certain degree of plasticity in response to visual loss. These findings may help improve diagnostic and therapeutic strategies for RP patients and contribute to the development of precision medicine. Full article

A substantial body of research suggests that early-life stress (ELS) is associated with neuropathology in adulthood. Maternal deprivation (MD) is a commonly utilised model in mice for the study of specific neurological diseases. The appropriate growth of dendrites is essential for the optimal functioning of the nervous system. However, the impact of ELS on interneuron dendritic morphology remains unclear. To ascertain whether ELS induces alterations in the morphology of GABAergic inhibitory interneurons in layers II/III of the medial entorhinal cortex (mEC), the somatosensory cortex (SSC), the motor cortex (MC), and the CA1 region of the hippocampus (Hp), 9-day-old male GAD-67-EGFP transgenic mice were subjected to a 24 h MD. At postnatal day 60 (P60), the animals were sacrificed, and their brains were subjected to morphological analyses. The results indicated that MD affected the dendritic morphology of GABAergic interneurons. The mean dendritic length and mean dendritic segments of the examined cortical areas, except for the MC, were significantly decreased, whereas the number of primary dendrites was unaffected. Furthermore, the density of GAD67-EGFP-positive interneurons was decreased in the mEC and Hp, but not in the somatosensory and MC. The induction of ELS through MD in a developmental time window when significant morphological changes occur rendered the developing cells particularly susceptible to stress, resulting in a significant reduction in the number of surviving interneurons at the adult stage. Full article