Cortical gyrification in relation to age and cognition in older adults

Gyrification of the cerebral cortex changes with aging and relates to development of cognitive function during early life and midlife. Little is known about how gyrification relates to age and cognitive function later in life. We investigated this in 4397 individuals (mean age: 63.5 years, range: 45.7 to 97.9) from the Rotterdam Study, a population-based cohort. Global and local gyrification were assessed from T1-weighted images. A measure for global cognition, the g-factor, was calculated from five cognitive tests. Older age was associated with lower gyrification (mean difference per year ​= ​−0.0021; 95% confidence interval ​= ​−0.0025; −0.0017). Non-linear terms did not improve the models. Age related to lower gyrification in the parietal, frontal, temporal and occipital regions, and higher gyrification in the medial prefrontal cortex. Higher levels of the g-factor were associated with higher global gyrification (mean difference per g-factor unit ​= ​0.0044; 95% confidence interval ​= ​0.0015; 0.0073). Age and the g-factor did not interact in relation to gyrification (p ​> ​0.05). The g-factor bilaterally associated with gyrification in three distinct clusters. The first cluster encompassed the superior temporal gyrus, the insular cortex and the postcentral gyrus, the second cluster the lingual gyrus and the precuneus, and the third cluster the orbitofrontal cortex. These clusters largely remained statistically significant after correction for cortical surface area. Overall, the results support the notion that gyrification varies with aging and cognition during and after midlife, and suggest that gyrification is a potential marker for age-related brain and co

Anomalous morphology in left hemisphere motor and premotor cortex of children who stutter

Stuttering is a neurodevelopmental disorder that affects the smooth flow of speech production. Stuttering onset occurs during a dynamic period of development when children first start learning to formulate sentences. Although most children grow out of stuttering naturally, ∼1% of all children develop persistent stuttering that can lead to significant psychosocial consequences throughout one’s life. To date, few studies have examined neural bases of stuttering in children who stutter, and even fewer have examined the basis for natural recovery versus persistence of stuttering. Here we report the first study to conduct surface-based analysis of the brain morphometric measures in children who stutter. We used FreeSurfer to extract cortical size and shape measures from structural MRI scans collected from the initial year of a longitudinal study involving 70 children (36 stuttering, 34 controls) in the 3–10-year range. The stuttering group was further divided into two groups: persistent and recovered, based on their later longitudinal visits that allowed determination of their eventual clinical outcome. A region of interest analysis that focused on the left hemisphere speech network and a whole-brain exploratory analysis were conducted to examine group differences and group × age interaction effects. We found that the persistent group could be differentiated from the control and recovered groups by reduced cortical thickness in left motor and lateral premotor cortical regions. The recovered group showed an age-related decrease in local gyrification in the left medial premotor cortex (supplementary motor area and and pre-supplementary motor area). These results provide strong evidence of a primary deficit in the left hemisphere speech network, specifically involving lateral premotor cortex and primary motor cortex, in persistent developmental stuttering. Results further point to a possible compensatory mechanism involving left medial premotor cortex in those who recover from childhood stuttering.This study was supported by Award Numbers R01DC011277 (SC) and R01DC007683 (FG) from the National Institute on Deafness and other Communication Disorders (NIDCD). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIDCD or the National Institutes of Health. (R01DC011277 - National Institute on Deafness and other Communication Disorders (NIDCD); R01DC007683 - National Institute on Deafness and other Communication Disorders (NIDCD))Accepted manuscrip

Rethinking Phylogeny and Ontogeny in Hominin Brain Evolution

Theories of hominin and human cognitive evolution have traditionally focused on the phylogeny of the human brain, and on comparisons of human and primate brains in relation to social or ecological variables. Far less attention has been paid to ontogenetic processes, despite the recognition that experience has a profound influence on adult cognition. In this paper we discuss the interplay between phylogeny and ontogeny by examining relationships between human brain size, developmental scheduling and cognition. The correlates of large brains include not only altered subsistence and life-history strategies to meet associated energetic costs, but also on macro- and micro-scale structural adaptations required to meet increased processing costs. This means that larger brains are of necessity more highly interconnected brains, with higher degrees of folding of the neocortex (gyrification) and higher ratios of myelinated connections between neurons (white matter) to neurons themselves (grey matter). Here we argue that the combination of these evolutionary trends underpins the complexity of human behaviour, as the neural circuits involved in cognitive mechanisms such as the mirror neuron system (the system governing motor emulation and imitation) and theory of mind (fundamental in social cognition) mature only slowly, and require considerable socially-scaffolded experience to develop to their full potential. These abilities are likely to be fundamental in characteristically human behaviours such as the cultural transmission of complex forms of tool manufacture and use, attested to in the archaeological record. Their elaborated modern human forms, we argue, are possible only in the context of the evolution of relatively slower trajectories of brain growth and hence longer periods during which the growing brain can be influenced by experience among modern humans relative to other primates. Here we review some of the differences in ontogenetic brain development between humans and other primates, and compare the rates and trajectories of neural development between ourselves and our closest living relatives the chimpanzees to suggest that the human pattern of expanded periods of growth coupled with slower trajectories of neural development is likely to have been of huge significance during hominin evolution. In addition, we discuss fossil and archaeological proxies which might allow the reconstruction of evolutionary patterns of development, suggesting that it is only post-Homo erectus and specifically among Homo heidelbergensis and Homo neanderthalensis populations that developmental patterns approximate those of modern humans, arguing for a similar – but not identical – role for socially-scaffolded learning of complex technical skills as among modern groups in these species

Puzzle Pieces: Neural Structure and Function in Prader-Willi Syndrome.

