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Human pose, defined as the spatial relationships between body parts, carries instrumental information supporting the understanding of motion and action of a person. A substantial body of previous work has identified cortical areas responsive to images of bodies and different body parts. However, the neural basis underlying the visual perception of body part relationships has received less attention. To broaden our understanding of body perception, we analyzed high-resolution fMRI responses to a wide range of poses from over 4,000 complex natural scenes. Using ground-truth annotations and an application of three-dimensional (3D) pose reconstruction algorithms, we compared similarity patterns of cortical activity with similarity patterns built from human pose models with different levels of depth availability and viewpoint dependency. Targeting the challenge of explaining variance in complex natural image responses with interpretable models, we achieved statistically significant correlations between pose models and cortical activity patterns (though performance levels are substantially lower than the noise ceiling). We found that the 3D view-independent pose model, compared with two-dimensional models, better captures the activation from distinct cortical areas, including the right posterior superior temporal sulcus (pSTS). These areas, together with other pose-selective regions in the LOTC, form a broader, distributed cortical network with greater view-tolerance in more anterior patches. We interpret these findings in light of the computational complexity of natural body images, the wide range of visual tasks supported by pose structures, and possible shared principles for view-invariant processing between articulated objects and ordinary, rigid objects., Competing Interests: Competing interests statement:The authors declare no competing interest.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterised by neuroinflammation, for which gut dysbiosis may be implicated. Our previous study showed that treatment with Pseudostellaria heterophylla aqueous extract and one of its cyclopeptides, heterophyllin B, attenuate memory deficits via immunomodulation and neurite regeneration. However, whether Pseudostellaria heterophylla polysaccharide (PH-PS) exerts neuroprotective effects against AD and its underlying mechanisms remain unclear. The infrared spectrum, molecular weight, and carbohydrate composition of the PH-PS were determined. The results showed that PH-PS (Mw 8.771 kDa) was composed of glucose (57.78 %), galactose (41.52 %), and arabinose (0.70 %). PH-PS treatment ameliorated learning and spatial memory deficits, reduced amyloid β build-up, and suppressed reactive glia and astrocytes in 5 × FAD mice. 16S rRNA sequencing further showed that PH-PS remodelled the intestinal flora composition by promoting probiotic microbiota, such as Lactobacillus, Muribaculum, Monoglobus, and [Eubacterium]_siraeum_group, and suppressing inflammation-related UCG-009 and Blautia. Additionally, PH-PS restored intestinal barrier function; ameliorated peripheral inflammation by reducing the secretion of inflammatory cytokines, thereby converting M1 microglia and A1 astrocyte toward beneficial M2 and A2 phenotypes; and contributed to Aβ plaques clearance by upregulation of insulin degradation enzyme and neprilysin. Collectively, our findings demonstrate that PH-PS may prevent the progression of AD via modulation of the gut microbiota and regulation of glial polarisation, which could provide evidence to design a potential diet therapy for preventing or curing AD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Zhiyou Yang reports financial support was provided by Guangdong Basic and Applied Basic Research Foundation (grant number 2022A1515011419). Zhiyou Yang reports financial support was provided by Key Project in Higher Education of Guangdong, China (grant number 2022ZDZX2029). Zhiyou Yang reports financial support was provided by Special Funds for Science and Technology Development of Zhanjiang City (230906164548778). Zhiyou Yang reports financial support was provided by Innovative Team Program of High Education of Guangdong Province (2021KCXTD021). If there are other authors, they 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 Elsevier B.V. All rights reserved.)

Human genetic studies indicate that suicidal ideation and behavior are both heritable. Most studies have examined associations between aberrant gene expression and suicide behavior, but behavior risk is linked to the severity of suicidal ideation. Through a gene network approach, this study investigates how gene co-expression patterns are associated with suicidal ideation and severity using RNA-seq data in peripheral blood from 46 live participants with elevated suicidal ideation and 46 with no ideation. Associations with the presence of suicidal ideation were found within 18 co-expressed modules (p < 0.05), as well as in 3 co-expressed modules associated with suicidal ideation severity (p < 0.05, not explained by severity of depression). Suicidal ideation presence and severity-related gene modules with enrichment of genes involved in defense against microbial infection, inflammation, and adaptive immune response were identified and investigated using RNA-seq data from postmortem brain that revealed gene expression differences with moderate effect sizes in suicide decedents vs. non-suicides in white matter, but not gray matter. Findings support a role of brain and peripheral blood inflammation in suicide risk, showing that suicidal ideation presence and severity are associated with an inflammatory signature detectable in blood and brain, indicating a biological continuity between ideation and suicidal behavior that may underlie a common heritability., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Objective: Multi-shot interleaved echo planer imaging (Ms-iEPI) can obtain diffusion-weighted images (DWI) with high spatial resolution and low distortion, but suffers from ghost artifacts introduced by phase variations between shots. In this work, we aim at solving the ms-iEPI DWI reconstructions under inter-shot motions and ultra-high b-values., Methods: An iteratively joint estimation model with paired phase and magnitude priors is proposed to regularize the reconstruction (PAIR). The former prior is low-rankness in the k-space domain. The latter explores similar edges among multi-b-value and multi-direction DWI with weighted total variation in the image domain. The weighted total variation transfers edge information from the high SNR images (b-value = 0) to DWI reconstructions, achieving simultaneously noise suppression and image edges preservation., Results: Results on simulated and in vivo data show that PAIR can remove inter-shot motion artifacts very well (8 shots) and suppress the noise under the ultra-high b-value (4000 s/mm 2 ) significantly., Conclusion: The joint estimation model PAIR with complementary priors has a good performance on challenging reconstructions under inter-shot motions and a low signal-to-noise ratio., Significance: PAIR has potential in advanced clinical DWI applications and microstructure research.

Cluster-wise inference is widely used in fMRI analysis. The cluster-level statistic is often obtained by counting the number of intra-cluster voxels which surpass a voxel-level statistical significance threshold. This measure can be sub-optimal regarding the power and false-positive error rate because the suprathreshold voxel count neglects the voxel-wise significance levels and ignores the dependence between voxels. This article aims to provide a new Integrated Cluster-wise significance Measure (ICM) for cluster-level significance determination in cluster-wise fMRI analysis by integrating cluster extent, voxel-level significance (e.g., p values), and activation dependence between within-cluster voxels. We develop a computationally efficient strategy for ICM based on probabilistic approximation theories. Consequently, the computational load for ICM-based cluster-wise inference (e.g., permutation tests) is affordable. We validate the proposed method via extensive simulations and then apply it to two fMRI data sets. The results demonstrate that ICM can improve the power with well-controlled family-wise error (FWE)., (© 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

Previous studies have revealed changed functional connectivity patterns between brain areas in chess players using resting-state functional magnetic resonance imaging (rs-fMRI). However, how to exactly characterize the voxel-wise whole brain functional connectivity pattern changes in chess players remains unclear. It could provide more convincing evidence for establishing the relationship between long-term chess practice and brain function changes. In this study, we employed newly developed whole brain functional connectivity pattern homogeneity (FcHo) method to identify the voxel-wise changes of functional connectivity patterns in 28 chess master players and 27 healthy novices. Seed-based functional connectivity analysis was used to identify the alteration of corresponding functional couplings. FcHo analysis revealed significantly increased whole brain functional connectivity pattern similarity in anterior cingulate cortex (ACC), anterior middle temporal gyrus (aMTG), primary visual cortex (V1), and decreased FcHo in thalamus and precentral gyrus in chess players. Resting-state functional connectivity analyses identified chess players showing decreased functional connections between V1 and precentral gyrus. Besides, a linear support vector machine (SVM) based classification achieved an accuracy of 85.45%, a sensitivity of 85.71% and a specificity of 85.19% to differentiate chess players from novices by leave-one-out cross-validation. Finally, correlation analyses revealed that the mean FcHo values of thalamus were significantly negatively correlated with the training time. Our findings provide new evidences for the important roles of ACC, aMTG, V1, thalamus and precentral gyrus in chess players. The findings also indicate that long-term professional chess training may enhance the semantic and episodic processing, efficiency of visual-motor transformation, and cognitive ability., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

