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Clozapine is the only antipsychotic approved for treating treatment-resistant schizophrenia (TRS), characterized by persistent positive symptoms despite adequate antipsychotic treatment. Unfortunately, clozapine demonstrates clinical efficacy in only ~30–60 % of patients with TRS (clozapine-responders; ClzR+), while the remaining ~40–70 % are left with no pharmacological recourse for improvement (clozapine-resistant; ClzR−). Mechanism(s) underlying clozapine's superior efficacy remain unclear. However, in vitro evidence suggests clozapine may mitigate glutamatergic dysregulations observed in TRS, by modulating astrocyte activity in ClzR+, but not ClzR−. A factor that if proven correct, may help the assessment of treatment response and development of more effective antipsychotics. To explore the presence of clozapine-astrocyte interaction and clinical improvement, we used 3 T proton-magnetic resonance spectroscopy to quantify levels of myo-Inositol, surrogate biomarker of astrocyte activity, in regions related to schizophrenia neurobiology: Dorsal-anterior-cingulate-cortex (dACC), left-dorsolateral-prefrontal-cortex (left-DLPFC), and left-striatum (left-striatum) of 157 participants (ClzR− = 30; ClzR+ = 37; responders = 38; controls = 52). Clozapine treatment was assessed using clozapine to norclozapine plasma levels, 11–12 h after last clozapine dose. Measures for symptom severity (i.e., Positive and Negative Symptoms Scale) and cognition (i.e., Mini-Mental State Examination) were also recorded. Higher levels of myo-Inositol were observed in TRS groups versus responders and controls (dACC (p < 0.001); left-striatum (p = 0.036); left-DLPFC (p = 0.023)). In ClzR+, but not ClzR−, clozapine to norclozapine ratios were positively associated with myo-Inositol levels (dACC (p = 0.004); left-DLPFC (p < 0.001)), and lower positive symptom severity (p < 0.001). Our results support growing in vitro evidence of clozapine-astrocyte interaction in clozapine-responders. Further research may determine the viability of clozapine-astrocyte interactions as an early marker of clozapine response. [ABSTRACT FROM AUTHOR]

To compare the GABA+/Glx (glutamate-glutamine) ratio in the prefrontal lobe under non-rapid eye movement sleep between patients with narcolepsy type 1 (NT1) and normal controls and explore the correlation between this difference and abnormal cognitive function, using synchronous electroencephalography-functional magnetic resonance spectroscopy (EEG-fMRS). MRS measurements of GABA+ and Glx concentrations as well as synchronous EEG data were obtained from 26 medication-naive patients with NT1 and 29 sex- and age-matched healthy community volunteers. Cognition was appraised with the Beijing version of the Montreal Cognitive Assessment, and daytime sleepiness was measured using the Epworth Sleepiness Scale. All subjects recorded a 2-week sleep log as well as an overnight polysomnography within 1 week before MR scanning to understand their sleep habits and determine sleep stages. After PSG, they also underwent multiple sleep latency trials. Patient/control group differences in the individual measurements of GABA+ and Glx and the GABA+/Glx ratio and their relationship with cognition were assessed. The GABA+/Glx ratio and GABA + levels of patients with narcolepsy were higher than those of the control group (P＜0.0001 and P = 0.0008, respectively). However, there was no significant difference in Glx levels (P = 0.6360). The GABA+/Glx ratio negatively correlated with abnormal cognitive function (r = −0.6710, P = 0.0002). Moreover, GABA + levels were inversely proportional to rapid eye movement sleep latency (REML) in patients with narcolepsy (r = −0.5019, P = 0.0106). The GABA+/Glx ratio in the prefrontal lobe was higher in NT1 patients during N2 sleep than in normal controls, mainly caused by GABA + levels; this ratio was negatively related to abnormal cognitive function. In addition, GABA + levels were inversely proportional to REML. • Narcolepsy type 1 affects GABA+ and Glx levels in the medial prefrontal cortex. • GABA+/Glx ratio is higher during the N2 sleep phase in patients with narcolepsy. • GABA+/Glx ratio is correlated with abnormal cognitive function in narcolepsy. • GABA + levels are inversely proportional to rapid eye movement sleep latency in patients with narcolepsy. [ABSTRACT FROM AUTHOR]

In this research, we present a novel solution to the problem of multi-robot task allocation (MRTA) by utilizing a variant of the state-of-art Deep Reinforcement Learning algorithm, Soft Actor-Critic (SAC) within Multirobot Navigation Systems(MRS). Our approach addresses the existing research gaps in MRTA for MRS, which have received limited attention and have proven challenging to solve using conventional methods. Through extensive simulation evaluations, we demonstrate that our system outperforms current state-of-the-art methods in terms of performance metrics. These findings highlight the effectiveness and superiority of our proposed approach in overcoming the inherent challenges of large-scale MRS. Additionally, we contribute to the field by proposing improvements to the Task Allocation Index (TAI) metric, enabling a more comprehensive evaluation of MRTA performance. [ABSTRACT FROM AUTHOR]

Around 30 % of schizophrenia patients do not respond sufficiently to conventional antipsychotic treatment. Glutamate and γ-aminobutyric acid (GABA) may be implicated in treatment resistant (TR) patients. Some data indicate that TR patients show increased glutamate levels compared to responders, but findings are inconclusive and limited in the early disease stage. Furthermore, the two neurotransmitters have rarely been assessed in conjunction. We therefore aimed to investigate the role of GABA+ and glutamate in first episode TR patients and explore whether these neurometabolites could be potential predictive markers for TR schizophrenia. We used proton magnetic resonance spectroscopy (MRS) to assess glutamate + glutamine (Glx) and GABA including macromolecules (GABA+) in the anterior cingulate cortex (ACC) of 58 first episode psychosis patients. At six months follow-up treatment response was determined and in a subgroup of 33 patients a follow-up MRS scan was acquired. Glx and GABA+ levels were not significantly different between TR patients and responders at baseline and the levels did not change at six months follow-up. The groups differed in voxel fractions, which could have influenced our results even though we corrected for these differences. Our findings do not provide evidence that ACC Glx or GABA+ levels are potential biomarkers for TR in first episode psychosis. Future research needs to take in to account voxel fractions and report potential differences. Comparison with previous literature suggests that illness duration, clozapine responsiveness and medication effects may partly explain the heterogeneous results on Glx and GABA+ levels in TR. [ABSTRACT FROM AUTHOR]

Elevated serum pro-inflammatory molecules have been reported in early psychosis. What is not known is whether peripheral inflammatory biomarkers are associated with CNS biomarkers. In the brain, release of pro-inflammatory molecules by microglial hyperactivity may lead to neuronal apoptosis seen in neurodegenerative disorders and account for loss of brain tissue observed in psychotic disorders. Neurochemical changes, including elevated glutamate levels, are also associated with neuroinflammation, present in early psychosis and change with antipsychotic treatment. Antipsychotic naïve patients with first episode psychosis (FEP) were studied as part of a collaborative project of neuroinflammation. In Study 1 we explored associations between plasma inflammatory molecules and neurometabolites in the dorsal caudate using magnetic resonance spectroscopy (1H-MRS) in N = 13 FEP participants. Study 2 examined the relationship between inflammatory molecules in the Plasma and CSF in N = 20 FEP participants. In Study 1, the proinflammatory chemokine MDC/CCL22 and IL10 were significantly positively correlated with Glutamate and Glx (glutamate + glutamine) levels in the dorsal caudate. In Study 2, plasma inflammatory molecules (MIP1β/CCL4, MCP1/CCL2, Eotaxin-1/CCL11 and TNFα) were significantly correlated with CSF MIP1β/CCL4, IL10, MCP1/CCL2 and Fractalkine/CX3CL1 and symptoms ratings. Plasma inflammatory biomarkers are elevated in early psychosis, associated with neurochemical markers as well as CSF inflammatory molecules found in neurodegenerative disorders. Future studies are needed that combine both peripheral and central biomarkers in both FEP and HC to better understand a potential neuroinflammatory subtype of psychosis likely to respond to targeted interventions. [ABSTRACT FROM AUTHOR]

Abnormal neurotransmitter levels have been reported in individuals at high risk for schizophrenia, leading to a shift in the excitatory/inhibitory balance. However, it is unclear whether these alterations predate the onset of clinically relevant symptoms. Our aim was to explore in vivo measures of excitatory/inhibitory balance in 22q11.2 deletion carriers, a population at genetic risk for psychosis. Glx (glutamate+glutamine) and GABA+ (gamma-aminobutyric acid with macromolecules and homocarnosine) concentrations were estimated in the anterior cingulate cortex, superior temporal cortex, and hippocampus using the Mescher-Garwood point-resolved spectroscopy (MEGA-PRESS) sequence and the Gannet toolbox in 52 deletion carriers and 42 control participants. T1-weighted images were acquired longitudinally and processed with FreeSurfer version 6 to extract hippocampal volume. Subgroup analyses were conducted in deletion carriers with psychotic symptoms. While no differences were found in the anterior cingulate cortex, deletion carriers had higher levels of Glx in the hippocampus and superior temporal cortex and lower levels of GABA+ in the hippocampus than control participants. We additionally found a higher Glx concentration in the hippocampus of deletion carriers with psychotic symptoms. Finally, more pronounced hippocampal atrophy was significantly associated with increased Glx levels in deletion carriers. We provide evidence for an excitatory/inhibitory imbalance in temporal brain structures of deletion carriers, with a further hippocampal Glx increase in individuals with psychotic symptoms that was associated with hippocampal atrophy. These results are in line with theories proposing abnormally enhanced glutamate levels as a mechanistic explanation for hippocampal atrophy via excitotoxicity. Our results highlight a central role of glutamate in the hippocampus of individuals at genetic risk for schizophrenia. [ABSTRACT FROM AUTHOR]