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder of genomic imprinting, presenting with a behavioural phenotype encompassing hyperphagia, intellectual disability, social and behavioural difficulties, and propensity to psychiatric illness. Research has tended to focus on the cognitive and behavioural investigation of these features, and, with the exception of eating behaviour, the neural physiology is currently less well understood. A systematic review was undertaken to explore findings relating to neural structure and function in PWS, using search terms designed to encompass all published articles concerning both in vivo and post-mortem studies of neural structure and function in PWS. This supported the general paucity of research in this area, with many articles reporting case studies and qualitative descriptions or focusing solely on the overeating behaviour, although a number of systematic investigations were also identified. Research to date implicates a combination of subcortical and higher order structures in PWS, including those involved in processing reward, motivation, affect and higher order cognitive functions, with both anatomical and functional investigations indicating abnormalities. It appears likely that PWS involves aberrant activity across distributed neural networks. The characterisation of neural structure and function warrants both replication and further systematic study

Altered Cortical Gyrification in Adults Who Were Born Very Preterm and Its Associations With Cognition and Mental Health

Background: The last trimester of pregnancy is a critical period for the establishment of cortical gyrification, and altered folding patterns have been reported following very preterm birth (\u3c 33 weeks of gestation) in childhood and adolescence. However, research is scant on the persistence of such alterations in adulthood and their associations with cognitive and psychiatric outcomes. Methods: We studied 79 very preterm and 81 age-matched full-term control adults. T1-weighted magnetic resonance images were used to measure a local gyrification index (LGI), indicating the degree of folding across multiple vertices of the reconstructed cortical surface. Group and group-by-sex LGI differences were assessed by means of per-vertex adjustment for cortical thickness and overall intracranial volume. Within-group correlations were also computed between LGI and functional outcomes, including general intelligence (IQ) and psychopathology. Results: Very preterm adults had significantly reduced LGI in extensive cortical regions encompassing the frontal, anterior temporal, and occipitoparietal lobes. Alterations in lateral fronto-temporal-parietal and medial occipitoparietal regions were present in both men and women, although men showed more extensive alterations. In both very preterm and control adults, higher LGI was associated with higher IQ and lower psychopathology scores, with the spatial distribution of these associations substantially differing between the two groups. Conclusions: Very preterm adults’ brains are characterized by significant and widespread local hypogyria, and these alterations might be implicated in cognitive and psychiatric outcomes. Gyrification reflects an early developmental process and provides a fingerprint for very preterm birth

Reduced cortical complexity in children with prader-willi syndrome and its association with cognitive impairment and developmental delay

Background: Prader-Willi Syndrome (PWS) is a complex neurogenetic disorder with symptoms involving not only hypothalamic, but also a global, central nervous system dysfunction. Previously, qualitative studies reported polymicrogyria in adults with PWS. However, there have been no quantitative neuroimaging studies of cortical morphology in PWS and no studies to date in children with PWS. Thus, our aim was to investigate and quantify cortical complexity in children with PWS compared to healthy controls. In addition, we investigated differences between genetic subtypes of PWS and the relationship between cortical complexity and intelligence within the PWS group.Methods: High-resolution structural magnetic resonance images were acquired in 24 children with genetically confirmed PWS (12 carrying a deletion (DEL), 12 with maternal uniparental disomy (mUPD)) and 11 age- and sex-matched typically developing siblings as healthy controls. Local gyrification index (lGI) was obtained using the FreeSurfer software suite.Results: Four large clusters, two in each hemisphere, comprising frontal, parietal and temporal lobes, had lower lGI in children with PWS, compared to healthy controls. Clusters with lower lGI also had significantly lower cortical surface area in children with PWS. No differences in cortical thickness of the clusters were found between the PWS and healthy controls. lGI correlated significantly with cortical surface area, but not with cortical thickness. Within the PWS group, lGI in both hemispheres correlated with Total IQ and Verbal IQ, but not with Performance IQ. Children with mUPD, compared to children with DEL, had two small clusters with lower lGI in the right hemisphere. lGI of these clusters correlated with cortical surface area, but not with cortical thickness or IQ.Conclusions: These results suggest that lower cortical complexity in children with PWS partially underlies cognitive impairment and developmental delay, probably due to alterations in gene networks that play a prominent role in early brain development

