Forever young(er): potential age-defying effects of long-term meditation on gray matter atrophy

While overall life expectancy has been increasing, the human brain still begins deteriorating after the first two decades of life and continues degrading further with increasing age. Thus, techniques that diminish the negative impact of aging on the brain are desirable. Existing research, although scarce, suggests meditation to be an attractive candidate in the quest for an accessible and inexpensive, efficacious remedy. Here, we examined the link between age and cerebral gray matter re-analyzing a large sample (n = 100) of long-term meditators and control subjects aged between 24 and 77 years. When correlating global and local gray matter with age, we detected negative correlations within both controls and meditators, suggesting a decline over time. However, the slopes of the regression lines were steeper and the correlation coefficients were stronger in controls than in meditators. Moreover, the age-affected brain regions were much more extended in controls than in meditators, with significant group-by-age interactions in numerous clusters throughout the brain. Altogether, these findings seem to suggest less age-related gray matter atrophy in long-term meditation practitioners.Nicolas Cherbuin is funded by Australian Research Council fellowship number 120100227

The impact of aging on subregions of the hippocampal complex in healthy adults

The hippocampal complex, an anatomical composite of several subregions, is known to decrease in size with increasing age. However, studies investigating which subregions are particularly prone to age-related tissue loss revealed conflicting findings. Possible reasons for such inconsistencies may reflect differences between studies in terms of the cohorts examined or techniques applied to define and measure hippocampal subregions. In the present study, we enhanced conventional MR-based information with microscopically defined cytoarchitectonic probabilities to investigate aging effects on the hippocampal complex in a carefully selected sample of 96 healthy subjects (48 males/48 females) aged 18-69 years. We observed significant negative correlations between age and volumes of the cornu ammonis, fascia dentata, subiculum, and hippocampal-amygdaloid transition area, but not the entorhinal cortex. The estimated age-related annual atrophy rates were most pronounced in the left and right subiculum with -0.23% and -0.22%, respectively. These findings suggest age-related atrophy of the hippocampal complex overall, but with differential effects in its subregions. If confirmed in future studies, such region-specific information may prove useful for the assessment of diseases and disorders known to modulate age-related hippocampal volume loss.NC is funded by Australian Research Council Future fellowship number 120100227. EL is funded by the Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health under award number R01HD081720 and further supported by the Cousins Center for Psychoneuroimmunology at the University of California, Los Angeles (UCLA)

Meditation effects within the hippocampal complex revealed by voxel-based morphometry and cytoarchitectonic probabilistic mapping.

Scientific studies addressing anatomical variations in meditators' brains have emerged rapidly over the last few years, where significant links are most frequently reported with respect to gray matter (GM). To advance prior work, this study examined GM characteristics in a large sample of 100 subjects (50 meditators, 50 controls), where meditators have been practicing close to 20 years, on average. A standard, whole-brain voxel-based morphometry approach was applied and revealed significant meditation effects in the vicinity of the hippocampus, showing more GM in meditators than in controls as well as positive correlations with the number of years practiced. However, the hippocampal complex is regionally segregated by architecture, connectivity, and functional relevance. Thus, to establish differential effects within the hippocampal formation (cornu ammonis, fascia dentata, entorhinal cortex, subiculum) as well as the hippocampal-amygdaloid transition area, we utilized refined cytoarchitectonic probabilistic maps of (peri-) hippocampal subsections. Significant meditation effects were observed within the subiculum specifically. Since the subiculum is known to play a key role in stress regulation and meditation is an established form of stress reduction, these GM findings may reflect neuronal preservation in long-term meditators-perhaps due to an attenuated release of stress hormones and decreased neurotoxicity

The Unique Brain Anatomy of Meditation Practitioners: Alterations in Cortical Gyrification