Adverse intrauterine events may profoundly impact fetal risk for future adult diseases. The mechanisms underlying this increased vulnerability are complex and remain poorly understood. Contemporary advances in fetal magnetic resonance imaging (MRI) have provided clinicians and scientists with unprecedented access to in vivo human fetal brain development to begin to identify emerging endophenotypes of neuropsychiatric disorders such as autism spectrum disorder, attention-deficit/hyperactivity disorder, and schizophrenia. In this review, we discuss salient findings of normal fetal neurodevelopment from studies using advanced, multimodal MRI that have provided unparalleled characterization of in utero prenatal brain morphology, metabolism, microstructure, and functional connectivity. We appraise the clinical utility of these normative data in identifying high-risk fetuses before birth. We highlight available studies that have investigated the predictive validity of advanced prenatal brain MRI findings and long-term neurodevelopmental outcomes. We then discuss how ex utero quantitative MRI findings can inform in utero investigations toward the pursuit of early biomarkers of risk. Lastly, we explore future opportunities to advance our understanding of the prenatal origins of neuropsychiatric disorders using precision fetal imaging. [ABSTRACT FROM AUTHOR]

To investigate the characteristics of fat content and component in IFP using hydrogen proton MR spectroscopy (1H-MRS), and to explore the correlation with the severity of OA, Hoffa-synovitis, and knee pain. 80 volunteers were enrolled. Subjects were grouped based on Kellgren-Lawrence (K-L) grading. Fat fraction (FF) and unsaturation index (UI) of IFP were measured using 1H-MRS. Hoffa-synovitis was evaluated based on the MRI Osteoarthritis Knee Score system (MOAKS). Knee pain was assessed by a self-administered Western Ontario and McMaster Osteoarthritis Index (WOMAC) questionnaire. One-way ANOVA or Kruskal-Wallis test and Spearman's correlation tests were applied for statistical analysis. After matching BMI, waistline, and K-L grade, a total of 64 knees were included and divided into 23 normal, 25 mild OA, and 16 advanced OA. The mean values were 76.79% ± 7.24%, 70.35% ± 7.42%, and 58.29% ± 10.32% for FF in the healthy controls, mild OA, and advanced OA group, and 6.36 ± 1.19%, 6.08 ± 1.35%, and 5.69 ± 1.78% for UI, respectively, the statistical difference was found for FF (p < 0.01). A good negative correlation was observed between the FF and the severity of OA, Hoffa-synovitis (r = −0.625, −0.758, respectively, p < 0.0001), and a weak inverse correlation with knee pain. FF alteration in IFP is associated with the severity of OA, Hoffa synovitis, and knee pain, and has the potential to be a new quantitative imaging biomarker in knee OA. [ABSTRACT FROM AUTHOR]

Epidemiologic, genetic, and neurobiological studies suggest considerable overlap between schizophrenia and mood disorders. Importantly, both disorders are associated with a broad range of cognitive deficits as well as altered glutamatergic and GABAergic neurometabolism. We conducted a systematic review of magnetic resonance spectroscopy (MRS) studies investigating the relationship between glutamatergic and GABAergic neurometabolites and cognition in schizophrenia spectrum disorders and mood disorders. A literature search in Pubmed of studies published before April 15, 2019 was conducted and 37 studies were deemed eligible for systematic review. We found that alterations in glutamatergic and GABAergic neurotransmission have been identified relatively consistently in both schizophrenia and mood disorders. However, because of the vast heterogeneity of published studies in terms of illness stage, medication exposure, MRS acquisition parameters and data post-processing strategies, we still do not understand the relationship between those neurotransmitters and cognitive dysfunction in mental illness, which is a critical initial step for rational drug development. Our findings emphasize the need for coordinated multi-center studies that characterize cognitive function and its biological substrates in large and well-defined clinical populations, using harmonized imaging sequences and analytical methods with the goal to elucidate the underlying pathophysiological mechanisms and to inform future clinical trials. [ABSTRACT FROM AUTHOR]

Transcranial direct current stimulation (tDCS) has wide ranging applications in neuro-behavioural and physiological research, and in neurological rehabilitation. However, it is currently limited by substantial inter-subject variability in responses, which may be explained, at least in part, by anatomical differences that lead to variability in the electric field (E-field) induced in the cortex. Here, we tested whether the variability in the E-field in the stimulated cortex during anodal tDCS, estimated using computational simulations, explains the variability in tDCS induced changes in GABA, a neurophysiological marker of stimulation effect. Data from five previously conducted MRS studies were combined. The anode was placed over the left primary motor cortex (M1, 3 studies, N = 24) or right temporal cortex (2 studies, N = 32), with the cathode over the contralateral supraorbital ridge. Single voxel spectroscopy was performed in a 2x2x2cm voxel under the anode in all cases. MRS data were acquired before and either during or after 1 mA tDCS using either a sLASER sequence (7T) or a MEGA-PRESS sequence (3T). sLASER MRS data were analysed using LCModel, and MEGA-PRESS using FID-A and Gannet. E-fields were simulated in a finite element model of the head, based on individual structural MR images, using SimNIBS. Separate linear mixed effects models were run for each E-field variable (mean and 95th percentile; magnitude, and components normal and tangential to grey matter surface, within the MRS voxel). The model included effects of time (pre or post tDCS), E-field, grey matter volume in the MRS voxel, and a 3-way interaction between time, E-field and grey matter volume. Additionally, we ran a permutation analysis using PALM to determine whether E-field anywhere in the brain, not just in the MRS voxel, correlated with GABA change. In M1, higher mean E-field magnitude was associated with greater anodal tDCS-induced decreases in GABA (t(24) = 3.24, p = 0.003). Further, the association between mean E-field magnitude and GABA change was moderated by the grey matter volume in the MRS voxel (t(24) = −3.55, p = 0.002). These relationships were consistent across all E-field variables except the mean of the normal component. No significant relationship was found between tDCS-induced GABA decrease and E-field in the temporal voxel. No significant clusters were found in the whole brain analysis. Our data suggest that the electric field induced by tDCS within the brain is variable, and is significantly related to anodal tDCS-induced decrease in GABA, a key neurophysiological marker of stimulation. These findings strongly support individualised dosing of tDCS, at least in M1. Further studies examining E-fields in relation to other outcome measures, including behaviour, will help determine the optimal E-fields required for any desired effects. • We study the link between individually simulated electric field dose and anodal tDCS-induced change in GABA in the cortex. • The electric field strength in the brain correlates with a decrease in GABA in the motor cortex. • The correlation between the electric field and GABA change is modulated by the amount of grey matter in the MRS voxel. • We find no association between the electric field and GABA in the temporal cortex. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is an aggressive head and neck malignancy, and radiotherapy (with or without chemotherapy) is the primary treatment modality. Reliable tumour assessment during the treatment phase, which can portend the efficacy of radiotherapy and early identification of potential treatment failure in radioresistant disease, has been implicit for better cancer management. Technological advancement in the last decade has fostered the development of functional magnetic resonance imaging (fMRI) techniques into a promising tool for diagnostic and therapeutic assessments in head and neck cancer. Apart from conventional morphological assessment, early detection of the physiological environment by fMRI allows a more thorough investigation in monitoring tumour response. This article discusses the relevant fMRI utilities in NPC as an early prognostic and monitoring tool for treatment. Challenges and future developments of fMRI in radiation oncology are also discussed. [ABSTRACT FROM AUTHOR]

• A concise overview of pH spectroscopy (MRS), spectroscopy imaging (MRSI) and imaging (MRI) measurement techniques. • pH-sensitive imaging with chemical exchange saturation transfer (CEST) MRI. • Examples of extracellular pH measurement in tumor with Biosensor Imaging of Redundant Deviation in Shifts (BIRDS) MRSI. • Examples of intracellular pH measurement in acute stroke with amide proton transfer (APT) MRI. Acid–base homeostasis and pH regulation are critical for normal tissue metabolism and physiology, and brain tissue pH alters in many diseased states. Several noninvasive tissue pH Magnetic Resonance (MR) techniques have been developed over the past few decades to shed light on pH change during tissue function and dysfunction. Nevertheless, there are still challenges for mapping brain pH noninvasively at high spatiotemporal resolution. To address this unmet biomedical need, chemical exchange saturation transfer (CEST) MR techniques have been developed as a sensitive means for non-invasive pH mapping. This article briefly reviews the basic principles of different pH measurement techniques with a focus on CEST imaging of pH. Emerging pH imaging applications in the tumor are provided as examples throughout the narrative, and CEST pH imaging in acute stroke is discussed in the final section. [ABSTRACT FROM AUTHOR]