1 H MRI maps brain structure and function non-invasively through versatile contrasts that exploit inhomogeneity in tissue micro-environments. Inferring histopathological information from magnetic resonance imaging (MRI) findings, however, remains challenging due to absence of direct links between MRI signals and cellular structures. Here, we show that deep convolutional neural networks, developed using co-registered multi-contrast MRI and histological data of the mouse brain, can estimate histological staining intensity directly from MRI signals at each voxel. The results provide three-dimensional maps of axons and myelin with tissue contrasts that closely mimic target histology and enhanced sensitivity and specificity compared to conventional MRI markers. Furthermore, the relative contribution of each MRI contrast within the networks can be used to optimize multi-contrast MRI acquisition. We anticipate our method to be a starting point for translation of MRI results into easy-to-understand virtual histology for neurobiologists and provide resources for validating novel MRI techniques., Competing Interests: ZL, CL, TA, ZD, PW, SS, FK, YG, LY, JZ No competing interests declared, (© 2022, Liang et al.)

Tryptophan is an essential amino acid critical for protein synthesis in humans that has emerged as a key player in the microbiota-gut-brain axis. It is the only precursor for the neurotransmitter serotonin, which is vital for the processing of emotional regulation, hunger, sleep, and pain, as well as colonic motility and secretory activity in the gut. Tryptophan catabolites from the kynurenine degradation pathway also modulate neural activity and are active in the systemic inflammatory cascade. Additionally, tryptophan and its metabolites support the development of the central and enteric nervous systems. Accordingly, dysregulation of tryptophan metabolites plays a central role in the pathogenesis of many neurologic and psychiatric disorders. Gut microbes influence tryptophan metabolism directly and indirectly, with corresponding changes in behavior and cognition. The gut microbiome has thus garnered much attention as a therapeutic target for both neurologic and psychiatric disorders where tryptophan and its metabolites play a prominent role. In this review, we will touch upon some of these features and their involvement in health and disease.

In order to explore the topological alterations in functional brain networks between multiple system atrophy (MSA) patients and healthy controls (HC), a new joint analysis method of static and dynamic functional connectivity (FC) is proposed in this paper. Twenty-four MSA patients and twenty HCs were enrolled in this study. We constructed static and dynamic brain networks from resting-state fMRI data and calculated four graph theory attributes. Statistical comparisons and correlation analysis were carried out for static and dynamic FC separately before combining both cases. We found decreased local efficiency (LE) and weighted degree (WD) in cerebellum from both static and dynamic graph attributes. For static FC alone, we identified increased betweenness centrality (BC) at left dorsolateral prefrontal cortex, left Cerebellum&#95;Crus9 and decreased WD at Vermis&#95;6. For dynamic FC alone, decreased BC, clustering coefficients and LE at several cortical regions and cerebellum were identified. All the features had significant correlation with total UMSARS scores. Receiver operating characteristic analysis showed that dynamic features had the highest area under the curve value. Our work not only added new evidence for the underlying neurobiology and disrupted dynamic disconnection syndrome of MSA, but also proved the possibility of disease diagnosis and progression tracking using rs-fMRI.

Background: In neuromyelitis optica spectrum disorder (NMOSD), clinical disability in NMOSD patients is relapse-related and progressive phase is rare. This observation raises the question whether there is any radiographic disease activity. The aim of present study was to determine the longitudinal changes in cerebral lesion number, lesion size, lesion-to-venule relationship, and morphological patterns of lesions in NMOSD using multiparametric 7T MR imaging. We also aimed to assess brain volume changes in NMOSD., Methods: A cohort of 22 patients with NMOSD underwent high-resolution 3D-susceptibility weighted imaging (SWI) and 2D-gradient-echo (GRE-T2*) weighted imaging on 7T MRI of brain at baseline and after ~2.8 years of follow-up. Morphologic imaging characteristics, and signal intensity patterns of lesions were recorded at both time points. Lesions were classified as "iron-laden" if they demonstrated hypointense signal on GRE-T2* images and/or SWI as well as hyperintense signal on quantitative susceptibility mapping (QSM). Lesions were considered "non-iron-laden" if they were hyperintense on GRE-T2*/SWI and isointense or hyperintense on QSM. Additionally, fractional brain parenchymal volume (fBPV) was computed at both time points., Results: A total of 169 lesions were observed at baseline. At follow-up, 6 new lesions were found in 5 patients. In one patient, a single lesion could not be detected on the follow-up scan. No appreciable change in lesion size and vessel-lesion relationship was observed at follow up. All lesions demonstrated hyperintense signal intensity on GRE-T2* weighted images and isointense signal on QSM at both time points. Therefore, these lesions were considered as non-associated with iron pathology. Additionally, no significant change in brain volume was observed: fBPV 0.78 ± 0.06 at baseline vs. 0.77 ± 0.05 at follow up, p>0.05., Conclusion: Cerebral lesions in NMOSD patients remain 'inert' and do not show any substantial variations in morphological characteristics during a 2-3-year follow-up period., Competing Interests: Declaration of Competing Interest We report no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Cannabinoids are reported to rescue cocaine-induced seizures (CISs), a severe complication in cocaine users. However, the molecular targets for cannabinoid therapy of CISs remain unclear. Here, we report that the systemic administration of cannabinoids alleviates CISs in a CB 1 /CB 2 -receptor-independent manner. In HEK293 cells and cortical neurons, cocaine-induced dysfunction of the glycine receptor (GlyR) is restored by cannabinoids. Such restoration is blocked by GlyRα1 S296A mutation. Consistently, the therapeutic effects of cannabinoids on CISs are also eliminated in GlyRα1 S296A mutant mice. Based on molecular dynamic simulation, the hydrogen-bonding interaction between cocaine and the GlyR is weakened by cannabinoid docking. Without altering cocaine distribution across the brain, cannabinoids significantly suppress cocaine-exaggerated neuronal excitability in the prefrontal cortex (PFC) and hippocampus by rehabilitating extra-synaptic GlyR function. Microinjection of cannabinoids into the PFC and hippocampus restores cocaine-puzzled neural activity and alleviates CISs. These findings suggest that using GlyR-hypersensitive cannabinoids may represent a potential therapeutic strategy for treating CISs., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Emotions are processed asymmetrically by the human brain. Frontal alpha asymmetry (FAA) as measured by electroencephalographic (EEG) power in the alpha band (8-13 Hz), is a sensitive indicator of asymmetric brain activity in the frontal cortex. The current study aimed to analyze the frontal EEG asymmetries in terms of valence and motivational direction. We presented 37 participants with three film excerpts that were selected from the standard emotional film database to elicit three target emotions: tenderness, anger, and neutrality. Participants' self-reports on their induced emotional responses and EEG signals were recorded and analyzed. The results showed that individuals displayed lower alpha power in the left hemisphere than the right hemisphere when they were watching a tender film, indicating that tenderness was positive and related to approach motivation. In contrast, when watching an angry movie, participants showed higher alpha power in the left hemisphere than the right hemisphere, suggesting that anger was negative and associated with withdrawal motivation. These findings help to link positive and approach-motivated tenderness with greater left hemispheric activation and state-anger with greater right hemispheric activation through the analysis of FAA.

