Income is associated with hippocampal/amygdala and education with cingulate cortex grey matter volume.

Income and education are both elements of a person's socioeconomic status, which is predictive of a broad range of life outcomes. The brain's gray matter volume (GMV) is influenced by socioeconomic status and mediators related to an unhealthy life style. We here investigated two independent general population samples comprising 2838 participants (all investigated with the same MRI-scanner) with regard to the association of indicators of the socioeconomic status and gray matter volume. Voxel-based morphometry without prior hypotheses revealed that years of education were positively associated with GMV in the anterior cingulate cortex and net-equivalent income with gray matter volume in the hippocampus/amygdala region. Analyses of possible mediators (alcohol, cigarettes, body mass index (BMI), stress) revealed that the relationship between income and GMV in the hippocampus/amygdala region was partly mediated by self-reported stressors, and the association of years of education with GMV in the anterior cingulate cortex by BMI. These results corrected for whole brain effects (and therefore not restricted to certain brain areas) do now offer possibilities for more detailed hypotheses-driven approaches.

The influence of microsatellite polymorphisms in sex steroid receptor genes ESR1, ESR2 and AR on sex differences in brain structure.

The androgen receptor (AR), oestrogen receptor alpha (ESR1) and oestrogen receptor beta (ESR2) play essential roles in mediating the effect of sex hormones on sex differences in the brain. Using Voxel-based morphometry (VBM) and gene sizing in two independent samples (discovery n â€‹= â€‹173, replication â€‹= â€‹61), we determine the common and unique influences on brain sex differences in grey (GM) and white matter (WM) volume between repeat lengths (n) of microsatellite polymorphisms AR(CAG)n, ESR1(TA)n and ESR2(CA)n. In the hypothalamus, temporal lobes, anterior cingulate cortex, posterior insula and prefrontal cortex, we find increased GM volume with increasing AR(CAG)n across sexes, decreasing ESR1(TA)n across sexes and decreasing ESR2(CA)n in females. Uniquely, AR(CAG)n was positively associated with dorsolateral prefrontal and orbitofrontal GM volume and the anterior corona radiata, left superior fronto-occipital fasciculus, thalamus and internal capsule WM volume. ESR1(TA)n was negatively associated with the left superior corona radiata, left cingulum and left inferior longitudinal fasciculus WM volume uniquely. ESR2(CA)n was negatively associated with right fusiform and posterior cingulate cortex uniquely. We thus describe the neuroanatomical correlates of three microsatellite polymorphisms of steroid hormone receptors and their relationship to sex differences.

Brain connectivity markers for the identification of effective contacts in subthalamic nucleus deep brain stimulation.

The clinical benefit of deep brain stimulation (DBS) for Parkinson's disease (PD) is relevant to the tracts adjacent to the stimulation site, but it remains unclear what connectivity pattern is associated with effective DBS. The aim of this study was to identify clinically effective electrode contacts on the basis of brain connectivity markers derived from diffusion tensor tractography. We reviewed 77 PD patients who underwent bilateral subthalamic nucleus DBS surgery. The patients were assigned into the training (n = 58) and validation (n = 19) groups. According to the therapeutic window size, all contacts were classified into effective and ineffective groups. The whole-brain connectivity of each contact's volume of tissue activated was estimated using tractography with preoperative diffusion tensor data. Extracted connectivity features were put into an all-relevant feature selection procedure within cross-validation loops, to identify features with significant discriminative power for contact classification. A total of 616 contacts on 154 DBS leads were discriminated, with 388 and 228 contacts being classified as effective and ineffective ones, respectively. After the feature selection, the connectivity of contacts with the thalamus, pallidum, hippocampus, primary motor area, supplementary motor area and superior frontal gyrus was identified to significantly contribute to contact classification. Based on these relevant features, the random forest model constructed from the training group achieved an accuracy of 84.9% in the validation group, to discriminate effective contacts from the ineffective. Our findings advanced the understanding of the specific brain connectivity patterns associated with clinical effective electrode contacts, which potentially guided postoperative DBS programming.

A multi-contrast MRI approach to thalamus segmentation.

