Brain Changes in Long-Term Zen Meditators Using Proton Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging: A Controlled Study

Introduction: This work aimed to determine whether 1H magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI) and diffusion tensor imaging (DTI) are correlated with years of meditation and psychological variables in long-term Zen meditators compared to healthy non-meditator controls. Materials and Methods: Design. Controlled, cross-sectional study. Sample. Meditators were recruited from a Zen Buddhist monastery. The control group was recruited from hospital staff. Meditators were administered questionnaires on anxiety, depression, cognitive impairment and mindfulness. 1H-MRS (1.5 T) of the brain was carried out by exploring four areas: both thalami, both hippocampi, the posterior superior parietal lobule (PSPL) and posterior cingulate gyrus. Predefined areas of the brain were measured for diffusivity (ADC) and fractional anisotropy (FA) by MR-DTI. Results: Myo-inositol (mI) was increased in the posterior cingulate gyrus and Glutamate (Glu), N-acetyl-aspartate (NAA) and N-acetyl-aspartate/Creatine (NAA/Cr) was reduced in the left thalamus in meditators. We found a significant positive correlation between mI in the posterior cingulate and years of meditation (r = 0.518; p = .019). We also found significant negative correlations between Glu (r =20.452; p = .045), NAA (r =20.617; p = .003) and NAA/Cr (r =20.448; P = .047) in the left thalamus and years of meditation. Meditators showed a lower Apparent Diffusion Coefficient (ADC) in the left posterior parietal white matter than did controls, and the ADC was negatively correlated with years of meditation (r =20.4850, p = .0066). Conclusions: The results are consistent with the view that mI, Glu and NAA are the most important altered metabolites. This study provides evidence of subtle abnormalities in neuronal function in regions of the white matter in meditators

Neuronal underpinnings of stuttering

Fluent speech production depends on robust connections between brain regions that are crucial for auditory processing, motor planning and execution. The ability of the speech apparatus to produce effortless, continuous and uninterrupted flow of speech is compromised in people who stutter (PWS). Stuttering is a multifactorial speech fluency disorder that results in unintended occurrences of sound syllable repetitions, prolongations, and blocks, particularly on the initial part of words and sentences. Decades of research on the topic have produced an extensive amount of data but the mechanism behind the symptoms associated with stuttering is not clear. The aim of the present study was to investigate the neuronal basis of stuttering by looking at the brains neurochemistry utilizing the proton magnetic resonance spectroscopy (1H - MRS) technique. In particular, we looked at the neurotransmitters N-acetyl Aspartate (NAA), an aggregate of Glutamate and Glutamine (Glx) and myo-inositol (mI) as potential candidates for understanding the biochemical manifestations of stuttering. We have also collected behavioral data from the PWS group and correlated it with their spectroscopy results. Finally, we combined the measurements of neuronal activity behind speech production, probed with functional magnetic resonance imaging (fMRI), with 1H-MRS measurements in order to achieve information on the interaction between neuronal activation and underlying neurochemical function. The inferior frontal gyrus (IFG) was chosen as a target region for this investigation, given its' involvement in speech motor control. Neurotransmitter mI showed the main group effect. The cerebral metabolite pattern of PWS is characterized by the pronounced reduction in myo-inositol level in the IFG. Myo- inositol is considered a glial marker and its concentration may reflect the condition of myelin in the brain. The myelination process is referred to as the maturation process of the fibers that facilitates rapid neural innervation of speech muscles underlying speech fluency. Hence, given the existing literature on the topic and our main findings we suggested that delayed or impaired myelination of the speech-related neuronal network in the postnatal period might be responsible for the later development of stuttering.Flytende tale er avhengig av solide forbindelser mellom hjerneområder involvert i auditorisk prosessering, motorisk planlegging og utførelse. Taleapparatets evne til uanstrengt å produsere flytende uforstyrret tale er forstyrret hos personer som stammer (PWS). Stamming er en sammensatt forstyrrelse av taleflyt som resulterer i ufrivillige gjentagelser av stavelser, utvidelser, og blokkeringer, spesielt i begynnelsen av ord og setninger. Gitt tiår med forskning på området er det ennå ikke klart hvilke mekanismer som ligger til grunn for stammingen. Hensikten med dette studiet har vært å utforske det nevrale grunnlaget til stamming ved å se på hjernens nevrokjemi ved å ta i bruk proton-magnetisk resonsansspektroskopi (1H-MRS) teknikk. Vi har sett på om nevrotransmitterene: N-acetyl Asparatate (NAA); glutamat og glutamin (Glx) og myo-inositol kan bidra til forståelsen av de biokjemiske manifestasjonene av stamming. Vi har også samlet inn atferdsdata fra PWS-gruppen og korrelert dette med spektroskopi-dataen. Til slutt kombinerte vi målingene av den nevral aktiviteten av taleproduksjon med 1H-MRS målingene for å se på interaksjon mellom nevral aktivering og underliggende nevrokjemisk funksjon. Inferior frontal gyrus (IFG) var målområdet for undersøkelsen, siden området er viktig for motorisk kontroll av tale. Nevrotransmitteren myo-inositol viste en hovedgruppeeffekt. Metabolittene i hjernen til personer som stammer var karakterisert av en tydelig reduksjon i nivå av myo-inositol i IFG. Myo-inositol er ansett som en glial markør, og dets konsentrasjon kan muligens fortelle om myelinets tilstand i hjernen. Myelineringsprosessen av nerveceller er en modningsprosess som fasiliterer rask signaloverføring fra hjernen til muskelfibrene involvert i tale. Vi foreslår derfor på bakgrunn av foreliggende litteratur på området og våre resultater at forsinket eller hemmet myelinering av tale-relaterte nevrale nettverk i spedbarnsperioden kan føre til senere utvikling av stamming.LOGO345MAPS-LOG0