• Ketamine modulates anterior cingulate cortex (ACC) activity over minutes and hours. • Changes in ACC activity correlate with ketamine's antidepressant effects. • Ketamine's effects on anhedonia depend on modulation of dorsal and subgenual ACC. • Ketamine's action on ACC may reduce emotional pain and rumination. • Rodent and non-human primate studies are key to understanding ketamine's effects. The subdivisions of the anterior cingulate cortex (ACC) – including subgenual, perigenual and dorsal zones – are implicated in the etiology, pathogenesis and treatment of major depression. We review an emerging body of evidence which suggests that changes in ACC activity are critically important in mediating the antidepressant effects of ketamine, the prototypical member of an emerging class of rapidly acting antidepressants. Infusions of ketamine induce acute (over minutes) and post-acute (over hours to days) modulations in subgenual and perigenual activity, and importantly, these changes can correlate with antidepressant efficacy. The subgenual and dorsal zones of the ACC have been specifically implicated in ketamine's anti-anhedonic effects. We emphasize the synergistic relationship between neuroimaging studies in humans and brain manipulations in animals to understand the causal relationship between changes in brain activity and therapeutic efficacy. We conclude with circuit-based perspectives on ketamine's action: first, related to ACC function in a central network mediating affective pain, and second, related to its role as the anterior node of the default mode network. [ABSTRACT FROM AUTHOR]

Temporal perceptual learning (TPL) constitutes a unique and profound demonstration of neural plasticity within the brain. Our understanding for the neurometabolic changes associated with TPL on the other hand has been limited in part by the use of traditional fMRI approaches. Since plasticity in the visual cortex has been shown to underlie perceptual learning of visual information, we tested the hypothesis that TPL of an auditory interval involves a similar change in plasticity of the auditory pathway and if so, whether these changes take place in a lower-order sensory-specific brain area such as the primary auditory cortex (A1), or a higher-order modality-independent brain area such as the inferior parietal cortex (IPC). This distinction will inform us of the mechanisms underlying perceptual learning as well as the locus of change as it relates to TPL. In the present study, we took advantage of a new technique: proton magnetic resonance spectroscopy (MRS) in combination with psychophysical measures to provide the first evidence of changes in neurometabolic processing following 5 days of temporal discrimination training. We measured the (E)xcitation-to-(I)nhibition ratio as an index of learning in the right IPC and left A1 while participants learned an auditory two-tone discrimination task. During the first day of training, we found a significant task-related increase in functional E/I ratio within the IPC. While the A1 exhibited the opposite pattern of neurochemical activity, this relationship did not reach statistical significance. After timing performance has reached a plateau, there were no further changes to functional E/I. These findings support the hypothesis that improvements in temporal discrimination relies on neuroplastic changes in the IPC, but it is possible that both areas work synergistically to acquire a temporal interval. • Does temporal perceptual learning affect regional neurochemical processes?. • Regional excitation-inhibition (E/I) ratio changes index regional plasticity. • Auditory temporal discrimination improved over five training days. • Significant interaction in the E/I ratio between region (A1/IPC) and day (first/last). • Effect driven by E/I ratio changes in the parietal lobe during first day of training. [ABSTRACT FROM AUTHOR]

Symptomatic carotid artery stenosis needs revascularization within 2 weeks by carotid endarterectomy (CEA) to reduce the risk of symptom recurrence; however, the optimal timing of intervention is yet to be defined in patients with large-volume cerebral ischemic lesion (LVCIL) and modified Rankin scale (mRS) score ≥3. The aim of this study was to determine the most appropriate timing for CEA in patients with a recent stroke and LVCIL. Data from patients with symptomatic carotid stenosis with LVCIL and mRS score of 3 or 4 from 2007 to 2017 were considered. Patients were submitted to CEA if they had a stable clinical condition and life expectancy >1 year. LVCIL was defined as a cerebral ischemic lesion of volume >4000 mm3. Perioperative stroke and death were evaluated by stratifying for timing of CEA by χ 2 test and multiple logistic regression. Patients with similar characteristics (LVCIL and mRS score of 3 or 4) unfit for CEA served as the control group for recurrence of stroke at 1-year follow-up. In an 11-year period, of a total 4020 CEAs, 126 (2.9%) were performed in patients with a moderate stroke and LVCIL occurring in the same admission. The patients' median age was 69 years (interquartile range [IQR], 10 years); 72% (91) were male, with mRS score of 3 (IQR, 1) and LVCIL volume of 20,000 mm3 (IQR, 47,000 mm3). The median time elapsed from symptoms to CEA was 7 weeks (IQR, 8 weeks). Overall perioperative stroke/death was 7.3% (eight strokes and one death). By selective timing evaluation of the postoperative events, CEA performed within 4 weeks was associated with a significantly higher rate of stroke/death compared with patients operated on after 4 weeks: 11.9% (8/67) vs 1.7% (1/59; P =.03). By logistic regression, CEA within 4 weeks was an independent (from sex, cerebral ischemic lesion volume, dyslipidemia, and carotid stenosis) predictor of postoperative stroke/death (odds ratio, 8.2; 95% confidence interval, 1.01-73). In the same period, 101 patients were considered unfit for CEA for dementia (n = 22), severe comorbidities (n = 55), or short (<1-year) life expectancy (n = 24), and 43 (43%) survived at 1 year. At 1 year, the perioperative/recurrent stroke after CEA vs patients unfit for CEA was similar (6.2% vs 13.9%; P =.11), but CEA performed after 4 weeks led to significantly lower perioperative/recurrent stroke (1.7% vs 13.9%; P =.02). The surgical risk of CEA in patients with a recent moderate-severe ischemic stroke and LVCIL is high. However, if the intervention is delayed >4 weeks, its benefit seems significant. [ABSTRACT FROM AUTHOR]

• N-acetyl aspartate is an important measure of neuronal metabolic health. • This meta-analysis synthesises results from 182 studies of this chemical in psychosis. • N-acetyl aspartate levels are reduced in the hippocampus in high risk of psychosis. • In first episode psychosis, levels are lower in the frontal cortex and thalamus. • In chronic schizophrenia, levels are lower in many cortical and white matter areas. N-acetyl-aspartate (NAA) is a readily measured marker of neuronal metabolism. Previous analyses in schizophrenia have shown NAA levels are low in frontal, temporal and thalamic regions, but may be underpowered to detect effects in other regions, in high-risk states and in first episode psychosis. We searched for magnetic resonance spectroscopy studies comparing NAA in chronic schizophrenia, first episode psychosis and high risk of psychosis to controls. 182 studies were included and meta-analysed using a random-effects model for each region and illness stage. NAA levels were significantly lower than controls in the frontal lobe [Hedge's g = -0.36, p < 0.001], hippocampus [-0.52, p < 0.001], temporal lobe [-0.35, p = 0.031], thalamus [-0.32, p = 0.012] and parietal lobe [-0.25, p = 0.028] in chronic schizophrenia, and lower than controls in the frontal lobe [-0.26, p = 0.002], anterior cingulate cortex [-0.24, p = 0.016] and thalamus [-0.28, p = 0.028] in first episode psychosis. NAA was lower in high-risk of psychosis in the hippocampus [-0.20, p = 0.049]. In schizophrenia, NAA alterations appear to begin in hippocampus, frontal cortex and thalamus, and extend later to many other regions. [ABSTRACT FROM AUTHOR]

With the increasing availability of ultra-high field MRI systems, studying non-proton nuclei (X-nuclei), such as 23Na and 31P has received great interest. X-nuclei are able to provide insight into important cellular processes and energy metabolism in tissues and by monitoring these nuclei closely it is possible to establish links to pathological conditions and neurodegenerative diseases. In order to investigate X-nuclei, a well-designed radiofrequency (RF) system with a multi-tuned RF coil is required. However, as the intrinsic sensitivity of non-proton nuclei is lower compared to 1H, it is important to ensure that the signal-to-noise ratio (SNR) of the X-nuclei is as high as possible. This review aims to give a comprehensive overview of previous efforts, with particular focus on the design concept of multi-tuned coils, predominantly for brain applications. In order to guide the readers, the main body of the review is categorised into two parts: state-of-the art according to the single or multiple design structures and emerging technologies. A more detailed description is given in each subsection relating to the specific design approaches of, mostly, double-tuned coils, including using traps, PIN-diodes, nested and metamaterial, together with explanations of their novelties, optimal solutions and trade-offs. [ABSTRACT FROM AUTHOR]