Thalamic alterations occur in many neurological disorders including Alzheimer's disease, Parkinson's disease and multiple sclerosis. Routine interventions to improve symptom severity in movement disorders, for example, often consist of surgery or deep brain stimulation to diencephalic nuclei. Therefore, accurate delineation of grey matter thalamic subregions is of the upmost clinical importance. MRI is highly appropriate for structural segmentation as it provides different views of the anatomy from a single scanning session. Though with several contrasts potentially available, it is also of increasing importance to develop new image segmentation techniques that can operate multi-spectrally. We hereby propose a new segmentation method for use with multi-modality data, which we evaluated for automated segmentation of major thalamic subnuclear groups using T1 -weighted, T2* -weighted and quantitative susceptibility mapping (QSM) information. The proposed method consists of four steps: Highly iterative image co-registration, manual segmentation on the average training-data template, supervised learning for pattern recognition, and a final convex optimisation step imposing further spatial constraints to refine the solution. This led to solutions in greater agreement with manual segmentation than the standard Morel atlas based approach. Furthermore, we show that the multi-contrast approach boosts segmentation performances. We then investigated whether prior knowledge using the training-template contours could further improve convex segmentation accuracy and robustness, which led to highly precise multi-contrast segmentations in single subjects. This approach can be extended to most 3D imaging data types and any region of interest discernible in single scans or multi-subject templates.

Laparoscopic sleeve gastrectomy induces sustained changes in gray and white matter brain volumes and resting functional connectivity in obese patients.

BACKGROUND: Obesity is associated with decreased brain gray- (GM) and white-matter (WM) volumes in regions. Laparoscopic sleeve gastrectomy (LSG) is an effective bariatric surgery associated with neuroplastic changes in patients with obesity at 1 month postLSG. OBJECTIVE: To investigate whether LSG can induce sustained neuroplastic recovery of brain structural abnormalities, and whether structural changes are accompanied by functional alterations. SETTING: University hospital, longitudinal study. METHODS: Structural magnetic resonance imaging and voxel-based morphometry analysis were employed to assess GM/WM volumes in 30 obese participants at preLSG and 1 and 3 months postLSG. One-way analysis of variance modeled time effects on GM/WM volumes, and then alterations in resting-state functional connectivity (RSFC) were assessed. RESULTS: Significant time effects on GM volumes were in caudate (F = 11.20), insula (INS; F = 10.11), posterior cingulate cortex (PCC; F = 13.32), and inferior frontal gyrus (F = 12.18), and on WM volumes in anterior cingulate cortex (F = 15.70), PCC (F = 15.56), and parahippocampus (F = 17.96, PFDR < .05). Post hoc tests showed significantly increased GM volumes in caudate (mean change ± SEM .018 ± .005 and P = .001, .031 ± .007 and P < .001), INS (.027 ± .008 and P = .003, .043 ± .009 and P < .001), and PCC (.008 ± .004 and P = .042, .026 ± .006 and P < .001), and increased WM volumes in anterior cingulate cortex (.029 ± .006 and P < .001, .041 ± .008 and P < .001), PCC (.017 ± .004 and P < .001, .032 ± .006 and P < .001), and parahippocampus (.031 ± .008 and P =.001, .075 ± .013 and P < .001) at 1 and 3 months postLSG compared with preLSG. Significant increases in GM volumes were in caudate (.013 ± .006 and P = .036), PCC (.019 ± .006 and P = .006), and inferior frontal gyrus (.019 ± .005 and P = .001), and in WM volumes in anterior cingulate cortex (.012 ± .005 and P = .028), PCC (.014 ± .006 and P = .017), and parahippocampus (.044 ± .014 and P = .003) at 3 relative to 1 month postLSG. GM volumes in INS and PCC showed a positive correlation at 1 (r = .57, P = .001) and 3 months postLSG (r = .55, P = .001). GM volume in INS and PCC were positively correlated with RSFC of INS-PCC (r = .40 and P = .03, r = .55 and P = .001) and PCC-INS (r = .37 and P = .046, r = .57 and P < .001) at 1 month postLSG. GM volume in INS was also positively correlated with RSFC of INS-PCC (r = .44, P = .014) and PCC-INS (r = .38, P = .037) at 3 months postLSG. CONCLUSION: LSG induces sustained structural brain changes, which might mediate long-term benefits of bariatric surgery in weight reduction. Associations between regional GM volume and RSFC suggest that LSG-induced structural changes contribute to RSFC changes.

