Search Results (3,603)

The transgenic animals have been yielding invaluable insights into amyloid pathology by replicating the key features of Alzheimer’s disease (AD). However, there is no clear relationship between senile plaques and memory deficits. Instead, cognitive impairment and synaptic dysfunction are particularly linked to a rise in Aβ_1-42 oligomer level. Thus, injection of Aβ_1-42 oligomers into a specific brain region is considered an alternative approach to investigate the effects of increased soluble Aβ species without any plaques, offering higher controllability, credibility and validity compared to the transgenic model. The hippocampal CA1 (cornu ammonis 1) region is selectively affected in the early stage of AD and specific targeting of CA1 region directly links Aβ oligomer-related pathology with memory impairment in early AD. Next, the inhibitory avoidance (IA) task, a learning paradigm to assess the synaptic basis of CA1-dependent contextual learning, triggers training-dependent synaptic plasticity similar to in vitro HFS (high-frequency stimulation). Given its reliability in assessing contextual memory and synaptic plasticity, this task provides an effective framework for studying early stage AD-related memory deficit. Therefore, in this review, we will focus on why Aβ_1-42 oligomer injection is a valid in vivo model to investigate the early stage of AD and why dorsal CA1 region serves as a target area to understand the adverse effects of Aβ_1-42 oligomers on contextual learning through the IA task. Full article

Background: We recently reported sex-dependent impairment in cognitive functions in male and female mice exposed for 24 h, 48 h or 15 days to 2G hypergravity (HG). Methods: In the present study, we investigated brain functional correlates by analyzing synaptic activity and plasticity in the CA1 area of the hippocampus in both genders of mice previously exposed to 2G for the same duration. This was assessed by electrophysiological extracellular recordings in ex vivo slice preparations. Results: Basal synaptic transmission and glutamate release were unchanged regardless of HG duration. However, plasticity was altered in a sex- and time-specific manner. In males, long-term potentiation (LTP) induced by strong high-frequency stimulation and NMDA receptor (NMDAr) activation was reduced by 26% after 24 h of exposure but recovered at later timepoints. This deficit was reversed by D-serine or glycine, suggesting decreased activation at the NMDAr co-agonist site. In females, LTP deficits (23%) were found only after 15 days following mild theta burst stimulation and were not reversed by D-serine. Long-term depression (LTD) was unaffected in both sexes. Conclusions: This study highlights, for the first time, sex-dependent divergence in the CA1 hippocampal plasticity timeline following 2G exposure. The synaptic changes depend on exposure duration and the stimulation protocol and could underlie the previously observed cognitive deficits. Full article

Introduction: Obesity is a rapidly increasing condition that leads to serious health issues. The sense of smell, one of the oldest senses related to energy metabolism, has been increasingly studied in relation to obesity. Objective: This study investigates the impact of childhood obesity on the volumes of the olfactory bulb and pituitary gland, exploring the relationship between body mass index and these brain structures. Method: This study included 146 participants aged 6–18 years with different body mass indices between 2021 and 2024 at Basaksehir Cam and Sakura City Hospital, Istanbul, Turkey. Participants were classified into normal weight, obese, and morbidly obese groups, and olfactory bulb and pituitary gland volumes were retrospectively analyzed. MRI scans were performed to exclude intracranial pathologies due to headache complaints, and patients with cranial pathologies were excluded from the study. Results: This study examined the olfactory bulb and pituitary gland volumes among normal weight, obese, and morbidly obese groups aged 6–18 years. In the morbidly obese group, right olfactory bulb area and right olfactory bulb volume were significantly higher compared to the other groups, while left olfactory bulb area was higher in both the obese and morbidly obese groups. Additionally, in the morbidly obese group, pituitary height was significantly lower than the other groups, and pituitary volume was also found to be reduced in morbid obesity. Conclusions: This study demonstrated that childhood obesity is linked to significant changes in the volumes of the olfactory bulb and pituitary gland. In morbidly obese children, an increase in pituitary volume and alterations in olfactory bulb volume suggest possible neuroanatomical adaptations. Full article

