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This article reviews the synergistic application of positron emission tomography-magnetic resonance imaging (PET-MRI) in neuroscience with relevance for psychiatry, particularly examining neurotransmission, epigenetics, and dynamic imaging methodologies. We begin by discussing the complementary insights that PET and MRI modalities provide into neuroreceptor systems, with a focus on dopamine, opioids, and serotonin receptors, and their implications for understanding and treating psychiatric disorders. We further highlight recent PET-MRI studies using a radioligand that enables the quantification of epigenetic enzymes, specifically histone deacetylases, in the brain in vivo. Imaging epigenetics is used to exemplify the impact the quantification of novel molecular targets may have, including new treatment approaches for psychiatric disorders. Finally, we discuss innovative designs involving functional PET using [ 18 F]FDG (fPET-FDG), which provides detailed information regarding dynamic changes in glucose metabolism. Concurrent acquisitions of fPET-FDG and functional MRI provide a time-resolved approach to studying brain function, yielding simultaneous metabolic and hemodynamic information and thereby opening new avenues for psychiatric research. Collectively, the review underscores the potential of a multimodal PET-MRI approach to advance our understanding of brain structure and function in health and disease, which could improve clinical care based on objective neurobiological features and treatment response monitoring. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1., (© 2024 International Society for Magnetic Resonance in Medicine.)

On the 20th anniversary of the Alzheimer's Disease Neuroimaging Initiative (ADNI), this paper provides a comprehensive overview of the role of arterial spin labeling (ASL) magnetic resonance imaging (MRI) in understanding perfusion changes in the aging brain and the relationship with Alzheimer's disease (AD) pathophysiology and its comorbid conditions. We summarize previously used acquisition protocols, available data, and the motivation for adopting a multi-post-labeling delay (PLD) acquisition scheme in the latest ADNI MRI protocol (ADNI 4). We also detail the process of setting up this scheme on different scanners, emphasizing the potential of ASL imaging in future AD research. HIGHLIGHTS: The Alzheimer's Disease Neuroimaging Initiative (ADNI) adopted multimodal arterial spin labeling magnetic resonance imaging (ASL MRI) to meet evolving biomarker requirements. The ADNI provides one of the largest multisite, multi-vendor ASL data collections. The ADNI 4 incorporates multi-post-labeling delay ASL techniques to jointly quantify cerebral blood flow and arterial transit time. ADNI 4 ASL MRI protocol is apt for detecting early Alzheimer's disease with cerebrovascular pathology., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

This systematic review considered evidence of children's and adolescents' typical brain connectivity development studied through resting-state functional magnetic resonance imaging (rs-fMRI). With aim of understanding the state of the art, what has been researched thus far and what remains unknown, this paper reviews 58 studies from 2013 to 2023. Considering the results, rs-fMRI stands out as an appropriate technique for studying language and attention within cognitive domains, and personality traits such as impulsivity and empathy. The most used analyses encompass seed-based, independent component analysis (ICA), the amplitude of the low frequency fluctuations (ALFF), and fractional ALFF (fALFF). The findings highlight key themes, including age-related changes in intrinsic connectivity, sex-specific patterns, and the relevance of the Default Mode Network (DMN). Overall, there is a need for longitudinal approaches to trace the typical developmental trajectory of neural networks from childhood through adolescence with fMRI at rest., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Cerebrovascular disease (CVD) manifests through a broad spectrum of mechanisms that negatively impact brain and cognitive health. Oftentimes, CVD changes (excluding acute stroke) are insufficiently considered in aging and dementia studies which can lead to an incomplete picture of the etiologies contributing to the burden of cognitive impairment. Our goal with this focused review is 3-fold. First, we provide a research update on the current magnetic resonance imaging methods that can measure CVD lesions as well as early CVD-related brain injury specifically related to small vessel disease. Second, we discuss the clinical implications and relevance of these CVD imaging markers for cognitive decline, incident dementia, and disease progression in Alzheimer disease, and Alzheimer-related dementias. Finally, we present our perspective on the outlook and challenges that remain in the field. With the increased research interest in this area, we believe that reliable CVD imaging biomarkers for aging and dementia studies are on the horizon.

Background: Stereotactic needle brain biopsy is a commonly used neurosurgical procedure. However, up to 15% of biopsies result in undiagnostic pathology reports. Repeat biopsy or continued management without a diagnosis are often considered after undiagnostic biopsies. There have been no reports about the role of postoperative imaging in predicting the diagnostic yield of stereotactic biopsies., Methods: We retrospectively assessed all stereotactic biopsies performed over an 11-year period. We performed fusion of immediate postoperative computed tomography (CT) with preoperative MRI, to document whether the air bubble in the postoperative CT was located within the targeted lesion. We then evaluated the association of this fusion-based accuracy assessment with the diagnostic yield of the biopsy., Results: Fewer than 5% of biopsies did not have an air bubble on postoperative CT. A total of 226 biopsies were performed for 219 patients. In our sample, 213 of 226 biopsies were accurate (94.2% accuracy rate), and 203 of 226 biopsies gave a definitive diagnosis (89.8% diagnostic rate). In those cases where the fusion was accurate, the diagnostic rate was 93.9%. When the fusion was inaccurate, the diagnostic rate was only 23.1% (odds ratio 51.5, 95% confidence interval 12.6-210.44, P < 0.001). Of all patient, imaging, surgical, and admission parameters, the only parameter that correlated with diagnostic outcome of the biopsy was the fusion construct accuracy., Conclusions: Fusion of immediate postoperative CT with preoperative imaging is predictive of the diagnostic rate. In cases where the pathology report following a biopsy is not diagnostic, this fusion may be useful in making decisions regarding repeat biopsy or considering other diagnostic options., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Metabolic disorders associated with obesity could lead to alterations in brain structure and function. Whether these changes can be reversed after weight loss is unclear. Bariatric surgery provides a unique opportunity to address these questions because it induces marked weight loss and metabolic improvements which in turn may impact the brain in a longitudinal fashion. Previous studies found widespread changes in grey matter (GM) and white matter (WM) after bariatric surgery. However, findings regarding changes in spontaneous neural activity following surgery, as assessed with the fractional amplitude of low frequency fluctuations (fALFF) and regional homogeneity of neural activity (ReHo), are scarce and heterogenous. In this study, we used a longitudinal design to examine the changes in spontaneous neural activity after bariatric surgery (comparing pre- to post-surgery), and to determine whether these changes are related to cardiometabolic variables., Methods: The study included 57 participants with severe obesity (mean BMI=43.1 ± 4.3 kg/m 2 ) who underwent sleeve gastrectomy (SG), biliopancreatic diversion with duodenal switch (BPD), or Roux-en-Y gastric bypass (RYGB), scanned prior to bariatric surgery and at follow-up visits of 4 months (N = 36), 12 months (N = 29), and 24 months (N = 14) after surgery. We examined fALFF and ReHo measures across 1022 cortical and subcortical regions (based on combined Schaeffer-Xiao parcellations) using a linear mixed effect model. Voxel-based morphometry (VBM) based on T1-weighted images was also used to measure GM density in the same regions. We also used an independent sample from the Human Connectome Project (HCP) to assess regional differences between individuals who had normal-weight (N = 46) or severe obesity (N = 46)., Results: We found a global increase in the fALFF signal with greater increase within dorsolateral prefrontal cortex, precuneus, inferior temporal gyrus, and visual cortex. This effect was more significant 4 months after surgery. The increase within dorsolateral prefrontal cortex, temporal gyrus, and visual cortex was more limited after 12 months and only present in the visual cortex after 24 months. These increases in neural activity measured by fALFF were also significantly associated with the increase in GM density following surgery. Furthermore, the increase in neural activity was significantly related to post-surgery weight loss and improvement in cardiometabolic variables, such as blood pressure. In the independent HCP sample, normal-weight participants had higher global and regional fALFF signals, mainly in dorsolateral/medial frontal cortex, precuneus and middle/inferior temporal gyrus compared to the obese participants. These BMI-related differences in fALFF were associated with the increase in fALFF 4 months post-surgery especially in regions involved in control, default mode and dorsal attention networks., Conclusions: Bariatric surgery-induced weight loss and improvement in metabolic factors are associated with widespread global and regional increases in neural activity, as measured by fALFF signal. These findings alongside the higher fALFF signal in normal-weight participants compared to participants with severe obesity in an independent dataset suggest an early recovery in the neural activity signal level after the surgery., (Copyright © 2021. Published by Elsevier Inc.)