Several cortical regions are reported to vary in meditation practitioners. However, prior analyses have focused primarily on examining gray matter or cortical thickness. Thus, additional effects with respect to other cortical features might have remained undetected. Gyrification (the pattern and degree of cortical folding) is an important cerebral characteristic related to the geometry of the brain’s surface. Thus, exploring cortical gyrification in long-term meditators may provide additional clues with respect to the underlying anatomical correlates of meditation. This study examined cortical gyrification in a large sample (n = 100) of meditators and controls, carefully matched for sex and age. Cortical gyrification was established by calculating mean curvature across thousands of vertices on individual cortical surface models. Pronounced group differences indicating larger gyrification in meditators were evident within the left precentral gyrus, right fusiform gyrus, right cuneus, as well as left and right anterior dorsal insula (the latter representing the global significance maximum). Positive correlations between gyrification and the number of meditation years were similarly pronounced in the right anterior dorsal insula. Although the exact functional implications of larger cortical gyrification remain to be established, these findings suggest the insula to be a key structure involved in aspects of meditation. For example, variations in insular complexity could affect the regulation of well-known distractions in the process of meditation, such as daydreaming, mind-wandering, and projections into past or future. Moreover, given that meditators are masters in introspection, awareness, and emotional control, increased insular gyrification may reflect an integration of autonomic, affective, and cognitive processes. Due to the cross-sectional nature of this study, further research is necessary to determine the relative contribution of nature and nurture to links between cortical gyrification and meditation

Associations between corpus callosum size and ADHD symptoms in older adults: The PATH through life study

Neuroimaging studies of attention-deficit/hyperactivity disorder (ADHD) have revealed deviations of the corpus callosum in children and adolescents. However, little is known about the link between callosal morphology and symptoms of inattention or hyperactivity in adulthood, especially later in life. Here, we investigated in a large population-based sample of 280 adults (150 males, 130 females) in their late sixties and early seventies whether ADHD symptoms correlate with callosal thickness. In addition, we tested for significant sex interactions, which were followed by correlation analyses stratified by sex. Within males, there were significant negative correlations with respect to inattention and hyperactivity in various callosal regions, including the anterior third, anterior and posterior midbody, isthmus, and splenium. A thinner corpus callosum may be associated with fewer fibers or less myelination of fibers. Thus, the observed negative correlations suggest impaired inter-hemispheric communication channels necessary to sustain motor control and attention, which may contribute to symptoms of hyperactivity, impulsivity and/or inattention. Interestingly, within females, callosal thickness was positively related to hyperactivity in a small area within the rostral body, suggesting a sexually dimorphic neurobiology of ADHD symptoms. Altogether, the present results may reflect a lasting relationship between callosal morphology and ADHD symptoms throughout life.The study was supported by NHMRC Grants 973302, 179805, 157125, 1063907 and ARC Grant 130101705. Nicolas Cherbuin is funded by ARC research fellowship 12010022, Kaarin Anstey by NHMRC research fellowships 1002560, and Debjani Das by NHMRC research fellowship 410215. This research was partly undertaken on the National Computational Infrastructure (NCI) facility in Canberra, Australia, which is supported by the Australian Commonwealth Government

Gender Differences in White Matter Microstructure

Sexual dimorphism in human brain structure is well recognised, but little is known about gender differences in white matter microstructure. We used diffusion tensor imaging to explore differences in fractional anisotropy (FA), an index of microstructural integrity.A whole brain analysis of 135 matched subjects (90 men and 45 women) using a 1.5 T scanner. A region of interest (ROI) analysis was used to confirm those results where proximity to CSF raised the possibility of partial-volume artefact.Men had higher fractional anisotropy (FA) in cerebellar white matter and in the left superior longitudinal fasciculus; women had higher FA in the corpus callosum, confirmed by ROI.The size of the differences was substantial--of the same order as that attributed to some pathology--suggesting gender may be a potentially significant confound in unbalanced clinical studies. There are several previous reports of difference in the corpus callosum, though they disagree on the direction of difference; our findings in the cerebellum and the superior longitudinal fasciculus have not previously been noted. The higher FA in women may reflect greater efficiency of a smaller corpus callosum. The relatively increased superior longitudinal fasciculus and cerebellar FA in men may reflect their increased language lateralisation and enhanced motor development, respectively

The Role of γ-Tubulin in Centrosomal Microtubule Organization

As part of a multi-subunit ring complex, γ-tubulin has been shown to promote microtubule nucleation both in vitro and in vivo, and the structural properties of the complex suggest that it also seals the minus ends of the polymers with a conical cap. Cells depleted of γ-tubulin, however, still display many microtubules that participate in mitotic spindle assembly, suggesting that γ-tubulin is not absolutely required for microtubule nucleation in vivo, and raising questions about the function of the minus end cap. Here, we assessed the role of γ-tubulin in centrosomal microtubule organisation using three-dimensional reconstructions of γ-tubulin-depleted C. elegans embryos. We found that microtubule minus-end capping and the PCM component SPD-5 are both essential for the proper placement of microtubules in the centrosome. Our results further suggest that γ-tubulin and SPD-5 limit microtubule polymerization within the centrosome core, and we propose a model for how abnormal microtubule organization at the centrosome could indirectly affect centriole structure and daughter centriole replication