Energy failure following traumatic brain injury: Potential mechanisms and impact of normobaric hyperoxia

Cerebral ischaemia is a frequent finding in post mortem studies following traumatic brain injury (TBI), but clinical studies using 15oxygen positron emission tomography (15O PET) suggest that classical ischaemia is uncommon beyond the first 24 hours after injury. Evidence of metabolic failure in the absence of classical ischaemia may represent ongoing neuronal dysfunction and progressive neuronal loss. Any therapeutic intervention that mitigates such metabolic derangements before they result in irreversible neuronal injury may improve tissue fate and improve the functional outcome for patients. Energy failure was spatially defined, characterised, and mapped using 15O and 18Fluoromisinidazole ([18F] FMISO) positron emission tomography. This enabled differentiation of classical ischaemia, diffusion hypoxia, and established infarction, and provided data on the dominant local mechanism at any given time after TBI. My thesis also aimed to examine the utility of diffusion tensor imaging and whole-brain proton MR spectroscopy (WB 1H MRS) as imaging biomarkers to investigate normobaric hyperoxia as a therapeutic option following traumatic brain injury (TBI). Using ([18F] FMISO PET evidence of tissue hypoxia consistent with microvascular ischaemia was found across the injured brain. The impact of normobaric hyperoxia (NBH) was examined in a clinical TBI cohort using diffusion tensor imaging and WB 1H MRS. Some evidence of benefit was found within the perilesional brain, but further studies should examine the value of a longer period of exposure to NBH and whether this has implications for functional outcome.AAGBI, MRC, Wellcome trus

Investigating Cortical Changes in Cervical Spondylotic Myelopathy Using Functional Magnetic Resonance Imaging, Proton Magnetic Resonance Spectroscopy and Diffusion Tensor Imaging