Neurodegenerative diseases (NDs), such as Alzheimer's disease (AD), Parkinson's disease (PD) and multiple sclerosis (MS), are relatively common and devastating neurological disorders. For example, there are 6 million individuals living with AD in the United States, a number that is projected to grow to 14 million by the year 2030. Importantly, AD, PD and MS are all characterized by the lack of a true disease-modifying therapy that is able to reverse or halt disease progression. In addition, the existing standard of care for most NDs only addresses the symptoms of the disease. Therefore, alternative strategies that target mechanisms underlying the neuropathogenesis of disease are much needed. Recent studies have indicated that metabolic alterations in neurons and glia are commonly observed in AD, PD and MS and lead to changes in cell function that can either precede or protect against disease onset and progression. Specifically, single-cell RNAseq studies have shown that AD progression is tightly linked to the metabolic phenotype of microglia, the key immune effector cells of the brain. However, these analyses involve removing cells from their native environment and performing measurements in vitro, influencing metabolic status. Therefore, technical approaches that can accurately assess cell-specific metabolism in situ have the potential to be transformative to our understanding of the mechanisms driving AD. Here, we review our current understanding of metabolism in both neurons and glia during homeostasis and disease. We also evaluate recent advances in metabolic imaging, and discuss how emerging modalities, such as fluorescence lifetime imaging microscopy (FLIM) have the potential to determine how metabolic perturbations may drive the progression of NDs. Finally, we propose that the temporal, regional, and cell-specific characterization of brain metabolism afforded by FLIM will be a critical first step in the rational design of metabolism-focused interventions that delay or even prevent NDs., (© 2021. The Author(s).)

Quantitative susceptibility mapping (QSM) and R2* mapping are MRI post-processing methods that quantify tissue magnetic susceptibility and transverse relaxation rate distributions. However, QSM and R2* acquisitions are relatively slow, even with parallel imaging. Incoherent undersampling and compressed sensing reconstruction techniques have been used to accelerate traditional magnitude-based MRI acquisitions; however, most do not recover the full phase signal, as required by QSM, due to its non-convex nature. In this study, a learning-based Deep Complex Residual Network (DCRNet) is proposed to recover both the magnitude and phase images from incoherently undersampled data, enabling high acceleration of QSM and R2* acquisition. Magnitude, phase, R2*, and QSM results from DCRNet were compared with two iterative and one deep learning methods on retrospectively undersampled acquisitions from six healthy volunteers, one intracranial hemorrhage and one multiple sclerosis patients, as well as one prospectively undersampled healthy subject using a 7T scanner. Peak signal to noise ratio (PSNR), structural similarity (SSIM), root-mean-squared error (RMSE), and region-of-interest susceptibility and R2* measurements are reported for numerical comparisons. The proposed DCRNet method substantially reduced artifacts and blurring compared to the other methods and resulted in the highest PSNR, SSIM, and RMSE on the magnitude, R2*, local field, and susceptibility maps. Compared to two iterative and one deep learning methods, the DCRNet method demonstrated a 3.2% to 9.1% accuracy improvement in deep grey matter susceptibility when accelerated by a factor of four. The DCRNet also dramatically shortened the reconstruction time of single 2D brain images from 36-140 seconds using conventional approaches to only 15-70 milliseconds., (Copyright © 2021. Published by Elsevier Inc.)

Children born extremely preterm (EP, <28 weeks' gestation) or extremely low birth weight (ELBW, <1,000 g) are a vulnerable population at high risk of working memory impairments. We aimed to examine changes in the brain structural connectivity networks thought to underlie working memory performance, after completion of a working memory training program (Cogmed) compared with a placebo program in EP/ELBW children. This was a double-blind, placebo-controlled randomized trial (the Improving Memory in a Preterm Randomised Intervention Trial). Children born EP/ELBW received either the Cogmed or placebo program at 7 years of age (n = 91). A subset of children had magnetic resonance imaging of the brain immediately pre- and 2 weeks post-training (Cogmed n = 28; placebo n = 27). T 1 -weighted and diffusion-weighted images were used to perform graph theoretical analysis of structural connectivity networks. Changes from pre-training to post-training in structural connectivity metrics were generally similar between randomized groups. There was little evidence that changes in structural connectivity metrics were related to changes in working memory performance from pre- to post-training. Overall, our results provide little evidence that the Cogmed working memory training program has training-specific effects on structural connectivity networks in EP/ELBW children., (© 2021 Wiley Periodicals LLC.)

The combination of transcranial direct current stimulation (tDCS) with functional magnetic resonance imaging (fMRI) can provide original data to investigate age-related brain changes. We examined neural activity modulations induced by two multifocal tDCS procedures based on two distinct montages fitting two N-back task-based fMRI patterns ("compensatory" and "maintenance") related to high working memory (WM) in a previous publication (Fernández-Cabello et al. Neurobiol Aging (2016);48:23-33). We included 24 participants classified as stable or decliners according to their 4-year WM trajectories following a retrospective longitudinal approach. Then, we studied longitudinal fMRI differences between groups (stable and decliners) and across multifocal tDCS montages ("compensatory" and "maintenance") applied using a single-blind sham-controlled cross-over design. Decliners evidenced over-activation of non-related WM areas after 4 years of follow-up. Focusing on tDCS effects, among the decliner group, the "compensatory"-tDCS montage reduced the activity over the posterior regions where these subjects showed longitudinal hyperactivation. These results reinforce the notion that tDCS effects are characterized by an activity reduction and might be more noticeable in compromised systems. Importantly, the data provide novel evidence that cognitive trajectories predict tDCS effects in older adults., (© 2021 Wiley Periodicals, Inc.)