The role of prophylactic antiepileptic drugs (AEDs) in preventing seizures and/or improving the outcomes after intracerebral hemorrhage (ICH) has remained controversial. The current guidelines have recommended against AED prophylaxis. However, these recommendations were based on older studies that had primarily used phenytoin as the AED of choice. Newer medications, such as levetiracetam, have yet to be extensively studied. We performed a retrospective review of patients with ICH from 2010 to 2015. The patient demographic data, seizure data, and outcomes were collected. The results were analyzed using descriptive statistics, binary logistic regression, and quantile regression. The primary outcome was seizure incidence. A total of 360 patients with a median age of 70 years had met the inclusion criteria. Of the 360 patients, 30 (8.3%) had had recorded seizure events, 54% were men, and 81% had a history of hypertension. The median admission National Institutes of Health stroke scale (NIHSS) score was 7 (interquartile range [IQR], 14), and the median discharge NIHSS score was 5.0 (IQR, 13). The median hematoma size was 7.1 mL (IQR, 13 mL), and 143 patients (40%) had had cortical involvement. Of the 360 patients, 273 (76%) had received prophylaxis and 87 (24%) had not. After adjustment for the admission NIHSS and the presence of cortical involvement, the rate of new seizure events after ICH remained significantly lower for the patients who had received AED prophylaxis (adjusted odds ratio, 0.28; 95% confidence interval, 0.11–0.71; P = 0.008). The administration of, predominantly, levetiracetam for AED prophylaxis after ICH reduced the odds of new seizure events, independently of the admission NIHSS score and the presence of cortical involvement. [ABSTRACT FROM AUTHOR]

Background: Trichotillomania (TTM) is a chronic and impairing psychiatric disorder with suspected dysfunctional cortico-striato-thalamo-cortical (CSTC) circuit activity reflecting excitatory/inhibitory signaling imbalance. TTM neurochemistry is understudied, with no prior research using magnetic resonance spectroscopy (MRS). This pilot investigation examined associations between TTM diagnosis, symptom severity, and response to behavioral treatment with MRS neurometabolites glutamate (Glu) and γ-aminobutyric acid (GABA) in CSTC structures.Methods: Proton echo-planar spectroscopic imaging (PEPSI) MRS was acquired from bilateral pregenual anterior cingulate cortex (pACC), caudate, putamen, globus pallidus, thalamus, and proximal white matter in 10 unmedicated girls with TTM, ages 9-17 years, before and after treatment, and from 13 age- and sex-matched healthy controls.Results: Nine of 10 TTM patients were treatment responders. Pretreatment mean Glu and GABA did not differ significantly between participants and controls. Pretreatment TTM symptoms were correlated with Glu in (left + right) pACC (r = 0.88, p = 0.02) and thalamus (r = 0.82, p = 0.012), and were negatively correlated with pACC GABA (r = -0.84, p = 0.034). Mean GABA in putamen increased 69% (baseline to post-treatment) (p = 0.027). Higher pretreatment Glu in caudate, putamen, globus pallidus, and thalamus predicted greater symptom decreases with treatment (all r < -0.6, p < 0.05); higher caudate GABA predicted less treatment-related symptom decline (r = 0.86, p = 0.014).Limitations: Small sample, GABA quantified with spectral fitting rather than editing.Conclusion: Consistent with other neuroimaging, MRS reveals discrete CSTC chemical changes with effective behavior therapy, and possibly with TTM etiology. TTM symptoms relate to excess excitatory versus inhibitory signaling in pACC and thalamus; symptom improvement may reflect reduced excitatory drive of the CSTC direct-pathway activity. [ABSTRACT FROM AUTHOR]

Background: Although there is growing evidence of alterations in the neurometabolite status associated with the pathophysiology of schizophrenia, how treatments influence these metabolite levels in patients with schizophrenia remains poorly studied.Methods: We conducted a literature search using Embase, Medline, and PsycINFO to identify proton magnetic resonance spectroscopy studies that compared neurometabolite levels before and after treatment in patients with schizophrenia. Six neurometabolites (glutamate, glutamine, glutamate + glutamine, gamma-aminobutyric acid, N-acetylaspartate, myo-inositol) and six regions of interest (frontal cortex, temporal cortex, parieto-occipital cortex, thalamus, basal ganglia, hippocampus) were investigated.Results: Thirty-two studies (n = 773 at follow-up) were included in our meta-analysis. Our results demonstrated that the frontal glutamate + glutamine level was significantly decreased (14 groups; n = 292 at follow-up; effect size = -0.35, P = 0.0003; I2 = 22%) and the thalamic N-acetylaspartate level was significantly increased (7 groups; n = 184 at follow-up; effect size = 0.47, P < 0.00001; I2 = 0%) after treatment in schizophrenia patients. No significant associations were found between neurometabolite changes and age, gender, duration of illness, duration of treatment, or baseline symptom severity.Conclusions: The current results suggest that glutamatergic neurometabolite levels in the frontal cortex and neuronal integrity in the thalamus in schizophrenia might be modified following treatment. [ABSTRACT FROM AUTHOR]

Background: Obsessive Compulsive Disorder (OCD) is characterized by hyperactivity in a network of forebrain structures, including the anterior cingulate cortex (ACC). Convergent evidence suggests that glutamatergic dysfunction may contribute to the disorder. Skin picking disorder (SPD) was listed as one of the obsessive-compulsive and related disorders, which is often comorbid with OCD and share overlapping phenomenology and pathophysiology. However, potential confounding effects between the two diagnostic effects on neurotransmitter levels remain largely unexamined.Methods: We examined the pregenual anterior cingulate cortex (pACC) glutamate and other neurochemicals in 62 subjects using a single-voxel acquisition 1H MRS at 3Tesla; of these, 47 subjects yielded usable measurements of both glutamate and glutamine and were included in the analysis (17 medicated with OCD alone, 13 medicated with comorbid OCD + SPD, 17 healthy control).Results: OCD with comorbid SPD showed significantly lower pACC glutamate than in patients without SPD (p = 0.001) or control subjects (p = 0.035). OCD without SPD subjects showed pACC glutamate levels indistinguishable from controls (p = 0.501). In the OCD with SPD subjects, glutamate was correlated with Y-BOCS total score in female patients (n = 9, r = 0.69, p = 0.041).Limitations: The main limitation of the study was the cross-sectional data. Our patients were on SSRI medication which may have modified the effect of SPD and OCD interaction on glutamate activity.Conclusion: Our results suggest that alterations of the glutamatergic system may play an important role in the pathophysiology of a subgroup of OCD and reduced pACC glutamate may be a biomarker of a distinct subset of OCD patients. [ABSTRACT FROM AUTHOR]

• rtPA is the first-line therapy in acute ischemic stroke within 4.5 h from onset. • People with pre-existing dementia or physical disability are excluded from rtPA. • Patients with mRS 2–3 may benefit from rtPA with a moderate risk of sICH/mortality. • mRS 2–3 may return to their previous QoL without substantial additional disability. Recombinant tissue plasminogen activator (rt-PA) is the first-line therapy demonstrated to be safe and effective in acute ischemic stroke. People with pre-existing severe dementia or physical disability are usually excluded from rt-PA. The aim of our study was to investigate rt-PA safety and effectiveness in acute stroke with pre-existing disability (mRS ≥ 2). The study encompassed 35 acute ischemic stroke patients with mRS ≥ 2 treated with rt-PA. In order to assess the differences in clinical outcome in three disability groups (mRS = 2; 3; 4/5), the following parameters were evaluated: intracerebral hemorrhage, mortality, NIHSS, ΔNIHSS and mRS. Baseline-NIHSS and age were not significantly different among groups. Mortality was higher in the pre-morbid mRS 4/5 group (44%) than in the pre-morbid mRS 2 (16.7%) and mRS 3 groups (21.4%). In survived patients, median ΔNIHSS% was higher in the mRS 2 and 3 groups (-63.3% and −92.3%, respectively) than in the mRS 4/5 group (−9.1%). The 247 rt-PA treated subjects with mRS < 2 in the same period showed lower mortality rate (4.7%), lower sICH (5%), lower mRS at discharge (median 1; range 0–6) and similar ΔNIHSS% (−75%). Patients with mRS 2 and 3 may benefit from rt-PA with a moderate risk of sICH and mortality. [ABSTRACT FROM AUTHOR]

In the era of integrated genomic-histologic analysis of brain tumors, new biomarkers have been introduced as diagnostic, prognostic, and therapeutic indicators. The analysis of the mutation in the isocitrate dehydrogenase (IDH) genes IDH1 and IDH2 has provided important diagnostic and prognostic information for patients affected by diffuse glioma (i.e., the presence of the mutation has been related to an increased survival rate). The reference standard of IDH mutation detection has been its assessment in surgical specimens, immunohistochemistry, and/or genetic sequencing. Knowing the IDH status information preoperatively would be of great importance, because it has been related to tumor progression and the response to treatment. The oncometabolite 2-hydroxyglutarate (2HG), accumulated in gliomas with IDH mutation status, can be detected in vivo using magnetic resonance spectroscopy (MRS). The 2HG-MRS technique remains technically challenging. We have summarized the results of the first pilot study in Australia, which included 10 patients affected by glioma. The data recorded from May 2017 to November 2018 were analyzed. In our exploratory study, we reached a sensitivity and specificity of 100%, confirming the strong predictive role of 2HG, as detected using MRS, in the diagnosis of glioma. In the present study, we have focused on methodological tips and future perspectives of the technique in the neuroimaging and neuro-oncological scenario. We would advocate the integration of 2HG-MRS into standard clinical practice. [ABSTRACT FROM AUTHOR]