Association of iron levels in hair with brain structures and functions in young adults.

BACKGROUND: Iron plays a critical role in normal brain functions and development, but it has also been known to have adverse neurological effects. METHODS: Here, we investigated the associations of iron levels in hair with regional gray matter volume (rGMV), regional cerebral blood flow (rCBF), fractional anisotropy (FA), mean diffusivity (MD), and cognitive differences in a study cohort of 590 healthy young adults. RESULTS: Our findings showed that high iron levels were associated with lower rGMV in areas including the hippocampus, lower rCBF in the anterior and posterior parts of the brain, greater FA in areas including the part of the splenium of the corpus callosum, lower MD in the overlapping area including the splenium of the corpus callosum, as well as greater MD in the left hippocampus and areas including the frontal lobe. CONCLUSION: These results are compatible with the notion that iron plays diverse roles in neural mechanisms in healthy young adults.

Morphological relationship between the superficial cortical and deep grey matter structures in adult human brains: a cadaveric study / Relación morfológica entre las estructuras superficiales de la sustancia gris cortical y profunda en los cerebros humanos adultos: un estudio en cadáveres

While various neurodegenerative diseases affect cortical mass differently, finding an optimal and accurate method for measuring the thickness and surface area of cerebral cortex remains a challenging problem due to highly convoluted surface of the cortex. We therefore investigated cortical thickness in a sample of cadaveric specimens at the Discipline of Clinical Anatomy, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, South Africa to provide some clue as to possible variations in the parameters. Following ethical approval, 60 brain samples were uniformly sectioned (5 mm thickness) and eight slices taken from each brain across regions of interest (ROI) prepared and stained by Mulligan's technique. Thickness was measured at selected angles (0º, 45º, 90º, 135º and 180º) for both right and left cerebral hemispheres. Mulligan's stain produced good cortical differentiation and clear images that enabled manual delineation of structures. Cortical thickness ranged from 3 to 5 millimeters across the ROI. Interestingly, there was rightward hemispheric asymmetry of cortical thickness of selective slices at suggested angles which is related to structurally and functionally important brain regions. Moreover, there was no significant correlation between the surface area of superficial cortex and the deep nuclei at the same level. The superficial cortex and deep nuclei are manifested independently in normal aging, neuropsychiatric or developmental disorders. Providing accurate morphometric evaluation of cortical thickness and area based on gross staining of the brain slices could provide qualitative data that may support the study of human cerebral cortex even in disease conditions.

Si bien varias enfermedades neurodegenerativas afectan a la masa cortical de manera diferente, encontrar un método óptimo y preciso para medir el grosor y el área de la superficie de la corteza cerebral sigue siendo un problema difícil debido a la superficie altamente enrevesada de la corteza. Por lo tanto, investigamos el grosor cortical en una muestra de cadáveres del Departamento de Anatomía Clínica de la Facultad de Medicina Nelson R. Mandela de la Universidad de KwaZulu-Natal, Sudáfrica, para proporcionar alguna pista sobre posibles variaciones en dichos parámetros. Después de la aprobación ética, 60 muestras de cerebro se seccionaron uniformemente (5 mm de grosor) y se tomaron ocho cortes de cada cerebro en regiones de interés (ROI) preparadas y teñidas con la técnica de Mulligan. El espesor se midió en los ángulos seleccionados (0º, 45º, 90º, 135º y 180º) para los hemisferios cerebrales derecho e izquierdo. La tinción de Mulligan produjo una buena diferenciación cortical e imágenes claras que permitieron la delineación manual de las estructuras. El grosor cortical osciló entre 3 y 5 milímetros a través del ROI. Curiosamente, hubo una asimetría hemisférica hacia la derecha del grosor cortical de los cortes en ángulos sugeridos que se relacionan con regiones cerebrales estructural y funcionalmente importantes. Además, no hubo una correlación significativa entre el área de la superficial de la corteza superficial y los núcleos profundos en el mismo nivel. La corteza superficial y los núcleos profundos se manifiestan de manera independiente en el envejecimiento normal, en los trastornos neuropsiquiátricos o del desarrollo. Realizar una evaluación morfométrica precisa del grosorcortical y el área basada en la tinción macroscópica de los cortes del cerebro, podría proporcionar datos cualitativos que puedan respaldar el estudio de la corteza cerebral humana incluso en condiciones de enfermedad.

