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Purpose: Detection and prediction of the rate of brain volume loss with age is a significant unmet need in patients with primary progressive multiple sclerosis (PPMS). In this study we construct detailed brain volume maps for PPMS patients. These maps compare age-related changes in both cortical and sub-cortical regions with those in healthy individuals. Methods: We conducted retrospective analyses of brain volume using T1-weighted Magnetic Resonance Imaging (MRI) scans of a large cohort of PPMS patients and healthy subjects. The volume of brain parenchyma (BP), cortex, white matter (WM), deep gray matter, thalamus, and cerebellum were measured using the robust SynthSeg segmentation tool. Age- and gender-related regression curves were constructed based on data from healthy subjects, with the 95% prediction interval adopted as the normality threshold for each brain region. Results: We analyzed 495 MRI scans from 169 PPMS patients, aged 20–79 years, alongside 563 exams from healthy subjects aged 20–86. Compared to healthy subjects, a higher proportion of PPMS patients showed lower than expected brain volumes in all regions except the cerebellum. The most affected areas were BP, WM, and thalamus. Lower brain volumes correlated with longer disease duration for BP and WM, and higher disability for BP, WM, cortex, and thalamus. Conclusions: Constructing age- and gender-related brain volume maps enabled identifying PPMS patients at a higher risk of brain volume loss. Monitoring these high-risk patients may lead to better treatment decisions and improve patient outcomes. [ABSTRACT FROM AUTHOR]

New human life begins in the uterus in a period of both extreme plasticity and sensitivity to environmental disturbances. The fetal stage is also a vital period for central nervous system development, with experiences at this point profoundly and permanently shaping brain structure and function. As such, some brain disorders may originate in utero. Glucocorticoids, a class of essential stress hormones, play indispensable roles in fetal development, but overexposure may have lasting impacts on the brain. In this review, we summarize data from recent clinical and non-clinical studies regarding alterations in fetal brains due to prenatal glucocorticoid overexposure that are associated with nervous system disorders. We discuss relevant changes to brain structure and cellular functions and explore the underlying molecular mechanisms. In addition, we summarize factors that may cause differential outcomes between varying brain regions, and outline clinically feasible intervention strategies that are expected to minimize negative consequences arising from fetal glucocorticoid overexposure. Finally, we highlight the need for experimental evidence aided by new technologies to clearly determine the effects of excessive prenatal glucocorticoid exposure. This review consolidates diverse findings to help researchers better understand the relationship between the prenatal glucocorticoid overexposure and the effects it has on various fetal brain regions, promoting further development of critical intervention strategies. [ABSTRACT FROM AUTHOR]

Children often show cognitive and affective traits that are similar to their parents. Although this indicates a transmission of phenotypes from parents to children, little is known about the neural underpinnings of that transmission. Here, we provide a general overview of neuroimaging studies that explore the similarity between parents and children in terms of brain structure and function. We notably discuss the aims, designs, and methods of these so-called intergenerational neuroimaging studies, focusing on two main designs: the parent-child design and the multigenerational design. For each design, we also summarize the major findings, identify the sources of variability between studies, and highlight some limitations and future directions. We argue that the lack of consensus in defining the parent-child transmission of brain structure and function leads to measurement heterogeneity, which is a challenge for future studies. Additionally, multigenerational studies often use measures of family resemblance to estimate the proportion of variance attributed to genetic versus environmental factors, though this estimate is likely inflated given the frequent lack of control for shared environment. Nonetheless, intergenerational neuroimaging studies may still have both clinical and theoretical relevance, not because they currently inform about the etiology of neuromarkers, but rather because they may help identify neuromarkers and test hypotheses about neuromarkers coming from more standard neuroimaging designs. Highlights: We review neuroimaging studies investigating neural markers of traits transmission. Studies have used both parent-child and multigenerational designs. Studies provide insights but suffer from lack of methodological standardization. Multigenerational studies should also account for shared environment. [ABSTRACT FROM AUTHOR]

Objectives: Prenatally diagnosed complex arachnoid cysts are very rare. While the true prenatal incidence is still unknown, they account for approximately 1% of intracranial masses in newborns. They rarely exhibit rapid growth or cause obstructive hydrocephalus, but if they increase to such a dimension during pregnancy, the ideal management is not well established. We present our detailed perinatal experience, covering prenatal diagnosis, a compassionate delivery process, and neonatal stabilization. Finally, a thorough postnatal neurosurgical intervention was performed. Initially, our focus was on the gradual reduction of cyst size as a primary effort, followed by subsequent definitive surgical treatment. Methods: This case series shows the treatment course of three fetuses with antenatally diagnosed large arachnoid cysts. We present pre- and postnatal management and imaging, as well as the surgical treatment plan and the available clinical course during follow-up. Results: Two girls and one boy were included in the current review. All three cases presented with prenatally diagnosed complex arachnoid cysts that increased in size during pregnancy. The mean gestational age at delivery was 35 weeks (range 32 to 37 weeks), and all patients were delivered by a caesarian section. Increasing head circumference and compression of brain structures were indications for delivery, as they are associated with a high risk of excess intracranial pressures and CSF diapedesis, as well as traumatic delivery and maternal complications. All cysts were supratentorial in location; one expanded into the posterior fossa, and one was a multicompartment cyst. All children underwent an initial surgical procedure within the first days of life. To relieve cyst pressure and achieve a reduction in head circumference, an ultrasound-guided or endoscopic-assisted internal shunt with drainage of the cyst to the ventricles or subdural/subarachnoid space was inserted. Definite surgical therapy consisted of cyst marsupialization and/or cysto-peritoneal shunt implantation. All children survived without severe neurodevelopmental impairments. Conclusion: With the cases presented, we demonstrate that the slow reduction of immense cyst size as an initial procedure until optimal requirements for final surgical treatment were achieved has proven to be optimal for neurological outcome. Special emphasis has to be taken on the delicate nature of premature newborn babies, and surgical steps have to be thoroughly considered within the interdisciplinary team. [ABSTRACT FROM AUTHOR]

Patients with pulmonary arterial hypertension (PAH) often present with anxiety, depression and cognitive deterioration. Structural changes in the cerebral cortex in PAH patients have also been reported in observational studies. PAH genome-wide association (GWAS) including 162,962 European individuals was used to assess genetically determined PAH. GWAS summary statistics were obtained for cognitive performance, depression, anxiety and alterations in cortical thickness (TH) or surface area (SA) of the brain cortex, respectively. Two-sample Mendelian randomization (MR) was performed. Finally, sensitivity analyses including Cochran's Q test, MR-Egger intercept test, leave-one-out analyses, and funnel plot was performed. PAH had no causal relationship with depression, anxiety, and cognitive performance. At the global level, PAH was not associated with SA or TH of the brain cortex; at the functional regional level, PAH increased TH of insula (P = 0.015), pars triangularis (P = 0.037) and pars opercularis (P = 0.010) without global weighted. After global weighted, PAH increased TH of insula (P = 0.004), pars triangularis (P = 0.032), pars opercularis (P = 0.007) and rostral middle frontal gyrus (P = 0.022) while reducing TH of inferior parietal (P = 0.004), superior parietal (P = 0.031) and lateral occipital gyrus (P = 0.033). No heterogeneity and pleiotropy were detected. The enrolled patients were all European and the causal relationship between PAH and the structure of the cerebral cortex in other populations remains unknown. Causal relationship between PAH and the brain cortical structure was implied, thus providing novel insights into the PAH associated neuropsychiatric symptoms. Using a Mendelian randomization study, a causal effect of PAH on the brain cortical structure was revealed, which suggested the presence of lung-brain axis. We acknowledge BioRender.com for the generation of cartoon figures. [Display omitted] • Using a Mendelian randomization study, we reveal the causal effect of PAH on the brain cortical structure, namely magnetic resonance imaging (MRI)-measure surficial areas and cortical thickness, which suggested the presence of lung-brain axis. • Using a Mendelian randomization study, it was revealed that PAH had no causal relationship with two kinds Neuropsychological disorders of depression and anxiety. • Using a Mendelian randomization study, it was revealed that PAH had no causal relationship with cognitive performance, in what is referred to general cognitive performance. fluid intelligence score and memory performance. [ABSTRACT FROM AUTHOR]

Background: Computer gaming has recently been suggested to be associated with benefits for cognition, but its impact on incident dementia remains uncertain. We aimed to investigate the observational associations of playing computer games with incident dementia, cognitive functions, and brain structural measures, and further explore the genetic associations between computer gaming and dementia. Methods: We included 471,346 White British participants without dementia at baseline based on the UK Biobank, and followed them until November 2022. We estimated the risk of dementia using Cox proportional hazard models, and assessed the changes of cognitive functions and brain structural measures using logistic regression models and linear regression models. Mendelian randomization (MR) analyses were performed to examine the association between genetically determined computer gaming and dementia. Results: High frequency of playing computer games was associated with decreased risk of incident dementia (HR, 0.81 [95% CI: 0.69, 0.94]). Individuals with high frequency of playing computer games had better performance in prospective memory (OR, 1.46 [1.26, 1.70]), reaction time (beta, -0.195 [-0.243, -0.147]), fluid intelligence (0.334 [0.286, 0.382]), numeric memory (0.107 [0.047, 0.166]), incorrect pairs matching (-0.253 [-0.302, -0.203]), and high volume of gray matter in hippocampus (0.078 [0.023, 0.134]). Genetically determined high frequency of playing computer games was associated with a low risk of dementia (OR, 0.37 [0.15, 0.91]). Conclusions: Computer gaming was associated with a decreased risk of dementia, favorable cognitive function, and better brain structure, suggesting that computer gaming could modulate cognitive function and may be a promising target for dementia prevention. [ABSTRACT FROM AUTHOR]