The major pathologies of Alzheimer's disease (AD) are amyloid plaques and hyperphosphorylated tau. The deposition of amyloid plaques leads to synaptic dysfunction, neuronal cell death, and cognitive impairment. Among the neurotransmitters, glutamate is the most abundant in the mammalian brain and plays an important role in synaptic plasticity. With respect to synaptic transmission, metabotropic glutamate receptor 5 (mGluR5) is highly affected by amyloid pathology. However, the neuropathologic changes in the protein expression of mGluR5 in AD remain unclear. Therefore, to elucidate the alteration in mGluR5 expression with the progression of AD, we performed serial behavioral tests, longitudinal imaging studies, and histopathological immunoassay for both 5xFAD (n = 14) mice and age-matched wild-type mice (n = 14). The 5xFAD mice started showing severe hyperactivity and memory impairment from 7 months of age. In addition, mGluR5 positron emission tomography revealed that while the binding values in the wild-type mice were similar over time, those in 5xFAD mice fluctuated from 5 months of age. Furthermore, the 5xFAD mice presented a 35% decrease in the binding values of their cortical and subcortical areas at 9 months of age compared with those at 3 months of age. Magnetic resonance spectroscopy and histopathological studies showed similar changes. In conclusion, mGluR5 availability changes with age, and mGluR5 positron emission tomography could successfully detect this synaptic change in the 5xFAD mice. • Metabotropic glutamate receptor 5 positron emission tomography revealed that while wild-type mice showed similar binding values over time, those in 5xFAD mice fluctuated from 5 months of age. • The pattern of metabotropic glutamate receptor 5 protein expression levels was consistent with in vivo positron emission tomography images. • From MR spectroscopy experiments, changes of neurochemicals in the 5xFAD were shown to be related to reduction of neuronal integrity, neurogenesis, and activation of glial cells. [ABSTRACT FROM AUTHOR]

The basal ganglia are strongly connected to the primary motor cortex (M1) and play a crucial role in movement control. Interestingly, several disorders showing abnormal neurotransmitter levels in basal ganglia also present concomitant anomalies in intracortical function within M1. The main aim of this study was to clarify the relationship between neurotransmitter content in the basal ganglia and intracortical function at M1 in healthy individuals. We hypothesized that neurotransmitter content of the basal ganglia would be significant predictors of M1 intracortical function. We combined magnetic resonance spectroscopy (MRS) and transcranial magnetic stimulation (TMS) to test this hypothesis in 20 healthy adults. An extensive TMS battery probing common measures of intracortical, and corticospinal excitability was administered, and GABA and glutamate-glutamine levels were assessed from voxels placed over the basal ganglia and the occipital cortex (control region). Regression models using metabolite concentration as predictor and TMS metrics as outcome measures showed that glutamate level in the basal ganglia significantly predicted short interval intracortical inhibition (SICI) and intracortical facilitation (ICF), while GABA content did not. No model using metabolite measures from the occipital control voxel was significant. Taken together, these results converge with those obtained in clinical populations and suggest that intracortical circuits in human M1 are associated with the neurotransmitter content of connected but distal subcortical structures crucial for motor function. • Basal ganglia have strong afferences and efferences with the primary motor cortex. • However, it's role on intracortical circuit activity is unknown. • TMS assesses intracortical inhibitory and excitatory activity of the motor cortex. • GABA and Glx levels were measured using mass resonance spectroscopy. • Glx levels in basal ganglia predict SICI and ICF. [ABSTRACT FROM AUTHOR]

The integration of artificial intelligence (AI) with modern healthcare has become increasingly prominent. The purpose of this study is to explore the impact of the novel computer-aided triage system based on artificial intelligence (AI-CTS) on endovascular therapy (EVT) in patients with large vascular occlusions (LVO). This study marks the first comprehensive systematic review and meta-analysis on the subject. A comprehensive study was performed on PubMed, Medline, Embase, Cochrane Library, and Chinese databases from their establishment to September 2023, in accordance with PRISMA recommendations. RevMan 5.4 software was used for summative analysis. The outcomes included door-to-groin (DTG) time, time from CT scan initiation to EVT, time from CT scan to reperfusion, and 90-day modified Rankin Scale (mRS). A total of 7 studies involving 752 participants were included in the meta-analysis. The pooled results demonstrated that patients in the post-AI group had less time of DTG [SMD, 0.54; 95% CI, 0.40–0.69; P < 0.00001] and CT scan to EVT [SMD, 0.57; 95% CI, 0.42–0.73; P < 0.00001], as well as less time of CTA to recanalization [SMD, 0.63; 95% CI, 0.36–0.90; P < 0.00001]. There was no significant difference between the 2 groups in terms of the mRS at 90 days [OR, 0.66; 95% CI, 0.43–1.01; P = 0.06]. The combination of AI-CTS and EVT has improved the therapy process for LVO patients. However, the improvement in mRS at 90 days was not significant; further research is warranted. [ABSTRACT FROM AUTHOR]

• Most midlife Singaporean women experience moderate to severe menopausal symptoms. • Ethnic differences in the prevalence and type of menopausal symptoms were observed. • A score of over 6 on the Menopause Rating Scale (MRS) was associated with menstrual irregularity at 25 years and poor performance on the repeated chair stand (RCS) test. • Moderate disability and poor self-rated health were associated with high MRS scores. • Lower education levels and age ≥65 were inversely associated with high MRS scores. Menopausal symptoms can substantially impact quality of life. We studied somatic, psychological, and urogenital symptoms and their associated factors. Cross-sectional study of healthy midlife Singaporean women from three major Asian ethnic groups. In 2014–16, women aged 45 to 69 attending well-woman clinics at the National University Hospital Singapore completed the Menopause Rating Scale (MRS). Sociodemographic, reproductive, medical, anthropometric, body composition, and physical performance characteristics were assessed using validated questionnaires and strict protocols. We analysed sub-scales and total scores by median split, and adjusted odds ratios using multivariable logistic regression. Of the 1054 eligible women, 62.6 % reported at least one moderate to extremely severe symptom. The top five menopausal symptoms were joint and muscle discomfort, sleep problems, vaginal dryness, physical and mental exhaustion, and hot flushes. Higher total scores on the MRS were associated with moderate disability (adjusted odds ratio: 9.80, 95 % confidence interval: 2.88–33.34), poorer self-rated health status (2.18, 1.60–2.97), menstrual irregularity at 25 years (1.63, 1.07–2.49), and slower chair stands (1.49, 1.09–2.03). Age ≥65 (0.54, 0.30–0.94) and a lower level of education (0.45, 0.26–0.76) had significant inverse associations with total MRS score. Menopausal symptoms were associated with disability, poorer health status, and weaker lower-body muscle strength. These data add to the limited Asian evidence and raise the profile of this important area of health. [ABSTRACT FROM AUTHOR]

Parkinson disease (PD) is the second most common neurodegenerative disease associated with aging. Dopaminergic neuronal degeneration and α-synuclein aggregation are commonly found in PD brain. Oxidative damage and inflammation often are considered as etiological factors of PD, although the detailed mechanisms still remain unknown. Gender and aging are two important risk factors to PD, and gene mutations and certain environmental factors have been implicated in this disease. The current study employed PTEN-induced putative kinase -1 (PINK1) knockout (KO) rats, since mutations in PINK-1 lead to familial PD. We evaluated the oxidative damage in the brain of PINK1 KO rats, and we used MRI and MRS to measure the ventricle sizes and neurochemical metabolite profiles in these rats as a function of age and gender. Distinct gender- and age-related alterations were found. The results are discussed with respect to the suitabililty of this unique rat as a faithful model of known characteristics of PD. PINK1 is a mitochondrial surveillance kinase that contributes to the processes involved in ridding the cell of damaged mitochondria. Mutations in the pink 1 gene lead to inherited Parkinson disease (PD). This study examined the effects of age and gender on the PINK1 knockout rat to determine its fidelity to certain biochemical and clinical characteristics of PD. Image 1 • Oxidative damage in the brain of PINK1 KO rats differed by age and gender. • Male PINK1 KO rats have larger brain ventricular size than female PINK1 KO rats. • Neurometabolites in the striatum of PINK1 KO rats differed by age and gender. [ABSTRACT FROM AUTHOR]