Optimal referencing for stereo-electroencephalographic (SEEG) recordings.

Stereo-electroencephalography (SEEG) is an intracranial recording technique in which depth electrodes are inserted in the brain as part of presurgical assessments for invasive brain surgery. SEEG recordings can tap into neural signals across the entire brain and thereby sample both cortical and subcortical sites. However, even though signal referencing is important for proper assessment of SEEG signals, no previous study has comprehensively evaluated the optimal referencing method for SEEG. In our study, we recorded SEEG data from 15 human subjects during a motor task, referencing them against the average of two white matter contacts (monopolar reference). We then subjected these signals to 5 different re-referencing approaches: common average reference (CAR), gray-white matter reference (GWR), electrode shaft reference (ESR), bipolar reference, and Laplacian reference. The results from three different signal quality metrics suggest the use of the Laplacian re-reference for study of local population-level activity and low-frequency oscillatory activity.

Cortical networks of the mouse brain elaborate within the gray matter.

In primates, proximal cortical areas are interconnected via within-cortex "intrinsic" pathway, whereas distant areas are connected via "extrinsic" white matter pathway. To date, such distinction has not been clearly done for small-brained mammals like rodents. In this study, we systematically analyzed the data of Allen Mouse Brain Connectivity Atlas to answer this question and found that the ipsilateral cortical connections in mice are almost exclusively contained within the gray matter, although we observed exceptions for projections from the retrosplenial area and the medial/orbital frontal areas. By analyzing axonal projections within the gray matter using Cortical Box method, which enabled us to investigate the layer patterns across different cortical areas, we obtained the following results. First, widespread axonal projections were observed in both upper and lower layers in the vicinity of injections, whereas highly specific "point-to-point" projections were observed toward remote areas. Second, such long-range projections were predominantly aligned in the anteromedial-posterolateral direction. Third, in the majority of these projections, the connecting axons traveled through layer 6. Finally, the projections from the primary and higher order areas to distant targets preferentially terminated in the middle and superficial layers, respectively, suggesting hierarchical connections similar to those of primates. Overall, our study demonstrated conspicuous differences in gray/white matter segregation of axonal projections between rodents and primates, despite certain similarities in the hierarchical cortical organization.

Neural encoding and production of functional morphemes in the posterior temporal lobe.

Morphemes are the smallest meaning-carrying units in human language, and are among the most basic building blocks through which humans express specific ideas and concepts. By using time-resolved cortical stimulations, neural recordings, and focal lesion evaluations, we show that inhibition of a small cortical area within the left dominant posterior-superior temporal lobe selectively impairs the ability to produce appropriate functional morphemes but does not distinctly affect semantic and lexical retrieval, comprehension, or articulation. Additionally, neural recordings within this area reveal the localized encoding of morphological properties and their planned production prior to speech onset. Finally, small lesions localized to the gray matter in this area result in a selective functional morpheme-production deficit. Collectively, these findings reveal a detailed division of linguistic labor within the posterior-superior temporal lobe and suggest that functional morpheme processing constitutes an operationally discrete step in the series of computations essential to language production.

Widespread associations between trait conscientiousness and thickness of brain cortical regions.

The neural correlates of human personality have been of longstanding interest; however, most studies in the field have relied on modest sample sizes and few replicable results have been reported to date. We investigated relationships between personality and brain gray matter in a sample of generally healthy, older (mean age 73 years) adults from Scotland drawn from the Lothian Birth Cohort 1936. Participants (N = 578) completed a brain MRI scan and self-reported Big Five personality trait measures. Conscientiousness trait scores were positively related to brain cortical thickness in a range of regions, including bilateral parahippocampal gyrus, bilateral fusiform gyrus, left cingulate gyrus, right medial orbitofrontal cortex, and left dorsomedial prefrontal cortex. These associations - most notably in frontal regions - were modestly-to-moderately attenuated by the inclusion of biomarker variables assessing allostatic load and smoking status. None of the other personality traits showed robust associations with brain cortical thickness, nor did we observe any personality trait associations with cortical surface area and gray matter volume. These findings indicate that brain cortical thickness is associated with conscientiousness, perhaps partly accounted for by allostatic load and smoking status.

