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Background: Cognitive function plays a crucial role in human life, and its maintenance and improvement are essential in both young and older adults. Since cognitive decline can be associated with oral function decline, preventing the decline in both cognitive and oral functions is an urgent social issue. Several training methods to improve each function have been proposed. Previous studies have indicated that greater brain activity during training is associated with increased benefits for cognitive function. Although adding cognitive function elements to oral function training may promote the activation of brain activity during oral function training, the effects have not been validated. The main purpose of this study is to develop a novel training program that combines oral function training with cognitive training, which is expected to activate key brain regions involved in oral and cognitive functions, such as the left dorsolateral prefrontal cortex (DLPFC) and right medial prefrontal cortex (mPFC). Methods: Four types of training programs combining oral and cognitive training: PaTaKaRa × calculation, lip exercise × N-back, tongue exercise × inhibition, and tongue exercise × memory, were developed. Each program had seven levels of difficulty [level 0 (no cognitive load) and level 6 (maximum difficulty)]. Twelve healthy young adults participated in the study and were instructed to perform all four programs. Brain activity in the left DLPFC and right mPFC were measured during each training session using two-channel near-infrared spectroscopy (NIRS). Results: No significant brain activity was observed during training at level 0. Brain activity in the left DLPFC was significantly increased at levels 1 and 2 and in the left DLPFC and right mPFC at level 6 during PaTaKaRa × calculation training. Brain activity in the left DLPFC was significantly increased at level 6 during tongue exercise × inhibition training. Brain activity in the left DLPFC and right mPFC was significantly increased at level 6 during lip exercise × N-back training. Conclusion: Oral function training did not significantly increase brain activity; nevertheless, oral function with cognitive training stimulated brain activity in the prefrontal cortex. Trial registration: : UMIN-CTR. ID: UMIN000039678. date: 06/03/2020. [ABSTRACT FROM AUTHOR]

Malignant (high-grade) gliomas are aggressive intrinsic brain tumors that diffusely infiltrate the brain parenchyma. They comprise of World Health Organization (WHO) grade III and IV gliomas. Ionizing radiation or irradiation (IR) is frequently utilized in the treatment of both primary as well as metastatic brain tumors. On the contrary, macrophages (MΦ) are the most copious infiltrating immune cells of all the different cell types colonizing glioma. MΦ at tumor milieu are referred to as tumor-associated macrophages (TAMΦ). In malignant gliomas milieu, TAMΦ are also polarized into two distinct phenotypes such as M1 TAMΦ or M2 TAMΦ, which are capable of inhibiting or promoting tumor growth, respectively. Cranial-IR such as x- and γ-IR are sufficient to induce the migration of peripherally derived MΦ into the brain parenchyma. The IR facilitate a more immunosuppressive milieu via the stimulation of efferocytosis in TAMΦ, and an upsurge of tumor cell engulfment by TAMΦ exhibited detrimental effect of the anti-tumoral immune response in glioma. The MΦ inside the tumor mass are associated with multiple phenomena that include IR resistance and enrichment of the M2 MΦ after IR is able to facilitate glioblastoma multiforme (GBM) recurrence. Reviews on the role of cranial IR-induced peripheral and brain-engrafting macrophages (BeMΦ) in glioma are lacking. Specifically, most studies on peripheral, intrinsic as well as beMΦ on IR focus on WHO grade III and IV. Thus, this review precisely focuses primary on WHO grade III as well as IV gliomas. [ABSTRACT FROM AUTHOR]

Background: Hypertension (HT) is a common chronic disease in older adults. It not only leads to dizziness and other symptoms affecting balance in older adults with HT but also affects the hemodynamics of the cerebral cortex. At present, potential neural mechanisms of balance control in older adults with HT are still unclear. Therefore, this study aimed to explore the differences in the center of pressure (COP) and cerebral cortex activation between older adults with HT and normotension (NT) during standing balance tasks. This study May provide guidance for the early detection of the risk of falls among older adults with HT and the development of clinical rehabilitation strategies. Methods: In this cross-sectional study, 30 older adults with NT (NT group) and 27 older adults with HT (HT group) were subjected to three conditions: task 1, standing with eyes open on a stable surface; task 2, standing with eyes closed on a stable surface; and task 3, standing with eyes open on the surface of the foam pad. Cortical hemodynamic reactions were measured using functional near-infrared spectroscopy, and COP parameters were measured using a force plate. Results: The mean velocity of the COP in the medial-lateral direction in the NT group was significantly higher than that in the HT group (F = 5.955, p = 0.018) during task 3. When proprioception was disturbed, the activation of the left premotor cortex and supplementary motor cortex in the HT group was significantly lower than that in the NT group (F = 14.381, p < 0.001). Conclusion: The standing balance function of older adults with HT does not appear to be worse based on COP parameters than those of older adults with NT. This study revealed that the changes in the central cortex related to standing balance appear to be more indicative of balance control deficits in older adults with HT than changes in peripheral COP parameters, suggesting the importance of the early evaluation of cortical activation in older adults with HT at risk of falls. [ABSTRACT FROM AUTHOR]

Introduction: At least one-third of the identified risk alleles from Genome-Wide Association Studies (GWAS) of Alzheimer's disease (AD) are involved in lipid metabolism, lipid transport, or direct lipid binding. In fact, a common genetic variant (e4) in a cholesterol and phospholipid transporter, Apolipoprotein E (APOEe4), is the primary genetic risk factor for late-onset AD. In addition to genetic variants, lipidomic studies have reported severe metabolic dysregulation in human autopsy brain tissue, cerebrospinal fluid, blood, and multiple mouse models of AD. Methods: We aimed to identify an overarching metabolic pathway in lipid metabolism by integrating analyses of lipidomics and transcriptomics from the Religious Order Study and Rush Memory Aging Project (ROSMAP) using differential analysis and network correlation analysis. Results: Coordinated differences in lipids were found to be dysregulated in association with both mild cognitive impairment (MCI) and APOEe4 carriers. Interestingly, these correlations were weakened when adjusting for education. Indeed, the cognitively non-impaired APOEe4 carriers have higher education levels in the ROSMAP cohort, suggesting that this lipid signature may be associated with a resilience phenotype. Network correlation analysis identified multiple differential lipids within a single module that are substrates and products in the Lands Cycle for acyl chain remodeling. In addition, our analyses identified multiple genes in the Lands Cycle acyl chain remodeling pathway, which were associated with cognitive decline independent of amyloid-ß (Aß) load and tau tangle pathologies. Discussion: Our studies highlight the critical differences in acyl chain remodeling in brain tissue from APOEe4 carriers and individual non-carriers with MCI. A coordinated lipid profile shift in dorsolateral prefrontal cortex from both APOEe4 carriers and MCI suggests differences in lipid metabolism occur early in disease stage and highlights lipid homeostasis as a tractable target for early disease modifying intervention. [ABSTRACT FROM AUTHOR]

Background: Olfactory dysfunction stands as one of the most prevalent non-motor symptoms in the initial stage of Parkinson's disease (PD). Nevertheless, the intricate mechanisms underlying olfactory deficits in Parkinson's disease still remain elusive. Methods: This study collected rs-fMRI data from 30 PD patients [15 with severe hyposmia (PD-SH) and 15 with no/mild hyposmia (PD-N/MH)] and 15 healthy controls (HC). To investigate functional segregation, the amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo) were utilized. Functional connectivity (FC) analysis was performed to explore the functional integration across diverse brain regions. Additionally, the graph theory-based network analysis was employed to assess functional networks in PD patients. Furthermore, Pearson correlation analysis was conducted to delve deeper into the relationship between the severity of olfactory dysfunction and various functional metrics. Results: We discovered pronounced variations in ALFF, ReHo, FC, and topological brain network attributes across the three groups, with several of these disparities exhibiting a correlation with olfactory scores. Conclusion: Using fMRI, our study analyzed brain function in PD-SH, PD-N/MH, and HC groups, revealing impaired segregation and integration in PD-SH and PD-N/MH. We hypothesize that changes in temporal, frontal, occipital, and cerebellar activities, along with aberrant cerebellum-insula connectivity and node degree and betweenness disparities, may be linked to olfactory dysfunction in PD patients. [ABSTRACT FROM AUTHOR]

Background: Visual perception of face images or face pareidolia can be evaluated with event-related potentials (ERP) for healthy subjects and patients with neurological conditions. In this study, we aimed to analyse event-related potential components such as P100, N100, N170, and vertex-positive potential (VPP) in response to face pareidolia perception in temporal lobe epilepsy (TLE) patients. Methods: ERPs were recorded during the pareidolia test. Waveforms were analzyed and current source density (CSD) maps were generated. Results: CSD profiles were shown to be interpretable when face and face pareidolia conditions. N100, P100, and N170 components showed larger amplitudes and longer latency in epilepsy patients in response to face pareidolia stimuli compared to real face images. However, the N170 component latency did not differ significantly between epilepsy patients and healthy participants, while the larger amplitude and longer latency of N100 and P100 responses were evoked in healthy patients. Conclusions: Our results indicate a difference in the neural mechanisms of processing real face information and pareidolia face-like information in TLE patients. [ABSTRACT FROM AUTHOR]