Cervical spondylotic myelopathy (CSM) is the most common cause of spinal cord dysfunction in older adults. CSM can present abruptly with severe symptoms of neurological impairment or insidiously with a slow stepwise deterioration. There is no current imaging modality or biomarker that can help predict which patient will successfully respond to conservative versus surgical treatment. The goal of this thesis was to follow CSM patients longitudinally to assess how brain function, metabolism, and structure correlate to clinical outcomes in the context of recovering neurological function following surgery. Chapter 1 of this thesis will provide a detailed literature review of the current controversies in treating CSM. Novel imaging techniques that can elucidate cortical adaptations in CSM patients will be discussed. Chapter 2 characterizes the metabolite profile of CSM patients and whether metabolites such as N-Acetylaspartate, a marker of neuronal health, can distinguish CSM patients from healthy controls. Chapter 3 will investigate whether metabolite changes in the primary motor cortex of CSM patients recover following successful surgical intervention and able to predict neurological recovery. The structural integrity of the white matter adjacent to the primary motor and sensory cortices will also be assessed. Chapter 4 will investigate the cortical adaptation and reorganization in mild and moderate CSM severities, prior to and following decompressive surgery. This thesis utilizes novel methods to explore how the cortex attempts to adapt and compensate for neurological deficit, distal to the site of injury, and identify new imaging biomarkers for characterization of CSM severity and predicting functional recovery

Magnetic resonance spectroscopy quality assessment at CUBIC and application to the study of the cerebellar deep nuclei in children with fetal alcohol spectrum disorder

Includes bibliographical references (leaves 73-79).In vivo magnetic resonance spectroscopy (MRS) is an imaging technique that allows the chemical study of human tissue non-invasively. The method holds great promise as a diagnostic tool once its reliability has been established. Inter-scanner variability has, however, hampered this from happening as results cannot easily be compared if acquired on different scanners. In this study a phantom was constructed to determine the localisation efficiency of the 3 T Siemens Allegra MRI scanner located at the Cape Universities Brain Imaging Centre (CUBIC). Sufficient localisation is the key to acquiring useful spectroscopic data as only the signal from a small volume of interest (VOI) is typically acquired. The phantom consisted of a Perspex cube located inside a larger Perspex sphere. Solutions of the cerebral metabolites N-acetyl aspartate (NAA) and choline (Cho) were placed in the inner cube and outer sphere respectively. The phantom was scanned at a range of voxel sizes and echo times in order to determine parameters that typically indicate the performance of the scanner in question. The resultant full width at half maximum (FWHM) and signal to noise ratio (SNR) values indicated that optimal results were obtained for a voxel with dimensions 20 x 20 x 20 mm3. The selection efficiency could not be measured due to limitations in the scanner, but two other performance parameters ' extra volume suppression (EVS) and contamination ' could be determined. The EVS showed that the scanner was able to eliminate the entire background signal from the out-of-voxel region when voxel sizes with dimensions (20 mm)3 and (30 mm)3 were used. This performance decreased to 96.2% for a voxel size of (50 mm)3. The contamination indicated that the unwanted signal, weighted by the respective proton densities of the chemicals, ranged from 12% in the (20 mm)3 voxel to 24% in the (50 mm)3 voxel. These ranges are well within acceptable limits for proton MRS. Analysis of the water suppression achieved in the scanner showed an efficiency of 98.84%, which is acceptable for proton spectroscopy. It was also found that manual iv shimming of the scanner improved the spectra obtained, as compared to the automated shimming performed by the scanner. The second objective of the study was to quantify absolute metabolite concentrations in the familiar SI units of mM as results were previously mostly expressed as metabolite ratios. The LCModel software was used to assess two methods of determining absolute metabolite concentrations and the procedure using water scaling consistently showed superior performance to a method using a calibration factor. The method employing water scaling was then applied to a study of fetal alcohol spectrum disorder (FASD) where the deep cerebellar nuclei of children with FASD and a control group were scanned. The cerebellar nuclei were of interest as children with FASD show a remarkably consistent deficit in eye blink conditioning (EBC). The cerebellar deep nuclei is known to play a critical role in the EBC response. The results show significant decreases in the myo-inositol (mI) and total choline (tCho) concentrations of children with FASD in the deep cerebellar nuclei compared to control children. The FAS/PFAS subjects have a mean mI concentration of 4.6 mM as compared to a mean of 5.3 mM in the controls. A Pearson correlation showed that there was a significant relationship between decreasing mI concentrations with increasing prenatal alcohol exposure. The mean tCho concentrations are 1.3 mM for FAS/PFAS and 1.5 mM for the controls. There was no significant differences between the heavily exposed group and either the FAS/PFAS or the control subjects for either metabolite. The decreased mI and tCho concentrations may indicate deficient calcium signalling or decreased cell membrane integrity ' both of which can explain the compromised cerebellar learning in FASD subjects