Brain–computer interface (BCI) technology holds promise for improving motor rehabilitation in stroke patients. This review explores the immediate and long-term effects of BCI training, shedding light on the potential benefits and challenges. Clinical studies have demonstrated that BCIs yield significant immediate improvements in motor functions following stroke. Patients can engage in BCI training safely, making it a viable option for rehabilitation. Evidence from single-group studies consistently supports the effectiveness of BCIs in enhancing patients’ performance. Despite these promising findings, the evidence regarding long-term effects remains less robust. Further studies are needed to determine whether BCI-induced changes are permanent or only last for short durations. While evaluating the outcomes of BCI, one must consider that different BCI training protocols may influence functional recovery. The characteristics of some of the paradigms that we discuss are motor imagery-based BCIs, movement-attempt-based BCIs, and brain-rhythm-based BCIs. Finally, we examine studies suggesting that integrating BCIs with other devices, such as those used for functional electrical stimulation, has the potential to enhance recovery outcomes. We conclude that, while BCIs offer immediate benefits for stroke rehabilitation, addressing long-term effects and optimizing clinical implementation remain critical areas for further investigation. Full article

Optically pumped magnetometer OPM-MEG has the potential to replace the traditional low-temperature superconducting quantum interference device SQUID-MEG. Coherence analysis can be used to evaluate the functional connectivity and reflect the information transfer process between brain regions. In this paper, a finger tapping movement paradigm based on auditory cues was used to measure the functional signals of the brain using OPM-MEG, and the coherence between the primary motor cortex (M1) and the primary motor area (PM) was calculated and analyzed. The results demonstrated that the coherence of the three frequency bands of Alpha (8–13 Hz), Beta (13–30 Hz), and low Gamma (30–45 Hz) and the selected reference signal showed roughly the same position, the coherence strength and coherence range decreased from Alpha to low Gamma, and the coherence coefficient changed with time. It was inferred that the change in coherence indicated different neural patterns in the contralateral motor cortex, and these neural patterns also changed with time, thus reflecting the changes in the connection between different functional areas in the time-frequency domain. In summary, OPM-MEG has the ability to measure brain coherence during finger movements and can characterize connectivity between brain regions. 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

Central nervous system (CNS) insulin signaling is involved in a broad array of cardiometabolic physiology, including glucose and lipid metabolism, feeding, energy expenditure, and blood pressure regulation. A key role for hypothalamic neuroendocrine and autonomic centers in regulating insulin-associated cardiovascular and metabolic physiology has been highlighted. However, it is still unclear which CNS site(s) initiate insulin-dependent neural cascades. While some investigations have suggested that circulating insulin can access hypothalamic regions by crossing the blood-brain barrier, other studies point to a necessity of other brain areas upstream of the hypothalamus to initiate central insulin actions. In this context, accumulating evidence points to a possible involvement of the sensory circumventricular organs (CVOs), unique areas located outside of the blood-brain barrier, in insulin-dependent cardiometabolic homeostasis. Here, the multifaceted roles for the sensory CVOs in cardiovascular and metabolic regulation, with a special emphasis on insulin receptor pathways, are discussed. Full article

Sudden Unexpected Death in Epilepsy (SUDEP) is a leading cause of mortality among individuals with epilepsy, particularly those with drug-resistant forms. This review explores the complex multisystem mechanisms underpinning SUDEP, integrating recent findings on brain, cardiac, and pulmonary dysfunctions. Background/Objectives: The main objective of this review is to elucidate how seizures disrupt critical physiological systems, especially the brainstem, heart, and lungs, contributing to SUDEP, with emphasis on respiratory control failure and autonomic instability. Methods: The literature from experimental models, clinical observations, neuroimaging studies, and genetic analyses was systematically examined. Results: SUDEP is frequently preceded by generalized tonic–clonic seizures, which trigger central and obstructive apnea, hypoventilation, and cardiac arrhythmias. Brainstem dysfunction, particularly in areas such as the pre-Bötzinger complex and nucleus tractus solitarius, plays a central role. Genetic mutations affecting ion channels (e.g., SCN1A, KCNQ1) and neurotransmitter imbalances (notably serotonin and GABA) exacerbate autonomic dysregulation. Risk is compounded by a prone sleeping position, reduced arousal capacity, and impaired ventilatory responses. Conclusions: SUDEP arises from a cascade of interrelated failures in respiratory and cardiac regulation initiated by seizure activity. The recognition of modifiable risk factors, implementation of monitoring technologies, and targeted therapies such as serotonergic agents may reduce mortality. Multidisciplinary approaches integrating neurology, cardiology, and respiratory medicine are essential for effective prevention strategies. Full article