Olfactory dysfunction (OD) is more common than hearing loss, partial blindness, or blindness and can have a significant impact on the quality of life. Moreover, unexplained OD is an early biomarker in neurodegenerative diseases and increases 5-year mortality risk. Structural alterations in olfactory eloquent brain regions may represent the neuroanatomical correlates of OD. Previous studies have demonstrated reduced gray matter (GM) volume in areas of presumed olfactory relevance in patients with OD. However, being cross-sectional in nature, these studies do not provide evidence of causality, for which longitudinal work is required. At present, however, longitudinal studies addressing olfactory structural plasticity are limited, both in number and methodological approach: to our knowledge, such work has not included parallel functional imaging to confirm the relevance of structural change. We therefore performed a longitudinal multimodal neuroimaging study investigating structural and functional plasticity in 24 patients undergoing surgical treatment for chronic rhinosinusitis, compared with 17 healthy controls. We demonstrated functionally significant structural plasticity within the orbitofrontal, anterior cingulate and insular cortices, and temporal poles in patients 3 months after surgery. Of interest, GM volume decreased in these regions, in association with increased psychophysical scores and BOLD signal. To our knowledge, this is the first study to demonstrate both structural and functional plasticity of the central olfactory networks, thereby confirming these areas as neuroanatomical correlates of olfactory function/dysfunction., (© 2021 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Neuroplasticity refers to the fact that our brain can partially modify both structure and function to adequately respond to novel environmental stimulations. Neuroplasticity mechanisms are not only operating during the acquisition of novel information (i.e., online) but also during the offline periods that take place after the end of the actual learning episode. Structural brain changes as a consequence of learning have been consistently demonstrated on the long term using non-invasive neuroimaging methods, but short-term changes remained more elusive. Fortunately, the swift development of advanced MR methods over the last decade now allows tracking fine-grained cerebral changes on short timescales beyond gross volumetric modifications stretching over several days or weeks. Besides a mere effect of time, post-learning sleep mechanisms have been shown to play an important role in memory consolidation and promote long-lasting changes in neural networks. Sleep was shown to contribute to structural modifications over weeks of prolonged training, but studies evidencing more rapid post-training sleep structural effects linked to memory consolidation are still scarce in human. On the other hand, animal studies convincingly show how sleep might modulate synaptic microstructure. We aim here at reviewing the literature establishing a link between different types of training/learning and the resulting structural changes, with an emphasis on the role of post-training sleep and time in tuning these modifications. Open questions are raised such as the role of post-learning sleep in macrostructural changes, the links between different MR structural measurement-related modifications and the underlying microstructural brain processes, and bidirectional influences between structural and functional brain changes., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Recent evidence indicates that both cardiovascular fitness and gross motor skill performance are related to enhanced neurocognitive functioning in children by influencing brain structure and functioning. This study investigates the role of white matter microstructure in the relationship of both cardiovascular fitness and gross motor skills with neurocognitive functioning in healthy children. In total 92 children (mean age 9.1 years, range 8.0-10.7) were included in this study. Cardiovascular fitness and gross motor skill performance were assessed using performance-based tests. Neurocognitive functioning was assessed using computerized tests (working memory, inhibition, interference control, information processing, and attention). Diffusion tensor imaging was used in combination with tract-based spatial statistics to assess white matter microstructure as defined by fractional anisotropy (FA), axial and radial diffusivity (AD, RD). The results revealed positive associations of both cardiovascular fitness and gross motor skills with neurocognitive functioning. Information processing and motor response inhibition were associated with FA in a cluster located in the corpus callosum. Within this cluster, higher cardiovascular fitness and better gross motor skills were both associated with greater FA, greater AD, and lower RD. No mediating role was found for FA in the relationship of both cardiovascular fitness and gross motor skills with neurocognitive functioning. The results indicate that cardiovascular fitness and gross motor skills are related to neurocognitive functioning as well as white matter microstructure in children. However, this study provides no evidence for a mediating role of white matter microstructure in these relationships., (© 2021 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Maternal childhood maltreatment and depression increase risks for the psychopathology of the offspring. This study employed a longitudinal dataset of mother-child dyads to investigate the developmental trajectories of brain functional networks and behaviors of children in relation with maternal childhood adverse experience and depression. Maternal childhood trauma was retrospectively assessed via childhood trauma questionnaire, whereas maternal depressive symptoms were prospectively evaluated during pregnancy and after delivery (n = 518). Child brain scans were acquired at age of 4.5, 6, and 7.5 years (n = 163) and behavioral problems were measured at 7.5 years using the Child Behavior Checklist. We found the functional connectivity of the language network with the sensorimotor, frontal, and attentional networks as a function of maternal adverse experience that interacted with sex and age. Girls exposed to mothers with depressive symptoms or childhood abuse showed the increased development of the functional connectivity of the language network with the visual networks, which was associated with social problems. Girls exposed to mothers with depressive symptoms showed the slower growth of the functional connectivity of the language network with the sensorimotor networks. Our findings, in a community sample, suggest the language network organization as neuroendophenotypes for maternal childhood trauma and depression., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ultra-high-field functional magnetic resonance imaging (fMRI) offers a way to new insights while increasing the spatial and temporal resolution. However, a crucial concern in 7T human MRI is the increase in power deposition, supervised through the specific absorption rate (SAR). The SAR limitation can restrict the brain coverage or the minimal repetition time of fMRI experiments. In the majority of today's studies fMRI relies on the well-known gradient-echo echo-planar imaging (GRE-EPI) sequence, which offers ultrafast acquisition. Commonly, the GRE-EPI sequence comprises two pulses: fat suppression and excitation. This work provides the means for a significant reduction in the SAR by circumventing the fat-suppression pulse. Without this fat-suppression, however, lipid signal can result in artifacts due to the chemical shift between the lipid and water signals. Our approach exploits a reconstruction similar to the simultaneous-multi-slice method to separate the lipid and water images, thus avoiding undesired lipid artifacts in brain images. The lipid-water separation is based on the known spatial shift of the lipid signal, which can be detected by the multi-channel coils sensitivity profiles. Our study shows robust human imaging, offering greater flexibility to reduce the SAR, shorten the repetition time or increase the volume coverage with substantial benefit for brain functional studies., (© 2021. The Author(s).)

Isoflurane, the most commonly used preclinical anesthetic, induces brain plasticity and long-term cellular and molecular changes leading to behavioral and/or cognitive consequences. These changes are most likely associated with network-level changes in brain function. To elucidate the mechanisms underlying long-term effects of isoflurane, we investigated the influence of a single isoflurane exposure on functional connectivity, brain electrical activity, and gene expression. Male Wistar rats (n = 22) were exposed to 1.8% isoflurane for 3 h. Control rats (n = 22) spent 3 h in the same room without exposure to anesthesia. After 1 month, functional connectivity was evaluated with resting-state functional magnetic resonance imaging (fMRI; n = 6 + 6) and local field potential measurements (n = 6 + 6) in anesthetized animals. A whole genome expression analysis (n = 10+10) was also conducted with mRNA-sequencing from cortical and hippocampal tissue samples. Isoflurane treatment strengthened thalamo-cortical and hippocampal-cortical functional connectivity. Cortical low-frequency fMRI power was also significantly increased in response to the isoflurane treatment. The local field potential results indicating strengthened hippocampal-cortical alpha and beta coherence were in good agreement with the fMRI findings. Furthermore, altered expression was found in 20 cortical genes, several of which are involved in neuronal signal transmission, but no gene expression changes were noted in the hippocampus. Isoflurane induced prolonged changes in thalamo-cortical and hippocampal-cortical function and expression of genes contributing to signal transmission in the cortex. Further studies are required to investigate whether these changes are associated with the postoperative behavioral and cognitive symptoms commonly observed in patients and animals., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

Background: The use of functional neuroimaging has been an extremely fruitful avenue for investigating the neural basis of human reward function. This approach has included identification of potential neurobiological mechanisms of psychiatric disease and examination of environmental, experiential, and biological factors that may contribute to disease risk via effects on the reward system. However, a central and largely unexamined assumption of much of this research is that neural reward function is an individual difference characteristic that is relatively stable and trait-like over time., Methods: In two independent samples of adolescents and young adults studied longitudinally (Ns = 145 & 139, 100% female and 100% male, ages 15-21 and 20-22, 2-4 scans and 2 scans respectively), we tested within-person stability of reward-task BOLD activation, with a median of 1 and 2 years between scans. We examined multiple commonly used contrasts of active states and baseline in both the anticipation and feedback phases of a card-guessing reward task. We examined the effects of cortical parcellation resolution, contrast, network (reward regions and resting-state networks), region-size, and activation strength and variability on the stability of reward-related activation., Results: In both samples, contrasts of an active state relative to a baseline were more stable (ICC: intra-class correlation; e.g., Win>Baseline; mean ICC = 0.13 - 0.33) than contrasts of two active states (e.g., Win>Loss; mean ICC = 0.048 - 0.05). Additionally, activation in reward regions was less stable than in many non-task networks (e.g., dorsal attention), and activation in regions with greater between-subject variability showed higher stability in both samples., Conclusions: These results show that some contrasts from functional neuroimaging activation during a card guessing reward task have partially trait-like properties in adolescent and young adult samples over 1-2 years. Notably, results suggest that contrasts intended to map cognitive function and show robust group-level effects (i.e. Win > Loss) may be less effective in studies of individual differences and disease risk. The robustness of group-level activation should be weighed against other factors when selecting regions of interest in individual difference fMRI studies., Competing Interests: Declaration of Competing Interest All authors have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier Inc.)