Background: Mitochondrial dysfunction is implicated in the neuropathology of bipolar disorder (BD). Higher circulating cell-free mitochondrial DNA (ccf-mtDNA), generally reflecting poorer mitochondrial health, has been associated with greater symptoms severity in BD. The current study examines the association of serum ccf-mtDNA and brain structure in relation to youth BD. We hypothesized that higher ccf-mtDNA will be associated with measures of lower brain structure, particularly in the BD group. Methods: Participants included 40 youth (BD, n = 19; Control group [CG], n = 21; aged 13–20 years). Serum ccf-mtDNA levels were assayed. T1-weighted brain images were acquired using 3T-MRI. Region of interest (ROI) analyses examined prefrontal cortex (PFC) and whole brain gray matter, alongside exploratory vertex-wise analyses. Analyses examined ccf-mtDNA main-effects and ccf-mtDNA-by-diagnosis interaction effects controlling for age, sex, and intracranial volume. Results: There was no significant difference in ccf-mtDNA levels between BD and CG. In ROI analyses, higher ccf-mtDNA was associated with higher PFC surface area (SA) (β = 0.32 p < 0.001) and PFC volume (β = 0.32 p = 0.002) in the overall sample. In stratified analyses, higher ccf-mtDNA was associated with higher PFC SA within both subgroups (BD: β = 0.39 p = 0.02; CG: β = 0.24 p = 0.045). Higher ccf-mtDNA was associated with higher PFC volume within the BD group (β = 0.39 p = 0.046). In vertex-wise analyses, higher ccf-mtDNA was associated with higher SA and volume in frontal clusters within the overall sample and within the BD group. There were significant ccf-mtDNA-by-diagnosis interactions in three frontal and parietal clusters, whereby higher ccf-mtDNA was associated with higher neurostructural metrics in the BD group but lower neurostructural metrics in CG. Conclusions: Contrasting our hypothesis, higher ccf-mtDNA was consistently associated with higher, rather than lower, regional neuralstructural metrics among youth with BD. While this finding may reflect a compensatory mechanism, future repeated-measures prospective studies evaluating the inter-relationship among ccf-mtDNA, mood, and brain structure across developmental epochs and illness stages are warranted. [ABSTRACT FROM AUTHOR]

Objectives: This study aimed to evaluate the potential clinical value of a new brain age prediction model as a single interpretable variable representing the condition of our brain. Among many clinical use cases, brain age could be a novel outcome measure to assess the preventive effect of life-style interventions. Methods: The REMEMBER study population (N = 742) consisted of cognitively healthy (HC,N = 91), subjective cognitive decline (SCD,N = 65), mild cognitive impairment (MCI,N = 319) and AD dementia (ADD,N = 267) subjects. Automated brain volumetry of global, cortical, and subcortical brain structures computed by the CE-labeled and FDA-cleared software icobrain dm (dementia) was retrospectively extracted from T1-weighted MRI sequences that were acquired during clinical routine at participating memory clinics from the Belgian Dementia Council. The volumetric features, along with sex, were combined into a weighted sum using a linear model, and were used to predict 'brain age' and 'brain predicted age difference' (BPAD = brain age–chronological age) for every subject. Results: MCI and ADD patients showed an increased brain age compared to their chronological age. Overall, brain age outperformed BPAD and chronological age in terms of classification accuracy across the AD spectrum. There was a weak-to-moderate correlation between total MMSE score and both brain age (r = -0.38,p <.001) and BPAD (r = -0.26,p <.001). Noticeable trends, but no significant correlations, were found between BPAD and incidence of conversion from MCI to ADD, nor between BPAD and conversion time from MCI to ADD. BPAD was increased in heavy alcohol drinkers compared to non-/sporadic (p =.014) and moderate (p =.040) drinkers. Conclusions: Brain age and associated BPAD have the potential to serve as indicators for, and to evaluate the impact of lifestyle modifications or interventions on, brain health. [ABSTRACT FROM AUTHOR]

Recent cellular-level volumetric brain reconstructions have revealed high levels of anatomic complexity. Determining which structural aspects of the brain to focus on, especially when comparing with computational models and other organisms, remains a major challenge. Here we quantify aspects of this complexity and show evidence that brain anatomy satisfies universal scaling laws, establishing the notion of structural criticality in the cellular structure of the brain. Our framework builds upon understanding of critical systems to provide clear guidance in selecting informative structural properties of cellular brain anatomy. As an illustration, we obtain estimates for critical exponents in the human, mouse and fruit fly brains and show that they are consistent between organisms, to the extent that data limitations allow. Such universal quantities are robust to many of the microscopic details of the cellular structures of individual brains, providing a key step towards generative computational models of the cellular structure of the brain, and also clarifying in which sense one animal may be a suitable anatomic model for another. Cellular-level partial brain reconstructions have revealed the anatomic complexity of the brains of multiple organisms. Here, the authors quantify aspects of this complexity, demonstrating that across organisms the cellular structure of the brain shows universal scaling properties associated with being in the vicinity of criticality. [ABSTRACT FROM AUTHOR]

Obesity and food addiction are associated with distinct brain signatures related to reward processing, and early life adversity (ELA) also increases alterations in these same reward regions. However, the neural mechanisms underlying the effect of early life adversity on food addiction are unknown. Therefore, the aim of this study was to examine the interactions between ELA, food addiction, and brain morphometry in individuals with obesity. 114 participants with high body mass index (BMI) underwent structural MRIs, and completed several questionnaires (e.g., Yale Food Addiction Scale (YFAS), Brief Resilience Scale (BRS), Early Traumatic Inventory (ETI)). Freesurfer 6 was applied to generate the morphometry of brain regions. A multivariate pattern analysis was used to derive brain morphometry patterns associated with food addiction. General linear modeling and mediation analyses were conducted to examine the effects of ELA and resilience on food addiction in individuals with obesity. Statistical significance was determined at a level of p < 0.05. High levels of ELA showed a strong association between reward control brain signatures and food addiction (p = 0.03). Resilience positively mediated the effect of ELA on food addiction (B = 0.02, p = 0.038). Our findings suggest that food addiction is associated with brain signatures in motivation and reward processing regions indicative of dopaminergic dysregulation and inhibition of cognitive control regions. These mechanistic variabilities along with early life adversity suggest increased vulnerability to develop food addiction and obesity in adulthood, which can buffer by the neuroprotective effects of resilience, highlighting the value of incorporating cognitive appraisal into obesity therapeutic regimens. [ABSTRACT FROM AUTHOR]

Background: Previous studies have linked adolescent motherhood to adverse neurodevelopmental outcomes in offspring, yet the sex-specific effect and underlying mechanisms remain unclear. Methods: This study included 6952 children aged 9–11 from the Adolescent Brain Cognitive Development study. The exposed group consisted of children of mothers < 20 years at the time of birth, while the unexposed group was composed of children of mothers aged 20–35 at birth. We employed a generalized linear mixed model to investigate the associations of adolescent motherhood with cognitive, behavioral, and autistic-like traits in offspring. We applied an inverse-probability-weighted marginal structural model to examine the potential mediating factors including adverse perinatal outcomes, family conflict, and brain structure alterations. Results: Our results revealed that children of adolescent mothers had significantly lower cognitive scores (β, − 2.11, 95% CI, − 2.90 to − 1.31), increased externalizing problems in male offspring (mean ratio, 1.28, 95% CI, 1.08 to 1.52), and elevated internalizing problems (mean ratio, 1.14, 95% CI, 0.99 to 1.33) and autistic-like traits (mean ratio, 1.22, 95% CI, 1.01 to 1.47) in female. A stressful family environment mediated ~ 70% of the association with internalizing problems in females, ~ 30% with autistic-like traits in females, and ~ 20% with externalizing problems in males. Despite observable brain morphometric changes related to adolescent motherhood, these did not act as mediating factors in our analysis, after adjusting for family environment. No elevated rate of adverse perinatal outcomes was observed in the offspring of adolescent mothers in this study. Conclusions: Our results reveal distinct sex-specific neurodevelopmental outcomes impacts of being born to adolescent mothers, with a substantial mediating effect of family environment on behavioral outcomes. These findings highlight the importance of developing sex-tailored interventions and support the hypothesis that family environment significantly impacts the neurodevelopmental consequences of adolescent motherhood. [ABSTRACT FROM AUTHOR]