Large-scale analysis of structural brain asymmetries in schizophrenia via the ENIGMA consortium

Left-right asymmetry is an important organizing feature of the healthy brain that may be altered in schizophrenia, but most studies have used relatively small samples and heterogeneous approaches, resulting in equivocal findings. We carried out the largest case-control study of structural brain asymmetries in schizophrenia, using MRI data from 5,080 affected individuals and 6,015 controls across 46 datasets in the ENIGMA consortium, using a single image analysis protocol. Asymmetry indexes were calculated for global and regional cortical thickness, surface area, and subcortical volume measures. Differences of asymmetry were calculated between affected individuals and controls per dataset, and effect sizes were meta-analyzed across datasets. Small average case-control differences were observed for thickness asymmetries of the rostral anterior cingulate and the middle temporal gyrus, both driven by thinner left-hemispheric cortices in schizophrenia. Analyses of these asymmetries with respect to the use of antipsychotic medication and other clinical variables did not show any significant associations. Assessment of age- and sex-specific effects revealed a stronger average leftward asymmetry of pallidum volume between older cases and controls. Case-control differences in a multivariate context were assessed in a subset of the data (N = 2,029), which revealed that 7% of the variance across all structural asymmetries was explained by case-control status. Subtle case-control differences of brain macro-structural asymmetry may reflect differences at the molecular, cytoarchitectonic or circuit levels that have functional relevance for the disorder. Reduced left middle temporal cortical thickness is consistent with altered left-hemisphere language network organization in schizophrenia

ENIGMA and global neuroscience: A decade of large-scale studies of the brain in health and disease across more than 40 countries

This review summarizes the last decade of work by the ENIGMA (Enhancing NeuroImaging Genetics through Meta Analysis) Consortium, a global alliance of over 1400 scientists across 43 countries, studying the human brain in health and disease. Building on large-scale genetic studies that discovered the first robustly replicated genetic loci associated with brain metrics, ENIGMA has diversified into over 50 working groups (WGs), pooling worldwide data and expertise to answer fundamental questions in neuroscience, psychiatry, neurology, and genetics. Most ENIGMA WGs focus on specific psychiatric and neurological conditions, other WGs study normal variation due to sex and gender differences, or development and aging; still other WGs develop methodological pipelines and tools to facilitate harmonized analyses of "big data" (i.e., genetic and epigenetic data, multimodal MRI, and electroencephalography data). These international efforts have yielded the largest neuroimaging studies to date in schizophrenia, bipolar disorder, major depressive disorder, post-traumatic stress disorder, substance use disorders, obsessive-compulsive disorder, attention-deficit/hyperactivity disorder, autism spectrum disorders, epilepsy, and 22q11.2 deletion syndrome. More recent ENIGMA WGs have formed to study anxiety disorders, suicidal thoughts and behavior, sleep and insomnia, eating disorders, irritability, brain injury, antisocial personality and conduct disorder, and dissociative identity disorder. Here, we summarize the first decade of ENIGMA's activities and ongoing projects, and describe the successes and challenges encountered along the way. We highlight the advantages of collaborative large-scale coordinated data analyses for testing reproducibility and robustness of findings, offering the opportunity to identify brain systems involved in clinical syndromes across diverse samples and associated genetic, environmental, demographic, cognitive, and psychosocial factors

Promising Links between Meditation and Reduced (Brain) Aging: An Attempt to Bridge Some Gaps between the Alleged Fountain of Youth and the Youth of the Field

Over the last decade, an increasing number of studies has reported a positive impact of meditation on cerebral aging. However, the underlying mechanisms for these seemingly brain-protecting effects are not well-understood. This may be due to the fact, at least partly, that systematic empirical meditation research has emerged only recently as a field of scientific scrutiny. Thus, on the one hand, critical questions remain largely unanswered; and on the other hand, outcomes of existing research require better integration to build a more comprehensive and holistic picture. In this article, we first review theories and mechanisms pertaining to normal (brain) aging, specifically focusing on telomeres, inflammation, stress regulation, and macroscopic brain anatomy. Then, we summarize existing research integrating the developing evidence suggesting that meditation exerts positive effects on (brain) aging, while carefully discussing possible mechanisms through which these effects may be mediated