In this study, we used magnetic resonance imaging (MRI) to identify the different brain phenotypes within apparently healthy children and to evaluate whether these phenotypes had different prenatal characteristics. We included 65 healthy children (mean age, 10 years old) with normal neurological examinations and without structural abnormalities. We performed cluster analyses to identify the different brain phenotypes in the brain MRI images. We performed descriptive analyses, including demographic and perinatal characteristics, to assess the differences between the clusters. We identified two clusters: Cluster 1, or the “small brain phenotype” (n = 44), which was characterized by a global reduction in the brain volumes, with smaller total intracranial volumes (1044.53 ± 68.37 vs. 1200.87 ± 65.92 cm3 (p < 0.001)), total grey-matter volumes (644.65 ± 38.85 vs. 746.79 ± 39.37 cm3 (p < 0.001)), and total white-matter volumes (383.68 ± 40.17 vs. 443.55 ± 36.27 cm3 (p < 0.001)), compared with Cluster 2, or the “normal brain phenotype” (n = 21). Moreover, almost all the brain areas had decreased volumes, except for the ventricles, caudate nuclei, and pallidum areas. The risk of belonging to “the small phenotype” was 82% if the child was preterm, 76% if he/she was born small for his/her gestational age and up to 80% if the mother smoked during the pregnancy. However, preterm birth appears to be the only substantially significant risk factor associated with decreased brain volumes.

This study explored the brain structural correlates of psychological flexibility (PF) as measured with the Psychological Inflexibility in Pain Scale (PIPS) in patients with fibromyalgia (FM). Structural magnetic resonance imaging data from 47 FM patients were used to identify Gray Matter Volume (GMV) alterations related to PIPS scores. Brain GMV clusters related to PIPS were then correlated with clinical and cognitive variables to further explore how emerged brain clusters were intertwined with FM symptomatology. Longitudinal changes in PIPS-related brain clusters values were assessed by studying pre–post data from 30 patients (15 allocated to a mindfulness-based stress reduction (MBSR) program and 15 to treatment-as-usual). Changes in PIPS-related brain clusters were also explored in participants showing greater/lower longitudinal changes in PIPS scores. PIPS scores were positively associated with GMV in a bilateral cluster in the ventral part of the bed nucleus of the stria terminalis (BNST). Significant associations between BNST cluster with functional impairment, depressive symptomatology, perceived stress and the nonjudging mindfulness facet were observed. Participants reporting greater pre–post increases in PIPS scores showed greater increases in BNST cluster values. These findings contribute to the understanding on the neurobiological bases of PF in FM and encourage further explorations of the role of the BNST in chronic pain.

The aims of this work were to evaluate whether the treatment of patients with fibromyalgia with memantine is associated with significant changes in metabolite concentrations in the brain, and to explore any changes in clinical outcome measures. Magnetic resonance spectroscopy was performed of the right anterior and posterior insula, both hippocampi and the posterior cingulate cortex. Questionnaires on pain, anxiety, depression, global function, quality of life and cognitive impairment were used. Ten patients were studied at baseline and after three months of treatment with memantine. Significant increases were observed in the following areas: N-acetylaspartate (4.47 at baseline vs. 4.71 at three months, p = 0.02) and N-acetylaspartate+N-acetylaspartate glutamate in the left hippocampus (5.89 vs. 5.98; p = 0.007); N-acetylaspartate+N-acetylaspartate glutamate in the right hippocampus (5.31 vs 5.79; p = 0.01) and the anterior insula (7.56 vs. 7.70; p = 0.033); glutamate+glutamine/creatine ratio in the anterior insula (2.03 vs. 2.17; p = 0.022) and the posterior insula (1.77 vs. 2.00; p = 0.004); choline/creatine ratio in the posterior cingulate (0.18 vs. 0.19; p = 0.023); and creatine in the right hippocampus (3.60 vs. 3.85; p = 0.007). At the three-month follow-up, memantine improved cognitive function assessed by the Cognition Mini-Exam (31.50, SD = 2.95 vs. 34.40, SD = 0.6; p = 0.005), depression measured by the Hamilton Depression Scale (7.70, SD = 0.81 vs. 7.56, SD = 0.68; p = 0.042) and severity of illness measured by the Clinical Global Impression severity scale (5.79, SD = 0.96 vs. 5.31, SD = 1.12; p = 0.007). Depression, clinical global impression and cognitive function showed improvement with memantine. Magnetic resonance spectroscopy could be useful in monitoring response to the pharmacological treatment of fibromyalgia.