Catlas: An magnetic resonance imaging-based three-dimensional cortical atlas and tissue probability maps for the domestic cat (Felis catus).

Brain atlases play an important role in effectively communicating results from neuroimaging studies in a standardized coordinate system. Furthermore, brain atlases extend analysis of functional magnetic resonance imaging (MRI) data by delineating regions of interest over which to evaluate the extent of functional activation as well as measures of inter-regional connectivity. Here, we introduce a three-dimensional atlas of the cat cerebral cortex based on established cytoarchitectonic and electrophysiological findings. In total, 71 cerebral areas were mapped onto the gray matter (GM) of an averaged T1-weighted structural MRI acquired at 7 T from eight adult domestic cats. In addition, a nonlinear registration procedure was used to generate a common template brain as well as GM, white matter, and cerebral spinal fluid tissue probability maps to facilitate tissue segmentation as part of the standard preprocessing pipeline for MRI data analysis. The atlas and associated files can also be used for planning stereotaxic surgery and for didactic purposes.

In vivo microscopic voxel-based morphometry with a brain template to characterize strain-specific structures in the mouse brain.

Hundreds of inbred mouse strains are established for use in a broad spectrum of basic research fields, including genetics, neuroscience, immunology, and cancer. Inbred mice exhibit identical intra-strain genetics and divergent inter-strain phenotypes. The cognitive and behavioral divergences must be controlled by the variances of structure and function of their brains; however, the underlying morphological features of strain-to-strain difference remain obscure. Here, in vivo microscopic magnetic resonance imaging was optimized to image the mouse brains by using an isotropic resolution of 80 µm. Next, in vivo templates were created from the data from four major inbred mouse strains (C57Bl/6, BALB/cBy, C3H/He, and DBA/2). A strain-mixed brain template was also created, and the template was then employed to establish automatic voxel-based morphometry (VBM) for the mouse brain. The VBM assessment revealed strain-specific brain morphologies concerning the gray matter volume of the four strains, with a smaller volume in the primary visual cortex for the C3H/He strain, and a smaller volume in the primary auditory cortex and field CA1 of the hippocampus for the DBA/2 strain. These findings would contribute to the basis of for understanding morphological phenotype of the inbred mouse strain and may indicate a relationship between brain morphology and strain-specific cognition and behavior.

Differential age-related gray and white matter impact mediates educational influence on elders' cognition.

High education, as a proxy of cognitive reserve (CR), has been associated with cognitive advantage amongst old adults and may operate through neuroprotective and/or compensation mechanisms. In neuromaging studies, indirect evidences of neuroprotection can be inferred from positive relationships between CR and brain integrity measures. In contrast, compensation allows high CR elders to sustain greater brain damage. We included 100 cognitively normal old-adults and investigated the associations and interactions between education, speed of processing (SP), memory and two brain integrity measures: cortical thickness (CTh) of gray matter (GM) and fractional anisotropy (FA) in the white matter (WM). High education was associated with better cognitive performance, enlarged CTh in frontal lobe areas and reduced measures of FA in several areas. Better SP performance in higher educated subjects was related to more preserved GM and WM, while memory status amongst high educated elders was better explained by a putative compensatory mechanism and independently from cerebrovascular risk indicators. Moreover, we analyzed the direct effect of age on measures of brain integrity and found a stronger negative effect on WM than in CTh, which was accentuated amongst the high CR sample. Our study suggests that the cognitive advantage associated to high education among healthy aging is related to the coexistence of both neuroprotective and compensatory mechanisms. In particular, high educated elders seem to have greater capacity to counteract a more abrupt age impact on WM integrity.

APOL1 renal-risk variants associate with reduced cerebral white matter lesion volume and increased gray matter volume.