Lead poisoning is a geochemical disease. On the other hand, lead is highly carcinogenic and exhibits liver and kidney toxicity. This element can also cross the blood-brain barrier, reduce learning and memory ability and damage the structure of the cerebral cortex and hippocampus. To further investigate the mechanism of lead neurotoxicity, 4-week-old Kunming mice were used to explore the effects of different concentrations of Pb 2+ (0, 2.4, 4.8 and 9.6 mM) for 9 days. In this study, pathological and ultrastructural changes in brain cells of the treated group were related to damages to mitochondria, chromatin and the nucleus. Lead content in blood was tested by atomic absorption spectroscopy, which showed high lead concentrations in the blood with increasing doses of lead. Distribution of lead in nerve cells was analysed by transmission electron microscopy with energy dispersive spectroscopy. Data showed the presence of lead in nucleopores, chromatin and nuclear membrane of nerve cells in the treatment groups, whereas lead content increased with increasing doses of lead acetate. Finally, microtubule-associated protein 2 (MAP2) mRNA and protein expression levels were detected by real-time PCR and Western blotting, which showed a reduction in MAP2 expression with increasing lead doses in the mouse brain. These findings suggest that acute lead poisoning can cause significant dose-dependent toxic effects on mouse brain function and can contribute to better understanding of lead-induced toxicity.

Purpose: To demonstrate the potential of imaging cerebral arteries and veins with ferumoxytol using susceptibility weighted imaging (SWI) and quantitative susceptibility mapping (QSM)., Materials and Methods: The relationships between ferumoxytol concentration and the apparent susceptibility at 1.5T, 3T, and 7T were determined using phantom data; the ability of visualizing subvoxel vessels was evaluated using simulations; and the feasibility of using ferumoxytol to enhance the visibility of small vessels was confirmed in three healthy volunteers at 7T(with doses 1 mg/kg to 4 mg/kg). The visualization of the lenticulostriate arteries and the medullary veins was assessed by two raters and the contrast-to-noise ratios (CNRs) of these vessels were measured., Results: The relationship between ferumoxytol concentration and susceptibility was linear with a slope 13.3 ± 0.2 ppm·mg -1 ·mL at 7T. Simulations showed that SWI data with an increased dose of ferumoxytol, higher echo time (TE), and higher imaging resolution improved the detection of smaller vessels. With 4 mg/kg ferumoxytol, voxel aspect ratio = 1:8, TE = 10 ms, the diameter of the smallest detectable artery was approximately 50μm. The rating score for arteries was improved from 1.5 ± 0.5 (precontrast) to 3.0 ± 0.0 (post-4 mg/kg) in the in vivo data and the apparent susceptibilities of the arteries (0.65 ± 0.02 ppm at 4 mg/kg) agreed well with the expected susceptibility (0.71 ± 0.05 ppm)., Conclusion: The CNR for cerebral vessels with ferumoxytol can be enhanced using SWI, and the apparent susceptibilities of the arteries can be reliably quantified using QSM. This approach improves the imaging of the entire vascular system outside the capillaries and may be valuable for a variety of neurodegenerative diseases which involve the microvasculature., Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:621-633., (© 2017 International Society for Magnetic Resonance in Medicine.)

Background: Although research has demonstrated that the mirror neuron system (MNS) plays a crucial role in both action imitation and action-related semantic processing, whether action-related words can inversely modulate the MNS activity remains unclear., Methods: Here, three types of task-irrelevant words (body parts, verbs, and manufactured objects) were presented to examine the modulation effect of these words on the MNS activity during action observation and imitation. Twenty-two participants were recruited for the fMRI scanning and remaining data from 19 subjects were reported here., Results: Brain activity results showed that word types elicited different modulation effects over nodes of the MNS (i.e., the right inferior frontal gyrus, premotor cortex, inferior parietal lobule, and STS), especially during the imitation stage. Compared with other word conditions, action imitation following manufactured objects words induced stronger activation in these brain regions during the imitation stage. These results were consistent in both task-dependent and -independent ROI analysis., Conclusion: Our findings thus provide evidence for the unique effect of object words on the MNS during imitation of action, which may also confirm the key role of goal inference in action imitation.

A better understanding of the effect of oxygen on brain electrophysiological activity may provide a more mechanistic insight into clinical studies that use oxygen treatment in pathological conditions, as well as in studies that use oxygen to calibrate functional magnetic resonance imaging (fMRI) signals. This study applied electroencephalography (EEG) in healthy subjects and investigated how high a concentration of oxygen in inhaled air (i.e., normobaric hyperoxia) alters brain activity under resting-state and task-evoked conditions. Study 1 investigated its impact on resting EEG and revealed that hyperoxia suppressed α (8-13Hz) and β (14-35Hz) band power (by 15.6±2.3% and 14.1±3.1%, respectively), but did not change the δ (1-3Hz), θ (4-7Hz), and γ (36-75Hz) bands. Sham control experiments did not result in such changes. Study 2 reproduced these findings, and, furthermore, examined the effect of hyperoxia on visual stimulation event-related potentials (ERP). It was found that the main peaks of visual ERP, specifically N1 and P2, were both delayed during hyperoxia compared to normoxia (P = 0.04 and 0.02, respectively). In contrast, the amplitude of the peaks did not show a change. Our results suggest that hyperoxia has a pronounced effect on brain neural activity, for both resting-state and task-evoked potentials.

Background: Intrauterine exposure to maternal smoking is linked to impaired executive function and behavioral problems in the offspring. Maternal smoking is associated with reduced fetal brain growth and smaller volume of cortical gray matter in childhood, indicating that prenatal exposure to tobacco may impact cortical development and manifest as behavioral problems. Cellular development is mediated by changes in epigenetic modifications such as DNA methylation, which can be affected by exposure to tobacco., Results: In this study, we sought to ascertain how maternal smoking during pregnancy affects global DNA methylation profiles of the developing dorsolateral prefrontal cortex (DLPFC) during the second trimester of gestation. When DLPFC methylation profiles (assayed via Illumina, HM450) of smoking-exposed and unexposed fetuses were compared, no differentially methylated regions (DMRs) passed the false discovery correction (FDR ≤ 0.05). However, the most significant DMRs were hypomethylated CpG Islands within the promoter regions of GNA15 and SDHAP3 of smoking-exposed fetuses. Interestingly, the developmental up-regulation of SDHAP3 mRNA was delayed in smoking-exposed fetuses. Interaction analysis between gestational age and smoking exposure identified significant DMRs annotated to SYCE3 , C21orf56 / LSS, SPAG1 and RNU12 / POLDIP3 that passed FDR. Furthermore, utilizing established methods to estimate cell proportions by DNA methylation, we found that exposed DLPFC samples contained a lower proportion of neurons in samples from fetuses exposed to maternal smoking. We also show through in vitro experiments that nicotine impedes the differentiation of neurons independent of cell death., Conclusions: We found evidence that intrauterine smoking exposure alters the developmental patterning of DNA methylation and gene expression and is associated with reduced mature neuronal content, effects that are likely driven by nicotine.