BACKGROUND:The practice of meditation has been shown to improve pain-related quality of life and also to alter brain activity. To assess brain volumetry in fibromyalgia (FM) patients, healthy meditators and healthy non-meditator control groups, and to elucidate the possible association between brain changes in meditators and years of meditation practice.METHODS:Twelve patients diagnosed with FM, eleven long-term Zen meditators and ten healthy control subjects closely matched for sex and age were recruited. A high resolution T1-3D sequence was acquired and a high-dimensional DARTEL normalization strategy was applied. Questionnaires on anxiety, depression and cognitive impairment were administered.RESULTS:There was a statistically significant increase in grey matter volume in the Brodmann area 20 (right and left inferior temporal gyri) in patients with fibromyalgia and a significant decrease in the meditator group as compared to controls. On the other hand, there was a significant increase in grey matter volume in fibromyalgia patients as compared to controls and meditators, to the right temporal gyrus (p=0.03, t=6.85) and left temporal gyrus (p=0.04, t=6.31). The number of months of meditation did not correlate with significant grey matter volume changes in the meditator group.CONCLUSIONS:FM and meditation appears to be reliably associated with altered anatomical structure in the Brodmann area 20 (in both inferior temporal gyri), and these changes are associated with anxiety and depression levels. In addition, exploratory morphometric analyses for fibromyalgia patients and meditators may reveal relevant brain regions showing structural diminution in meditation practitioners. Morphologic changes might predispose toward vulnerability to develop a chronic pain state. Such structural diminutions could potentially indicate functional benefits.

Purpose To identify differences in neuronal tissue from retinal and brain structures in children born small for gestational age (SGA) with no abnormality in neonatal brain ultrasonography and no previous neurological impairment, and to evaluate the relationship between retinal structure and brain changes in school-age children born SGA. Methods Two cohorts of children were recruited: 25 children born SGA and 25 children born with an appropriate birth weight according to gestational age. All the children underwent an ophthalmic examination, which included retinal imaging using spectral-domain optical coherence tomography, and a brain MRI. MRI images were automatically segmented and global and regional brain volumes were obtained. Results Although visual function did not differ between both groups, the complex ganglion cell and inner plexiform layers (GCL-IPL) was thinner in SGA children. Total intracranial volume, and global grey and white matter volumes in brain and cerebellum were correlated with birthweight centile, as were certain regional volumes (temporal and parietal lobes, hippocampus and putamen). Abnormal GCL-IPL measurements accurately identified SGA children with the most severe grey and white matter changes in the brain. Conclusions SGA children, both preterm and term born, showed evidence of structural abnormalities in the retina, which may be an accurate and non-invasive biomarker of neuronal damage in brain tissue.