Our behavior and mental states are constantly shaped by our environment and experiences. However, little is known about the response of brain functional connectivity to environmental, physiological, and behavioral changes on different timescales, from days to months. This gives rise to an urgent need for longitudinal studies that collect high-frequency data. To this end, for a single subject, we collected 133 days of behavioral data with smartphones and wearables and performed 30 functional magnetic resonance imaging (fMRI) scans measuring attention, memory, resting state, and the effects of naturalistic stimuli. We find traces of past behavior and physiology in brain connectivity that extend up as far as 15 days. While sleep and physical activity relate to brain connectivity during cognitively demanding tasks, heart rate variability and respiration rate are more relevant for resting-state connectivity and movie-watching. This unique data set is openly accessible, offering an exceptional opportunity for further discoveries. Our results demonstrate that we should not study brain connectivity in isolation, but rather acknowledge its interdependence with the dynamics of the environment, changes in lifestyle, and short-term fluctuations such as transient illnesses or restless sleep. These results reflect a prolonged and sustained relationship between external factors and neural processes. Overall, precision mapping designs such as the one employed here can help to better understand intraindividual variability, which may explain some of the observed heterogeneity in fMRI findings. The integration of brain connectivity, physiology data and environmental cues will propel future environmental neuroscience research and support precision healthcare. Functional brain activity is often measured during a single scanning session which neglects behavioral, physiological and lifestyle effects on brain activity. This study presents functional neuroimaging data from 30 neuroimaging session across 15 weeks from one participant and reveals relationships between human daily behavior and brain function under different stimuli. [ABSTRACT FROM AUTHOR]

Intracerebral hemorrhage (ICH) is a severe condition characterized by bleeding within brain tissue. Primary brain injury in ICH results from a mechanical insult caused by blood accumulation, whereas secondary injury involves inflammation, oxidative stress, and disruption of brain physiology. miR-195-5p may participate in ICH pathology by regulating cell proliferation, oxidative stress, and inflammation. Therefore, we assessed the performance of miR-195-5p in alleviating ICH-induced secondary brain injury. ICH was established in male Sprague–Dawley rats (7 weeks old, 200–250 g) via the stereotaxic intrastriatal injection of type IV bacterial collagenase, after which miR-195-5p was administered intravenously. Neurological function was assessed using corner turn and forelimb grip strength tests. Protein expression was assessed by western blotting and ELISA. The miR-195-5p treatment significantly improved neurological function; modulated macrophage polarization by promoting anti-inflammatory marker (CD206 and Arg1) production and inhibiting pro-inflammatory marker (CD68 and iNOS) production; enhanced Akt signalling, reduced oxidative stress by increasing Sirt1 and Nrf2 levels, and attenuated inflammation by decreasing NF-κB activation; inhibited apoptosis via increased Bcl-2 and decreased cleaved caspase-3 levels; and regulated synaptic plasticity by modulating NMDAR2A, NMDAR2B, BDNF, and TrkB expression and ERK and CREB phosphorylation. In conclusion, miR-195-5p exerts neuroprotective effects in ICH by reducing inflammation and oxidative stress, inhibiting apoptosis, and restoring synaptic plasticity, ultimately restoring behavioral recovery, and represents a promising therapeutic agent that warrants clinical studies. [ABSTRACT FROM AUTHOR]

Objective: Understanding neural mechanisms underlying cognitive workload is crucial for advancing our knowledge of human cognition and mental processes. In this study, we utilized electroencephalography (EEG) analysis to investigate brain activity associated with varying mental cognitive workloads from a psychological perspective. Method: We employed a publicly accessible EEG dataset consisting of a cohort of 36 healthy volunteers (75% female), aged 18 to 26 years, while the participants were at rest or engaged in an arithmetic task to explore mental cognitive workload. After preprocessing to reduce noise and various artifacts and to obtain a clean signal for every subject, functional connectivity and complexity features were calculated from EEGs through the coherence and permutation entropy algorithms, respectively. Then, repeated measures analysis of variance (ANOVA) was conducted to assess the differences in complexity and connectivity measures across various brain regions between the rest and task states. Results: Brain sites showed significant within-subject effects, and the interaction between states and channels was significant for connectivity values (F = 3.68, P = 0.034). Post hoc comparisons indicated that FP1-F7, FP1-F8 and FP1- Fz connectivity were significantly lower during the task state compared to the rest state (P < 0.05). Moreover, F4-P3, F4- P4, FP1-O1, FP2-O2, F3-O1, F4-O1, F8-O1, C4-O1, F3-O2, F4-O2, F7-O2, F8-O2, Fz-O1, Fz-O2, Cz-O1 and Fz-P4 connectivity were significantly higher during the arithmetic task state (P < 0.05). Furthermore, brain sites showed significant within-subject effects and the interaction between states and channels was significant for entropy values (F = 3.50, P = 0.041). Post hoc comparisons indicated that the permutation entropy was significantly higher in the FP1, T3, T4, P4 and Pz channels during the arithmetic task compared to the rest state (P < 0.05). Conclusion: During arithmetic tasks, the increased connectivity in the frontoparietal and frontooccipital networks and heightened complexity in the prefrontal, temporal and parietal lobes reflect the collaborative engagement of brain areas specialized in numerical processing, attention, working memory, cognitive control, and visual-spatial cognition. These changes in connectivity and complexity facilitate the integration of multiple cognitive processes essential for effective arithmetic problem-solving. [ABSTRACT FROM AUTHOR]

Objective: Parkinson's disease dementia (PDD) and Dementia with Lewy bodies (DLB) are two syndromes categorized under synucleinopathy, sharing comparable symptoms. The identification of biomarkers would offer an accurate approach for improved diagnosis, treatment, and monitoring of treatment efficacy for these distinct forms of dementia. Method: This study utilized spectral analysis and nonlinear dynamic analysis to compare electroencephalogram (EEG) characteristics between PDD and DLB patients. EEG data was collected from 30 PDD patients, 36 DLB patients, and 36 healthy subjects at rest. Following a conditioning phase to minimize noise and eliminate artifacts, we derived spectral and complexity features using Welch's method and sample entropy. Analysis of variance with repeated measures was performed to compare spectral features and nonlinear dynamics of brain activity between the groups. Results: Post hoc comparison showed that in the control group, the power of delta and theta bands was lower and the power of alpha and beta bands was higher than in patients with PDD and DLB. (P < 0.05). In the theta and alpha bands, the PDD group showed greater power than the DLB group (P < 0.05). Furthermore, there was a significant main effect of diagnosis (F = 4.67, P = 0.007), and also the diagnosis by region interaction for complexity values (F = 4.58, P = 0.009). Post hoc analysis showed that the EEG complexity of the control group was significantly higher than that of the PDD and DLB groups in the frontal, central, temporal and parietal regions (P < 0.05). Moreover, the EEG complexity of the PDD group was significantly higher than that of the DLB group in the central, temporal and parietal regions (P < 0.05). Conclusion: Although both PDD and DLB had almost similar patterns compared to the control group, they showed differences in the EEG power spectrum and its nonlinear dynamics. Our findings indicated marked diffuse slowing and lower cortical complexity or activity in DLB patients compared to PDD in all regions, especially in the central, temporal and parietal areas. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to assess the reliability of resting-state functional magnetic resonance imaging (rest-fMRI) in mapping language areas for preoperative planning, versus standard task-based techniques, which are at times difficult to perform in clinical settings. Our study also aimed to evaluate the overlap between language areas identified through rest-fMRI and the standard task-fMRI, in neurosurgical cases. Materials and Methods Using a seed-based analysis of rest-fMRI with multiple template seeds, we identified functionally connected language regions in patients undergoing preoperative language mapping. Four language task paradigms (word, verb, picture, and semantics) were evaluated. We quantified the degree of overlap between language areas identified on rest-fMRI and task-fMRI, categorizing the results as more than 50% or less than 50% overlap. Results Seventy-seven percent of patients demonstrated an overlap exceeding 50% between rest- and task-fMRI maps, with the left Broca's area being the most frequently observed region of overlap. This finding was noted even in cases with lesions in Broca's or Wernicke's areas, highlighting the method's robustness. The verb task showed the best blood-oxygen-level dependent activity and overlap with rest-fMRI, highlighting its reliability. To identify a specific language area, the contralateral seed of the same area most commonly displayed connectivity with the area of interest. Conclusion Our findings demonstrate the potential of using rest-fMRI in accurately mapping eloquent language areas, in clinical settings The strong concordance observed, especially in the left Broca's area, underscores the reliability of this method. Further research and larger studies are essential to validate these results, potentially establishing the use of routine rest-fMRI, in clinical preoperative workup. [ABSTRACT FROM AUTHOR]