Brain connectivity analysis plays an essential role in the research of working memory that involves complex coordination of various brain regions. In this research, we present a comprehensive view of trans-states brain connectivity variation based on continuous scalp EEG, extending beyond traditional stimuli-lock averaging or restriction to short time scales of hundreds of milliseconds after stimulus onset. The scalp EEG was collected under three conditions: quiet, memory, and control. The only difference between the memory and control conditions was that in the memory condition, subjects made an effort to retain information. We started our investigation with calibrations of Pearson correlation in EEG analysis and then derived two indices, link strength and node connectivity, to make comparisons between different states. Finally, we constructed and studied trans-state brain connectivity variation topography. Comparing memory and control states with quiet state, we found that the beta topography highlights links between T5/T6 and O1/O2, which represents the visual ventral stream, and the gamma topography conveys strengthening of inter-hemisphere links and weakening of intra-hemisphere frontal-posterior links, implying parallel inter-hemisphere coordination combined with sequential intra-hemisphere coordination when subjects are confronted with visual stimuli and a motor task. For comparison between memory and control states, we also found that the node connectivity of T6 stands out in gamma topography, which provides strong proof from scalp EEG for the information binding or relational processing function of the temporal lobe in memory formation. To our knowledge, this is the first time for any method to effectively capture brain connectivity variation associated with working memory from a relatively large scale both in time (from a second to a minute) and in space (from the scalp). The method can track brain activity continuously with minimal manual interruptions; therefore, it has promising potential in applications such as brain computer interfaces and brain training., Competing Interests: The authors have declared that no competing interests exist.

Cerebrovascular reactivity measures vascular regulation of cerebral blood flow and is responsible for maintaining healthy neurovascular coupling. Multiple sclerosis exhibits progressive neurodegeneration and global cerebrovascular reactivity deficits. This study investigates varied degrees of cerebrovascular reactivity impairment in different brain networks, which may be an underlying cause for functional changes in the brain, affecting long-distance projection integrity and cognitive function; 28 multiple sclerosis and 28 control subjects underwent pseudocontinuous arterial spin labeling perfusion MRI to measure cerebral blood flow under normocapnia (room air) and hypercapnia (5% carbon dioxide gas mixture) breathing. Cerebrovascular reactivity, measured as normocapnic to hypercapnic cerebral blood flow percent increase normalized by end-tidal carbon dioxide change, was determined from seven functional networks (default mode, frontoparietal, somatomotor, visual, limbic, dorsal, and ventral attention networks). Group analysis showed significantly decreased cerebrovascular reactivity in patients compared to controls within the default mode, frontoparietal, somatomotor, and ventral attention networks after multiple comparison correction. Regression analysis showed a significant correlation of cerebrovascular reactivity with lesion load in the default mode and ventral attention networks and with gray matter atrophy in the default mode network. Functional networks in multiple sclerosis patients exhibit varied amounts of cerebrovascular reactivity deficits. Such blood flow regulation abnormalities may contribute to functional communication disruption in multiple sclerosis., (© The Author(s) 2016.)

Background and Purpose: Although NAA is often used as a marker of neuronal health and integrity in neurologic disorders, its normal response to physiologic challenge is not well-established and its changes are almost always attributed exclusively to brain pathology. The purpose of this study was to test the hypothesis that the neuronal cell marker NAA, often used to assess neuronal health and integrity in neurologic disorders, is not confounded by (possibly transient) physiologic changes. Therefore, its decline, when observed by using (1)H-MR spectroscopy, can almost always be attributed exclusively to brain pathology., Materials and Methods: Twelve healthy young male adults underwent a transient hypercapnia challenge (breathing 5% CO2 air mixture), a potent vasodilator known to cause a substantial increase in CBF and venous oxygenation. We evaluated their whole-brain NAA by using nonlocalizing proton MR spectroscopy, venous oxygenation with T2-relaxation under spin-tagging MR imaging, CBF with pseudocontinuous arterial spin-labeling, and the cerebral metabolic rate of oxygen, during normocapnia (breathing room air) and hypercapnia., Results: There was insignificant whole-brain NAA change (P = .88) from normocapnia to hypercapnia and back to normocapnia in this cohort, as opposed to highly significant increases: 28.0 ± 10.3% in venous oxygenation and 49.7 ± 16.6% in global CBF (P < 10(-4)); and a 6.4 ± 10.9% decrease in the global cerebral metabolic rate of oxygen (P = .04)., Conclusions: Stable whole-brain NAA during normocapnia and hypercapnia, despite significant global CBF and cerebral metabolic rate of oxygen changes, supports the hypothesis that global NAA changes are insensitive to transient physiology. Therefore, when observed, they most likely reflect underlying pathology resulting from neuronal cell integrity/viability changes, instead of a response to physiologic changes., (© 2015 by American Journal of Neuroradiology.)

Homotopy reflects the intrinsic functional architecture of the brain through synchronized spontaneous activity between corresponding bilateral regions, measured as voxel mirrored homotopic connectivity (VMHC). Hypercapnia is known to have clear impact on brain hemodynamics through vasodilation, but have unclear effect on neuronal activity. This study investigates the effect of hypercapnia on brain homotopy, achieved by breathing 5% carbon dioxide (CO2 ) gas mixture. A total of 14 healthy volunteers completed three resting state functional MRI (RS-fMRI) scans, the first and third under normocapnia and the second under hypercapnia. VMHC measures were calculated as the correlation between the BOLD signal of each voxel and its counterpart in the opposite hemisphere. Group analysis was performed between the hypercapnic and normocapnic VMHC maps. VMHC showed a diffused decrease in response to hypercapnia. Significant regional decreases in VMHC were observed in all anatomical lobes, except for the occipital lobe, in the following functional hierarchical subdivisions: the primary sensory-motor, unimodal, heteromodal, paralimbic, as well as in the following functional networks: ventral attention, somatomotor, default frontoparietal, and dorsal attention. Our observation that brain homotopy in RS-fMRI is affected by arterial CO2 levels suggests that caution should be used when comparing RS-fMRI data between healthy controls and patients with pulmonary diseases and unusual respiratory patterns such as sleep apnea or chronic obstructive pulmonary disease., (Copyright © 2015 Wiley Periodicals, Inc.)

Objective: The analysis of the MR phase provides additional information on the tissue microstructure. In multiple sclerosis (MS) lesions phase alterations may reflect different stages of inflammatory activity. Here we investigated lesion morphology in MS patients with short and long disease duration on T2* weighted, phase, magnitude and susceptibility weighted imaging (SWI) at 7 Tesla (T)., Methods: 17 MS or clinically isolated syndrome patients with short (<60 months) and 11 with long (>60 months) disease duration underwent 7 T MRI. Lesions were subsequently analyzed side-by-side with regard to morphology and visibility on T2* weighted, SWI, magnitude and SWI-filtered phase images., Results: 126 of 192 T2* weighted lesions (65.6%) were characterized by a phase alteration pattern, and hence could be differentiated on phase images. In detail, a significantly reduced proportion of lesions showing phase alterations was detectable in patients with longer disease duration (mean±SD 51 ± 37%, range 0-100%) compared to patients with short disease duration (mean ± SD 90 ± 19.5%, range 50-100%, p = 0.003)., Conclusion: This cross-sectional study identified different patterns of phase changes in lesions of MS patients with short and long standing disease. Longitudinal studies are warranted to prove that MR phase imaging is useful in determining the activity and the developmental stage of individual MS plaques.

The brain is a spatially heterogeneous and temporally dynamic organ, with different regions requiring different amount of blood supply at different time. Therefore, the ability of the blood vessels to dilate or constrict, known as Cerebral-Vascular-Reactivity (CVR), represents an important domain of vascular function. An imaging marker representing this dynamic property will provide new information of cerebral vessels under normal and diseased conditions such as stroke, dementia, atherosclerosis, small vessel diseases, brain tumor, traumatic brain injury, and multiple sclerosis. In order to perform this type of measurement in humans, it is necessary to deliver a vasoactive stimulus such as CO2 and/or O2 gas mixture while quantitative brain magnetic resonance images (MRI) are being collected. In this work, we presented a MR compatible gas-delivery system and the associated protocol that allow the delivery of special gas mixtures (e.g., O2, CO2, N2, and their combinations) while the subject is lying inside the MRI scanner. This system is relatively simple, economical, and easy to use, and the experimental protocol allows accurate mapping of CVR in both healthy volunteers and patients with neurological disorders. This approach has the potential to be used in broad clinical applications and in better understanding of brain vascular pathophysiology. In the video, we demonstrate how to set up the system inside an MRI suite and how to perform a complete experiment on a human participant.