Neuroimaging techniques that can sensitivity characterize healthy brain aging and detect subtle neuropathologies have enormous potential to assist in the early detection of neurodegenerative conditions such as Alzheimer's disease. Magnetic resonance elastography (MRE) has recently emerged as a reliable, high-resolution, and especially sensitive technique that can noninvasively characterize tissue biomechanical properties (i.e., viscoelasticity) in vivo in the living human brain. Brain tissue viscoelasticity provides a unique biophysical signature of neuroanatomy that are representative of the composition and organization of the complex tissue microstructure. In this article, we detail how progress in brain MRE technology has provided unique insights into healthy brain aging, neurodegeneration, and structure-function relationships. We further discuss additional promising technical innovations that will enhance the specificity and sensitivity for brain MRE to reveal considerably more about brain aging as well as its potentially valuable role as an imaging biomarker of neurodegeneration. MRE sensitivity may be particularly useful for assessing the efficacy of rehabilitation strategies, assisting in differentiating between dementia subtypes, and in understanding the causal mechanisms of disease which may lead to eventual pharmacotherapeutic development., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

Psychological androgyny has long been associated with greater cognitive flexibility, adaptive behavior, and better mental health, but whether a similar concept can be defined using neural features remains unknown. Using the neuroimaging data from 9620 participants, we found that global functional connectivity was stronger in the male brain before middle age but became weaker after that, when compared with the female brain, after systematic testing of potentially confounding effects. We defined a brain gender continuum by estimating the likelihood of an observed functional connectivity matrix to represent a male brain. We found that participants mapped at the center of this continuum had fewer internalizing symptoms compared with those at the 2 extreme ends. These findings suggest a novel hypothesis proposing that there exists a neuroimaging concept of androgyny using the brain gender continuum, which may be associated with better mental health in a similar way to psychological androgyny., (© The Author(s) 2021. Published by Oxford University Press.)

Resting-state functional connectivity is suggested to be cross-sectionally associated with both vascular burden and Alzheimer's disease (AD) pathology. However, evidence is lacking regarding longitudinal changes in functional connectivity. This study includes 247 cognitively unimpaired individuals with a family history of sporadic AD (185 women/ 62 men; mean [SD] age of 63 [5.3] years). Plasma total-, HDL-, and LDL-cholesterol and systolic and diastolic blood pressure were measured at baseline. Global (whole-brain) brain functional connectivity and connectivity from canonical functional networks were computed from resting-state functional MRI obtained at baseline and ~3.5 years of annual follow-ups, using a predefined functional parcellation. A subsample underwent Aβ- and tau-PET (n=91). Linear mixed-effects models demonstrated that global functional connectivity increased over time across the entire sample. In contrast, higher total-cholesterol and LDL-cholesterol levels were associated with greater reduction of functional connectivity in the default-mode network over time. In addition, higher diastolic blood pressure was associated with global functional connectivity reduction. The associations were similar when the analyses were repeated using two other functional brain parcellations. Aβ and tau deposition in the brain were not associated with changes in functional connectivity over time in the subsample. These findings provide evidence that vascular burden is associated with a decrease in functional connectivity over time in older adults with elevated risk for AD. Future studies are needed to determine if the impact of vascular risk factors on functional brain changes precede the impact of AD pathology on functional brain changes., Competing Interests: Declaration of Competing Interest The authors declare no competing financial conflicts of interests., (Copyright © 2021. Published by Elsevier Inc.)

Recent advances in automated face recognition algorithms have increased the risk that de-identified research MRI scans may be re-identifiable by matching them to identified photographs using face recognition. A variety of software exist to de-face (remove faces from) MRI, but their ability to prevent face recognition has never been measured and their image modifications can alter automated brain measurements. In this study, we compared three popular de-facing techniques and introduce our mri&#95;reface technique designed to minimize effects on brain measurements by replacing the face with a population average, rather than removing it. For each technique, we measured 1) how well it prevented automated face recognition (i.e. effects on exceptionally-motivated individuals) and 2) how it altered brain measurements from SPM12, FreeSurfer, and FSL (i.e. effects on the average user of de-identified data). Before de-facing, 97% of scans from a sample of 157 volunteers were correctly matched to photographs using automated face recognition. After de-facing with popular software, 28-38% of scans still retained enough data for successful automated face matching. Our proposed mri&#95;reface had similar performance with the best existing method (fsl&#95;deface) at preventing face recognition (28-30%) and it had the smallest effects on brain measurements in more pipelines than any other, but these differences were modest., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Approximately one in five children worldwide suffers from childhood malnutrition and its complications, including increased susceptibility to inflammation and infectious diseases. Due to improved early interventions, most of these children now survive early malnutrition, even in low-resource settings (LRS). However, many continue to exhibit neurodevelopmental deficits, including low IQ, poor school performance, and behavioral problems over their lifetimes. Most studies have relied on neuropsychological tests, school performance, and mental health and behavioral measures. Few studies, in contrast, have assessed brain structure and function, and to date, these have mainly relied on low-cost techniques, including electroencephalography (EEG) and evoked potentials (ERP). The use of more advanced methods of neuroimaging, including magnetic resonance imaging (MRI) and functional near-infrared spectroscopy (fNIRS), has been limited by cost factors and lack of availability of these technologies in developing countries, where malnutrition is nearly ubiquitous. This report summarizes the current state of knowledge and evidence gaps regarding childhood malnutrition and the study of its impact on neurodevelopment. It may help to inform the development of new strategies to improve the identification, classification, and treatment of neurodevelopmental disabilities in underserved populations at the highest risk for childhood malnutrition., (Copyright © 2021. Published by Elsevier Inc.)

Background: Depression has been associated with decreased regional grey matter volume, which might partly be explained by an unhealthier lifestyle in depressed individuals which has been ignored by most earlier studies. Also, the longitudinal nature of depression, lifestyle and brain structure associations is largely unknown. This study investigates the relationship of depression and lifestyle with brain structure cross-sectionally and longitudinally over up to 9 years., Methods: We used longitudinal structural MRI data of persons with depression and/or anxiety disorders and controls (N unique participants  = 347, N observations  = 609). Cortical thickness of medial orbitofrontal cortex (mOFC), rostral anterior cingulate cortex (rACC) and hippocampal volume were derived using FreeSurfer. Using Generalized Estimating Equations, we investigated associations of depression and lifestyle (Body mass index (BMI), smoking, alcohol consumption, physical activity and sleep duration) with brain structure and change in brain structure over 2 (n = 179) and 9 years (n = 82)., Results: Depression status (B = -.053, p = .002) and severity (B = -.002, p = .002) were negatively associated with rACC thickness. mOFC thickness was negatively associated with BMI (B = -.004, p < .001) and positively with moderate alcohol consumption (B = .030, p = .009). All associations were independent of each other. No associations were observed between (change in) depression, disease burden or lifestyle factors with brain change over time., Conclusions: Depressive symptoms and diagnosis were independently associated with thinner rACC, BMI with thinner mOFC, and moderate alcohol consumption with thicker mOFC. No longitudinal associations were observed, suggesting that regional grey matter alterations are a long-term consequence or vulnerability indicator for depression but not dynamically or progressively related to depression course trajectory., Competing Interests: Declaration of Competing Interest BP has received (non-related) research grants from Boehringer Ingelheim and Jansen Research. None of the other authors declare conflicts of interest., (Copyright © 2021. Published by Elsevier Inc.)