The hippocampus is a brain structure that plays key roles in a variety of cognitive processes. Critically, a wide range of neurological disorders are associated with degeneration of the hippocampal microstructure, defined as neurons, dendrites, glial cells, and more. Thus, the hippocampus is a key target for methods that are sensitive to these microscale properties. Diffusion MRI is one such method, which can noninvasively probe neural architecture. Here we review the extensive use of diffusion MRI to capture hippocampal microstructure in both health and disease. The results of these studies indicate that (1) diffusion tensor imaging is sensitive but not specific to the hippocampalmicrostructure; (2) biophysical modeling of diffusionMRI signals is a promising avenue to capture more specific aspects of the hippocampal microstructure; (3) use of ultra-short diffusion times have shown unique laminar-specific microstructure and response to hippocampal injury; (4) dispersion of microstructure is likely abundant in the hippocampus; and (5) the angular richness of the diffusion MRI signal can be leveraged to improve delineation of the internal hippocampal circuitry. Overall, extant findings suggest that diffusion MRI offers a promising avenue for characterizing hippocampal microstructure. [ABSTRACT FROM AUTHOR]

Background: Migraine is a neurological disease with a significant genetic component and is characterized by recurrent and prolonged episodes of headache. Previous epidemiological studies have reported a higher risk of dementia in migraine patients. Neuroimaging studies have also shown structural brain atrophy in regions that are common to migraine and dementia. However, these studies are observational and cannot establish causality. The present study aims to explore the genetic causal relationship between migraine and dementia, as well as the mediation roles of brain structural changes in this association using Mendelian randomization (MR). Methods: We collected the genome-wide association study (GWAS) summary statistics of migraine and its two subtypes, as well as four common types of dementia, including Alzheimer's disease (AD), vascular dementia, frontotemporal dementia, and Lewy body dementia. In addition, we collected the GWAS summary statistics of seven longitudinal brain measures that characterize brain structural alterations with age. Using these GWAS, we performed Two-sample MR analyses to investigate the causal effects of migraine and its two subtypes on dementia and brain structural changes. To explore the possible mediation of brain structural changes between migraine and dementia, we conducted a two-step MR mediation analysis. Results: The MR analysis demonstrated a significant association between genetically predicted migraine and an increased risk of AD (OR = 1.097, 95% CI = [1.040, 1.158], p = 7.03 × 10− 4). Moreover, migraine significantly accelerated annual atrophy of the total cortical surface area (-65.588 cm2 per year, 95% CI = [-103.112, -28.064], p = 6.13 × 10− 4) and thalamic volume (-9.507 cm3 per year, 95% CI = [-15.512, -3.502], p = 1.91 × 10− 3). The migraine without aura (MO) subtype increased the risk of AD (OR = 1.091, 95% CI = [1.059, 1.123], p = 6.95 × 10− 9) and accelerated annual atrophy of the total cortical surface area (-31.401 cm2 per year, 95% CI = [-43.990, -18.811], p = 1.02 × 10− 6). The two-step MR mediation analysis revealed that thalamic atrophy partly mediated the causal effect of migraine on AD, accounting for 28.2% of the total effect. Discussion: This comprehensive MR study provided genetic evidence for the causal effect of migraine on AD and identified longitudinal thalamic atrophy as a potential mediator in this association. These findings may inform brain intervention targets to prevent AD risk in migraine patients. [ABSTRACT FROM AUTHOR]

Technical development over the last few decades has resulted in the emergence of complex data, in many cases functional data (FD). This type of data can emerge in many medical studies which are geared towards detecting diseases, predicting their course or evaluating the response to a therapy, to name a few. Thus, it is very useful to have statistical methods enabling us to evaluate diagnostic tests based on functional biomarkers. In fact, a diagnostic test that uses functional variables as biomarkers has been developed recently. Their authors proposed a functional version of ROC analysis, resulting in an empirical estimate of the functional ROC curve. In order to improve this methodology, the present paper proposes a procedure to obtain a smooth version of non-parametric estimator of the ROC curve. In addition, a comprehensive simulation study lets to investigate the discriminatory and predictive abilities of the resulting functional diagnostic test. Two examples with real medical data illustrate the approach developed: one deals with gene expression levels for tumoural/normal samples of prostate cancer; the other dataset is about white matter structures in the brain in multiple sclerosis patients. [ABSTRACT FROM AUTHOR]

Paraventricular thalamus (PVT) plays important roles in the regulation of emotion and motivation through connecting many brain structures including the midbrain and the limbic system. Although acetylcholine (ACh) neurons of the midbrain were reported to send projections to PVT, little is known about how cholinergic signaling regulates PVT neurons. Here, we used both RNAscope and slice patch‐clamp recordings to characterize cholinergic receptor expression and ACh modulation of PVT neurons in mice. We found ACh excited a majority of anterior PVT (aPVT) neurons but predominantly inhibited posterior PVT (pPVT) neurons. Compared to pPVT with more inhibitory M2 receptors, aPVT expressed higher levels of all excitatory receptor subtypes including nicotinic α4, α7, and muscarinic M1 and M3. The ACh‐induced excitation was mimicked by nicotine and antagonized by selective blockers for α4β2 and α7 nicotinic ACh receptor (nAChR) subtypes as well as selective antagonists for M1 and M3 muscarinic ACh receptors (mAChR). The ACh‐induced inhibition was attenuated by selective M2 and M4 mAChR receptor antagonists. Furthermore, we found ACh increased the frequency of excitatory postsynaptic currents (EPSCs) on a majority of aPVT neurons but decreased EPSC frequency on a larger number of pPVT neurons. In addition, ACh caused an acute increase followed by a lasting reduction in inhibitory postsynaptic currents (IPSCs) on PVT neurons of both subregions. Together, these data suggest that multiple AChR subtypes coordinate a differential modulation of ACh on aPVT and pPVT neurons. [ABSTRACT FROM AUTHOR]

The central nervous system (CNS) is widely recognized as the only organ system without lymphatic capillaries to promote the removal of interstitial metabolic by‐products. Thus, the newly identified glymphatic system which provides a pseudolymphatic activity in the nervous system has been focus of latest research in neurosciences. Also, findings reported that, sleep stimulates the elimination actions of glymphatic system and is linked to normal brain homeostatis. The CNS is cleared of potentially hazardous compounds via the glymphatic system, particularly during sleep. Any age‐related alterations in brain functioning and pathophysiology of various neurodegenerative illnesses indicates the disturbance of the brain's glymphatic system. In this context, β‐amyloid as well as tau leaves the CNS through the glymphatic system, it's functioning and CSF discharge markedly altered in elderly brains as per many findings. Thus, glymphatic failure may have a potential mechanism which may be therapeutically targetable in several neurodegenerative and age‐associated cognitive diseases. Therefore, there is an urge to focus for more research into the connection among glymphatic system and several potential brain related diseases. Here, in our current review paper, we reviewed current research on the glymphatic system's involvement in a number of prevalent neurodegenerative and neuropsychiatric diseases and, we also discussed several therapeutic approaches, diet and life style modifications which might be used to acquire a more thorough performance and purpose of the glymphatic system to decipher novel prospects for clinical applicability for the management of these diseases. Key points: Age‐associated dementia is growing rapidly leading to various neurological diseases and is currently one of the prime reasons for diseases and related morbidity which impacts a wide range of populations.Recently discovered glymphatic system, through which CNS is cleared of potentially harmful substances and plays a significant role in modulating various neurodegenerative and neuropsychiatric illnesses.To avert these diseases various natural interventions like traditional herbal medicine, non‐invasive neurological stimulation, regular sleep cycle and dietary additives may ameliorate disease pathogenesis by improving glymphatic activity are recently identified.Furthermore, investigations are going on the role of nutrigenomics and micronutrients in boosting the activity of glymphatic clearance in various neurological diseases. [ABSTRACT FROM AUTHOR]

Depression and Alzheimer's disease (AD) are substantial public health concerns. In the past decades, a link between the 2 disease entities has received extensive acknowledgment, yet the complex nature of this relationship demands further clarification. Some evidence indicates that midlife depression may be an AD risk factor, while a chronic course of depression in late life may be a precursor to or symptom of dementia. Recently, multiple pathophysiological mechanisms have been proposed to underlie the bidirectional relationship between depression and AD, including genetic predisposition, immune dysregulation, accumulation of AD-related biomarkers (e.g., amyloid-β and tau), and alterations in brain structure. Accordingly, numerous therapeutic approaches, such as pharmacology treatments, psychotherapy, and lifestyle interventions, have been suggested as potential means of interfering with these pathways. However, the current literature on this topic remains fragmented and lacks a comprehensive review characterizing the association between depression and AD. In this review, we aim to address these gaps by providing an overview of the co-occurrence and temporal relationship between depression and AD, as well as exploring their underlying mechanisms. We also examine the current therapeutic regimens for depression and their implications for AD management and outline key challenges facing the field. [ABSTRACT FROM AUTHOR]