Importance: Cerebrovascular reactivity (CVR) is an inherent indicator of the dilatory capacity of cerebral arterioles for a vasomotor stimulus for maintaining a spontaneous and instant increase of cerebral blood flow (CBF) in response to neural activation. The integrity of this mechanism is essential to preserving healthy neurovascular coupling; however, to our knowledge, no studies have investigated whether there are CVR abnormalities in multiple sclerosis (MS)., Objective: To use hypercapnic perfusion magnetic resonance imaging to assess CVR impairment in patients with MS., Design, Setting, and Participants: A total of 19 healthy volunteers and 19 patients with MS underwent perfusion magnetic resonance imaging based on pseudocontinuous arterial spin labeling to measure CBF at normocapnia (ie, breathing room air) and hypercapnia. The hypercapnia condition is achieved by breathing 5% carbon dioxide gas mixture, which is a potent vasodilator causing an increase of CBF., Main Outcomes and Measures: Cerebrovascular reactivity was calculated as the percent increase of normocapnic to hypercapnic CBF normalized by the change in end-tidal carbon dioxide, which was recorded during both conditions. Group analysis was performed for regional and global CVR comparison between patients and controls. Regression analysis was also performed between CVR values, lesion load, and brain atrophy measures in patients with MS., Results: A significant decrease of mean (SD) global gray matter CVR was found in patients with MS (3.56 [0.81]) compared with healthy controls (5.08 [1.56]; P = .001). Voxel-by-voxel analysis showed diffuse reduction of CVR in multiple regions of patients with MS. There was a significant negative correlation between gray matter CVR and lesion volume (R = 0.6, P = .004) and a significant positive correlation between global gray matter CVR and gray matter atrophy index (R = 0.5, P = .03)., Conclusions and Relevance: Our quantitative imaging findings suggest impairment in functional cerebrovascular pathophysiology, by measuring a diffuse decrease in CVR, which may be the underlying cause of neurodegeneration in MS.

Clinical studies find that childhood adversity and stressful life events in adulthood increase the risk for major depression and for suicide. The predispositions to either major depression or suicide are thought to depend on genetic risk factors or epigenetic effects. We investigated DNA methylation signatures postmortem in brains of suicides with diagnosis of major depressive disorder. DNA methylation levels were determined at single C-phosphate-G (CpG) resolution sites within ventral prefrontal cortex of 53 suicides and nonpsychiatric controls, aged 16 to 89 years. We found that DNA methylation increases throughout the lifespan. Suicides showed an 8-fold greater number of methylated CpG sites relative to controls (P < 2.2 x 10(-16)), with greater DNA methylation changes over and above the increased methylation observed in normal aging. This increased DNA methylation may be a significant contributor to the neuropathology and psychopathology underlying the risk of suicide in depression.

The development of chemical exchange saturation transfer (CEST) and magnetization transfer (MT) contrast in MRI has enabled the enhanced detection of metabolites and biomarkers in vivo. In brain MRI, the separation between CEST and MT contrast has been particularly difficult due to overlaps in the frequency responses of the contrast mechanisms. We demonstrate here that MT and CEST contrast can be separated in the brain by the so-called uniform-MT (uMT) technique, thus opening the door to addressing long-standing ambiguities in this field. These methods could be useful for keeping track of important endogenous metabolites and for providing an improved understanding of neurological and neurodegenerative disorders. Examples are shown from white and gray matter regions in healthy volunteers and patients with multiple sclerosis, which demonstrated that the MT effects in the brain were asymmetric and that the uMT method could make them uniform., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Previous studies involving inner city populations detected higher cerebral white matter hyperintensity (WMH) scores in African Americans (AAs) compared with European Americans (EAs). This finding might be attributable to the higher prevalence of cardiovascular disease (CVD) risk factors and poorer access to healthcare in AAs. Despite racial differences in CVD risk factor profiles, AAs have paradoxically lower levels of subclinical CVD. We hypothesized that AAs with diabetes and good access to healthcare would have comparable or lower levels of WMH as EAs. Racial differences in the distribution of WMH were analyzed in 46 AAs and 156 EAs with type 2 diabetes enrolled in the Diabetes Heart Study (DHS)-Mind, and replicated in a sample of 113 AAs and 61 EAs patients who had clinically indicated cerebral magnetic resonance imaging. Wilcoxon 2-sample tests and linear models were used to compare the distribution of WMH in AAs and EAs and to test for association between WMH and race. The unadjusted mean WMH score from the Diabetes Heart Study-Mind was 1.9 in AAs and 2.3 in EAs (P = .3244). Among those with clinically indicated magnetic resonance imaging, the mean WMH score was 2.9 in AAs and 3.9 in EAs (P = .0503). Adjustment for age and sex produced no statistically significant differences in WMH score between AAs and EAs. These independent datasets reveal comparable WMH scores in AAs and EAs, suggesting that disparities in access to healthcare and environmental exposures likely underlie the previously reported excess burden of WMH in AAs., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

With an annual incidence of 50/100,000 people, nearly 1% of the population suffers from epilepsy. Treatment with antiepileptic medication fails to achieve seizure remission in 20-30% of patients. One treatment option for refractory epilepsy patients who would not otherwise be surgical candidates is electrical stimulation of the brain, which is a rapidly evolving and reversible adjunctive therapy. Therapeutic stimulation can involve direct stimulation of the brain nuclei or indirect stimulation of peripheral nerves. There are three stimulation modalities that have class I evidence supporting their uses: vagus nerve stimulation (VNS), stimulation of the anterior nuclei of the thalamus (ANT), and, the most recently developed, responsive neurostimulation (RNS). While the other treatment modalities outlined deliver stimulation regardless of neuronal activity, the RNS administers stimulation only if triggered by seizure activity. The lower doses of stimulation provided by such responsive devices can not only reduce power consumption, but also prevent adverse reactions caused by continuous stimulation, which include the possibility of habituation to long-term stimulation. RNS, as an investigational treatment for medically refractory epilepsy, is currently under review by the FDA. Eventually systems may be developed to enable activation by neurochemical triggers or to wirelessly transmit any information gathered. We review the mechanisms, the current status, the target options, and the prospects of RNS for the treatment of medically intractable epilepsy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

In this study, venous oxygen saturation and oxygen metabolic changes in multiple sclerosis (MS) patients were assessed using a recently developed T2-relaxation-under-spin-tagging (TRUST) magnetic resonance imaging (MRI), which measures the superior sagittal venous sinus blood oxygenation (Yv) and cerebral metabolic rate of oxygen (CMRO(2)), an index of global oxygen consumption. Thirty patients with relapsing-remitting MS and 30 age-matched healthy controls were studied using TRUST at 3 T MR. The mean expanded disability status scale (EDSS) of the patients was 2.3 (range, 0 to 5.5). We found significantly increased Yv (P<0.0001) and decreased CMRO(2) (P=0.003) in MS patients (mean±s.d.: 65.9%±5.1% and 138.8±35.4 μmol per 100 g per minute) as compared with healthy control subjects (60.2%±4.0% and 180.2±24.8 μmol per 100 g per minute, respectively), implying decrease of oxygen consumption in MS. There was a significant positive correlation between Yv and EDSS and between Yv and lesion load in MS patients (n=30); on the contrary, there was a significant negative correlation between CMRO(2) and EDSS and between CMRO(2) and lesion load (n=12). There was no correlation between Yv and brain atrophy measures. This study showed preliminary evidence of the potential utility of TRUST in global oxygen metabolism. Our results of significant underutilization of oxygen in MS raise important questions regarding mitochondrial respiratory dysfunction and neurodegeneration of the disease.