Normal aging is characterized by structural and functional changes in the brain contributing to cognitive decline. Structural connectivity (SC) describes the anatomical backbone linking distinct functional subunits of the brain and disruption of this communication is thought to be one of the potential contributors for the age-related deterioration observed in cognition. Several studies already explored brain network's reorganization during aging, but most focused on average connectivity of the whole-brain or in specific networks, such as the resting-state networks. Here, we aimed to characterize longitudinal changes of white matter (WM) structural brain networks, through the identification of sub-networks with significantly altered connectivity along time. Then, we tested associations between longitudinal changes in network connectivity and cognition. We also assessed longitudinal changes in topological properties of the networks. For this, older adults were evaluated at two timepoints, with a mean interval time of 52.8 months (SD = 7.24). WM structural networks were derived from diffusion magnetic resonance imaging, and cognitive status from neurocognitive testing. Our results show age-related changes in brain SC, characterized by both decreases and increases in connectivity weight. Interestingly, decreases occur in intra-hemispheric connections formed mainly by association fibers, while increases occur mostly in inter-hemispheric connections and involve association, commissural, and projection fibers, supporting the last-in-first-out hypothesis. Regarding topology, two hubs were lost, alongside with a decrease in connector-hub inter-modular connectivity, reflecting reduced integration. Simultaneously, there was an increase in the number of provincial hubs, suggesting increased segregation. Overall, these results confirm that aging triggers a reorganization of the brain structural network., (© 2021 The Authors. Journal of Neuroscience Research published by Wiley Periodicals LLC.)

Human neuroimaging has had a major impact on the biological understanding of epilepsy and the relationship between pathophysiology, seizure management, and outcomes. This review highlights notable recent advancements in hardware, sequences, methods, analyses, and applications of human neuroimaging techniques utilized to assess epilepsy. These structural, functional, and metabolic assessments include magnetic resonance imaging (MRI), positron emission tomography (PET), and magnetoencephalography (MEG). Advancements that highlight non-invasive neuroimaging techniques used to study the whole brain are emphasized due to the advantages these provide in clinical and research applications. Thus, topics range across presurgical evaluations, understanding of epilepsy as a network disorder, and the interactions between epilepsy and comorbidities. New techniques and approaches are discussed which are expected to emerge into the mainstream within the next decade and impact our understanding of epilepsies. Further, an increasing breadth of investigations includes the interplay between epilepsy, mental health comorbidities, and aberrant brain networks. In the final section of this review, we focus on neuroimaging studies that assess bidirectional relationships between mental health comorbidities and epilepsy as a model for better understanding of the commonalities between both conditions., (© 2021. The American Society for Experimental NeuroTherapeutics, Inc.)

Brain atlases and templates are at the heart of neuroimaging analyses, for which they facilitate multimodal registration, enable group comparisons and provide anatomical reference. However, as atlas-based approaches rely on correspondence mapping between images they perform poorly in the presence of structural pathology. Whilst several strategies exist to overcome this problem, their performance is often dependent on the type, size and homogeneity of any lesions present. We therefore propose a new solution, referred to as Virtual Brain Grafting (VBG), which is a fully-automated, open-source workflow to reliably parcellate magnetic resonance imaging (MRI) datasets in the presence of a broad spectrum of focal brain pathologies, including large, bilateral, intra- and extra-axial, heterogeneous lesions with and without mass effect. The core of the VBG approach is the generation of a lesion-free T1-weighted image, which enables further image processing operations that would otherwise fail. Here we validated our solution based on Freesurfer recon-all parcellation in a group of 10 patients with heterogeneous gliomatous lesions, and a realistic synthetic cohort of glioma patients (n = 100) derived from healthy control data and patient data. We demonstrate that VBG outperforms a non-VBG approach assessed qualitatively by expert neuroradiologists and Mann-Whitney U tests to compare corresponding parcellations (real patients U(6,6) = 33, z = 2.738, P < .010, synthetic-patients U(48,48) = 2076, z = 7.336, P < .001). Results were also quantitatively evaluated by comparing mean dice scores from the synthetic-patients using one-way ANOVA (unilateral VBG = 0.894, bilateral VBG = 0.903, and non-VBG = 0.617, P < .001). Additionally, we used linear regression to show the influence of lesion volume, lesion overlap with, and distance from the Freesurfer volumes of interest, on labeling accuracy. VBG may benefit the neuroimaging community by enabling automated state-of-the-art MRI analyses in clinical populations using methods such as FreeSurfer, CAT12, SPM, Connectome Workbench, as well as structural and functional connectomics. To fully maximize its availability, VBG is provided as open software under a Mozilla 2.0 license (https://github.com/KUL-Radneuron/KUL&#95;VBG)., (Copyright © 2021. Published by Elsevier Inc.)

In the past decades, many neuroimaging studies have aimed to improve the scientific understanding of human neurodegenerative diseases using MRI and PET. This article is designed to provide an overview of the major classes of brain imaging and how/why they are used in this line of research. It is intended as a primer for individuals who are relatively unfamiliar with the methods of neuroimaging research to gain a better understanding of the vocabulary and overall methodologies. It is not intended to describe or review any research findings for any disease or biology, but rather to broadly describe the imaging methodologies that are used in conducting this neurodegeneration research. We will also review challenges and strategies for analyzing neuroimaging data across multiple sites and studies, i.e., harmonization and standardization of imaging data for multi-site and meta-analyses., (© 2021. The American Society for Experimental NeuroTherapeutics, Inc.)

Recent work has demonstrated that individual-specific variations in functional networks (termed "network variants") can be identified in individuals using resting state functional magnetic resonance imaging (fMRI). These network variants exhibit reliability over time, suggesting that they may be trait-like markers of individual differences in brain organization. However, while networks variants are reliable at rest, is is still untested whether they are stable between task and rest states. Here, we use precision data from the Midnight Scan Club (MSC) to demonstrate that (1) task data can be used to identify network variants reliably, (2) these network variants show substantial spatial overlap with those observed in rest, although state-specific effects are present, (3) network variants assign to similar canonical functional networks in task and rest states, and (4) single tasks or a combination of multiple tasks produce similar network variants to rest. Together, these findings further reinforce the trait-like nature of network variants and demonstrate the utility of using task data to define network variants., (Copyright © 2021. Published by Elsevier Inc.)

Objective: To establish normative reference values for total grey matter cerebral blood flow (CBF GM ) measured using pseudo-continuous arterial spin labelling (pCASL) MRI in a large cohort of community-dwelling adults aged 54 years and older., Background: Quantitative assessment of CBF GM may provide an imaging biomarker for the early detection of those at risk of neurodegenerative diseases, such as Alzheimer's and dementia. However, the use of this method to differentiate normal age-related decline in CBF GM from pathological reduction has been hampered by the lack of reference values for cerebral perfusion., Methods: The study cohort comprised a subset of wave 3 (2014-2015) participants from The Irish Longitudinal Study on Ageing (TILDA), a large-scale prospective cohort study of individuals aged 50 and over. Of 4309 participants attending for health centre assessment, 578 individuals returned for 3T multi-parametric MRI brain examinations. In total, CBF GM data acquired from 468 subjects using pCASL-MRI were included in this analysis. Normative values were estimated using Generalised Additive Models for Location Shape and Scale (GAMLSS) and are presented as percentiles, means and standard deviations., Results: The mean age of the cohort was 68.2 ± 6.9 years and 51.7% were female. Mean CBF GM for the cohort was 36.5 ± 8.2 ml/100 g/min. CBF GM decreased by 0.2 ml/100 g/min for each year increase in age (95% CI = -0.3, -0.1; p ≤ 0.001) and was 3.1 ml/100 g/min higher in females (95% CI = 1.6, 4.5; p ≤ 0.001)., Conclusions: This study is by far the largest single-site study focused on an elderly community-dwelling cohort to present normative reference values for CBF GM measured at 3T using pCASL-MRI. Significant age- and sex-related differences exist in CBF GM ., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

Cognitive states, such as rest and task engagement, share an 'intrinsic' functional network organization that is subject to minimal variation over time and yields stable signatures within an individual. Importantly, there are also transient state-specific functional connectivity (FC) patterns that vary across neural states. Here, we examine functional brain organization differences that underlie distinct states in a cross-sectional developmental sample. We compare FC fMRI data acquired during naturalistic viewing (i.e., movie-watching) and resting-state paradigms in a large cohort of 157 children and young adults aged 6-20. Naturalistic paradigms are commonly implemented in pediatric research because they maintain the child's attention and contribute to reduced head motion. It remains unknown, however, to what extent the brain-wide functional network organization is comparable during movie-watching and rest across development. Here, we identify a widespread FC pattern that predicts whether individuals are watching a movie or resting. Specifically, we develop a model for prediction of multilevel neural effects (termed PrimeNet), which can with high reliability distinguish between movie-watching and rest irrespective of age and that generalizes across movies. In turn, we characterize FC patterns in the most predictive functional networks for movie-watching versus rest and show that these patterns can indeed vary as a function of development. Collectively, these effects highlight a 'core' FC pattern that is robustly associated with naturalistic viewing, which also exhibits change across age. These results, focused here on naturalistic viewing, provide a roadmap for quantifying state-specific functional neural organization across development, which may reveal key variation in neurodevelopmental trajectories associated with behavioral phenotypes., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021. Published by Elsevier Inc.)