espanolContextualizacion teorica/antecedentes. La practica de la meditacion ha demostrado mejorar la calidad de vida en relacion con el dolor padecido, asi como alterar la actividad cerebral. Se evalua la volumetria cerebral en pacientes de fibromialgia (FM), con grupos de control de meditadores y no-meditadores sanos, para dilucidar la posible asociacion entre los cambios cerebrales en meditadores y los anos de practica de la meditacion. Metodologia. La muestra se compone de doce pacientes diagnosticados con FM, once meditadores Zen consolidados y diez sujetos control sanos clasificados por edad y sexo. Los sujetos se exploraron con una secuencia de Resonancia Magnetica T1-3D de alta resolucion y las imagenes se analizaron mediante una estrategia de normalizacion DARTEL (Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra) de alta dimensionalidad. Se administraron cuestionarios sobre ansiedad, depresion y deterioro cognitivo. Resultados. Se observo un incremento estadisticamente significativo en el volumen de la sustancia gris en el area 20 de Brodmann (giro inferior temporal derecho e izquierdo) en los pacientes con fibromialgia y una disminucion significativa en el grupo de meditadores en comparacion con el grupo control. Por otra parte, se observo un incremento significativo del volumen de sustancia gris en pacientes con fibromialgia en comparacion con el grupo control y el grupo de meditadores en los giros temporales derechos (p=0.03, t=6.85) e izquierdos (p=0.04, t=6.31). El numero de meses de practica de la meditacion no correlaciono con cambios significativos en el volumen de sustancia gris en el grupo de meditadores. Conclusiones. La fibromialgia y la meditacion parecen estar asociadas de manera fiable con alteraciones anatomicas localizadas en el area 20 de Brodmann (giro inferior y temporal), estando a su vez estos cambios asociados con los niveles de ansiedad y depresion. Ademas, los analisis morfologicos exploratorios en los pacientes con fibromialgia y los meditadores, pueden revelar disminuciones estructurales relevantes en regiones cerebrales en los practicantes de meditacion. Los cambios morfologicos podrian suponer una mayor predisposicion al desarrollo de un estado de dolor cronico, mientras que tales disminuciones estructurales podrian indicar potenciales beneficios funcionales. EnglishBackground. The practice of meditation has been shown to improve pain-related quality of life and also to alter brain activity. To assess brain volumetry in fibromyalgia (FM) patients, healthy meditators and healthy non-meditator control groups, and to elucidate the possible association between brain changes in meditators and years of meditation practice. Methods. Twelve patients diagnosed with FM, eleven long-term Zen meditators and ten healthy control subjects closely matched for sex and age were recruited. A high resolution T1-3D sequence was acquired and a high-dimensional DARTEL normalization strategy was applied. Questionnaires on anxiety, depression and cognitive impairment were administered. Results. There was a statistically significant increase in grey matter volume in the Brodmann area 20 (right and left inferior temporal gyri) in patients with fibromyalgia and a significant decrease in the meditator group as compared to controls. On the other hand, there was a significant increase in grey matter volume in fibromyalgia patients as compared to controls and meditators, to the right temporal gyrus (p=0.03, t=6.85) and left temporal gyrus (p=0.04, t=6.31). The number of months of meditation did not correlate with significant grey matter volume changes in the meditator group. Conclusions. FM and meditation appears to be reliably associated with altered anatomical structure in the Brodmann area 20 (in both inferior temporal gyri), and these changes are associated with anxiety and depression levels. In addition, exploratory morphometric analyses for fibromyalgia patients and meditators may reveal relevant brain regions showing structural diminution in meditation practitioners. Morphologic changes might predispose toward vulnerability to develop a chronic pain state. Such structural diminutions could potentially indicate functional benefits.

The EUDAIMON study focuses on fibromyalgia syndrome (FMS), a prevalent chronic condition characterized by pain, fatigue, cognitive problems and distress. According to recent reviews and meta-analyses, Mindfulness-Based Stress Reduction (MBSR) is a promising therapeutic approach for patients with FMS. The measurement of biomarkers as part of the analysis of MBSR effects would help to identify the neurobiological underpinnings of MBSR and increase our knowledge of FMS pathophysiology. The main objectives of this 12-month RCT are: firstly, to examine the effectiveness and cost-utility for FMS patients of MBSR as an add-on to treatment as usual (TAU) versus TAU + the psychoeducational programme FibroQoL, and versus TAU only; secondly, to examine pre-post differences in brain structure and function, as well as levels of specific inflammatory markers in the three study arms and; thirdly, to analyse the role of some psychological variables as mediators of 12-month clinical outcomes.