Background/Objectives: The composition of the thrombus is not taken into account in the etiology determination of patients with acute ischemic stroke (AIS); however, it varies depending on the origin of the thrombus, as atherothrombotic thrombi contain more red blood cells and cardioembolic thrombi contain more fibrin and platelets. Radiomics has the potential to provide quantitative imaging data that may vary depending on the composition of thrombi. The aim of this study is to predict cardioembolic and atherothrombotic thrombi using radiomic features (RFs) from non-contrast computed tomography (NCCT) brain scans. Methods: A total of 845 RFs were extracted from each of the 41 patients included in the study. A predictive model was used to classify patients as either cardioembolic or atherothrombotic, and the results were compared with the TOAST criteria-based classification. Results: Ten RFs (one shape feature and nine texture features) were found to demonstrate a statistically significant correlation with cardioembolic or atherothrombotic origins. The predictive radiomics model achieved an area under the curve (AUC) of 0.842 and an accuracy of 0.902 (p < 0.001) in classifying stroke etiology. Conclusions: Radiomics based on NCCT can help to determine the etiology of AIS. Full article

The intranasal delivery of exogenous mitochondria is a potential therapy for Parkinson’s disease (PD). The regulatory mechanisms and effectiveness in genetic models remains uncertain, as well as the impact of modulating the mitochondrial permeability transition pore (mPTP) in grafts. Utilizing UQCRC1 (p.Tyr314Ser) knock-in mice, and a cellular model, this study validated the transplantation of mitochondria with or without cyclosporin A (CsA) preloading as a method to treat mitochondrial dysfunction and improve disease progression through intranasal delivery. Liver-derived mitochondria were labeled with bromodeoxyuridine (BrdU), incubated with CsA to inhibit mPTP opening, and were administered weekly via the nasal route to 6-month-old mice for six months. Both treatment groups showed significant locomotor improvements in open-field tests. PET imaging showed increased striatal tracer uptake, indicating enhanced dopamine synthesis capacity. The immunohistochemical analysis revealed increased neuron survival in the dentate gyrus, a higher number of tyrosine hydroxylase (TH)-positive neurons in the substantia nigra (SN) and striatum (ST), and a thicker granule cell layer. In SN neurons, the function of mitochondrial complex III was reinstated. Additionally, the CsA-accumulated mitochondria reduced more proinflammatory cytokine levels, yet their therapeutic effectiveness was similar to that of unmodified mitochondria. External mitochondria were detected in multiple brain areas through BrdU tracking, showing a 3.6-fold increase in the ST compared to the SN. In the ST, about 47% of TH-positive neurons incorporated exogenous mitochondria compared to 8% in the SN. Notably, GFAP-labeled striatal astrocytes (ASTs) also displayed external mitochondria, while MBP-labeled striatal oligodendrocytes (OLs) did not. On the other hand, fewer ASTs and increased OLs were noted, along with lower S100β levels, indicating reduced reactive gliosis and a more supportive environment for OLs. Intranasally, mitochondrial transplantation showed neuroprotective effects in genetic PD, validating a noninvasive therapeutic approach. This supports mitochondrial recovery and is linked to anti-inflammatory responses and glial modulation. Full article

Investigating brain area functions requires advanced technologies, but meaningful insights depend on correlating neural signals with behavior. Traditional mice behavior annotation methods, including manual and semi-automated approaches, are limited by subjectivity and time constraints. To overcome these limitations, our study employs the YOLO neural network for precise mice tracking and composite RGB frames for behavioral scoring. Our model, trained on over 10,000 frames, accurately classifies sitting, running, and grooming behaviors. Additionally, we provide statistical metrics and data visualization tools. We further combined AI-powered behavior labeling to examine hippocampal neuronal activity using fluorescence microscopy. To analyze neuronal circuit dynamics, we utilized a manifold analysis approach, revealing distinct functional patterns corresponding to transgenic 5xFAD Alzheimer’s model mice. This open-source software enhances the accuracy and efficiency of behavioral and neural data interpretation, advancing neuroscience research. Full article

Despite decades of intense interest and investment in cognitive science, there remains a not only incomplete but also highly inconsistent body of evidence regarding how adult brains recover from even the most focal injuries associated with stroke. In this paper, I provide a broad narrative review of the studies of post-stroke aphasia recovery that have sought to identify the mechanisms of language recovery through longitudinal functional imaging. I start with studies that used functional imaging in groups of neurotypical individuals that have revealed areas of the brain that are reliably activated by language tasks and are functionally connected, referred to here as the “language network.” I then review group studies in which functional imaging data were averaged across groups of people with post-stroke aphasia to characterize the neurobiology of recovery. These group studies of post-stroke aphasia have yielded very different results and have led to conflicting conclusions. Subsequently, I examine results of studies of single subjects that have employed longitudinal functional imaging to identify mechanisms of language recovery. Together, these single subject studies make it clear that mechanisms of neural recovery are far from uniform, even in people with very similar lesions and time since stroke. On this basis, I argue that it is not justifiable to average functional imaging data across individuals with post-stroke aphasia to draw meaningful insights into how brain networks change to support language recovery. Each individual’s brain networks change over time, but in divergent ways that depend on the extent of disruption to the normal language network, interventions to facilitate recovery, the health of the intact brain, and other variables yet to be identified. While averaging results across participants with post-stroke aphasia might be able to identify certain changes in the networks that are correlated with specific language gains, uncovering the range of mechanisms and dynamics of language recovery after stroke requires longitudinal imaging of individuals. Full article