Frontotemporal dementia encompasses a group of clinical syndromes defined pathologically by degeneration of the frontal and temporal lobes. Historically, these syndromes have been challenging to diagnose, with an average of about three years between the time of symptom onset and the initial evaluation and diagnosis. Research in the field of neuroimaging has revealed numerous biomarkers of the various frontotemporal dementia syndromes, which has provided clinicians with a method of narrowing the differential diagnosis and improving diagnostic accuracy. As such, neuroimaging is considered a core investigative tool in the evaluation of neurodegenerative disorders. Furthermore, patterns of neurodegeneration correlate with the underlying neuropathological substrates of the frontotemporal dementia syndromes, which can aid clinicians in determining the underlying etiology and improve prognostication. This review explores the advancements in neuroimaging and discusses the phenotypic and pathologic features of behavioral variant frontotemporal dementia, semantic variant primary progressive aphasia, and nonfluent variant primary progressive aphasia, as seen on structural magnetic resonance imaging and positron emission tomography., (© 2021. The Author(s).)

Accurate knowledge of adult human brain volume (BV) is critical for studies of aging- and disease-related brain alterations, and for monitoring the trajectories of neural and cognitive functions in conditions like Alzheimer's disease and traumatic brain injury. This scoping meta-analysis aggregates normative reference values for BV and three related volumetrics-gray matter volume (GMV), white matter volume (WMV) and cerebrospinal fluid volume (CSFV)-from typically-aging adults studied cross-sectionally using magnetic resonance imaging (MRI). Drawing from an aggregate sample of 9473 adults, this study provides (A) regression coefficients β describing the age-dependent trajectories of volumetric measures by sex within the range from 20 to 70 years based on both linear and quadratic models, and (B) average values for BV, GMV, WMV and CSFV at the representative ages of 20 (young age), 45 (middle age) and 70 (old age). The results provided synthesize ~20 years of brain volumetrics research and allow one to estimate BV at any age between 20 and 70. Importantly, however, such estimates should be used and interpreted with caution because they depend on MRI hardware specifications (e.g. scanner manufacturer, magnetic field strength), data acquisition parameters (e.g. spatial resolution, weighting), and brain segmentation algorithms. Guidelines are proposed to facilitate future meta- and mega-analyses of brain volumetrics.

In this paper, the structural and functional imaging changes associated with sporadic and genetic Parkinson's disease and atypical Parkinsonian variants are reviewed. The role of imaging for supporting diagnosis and detecting subclinical disease is discussed, and the potential use and drawbacks of using imaging biomarkers for monitoring disease progression is debated. Imaging changes associated with nonmotor complications of PD are presented. The similarities and differences in imaging findings in Lewy body dementia, Parkinson's disease dementia, and Alzheimer's disease are discussed., (© 2021. The Author(s).)

It has been suggested that specific forms of cognition in older age rely largely on late-life specific mechanisms. Here instead, we tested using task-fMRI (n = 540, age 6-82 years) whether the functional foundations of successful episodic memory encoding adhere to a principle of lifespan continuity, shaped by developmental, structural, and evolutionary influences. We clustered regions of the cerebral cortex according to the shape of the lifespan trajectory of memory activity in each region so that regions showing the same pattern were clustered together. The results revealed that lifespan trajectories of memory encoding function showed a continuity through life but no evidence of age-specific mechanisms such as compensatory patterns. Encoding activity was related to general cognitive abilities and variations of grey matter as captured by a multi-modal independent component analysis, variables reflecting core aspects of cognitive and structural change throughout the lifespan. Furthermore, memory encoding activity aligned to fundamental aspects of brain organization, such as large-scale connectivity and evolutionary cortical expansion gradients. Altogether, we provide novel support for a perspective on memory aging in which maintenance and decay of episodic memory in older age needs to be understood from a comprehensive life-long perspective rather than as a late-life phenomenon only., (© The Author(s) 2020. Published by Oxford University Press.)

Importance: Although magnetic resonance imaging (MRI) is useful for monitoring disease dissemination in space and over time and excluding multiple sclerosis (MS) mimics, there has been less application of MRI to progressive MS, including diagnosing primary progressive (PP) MS and identifying patients with relapsing-remitting (RR) MS who are at risk of developing secondary progressive (SP) MS. This review addresses clinical application of MRI for both diagnosis and prognosis of progressive MS., Observations: Although nonspecific, some spinal cord imaging features (diffuse abnormalities and lesions involving gray matter [GM] and ≥2 white matter columns) are typical of PPMS. In patients with PPMS and those with relapse-onset MS, location of lesions in critical central nervous system regions (spinal cord, infratentorial regions, and GM) and MRI-detected high inflammatory activity in the first years after diagnosis are risk factors for long-term disability and future progressive disease course. These measures are evaluable in clinical practice. In patients with established MS, GM involvement and neurodegeneration are associated with accelerated clinical worsening. Subpial demyelination and slowly expanding lesions are novel indicators of progressive MS., Conclusions and Relevance: Diagnosis of PPMS is more challenging than diagnosis of RRMS. No qualitative clinical, immunological, histopathological, or neuroimaging features differentiate PPMS and SPMS; both are characterized by imaging findings reflecting neurodegeneration and are also impacted by aging and comorbidities. Unmet diagnostic needs include identification of MRI markers capable of distinguishing PPMS from RRMS and predicting the evolution of RRMS to SPMS. Integration of multiple parameters will likely be essential to achieve these aims.

The World Health Organization promotes physical exercise and a healthy lifestyle as means to improve youth development. However, relationships between physical lifestyle and human brain development are not fully understood. Here, we asked whether a human brain-physical latent mode of covariation underpins the relationship between physical activity, fitness, and physical health measures with multimodal neuroimaging markers. In 50 12-year old school pupils (26 females), we acquired multimodal whole-brain MRI, characterizing brain structure, microstructure, function, myelin content, and blood perfusion. We also acquired physical variables measuring objective fitness levels, 7 d physical activity, body mass index, heart rate, and blood pressure. Using canonical correlation analysis, we unravel a latent mode of brain-physical covariation, independent of demographics, school, or socioeconomic status. We show that MRI metrics with greater involvement in this mode also showed spatially extended patterns across the brain. Specifically, global patterns of greater gray matter perfusion, volume, cortical surface area, greater white matter extra-neurite density, and resting state networks activity covaried positively with measures reflecting a physically active phenotype (high fit, low sedentary individuals). Showing that a physically active lifestyle is linked with systems-level brain MRI metrics, these results suggest widespread associations relating to several biological processes. These results support the notion of close brain-body relationships and underline the importance of investigating modifiable lifestyle factors not only for physical health but also for brain health early in adolescence. SIGNIFICANCE STATEMENT An active lifestyle is key for healthy development. In this work, we answer the following question: How do brain neuroimaging markers relate with young adolescents' level of physical activity, fitness, and physical health? Combining advanced whole-brain multimodal MRI metrics with computational approaches, we show a robust relationship between physically active lifestyles and spatially extended, multimodal brain imaging-derived phenotypes. Suggesting a wider effect on brain neuroimaging metrics than previously thought, this work underlies the importance of studying physical lifestyle, as well as other brain-body relationships in an effort to foster brain health at this crucial stage in development., (Copyright © 2021 Salvan et al.)