Objectives Generativity, the desire and action to improve the well-being of younger generations, is associated with purpose in life among older adults. However, the neurobehavioral factors supporting the relationship between generativity and purpose in life remain unknown. This study aims to identify the functional neuroanatomy of generativity and mechanisms linking generativity with purpose in life in at-risk older adults. Methods Fifty-eight older adults (mean age = 70.8, SD =  5.03, 45 females) with a family history of Alzheimer's disease (AD) were recruited from the PREVENT-AD cohort. Participants underwent brain imaging and completed questionnaires assessing generativity, social support, and purpose in life. Mediation models examined whether social support mediated the association between generativity and purpose in life. Seed-to-voxel analyses investigated the association between generativity and resting-state functional connectivity (rsFC) to the ventromedial prefrontal cortex (vmPFC) and ventral striatum (VS), and whether this rsFC moderated the relationship between generativity and purpose in life. Results Affectionate social support mediated the association between generative desire and purpose in life. Generative desire was associated with rsFC between VS and precuneus, and, vmPFC and right dorsolateral prefrontal cortex (rdlPFC). The vmPFC–rdlPFC rsFC moderated the association between generative desire and purpose in life. Discussion These findings provide insight into how the brain supports complex social behavior and, separately, purpose in life in at-risk aging. Affectionate social support may be a putative target process to enhance purpose in life in older adults. This knowledge contributes to future developments of personalized interventions that promote healthy aging. [ABSTRACT FROM AUTHOR]

Objectives It is well known that low educational attainment is associated with cognitive function decline in older age. Childhood book availability may help to preserve cognitive function in older adults with low education. The study objective was to examine the association between childhood book availability and cognitive function among older adults with low educational attainment, and to investigate the mediating effect of the volume of reading-related brain regions (e.g. superior temporal cortex). Methods A cross-sectional study of community-dwelling older Japanese adults aged 65–84 years was conducted (n  = 474). Cognitive function was assessed using the Mini-Mental State Examination (MMSE). Childhood book availability was assessed using a retrospective questionnaire. Brain region volume was measured using magnetic resonance imaging. Multivariate regression modeling and structural equation modeling were used for analysis. Results Both high educational attainment and childhood book availability were independently associated with high MMSE score. Stratification of educational level showed that childhood book availability was positively associated with MMSE score among participants with low educational attainment (coefficient = 1.48, 95% confidence interval [CI]: 0.31 to 2.66), but not among those with moderate or high educational attainment (coefficient = −0.01, 95% CI: −1.44 to 1.42 and −1.21, 95% CI: −3.85 to 1.42, respectively). Among participants with low educational attainment, left superior temporal cortex volume mediated the association between childhood book availability and MMSE score. Discussion The availability of books in childhood helps to preserve cognitive function in older adults with low education via left superior temporal cortex volume. Further research is needed to replicate these findings. [ABSTRACT FROM AUTHOR]

The exploration of cannabis, particularly its legitimisation and multifaceted uses, is pivotal in understanding its historical significance, chemical composition, therapeutic potential, and societal implications. This narrative review traverses millennia of cannabis usage for medicinal, recreational, and spiritual purposes, juxtaposed with contemporary legislative shifts, notably in the United States. As perceptions evolve, especially with state-level legalisation contrasting federal prohibition, the review scrutinises the burgeoning use of cannabis products, particularly among youth, and the evolving regulatory frameworks. Neurological effects of cannabis use, including impacts on brain structure and function, are examined alongside potential benefits and risks in various medical contexts. Challenges in conducting rigorous clinical research, primarily due to legal and pharmaceutical constraints, are outlined. The review delves into the complexities of cannabis usage during pregnancy and the conflicting scientific data, presenting challenges in advising expectant mothers. Cannabis' diverse applications in treating various disorders, ranging from chronic pain to neurological conditions, are explored, shedding light on the potential benefits and limitations. The review highlights the pharmacological dynamics and clinical implications of cannabis-based therapies, emphasising the need for further research to elucidate their efficacy and long-term safety comprehensively. Moreover, the review discusses the pros and cons of CB therapy with high-Cannabidiol (CBD) medicinal cannabis, addressing challenges such as product quality, safety concerns, potential psychoactive effects, drug interactions, and limited research. It underscores the importance of informed decision-making and personalised guidance in navigating the complexities of CB therapy. In conclusion, while cannabis exhibits a wide range of potential medical applications, further research is essential to fully comprehend its therapeutic potential and weigh the associated risks. The review contributes to informed discourse and evidence-based policymaking, emphasising the need for continued research to unlock the full potential of cannabis in healthcare. [ABSTRACT FROM AUTHOR]

Purpose: Knowledge of neurovascular anatomy is vital for neurosurgeons, neurologists, neuro-radiologists and anatomy students, amongst others, to fully comprehend the brain's anatomy with utmost depth. This paper aims to enhance the foundational knowledge of novice physicians in this area. Method: A comprehensive literature review was carried out by searching the PubMed and Google Scholar databases using primary keywords related to brain vasculature, without date restrictions. The identified literature was meticulously examined and scrutinized. In the process of screening pertinent papers, further articles and book chapters were obtained through analysis and additional assessing of the reference lists. Additionally, four formalin-fixed, color latex-injected cadaveric specimens preserved in 70% ethanol solution were dissected under surgical microscope (Leica Microsystems Inc, 1700 Leider Ln, Buffalo Grove, IL 60089 USA). Using microneurosurgical as well as standard instruments, and a high-speed surgical drill (Stryker Instruments 1941 Stryker Way Portage, MI 49002 USA). Ulterior anatomical dissection was documented in microscopic images. Results: Encephalic circulation functions as a complex network of intertwined vessels. The Internal Carotid Arteries (ICAs) and the Vertebral Arteries (VAs), form the anterior and posterior arterial circulations, respectively. This work provides a detailed exploration of the neurovascular anatomy of the anterior circulation and its key structures, such as the Anterior Cerebral Artery (ACA) and the Middle Cerebral Artery (MCA). Embryology is also briefly covered, offering insights into the early development of the vascular structures of the central nervous system. Cerebral venous system was detailed, highlighting the major veins and tributaries involved in the drainage of blood from the intracranial compartment, with a focus on the role of the Internal Jugular Veins (IJVs) as the primary, although not exclusive, deoxygenated blood outflow pathway. Conclusion: This work serves as initial guide, providing essential knowledge on neurovascular anatomy, hoping to reduce the initial impact when tackling the subject, albeit the intricate vasculature of the brain will necessitate further efforts to be conquered, that being crucial for neurosurgical and neurology related practice and clinical decision-making. [ABSTRACT FROM AUTHOR]

High-intensity magnetic resonance-guided focused ultrasound (MRgFUS) is a non-invasive therapy to lesion brain tissue, used clinically in patients and pre-clinically in several animal models. Challenges with focused ablation in rodent brains can include skull and near-field heating and accurately targeting small and deep brain structures. We overcame these challenges by creating a novel method consisting of a craniectomy skull preparation, a high-frequency transducer (3 MHz) with a small ultrasound focal spot, a transducer positioning system with an added manual adjustment of ∼0.1 mm targeting accuracy, and MR acoustic radiation force imaging for confirmation of focal spot placement. The study consisted of two main parts. First, two skull preparation approaches were compared. A skull thinning approach (n = 7 lesions) was compared to a craniectomy approach (n = 22 lesions), which confirmed a craniectomy was necessary to decrease skull and near-field heating. Second, the two transducer positioning systems were compared with the fornix chosen as a subcortical ablation target. We evaluated the accuracy of targeting using histologic methods from a high-frequency transducer with a small ultrasound focal spot and MR acoustic radiation force imaging. Comparing a motorized adjustment system (∼1 mm precision, n = 17 lesions) to the motorized system with an added micromanipulator (∼0.1 mm precision, n = 14 lesions), we saw an increase in the accuracy of targeting the fornix by 133%. The described work allows for repeatable and accurate targeting of small and deep structures in the rodent brain, such as the fornix, enabling the investigation of neurological disorders in chronic disease models. [ABSTRACT FROM AUTHOR]

Production of metal debris from implant wear and corrosion processes is now a well understood occurrence following hip arthroplasty. Evidence has shown that metal ions can enter the bloodstream and travel to distant organs including the brain, and in extreme cases, can induce sensorial and neurological diseases. Our objective was tosimultaneously analyze brain anatomy and physiology in patients with long‐term and well‐functioning implants. Included were subjects who had received total hip or hip resurfacing arthroplastywith an implantation time of a minimum of 7 years (n = 28) and age‐ and sex‐matched controls (n = 32). Blood samples were obtained to measure ion concentrations of cobalt and chromium, and the Montreal Cognitive Assessment was performed. 3T MRI brain scans were completed with an MPRAGE sequence for ROI segmentation and multiecho gradient echo sequences to generate QSM and R2* maps. Mean QSM and R2* values were recorded for five deep brain and four middle and cortical brain structures on both hemispheres: pallidum, putamen, caudate, amygdala, hippocampus, anterior cingulate, inferior temporal, and cerebellum. No differences in QSM or R2* or cognition scores were found between both groups (p > 0.6654). No correlation was found between susceptibility and blood ion levels for cobalt or chromium in any region of the brain. No correlation was found between blood ion levels and cognition scores. Clinical significance: Results suggest that metal ions released by long‐term and well‐functioning implants do not affect brain integrity. [ABSTRACT FROM AUTHOR]