Multimodal neuroimaging signatures of early cART-treated paediatric HIV - Distinguishing perinatally HIV-infected 7-year-old children from uninfected controls

Introduction: HIV-related brain alterations can be identified using neuroimaging modalities such as proton magnetic resonance spectroscopy (1H-MRS), structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI), and functional MRI (fMRI). However, few studies have combined multiple MRI measures/features to identify a multivariate neuroimaging signature that typifies HIV infection. Elastic net (EN) regularisation uses penalised regression to perform variable selection, shrinking the weighting of unimportant variables to zero. We chose to use the embedded feature selection of EN logistic regression to identify a set of neuroimaging features characteristic of paediatric HIV infection. We aimed to determine 1) the most useful features across MRI modalities to separate HIV+ children from HIV- controls and 2) whether better classification performance is obtained by combining multimodal MRI features rather than using features from a single modality. Methods: The study sample comprised 72 HIV+ 7-year-old children from the Children with HIV Early Antiretroviral Therapy (CHER) trial in Cape Town, who initiated combination antiretroviral therapy (cART) in infancy and had their viral loads suppressed from a young age, and 55 HIV- control children. Neuroimaging features were extracted to generate 7 MRI-derived sets. For sMRI, 42 regional brain volumes (1st set), mean cortical thickness and gyrification in 68 brain regions (2nd and 3rd set) were used. For DTI data: radial (RD), axial (AD), mean (MD) diffusivities, and fractional anisotropy (FA) in each of 20 atlas regions were extracted for a total of 80 DTI features (4th set). For 1H-MRS, concentrations of 14 metabolites and their ratios to creatine in the basal ganglia, peritrigonal white matter, and midfrontal gray matter voxels (5th, 6th and 7th set) were considered. A logistic EN regression model with repeated 10-fold cross validation (CV) was implemented in R, initially on each feature set separately. Sex, age and total intracranial volume (TIV) were included as confounders with no shrinkage penalty. For each model, the classification performance for HIV+ vs HIV- was assessed by computing accuracy, specificity, sensitivity, and mean area under the receiver operator characteristic curve (AUC) across 10 CV folds and 100 iterations. To combine feature sets, the best performing set was concatenated with each of the other sets and further EN regressions were run. The combination giving the largest AUC was combined with each of the remaining sets until there was no further increase in AUC. Two concatenation techniques were explored: nested and non-nested modelling. All models were assessed for their goodness of fit using χ 2 likelihood ratio tests for non-nested models and Akaike information criterion (AIC) for nested models. To identify features most useful in distinguishing HIV infection, the EN model was retrained on all the data, to find features with non-zero weights. Finally, multivariate imputation using chained equations (MICE) was explored to investigate the effect of increased sample size on classification and feature selection. Results: The best performing modality in the single modality analysis was sMRI volume

Quantitative MRI brain in congenital adrenal hyperplasia: in vivo assessment of the cognitive and structural impact of steroid hormones