In stroke rehabilitation, what is the effect of adding non-stimulation-based priming prior to task-specific practice on activity and motor impairment outcomes compared with task-specific practice alone? Systematic review with meta-analysis. Adult stroke survivors. The experimental groups completed a non-stimulation priming intervention prior to task-specific practice. The priming interventions were: motor imagery; action observation; combined motor imagery and action observation; mirror therapy; movement-based priming; and aerobic exercise-based priming. The control groups completed task-specific practice alone. Upper and lower limb activity and motor impairment. Twenty-four trials involving 803 participants were included in this systematic review. Twenty trials were included in the meta-analyses of activity outcomes and 11 trials in the meta-analyses of impairment outcomes. Four trials examined the effect of motor imagery priming prior to task-specific practice on activity outcomes (SMD 0.48, 95% CI 0.13 to 0.82). Three trials examined the effect of motor imagery priming prior to task-specific practice on motor impairment outcomes (SMD 0.51, 95% CI 0.12 to 0.89). Nine trials examined the effect of action observation priming prior to task-specific practice on activity outcomes (SMD 0.18, 95% CI –0.06 to 0.41). Two trials examined the effect of movement-based priming prior to task-specific practice on activity outcomes (SMD –0.11, 95% CI –0.64 to 0.42). Three trials examined the effect of aerobic exercise priming prior to task-specific practice on activity outcomes (SMD 0.30, 95% CI –0.19 to 0.80). The quality of the evidence was low to moderate. In stroke rehabilitation, motor imagery priming implemented prior to task-specific training has a very small to large effect on activity and motor impairment outcomes. Action observation priming implemented prior to task-specific training has a negligible to small effect on activity outcomes. Movement-based and aerobic exercise-based priming do not have any clear effect on outcomes. CRD42020093519. [ABSTRACT FROM AUTHOR]

Background: Although depression symptoms are commonly reported in patients with subcortical vascular mild cognitive impairment (svMCI), their impact on brain functions remains largely unknown, with diagnoses mainly dependent on behavioral assessments. Methods: In this study, we analyzed resting-state fMRI data from a cohort of 34 svMCI patients, comprising 18 patients with depression symptoms (svMCI+D) and 16 patients without (svMCI-D), along with 34 normal controls (NC). The study used the fraction of the amplitude of low-frequency fluctuations (fALFF), resting-state functional connectivity, correlation analyses, and support vector machine (SVM) techniques. Results: The fALFF of the right cerebellum (CERE.R) differed among the svMCI+D, svMCI-D, and NC groups. Specifically, the regional mean fALFF of CERE. R was lower in svMCI-D patients compared to NC but higher in svMCI+D patients compared to svMCI-D patients. Moreover, the adjusted fALFF of CERE. R showed a significant correlation with Montreal Cognitive Assessment (MOCA) scores in svMCI-D patients. The fALFF of the right orbital part of the superior frontal gyrus was significantly correlated with Hamilton Depression Scale scores in svMCI+D patients, whereas the fALFF of the right postcingulate cortex (PCC.R) showed a significant correlation with MOCA scores in svMCI-D patients. Furthermore, RSFC between PCC. R and right precuneus, as well as between CERE. R and the right lingual gyrus (LING.R), was significantly reduced in svMCI-D patients compared to NC. In regional analyses, the adjusted RSFC between PCC. R and PreCUN. R, as well as between CERE. R and LING. R, was decreased in svMCI-D patients compared to NC but increased in svMCI+D patients compared to svMCI-D. Further SVM analyses achieved good performances, with an area under the curve (AUC) of 0.82 for classifying svMCI+D, svMCI-D, and NC; 0.96 for classifying svMCI+D and svMCI-D; 0.82 for classifying svMCI+D and NC; and 0.92 for classifying svMCI-D and NC. Conclusion: The study revealed disruptive effects of cognitive impairment, along with both disruptive and complementary effects of depression symptoms on spontaneous brain activity in svMCI. Moreover, these findings suggest that the identified features might serve as potential biomarkers for distinguishing between svMCI+D, svMCI-D, and NC, thereby guiding clinical treatments such as transcranial magnetic stimulation for svMCI. [ABSTRACT FROM AUTHOR]

Objective: Cognitive decline is often considered an inevitable aspect of aging; however, recent research has identified a subset of older adults known as "superagers" who maintain cognitive abilities comparable to those of younger individuals. Investigating the neurobiological characteristics associated with superior cognitive function in superagers is essential for understanding "successful aging." Evidence suggests that the gut microbiome plays a key role in brain function, forming a bidirectional communication network known as the microbiome-gut-brain axis. Alterations in the gut microbiome have been linked to cognitive aging markers such as oxidative stress and inflammation. This study aims to investigate the unique patterns of the gut microbiome in superagers and to develop machine learning-based predictive models to differentiate superagers from typical agers. Methods: We recruited 161 cognitively unimpaired, community-dwelling volunteers aged 60 years or from dementia prevention centers in Seoul, South Korea. After applying inclusion and exclusion criteria, 115 participants were included in the study. Following the removal of microbiome data outliers, 102 participants, comprising 57 superagers and 45 typical agers, were finally analyzed. Superagers were defined based on memory performance at or above average normative values of middle-aged adults. Gut microbiome data were collected from stool samples, and microbial DNA was extracted and sequenced. Relative abundances of bacterial genera were used as features for model development. We employed the LightGBM algorithm to build predictive models and utilized SHAP analysis for feature importance and interpretability. Results: The predictive model achieved an AUC of 0.832 and accuracy of 0.764 in the training dataset, and an AUC of 0.861 and accuracy of 0.762 in the test dataset. Significant microbiome features for distinguishing superagers included Alistipes, PAC001137_g, PAC001138_g, Leuconostoc, and PAC001115_g. SHAP analysis revealed that higher abundances of certain genera, such as PAC001138_g and PAC001115_g, positively influenced the likelihood of being classified as superagers. Conclusion: Our findings demonstrate the machine learning-based predictive models using gut-microbiome features can differentiate superagers from typical agers with a reasonable performance. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is increasingly recognized as being intertwined with the dysregulation of lipid metabolism. Lipids are a significant class of nutrients vital to all organisms, playing crucial roles in cellular structure, energy storage, and signaling. Alterations in the levels of various lipids in AD brains and dysregulation of lipid pathways and transportation have been implicated in AD pathogenesis. Clinically, evidence for a high-fat diet firmly links disrupted lipid metabolism to the pathogenesis and progression of AD, although contradictory findings warrant further exploration. In view of the significance of various lipids in brain physiology, the discovery of complex and diverse mechanisms that connect lipid metabolism with AD-related pathophysiology will bring new hope for patients with AD, underscoring the importance of lipid metabolism in AD pathophysiology, and promising targets for therapeutic intervention. Specifically, cholesterol, sphingolipids, and fatty acids have been shown to influence amyloid-beta (Ab) accumulation and tau hyperphosphorylation, which are hallmarks of AD pathology. Recent studies have highlighted the potential therapeutic targets within lipid metabolism, such as enhancing apolipoprotein E lipidation, activating liver X receptors and retinoid X receptors, and modulating peroxisome proliferator-activated receptors. Ongoing clinical trials are investigating the efficacy of these strategies, including the use of ketogenic diets, statin therapy, and novel compounds like NE3107. The implications of these findings suggest that targeting lipid metabolism could offer new avenues for the treatment and management of AD. By concentrating on alterations in lipid metabolism within the central nervous system and their contribution to AD development, this review aims to shed light on novel research directions and treatment approaches for combating AD, offering hope for the development of more effective management strategies. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore and evaluate the efficacy of non-invasive brain stimulation (NIBS) as a standalone or coupled intervention and understand its mechanisms to produce positive alterations in neuroplasticity and behavioral outcomes after acquired brain injury (ABI). Data sources: Cochrane Library, Web of Science, PubMed, and Google Scholar databases were searched from January 2013 to January 2024. Study selection: Using the PICO framework, transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) randomized controlled trials (RCTs), retrospective, pilot, open-label, and observational large group and single-participant case studies were included. Two authors reviewed articles according to pre-established inclusion criteria. Data extraction: Data related to participant and intervention characteristics, mechanisms of change, methods, and outcomes were extracted by two authors. The two authors performed quality assessments using SORT. Results: Twenty-two studies involving 657 participants diagnosed with ABIs were included. Two studies reported that NIBS was ineffective in producing positive alterations or behavioral outcomes. Twenty studies reported at least one, or a combination of, positively altered neuroplasticity and improved neuropsychological, neuropsychiatric, motor, or somatic symptoms. Twentyeight current articles between 2020 and 2024 have been studied to elucidate potential mechanisms of change related to NIBS and other mediating or confounding variables. Discussion: tDCS and TMS may be efficacious as standalone interventions or coupled with neurorehabilitation therapies to positively alter maladaptive brain physiology and improve behavioral symptomology resulting from ABI. Based on postintervention and follow-up results, evidence suggests NIBS may offer a direct or mediatory contribution to improving behavioral outcomes post-ABI. Conclusion: More research is needed to better understand the extent of rTMS and tDCS application in affecting changes in symptoms after ABI. [ABSTRACT FROM AUTHOR]