Solitary fibrous tumor/hemangiopericytoma (SFT/HPC) and meningioma exhibit similar radiographic features; however, they differ in their prognoses. Preoperative differentiation between them is important for determining the treatment and follow-up plan. The aim of this study was to determine the factors that can be used to differentiate SFT/HPC from meningioma and World Health Organization (WHO) grade I from grade II meningioma. The analysis included 84 cases: 5 of SFT/HPC, 72 of WHO grade I meningioma, and 7 of WHO grade II meningioma. Clinical characteristics and conventional magnetic resonance imaging, perfusion magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) LCModel parameters were evaluated via multivariate logistic regression analysis to identify the factors that distinguish SFT/HPC from meningioma. Patients with SFT/HPC were mostly men and were younger than those with meningioma. The percentage of T2-weighted images in meningioma was greater than that in SFT/HPC. There were significant differences between SFT/HPC and meningioma in levels of glutamate, phosphocholine, myo-inositol, or glycerophosphocholine + phosphocholine derived from long echo-time MRS, and myo-inositol derived from short echo-time MRS. Stepwise logistic regression analysis revealed that the age of <45 years and myo-inositol in short echo-time MRS of ≧6.347 were associated with a diagnosis of SFT/HPC with high sensitivity and specificity. However, no factors were found that differentiated WHO grade I meningioma from WHO grade II meningioma. Age and myo-inositol level calculated from MRS are useful factors for distinguishing SFT/HPC from meningioma preoperatively. [ABSTRACT FROM AUTHOR]

Although the treatment strategies for malignant lymphomas and gliomas differ, it is usually difficult to preoperatively distinguish between them. Magnetic resonance spectroscopy (MRS) was recently reported to be useful for preoperative diagnoses; however, MRS data analysis using LCModel, which is a quantitative and objective method, was performed in only a few of the existing reports. The clinical characteristics, conventional magnetic resonance imaging findings, and MRS parameters using LCModel were evaluated to identify the factors that can help distinguish between malignant lymphomas and enhanced gliomas. In total, 59 cases were evaluated, including 13 cases of malignant lymphoma, 1 case of pilocytic astrocytoma, 5 cases of grade Ⅱ glioma, 5 cases of grade Ⅲ glioma, and 35 cases of glioblastoma. There was no correlation between clinical characteristics (sex and age) and diagnosis. Neither T1- nor T2-weighted image was useful for differentiation between the 2 forms of tumors, but the apparent diffusion coefficient minimum value was useful for distinguishing malignant lymphomas from gliomas, with an area under the curve (AUC) value of 0.852. MRS analysis using LCModel revealed differences in glutamate (Glu), N-acetylaspartate (NAA) + N-acetylaspartylglutamate (NAAG), Glu + glutamine, and Lipid (Lip) 13a + Lip13b between malignant lymphomas and gliomas. The largest AUC was 0.904, which was obtained for the Glu level, followed by 0.883 and 0.866 for NAA + NAAG and Lip13a + Lip13b, respectively. Quantitative analysis of proton-MRS using LCModel is considered to be a valuable method for distinguishing between gliomas and malignant lymphomas. [ABSTRACT FROM AUTHOR]

Cancer treatments are developing fast and the number of cancer survivors could arise to 20 million in United State by 2025. However, a large fraction of cancer survivors demonstrate cognitive dysfunction and associated decreased quality of life both shortly, and often long-term, after chemotherapy treatment. The etiologies of chemotherapy induced cognitive impairment (CICI) are complicated, made more so by the fact that many anti-cancer drugs cannot cross the blood-brain barrier (BBB). Multiple related factors and confounders lead to difficulties in determining the underlying mechanisms. Chemotherapy induced, oxidative stress-mediated tumor necrosis factor-alpha (TNF-α) elevation was considered as one of the main candidate mechanisms underlying CICI. Doxorubicin (Dox) is a prototypical reactive oxygen species (ROS)-generating chemotherapeutic agent used to treat solid tumors and lymphomas as part of multi-drug chemotherapeutic regimens. We previously reported that peripheral Dox-administration leads to plasma protein damage and elevation of TNF-α in plasma and brain of mice. In the present study, we used TNF-α null (TNFKO) mice to investigate the role of TNF-α in Dox-induced, oxidative stress-mediated alterations in brain. We report that Dox-induced oxidative stress in brain is ameliorated and brain mitochondrial function assessed by the Seahorse-determined oxygen consumption rate (OCR) is preserved in brains of TNFKO mice. Further, we show that Dox-decreased the level of hippocampal choline-containing compounds and brain phospholipases activity are partially protected in TNFKO group in MRS study. Our results provide strong evidence that Dox-targeted mitochondrial damage and levels of brain choline-containing metabolites, as well as phospholipases changes decreased in the CNS are associated with oxidative stress mediated by TNF-α. These results are consistent with the notion that oxidative stress and elevated TNF-α in brain underlie the damage to mitochondria and other pathological changes that lead to CICI. The results are discussed with reference to our identifying a potential therapeutic target to protect against cognitive problems after chemotherapy. [ABSTRACT FROM AUTHOR]

Background: Lamotrigine is a useful treatment in bipolar depression but requires several weeks of dose titration before its clinical effects can be assessed. Animal experimental studies suggest that lamotrigine lowers glutamate release. The aim of the current study was to assess the effect of lamotrigine on brain glutamate in depressed bipolar patients and to determine whether baseline glutamate could be used to predict clinical response.Methods: We studied 21 bipolar patients who received lamotrigine treatment for a current episode of depression. Before starting lamotrigine and after 10-12 weeks treatment, patients underwent proton magnetic resonance spectroscopy (MRS) scanning at 3 Tesla where levels of glutamate (measured as Glx) were determined in anterior cingulate cortex (ACC).Results: Overall, lamotrigine treatment had no significant effect on Glx levels in ACC. However, in patients who responded clinically to lamotrigine treatment Glx concentrations were significantly increased. Baseline levels of Glx did not predict response to lamotrigine.Limitations: The main limitation of the study was the modest sample size. Most patients were medicated which may have modified the effect of lamotrigine on glutamate activity. MRS at 3T cannot give a reliable estimate of glutamate separate from its main metabolite, glutamine, and thus changes in Glx may not give a precise estimate of effects of lamotrigine on glutamate itself.Conclusion: Lamotrigine does not appear to have a direct effect on glutamate levels in ACC in bipolar patients. However, therapeutic improvement during lamotrigine was associated with increased Glx, suggesting that alterations in glutamatergic activity might be related to recovery from bipolar depression. [ABSTRACT FROM AUTHOR]

Highlights • Proton Magnetic Resonance Spectroscopy (1H-MRS) is a powerful technique used to assess neurometabolite levels in vivo. • Over the last decade 1H-MRS has been increasingly applied to the study of age-related changes in central neurochemistry. • Overall, aging is associated with decreased N-acetyl aspartate (NAA) and increased Myo-inositol concentrations. • Greater NAA levels are consistently associated with better cognitive performance. • MRS shows great promise for understanding neurochemical and neurocognitive changes in aging. Abstract Magnetic resonance spectroscopy (MRS) holds promise for understanding neurochemical mechanisms associated with human cognitive aging in vivo. Recent advances in magnetic field strength and methods provide the opportunity to examine neurometabolites with greater accuracy and detail. The current review summarizes recent literature on age-associated neurometabolite changes as measured by proton MRS, and the associations with cognition in non-clinical populations. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, 179 studies were screened for review, of these, 42 were eligible. When a subset of studies were assessed based on voxel placement, magnetic field strength and sample size, N acetyl aspartate (NAA) concentration was consistently reduced with age predominantly in the frontal lobe and Myo -inositol (mI) concentration increased with age consistently in the posterior cingulate cortex (PCC). These findings are of particular interest as these NAA and mI changes mirror neurometabolite changes often seen in Alzheimer disease. The findings of this review provide further evidence of the potential for 1H-MRS to track age-related neurometabolite changes. [ABSTRACT FROM AUTHOR]

Purpose: Although brain magnetic resonance spectroscopy (MRS) imaging findings in adult Wilson disease (WD) have been explained in extensive details, a paucity of information currently exists regarding brain MRS imaging findings in pediatric WD. The purpose of this study was to clarify the role of brain MRS in detecting early metabolite abnormalities in children with WD.Patient and Methods: A case-controlled prospective study included 26 children with WD and 26 healthy controls. All children were subjected to examination on a 1.5 T MRI scanner. The spectra of N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr), as well as the metabolite ratios of NAA/Cho, NAA/Cr, and Cho/Cr, were measured and compared between two groups.Results: Eight patients revealed increased signal intensity in the basal ganglia at T1-weighted images. When compared with healthy controls, WD patients showed a significant decrease (p <  0.05) in NAA (63.8 ± 9.6 vs 97.6 ± 3.8), Cho (46.7 ± 8.9 vs 87.3 ± 4.7), Cr (44 ± 10.1 vs 81.9 ± 4.05), NAA/Cho (1.92 ± 1.2 vs 3.34 ± 0.55), NAA/Cr (1.29 ± 0.7 vs 2.46 ± 0.34), and Cho/Cr (0.78 ± 0.4 vs 2 ± 0.13). Patients complicated with liver cell failure showed a significant decrease in all previous parameters (p <  0.05) than patients without complications. Patients with mixed neurological and hepatic diseases showed a severe reduction in NAA, NAA/Cr, and NAA/Cho compared with patients with hepatic disease only.Conclusion: MRS in pediatric WD detects early neurological changes even with normal MRI. [ABSTRACT FROM AUTHOR]