Objective: Along with the known effects of stress on brain structure and inflammatory processes, increasing evidence suggest a role of chronic stress in the pathogenesis of Alzheimer's disease (AD). We investigated the association of accumulated stressful life events (SLEs) with AD pathologies, neuroinflammation, and gray matter (GM) volume among cognitively unimpaired (CU) individuals at heightened risk of AD. Methods: This cross‐sectional cohort study included 1,290 CU participants (aged 48–77) from the ALFA cohort with SLE, lumbar puncture (n = 393), and/or structural magnetic resonance imaging (n = 1,234) assessments. Using multiple regression analyses, we examined the associations of total SLEs with cerebrospinal fluid (1) phosphorylated (p)‐tau181 and Aβ1–42/1–40 ratio, (2) interleukin 6 (IL‐6), and (3) GM volumes voxel‐wise. Further, we performed stratified and interaction analyses with sex, history of psychiatric disease, and evaluated SLEs during specific life periods. Results: Within the whole sample, only childhood and midlife SLEs, but not total SLEs, were associated with AD pathophysiology and neuroinflammation. Among those with a history of psychiatric disease SLEs were associated with higher p‐tau181 and IL‐6. Participants with history of psychiatric disease and men, showed lower Aβ1–42/1–40 with higher SLEs. Participants with history of psychiatric disease and women showed reduced GM volumes in somatic regions and prefrontal and limbic regions, respectively. Interpretation: We did not find evidence supporting the association of total SLEs with AD, neuroinflammation, and atrophy pathways. Instead, the associations appear to be contingent on events occurring during early and midlife, sex and history of psychiatric disease. ANN NEUROL 2024;95:1058–1068 [ABSTRACT FROM AUTHOR]

Physical activity is a protective factor against brain atrophy, while loss of brain volume could also be a determinant of physical activity. Therefore, we aimed to explore the bidirectional association of physical activity with brain structures in middle-aged and older adults from the UK Biobank. Overall, 3027 participants (62.45 ± 7.27 years old, 51.3% females) had data at two time points. Hippocampal volume was associated with total (β=0.048, p FDR =0.016) and household (β=0.075, p FDR <0.001) physical activity. Global fractional anisotropy (β=0.042, p FDR =0.028) was also associated with household physical activity. In the opposite direction, walking was negatively associated with white matter volume (β=-0.026, p FDR =0.008). All these associations were confirmed by the linear mixed models. Interestingly, sports at baseline were linked to hippocampal and frontal cortex volumes at follow-up but these associations disappeared after adjusting for multiple comparisons (p all >0.104). In conclusion, we found more consistent evidence that a healthier brain structure predicted higher physical activity levels than for the inverse, more established relationship. • The association between brain structure and physical activity seems more consistent. • Hippocampal, and global fractional anisotropy linked to housework at follow-up. • Sports were borderline linked to hippocampal and frontal volumes at follow-up. [ABSTRACT FROM AUTHOR]

Greater engagement in cognitively stimulating activities (CSA) during adulthood has been shown to protect against neurocognitive decline, but no studies have investigated whether CSA during childhood protects against effects of brain changes on cognition later in life. The current study tested the moderating role of childhood CSA in the relationships between brain structure and cognitive performance during adulthood. At baseline (N=250) and 5-year follow-up (N=204) healthy adults aged 20–80 underwent MRI to assess four structural brain measures and completed neuropsychological tests to measure three cognitive domains. Participants were categorized into low and high childhood CSA based on self-report questionnaires. Results of multivariable linear regressions analyzing interactions between CSA, brain structure, and cognition showed that higher childhood CSA was associated with a weaker relationship between cortical thickness and memory at baseline, and attenuated the effects of change in cortical thickness and brain volume on decline in processing speed over time. These findings suggest higher CSA during childhood may mitigate the effects of brain structure changes on cognitive function later in life. • Childhood cognitively stimulating activities (CSA) impact adult cognitive function. • Childhood CSA attenuates relationship between cortical thickness and memory. • CSA mitigates effect of cortical thickness and brain volume on speed longitudinally. • Childhood CSA may contribute to cognitive reserve that is protective later in life.. [ABSTRACT FROM AUTHOR]

Focal structural damage to white matter tracts can result in functional deficits in stroke patients. Traditional voxel‐based lesion‐symptom mapping is commonly used to localize brain structures linked to neurological deficits. Emerging evidence suggests that the impact of structural focal damage may extend beyond immediate lesion sites. In this study, we present a disconnectome mapping approach based on support vector regression (SVR) to identify brain structures and white matter pathways associated with functional deficits in stroke patients. For clinical validation, we utilized imaging data from 340 stroke patients exhibiting motor deficits. A disconnectome map was initially derived from lesions for each patient. Bootstrap sampling was then employed to balance the sample size between a minority group of patients exhibiting right or left motor deficits and those without deficits. Subsequently, SVR analysis was used to identify voxels associated with motor deficits (p <.005). Our disconnectome‐based analysis significantly outperformed alternative lesion‐symptom approaches in identifying major white matter pathways within the corticospinal tracts associated with upper–lower limb motor deficits. Bootstrapping significantly increased the sensitivity (80%–87%) for identifying patients with motor deficits, with a minimum lesion size of 32 and 235 mm3 for the right and left motor deficit, respectively. Overall, the lesion‐based methods achieved lower sensitivities compared with those based on disconnection maps. The primary contribution of our approach lies in introducing a bootstrapped disconnectome‐based mapping approach to identify lesion‐derived white matter disconnections associated with functional deficits, particularly efficient in handling imbalanced data. [ABSTRACT FROM AUTHOR]

Visual circuit development is characterized by subdivision of neuropils into layers that house distinct sets of synaptic connections. We find that, in the Drosophila medulla, this layered organization depends on the axon guidance regulator Plexin A. In Plexin A null mutants, synaptic layers of the medulla neuropil and arborizations of individual neurons are wider and less distinct than in controls. Analysis of semaphorin function indicates that Semaphorin 1a, acting in a subset of medulla neurons, is the primary partner for Plexin A in medulla lamination. Removal of the cytoplasmic domain of endogenous Plexin A has little effect on the formation of medulla layers; however, both null and cytoplasmic domain deletion mutations of Plexin A result in an altered overall shape of the medulla neuropil. These data suggest that Plexin A acts as a receptor to mediate morphogenesis of the medulla neuropil, and as a ligand for Semaphorin 1a to subdivide it into layers. Its two independent functions illustrate how a few guidance molecules can organize complex brain structures by each playing multiple roles. [ABSTRACT FROM AUTHOR]

Consciousness can be conceptualized as varying along at least two dimensions: the global state of consciousness and the content of conscious experience. Here, we highlight the cellular and systems-level contributions of the thalamus to conscious state and then argue for thalamic contributions to conscious content, including the integrated, segregated, and continuous nature of our experience. We underscore vital, yet distinct roles for core- and matrix-type thalamic neurons. Through reciprocal interactions with deep-layer cortical neurons, matrix neurons support wakefulness and determine perceptual thresholds, whereas the cortical interactions of core neurons maintain content and enable perceptual constancy. We further propose that conscious integration, segregation, and continuity depend on the convergent nature of corticothalamic projections enabling dimensionality reduction, a thalamic reticular nucleus-mediated divisive normalization-like process, and sustained coherent activity in thalamocortical loops, respectively. Overall, we conclude that the thalamus plays a central topological role in brain structures controlling conscious experience. Cellular and systems neuroscience points to a thalamic contribution to consciousness. Matrix-thalamocortical loops support wakefulness and perceptual threshold, and core-thalamocortical loops maintain content and enable perceptual constancy. The mesoscale architecture of these loops may explain general properties of conscious contents. [ABSTRACT FROM AUTHOR]

Animals must distinguish the sensory consequences of self-generated movements (reafference) from those of other-generated movements (exafference). Only self-generated movements entail the production of motor copies (i.e., corollary discharges), which are compared with reafference in the cerebellum to compute predictive or internal models of movement. Internal models emerge gradually over the first three postnatal weeks in rats through a process that is not yet fully understood. Previously, we demonstrated in postnatal day (P) 8 and P12 rats that precerebellar nuclei convey corollary discharge and reafference to the cerebellum during active (REM) sleep when pups produce limb twitches. Here, recording from a deep cerebellar nucleus (interpositus, IP) in P12 rats of both sexes, we compared reafferent and exafferent responses with twitches and limb stimulations, respectively. As expected, most IP units showed robust responses to twitches. However, in contrast with other sensory structures throughout the brain, relatively few IP units showed exafferent responses. Upon finding that exafferent responses occurred in pups under urethane anesthesia, we hypothesized that urethane inhibits cerebellar cortical cells, thereby disinhibiting exafferent responses in IP. In support of this hypothesis, ablating cortical tissue dorsal to IP mimicked the effects of urethane on exafference. Finally, the results suggest that twitch-related corollary discharge and reafference are conveyed simultaneously and in parallel to cerebellar cortex and IP. Based on these results, we propose that twitches provide opportunities for the nascent cerebellum to integrate somatotopically organized corollary discharge and reafference, thereby enabling the development of closed-loop circuits and, subsequently, internal models. [ABSTRACT FROM AUTHOR]