Magnetoencephalography/electroencephalography (M/EEG) can provide insights into migraine pathophysiology and help develop clinically valuable biomarkers. To integrate and summarize the existing evidence on changes in brain function in migraine, we performed a systematic review and meta-analysis (PROSPERO CRD42021272622) of resting-state M/EEG findings in migraine. We included 27 studies after searching MEDLINE, Web of Science Core Collection, and EMBASE. Risk of bias was assessed using a modified Newcastle–Ottawa Scale. Semi-quantitative analysis was conducted by vote counting, and meta-analyses of M/EEG differences between people with migraine and healthy participants were performed using random-effects models. In people with migraine during the interictal phase, meta-analysis revealed higher power of brain activity at theta frequencies (3–8 Hz) than in healthy participants. Furthermore, we found evidence for lower alpha and beta connectivity in people with migraine in the interictal phase. No associations between M/EEG features and disease severity were observed. Moreover, some evidence for higher delta and beta power in the premonitory compared to the interictal phase was found. Strongest risk of bias of included studies arose from a lack of controlling for comorbidities and non-automatized or non-blinded M/EEG assessments. These findings can guide future M/EEG studies on migraine pathophysiology and brain-based biomarkers, which should consider comorbidities and aim for standardized, collaborative approaches. [ABSTRACT FROM AUTHOR]

Background: The overlapping clinical manifestations in parkinsonian variant of multiple system atrophy (MSA-P) and Parkinson's Disease (PD) can complicate clinical diagnostic accuracy, particularly in the early stage. The study aims to uncover the patterns of brain function in the initial phase of the two conditions. Methods: We recruited 24 MSA-P patients, 34 PD patients and 27 healthy controls (HC). Voxel-wise fractional amplitude of low-frequency fluctuation (fALFF) was compared to characterize regional brain function, followed by seedbased functional connectivity (FC) analysis. Receiver operating characteristic (ROC) analyses were used to examine the diagnostic accuracy of fALFF. Results: Compared to HC, decreased fALFF was observed in the bilateral basal ganglia (BG) of MSA-P patients, while decreased fALFF was identified in the left BG of PD patients. Additionally, elevated fALFF was found in the superior cerebellum for MSA-P patients and the temporo-occipital cortex for PD patients. Furthermore, PD patients exhibited increased FC in the cortico-striatal loop compared to MSA-P patients. The fALFF of the left caudate distinguished MSA-P from HC with an area under the curve (AUC) of 0.838 (p < 0.001) and from PD with an AUC of 0.772 (p < 0.001). The fALFF of the left putamen distinguished PD from HC with an AUC of 0.736 (p = 0.002). Conclusion: Our findings indicated common and distinct abnormalities in spontaneous brain activity within BG, cerebellum, and cortices in early-stage MSA-P and PD patients. PD patients employed more compensatory mechanisms than MSA-P patients. Furthermore, fALFF may aid in early differentiation between MSA-P and PD. [ABSTRACT FROM AUTHOR]

Oscillations, a highly conserved brain function across mammalian species, play a pivotal role in both brain physiology and pathology. Traumatic brain injury (TBI) frequently results in subacute and chronic alterations in brain oscillations, which are often associated with complications like post-traumatic epilepsy (PTE) in patients and animal models. We recently conducted longitudinal recordings of local field potential from the contralateral hippocampus of 12 strains of recombinant inbred Collaborative Cross (CC) mice and classical laboratory inbred C57BL/6  J mice after lateral fluid percussion injury. In this study, we profiled the acute (<12  h post-injury) and subacute (12–48  h post-injury) hippocampal oscillatory responses to TBI and evaluated their predictive value for PTE. We found dynamic high-amplitude rhythmic spikes with elevated power density and reduced signal complexity that prevailed exclusively during the acute phase in CC031 mice, which later developed PTE. This characteristic early brain oscillatory alteration was absent in CC031 sham controls, as well as in other CC strains and reference C57BL/6  J mice that did not develop PTE after TBI. Our findings offer quantitative measures linking early hippocampal brain oscillation to PTE at a population level in mice. These insights enhance understanding of circuit mechanisms and suggest potential targets for neuromodulatory intervention. [ABSTRACT FROM AUTHOR]

Introduction: Patients with coronary artery disease (CAD) have a higher risk of developing cognitive impairment and mental health disorders compared to the general population. Physical exercise might improve their brain health. The overall goal of the HEART-BRAIN randomized controlled trial (RCT) is to investigate the effects of different types of exercise on brain health outcomes in patients with CAD, and the underlying mechanisms. Methods: This three-arm, single-blinded RCT will include 90 patients with CAD (50-75 years). Participants will be randomized into: (1) control group--usual care (n = 30), (2) aerobic high-intensity interval training (HIIT) (n = 30), or (3) HIIT combined with resistance exercise training (n = 30). The 12-week intervention includes 3 supervised sessions (45-min each) per week for the exercise groups. Outcomes will be assessed at baseline and post-intervention. The primary outcome is to determine changes in cerebral blood flow assessed by magnetic resonance imaging. Secondary outcomes include changes in brain vascularization, cognitive measures (i.e., general cognition, executive function and episodic memory), and cardiorespiratory fitness. Additional health-related outcomes, and several potential mediators and moderators will be investigated (i.e., brain structure and function, cardiovascular and brain-based biomarkers, hemodynamics, physical function, body composition, mental health, and lifestyle behavior). Conclusion: The HEART-BRAIN RCT will provide novel insights on how exercise can impact brain health in patients with CAD and the potential mechanisms explaining the heart-brain connection, such as changes in cerebral blood flow. The results may have important clinical implications by increasing the evidence on the effectiveness of exercise-based strategies to delay cognitive decline in this high-risk population. [ABSTRACT FROM AUTHOR]

Introduction: Auditory training (AT) exercises as the main part of auditory rehabilitation have emerged as a promising method for enhancing auditory perception and communication skills in individuals with hearing impairments or difficulties in auditory processing. Through AT, the central auditory nervous system (CANS) undergoes changes that optimize neural circuits, resulting in improved auditory perception. Auditory-evoked potentials (AEPs), including the auditory brainstem responses (ABRs) and cortical auditory-evoked potentials (CAEPs), offer objective measurements of neural responses and serve as valuable biomarkers to assess the effectiveness of AT. Methods: For this systematic review, we conducted a comprehensive search in multiple databases, including MEDLINE (via PubMed), Science Direct, Web of Science, and SciELO, up until August 18, 2023. There were no study type restrictions or limitations on publication time. Following a careful assessment of the article quality and their alignment with the inclusion and exclusion criteria, a total of 25 articles were selected for inclusion in this study. Results: Based on the findings of the reviewed studies, it has been reported that AT exercises lead to an increase in the amplitude of waves in both brainstem and cortical AEPs, with the exception of P1 and N2 waves. Furthermore, it has been observed that the latency of these responses decreases following AT. Conclusion: The application of brainstem and cortical AEPs as objective electrophysiological tools holds promise in assessing the effectiveness of AT exercises and confirming the selected approach for AT. [ABSTRACT FROM AUTHOR]

Simple Summary: Advances in pain research challenge the concept that animals lack pain senses, showing that they have similar neural pathways to humans and experience pain similarly. Understanding brain circuits for effective pain control is crucial for adjusting pain control to individual patient responses and conditions. Pain management in oncological patients aims to lessen the impact of tumor cell development and its consequences on the immune system. Researchers have focused on improving algological approaches to better respond to patient needs, which requires a deeper understanding of how analgesics work, interact with other drugs, and affect patients' conditions. Opioids, although linked to tumor progression, remain the mainstay for managing oncologic pain. Advancements in understanding pain physiopathology have historically challenged animals' absence of pain senses. Studies have demonstrated that animals have comparable neural pain pathways, suggesting that cats and dogs likely experience pain similarly to humans. Understanding brain circuits for effective pain control has been crucial to adjusting pain management to the patient's individual responses and current condition. The refinement of analgesic strategies is necessary to better cater to the patient's demands. Cancer pain management searches to ascertain analgesic protocols that enhance patient well-being by minimizing or abolishing pain and reducing its impact on the immune system and cancer cells. Due to their ability to reduce nerve sensitivity, opioids are the mainstay for managing moderate and severe acute pain; however, despite their association with tumor progression, specific opioid agents have immune-protective properties and are considered safe alternatives to analgesia for cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The survival of glioblastoma (GBM) patients remains at just 12–15 months with a 5% 5 year survival despite them undergoing a harsh and brutal treatment regimen involving surgery, radiation and chemotherapy. This is because GBMs are impossible to completely resect and almost always recur at the borders of the resection margin, while the presence of the blood–brain barrier limits the amount of chemotherapy that can access the brain, requiring the patient to receive high and extremely toxic doses of chemotherapy. In this study, we demonstrate that local delivery of the chemotherapeutic drug irinotecan directly into the border of the resection margin offers a safe route of administration with none of the normal side effects associated with traditional chemotherapy. Glioblastomas are impossible to completely resect and almost always recur at the borders of the resection margin. There is no established chemotherapy regimen available to patients who recur, while systemic treatment is hampered by the blood–brain barrier. Here, we report on the first evaluation in humans of the intraparenchymal injection of irinotecan into the resection cavity after surgical resection of recurrent glioblastoma patients. The cytotoxicity of irinotecan was compared to SN-38 in primary cells from recurrent glioblastoma patients. Irinotecan was injected at multiple (~30) sites of the resection cavity wall at a depth of 3 to 5 mm. SN-38 was more cytotoxic than irinotecan at concentrations below 1 µM due to enzyme kinetics. The intraparenchymal administration of irinotecan was safe, with good wound healing and an absence of swelling, inflammation, or pseudo-abscess formation. The median survival post irinotecan administration was 32.6 weeks. The median overall survival was 30.5 months, with a two-year survival rate of 56%. This study demonstrates that local delivery of irinotecan into the brain parenchyma offers a safe route of administration over systemic delivery in the treatment of recurrent glioblastoma. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (T1DM) can result in complications such as retinopathy, nephropathy, and peripheral neuropathy, which can lead to brain dysfunction. In this study, we investigated the effects of T1DM on cerebral neurovascular function in mice. Streptozotocin (STZ) is known to induce T1DM in animals; thus, we used an STZ-induced diabetes model to evaluate the effects of hyperglycemia on brain morphology and neurovascular tissue. Neurovascular coupling is the connection between neuronal activity and cerebral blood flow that maintains brain function. The ECoG-LSCI technique combines electrocorticography (ECoG) and laser speckle contrast imaging (LSCI) to detect cortical spreading depression (CSD) as a marker of neurovascular coupling and measure corresponding neurovascular function. Our results suggested that in the STZ group, hyperglycemia affected excitatory neurotransmission and metabolism, leading to reductions in intercellular signaling, somatosensory evoked potential (SSEP) amplitudes, and CSD transmission rates. Western blot data further revealed that brain-derived neurotrophic factor (BDNF) and neuronal nuclear antigen levels were reduced in the STZ group. Abnormalities in glucose metabolism in the brain and increased phosphorylation of AKT and GSK3 are hypothesized to be responsible for these decreases. Overall, this study highlights the importance of glucose metabolism in normal brain physiology and demonstrates that hyperglycemia disrupts neurovascular coupling and affects cerebral neurovascular function and that the degree of CSD is positively correlated with the extent of brain tissue damage. Further research is essential to gain a complete understanding of the related mechanisms and the implications of these findings. [ABSTRACT FROM AUTHOR]