Abstract The underlying mechanisms of autism and schizophrenia are poorly understood, partly due to a lack of dimension-specific research. Aberrant excitatory and inhibitory neurotransmission are implicated in both conditions, particularly in social dysfunction. This study investigates the extent to which the degree of autistic tendency and psychosis-proneness exclusively and interactively predict excitatory and inhibitory neurotransmitter concentrations in the superior temporal cortex (STC). In 38 adults (18 male, 18–40 years), we obtained autistic tendencies (Autism-Spectrum Quotient [AQ]) and psychosis-proneness scores (Schizotypal Personality Questionnaire [PP]); magnetic resonance spectroscopy (MRS) quantified glutamate and GABA+ concentrations from the STC. Results demonstrated a negative AQ/PP interaction with glutamate concentration for the left STC voxel, where PP increased with glutamate for average AQ, while AQ decreased with glutamate for average-high PP. There was a negative AQ/PP interaction with glutamate/GABA+ ratio for the right STC, AQ increasing with glutamate/GABA+ for low-average PP, while PP decreased with glutamate/GABA+ for high AQ. Consistent with animal studies, we also reveal that overall reduced glutamate/GABA+ ratio might be precipitated by increased right hemisphere GABA+ concentrations. These findings illustrate the importance of considering the concurrent effects of autism and psychosis dimensions on understanding the pathophysiological mechanisms implicated in either condition, and can advance psychopharmacological research into better treatment options for patients. Highlights • Autism and psychosis are both associated with excitation-inhibition imbalance. • Glutamate (Glu) and GABA putatively measure excitation and inhibition, respectively. • Autism and psychosis traits interactively associated with reduced right Glu/GABA • Findings highlight the importance of considering autism and psychosis concurrently • May provide better understanding of their pathophysiological mechanisms [ABSTRACT FROM AUTHOR]

Highlights • Decreased SERT density is consistently associated with heavy MDMA use. • No dose-response relationship was found. • Positive associations with time of abstinence might indicate that alterations are reversible. • No alterations were observed in terms of neurochemical markers and cerebral blood flow. • Limited significance for the majority of MDMA users and for the potential therapeutic use of MDMA. Abstract In this meta-analysis, we aimed to assess the evidence from neuroimaging studies for chronic alterations in the brains of MDMA users. The databases PubMed, Embase, and Web of Science were searched for studies published from inception to August 24, 2018, without any language restriction. Sixteen independent studies comprising 356 MDMA users and 311 controls were included. Of these, five studies investigated frontal and occipital N -acetylaspartate/creatine and myo-inositol/creatine ratios, three studies assessed basal ganglia blood flow and ten studies investigated serotonin transporter (SERT) density in various regions. We found significantly decreased SERT density in eight of 13 investigated regions. Meta-regression indicated a positive association with abstinence, but none with lifetime episodes of use. Therefore, other variables (such as doses taken per occasion) might be more important determinants. Positive associations between time of abstinence and SERT density might indicate that these alterations are reversible to some extent. Furthermore, there were no significant differences between user and control groups in terms of neurochemical ratios in the frontal and occipital lobes and blood flow in the basal ganglia. Overall, MDMA user groups showed heavy use patterns and study quality was poor. [ABSTRACT FROM AUTHOR]

Good outcome in patients following cardiac arrest (CA) is usually defined as Cerebral Performance Category (CPC) 1–2, while CPC 3 is debated, and CPC 4–5 represent poor outcome. We aimed to assess when the modified Rankin Scale (mRS) can improve CPC outcome description, especially in CPC 3. We further aimed to correlate neuron specific enolase (NSE) with both functional measures to explore their relationship with neuronal damage. Peak NSE within the first 48 hours, and CPC and mRS at 3 months were prospectively collected for 665 consecutive comatose adults following CA treated between April 2016 and April 2023. For each CPC category, mRS was described. We considered good outcome as mRS 1–3, in line with existing recommendations. CPC and mRS were correlated to peak serum NSE using non-parametric assessments. CPC 1, 2, 4 and 5 correlated almost perfectly with mRS in terms of good and poor outcomes. However, CPC 3 was heterogeneously associated to the dichotomized mRS (53.1% had good outcome (mRS 0–3), 46.9% poor outcome (mRS 4–6)). NSE was strongly correlated with CPC (Spearman's rho 0.616, P < 0.001) and mRS (Spearman's rho 0.613, P < 0.001). CPC and mRS correlate similarly with neuronal damage. Whilst CPC 1–2 and CPC 4–5 are strongly associated with mRS 0–3 and, respectively, with mRS 5–6, CPC 3 is heterogenous: both good and poor mRS scores are found within this category. Therefore, we suggest that the mRS should be routinely assessed in patients with CPC 3 to refine outcome description. [ABSTRACT FROM AUTHOR]

Highlights • ASL, DTI and MRS scans were acquired from an 8-months-old mouse model of Alzheimer’s disease. • Immune-histochemical staining and ultrastructure were performed to validate the corresponding results of MRI. • ASL revealed CBF was lower in AD mice, especially in left hippocampus, left thalamus and right cortex. • MRS showed the metabolic changes of AD mice in hippocampus were more serious than that in cortex. • The results of DTI were not as significant as ASL and MRS. Abstract Transgenic animal models of Alzheimer’s disease (AD) can mimic pathological and behavioral changes occurring in AD patients, and are usually viewed as the first choice for testing novel therapeutics. Validated biomarkers, particularly non-invasive ones, are urgently needed for AD diagnosis or evaluation of treatment results. However, there are few studies that systematically characterize pathological changes in AD animal models. Here, we investigated the brain of 8-month-old amyloid precursor protein/presenilin 1 (APP/PS1) transgenic and wild-type (WT) mice, employing 7.0-T magnetic resonance imaging (MRI). Magnetic resonance spectroscopy (MRS), diffusion tensor imaging (DTI), and arterial spin labeling (ASL) were obtained through micro-MRI scanning. After MRI examination in both transgenic (n = 12) and WT (n = 12) mice, immunohistochemical staining and ultrastructural analysis were subsequently performed. Cerebral blood flow (CBF) was significantly decreased in the left hippocampus, left thalamus, and right cortex of AD mice (P < 0.05). Moreover, MRS showed significantly changed NAA/Cr, Glu/Cr, and mI/Cr ratios in the hippocampus of transgenic mice. While only NAA/Cr and mI/Cr ratios varied significantly in the cortex of transgenic mice. Regarding DTI imaging, however, the values of FA, MD, DA and DR were not significantly different between transgenic and WT mice. Finally, it is worth noting that pathological damage of metabolism, CBF, and white matter was more distinct between transgenic and WT mice by pathological examination. Altogether, our results suggest that intravital imaging evaluation of 8-month-old APP/PS1 transgenic mice by MRS and ASL is an alternative tool for AD research. [ABSTRACT FROM AUTHOR]

Highlights • We used bistable stimuli to examine individual differences in perceptual organization. • Aging reduced perceptual switching rates of auditory streaming and visual plaids. • Effective volitional control was correlated with GABA levels in sensory areas. • Sequential scene analysis is influenced by both age-related and neurochemical factors. Abstract Age-related changes in auditory and visual perception have an impact on the quality of life. It has been debated how perceptual organization is influenced by advancing age. From the neurochemical perspective, we investigated age effects on auditory and visual bistability. In perceptual bistability, a sequence of sensory inputs induces spontaneous switching between different perceptual objects. We used different modality tasks of auditory streaming and visual plaids. Young and middle-aged participants (20–60 years) were instructed to indicate by a button press whenever their perception changed from one stable state to the other. The number of perceptual switches decreased with participants' ages. We employed magnetic resonance spectroscopy to measure non-invasively concentrations of the inhibitory neurotransmitter (γ-aminobutyric acid, GABA) in the brain regions of interest. When participants were asked to voluntarily modulate their perception, the amount of effective volitional control was positively correlated with the GABA concentration in the auditory and motion-sensitive areas corresponding to each sensory modality. However, no correlation was found in the prefrontal cortex and anterior cingulate cortex. In addition, effective volitional control was reduced with advancing age. Our results suggest that sequential scene analysis in auditory and visual domains is influenced by both age-related and neurochemical factors. [ABSTRACT FROM AUTHOR]

