7,950 research outputs found
Recommended from our members
Structural Neuroimaging of Anorexia Nervosa: Future Directions in the Quest for Mechanisms Underlying Dynamic Alterations.
Anorexia nervosa (AN) is a serious eating disorder characterized by self-starvation and extreme weight loss. Pseudoatrophic brain changes are often readily visible in individual brain scans, and AN may be a valuable model disorder to study structural neuroplasticity. Structural magnetic resonance imaging studies have found reduced gray matter volume and cortical thinning in acutely underweight patients to normalize following successful treatment. However, some well-controlled studies have found regionally greater gray matter and persistence of structural alterations following long-term recovery. Findings from diffusion tensor imaging studies of white matter integrity and connectivity are also inconsistent. Furthermore, despite the severity of AN, the number of existing structural neuroimaging studies is still relatively low, and our knowledge of the underlying cellular and molecular mechanisms for macrostructural brain changes is rudimentary. We critically review the current state of structural neuroimaging in AN and discuss the potential neurobiological basis of structural brain alterations in the disorder, highlighting impediments to progress, recent developments, and promising future directions. In particular, we argue for the utility of more standardized data collection, adopting a connectomics approach to understanding brain network architecture, employing advanced magnetic resonance imaging methods that quantify biomarkers of brain tissue microstructure, integrating data from multiple imaging modalities, strategic longitudinal observation during weight restoration, and large-scale data pooling. Our overarching objective is to motivate carefully controlled research of brain structure in eating disorders, which will ultimately help predict therapeutic response and improve treatment
Developmental imaging genetics: challenges and promises for translational research
Advances in molecular biology, neuroimaging, genetic epidemiology, and developmental psychopathology have provided a unique opportunity to explore the interplay of genes, brain, and behavior within a translational research framework. Herein, we begin by outlining an experimental strategy by which genetic effects on brain function can be explored using neuroimaging, namely, imaging genetics. We next describe some major findings in imaging genetics to highlight the effectiveness of this strategy for delineating biological pathways and mechanisms by which individual differences in brain function emerge and potentially bias behavior and risk for psychiatric illness. We then discuss the importance of applying imaging genetics to the study of psychopathology within a developmental framework. By beginning to move toward a systems-level approach to understanding pathways to behavioral outcomes as they are expressed across development, it is anticipated that we will move closer to understanding the complexities of the specific mechanisms involved in the etiology of psychiatric disease. Despite the numerous challenges that lie ahead, we believe that developmental imaging genetics has potential to yield highly informative results that will ultimately translate into public health benefits. We attempt to set out guidelines and provide exemplars that may help in designing fruitful translational research applications that incorporate a developmental imaging genetics strategy
Measuring cortical connectivity in Alzheimer's disease as a brain neural network pathology: Toward clinical applications
Objectives: The objective was to review the literature on diffusion tensor imaging as well as resting-state functional magnetic
resonance imaging and electroencephalography (EEG) to unveil neuroanatomical and neurophysiological substrates of
Alzheimer’s disease (AD) as a brain neural network pathology affecting structural and functional cortical connectivity
underlying human cognition. Methods: We reviewed papers registered in PubMed and other scientific repositories on the
use of these techniques in amnesic mild cognitive impairment (MCI) and clinically mild AD dementia patients compared to
cognitively intact elderly individuals (Controls). Results: Hundreds of peer-reviewed (cross-sectional and longitudinal) papers
have shown in patients with MCI and mild AD compared to Controls (1) impairment of callosal (splenium), thalamic,
and anterior–posterior white matter bundles; (2) reduced correlation of resting state blood oxygen level-dependent activity
across several intrinsic brain circuits including default mode and attention-related networks; and (3) abnormal power
and functional coupling of resting state cortical EEG rhythms. Clinical applications of these measures are still limited.