Adverse childhood experiences (ACEs; e.g., physical abuse) can impact lifelong mental health both directly and intergenerationally, with effects transmitted from the parent to the child. Several physiological mechanisms have been proposed to explain the impacts of ACEs on mental health. The purpose of this narrative review was to synthesize and critique the peer-reviewed literature on physiological mechanisms proposed to underlie the impacts of ACEs on mental health, specifically: (1) hypothalamic–pituitary–adrenal axis functioning, (2) inflammation, (3) genetic inheritance and differential susceptibility, (4) epigenetics, (5) brain structure and function, (6) oxidative stress, and (7) metabolic profiles. We searched Google Scholar using variations of the terms "adverse childhood experiences", "mechanisms", and "mental health" to locate relevant peer-reviewed literature. We also mined citations of the identified literature to find additional important sources. The role of inflammation in the etiology of mental health conditions among those exposed to ACEs appeared promising, followed by hypothalamic–pituitary–adrenal axis functioning, brain structure and function, genetics, epigenetics, metabolism, and lastly, oxidative stress. Replication studies that examine the associations among ACEs, genetic inheritance and differential susceptibility, epigenetics, oxidative stress, and metabolism are required to better define links with mental health. [ABSTRACT FROM AUTHOR]

During continuous speech perception, endogenous neural activity becomes time-locked to acoustic stimulus features, such as the speech amplitude envelope. This speech–brain coupling can be decoded using non-invasive brain imaging techniques, including electroencephalography (EEG). Neural decoding may provide clinical use as an objective measure of stimulus encoding by the brain—for example during cochlear implant listening, wherein the speech signal is severely spectrally degraded. Yet, interplay between acoustic and linguistic factors may lead to top-down modulation of perception, thereby complicating audiological applications. To address this ambiguity, we assess neural decoding of the speech envelope under spectral degradation with EEG in acoustically hearing listeners (n = 38; 18–35 years old) using vocoded speech. We dissociate sensory encoding from higher-order processing by employing intelligible (English) and non-intelligible (Dutch) stimuli, with auditory attention sustained using a repeated-phrase detection task. Subject-specific and group decoders were trained to reconstruct the speech envelope from held-out EEG data, with decoder significance determined via random permutation testing. Whereas speech envelope reconstruction did not vary by spectral resolution, intelligible speech was associated with better decoding accuracy in general. Results were similar across subject-specific and group analyses, with less consistent effects of spectral degradation in group decoding. Permutation tests revealed possible differences in decoder statistical significance by experimental condition. In general, while robust neural decoding was observed at the individual and group level, variability within participants would most likely prevent the clinical use of such a measure to differentiate levels of spectral degradation and intelligibility on an individual basis. [ABSTRACT FROM AUTHOR]

Background: There is a lack of further exploration of the epileptogenic network of specific types of epilepsy, such as unilateral hippocampal sclerosis (HS), and there is an urgent need to find exact evidence to confirm the consistency of its brain network changes. Methods: We enrolled 22 mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE-HS) patients to compare the differences in brain activity between 22 healthy controls (HCs) and them. Resting-state electroencephalography (EEG) was also measured. Then, we calculated the power spectral density and phase locking values in and between these electrodes. Results: The results showed the increased theta power was related to the high severity of epilepsy in the temporal, parietal, and central regions in mTLE-HS patients, and there were positive correlations between theta power in the contralateral temporal region and seizure frequency. Theta power in the ipsilateral parietal lobe is positively correlated with the number of anti-seizure medications (ASMs), but not with the usage of third-generation ASMs. Meanwhile, the temporal lobe of mTLE-HS patients had more connectivity with parietal lobe and central region. Conclusions: Theta power is an important EEG indicator of mTLE-HS, positively correlates with epilepsy severity and seizure frequency, and has network properties that can be observed outside the lesion. Moreover, the usage of third-generation ASMs did not affect the risk of increased theta power. Lastly, the temporoparietal and temporal-central networks are likely to be causative pathways in epilepsy patients with cognitive impairment. This study provides a potential guideline for the treatment of mTLE-HS in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma, a high-grade primary brain cancer, has a median survival of approximately 14 months. Post-mortem brain donation provides insight to pathogenesis along with spatial and temporal heterogeneity. Post-mortem brain biobanking programs are increasing in number and the need to understand and improve the associated human experience is pressing. This study aims to qualitatively explore the experiences of next of kin (NOK) following the death and brain donation of a loved one and to understand the impact such programs have on NOK carers. Method: We interviewed 29 NOK following the death of their loved one and subsequent brain donation. Thematic analysis was conducted on the transcribed, qualitative interviews. Results: Four themes were identified; (1) Brain donation is a straightforward decision grounded in altruism and pragmatism; (2) Supporting donors is a source of comfort, pride and empowerment; (3) Brain donation can provide meaning for suffering and tragedy and (4) Perceptions of procedures and processes when supporting a loved one to donate. Insights into areas for improvement, for example transporting donors following a home death and the role of the body bag were also noted. Conclusion: Supporting a loved one to donate their brain can be a positive experience providing a source of hope, empowerment and purpose for NOK. Data indicating areas for consideration are broadly relevant for improving the delivery of brain donation programs for future donors and their loved ones. Plain language summary: Understanding how loved ones feel about someone close to them donating their brain to research after their death from brain cancer The act of donating brain tissue after death from brain cancer is a huge gift to medical research and may have an impact on the ability of the scientific community to improve outcomes for people diagnosed with brain cancers. While we understand how valuable these donations are for research, we need more work to understand how these donations impact the people who donate and those who love and support them. This paper explores the experiences of people who have lost someone to brain cancer who then went on to donate their brain tissue after their death. Through the use of interviews, it explores the impact that the donation has on a loved one or next of kin from providing a source of comfort, empowerment, pride or an alternative to 'senseless' suffering and tragedy. It also provides areas that should be considered by people who are facilitating brain donations to ensure that any potential, harm or upset can be minimized. [ABSTRACT FROM AUTHOR]

Brain organoids have become a valuable tool for studying human brain development, disease modeling, and drug testing. However, generating brain organoids with mature neurons is time-intensive and often incomplete, limiting their utility in studying age-related neurodegenerative diseases such as Alzheimer's disease (AD). Here, we report the generation of 3D brain organoids from human fibroblasts through direct reprogramming, with simplicity, efficiency, and reduced variability. We also demonstrate that induced brain organoids from APOE ε4 AD patient fibroblasts capture some disease-specific features and pathologies associated with APOE ε4 AD. Moreover, APOE ε4-induced brain organoids with mutant APP overexpression faithfully recapitulate the acceleration of AD-related pathologies, providing a more physiologically relevant and patient-specific model of familial AD. Importantly, transcriptome analysis reveals that gene sets specific to APOE ε4 patient-induced brain organoids are highly similar to those of APOE ε4 post-mortem AD brains. Overall, induced brain organoids from direct reprogramming offer a promising approach for more efficient and controlled studies of neurodegenerative disease modeling. [ABSTRACT FROM AUTHOR]