Background: There continues to be growing interest in the Science of Learning including identifying applications for findings from this work outside the laboratory to support learning. Presently, there exists a gap in our understanding of learning during healthy adulthood as well as effective ways in which that learning can be improved. Developing a more comprehensive understanding of learning during adulthood, and effective ways of improving that learning, are crucial goals given the impact of a rapidly aging global population. The main objective of the proposed systematic review is to identify and synthesize all recent cognitive and brain research investigating learning across the adult lifespan. Methods: Searches will be performed across Scopus, Web of Science, and ProQuest databases. Both published and unpublished literature will be screened for inclusion. Included articles will be limited to research in healthy adult samples reporting measures of learning-related cognition, brain structure or function and their relationship with age, or the impact of interventions to improve learning. All steps of the review will be performed by three trained reviewers. Tabular, narrative, and quantitative syntheses will be provided based on the characteristics of included studies. Discussion: Findings from the proposed review will contribute to our understanding of learning in adulthood. Additionally, this review will identify research gaps in need of further investigation and relevant findings for translation, informing the scope of future funding priorities in the Science of Learning. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea (OSA) is a pervasive, chronic sleep-related respiratory condition that causes brain structural alterations and cognitive impairments. However, the causal association of OSA with brain morphology and cognitive performance has not been determined. Methods: We conducted a two-sample bidirectional Mendelian randomization (MR) analysis to investigate the causal relationship between OSA and a range of neurocognitive characteristics, including brain cortical structure, brain subcortical structure, brain structural change across the lifespan, and cognitive performance. Summary-level GWAS data for OSA from the FinnGen consortium was used to identify genetically predicted OSA. Data regarding neurocognitive characteristics were obtained from published meta-analysis studies. Linkage disequilibrium score regression analysis was employed to reveal genetic correlations between OSA and related traits. Results: Our MR study provided evidence that OSA was found to significantly increase the volume of the hippocampus (IVW β (95% CI) = 158.997 (76.768 to 241.227), P = 1.51e-04), with no heterogeneity and pleiotropy detected. Nominally causal effects of OSA on brain structures, such as the thickness of the temporal pole with or without global weighted, amygdala structure change, and cerebellum white matter change covering lifespan, were observed. Bidirectional causal links were also detected between brain cortical structure, brain subcortical, cognitive performance, and OSA risk. LDSC regression analysis showed no significant correlation between OSA and hippocampus volume. Conclusions: Overall, we observed a positive association between genetically predicted OSA and hippocampus volume. These findings may provide new insights into the bidirectional links between OSA and neurocognitive features, including brain morphology and cognitive performance. [ABSTRACT FROM AUTHOR]

Background: Episodic memory (EM) deteriorates as a result of normal aging as well as Alzheimer's disease. The neural underpinnings of such age-related memory impairments in older individuals are not well-understood. Although previous research has unveiled the association between gray matter volume (GMV) and EM in the elderly population, such findings exhibit variances across distinct age cohorts. Consequently, an investigation into the dynamic evolution of this relationship with advancing age is imperative. Result: The present study utilized a sliding window approach to examine how the correlation between EM and GMV varied with age in a cross-sectional sample of 926 Chinese older adults. We found that both verbal EM (VEM) and spatial EM (SEM) exhibited positive correlations with GMV in extensive areas primarily in the temporal and frontal lobes and that these correlations typically became stronger with older age. Moreover, there were variations in the strength of the correlation between EM and GMV with age, which differed based on sex and the specific type of EM. Specifically, the association between VEM and GMVs in the insula and parietal regions became stronger with age for females but not for males, whereas the association between SEM and GMVs in the parietal and occipital regions became stronger for males but not for females. At the brain system level, there is a significant age-related increase in the correlations between both types of EM and the GMV of both the anterior temporal (AT) system and the posterior medial (PM) system in male group. In females, both types of EM show stronger age-related correlations with the GMV of the AT system compared to males. Conclusions: Our study revealed a significant positive correlation between GMV in most regions associated with EM and age, particularly in the frontal and temporal lobes. This discovery offers new insights into the connection between brain structure and the diminishing episodic memory function among older individuals. [ABSTRACT FROM AUTHOR]

Microglia activation by proinflammatory stimuli, including lipopolysaccharide (LPS), is considered among the risk factors for neurodegeneration, although LPS treatment may also have a neuroprotective effect, necessitating further analysis of the relationship between microglial activation and cell death regulators. Here, we carried out a comparative analysis of the expression of Iba-1, a protein marker for microglia activation, and caspase-3, a key executor protease of apoptosis, in the brainstem and prefrontal cortex of Wistar rats, depending on LPS dose and schedule of its intraperitoneal administration. One day after a single LPS administration at a dose of 0.5 mg/kg, Iba-1 and caspase-3 expression levels were indistinguishable from control values in both brain structures. A fourfold LPS administration at the same dose over 7 days (once in 2 days) led to a significant increase in Iba-1 expression levels in the brainstem one day after the last injection, which was accompanied by a significant decrease in caspase-3 expression. In the brainstem, the same effects were observed 7 days after a single LPS administration at a higher dose of 5 mg/kg. In the frontal cortex, by contrast, no changes in caspase-3 expression were found in a 7-day experiment, while Iba-1 expression rose only following a single LPS administration at 5 mg/kg. The detected decrease in caspase-3 expression in the brainstem under neuroinflammatory conditions may reflect the development of adaptive neuroprotective processes, particularly important for the brain structure responsible for such key body's functions as respiration, blood pressure, and heartbeat. [ABSTRACT FROM AUTHOR]

Introduction: The study aimed to investigate the mechanisms of impairment and recovery in graph naming functions among patients with aphasia due to cerebral infarction. Specifically, the study compared immediate effects of transcranial direct current stimulation (tDCS) treatment in patients at different stages postinfarction: the acute phase (AP) and the recovery period (RP). Methods: Twenty-eight patients were selected, consisting of 16 in the AP and 12 in the RP, along with 18 healthy controls. Both patient groups underwent 2 weeks of tDCS treatment. Posttreatment changes in functional connectivity (FC) within language-related brain regions, as well as in graph naming abilities, were assessed in both patient groups. Results: Both AP and RP groups exhibited significant improvements in graph naming ability following tDCS treatment. Compared to healthy controls, patients showed decreased FC in multiple brain regions of both hemispheres, particularly in the dominant hemisphere. Posttreatment assessments revealed significant increases in FC within the bilateral frontotemporal lobes for both AP and RP groups, and within the bilateral temporo-occipital regions for the AP group. Moreover, the RP group demonstrated decreased FC in the left temporal lobe posttreatment, which had shown increased FC pre-treatment. Conclusions: This study suggests that tDCS can effectively enhance graph naming functions in patients with postinfarction aphasia. The therapeutic effects appear to be mediated by enhancing FC within bilateral frontotemporal lobes. [ABSTRACT FROM AUTHOR]

Background: Critical adolescent neural refinement is controlled by the DCC (deleted in colorectal cancer) protein, a receptor for the netrin-1 guidance cue. We sought to describe the effects of reduced DCC on neuroanatomy in the adolescent and adult mouse brain. Methods: We examined neuronal connectivity, structural covariance, and molecular processes in a DCC -haploinsufficient mouse model, compared with wild-type mice, using new, custom analytical tools designed to leverage publicly available databases from the Allen Institute. Results: We included 11 DCC -haploinsufficient mice and 16 wild-type littermates. Neuroanatomical effects of DCC haploinsufficiency were more severe in adolescence than adulthood and were largely restricted to the mesocorticolimbic dopamine system. The latter finding was consistent whether we identified the regions of the mesocorticolimbic dopamine system a priori or used connectivity data from the Allen Brain Atlas to determine de novo where these dopamine axons terminated. Covariance analyses found that DCC haploinsufficiency disrupted the coordinated development of the brain regions that make up the mesocorticolimbic dopamine system. Gene expression maps pointed to molecular processes involving the expression of DCC , UNC5C (encoding DCC's co-receptor), and NTN1 (encoding its ligand, netrin-1) as underlying our structural findings. Limitations: Our study involved a single sex (males) at only 2 ages. Conclusion: The neuroanatomical phenotype of DCC haploinsufficiency described in mice parallels that observed in DCC -haploinsufficient humans. It is critical to understand the DCC- haploinsufficient mouse as a clinically relevant model system. [ABSTRACT FROM AUTHOR]

Background: Neuroimaging studies have revealed abnormal functional interaction during the processing of emotional faces in patients with major depressive disorder (MDD), thereby enhancing our comprehension of the pathophysiology of MDD. However, it is unclear whether there is abnormal directional interaction among face-processing systems in patients with MDD. Methods: A group of patients with MDD and a healthy control group underwent a face-matching task during functional magnetic resonance imaging. Dynamic causal modelling (DCM) analysis was used to investigate effective connectivity between 7 regions in the face-processing systems. We used a Parametric Empirical Bayes model to compare effective connectivity between patients with MDD and controls. Results: We included 48 patients and 44 healthy controls in our analyses. Both groups showed higher accuracy and faster reaction time in the shape-matching condition than in the face-matching condition. However, no significant behavioural or brain activation differences were found between the groups. Using DCM, we found that, compared with controls, patients with MDD showed decreased self-connection in the right dorsolateral prefrontal cortex (DLPFC), amygdala, and fusiform face area (FFA) across task conditions; increased intrinsic connectivity from the right amygdala to the bilateral DLPFC, right FFA, and left amygdala, suggesting an increased intrinsic connectivity centred in the amygdala in the right side of the face-processing systems; both increased and decreased positive intrinsic connectivity in the left side of the face-processing systems; and comparable task modulation effect on connectivity. Limitations: Our study did not include longitudinal neuroimaging data, and there was limited region of interest selection in the DCM analysis. Conclusion: Our findings provide evidence for a complex pattern of alterations in the face-processing systems in patients with MDD, potentially involving the right amygdala to a greater extent. The results confirm some previous findings and highlight the crucial role of the regions on both sides of face-processing systems in the pathophysiology of MDD. [ABSTRACT FROM AUTHOR]