Highlight • Eighteen clinical scanners were enrolled in an MR-spectroscopy intercomparison study. • The feasibility of a quality control protocol for routine MR-spectroscopy was proved. • The water linewidth at isocenter was less than 0.03 ppm for 1.5 T and 3 T scanners. • The area under the water peak varied linearly with the acquisition voxel volume. • The coefficient of variation for repeated measurements of phantom T 2 was less than 9%. Abstract Purpose The aim of this study was to propose and validate across various clinical scanner systems a straightforward multiparametric quality assurance procedure for proton magnetic resonance spectroscopy (MRS). Methods Eighteen clinical 1.5 T and 3 T scanner systems for MRS, from 16 centres and 3 different manufacturers, were enrolled in the study. A standard spherical water phantom was employed by all centres. The acquisition protocol included 3 sets of single (isotropic) voxel (size 20 mm) PRESS acquisitions with unsuppressed water signal and acquisition voxel position at isocenter as well as off-center, repeated 4/5 times within approximately 2 months. Water peak linewidth (LW) and area under the water peak (AP) were estimated. Results LW values [mean (standard deviation)] were 1.4 (1.0) Hz and 0.8 (0.3) Hz for 3 T and 1.5 T scanners, respectively. The mean (standard deviation) (across all scanners) coefficient of variation of LW and AP for different spatial positions of acquisition voxel were 43% (20%) and 11% (11%), respectively. The mean (standard deviation) phantom T 2 values were 1145 (50) ms and 1010 (95) ms for 1.5 T and 3 T scanners, respectively. The mean (standard deviation) (across all scanners) coefficients of variation for repeated measurements of LW, AP and T 2 were 25% (20%), 10% (14%) and 5% (2%), respectively. Conclusions We proposed a straightforward multiparametric and not time consuming quality control protocol for MRS, which can be included in routine and periodic quality assurance procedures. The protocol has been validated and proven to be feasible in a multicentre comparison study of a fairly large number of clinical 1.5 T and 3 T scanner systems. [ABSTRACT FROM AUTHOR]

Proton magnetic resonance spectroscopy measurements of glutamate and GABA are important in neuropsychiatric research. Some study designs require simultaneous measurement of both metabolites. GABA measurement requires specialized pulse sequences, the most common approach being J-difference spectral editing with MEGA-PRESS. This method enables two different strategies for concurrently measuring glutamate - from either off-resonance or difference spectra. However, it is uncertain how either strategy compares to conventional glutamate measurements. Here we compared these approaches in 49 subjects (28 healthy volunteers and 21 first-episode psychosis patients), in whom both PRESS (TE 80) and MEGA-PRESS (TE 68) spectra were obtained from dorsolateral prefrontal cortex. Glutamate and glx estimates from MEGA-PRESS difference and off-resonance spectra were compared to glutamate and glx estimates from PRESS spectra using correlational analyses. In healthy volunteers, correlations between PRESS and MEGA-PRESS off-resonance values were r ≥ 0.88 and were significantly higher than correlations between PRESS and MEGA-PRESS difference spectrum values ( r ≤ 0.36). Patients showed a similar pattern. Lower correlations with difference spectrum values may reflect a disproportionate impact of field instabilities on co-edited glutamate signals. The results suggest that MEGA-PRESS off-resonance spectra can substitute for separately-acquired PRESS spectra in studies requiring simultaneous glutamate and GABA measurements. [ABSTRACT FROM AUTHOR]

13C Magnetic Resonance Spectroscopy (MRS) using hyperpolarized 13C-labeled pyruvate as a substrate offers a measure of pyruvate-lactate interconversion and is thereby a marker of the elevated aerobic glycolysis (Warburg effect) generally exhibited by cancer cells. Here, we aim to compare hyperpolarized [1-13C]pyruvate MRS with simultaneous 18F-2-fluoro-2-deoxy-d-glucose (FDG) PET in a cross-sectional study of canine cancer patients.Methods: Canine cancer patients underwent integrated PET/MRI using a clinical whole-body system. Hyperpolarized [1-13C]pyruvate was obtained using dissolution-DNP. 18F-FDG PET, dynamic 13C MRS, 13C MRS Imaging (MRSI) and anatomical 1H MRI was acquired from 17 patients. Apparent pyruvate-to-lactate rate constants were estimated from dynamic 13C MRS. 18F-FDG Standard Uptake Values and maximum [1-13C]lactate-to-total-13C ratios were obtained from tumor regions of interest. Following inspection of data, patients were grouped according to main cancer type and linear regression between measures of lactate generation and 18F-FDG uptake were tested within groups. Between groups, the same measures were tested for group differences.Results: The main cancer types of the 17 patients were sarcoma (n = 11), carcinoma (n = 5) and mastocytoma (n = 1). Significant correlations between pyruvate-to-lactate rate constants and 18F-FDG uptake were found for sarcoma patients, whereas no significant correlations appeared for carcinoma patients. The sarcoma patients showed a non-significant trend towards lower 18F-FDG uptake and higher lactate generation than carcinoma patients. However, the ratio of lactate generation to 18F-FDG uptake was found to be significantly higher in sarcoma as compared to carcinoma. The results were found both when lactate generation was estimated as an apparent pyruvate-to-lactate rate constant from dynamic 13C MRS and as an [1-13C]lactate to total 13C ratio from 13C MRSI.Conclusions: A comparison of hyperpolarized [1-13C]pyruvate MRS with simultaneous 18F-FDG PET indicate that lactate generation and 18F-FDG uptake in cancers can be related and that their relation depend on cancer type. This finding could be important for the interpretation and eventual clinical implementation of hyperpolarized 13C. In addition, the differences between the two modalities may allow for better metabolic phenotyping performing hybrid imaging in the form of hyperPET. [ABSTRACT FROM AUTHOR]

A small plasmid designated pCS36-4CPA with a size of 5217 base pairs and G-C content of 50.74% was isolated from Citrobacter sp. 36-4CPA. The origin of replication ( ori ) of the plasmid was identified as a region of about 800 bp in length with an identity of 67.1% to the ColE1 plasmid at the nucleotide level. The replication region contained typical elements of ColE1-like plasmids: RNA I and RNA II with their corresponding −10 and −35 boxes, a single-strand initiation site ( ssi ), and a lagging-strand termination site ( terH ). As seen in other ColE1-like plasmids, pCS36-4CPA carried mobilisation machinery that include mobABCD genes but it did not possess the rom gene. Analysis of the multimer resolution site ( mrs ) was performed and XerC and XerD binding sites were identified. Also, the 70-nt transcript Rcd of pCS36-4CPA was predicted and similarity of the transcript’s secondary structure with those of the ColE1-family was shown. The cargo module of pCS36-4CPA contained three open reading frames (ORFs). Two of them (ORF5 and ORF6) showed no significant homology to any known gene sequences but contained putative THAP DNA-binding (DBD) and type II restriction endonuclease Eco O109I domains. The seventh open reading frame (ORF7) encodes YhdJ-like DNA modification methylase. The region highly homologous to pCS36-4CPA was found in the Salmonella phage SE2 genome. [ABSTRACT FROM AUTHOR]

Recent observations of the Greenland ice sheet show an increase of the area affected by progressive melt of snow and ice, thus resulting in production of the additional meltwater. In 2011, an important storage of meltwater in the firn has been observed in the S-E Greenland. This water does not freeze during the wintertime and forms a perennial firn aquifer. The aquifer spatial extent has been initially monitored with combined ground and airborne radar observations, but these geophysical techniques are not able to inform us on the amount of meltwater stored at depth. In this study, we use the magnetic resonance soundings (MRS) method for estimating the volume of water stored in the Greenland ice sheet firn and mapping its spatial variability. Our study area covers a firn aquifer along a 16-km E-W transect, ranging between elevations of 1520 and 1760 m. In July 2015 and July 2016, we performed MRS measurements that allow estimating the water volume in the studied area as well as the one-year water volume evolution. Water storage is not homogeneous, fluctuating between 0.2 and 2 m 3 /m 2 , and contains discontinuities in the hydrodynamic properties. We estimate an average volume of water stored in the firn in 2016 to be 0.76 m 3 /m 2 , which corresponds to a 0.76-m-thick layer of bulk water. MRS monitoring reveals that from April 2015 to July 2016 the volume of water stored at the location of our transect increases by about 36%. We found MRS-estimated depth to water in a good agreement with that obtained with the ground penetrating radar (GPR). [ABSTRACT FROM AUTHOR]

NAD metabolism and the NAD biosynthetic enzymes nicotinamide nucleotide adenylyltransferases (NMNATs) are thought to play a key neuroprotective role in tauopathies, including Alzheimer’s disease. Here, we investigated whether modulating the expression of the NMNAT nuclear isoform NMNAT1, which is important for neuronal maintenance, influences the development of behavioral and neuropathological abnormalities in htau mice, which express non-mutant human tau isoforms and represent a model of tauopathy relevant to Alzheimer’s disease. Prior to the development of cognitive symptoms, htau mice exhibit tau hyperphosphorylation associated with a selective deficit in food burrowing, a behavior reminiscent to activities of daily living which are impaired early in Alzheimer’s disease. We crossed htau mice with Nmnat1 transgenic and knockout mice and tested the resulting offspring until the age of 6 months. We show that overexpression of NMNAT1 ameliorates the early deficit in food burrowing characteristic of htau mice. At 6 months of age, htau mice did not show neurodegenerative changes in both the cortex and hippocampus, and these were not induced by downregulating NMNAT1 levels. Modulating NMNAT1 levels produced a corresponding effect on NMNAT enzymatic activity but did not alter NAD levels in htau mice. Although changes in local NAD levels and subsequent modulation of NAD-dependent enzymes cannot be ruled out, this suggests that the effects seen on behavior may be due to changes in tau phosphorylation. Our results suggest that increasing NMNAT1 levels can slow the progression of symptoms and neuropathological features of tauopathy, but the underlying mechanisms remain to be established. [ABSTRACT FROM AUTHOR]