The most prevalent cause of dementia is Alzheimer's disease. Cognitive decline and accelerating memory loss characterize it. Alzheimer's disease advances sequentially, starting with preclinical stages, followed by mild cognitive and/or behavioral impairment, and ultimately leading to Alzheimer's disease dementia. In recent years, healthcare providers have been advised to make an earlier diagnosis of Alzheimer's, prior to individuals developing Alzheimer's disease dementia. Regrettably, the identification of early-stage Alzheimer's disease in clinical settings can be arduous due to the tendency of patients and healthcare providers to disregard symptoms as typical signs of aging. Therefore, accurate and prompt diagnosis of Alzheimer's disease is essential in order to facilitate the development of disease-modifying and secondary preventive therapies prior to the onset of symptoms. There has been a notable shift in the goal of the diagnosis process, transitioning from merely confirming the presence of symptomatic AD to recognizing the illness in its early, asymptomatic phases. Understanding the evolution of disease-modifying therapies and putting effective diagnostic and therapeutic management into practice requires an understanding of this concept. The outcomes of this study will enhance indepth knowledge of the current status of Alzheimer's disease's diagnosis and treatment, justifying the necessity for the quest for potential novel biomarkers that can contribute to determining the stage of the disease, particularly in its earliest stages. Interestingly, latest clinical trial status on pharmacological agents, the nonpharmacological treatments such as behavior modification, exercise, and cognitive training as well as alternative approach on phytochemicals as neuroprotective agents have been covered in detailed. [ABSTRACT FROM AUTHOR]

Introduction: Numerous studies have highlighted cognitive benefits in lifelong bilinguals during aging, manifesting as superior performance on cognitive tasks compared to monolingual counterparts. Yet, the cognitive impacts of acquiring a new language in older adulthood remain unexplored. In this study, we assessed both behavioral and fMRI responses during a Stroop task in older adults, preand post language-learning intervention. Methods: A group of 41 participants (age:60-80) from a predominantly monolingual environment underwent a four-month online language course, selecting a new language of their preference. This intervention mandated engagement for 90 minutes a day, five days a week. Daily tracking was employed to monitor progress and retention. All participants completed a color-word Stroop task inside the scanner before and after the language instruction period. Results: We found that performance on the Stroop task, as evidenced by accuracy and reaction time, improved following the language learning intervention. With the neuroimaging data, we observed significant differences in activity between congruent and incongruent trials in key regions in the prefrontal and parietal cortex. These results are consistent with previous reports using the Stroop paradigm. We also found that the amount of time participants spent with the language learning program was related to differential activity in these brain areas. Specifically, we found that people who spent more time with the language learning program showed a greater increase in differential activity between congruent and incongruent trials after the intervention relative to before. Discussion: Future research is needed to determine the optimal parameters for language learning as an effective cognitive intervention for aging populations. We propose that with sufficient engagement, language learning can enhance specific domains of cognition such as the executive functions. These results extend the understanding of cognitive reserve and its augmentation through targeted interventions, setting a foundation for future investigations. [ABSTRACT FROM AUTHOR]

Background and objectives: Cognitive reserve (CR) is a property of the brain that allows for better-than-expected cognitive performance relative to the degree of brain change over the course of life. However, neurophysiological markers of CR remain under-investigated. Electroencephalography (EEG) features may function as suitable neurophysiological markers of CR. To assess this, we investigated whether the dorsal attention network (DAN) and ventral attention network (VAN) activities, as measured during resting-state EEG, moderate the relationship between hippocampal volume and episodic memory. Methods: Participants were recruited as part of the National Center for Geriatrics and Gerontology-Study of Geriatric Syndromes. Hippocampal volume was determined using magnetic MRI, and episodic memory was measured using word lists. After testing the effect of hippocampal volume on memory performance using multiple regression analysis, we evaluated the interactions between hippocampal volume and DAN and VAN network activities. We further used the Johnson-Neyman technique to quantify the moderating effects of DAN and VAN network activities on the relationship between hippocampal volume and word list memory, as well as to identify specific ranges of DAN and VAN network activity with significant hippocampal-memory association. Results: A total of 449 participants were included in this study. Our analysis revealed significant moderation of DAN with a slope of β = -0.00012 (95% CI: -0.00024; -0.00001, p = 0.040), and VAN with a slope of β = 0.00014 (95% CI: 0.00001; 0.00026, p = 0.031). Further, we found that a larger hippocampal volume was associated with improved memory performance, and that this association became stronger as the DAN activity decreased until a limit of DAN activity of 944.9, after which the hippocampal volume was no longer significantly related to word-list memory performance. For the VAN, we found that a higher hippocampal volume was more strongly associated with better memory performance when VAN activity was higher. However, when VAN activity extended beyond -914.6, the hippocampal volume was no longer significantly associated with word-list memory. Discussion: Our results suggest that attentional networks help to maintain memory performance in the face of age-related structural decline, meeting the criteria for the neural implementation of cognitive reserve. [ABSTRACT FROM AUTHOR]

Ageing is characterized by a gradual decline in the efficiency of physiological functions and increased vulnerability to diseases. Ageing affects the entire body, including physical, mental, and social well-being, but its impact on the brain and cognition can have a particularly significant effect on an individual's overall quality of life. Therefore, enhancing lifespan and physical health in longevity studies will be incomplete if cognitive ageing is over looked. Promoting successful cognitive ageing encompasses the objectives of mitigating cognitive decline, as well as simultaneously enhancing brain function and cognitive reserve. Studies in both humans and animal models indicate that cognitive decline related to normal ageing and age-associated brain disorders are more likely linked to changes in synaptic connections that form the basis of learning and memory. This activitydependent synaptic plasticity reorganises the structure and function of neurons not only to adapt to new environments, but also to remain robust and stable over time. Therefore, understanding the neural mechanisms that are responsible for age-related cognitive decline becomes increasingly important. In this review, we explore the multifaceted aspects of healthy brain ageing with emphasis on synaptic plasticity, its adaptive mechanisms and the various factors affecting the decline in cognitive functions during ageing. We will also explore the dynamic brain and neuroplasticity, and the role of lifestyle in shaping neuronal plasticity. [ABSTRACT FROM AUTHOR]

Background: Schizophrenia (SCZ) is characterized by cognitive deficits that are linked to prefrontal cortex dysfunction. While transcranial direct current stimulation (tDCS) shows promise for improving cognition, the effects of intensified 3mA tDCS protocols on brain physiology are unknown. This project aims to elucidate the neurophysiological and cognitive effects of an intensified prefrontal tDCS protocol in SCZ. Methods: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham-controlled, trial. Forty-eight participants with SCZ and cognitive impairment (measured via a set of executive functions tests) will be randomly allocated to receive either a single session of active (n = 24) or sham (n = 24) tDCS (20-min, 3-mA). The anodal and cathodal electrodes are positioned over the left and right DLPFC respectively. The stimulation occurs concurrently with the working memory task, which is initiated precisely 5 minutes after the onset of tDCS. Structural and resting-state (rs-fMRI) scans are conducted immediately before and after both active and sham tDCS using a 3 Tesla scanner (Siemens Prisma model) equipped with a 64-channel head coil. The primary outcome will be changes in brain activation (measures vis BOLD response) and working memory performance (accuracy, reaction time). Discussion: The results of this study are helpful in optimizing tDCS protocols in SCZ and inform us of neurocognitive mechanisms underlying 3 mA stimulation. This study will additionally provide initial safety and efficacy data on a 3 mA tDCS protocol to support larger clinical trials. Positive results could lead to rapid and broader testing of a promising tool for debilitating symptoms that affect the majority of patients with SCZ. The results will be made available through publications in peer-reviewed journals and presentations at national and international conferences. [ABSTRACT FROM AUTHOR]

One of the puzzling aspects of sporadic Alzheimer's disease (AD) is how it commences. Changes in one key brain peptide, amyloid-beta (Aß), accompany disease progression, but whether this comprises a trigger or a consequence of AD is still a topic of debate. It is clear however that the cerebral presence of oligomeric Aß (1-42) is a key factor in early AD-pathogenesis. Furthermore, treatment of rodent brains with oligomeric Aß (1-42) either in vitro or in vivo, acutely impairs hippocampal synaptic plasticity, creating a link between Aß-pathology and learning impairments. Here, we show that a once-off inoculation of the brains of healthy adult rats with oligomeric Aß (1-42) exerts debilitating effects on the long-term viability of the hippocampus, one of the primary targets of AD. Changes are progressive: months after treatment, synaptic plasticity, neuronal firing and spatial learning are impaired and expression of plasticityrelated proteins are changed, in the absence of amyloid plaques. Early changes relate to activation of microglia, whereas later changes are associated with a reconstruction of astroglial morphology. These data suggest that a disruption of Aß homeostasis may suffice to trigger an irreversible cascade, underlying progressive loss of hippocampal function, that parallels the early stages of AD. [ABSTRACT FROM AUTHOR]