Clinical and animal studies suggest that multiple brain systems are involved in mediating reward-motivated and related emotional behavior including the consumption of commonly used drugs and palatable food, and there is evidence that the repeated ingestion of or exposure to these rewarding substances may in turn stimulate these brain systems to produce an overconsumption of these substances along with co-occurring emotional disturbances. To understand this positive feedback loop, this review focuses on a specific population of hypothalamic peptide neurons expressing melanin-concentrating hormone (MCH), which are positively related to dopamine reward and project to forebrain areas that mediate this behavior. It also examines neurons expressing the peptide hypocretin/orexin (HCRT) that are anatomically and functionally linked to MCH neurons and the molecular systems within these peptide neurons that stimulate their development and ultimately affect behavior. This report first describes evidence in animals that exposure in adults and during adolescence to rewarding substances, such as the drugs alcohol, nicotine and cocaine and palatable fat-rich food, stimulates the expression of MCH as well as HCRT and their intracellular molecular systems. It also increases reward-seeking and emotional behavior, leading to excess consumption and abuse of these substances and neurological conditions, completing this positive feedback loop. Next, this review focuses on the model involving embryonic exposure to these rewarding substances. In addition to revealing a similar positive feedback circuit, this model greatly advances our understanding of the diverse changes that occur in these neuropeptide/molecular systems in the embryo and how they relate, perhaps causally, to the disturbances in behavior early in life that predict a later increased risk of developing substance use disorders. Studies using this model demonstrate in animals that embryonic exposure to these rewarding substances, in addition to stimulating the expression of peptide neurons, increases the intracellular molecular systems in neuroprogenitor cells that promote their development. It also alters the morphology, migration, location and neurochemical profile of the peptide neurons and causes them to develop aberrant neuronal projections to forebrain structures. Moreover, it produces disturbances in behavior at a young age, which are sex-dependent and occur in females more than in males, that can be directly linked to the neuropeptide/molecular changes in the embryo and predict the development of behavioral disorders later in life. These results supporting the close relationship between the brain and behavior are consistent with clinical studies, showing females to be more vulnerable than males to developing substance use disorders with co-occurring emotional conditions and female offspring to respond more adversely than male offspring to prenatal exposure to rewarding substances. It is concluded that the continued consumption of or exposure to rewarding substances at any stage of life can, through such peptide brain systems, significantly increase an individual’s vulnerability to developing neurological disorders such as substance use disorders, anxiety, depression, or cognitive impairments. Full article

Background: Chronic primary orofacial pain (COFP) affects approximately 7% of the population and often leads to reduced quality of life. Patients frequently undergo multiple assessments and treatments across healthcare disciplines, often without a definitive diagnosis. The 2019 ICD-11 classification of chronic primary pain clusters together COFP subtypes based on chronicity and associated functional and emotional impairment. Objective: This study aimed to evaluate whether these subtypes of COFP share common underlying mechanisms by comparing neuroimaging findings. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Searches were performed using Medline (OVID) and Scopus up to April 2025. Inclusion criteria focused on MRI-based neuroimaging studies of participants diagnosed with COFP subtypes. Data extraction included participant demographics, imaging modality, brain regions affected, and pain assessment tools. Quality assessment used a modified Coleman methodological score. Results: Fourteen studies met the inclusion criteria, all utilising MRI and including two COFP subtypes (temporomandibular disorder and burning mouth syndrome). Resting- and task-state imaging revealed overlapping alterations in several brain regions, including the thalamus, somatosensory cortices (S1, S2), cingulate cortex, insula, prefrontal cortex, basal ganglia, medial temporal lobe, and primary motor area. These changes were consistent across both TMD and BMS populations. Conclusions: The findings suggest that chronic primary orofacial pain conditions (TMD and BMS) may share common central neuroplastic changes, supporting the hypothesis of a unified pathophysiological mechanism. This has implications for improving diagnosis and treatment strategies, potentially leading to more targeted and effective care for these patients. 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