MethylomeDB (http://epigenomics.columbia.edu/methylomedb/index.html) is a new database containing genome-wide brain DNA methylation profiles. DNA methylation is an important epigenetic mark in the mammalian brain. In human studies, aberrant DNA methylation alterations have been associated with various neurodevelopmental and neuropsychiatric disorders such as schizophrenia, and depression. In this database, we present methylation profiles of carefully selected non-psychiatric control, schizophrenia, and depression samples. We also include data on one mouse forebrain sample specimen to allow for cross-species comparisons. In addition to our DNA methylation data generated in-house, we have and will continue to include published DNA methylation data from other research groups with the focus on brain development and function. Users can view the methylation data at single-CpG resolution with the option of wiggle and microarray formats. They can also download methylation data for individual samples. MethylomeDB offers an important resource for research into brain function and behavior. It provides the first source of comprehensive brain methylome data, encompassing whole-genome DNA methylation profiles of human and mouse brain specimens that facilitate cross-species comparative epigenomic investigations, as well as investigations of schizophrenia and depression methylomes.

DNA methylation is essential in brain function and behavior; therefore, understanding the role of DNA methylation in brain-based disorders begins with the study of DNA methylation profiles in normal brain. Determining the patterns and scale of methylation conservation and alteration in an evolutionary context enables the design of focused but effective methylation studies of disease states. We applied an enzymatic-based approach, Methylation Mapping Analysis by Paired-end Sequencing (Methyl-MAPS), which utilizes second-generation sequencing technology to provide an unbiased representation of genome-wide DNA methylation profiles of human and mouse brains. In this large-scale study, we assayed CpG methylation in cerebral cortex of neurologically and psychiatrically normal human postmortem specimens, as well as mouse forebrain specimens. Cross-species human-mouse DNA methylation conservation analysis shows that DNA methylation is not correlated with sequence conservation. Instead, greater DNA methylation conservation is correlated with increasing CpG density. In addition to CpG density, these data show that genomic context is a critical factor in DNA methylation conservation and alteration signatures throughout mammalian brain evolution. We identify key genomic features that can be targeted for identification of epigenetic loci that may be developmentally and evolutionarily conserved and wherein aberrations in DNA methylation patterns can confer risk for disease.

Background and Purpose: Experimental studies have suggested a role for iron accumulation in the pathology of TBI. Magnetic field correlation MR imaging is sensitive to the presence of non-heme iron. The aims of this study are to 1) assess the presence, if any, and the extent of iron deposition in the deep gray matter and regional white matter of patients with mTBI by using MFC MR imaging; and 2) investigate the association of regional brain iron deposition with cognitive and behavioral performance of patients with mTBI., Materials and Methods: We prospectively enrolled 28 patients with mTBI. Eighteen healthy subjects served as controls. The subjects were administered the Stroop color word test, the Verbal Fluency Task, and the Post-Concussion Symptoms Scale. The MR imaging protocol (on a 3T imager) consisted of conventional brain imaging and MFC sequences. After the calculation of parametric maps, MFC was measured by using a region of interest approach. MFC values across groups were compared by using analysis of covariance, and the relationship of MFC values and neuropsychological tests were evaluated by using Spearman correlations., Results: Compared with controls, patients with mTBI demonstrated significant higher MFC values in the globus pallidus (P = .002) and in the thalamus (P = .036). In patients with mTBI, Stroop test scores were associated with the MFC value in frontal white matter (r = -0.38, P = .043)., Conclusions: MFC values were significantly elevated in the thalamus and globus pallidus of patients with mTBI, suggesting increased accumulation of iron. This supports the hypothesis that deep gray matter is a site of injury in mTBI and suggests a possible role for iron accumulation in the pathophysiological events after mTBI.

Epidemiological investigations reveal that high fluoride and low iodine have strong adverse effects on the intelligence quotient (IQ) of children. Studies also report that in some high fluoride areas, iodine deficiency also exists, especially in China. Here, with the proteomic techniques, we first report on the proteomic changes in brain proteins in offspring rats at postnatal day 20 exposed to high fluoride and/or low iodine. To investigate molecular mechanisms of central neural system injury induced by the above two elements, proteins were isolated and profiled by two-dimensional gel electrophoresis (2DE). By the analysis of Image-Master 2D Elite software, 71 protein spots in 2DE gels of treatment groups were gained and up- or down-regulated by two folds, and 5 proteins were regulated by five folds, with the comparison to the control group. The proteins changed by five folds were identified by matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The identified proteins are mainly related with cellular signaling, energy metabolism, and protein metabolism and provide a valuable clue to explore the mechanism underlining the neurotoxicity of high fluoride and low iodine. Moreover, these results could provide potential biomarkers for hazards caused by excessive fluoride and low iodine.

Propofol has been used for many years but its functional target in the intact brain remains unclear. In the present study, we used functional magnetic resonance imaging to demonstrate blood oxygen level dependence signal changes in the normal human brain during propofol anesthesia and explored the possible action targets of propofol. Ten healthy subjects were enrolled in two experimental sessions. In session 1, the Observer's Assessment of Alertness/Sedation Scale was performed to evaluate asleep to awake/alert status. In session 2, images with blood oxygen level dependence contrast were obtained with echo-planar imaging on a 1.5-T Philips Gyroscan Magnetic Resonance System and analyzed. In both sessions, subjects were intravenously administered with saline (for 3 min) and then propofol (for 1.5 min) and saline again (for 10.5 min) with a constant speed infusion pump. Observer's Assessment of Alertness/Sedation Scale scoring showed that the subjects experienced conscious–sedative–unconscious–analepsia, which correlated well with the signal decreases in the anesthesia states. Propofol induced significant signal decreases in hypothalamus (18.2%±3.6%), frontal lobe (68.5%±11.2%), and temporal lobe (34.7%±6.1%). Additionally, the signals at these three sites were fulminant and changed synchronously. While in the thalamus, the signal decrease was observed in 5 of 10 of the subjects and the magnitude of decrease was 3.9%±1.6%. These results suggest that there is most significant inhibition in hypothalamus, frontal lobe, and temporal in propofol anesthesia and moderate inhibition in thalamus. These brain regions might be the targets of propofol anesthesia in human brain., (© 2010 Wiley-Liss, Inc.)

Though widely used in anesthesia for many years, the mechanism underlying propofol anesthesia on human is not clear. Animal studies have already demonstrated that propofol functioned mainly by affecting neurotransmitters release. In our study, 10 healthy volunteers ranging from 20 to 40 years old were enrolled. With the help of target-controlled infusion pump, propofol was delivered intravenously. The target-controlled concentration (TCC) of propofol was gradually elevated from 0.5 to 3.0 microg/ml (for 6 steps with an increment of 0.5 microg/ml). During each step the Observer's Assessment of Alertness/Sedation Scale (OAA/S) was performed to evaluate asleep to awake/alert status. Magnetic resonance spectroscopy (MRS) was performed to evaluate neurotransmitters (choline compounds (Cho), creatine (Cr), glutamate (GLU), gamma-aminobutyric acid (GABA) and N-acetyl aspartate (NAA)) changes in brains following propofol anesthesia. OAA/S scoring showed that when the TCCs of propofol were 0, 1.5 and 3.0 microg/ml, the volunteers were in awake, sedative and unconscious, respectively. Significantly down-regulated Cho and GLU, but up-regulated GABA was observed in unconscious state in all the detected regions. NAA was decreased in unconscious status only in the hippocampus and thalamus. There was no obvious change in Cr levels in any statuses or brain regions. Our results indicate that propofol has an impact on the levels of neurotransmitters such as NAA, GLU, GABA and Cho in normal human brain. During propofol anesthesia, enhancement of inhibition or suppression of excitation may each play key roles in different brain regions.