Objective: To determine whether 24 weeks of high-intensity progressive aerobic exercise (PAE) affects brain MRI measures in people with multiple sclerosis (MS)., Methods: We conducted a randomized, controlled, phase 2 trial (with a crossover follow-up) including an exercise group (supervised PAE followed by self-guided physical activity) and a waitlist group (habitual lifestyle followed by supervised PAE). Mildly to severely impaired patients with MS aged 18-65 years were randomized (1:1). The primary outcome was percentage brain volume change (PBVC) after 24 weeks, analyzed using the intention-to-treat principle., Results: Eighty-six participants were recruited. PBVC did not change over the intervention period (mean between-group change +0.12%, 95% confidence interval [CI] -0.27 to 0.51, p = 0.55). In contrast, cardiorespiratory fitness (+3.5 mL O 2 /min/kg, 2.0 to 5.1, p < 0.01) and annualized relapse rate (0.00, 0.00-0.07 vs +0.45, 0.28 to 0.61, p < 0.01) improved in the exercise group., Conclusion: These findings do not support a neuroprotective effect of PAE in terms of total brain atrophy in people with MS and it did not lead to a statistically significant difference in gray matter parenchymal fraction. PAE led to improvements in cardiorespiratory fitness and a lower relapse rate. While these exploratory findings cautiously support PAE as a potential adjunct disease-modifying treatment in MS, further investigations are warranted., Clinicaltrialsgov Identifier: NCT02661555., Classification of Evidence: This study provides Level I evidence that 24 weeks of high-intensity PAE did not elicit disease-modifying effects in PBVC in people with MS. Exploratory analyses showed that PAE may reduce relapse rate., (© 2020 American Academy of Neurology.)

Children and adolescents show high variability in brain development. Brain age-the estimated biological age of an individual brain-can be used to index developmental stage. In a longitudinal sample of adolescents (age 9-23 years), including monozygotic and dizygotic twins and their siblings, structural magnetic resonance imaging scans (N = 673) at 3 time points were acquired. Using brain morphology data of different types and at different spatial scales, brain age predictors were trained and validated. Differences in brain age between males and females were assessed and the heritability of individual variation in brain age gaps was calculated. On average, females were ahead of males by at most 1 year, but similar aging patterns were found for both sexes. The difference between brain age and chronological age was heritable, as was the change in brain age gap over time. In conclusion, females and males show similar developmental ("aging") patterns but, on average, females pass through this development earlier. Reliable brain age predictors may be used to detect (extreme) deviations in developmental state of the brain early, possibly indicating aberrant development as a sign of risk of neurodevelopmental disorders., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

The biological mediators that support cognitive-control and long-term weight-loss after laparoscopic sleeve gastrectomy (LSG) remain unclear. We measured peripheral appetitive hormones and brain functional-connectivity (FC) using magnetic-resonance-imaging with food cue-reactivity task in 25 obese participants at pre, 1 month, and 6 month after LSG, and compared with 30 normal weight controls. We also used diffusion-tensor-imaging to explore whether LSG increases brain structural-connectivity (SC) of regions involved in food cue-reactivity. LSG significantly decreased BMI, craving for high-calorie food cues, ghrelin, insulin, and leptin levels, and increased self-reported cognitive-control of eating behavior. LSG increased FC between the right dorsolateral prefrontal cortex (DLPFC) and the pregenual anterior cingulate cortex (pgACC) and increased SC between DLPFC and ACC at 1 month and 6 month after LSG. Reduction in BMI correlated negatively with increased FC of right DLPFC-pgACC at 1 month and with increased SC of DLPFC-ACC at 1 month and 6 month after LSG. Reduction in craving for high-calorie food cues correlated negatively with increased FC of DLPFC-pgACC at 6 month after LSG. Additionally, SC of DLPFC-ACC mediated the relationship between lower ghrelin levels and greater cognitive control. These findings provide evidence that LSG improved functional and structural connectivity in prefrontal regions, which contribute to enhanced cognitive-control and sustained weight-loss following surgery., (© The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com.)

Background: Recent cross-sectional studies highlighted the loss of dopaminergic neurons in the ventral tegmental area (VTA) as an early pathophysiological event in Alzheimer's disease (AD)., Objective: In this study, we longitudinally investigated by resting-state fMRI (rs-fMRI) a cohort of patients with mild cognitive impairment (MCI) due to AD to evaluate the impact of VTA disconnection in predicting the conversion to AD., Methods: A cohort of 35 patients with MCI due to AD were recruited and followed-up for 24 months. They underwent cognitive evaluation and rs-fMRI to assess VTA connectivity at baseline and at follow-up., Results: At 24-month follow-up, 16 out of 35 patients converted to AD. Although converters and non-converters to AD did not differ in demographic and behavioral characteristics at baseline, the first group showed a significant reduction of VTA-driven connectivity in the posterior cingulate and precentral cortex. This pattern of additional disconnection in MCI-Converters compared to non-converters remained substantially unchanged at 24-month follow-up., Conclusion: This study reinforces the hypothesis of an early contribution of dopaminergic dysfunction to AD evolution by targeting the default-mode network. These results have potential implications for AD staging and prognosis and support new opportunities for therapeutic interventions to slow down disease progression.

Objective: The aim of this study was to determine common structural and functional networks associated with asymmetric step length after unilateral ischemic stroke., Methods: Thirty-nine chronic stroke patients were divided into two groups, based on the presence or absence of asymmetric step length. In each group, each lesion was mapped onto a brain magnetic resonance image. The structural and functional networks of brain regions connected to each lesion were identified using a public diffusion tensor and resting state function magnetic resonance image dataset. To identify brain regions associated with asymmetric step length, we conducted voxel-wise independent sample t-tests for structural and function lesion network maps., Results: At least 85% of lesions showed functional network overlap in the bilateral frontal lobe. Functional connectivity of the dorsolateral prefrontal cortex in the contralesional hemisphere was significantly decreased in group 1 compared to that in group 2., Conclusions: The dorsolateral prefrontal cortex may have an important role in compensating for an asymmetric step length after a unilateral stroke.

Objective: The "Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)" disease caused a challenging and threating pandemic (COVID-19) worldwide with a great loss to life and the global economy. SARS-CoV-2 mainly involves the respiratory system, however, with Magnetic Resonance Imaging (MRI), neurological and special senses clinical manifestations have been reported rarely. The present study aims to investigate the MRI findings, clinical manifestations of neurological and special senses involvement in SARS-CoV-2 patients., Materials and Methods: In this study, 284 articles from the databases "Pub-Med, Web of Science-Clarivate Analytics, Embase and Google Scholar" were identified. The keywords, coronavirus, SARS-CoV-2, COVID-19 pandemic, MRI, brain, special senses, neurological involvement were entered into the search engines and the concerned documents were selected and reviewed. The descriptive information was recorded from the particular studies; finally, we included 48 publications., Results: The common neurological manifestations in SARS-CoV-2 patients were headache, impaired consciousness, acute cerebrovascular disease, ataxia, tremors, meningitis, encephalitis, cerebral bleeding, subarachnoid hemorrhage, frontal lobe, temporal lobe and intracerebral hematoma, hemiparesis and seizures. However, common special senses manifestations in SARS-CoV-2 patients were olfactory, auditory and gustatory disorders including red eyes, painless monocular visual disturbance, anosmia, ageusia, dysgeusia, dysosmia and hypoacusis. Moreover, the MRI findings identified in SARS-CoV-2 patients were isolated oval-shaped lesion in the corpus callosum, bilateral basal ganglia hemorrhage, ischemic lesions involving the corpus callosum, basal ganglia, cerebellum and vasogenic edema extending to the cerebral peduncles, pons and ventricles., Conclusions: The neurologic manifestations of SARS-CoV-2 patients are highly variable. The SARS-COV-2 exerts its damaging effects on the nervous system and special senses by developing determinant numerous neurological and special senses' clinical manifestations. Physicians with the help of MRI must rule out the neurological and special senses manifestations among SARS-CoV-2 patients.