Emerging evidence suggests proton radiation therapy may offer cognitive sparing advantages over photon radiation therapy, yet dosimetry has not been compared previously. The purpose of this study was to examine dosimetric correlates of cognitive outcomes in children with medulloblastoma treated with proton versus photon radiation therapy. In this retrospective, bi-institutional study, dosimetric and cognitive data from 75 patients (39 photon and 36 proton) were analyzed. Doses to brain structures were compared between treatment modalities. Linear mixed-effects models were used to create models of global IQ and cognitive domain scores. The mean dose and dose to 40% of the brain (D40) were 2.7 and 4.1 Gy less among proton-treated patients compared with photon-treated patients (P =.03 and.007, respectively). Mean doses to the left and right hippocampi were 11.2 Gy lower among proton-treated patients (P <.001 for both). Mean doses to the left and right temporal lobes were 6.9 and 7.1 Gy lower with proton treatment, respectively (P <.001 for both). Models of cognition found statistically significant associations between higher mean brain dose and reduced verbal comprehension, increased right temporal lobe D40 with reduced perceptual reasoning, and greater left temporal mean dose with reduced working memory. Higher brain D40 was associated with reduced processing speed and global IQ scores. Proton therapy reduces doses to normal brain structures compared with photon treatment. This leads to reduced cognitive decline after radiation therapy across multiple intellectual endpoints. Proton therapy should be offered to children receiving radiation for medulloblastoma. [ABSTRACT FROM AUTHOR]

Introduction: Growth-restricted fetuses may have changes in their neuroanatomical structures that can be detected in prenatal imaging. We aim to compare corpus callosal length (CCL) and cerebellar vermian height (CVH) measurements between fetal growth restriction (FGR) and control fetuses and to correlate them with cerebral Doppler velocimetry in growth-restricted fetuses. Methods: This was a prospective cohort of FGR after 20 weeks of gestation with ultrasound measurements of CCL and CVH. Control cohort was assembled from fetuses without FGR who had growth ultrasound after 20 weeks of gestation. We compared differences of CCL or CVH between FGR and controls. We also tested for the correlations of CCL and CVH with middle cerebral artery (MCA) pulsatility index (PI) and vertebral artery (VA) PI in the FGR group. CCL and CVH measurements were adjusted by head circumference (HC). Results: CCL and CVH were obtained in 68 and 55 fetuses, respectively. CCL/HC was smaller in FGR fetuses when compared to control fetuses (difference = 0.03, 95% CI: [0.02, 0.04], p < 0.001). CVH/HC was larger in FGR fetuses compared to NG fetuses (difference = 0.1, 95% CI: [−0.01, 0.02], p = < 0.001). VA PI multiples of the median were inversely correlated with CVH/HC (rho = −0.53, p = 0.007), while CCL/HC was not correlated with VA PI. Neither CCL/HC nor CVH/HC was correlated with MCA PI. Conclusions: CCL/HC and CVH/HC measurements show differences in growth-restricted fetuses compared to a control cohort. We also found an inverse relationship between VA PI and CVH/HC. The potential use of neurosonography assessment in FGR assessment requires continued explorations. Plain Language Summary: In this study, we compared ultrasound measurements of several brain structures in fetuses with reduced or normal growth. We also evaluated the correlation of the size/length of these brain structures to blood flow of several blood vessels to the brain. We found that measurements of the small brain (CVH) are larger in pregnancies with growth problems. We also found that the blood flow of the vessel in the back side of the brain (vertebral artery [VA] Doppler) is inversely correlated with the CVH. These findings add to the literature on the use of ultrasound specifically to assess brain structures in pregnancies that are affected by growth problems. Deeper understanding of these associations may help establish which pregnancies with growth problems may need the most help later in life. [ABSTRACT FROM AUTHOR]

Brain-imaging-genetic analysis is an emerging field of research that aims at aggregating data from neuroimaging modalities, which characterize brain structure or function, and genetic data, which capture the structure and function of the genome, to explain or predict normal (or abnormal) brain performance. Brain-imaging-genetic studies offer great potential for understanding complex brain-related diseases/disorders of genetic etiology. Still, a combined brain-wide genome-wide analysis is difficult to perform as typical datasets fuse multiple modalities, each with high dimensionality, unique correlational landscapes, and often low statistical signal-to-noise ratios. In this review, we outline the progress in brain-imaging-genetic methodologies starting from early massive univariate to current deep learning approaches, highlighting each approach's strengths and weaknesses and elongating it with the field's development. We conclude by discussing selected remaining challenges and prospects for the field. [ABSTRACT FROM AUTHOR]

Aim: Many authors have suggested that intimate partner violence (IPV) perpetrators present an imbalance between both branches of the autonomous nervous system when coping with acute stress. Concretely, there is a predominance of the sympathetic branches over the parasympathetic ones when recovering from stress. This imbalance can be explained by their tendency toward anger rumination, and more concretely, by their focus on thoughts of revenge during this period. Unfortunately, there is a gap in the scientific literature in terms of using magnetic resonance imaging (MRI) techniques to assess which brain structures would explain this tendency of IPV perpetrators when coping with acute stress. Method: The main objective of this study was to assess whether the gray matter volume (GMV) of relevant brain structures, signaled in previous scientific literature, moderates the association between thoughts of revenge and sympathetic activation during the recovery period, based on skin conductance levels (SCL) after being exposed to stress, in a group of IPV perpetrators (n = 58) and non-violent men (n = 61). Results: This study highlighted that the GMV of the left nucleus accumbens, right lobules of the cerebellum, and inferior temporal gyrus in IPV perpetrators moderated the association between thoughts of revenge and SCL during the recovery period. Accordingly, the higher the thoughts of revenge, the higher the sympathetic predominance (or higher SCL levels), especially among IPV perpetrators with the lowest GMV of these brain structures. Nonetheless, those variables were unrelated in the control group. Conclusions: Our study highlights the involvement of certain brain structures and how they explain the tendency of some IPV perpetrators to ruminate anger or, more precisely, to focus on thoughts of revenge when they recover from acute stress. These results reinforce the need to incorporate neuroimaging techniques during screening processes to properly understand how IPV perpetrators deal with stress, which in turn helps target their needs and design concrete intervention modules. [ABSTRACT FROM AUTHOR]

Caviomorph rodents are an exceptional model for studying the effects of ecological factors and size relations on brain evolution. These mammals are not only speciose and ecologically diverse but also present wide body size disparity, especially when considering their fossil relatives. Here, we described the brain anatomy of the largest known rodent, Josephoartigasia monesi, uncovering distinctive features within this species regarding other taxa. Albeit resembling extant pacarana Dinomys branickii, J. monesi stands out due to its longer olfactory tract and well-developed sagittal sinus. Challenging the previous hypothesis that giant rodents possessed comparatively smaller brains, we found that J. monesi and another giant extinct rodent, Neoepiblema acreensis, are within the encephalization range of extant caviomorphs. This was unraveled while developing the a Phylogenetic Encephalization Quotient (PEQ) for Caviomorpha. With PEQ, we were able to trace brain-size predictions more accurately, accounting for species-shared ancestry while adding the extinct taxa phenotypic diversity into the prediction model. According to our results, caviomorphs encephalization patterns are not the product of ecological adaptations, and brain allometry is highly conservative within the clade. We challenge future studies to investigate caviomorphs encephalization within different taxonomic ranks while increasing the sampled taxa diversity, especially of extinct forms, in order to fully comprehend the magnitude of this evolutionary stasis. [ABSTRACT FROM AUTHOR]

Infants born extremely preterm are at risk for compromised cognitive and motor outcome. There are various possibilities as to why this occurs. The "two-hit" hypothesis consists of interrelated developmental disruptions and insults. Both specifically affect the transient subplate neuronal layer (SNL) and the early development of brain circuitry. The SNL, analogous to a switchboard, is critical in connecting cortical and lower brain centers and is highly susceptible to disruptions and insults, producing dysfunctional neural networks. Damage to the SNL provides the putative link between atypical early brain development and later cognitive and academic function that require complex neural circuitry. This, in turn, has major ramifications for developmental assessment and prediction. Key Points Preterm brains are highly susceptible to disruptions and insults, this being the two-hit hypothesis. There is a variation in which low-grade stressors "sensitize" the infant increasing susceptibility to a second stressor-causing brain damage. Subplate neuronal layer damage compromises outcome by interfering with thalamocortical connections. Combining neuroimaging and developmental testing is the best way to gain insight into these processes. Atypical early brain development may not be evident until the network is mature and challenged. [ABSTRACT FROM AUTHOR]