To assess apolipoprotein L1 gene (APOL1) renal-risk-variant effects on the brain, magnetic resonance imaging (MRI)-based cerebral volumes and cognitive function were assessed in 517 African American-Diabetes Heart Study (AA-DHS) Memory IN Diabetes (MIND) and 2568 hypertensive African American Systolic Blood Pressure Intervention Trial (SPRINT) participants without diabetes. Within these cohorts, 483 and 197 had cerebral MRI, respectively. AA-DHS participants were characterized as follows: 60.9% female, mean age of 58.6 years, diabetes duration 13.1 years, estimated glomerular filtration rate of 88.2 ml/min/1.73 m(2), and a median spot urine albumin to creatinine ratio of 10.0 mg/g. In additive genetic models adjusting for age, sex, ancestry, scanner, intracranial volume, body mass index, hemoglobin A1c, statins, nephropathy, smoking, hypertension, and cardiovascular disease, APOL1 renal-risk-variants were positively associated with gray matter volume (ß = 3.4 × 10(-3)) and negatively associated with white matter lesion volume (ß = -0.303) (an indicator of cerebral small vessel disease) and cerebrospinal fluid volume (ß= -30707) (all significant), but not with white matter volume or cognitive function. Significant associations corresponding to adjusted effect sizes (ß/SE) were observed with gray matter volume (0.16) and white matter lesion volume (-0.208), but not with cerebrospinal fluid volume (-0.251). Meta-analysis results with SPRINT Memory and Cognition in Decreased Hypertension (MIND) participants who had cerebral MRI were confirmatory. Thus, APOL1 renal-risk-variants are associated with larger gray matter volume and lower white matter lesion volume suggesting lower intracranial small vessel disease.

Reproducibility of hormone-driven regional grey matter volume changes in women using SPM8 and SPM12.

Aim of this work was to evaluate the reproducibility of hormone driven regional grey matter volume differences in women, and their correlations with premenstrual symptoms, as determined by voxel-based morphometry (VBM). After data quality control, a total of 138 T1-weighted MR images were included in this longitudinal study, and were analyzed as three different subgroups. Women with a natural menstrual cycle were scanned at three time-points: follicular, ovulatory and luteal phase. Two groups of women, using androgenic and anti-androgenic hormonal contraceptives, respectively, were scanned twice: during the pill-free week and during pill intake. Additionally, subjects were asked to complete a "daily rating of severity of problems" questionnaire, to quantify premenstrual symptoms. All data were analyzed using SPM8 and SPM12 with identical parameter settings. In the natural menstrual cycle group, the regional grey matter volume of the insula is larger at ovulation, as compared to the luteal phase. Premenstrual symptoms correlate differently with regional grey matter volumes between women with a natural cycle and hormonal contraceptive users. Changes in hormonal environment can to various extents affect VBM findings in women. We suggest that researchers take these confounding factors into account while applying this technique, to avoid heterogeneity in data acquisition and to safeguard the sensitivity of findings. Additionally, we suggest validating the consistency of results using more than one software package.

Neurocognition across the spectrum of mucopolysaccharidosis type I: Age, severity, and treatment.

OBJECTIVES: Precise characterization of cognitive outcomes and factors that contribute to cognitive variability will enable better understanding of disease progression and treatment effects in mucopolysaccharidosis type I (MPS I). We examined the effects on cognition of phenotype, genotype, age at evaluation and first treatment, and somatic disease burden. METHODS: Sixty patients with severe MPS IH (Hurler syndrome treated with hematopoietic cell transplant and 29 with attenuated MPS I treated with enzyme replacement therapy), were studied with IQ measures, medical history, genotypes. Sixty-seven patients had volumetric MRI. Subjects were grouped by age and phenotype and MRI and compared to 96 normal controls. RESULTS: Prior to hematopoietic cell transplant, MPS IH patients were all cognitively average, but post-transplant, 59% were below average, but stable. Genotype and age at HCT were associated with cognitive ability. In attenuated MPS I, 40% were below average with genotype and somatic disease burden predicting their cognitive ability. White matter volumes were associated with IQ for controls, but not for MPS I. Gray matter volumes were positively associated with IQ in controls and attenuated MPS I patients, but negatively associated in MPS IH. CONCLUSIONS: Cognitive impairment, a major difficulty for many MPS I patients, is associated with genotype, age at treatment and somatic disease burden. IQ association with white matter differed from controls. Many attenuated MPS patients have significant physical and/or cognitive problems and receive insufficient support services. Results provide direction for future clinical trials and better disease management.

Hippocampal volume and functional connectivity changes during the female menstrual cycle.