Abstract Context Brain white matter hyper-intensities are seen on routine clinical imaging in 46% of adults with congenital adrenal hyperplasia (CAH). The extent and functional relevance of these abnormalities have not been studied using quantitative MRI analysis. Objective To examine white matter microstructure, neural volumes and CNS metabolites in CAH due to 21-hydroxylase deficiency (21OHD) and to determine whether identified abnormalities are associated with cognition, glucocorticoid and androgen exposure. Design, setting and participants A cross-sectional study at a tertiary hospital including 19 females (18-50 years) with 21OHD and 19 age-matched healthy females. Main outcome measure Recruits underwent cognitive assessment and brain imaging including; diffusion weighted imaging of white matter, T1-weighted volumetry and magnetic resonance spectroscopy for neural metabolites. We evaluated white matter microstructure using tract-based spatial statistics. We compared cognitive scores, neural volumes and metabolites between groups and relationships between glucocorticoid exposure, MRI and neurologic outcomes. Results Patients with 21OHD had widespread reductions in white matter structural integrity, reduced volumes of right hippocampus, bilateral thalami, cerebellum and brainstem, and reduced mesial temporal lobe total choline content. Working memory, processing speed, and digit span and matrix reasoning scores were reduced in patients with 21OHD, despite similar education and intelligence to controls. 21OHD individuals exposed to higher glucocorticoid doses had greater abnormalities in white matter microstructure and cognitive performance. Conclusion For the first time we demonstrate that 21OHD and current glucocorticoid replacement regimens have a profound impact on brain morphology and function. If reversible, these CNS markers represent a potential target for treatment

Brain imaging and human nutrition: which measures to use in intervention studies?

The present review describes brain imaging technologies that can be used to assess the effects of nutritional interventions in human subjects. Specifically, we summarise the biological relevance of their outcome measures, practical use and feasibility, and recommended use in short- and long-term nutritional studies. The brain imaging technologies described consist of MRI, including diffusion tensor imaging, magnetic resonance spectroscopy and functional MRI, as well as electroencephalography/magnetoencephalography, near-IR spectroscopy, positron emission tomography and single-photon emission computerised tomography. In nutritional interventions and across the lifespan, brain imaging can detect macro- and microstructural, functional, electrophysiological and metabolic changes linked to broader functional outcomes, such as cognition. Imaging markers can be considered as specific for one or several brain processes and as surrogate instrumental endpoints that may provide sensitive measures of short- and long-term effects. For the majority of imaging measures, little information is available regarding their correlation with functional endpoints in healthy subjects; therefore, imaging markers generally cannot replace clinical endpoints that reflect the overall capacity of the brain to behaviourally respond to specific situations and stimuli. The principal added value of brain imaging measures for human nutritional intervention studies is their ability to provide unique in vivo information on the working mechanism of an intervention in hypothesis-driven research. Selection of brain imaging techniques and target markers within a given technique should mainly depend on the hypothesis regarding the mechanism of action of the intervention, level (structural, metabolic or functional) and anticipated timescale of the intervention's effects, target population, availability and costs of the technique

Role of magnetic resonance spectroscopy in cerebral glutathione quantification for youth mental health:A systematic review

AIM: Oxidative stress is strongly implicated in many psychiatric disorders, which has resulted in the development of new interventions to attempt to perturb this pathology. A great deal of attention has been paid to glutathione, which is the brain's dominant antioxidant and plays a fundamental role in removing free radicals and other reactive oxygen species. Measurement of glutathione concentration in the brain in vivo can provide information on redox status and potential for oxidative stress to develop. Glutathione might also represent a marker to assess treatment response. METHODS: This paper systematically reviews studies that assess glutathione concentration (measured using magnetic resonance spectroscopy) in various mental health conditions. RESULTS: There is limited evidence showing altered brain glutathione concentration in mental disorders; the best evidence suggests glutathione is decreased in depression, but is not altered in bipolar disorder. The review then outlines the various methodological options for acquiring glutathione data using spectroscopy. CONCLUSIONS: Analysis of the minimum effect size measurable in existing studies indicates that increased number of participants is required to measure subtle but possibly important differences and move the field forward