Cerebral metabolic rate of oxygen (CMRO(2)) is an important marker for brain function and brain health. Existing techniques for quantification of CMRO(2) with positron emission tomography (PET) or MRI involve special equipment and/or exogenous agents, and may not be suitable for routine clinical studies. In the present study, a noninvasive method is developed to estimate whole-brain CMRO(2) in humans. This method applies phase-contrast MRI for quantitative blood flow measurement and T(2)-relaxation-under-spin-tagging (TRUST) MRI for venous oxygenation estimation, and uses the Fick principle of arteriovenous difference for the calculation of CMRO(2). Whole-brain averaged CMRO(2) values in young, healthy subjects were 132.1 +/- 20.0 micromol/100 g/min, in good agreement with literature reports using PET. Various acquisition strategies for phase-contrast and TRUST MRI were compared, and it was found that nongated phase-contrast and sagittal sinus (SS) TRUST MRI were able to provide the most efficient and accurate estimation of CMRO(2). In addition, blood flow and venous oxygenation were found to be positively correlated across subjects. Owing to the noninvasive nature of this method, it may be a convenient and useful approach for assessment of brain metabolism in brain disorders as well as under various physiologic conditions., ((c) 2009 Wiley-Liss, Inc.)

Purpose: To investigate whether the variable forms of putative iron deposition seen with susceptibility weighted imaging (SWI) will lead to a set of multiple sclerosis (MS) lesion characteristics different than that seen in conventional MR imaging., Materials and Methods: Twenty-seven clinically definite MS patients underwent brain scans using magnetic resonance imaging including: pre- and postcontrast T1-weighted imaging, T2-weighted imaging, FLAIR, and SWI at 1.5 T, 3 T, and 4 T. MS lesions were identified separately in each imaging sequence. Lesions identified in SWI were reevaluated for their iron content using the SWI filtered phase images., Results: There were a variety of new lesion characteristics identified by SWI, and these were classified into six types. A total of 75 lesions were seen only with conventional imaging, 143 only with SWI, and 204 by both. From the iron quantification measurements, a moderate linear correlation between signal intensity and iron content (phase) was established., Conclusion: The amount of iron deposition in the brain may serve as a surrogate biomarker for different MS lesion characteristics. SWI showed many lesions missed by conventional methods and six different lesion characteristics. SWI was particularly effective at recognizing the presence of iron in MS lesions and in the basal ganglia and pulvinar thalamus., (Copyright (c) 2009 Wiley-Liss, Inc.)

Although BOLD functional MRI (fMRI) provides a useful tool for probing neuronal activities, large intersubject variations in signal amplitude are commonly observed. Understanding the physiologic basis for these variations will have a significant impact on many fMRI studies. First, the physiologic modulator can be used as a regressor to reduce variations across subjects, thereby improving statistical power for detecting group differences. Second, if a pathologic condition or a drug treatment is shown to change fMRI responses, monitoring this modulatory parameter is useful in correctly interpreting the fMRI changes to neuronal deficits/recruitments. Here we present evidence that the task-evoked fMRI signals are modulated by baseline blood oxygenation. To measure global blood oxygenation, we used a recently developed technique, T(2) relaxation under spin-tagging (TRUST) MRI, which yielded baseline oxygenation of 63.7% +/- 7.2% in the sagittal sinus with an estimation error of 1.3%. It was found that individuals with higher baseline oxygenation tend to have a smaller fMRI signal, and vice versa. For every 10% difference in baseline oxygenation across subjects, BOLD and cerebral blood flow (CBF) signals differ by -0.4% and -30.0%, respectively, when using visual stimulation. TRUST MRI is a useful measurement for fMRI studies to control for the modulatory effects of baseline oxygenation that are unique to each subject., ((c) 2008 Wiley-Liss, Inc.)

Background: Although the role of vascular pathology in multiple sclerosis (MS) lesions was suggested long ago, the derivation of these lesions from the vasculature has been difficult to assess in vivo. Ultrahigh-field (eg, 7-T) magnetic resonance imaging (MRI) has become a tool for assessing vascular involvement in MS lesions owing to markedly increased image resolution and susceptibility contrast of venous blood., Objective: To describe the perivenous association of MS lesions on high-resolution and high-contrast 7-T susceptibility-sensitive MRI., Design: Case study., Setting: University hospital., Patients: Two women with clinically definite relapsing-remitting MS., Results: We demonstrated markedly enhanced detection of unique microvascular involvement associated with most of the visualized MS lesions with abnormal signals on and around the venous wall on 7-T compared with 3-T MRI., Conclusions: These findings, which have never been shown on conventional fields of MRI, not only allow for direct evidence of vascular pathogenesis in MS in vivo but also have important implications for monitoring lesion activity and therapeutic response.

Aim: To examine brain damage following different degrees of acute normovolemic hemodilution combined with controlled hypotension (ANH-CH) by neuronal morphological analysis and investigate the expression of nuclear factor-kappa B (NF-kappaB) activity and tumor necrosis factor-alpha (TNF-alpha) in the rat., Methods: Forty rats were randomly assigned to receive a sham operation or ANH-CH (with hematocrit 30%, 25%, 20%, and 15%). ANH was performed after baseline physiological parameters had been monitored for 20 minutes. CH was induced 30 minutes later using sodium nitroprusside and mean arterial pressure was maintained at 50-60 mm Hg for 1 hour. Rats were euthanatized 3 and a half hours after operation. TNF-alpha levels and NF-kappaB activities in cerebral temporal cortex were measured. Ultrastructural alterations in the CA1 region of the rat hippocampi were observed. Changes in mitochondria were evaluated semiquantitatively., Results: Marked ultrastructural alterations, such as mitochondrial denaturalization and nucleus distortion, were observed in the CA1 region of the hippocampus in the ANH-CH hematocrit 20% group and ANH-CH hematocrit 15% group. TNF-alpha expression and NF-kappaB activity in the cerebral temporal cortex significantly increased in all ANH-CH groups and peaked in the ANH-CH hematocrit 25% group., Conclusion: Severe ANH-CH with hematocrit < or =20% may induce cerebral damage and should be avoided. NF-kappaB activation and TNF-alpha expression may play a functional role under the ischemic condition. A better understanding of the role of NF-kappaB and TNF-alpha in the brain may lead to a novel approach for preventing and treating various neurological disorders.

Background and Purpose: Deposition of iron has been recognized recently as an important factor of pathophysiologic change including neurodegenerative processes in multiple sclerosis (MS). We propose that there is an excess accumulation of iron in the deep gray matter in patients with MS that can be measured with a newly developed quantitative MR technique--magnetic field correlation (MFC) imaging., Materials and Methods: With a 3T MR system, we studied 17 patients with relapsing-remitting MS and 14 age-matched healthy control subjects. We acquired MFC imaging using an asymmetric single-shot echo-planar imaging sequence. Regions of interest were selected in both deep gray matter and white matter regions, and the mean MFC values were compared between patients and controls. We also correlated the MFC data with lesion load and neuropsychologic tests in the patients., Results: MFC measured in the deep gray matter in patients with MS was significantly higher than that in the healthy controls (P < or = .03), with an average increase of 24% in the globus pallidus, 39.5% in the putamen, and 30.6% in the thalamus. The increased iron deposition measured with MFC in the deep gray matter in the patients correlated positively with the total number of MS lesions (thalamus: r = 0.61, P = .01; globus pallidus: r = 0.52, P = .02). A moderate but significant correlation between the MFC value in the deep gray matter and the neuropsychologic tests was also found., Conclusion: Quantitative measurements of iron content with MFC demonstrate increased accumulation of iron in the deep gray matter in patients with MS, which may be associated with the disrupted iron outflow pathway by lesions. Such abnormal accumulation of iron may contribute to neuropsychologic impairment and have implications for neurodegenerative processes in MS.