OBJECTIVE:To assess the accuracy of magnetic resonance spectroscopy (1H-MRS) and brain volumetry in mild cognitive impairment (MCI) to predict conversion to probable Alzheimer's disease (AD).METHODS:Forty-eight patients fulfilling the criteria of amnestic MCI who underwent a conventional magnetic resonance imaging (MRI) followed by MRS, and T1-3D on 1.5 Tesla MR unit. At baseline the patients underwent neuropsychological examination. 1H-MRS of the brain was carried out by exploring the left medial occipital lobe and ventral posterior cingulated cortex (vPCC) using the LCModel software. A high resolution T1-3D sequence was acquired to carry out the volumetric measurement. A cortical and subcortical parcellation strategy was used to obtain the volumes of each area within the brain. The patients were followed up to detect conversion to probable AD.RESULTS:After a 3-year follow-up, 15 (31.2%) patients converted to AD. The myo-inositol in the occipital cortex and glutamate+glutamine (Glx) in the posterior cingulate cortex predicted conversion to probable AD at 46.1% sensitivity and 90.6% specificity. The positive predictive value was 66.7%, and the negative predictive value was 80.6%, with an overall cross-validated classification accuracy of 77.8%. The volume of the third ventricle, the total white matter and entorhinal cortex predict conversion to probable AD at 46.7% sensitivity and 90.9% specificity. The positive predictive value was 70%, and the negative predictive value was 78.9%, with an overall cross-validated classification accuracy of 77.1%. Combining volumetric measures in addition to the MRS measures the prediction to probable AD has a 38.5% sensitivity and 87.5% specificity, with a positive predictive value of 55.6%, a negative predictive value of 77.8% and an overall accuracy of 73.3%.CONCLUSION:Either MRS or brain volumetric measures are markers separately of cognitive decline and may serve as a noninvasive tool to monitor cognitive changes and progression to dementia in patients with amnestic MCI, but the results do not support the routine use in the clinical settings.

Purpose: The diagnosis of intracranial tuberculomas is often challenging. Our purpose is to describe the most common metabolic patterns of tuberculomas by MR spectroscopy (MRS) with emphasis on potential specific markers.Methods: Single-voxel MRS short echo time was performed in 13 cases of tuberculomas proven by histology and/or response to anti-mycobacterial therapy. For comparison MRS was also performed in 19 biopsy-proven malignant tumors (13 high-grade gliomas and six metastasis). Presence of metabolic peaks was assessed visually and categorical variables between groups were compared using chi-square. Metabolite ratios were compared using Mann-Whitney test and diagnostic accuracy of the metabolite ratios was compared using receiver-operating characteristic (ROC) curves analysis.Results: Spectroscopic peaks representing lipids and glutamate/glutamine (Glx) as well as a peak at similar to 3.8 ppm were well defined in 77% (10/13), 77% (10/13) and 69% (nine of 13) of tuberculomas, respectively. Lipid and Glx peaks were also present in most of the malignant lesions, 79% (15/19) and 74% (14/19) respectively. However, a peak at similar to 3.8 ppm was present in only similar to 0% (two of 19) of the tumor cases (p<0.001). Higher Cho/Cr and mI/Cr ratios helped discriminate malignant lesions with an area under the ROC curve of 0.86 (SE: 0.078, p<0.002, CI: 0.7-1) and 0.8 (SE: 0.1, p<0.009, CI: 0.6-1), respectively. Threshold values between 1.7-1.9 for Cho/Cr and 0.8-0.9 for mI/Cr provided high specificity (91% for both metabolites) and adequate sensitivity (75% and 80%, respectively) for discrimination of malignant lesions.Conclusion: A singlet peak at similar to 3.8 ppm is present in the majority of tuberculomas and absent in most malignant tumors, potentially a marker to differentiate these lesions. The assignment of the peak is difficult from our analysis; however, guanidinoacetate (Gua) is a possibility. Higher Cho/Cr and mI/Cr ratios should favor malignant lesions over tuberculomas. The presence of lipids and Glx is non-specific.