Objective: Temporal lobe epilepsy (TLE) accompanied by hippocampal sclerosis (HS) is the most common type of focal epilepsies. Hemispheric asymmetry is a feature of brain organization in both invertebrates and vertebrates and may be the key to some neurodegenerative diseases. In this context, we aimed to investigate the volumetric asymmetry difference in cerebral structures between TLE patients and the healthy control group, based on magnetic resonance imaging (MRI) data that may be used as a new neuroimaging marker for TLE cases. Patients and Methods: In this retrospective study the cranial MRIs of fourteen clinically manifesting, radiologically HS-identified, and diagnosed TLE patients and fourteen healthy individuals from the Radiology Department of Yeditepe University Hospital were evaluated. Volume measurements and asymmetry index (AI) calculations in the total brain, hippocampus, temporal lobe, amygdala, thalamus, nucleus accumbens (NAc), premotor cortex, primary and somatosensory cortices were performed using the medical NeuroQuant® software. A negative AI value represented asymmetry towards the right due to reduced left hemispheric volume; a positive AI value represented asymmetry towards the left due to reduced right hemispheric volume. Subsequently, differences in volume and asymmetric patterns were investigated among TLE subgroups (right and left-sided TLE) and controls. Results: The left-sided TLE patients showed significant bilateral total brain volume reduction compared to the control group. Significant ipsilateral volumetric declines were also detected in the premotor cortex, the temporal lobe, and NAc with remarkable asymmetry to the right side. No significant changes were detected in right-sided TLE patients compared to the other groups. Conclusion: Overall, findings suggest that TLE patients had volumetric alterations with symmetry changes beyond the mesial temporal structures. With further investigations, the asymmetry measures can provide additional knowledge for TLE diagnosis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is a common type of neurodegenerative condition characterized by progressive neural deterioration. The anatomical changes associated with individuals affected by Alzheimer's disease include the loss of tissue in various areas of the brain. Magnetic Resonance Imaging (MRI) is commonly used as a noninvasive tool to assess the neural structure of the brain for diagnosing Alzheimer's disease. In this study, an integrated Improved Fuzzy C-means method with improved watershed segmentation was employed to segment the brain tissue components affected by this disease. These segmented features were fed into a hybrid technique for classification. Specifically, a hybrid Convolutional Neural Network–Long Short-Term Memory classifier with 14 layers was developed in this study. The evaluation results revealed that the proposed method achieved an accuracy of 98.13% in classifying segmented brain images according to different disease severities. [ABSTRACT FROM AUTHOR]

Brain magnetic resonance imaging (MRI) is crucial for diagnosing and understanding neurological disorders, but inherent limitations hinder the visualization of fine details in brain structures. The emergence of super‐resolution techniques, especially deep‐learning methods, has improved imaging quality of MRI, by increasing MRI spatial resolution. At present, deep‐learning algorithms mostly performed super‐resolution on 2D MRI images. However, considering 3D nature of MRI, 3D models are more suitable for brain MRI super‐resolution. To achieve finer brain structural details, this study proposes a 3D brain MRI super‐resolution method based on diffusion model (3D‐SRDM), which is a fast and easily trainable neural network for the generation of high‐resolution brain MRI images. In our 3D‐SRDM model, the self‐attention module in U‐Net is replaced with 3D spatial attention mechanism. The network structure of 3D‐SRDM is optimized to reduce training parameters. Moreover, accelerated sampling from denoising diffusion implicit model is also incorporated to reduce time consumption. By these optimizations, compared with original diffusion model, the proposed model can achieve about 10‐ and 5‐fold speed increase at 4× and 8× super‐resolution of 3D brain MRI volumes, respectively, almost without affecting image quality. Thus, 3D‐SRDM has potential application value in efficiently generating high‐resolution 3D brain MRI images, thus facilitating the doctors' diagnosis. [ABSTRACT FROM AUTHOR]

The causal relationship between gut microbiota and cerebral cortex development remains unclear. We aimed to scrutinize the plausible causal impact of gut microbiota on cortical thickness via Mendelian randomization (MR) study. Genome-wide association study (GWAS) data for 196 gut microbiota phenotypes (N = 18,340) were obtained as exposures, and GWAS data for cortical thickness-related traits (N = 51,665) were selected as outcomes. Inverse variance weighted was used as the main estimate method. A series of sensitivity analyses was used to test the robustness of the estimates including Cochran's Q test, MR-Egger intercept analysis, Steiger filtering, scatter plot funnel plot and leave-one-out analysis. Genetic prediction of high Bacillales (β = 0.005, P = 0.032) and Lactobacillales (β = 0.010, P = 0.012) abundance was associated with a potential increase in global cortical thickness. For specific functional brain subdivisions, genetically predicted order Lactobacillales would potentially increase the thickness of the fusiform (β = 0.014, P = 0.016) and supramarginal (β = 0.017, P = 0.003). Meanwhile, order Bacillales would increase the thickness of fusiform (β = 0.007, P = 0.039), insula (β = 0.011, P = 0.003), rostralanteriorcingulate (β = 0.014, P = 0.002) and supramarginal (β = 0.006, P = 0.043). No significant estimates of heterogeneity or pleiotropy were found. Through MR studies, we discovered genetic prediction of the Lactobacillales and Bacillales orders potentially linked to cortical thickness, affirming gut microbiota may enhance brain structure. Genetically predicted supramarginal and fusiform may be potential targets. • Our study demonstrated the causal associations between gut microbiota and cortical thickness. • A systematic investigation between gut microbiota and cortical thickness was carried out. • We discovered genetic prediction of the Lactobacillales and Bacillales orders may potentially enhance brain structure. • Our research suggested fusiform and supramarginal as possible brain regions for investigating the microbiota-gut-brain axis. [ABSTRACT FROM AUTHOR]

The study of the effects of aging on neural activity in the human brain has attracted considerable attention in neurophysiological, neuropsychiatric, and neurocognitive research, as it is directly linked to an understanding of the neural mechanisms underlying the disruption of the brain structures and functions that lead to age-related pathological disorders. Electroencephalographic (EEG) signals recorded during resting-state conditions have been widely used because of the significant advantage of non-invasive signal acquisition with higher temporal resolution. These advantages include the capability of a variety of linear and nonlinear signal analyses and state-of-the-art machine-learning and deep-learning techniques. Advances in artificial intelligence (AI) can not only reveal the neural mechanisms underlying aging but also enable the assessment of brain age reliably by means of the age-related characteristics of EEG signals. This paper reviews the literature on the age-related features, available analytic methods, large-scale resting-state EEG databases, interpretations of the resulting findings, and recent advances in age-related AI models. [ABSTRACT FROM AUTHOR]

In a recent proteome-wide study, we identified several candidate proteins for drug discovery whose cortical abundance was associated with cognitive resilience to late-life brain pathologies. This study examines the extent to which these proteins are associated with the brain structures of cognitive resilience in decedents from the Religious Orders Study and Memory and Aging Project. Six proteins were associated with brain morphometric characteristics related to higher resilience (i.e., larger anterior and medial temporal lobe volumes), and five were associated with morphometric characteristics related to lower resilience (i.e., enlarged ventricles). Two synaptic proteins, RPH3A and CPLX1, remained inversely associated with the lower resilience signature, after further controlling for 10 neuropathologic indices. These findings suggest preserved brain structure in periventricular regions as a potential mechanism by which RPH3A and CPLX1 are associated with cognitive resilience. Further work is needed to elucidate other mechanisms by which targeting these proteins can circumvent the effects of pathology on individuals at risk for cognitive decline. • We identified two morphometric brain signatures of cognitive resilience • Larger anterior and medial temporal volumes were associated with higher resilience • Larger ventricles were associated with lower resilience • Six previously identified cortical resilience proteins were linked to the volumes • RPH3A and CPLX1 were related to smaller ventricles beyond neuropathological burden. [ABSTRACT FROM AUTHOR]

Introduction: Recent research indicates that some brain structures show alterations in conditions such as Autism Spectrum Disorder (ASD). Among them, are the basal ganglia that are involved in motor, cognitive and behavioral neural circuits. Objective: Review the literature that describes possible volumetric alterations in the basal ganglia of individuals with ASD and the impacts that these changes have on the severity of the condition. Methodology: This systematic review was registered in the design and reported according to the PRISMA Items and registered in PROSPERO (CRD42023394787). The study analyzed data from published clinical, case‐contemplate, and cohort trials. The following databases were consulted: PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials, using the Medical Subject Titles (MeSH) "Autism Spectrum Disorder" and "Basal Ganglia". The last search was carried out on February 28, 2023. Results: Thirty‐five eligible articles were collected, analyzed, and grouped according to the levels of alterations. Conclusion: The present study showed important volumetric alterations in the basal ganglia in ASD. However, the examined studies have methodological weaknesses that do not allow generalization and correlation with ASD manifestations. [ABSTRACT FROM AUTHOR]