Patterns of change in whole-brain functional networks remain poorly understood in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD). We conducted a prospective research to investigate the topological properties of whole-brain functional networks in those patients using a graph-based network analysis. Resting-state functional magnetic resonance imaging was performed on 51 ESRD patients (25 HD and 26 nondialysis patients) and 36 healthy controls (HCs). We compared the topological properties of brain functional networks among the three groups, and analyzed the relationships between those significant parameters and clinical variables in ESRD patients. Progressively disrupted global topological organizations were observed from nondialysis patients to HD patients compared with HCs (all p < 0.05 after Bonferroni correction). HD patients, relative to HCs, showed significantly decreased nodal centralities in the left temporal pole: superior temporal gyrus, bilateral median cingulate and paracingulate gyri, bilateral hippocampus, bilateral parahippocampal gyrus, and bilateral amygdala, and showed increased nodal centralities in the orbital part of the bilateral middle frontal gyrus, left cuneus, and left superior occipital gyrus (all p < 0.05 after Bonferroni correction). Furthermore, nodal centralities in the bilateral hippocampus were significantly decreased in HD patients compared with nondialysis patients (p < 0.05 after Bonferroni correction). Dialysis duration negatively correlated with global efficiency in ESRD patients undergoing HD (r = -0.676, FDR q = 0.004). This study indicates that ESRD patients exhibit disruptions in brain functional networks, which are more severe in HD patients, and these alterations are correlated with cognitive performance and clinical markers., (© 2020 Wiley Periodicals LLC.)

Objectives: The aim of this longitudinal study was to clarify whether significant alterations in structural connectivity occur over time in patients with newly diagnosed focal epilepsy of unknown origin., Methods: A total of 40 patients with newly diagnosed focal epilepsy of unknown origin and with normal brain magnetic resonance imaging (MRI) on visual inspection were enrolled. All subjects underwent MRI twice involving three-dimensional volumetric T1-weighted imaging, which were suitable for structural volume analysis. Gray matter volumes were obtained using the FreeSurfer image analysis suite, and structural connectivity analyses were performed using Matlab-based BRain Analysis using graPH theory software., Results: The median interval between the two MRI scans was 18.5 months in patients with epilepsy. There was a general tendency toward decreased gray matter volumes on the second scan compared with the initial scan. However, the volumes of the right and left thalamus and brainstem on the second MRI scan had an increased tendency compared with those on the initial MRI scan. In measures of connectivity, there were significant differences between the two MRI scans. The mean clustering coefficient, global efficiency, local efficiency, and the small-worldness index were significantly increased, whereas the characteristic path length was decreased on the second MRI scan compared with the initial MRI scan., Conclusions: The structural connectivity in patients with newly diagnosed focal epilepsy of unknown origin increases over time in the initial stage. These alterations and increases in structural connectivity may be related to underlying epileptogenicity in the initial stages of epilepsy., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Rationale: Previous studies have suggested that chronic cannabis use has been associated with increased blood oxygen level-dependent (BOLD) response during a response inhibition task; however, these studies primarily included males., Objectives: We investigated whether gender moderated the effects of cannabis use on BOLD response and behavioral performance during a Go-NoGo task in adolescents and young adults following 2 weeks of monitored abstinence., Methods: Participants included 77 16-26-year olds (MJ = 36, controls = 41). An emotion-based Go-NoGo task required participants to inhibit their response during a calm face. A whole-brain analysis looked at differences between cannabis group, gender, and their interaction., Results: Significant greater BOLD responses were observed in cannabis users compared with that in controls in the left frontal cortex, left cingulate cortex, and the left thalamus during correct response inhibitions; gender did not moderate these effects., Conclusion: Supporting previous research, cannabis users showed greater BOLD responses in core areas associated with response inhibition during a Go-NoGo task, even after a minimum of 2 weeks of abstinence.

Objective: The disconnectivity hypothesis postulates that partial loss of connecting white matter fibers between brain regions contributes to the development of dementia. Using diffusion MRI to quantify global and tract-specific white matter microstructural integrity, we tested this hypothesis in a longitudinal population-based study., Methods: Global and tract-specific fractional anisotropy (FA) and mean diffusivity (MD) were obtained in 4,415 people without dementia (mean age 63.9 years, 55.0% women) from the prospective population-based Rotterdam Study with brain MRI between 2005 and 2011. We modeled the association of these diffusion measures with risk of dementia (follow-up until 2016) and with changes on repeated cognitive assessment after on average 5.4 years, adjusting for age, sex, education, macrostructural MRI markers, depressive symptoms, cardiovascular risk factors, and APOE genotype., Results: During a median follow-up of 6.8 years, 101 participants had incident dementia, of whom 83 had clinical Alzheimer disease (AD). Lower global values of FA and higher values of MD were associated with an increased risk of dementia (adjusted hazard ratio [95% confidence interval (CI)] per SD increase for MD 1.79 [1.44-2.23] and FA 0.65 [0.52-0.80]). Similarly, lower global values of FA and higher values of MD related to more cognitive decline in people without dementia (difference in global cognition per SD increase in MD [95% CI] was -0.04 [-0.07 to -0.01]). Associations were most profound in the projection, association, and limbic system tracts., Conclusions: Structural disconnectivity is associated with an increased risk of dementia and more pronounced cognitive decline in the general population., (© 2020 American Academy of Neurology.)

Research suggests that the aging relates to variability of resting-state fMRI (rs-fMRI) signal and the functional connectivity. However, the association between the spatial and temporal activity of resting-state fMRI signal was less documented. We recruited 477 healthy Han Chinese participants, who were separated into young, middle and old groups to investigate the relationship between the variability and global functional connectivity (gFC) in different age ranges using standard deviation (SD) of time series and gFC, respectively. Our analysis revealed the changing patterns during healthy aging: 1) 17 brain regions(Olfactory&#95;L, Orbital&#95;L etc.) were identified to have significant association of age with both SD and gFC respectively by linear regression analysis; 2) Two typical associations could be observed between SD and gFC: positive and negative correlations; 3) The variation ratio of SD to gFC was changing with age at the voxel level by using unsupervised clustering method. It is the first time to combine voxel-wise variability and gFC together for the study of age-related changes with rs-fMRI signal. This study may provide a new clue for understanding the synchronization of human brain based on SD and gFC due to the effect of aging., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

There is considerable interest in the long-term brain health of retired contact and collision sport athletes; however, little is known about possible underlying changes in functional brain connectivity in this group. We evaluated whole-brain functional connectivity patterns using multi-voxel pattern analysis (MVPA) to determine whether alterations in functional connectivity distinguish retired professional athletes from a matched group of healthy community control subjects. Thirty-two retired athletes with a history of multiple self-reported sport-related concussions and 36 healthy community control subjects who were similar in age and education, completed functional magnetic resonance imaging. We identified brain regions with abnormal functional connectivity patterns using whole-brain MVPA as implemented in the Conn toolbox. First-level MVPA was performed using 64 principal component analysis (PCA) components. Second-level F test was performed using the first three MVPA components for retired athletes > controls group contrast. Post hoc seed-to-voxel analyses using the MVPA cluster results as seeds were performed to characterize functional connectivity abnormalities from brain regions identified by MVPA. MVPA revealed one cluster of abnormal functional connectivity located in cerebellar lobule V. This region of lobule V corresponded to the ventral attention network. Post hoc seed-to-voxel analysis using the cerebellar MVPA cluster as a seed revealed multiple areas of cerebral cortical hyper-connectivity and hypo-connectivity in retired athletes when compared with controls. This initial report suggests that cerebellar dysfunction might be present and clinically important in some retired athletes.