Gyrification in relation to cortical thickness in the congenitally blind

Greater cortical gyrification (GY) is linked with enhanced cognitive abilities and is also negatively related to cortical thickness (CT). Individuals who are congenitally blind (CB) exhibits remarkable functional brain plasticity which enables them to perform certain non-visual and cognitive tasks with supranormal abilities. For instance, extensive training using touch and audition enables CB people to develop impressive skills and there is evidence linking these skills to cross-modal activations of primary visual areas. There is a cascade of anatomical, morphometric and functional-connectivity changes in non-visual structures, volumetric reductions in several components of the visual system, and CT is also increased in CB. No study to date has explored GY changes in this population, and no study has explored how variations in CT are related to GY changes in CB. T1-weighted 3D structural magnetic resonance imaging scans were acquired to examine the effects of congenital visual deprivation in cortical structures in a healthy sample of 11 CB individuals (6 male) and 16 age-matched sighted controls (SC) (10 male). In this report, we show for the first time an increase in GY in several brain areas of CB individuals compared to SC, and a negative relationship between GY and CT in the CB brain in several different cortical areas. We discuss the implications of our findings and the contributions of developmental factors and synaptogenesis to the relationship between CT and GY in CB individuals compared to SC. F

Doctor of Philosophy

dissertationNeurodegenerative diseases are an increasing health care problem in the United States. Quantitative neuroimaging provides a noninvasive method to illuminate individual variations in brain structure to better understand and diagnose these disorders. The overall objective of this research is to develop novel clinical tools that summarize and quantify changes in brain shape to not only help better understand age-appropriate changes but also, in the future, to dissociate structural changes associated with aging from those caused by dementing neurodegenerative disorders. Because the tools we will develop can be applied for individual assessment, achieving our goals could have a significant clinical impact. An accurate, practical objective summary measure of the brain pathology would augment current subjective visual interpretation of structural magnetic resonance images. Fractal dimension is a novel approach to image analysis that provides a quantitative measure of shape complexity describing the multiscale folding of the human cerebral cortex. Cerebral cortical folding reflects the complex underlying architectural features that evolve during brain development and degeneration including neuronal density, synaptic proliferation and loss, and gliosis. Building upon existing technology, we have developed innovative tools to compute global and local (voxel-wise and regional) cerebral cortical fractal dimensions and voxel-wise cortico-fractal surfaces from high-contrast MR images. Our previous research has shown that fractal dimension correlates with cognitive function and changes during the course of normal aging. We will now apply unbiased diffeomorphic atlasing methodology to dramatically improve the alignment of complex cortical surfaces. Our novel methods will create more accurate, detailed geometrically averaged images to take into account the intragroup differences and make statistical inferences about spatiotemporal changes in shape of the cerebral cortex across the adult human lifespan

Structural brain connectivity of HIV-positive children: a graph network analysis study

Vertical transmission of human immunodeficiency virus (HIV) from mother to child is a major problem in sub-Saharan Africa. As in adults, a variety of cognitive impairments may be evident in HIV infected children being treated with combined antiretroviral therapy (ART). The HIV virus compromises visual perception, attention, memory, language and executive functioning. Prior imaging studies have shown abnormal brain structure in adults and children infected by HIV. Graph theory analyses have been applied to HIV neuropathogenesis previously, these have demonstrated significant disruptions to brain connectivity in older HIV+ adults on treatment. However, no previous studies have investigated the same topological organization or structural connectivity of brain structure in infected children, or correlated this with markers of disease severity. The aims of this project were first, to delineate the topological organization of brain structure in children living with HIV currently on treatment and contrast it with healthy HIV negative children, second to investigate differences in measures of brain structure between healthy controls and children living with HIV and third to correlate brain imaging measures with markers of disease severity. The studies presented here examine the structural connectivity between nodes in the brain by utilizing magnetic resonance imaging and graph theory methods, and also investigated gray matter structure and cortical complexity. Children living with HIV displayed abnormal structural connectivity in regions of the dorsal posterior cingulate and inferior frontal gyrus of the frontal lobe, as well as in superior regions of the temporal lobe when compared to healthy HIV negative children. Significantly decreased cortical thickness was found in precentral and postcentral regions and the superior and middle frontal regions of children living with HIV compared to the healthy group. Deficits in cortical complexity of the inferior frontal gyrus and fusiform gyri were also apparent in the HIV infected group. Cortical thickness, surface area and gyrification were positively associated with CD4 count as a marker of disease severity. In conclusion, this project demonstrated abnormal brain structure and structural connectivity of brain structure in regions involved with motor development, executive function, and language fluency and generation in treated children living with HIV. Abnormal structural connectivity may indicate disruption to brain network integrity in developing children. Even in the post-ART era, infected children remain at risk for abnormal brain development. Longitudinal studies in larger cohorts are needed to address the issue of changes in brain structure and topology over time during adolescent brain development