Hippocampal volume has been shown to be sensitive to variations in estrogen and progesterone levels across rodents' estrous cycle. However, little is known about the covariation of hormone levels and brain structure in the course of the human menstrual cycle. Here, we examine this covariation with a multi-method approach that includes several brain imaging methods and hormonal assessments. We acquired structural and functional scans from 21 naturally cycling women on four time points during their cycles (early follicular phase, late follicular phase, ovulation and luteal phase). Hormone blood concentrations and cognitive performance in different domains were assessed on each of the measurement occasions. Structural MRI images were processed by means of whole-brain voxel-based morphometry and FreeSurfer. With either method, bilateral increases in hippocampal volume were found in the late follicular phase relative to the early follicular phase. The gray matter probability in regions of hippocampal volume increase was associated with lower mean diffusivity in the same region. In addition, we observed higher functional connectivity between the hippocampi and the bilateral superior parietal lobe in the late follicular phase. We did not find any reliable cycle-related performance variations on the cognitive tasks. The present results show that hormonal fluctuations covary with hippocampal structure and function in the course of the human menstrual cycle.

Quantification of microscopic diffusion anisotropy disentangles effects of orientation dispersion from microstructure: applications in healthy volunteers and in brain tumors.

The anisotropy of water diffusion in brain tissue is affected by both disease and development. This change can be detected using diffusion MRI and is often quantified by the fractional anisotropy (FA) derived from diffusion tensor imaging (DTI). Although FA is sensitive to anisotropic cell structures, such as axons, it is also sensitive to their orientation dispersion. This is a major limitation to the use of FA as a biomarker for "tissue integrity", especially in regions of complex microarchitecture. In this work, we seek to circumvent this limitation by disentangling the effects of microscopic diffusion anisotropy from the orientation dispersion. The microscopic fractional anisotropy (µFA) and the order parameter (OP) were calculated from the contrast between signal prepared with directional and isotropic diffusion encoding, where the latter was achieved by magic angle spinning of the q-vector (qMAS). These parameters were quantified in healthy volunteers and in two patients; one patient with meningioma and one with glioblastoma. Finally, we used simulations to elucidate the relation between FA and µFA in various micro-architectures. Generally, µFA was high in the white matter and low in the gray matter. In the white matter, the largest differences between µFA and FA were found in crossing white matter and in interfaces between large white matter tracts, where µFA was high while FA was low. Both tumor types exhibited a low FA, in contrast to the µFA which was high in the meningioma and low in the glioblastoma, indicating that the meningioma contained disordered anisotropic structures, while the glioblastoma did not. This interpretation was confirmed by histological examination. We conclude that FA from DTI reflects both the amount of diffusion anisotropy and orientation dispersion. We suggest that the µFA and OP may complement FA by independently quantifying the microscopic anisotropy and the level of orientation coherence.

Serial longitudinal magnetic resonance imaging data indicate non-linear regional gray matter volume recovery in abstinent alcohol-dependent individuals.

The trajectory of regional volume changes during the first year of sustained abstinence in those recovering from an alcohol use disorder is unclear because previous research typically employed only two assessment points. To better understand the trajectory of regional brain volume recovery in treatment-seeking alcohol-dependent individuals (ALC), regional brain volumes were measured after 1 week, 1 month and 7.5 months of sustained abstinence via magnetic resonance imaging at 1.5 T. ALC showed significant volume increases in frontal, parietal and occipital gray matter (GM) and white matter (WM), total cortical GM and total lobar WM, thalamus and cerebellum, and decreased ventricular volume over 7.5 months of abstinence. Volume increases in regional GM were significantly greater over 1 week to 1 month than from 1 month to 7.5 months of abstinence, indicating a non-linear rate of change in regional GM over 7.5 months. Overall, regional lobar WM showed linear volume increases over 7.5 months. With increasing age, smoking ALC showed lower frontal and total cortical GM volume recovery than non-smoking ALC. Despite significant volume increases, ALC showed smaller GM volumes in all regions, except the frontal cortex, than controls after 7.5 months of abstinence. ALC and controls showed no regional WM volume differences at any assessment point. In non-smoking ALC only, increasing regional GM and WM volumes were related to improving processing speed. Findings may indicate a differential rate of recovery of cell types/cellular components contributing to GM and WM volume during early abstinence, and that GM volume deficits persist after 7.5 months of sustained sobriety in this ALC cohort.