SummaryAimTo evaluate the efficacy of memantine on metabolite levels in different areas of the brain and to determine whether changes in metabolite levels correlate with clinical variables in Fibromyalgia (FM) patients.MethodsDoubled‐blind parallel randomized controlled trial. Twenty‐five patients diagnosed with FM were enrolled in the study. Patients were administered questionnaires on pain, anxiety, depression, quality of life, and cognitive impairment, and single‐voxel MRS of the brain was performed. All assessments were performed at baseline and after 6 months of treatment with memantine or placebo.ResultsPatients treated with memantine exhibited a significant increase in the glutamate (P = 0.010), glutamate/creatine ratio (P = 0.013), combined glutamate + glutamine (P = 0.016) and total N‐acetyl‐aspartate (NAA+NAAG) (P = 0.034) in the posterior cingulate cortex compared with those on placebo. Furthermore, the memantine group exhibited increases in creatine (P = 0.013) and choline (Cho) (P = 0.025) in the right posterior insula and also a correlation between choline and the Fibromyalgia Impact Questionnaire (FIQ) in the posterior insula (P = 0.050) was observed.ConclusionMemantine treatment resulted in an increase in cerebral metabolism in FM patients, suggesting its utility for the treatment of the illness.

Magnetic resonance spectroscopy (MRS) is widely available in major institutions for clinical practice and research. In this chapter, the use of MRS in neurodegenerative diseases such as Alzheimer's disease, Parkinson disease (disorders of the substantia nigra), psychiatric and vascular disorders, intracranial neoplasms, infections, demyelinating diseases, developmental disorders, and epilepsy are covered. The topics are based on the authors' experience and supported by comprehensive references.

Rationale and Objectives: The aim of the study was to analyze 1) whether the metabolite levels in the posterior cingulate cortex (PCC) are different in healthy individuals compared to a group of patients with cognitive impairment and/or pain and 2) whether there exists a correlation between brain metabolites and the age of a patient.Materials and Methods: Two hundred seven patients with cognitive impairment and/or pain (66 mild cognitive impairment, 54 fibromyalgia, 36 Alzheimer disease, 33 interictal migraine, 10 somatization disorder, and 8 after trigeminal neuralgia, and 193 healthy participants adjusted for gender and age. Proton magnetic resonance spectroscopy (MRS) of the brain was performed with the voxel placed in the ventral PCC and postprocessed with LCModel (Stephen Provencher, Oakville, Ontario, Canada).Results: Using linear regression and adjusting for gender and age, mean brain metabolite values for the pathological group, when compared-to healthy controls, were significantly lower in N-acetylaspartate (P = .003) and N-acetylaspartate/creatine (P = .015) and significantly greater in glutamate + glutamine (P < .001) and glutamate + glutamine/creatine (P < .000). All metabolites were significantly correlated with age: glutamate, glutamate + glutamine, N-acetylaspartate, and their creatine ratios exhibited a negative correlation, whereas myoinositol and choline exhibited a positive correlation.Conclusions: Although the number of patients is relatively small with heterogeneous state of disease, MRS in PCC may serve as a useful noninvasive tool for diagnostic of patients with cognitive impairment and pain.

To evaluate the efficacy of memantine on metabolite levels in different areas of the brain and to determine whether changes in metabolite levels correlate with clinical variables in Fibromyalgia (FM) patients. Doubled-blind parallel randomized controlled trial. Twenty-five patients diagnosed with FM were enrolled in the study. Patients were administered questionnaires on pain, anxiety, depression, quality of life, and cognitive impairment, and single-voxel MRS of the brain was performed. All assessments were performed at baseline and after 6 months of treatment with memantine or placebo. Patients treated with memantine exhibited a significant increase in the glutamate ( P  = 0.010), glutamate/creatine ratio ( P  = 0.013), combined glutamate + glutamine ( P  = 0.016) and total N -acetyl-aspartate (NAA+NAAG) ( P  = 0.034) in the posterior cingulate cortex compared with those on placebo. Furthermore, the memantine group exhibited increases in creatine ( P  = 0.013) and choline (Cho) ( P  = 0.025) in the right posterior insula and also a correlation between choline and the Fibromyalgia Impact Questionnaire (FIQ) in the posterior insula ( P  = 0.050) was observed. Memantine treatment resulted in an increase in cerebral metabolism in FM patients, suggesting its utility for the treatment of the illness.

INTRODUCTION:This work aimed to determine whether (1)H 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. (1)H-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 = -0.452; p = .045), NAA (r = -0.617; p = .003) and NAA/Cr (r = -0.448; 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 = -0.4850, 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.