Synapses are fundamental to the function of the central nervous system and are implicated in a number of brain disorders. Despite their pivotal role, a comprehensive imaging resource detailing the distribution of synapses in the human brain has been lacking until now. Here, we employ high-resolution PET neuroimaging in healthy humans (17F/16M) to create a 3D atlas of the synaptic marker Synaptic Vesicle glycoprotein 2A (SV2A). Calibration to absolute density values (pmol/ml) was achieved by leveraging postmortem human brain autoradiography data. The atlas unveils distinctive cortical and subcortical gradients of synapse density that reflect functional topography and hierarchical order from core sensory to higher-order integrative areas-a distribution that diverges from SV2A mRNA patterns. Furthermore, we found a positive association between IQ and SV2A density in several higher-order cortical areas. This new resource will help advance our understanding of brain physiology and the pathogenesis of brain disorders, serving as a pivotal tool for future neuroscience research. [ABSTRACT FROM AUTHOR]

Simple Summary: This study explores the use of intraoperative magnetic resonance imaging (iMRI) in the surgical resection of brain metastases (BMs). The research aims to determine how iMRI can improve the precision of tumor removal, thereby enhancing patient outcomes. By providing real-time, high-resolution images during surgery, iMRI assists surgeons in achieving more complete tumor resection, potentially reducing recurrence rates and improving survival chances. Integrating iMRI into surgical protocols helps preserve neurological functions, especially for patients with BM in critical brain areas. This study highlights the safety and effectiveness of iMRI in neurosurgery and suggests its broader adoption for the better management of BMs. Intraoperative magnetic resonance imaging (iMRI) has witnessed significant growth in the field of neurosurgery, particularly in glioma surgery, enhancing image-guided neuronavigation and optimizing the extent of resection (EOR). Despite its extensive use in the treatment of gliomas, its utility in brain metastases (BMs) remains unexplored. This study examined the effect of iMRI on BM resection. This retrospective study was conducted at the neurosurgical center of the University Hospital of the Technical University of Munich and involved 25 patients with BM who underwent resection using 3-Tesla iMRI between 2018 and 2022. Volumetric measurements of the resected contrast-enhancing metastases were performed using preoperative, intraoperative, and postoperative MRI images. The Karnofsky Performance Score (KPS) and neurological status of the patients were assessed pre- and postoperatively. Local recurrence and in-brain progression were reported in patients who underwent follow-up MRI at 3 and 6 months postoperatively. In this cohort (n = 25, mean age 63.6 years), non-small-cell lung cancer (NSCLC) was the most common origin (28%). The mean surgical duration was 219.9 min, and that of iMRI was 61.7 min. Indications for iMRI were primarily associated with preoperative imaging, suggesting an unclear entity that is often suspicious for glioma. Gross total resection (GTR) was achieved in 21 patients (84%). Continued resection was pursued after iMRI in six cases (24%), resulting in an improved EOR of 100% in five cases and 97.6% in one case. Neurological status postoperatively remained stable in 60%, improved in 24%, and worsened in 16% of patients. No wound healing or postoperative complications were observed. Among the thirteen patients who underwent follow-up MRI 3 months postoperatively, one patient showed local recurrence at the site of resection, and seven patients showed in-brain progression. Of the eight patients who underwent a 6-month follow-up MRI, two showed local recurrence, while three exhibited in-brain progression. The observed favorable profiles of GTR, coupled with the notable absence of wound-healing problems and acute postoperative complications, affirm the safety and feasibility of incorporating iMRI into the neurosurgical workflow for resecting BM with specific indications. The real-time imaging capabilities of iMRI offer unparalleled precision, aiding meticulous tumor delineation and informed decision-making, ultimately contributing to improved patient outcomes. Although our experience suggests the potential benefits of iMRI as a safe tool for enhancing EOR, we acknowledge the need for larger prospective clinical trials. Comprehensive investigations on a broader scale are imperative to further elucidate the specific indications for iMRI in the context of BMs and to study its impact on survival. Rigorous prospective studies will refine our understanding of the clinical scenarios in which iMRI can maximize its impact, guiding neurosurgeons toward more informed and tailored decision-making. [ABSTRACT FROM AUTHOR]

Introduction: Carotid endarterectomy is performed for patients with symptomatic carotid artery occlusions. Surgery can be performed under general and regional anesthesia. Traditionally, surgery is performed under deep cervical plexus block which is technically difficult to perform and can cause serious complications. This case series describes 5 cases in which an intermediate cervical plexus block was used in combination with a superficial cervical plexus block for Carotid endarterectomy surgery. Methods: Five patients who were classified as American Society of Anesthesiologists 2–3 were scheduled for Carotid endarterectomy due to symptoms and more than 70% occlusion of the carotid arteries. The procedures were carried out in the University Teaching Hospital- Peradeniya, Sri Lanka. All patients were given superficial cervical plexus block followed by intermediate cervical plexus block using 2% lignocaine and 0.5% plain bupivacaine. Results: Adequate anesthesia was achieved in 4 patients, and local infiltration was necessary in 1 patient. Two patients developed hoarseness of the voice, which settled 2 h after surgery. Hemodynamic fluctuations were observed in all 5 patients. No serious complications were observed. All 5 patients had uneventful recoveries. Discussions: Regional anesthesia for CEA is preferable in patients who are medically complicated to undergo anesthesia or in patients for whom cerebral monitoring is not available. Intermediate cervical plexus block is described for thyroid surgeries in literature, but not much details on its use for carotid surgeries. Deep cervical plexus blocks has few serious complications which is not there with the use of ICPB making it a good alternative for CEA surgeries. Conclusions: Superficial cervical plexus block and intermediate cervical plexus block can be used effectively for providing anesthesia for patients undergoing Carotid endarterectomy. It is safe and easier to conduct than deep cervical plexus block and enables monitoring of cerebral function. [ABSTRACT FROM AUTHOR]

Gene expression is a critical component of brain physiology, but monitoring this expression in the living brain represents a major challenge. Here, we introduce a new paradigm called recovery of markers through insonation (REMIS) for noninvasive measurement of gene expression in the brain with cell type, spatial, and temporal specificity. Our approach relies on engineered protein markers that are produced in neurons but exit into the brain's interstitium. When ultrasound is applied to targeted brain regions, it opens the blood-brain barrier and releases these markers into the bloodstream. Once in blood, the markers can be readily detected using biochemical techniques. REMIS can noninvasively confirm gene delivery and measure endogenous signaling in specific brain sites through a simple insonation and a subsequent blood test. REMIS is reliable and demonstrated consistent improvement in recovery of markers from the brain into the blood. Overall, this work establishes a noninvasive, spatially specific method of monitoring gene delivery and endogenous signaling in the brain. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) survivors face debilitating long-term psychosocial consequences, including social isolation and depression. TBI modifies neurovascular physiology and behavior but the chronic physiological implications of altered brain perfusion on social interactions are unknown. Adult C57/BL6 male mice received a moderate cortical TBI, and social behaviors were assessed at baseline, 3-, 7-, 14-, 30-, and 60-days post injury (dpi). Magnetic resonance imaging (MRI, 9.4T) using dynamic susceptibility contrast perfusion weighted MRI were acquired. At 60dpi mice underwent histological angioarchitectural mapping. Analysis utilized standardized protocols followed by cross-correlation metrics. Social behavior deficits at 60dpi emerged as reduced interactions with a familiar cage-mate (partner) that mirrored significant reductions in cerebral blood flow (CBF) at 60dpi. CBF perturbations were dynamic temporally and across brain regions including regions known to regulate social behavior such as hippocampus, hypothalamus, and rhinal cortex. Social isolation in TBI-mice emerged with a significant decline in preference to spend time with a cage mate. Cortical vascular density was also reduced corroborating the decline in brain perfusion and social interactions. Thus, the late emergence of social interaction deficits mirrored the reduced vascular density and CBF in regions known to be involved in social behaviors. Vascular morphology and function improved prior to the late decrements in social function and our correlations strongly implicate a linkage between vascular density, cerebral perfusion, and social interactions. Our study provides a clinically relevant timeline of alterations in social deficits alongside functional vascular recovery that can guide future therapeutics. [ABSTRACT FROM AUTHOR]

Purpose: A growing body of evidence has shown that electroencephalography (EEG) is an interesting method of assessing the underlying brain physiology associated with disordered eating. Using EEG, we sought to evaluate brain reactivity to hyper-palatable food cues in undergraduate students with disordered eating behavior (DEB). Methods: After assessing the eating behaviors of twenty-six undergraduate students using the Eating Attitudes Test (EAT-26), electroencephalographic signals were recorded while the participants were presented with pictures of hyper-palatable food. The current study used a temporospatial principal component analysis (PCA) approach to identify event-related potential (ERP) responses that differed between DEB and non-DEB individuals. Results: A temporospatial PCA applied to the ERPs identified a positivity with a maximum amplitude at 347 ms at the occipital–temporal electrodes in response to pictures of hyper-palatable food. This positivity was correlated with the EAT-26 scores. Participants with DEB showed reduced positivities in this component compared with those without DEB. Conclusion: Our findings may reflect greater motivated attention toward hyper-palatable food cues in undergraduate students with DEB. These results are an important step toward obtaining a more refined understanding of specific abnormalities related to reactivity to food cues in this population. [ABSTRACT FROM AUTHOR]