Objective: To observe effects of oral intake of lead on the expression of Hoxa9 gen and the ability of learning and memory and explore the the toxic molecular mechanisms of lead., Methods: Thirty male Wistar rats were chosen and randomly divided into the low lead dosage group, the high lead dosage group and the control group, 10 rats in each group. The low lead dosage group and the high lead dosage group were given respectively 0.06%, 0.2% lead acetate orally while the control group was given distilled water orally. The Y-maze test was used to measure the ability of learning and memory, the graphite heat atomic absorption spectrum method to determine the lead concentration in blood and brain, and the in situ hybridization (ISH) method to determine the expression of Hoxa9 mRNA in brain., Results: (1) The number of electric shocks of the lead poisoned rats were significantly increased over time. The number of electric shocks of the lead poisoning rats was much higher than that of the control group (P < 0.01) (at the end of the experiment, the low lead dosage group: 31.8 +/- 2.26; the high lead dosage group: 37.3 +/- 1.70; the control group: 18.4 +/- 1.51). (2) The brain of the lead poisoned rats including the hippocampus, the cerebellum and the cerebral cortex were significantly atrophic and the apoptosis and necrosis occurred in the cells of the brain. Purkinje's cells in the cerebellum showed significant necrosis and disappearance. The structure of brain in rats of the control group demonstrated no atrophy. (3) The expression of Hoxa9 mRNA in the lead poisoned rats was significantly decreased compared with the control group. There were few Hoxa9 positive cells in the brain of the lead poisoned rats, but many of them were observed in the control group., Conclusion: Lead may inhibit the expression of Hoxa9 and induce atrophy and necrosis of brain, which gives rise to a damage of learning and memory.

Quantitative determination of cerebral blood volume (CBV) is important for understanding brain physiology and pathophysiology. In this work, a novel approach is presented for accurate measurement of absolute CBV (aCBV) using vascular-space-occupancy (VASO) MRI, a blood-nulling pulse sequence, in combination with the T(1) shortening property of Gd-DTPA. Two VASO images with identical imaging parameters are acquired before and after contrast agent injection, resulting in a subtracted image that reflects the amount of blood present in the brain, i.e., CBV. With an additional normalizing factor, aCBV in units of milliliters of blood per 100 mL of brain can be estimated. Experimental results at 1.5 and 3 T systems showed that aCBV maps with high spatial resolution can be obtained with high reproducibility. The averaged aCBV values in gray and white matter were 5.5 +/- 0.2 and 1.4 +/- 0.1 mL of blood/100 mL of brain, respectively. Compared to dynamic susceptibility contrast techniques, VASO MRI is based upon a relatively straightforward theory and the calculation of CBV does not require measurement of an arterial input function. In comparison with previous pre/postcontrast difference approaches, VASO MRI provides maximal signal difference between pre- and postcontrast situation and does not require the use of whole blood for signal normalization.

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that is the most common cause of nontraumatic disability in young adults in the United States. In recent years, magnetic resonance imaging (MRI) has been established as an important paraclinical tool in MS for the assessment of clinical diagnosis, natural history, and treatment effects. In MS studies, there are many advantages to having a sensitive and reliable in vivo method for investigating the specific pathological changes of white matter and its integrity during the disease process. As a consequence, in the past decade, the application of MRI to the study of MS has been explored from conventional MRI to new advanced quantitative techniques with greater pathological specificity and sensitivity. Diffusion tensor imaging (DTI) is one of the most promising techniques with regard to MS. It quantifies the amount of nonrandom water diffusion within tissues and provides unique in vivo information about the pathological processes that affect water diffusion as a result of brain microstructural damage. This review outlines the current state of the art and future direction of DTI and fiber tractography in the study of MS disease.

In this study, we describe prominent perivenular spaces as a sign that is seen on high-resolution (512 x 512) transverse T2-weighted MR images in patients with multiple sclerosis. The observed widening of perivenular space is depicted as a stringlike hyperintensity projecting radially and aligned with multiple sclerosis lesions (usually small), following the course and configuration of deep venular structures. This widening may be an important sign in differentiating primary (ie, in multiple sclerosis) from secondary causes of demyelination.

The advent of MRI has made a remarkable progress in the understanding of age-related brain changes providing a noninvasive tool to study in vivo the normally aging individuals at multiple time points. However, conventional MRI techniques are unable to detect and quantify age-related microstructural changes that have been documented at the post-mortem examination of brain tissues. More sophisticated, quantitative MR techniques such as magnetization transfer imaging, diffusion tensor imaging, and proton MR spectroscopy have been shown to be sensitive to microstructural and metabolic changes that occur in gray and white matter over the course of life span. This review highlights some of these innovative, quantitative MR techniques that are particularly relevant for the study of occult age-related brain tissue changes. Characterization of the in vivo patterns of molecular and cellular changes that occur in the normal aging brain is of crucial importance to understand the pathophysiology of normal cognitive decline and to interpret observed changes in neurodegenerative diseases.

Multiple sclerosis (MS) has traditionally been viewed as an inflammatory demyelinating white matter (WM) disease of the central nervous system. However, recent pathology and MRI studies have shown lesions in the gray matter (GM) as well. To ascertain the extent of GM involvement, we obtained with nonlocalizing proton MR spectroscopy the concentration of N-acetylaspartate (NAA), a metabolite found almost exclusively in neuronal cells, T2-lesion loads, and GM and WM fractions in the entire brain of 71 relapsing-remitting (RR) MS patients (51 women, 20 men, 25-55 years old) and 41 healthy controls (27 women, 14 men, 23-55 years old). The average whole-brain NAA (WBNAA) difference between the patients and the controls was -2.9 mM (-22%, P < 0.0001); range: +1.2 to -7.8 mM (+8% to -63%). The patients' median T2 lesion volume was 5.5 (range: 0.140-28) cm(3). GM and WM comprised 50.4 +/- 3.8% and 30.4 +/- 5.0% (mean +/- standard deviation), respectively, of the total brain volume in the patients; 53.8 +/- 3.7% and 35.4 +/- 4.7% in the controls. Because WM and GM constitute approximately 40% and 60% of the brain parenchyma, respectively, and the NAA concentration in the former is 2/3 of the latter, WBNAA loss greater than 40% x 2/3 = 27% cannot be explained in terms of WM (axonal) pathology alone and must include widespread GM (neuronal) deficits. Therefore, the concept of MS, even at its earlier stages, as a WM disease might need to be reexamined.

Global brain atrophy estimated using MRI and whole brain N-acetylaspartate (WBNAA) concentration measured with proton MR spectroscopy were obtained in 42 patients with relapsing-remitting multiple sclerosis and 41 matched control subjects. Patients exhibited cross-sectional atrophy (0.5%; p = 0.033) and WBNAA decline (1.8%/y; p = 0.005) vs disease duration. The 3.6-fold rate disparity between the two processes suggests that neuronal/axonal dysfunction (N-acetylaspartate decline) precedes parenchyma loss, not its consequence (i.e., is an earlier, more sensitive specific metric of the ongoing disease activity).