Objective. To investigate if the use of vision therapy (VT) in convergence insufficiency (CI) has a significant neural impact and how it correlates with the clinical changes occurring with this option of treatment. Methods. A systematic review of the scientific literature was carried out in the PubMed and Scopus databases, where all the scientific literature on the neural impact of VT in CI was analyzed. A total of 17 articles were initially found and a detailed analysis was carried out. After full‐text reading, only four studies met the defined inclusion criteria. The following data from them were extracted: CI cases and controls, clinical and neural parameters evaluated, the neural response to VT observed, type of study, and VT performed. The quality of the studies was assessed using the GRADE tool. Results. Some neural changes have been reported after VT in CI with the use of functional magnetic resonance imaging (fMRI). Specifically, a modification of the functional activity of some brain areas (especially front fields, oculomotor vermis, and cerebellum) was found. However, contradictory findings in terms of the change in functional activity (increase or decrease) were found that might be associated to differences in fMRI protocols. In the GRADE analysis, serious concerns were found in the categories of risk of bias, inconsistency, indirectness, and imprecision, so the certainty of evidence for each outcome was very low. Conclusion. The research performed to this date does not allow confirming if there are neural changes occurring after vision therapy in patients with CI because the quality of the research performed on this issue is very low, with several methodological concerns. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases, and the most prevalent form of dementia. The main hallmarks for the diagnosis of AD are extracellular amyloid-beta (Aβ) plaque deposition and intracellular accumulation of highly hyperphosphorylated Tau protein as neurofibrillary tangles. The brain consumes more oxygen than any other organs, so it is more easily to be affected by hypoxia. Hypoxia has long been recognized as one of the possible causes of AD and other neurodegenerative diseases, but the exact mechanism has not been clarified. In this review, we will elucidate the connection between hypoxia-inducible factors-1α and AD, including its contribution to AD and its possible protective effects. Additionally, we will discuss the relationship between oxidative stress and AD as evidence show that oxidative stress acts on AD-related pathogenic factors such as mitochondrial dysfunction, Aβ deposition, inflammation, etc. Currently, there is no cure for AD. Given the close association between hypoxia, oxidative stress, and AD, along with current research on the protective effects of antioxidants against AD, we speculate that antioxidants could be a potential therapeutic approach for AD and worth further study. [ABSTRACT FROM AUTHOR]

Despite extensive studies published on the canine brain, inconsistencies and disagreements in the nomenclature and representation of various cerebral structures continue to exist. This study aimed to create a comprehensive mapping of the external architecture of the mesocephalic canine brain with a focus on the major gyri and sulci. Standardized dissection techniques were used on 20 ethically sourced brains obtained from 6 to 10-year-old dogs that were free of neurological disorders. Distinct gyri and sulci with unique locations and bordering structures were observed. Thus, it was possible to identify the often-ignored subprorean gyrus. In addition, this study was able to illustrate the unique locations and bordering structures of gyri and sulci. The findings can contribute to a consensus among researchers on the canine brain anatomy and assist in clarifying the inconsistencies in cerebral structure representation. Furthermore, the results of this study may hold significant implications for veterinary medicine and neuroscience and serve as a foundation for the development of diagnostic and therapeutic approaches for various neurological diseases in dogs. Our findings offer valuable insights into the unique evolutionary adaptations and specialized behaviors of the canine brain, thereby increasing awareness about the neural structures that enable dogs to demonstrate their unique traits. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) and inflammatory bowel disease (IBD) are chronic diseases affecting the central nervous system and gastrointestinal tract, respectively. Recent research suggests a bidirectional relationship between neurodegeneration in PD and intestinal inflammation in IBD. PD patients may experience gastrointestinal dysfunction over a decade before motor symptom onset, and IBD may increase the risk of developing PD. Despite the "gut-brain axis" concept, the underlying pathophysiological mechanisms of this potential association remain unclear. This study aimed to investigate the biological mechanisms of differentially expressed genes in PD and IBD using bioinformatics tools, providing novel insights into the co-diagnosis and treatment of these diseases. We constructed a gene marker for disease diagnosis and identified five important genes (BTK, NCF2, CRH, FCGR3A and SERPINA3). Through nomogram and decision tree analyses, we found that both the IBD and PD required only the expression levels of BTK and NCF2 for accurate discrimination. Additionally, small molecule drugs RO-90-7501 and MST-312 may be useful for the treatment of both IBD and PD. These findings offer new perspectives on the co-diagnosis and treatment of PD and IBD, and suggest that targeting BTK may be a promising therapeutic strategy for both diseases. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder caused by the accumulation of amyloid‐beta (Aβ) proteins and neurofibrillary tangles in the brain. There have been recent advancements in antiamyloid therapy for AD. This narrative review explores the recent advancements and challenges in antiamyloid therapy. In addition, a summary of evidence from antiamyloid therapy trials is presented with a focus on lecanemab. Lecanemab is the most recently approved monoclonal antibody that targets Aβ protofibrils for the treatment of patients with early AD and mild cognitive impairment (MCI). Lecanemab was the first drug shown to slow cognitive decline in patients with MCI or early onset AD dementia when administered as an infusion once every two weeks. In the Clarity AD trial, lecanemab was associated with infusion‐site reactions (26.4%) and amyloid‐related imaging abnormalities (12.6%). The clinical relevance and long‐term side effects of lecanemab require further longitudinal observation. However, several challenges must be addressed before the drug can be routinely used in clinical practice. The drug's route of administration, need for imaging and genetic testing, affordability, accessibility, infrastructure, and potential for serious side effects are some of these challenges. Lecanemab's approval has fueled interest in the potential of other antiamyloid therapies, such as donanemab. Future research must focus on developing strategies to prevent AD; identify easy‐to‐use validated plasma‐based assays; and discover newer user‐friendly, and cost‐effective drugs that target multiple pathways in AD pathology. [ABSTRACT FROM AUTHOR]

Introduction: Studies on the aging brain often occur in active settings, but comparatively few investigate brain activity in resting states. However, exploring brain activity in a resting state offers valuable insights into spontaneous neural processes unaffected by task-specific influences. Objective: To investigate the relationship between self-care practices, cognitive function, and patterns of brain activity in healthy older adults, taking into account predictions from aging brain models. Methodology: 77 older adults aged 61 to 87 completing a self-care practices questionnaire, neuropsychological tests, and resting-state electroencephalogram (EEG) recordings. Participants were classified into two groups according to their self-care practices: traditional self-care (T-SC) and developmental self-care (D-SC). Results: Although neuropsychological tests did not yield significant differences between the D-SC and T-SC groups, patterns of brain activity revealed distinct behaviors. The T-SC group demonstrated patterns more consistent with established aging brain models, contrasting with the D-SC group, which exhibited brain activity akin to that observed in younger adults. Specifically, the T-SC group displayed hyperactivation related to memory and executive function performance, alongside heightened alpha power in posterior regions. Furthermore, bilateral frontal activation in the beta band was evident. Conclusions: The findings suggest a nuanced relationship between self-care practices and brain activity in older adults. While the T-SC group demonstrated brain activity patterns consistent with conservative aging, indicating the preservation of typical aging characteristics, the D-SC group displayed activity suggestive of a potential protective effect. This effect may be linked to self-care strategies that foster development and resilience in cognitive aging. [ABSTRACT FROM AUTHOR]

As the most common cause of dementia, Alzheimer's disease (AD) is characterized by neurodegeneration and synaptic loss with an increasing prevalence in the elderly. Increased inflammatory responses triggers brain cells to produce pro-inflammatory cytokines and accelerates the Aβ accumulation, tau protein hyper-phosphorylation leading to neurodegeneration. Therefore, in this paper, we discuss the current understanding of how inflammation affects brain activity to induce AD pathology, the inflammatory biomarkers and possible therapies that combat inflammation for AD. [ABSTRACT FROM AUTHOR]

Introduction: Older adults experience less anxiety. We examined how memory of negative emotional images varied with age and may reflect age-related differences in anxiety. Methods: Fifty-one adults, age 22-80 years, underwent imaging with a memory task where negative and neutral images were displayed pseudo-randomly. They were queried post-scan about the images inter-mixed with an equal number of images never displayed. Sensitivity (d') and reporting bias (Z-score of false alarm rate; Z[FAR]) were quantified with signal detection theory. Results: Age was negatively correlated with both Spielberg State Trait Anxiety Inventory (STAI) state score and d' (negative - neutral) and positively with Z[FAR] (negative - neutral). However, STAI score and d' or Z[FAR] (negative - neutral) were not significantly correlated. In whole-brain regression, STAI score was correlated with higher activity of the right middle/superior temporal gyri/temporal parietal junction (MTG/STG/TPJ) for "negative correct - incorrect" - "neutral correct - incorrect" trials. Further, the MTG/STG/TPJ activity (β) was also negatively correlated with age. Mediation analyses supported a complete mediation model of age → less anxiety → less MTG/STG/TPJ β. Discussion: Together, the findings demonstrated age-related changes in negative emotional memory and how age-related reduction in anxiety is reflected in diminished temporoparietal cortical activities during encoding of negative emotional memory. [ABSTRACT FROM AUTHOR]