Conclusions: Structural and functional (in vivo) cortical connectivity measures represent a reliable marker of cerebral
reserve capacity and should be used to predict and monitor the evolution of AD and its relative impact on cognitive domains
in pre-clinical, prodromal, and dementia stages of AD. (JINS, 2016, 22, 138–163
Genetic and Neuroanatomical Support for Functional Brain Network Dynamics in Epilepsy
Focal epilepsy is a devastating neurological disorder that affects an
overwhelming number of patients worldwide, many of whom prove resistant to
medication. The efficacy of current innovative technologies for the treatment
of these patients has been stalled by the lack of accurate and effective
methods to fuse multimodal neuroimaging data to map anatomical targets driving
seizure dynamics. Here we propose a parsimonious model that explains how
large-scale anatomical networks and shared genetic constraints shape
inter-regional communication in focal epilepsy. In extensive ECoG recordings
acquired from a group of patients with medically refractory focal-onset
epilepsy, we find that ictal and preictal functional brain network dynamics can
be accurately predicted from features of brain anatomy and geometry, patterns
of white matter connectivity, and constraints complicit in patterns of gene
coexpression, all of which are conserved across healthy adult populations.
Moreover, we uncover evidence that markers of non-conserved architecture,
potentially driven by idiosyncratic pathology of single subjects, are most
prevalent in high frequency ictal dynamics and low frequency preictal dynamics.
Finally, we find that ictal dynamics are better predicted by white matter
features and more poorly predicted by geometry and genetic constraints than
preictal dynamics, suggesting that the functional brain network dynamics
manifest in seizures rely on - and may directly propagate along - underlying
white matter structure that is largely conserved across humans. Broadly, our
work offers insights into the generic architectural principles of the human
brain that impact seizure dynamics, and could be extended to further our
understanding, models, and predictions of subject-level pathology and response
to intervention
Grey-matter texture abnormalities and reduced hippocampal volume are distinguishing features of schizophrenia
Neurodevelopmental processes are widely believed to underlie schizophrenia. Analysis of
brain texture from conventional magnetic resonance imaging (MRI) can detect disturbance in
brain cytoarchitecture. We tested the hypothesis that patients with schizophrenia manifest
quantitative differences in brain texture that, alongside discrete volumetric changes, may
serve as an endophenotypic biomarker. Texture analysis (TA) of grey matter distribution and
voxel-based morphometry (VBM) of regional brain volumes were applied to MRI scans of 27
patients with schizophrenia and 24 controls. Texture parameters (uniformity and entropy)
were also used as covariates in VBM analyses to test for correspondence with regional brain
volume. Linear discriminant analysis tested if texture and volumetric data predicted
diagnostic group membership (schizophrenia or control). We found that uniformity and
entropy of grey matter differed significantly between individuals with schizophrenia and
controls at the fine spatial scale (filter width below 2 mm). Within the schizophrenia group,
these texture parameters correlated with volumes of the left hippocampus, right amygdala
and cerebellum. The best predictor of diagnostic group membership was the combination of
fine texture heterogeneity and left hippocampal size. This study highlights the presence of
distributed grey-matter abnormalities in schizophrenia, and their relation to focal structural
abnormality of the hippocampus. The conjunction of these features has potential as a
neuroimaging endophenotype of schizophrenia
From early markers to neuro-developmental mechanisms of autism
A fast growing field, the study of infants at risk because of having an older sibling with autism (i.e. infant sibs) aims to identify the earliest signs of this disorder, which would allow for earlier diagnosis and intervention. More importantly, we argue, these studies offer the opportunity to validate existing neuro-developmental models of autism against experimental evidence. Although autism is mainly seen as a disorder of social interaction and communication, emerging early markers do not exclusively reflect impairments of the “social brain”. Evidence for atypical development of sensory and attentional systems highlight the need to move away from localized deficits to models suggesting brain-wide involvement in autism pathology. We discuss the implications infant sibs findings have for future work into the biology of autism and the development of interventions
Environmental and genetic influences on neurocognitive development: the importance of multiple methodologies and time-dependent intervention
Genetic mutations and environmental factors dynamically influence gene expression and developmental trajectories at the neural, cognitive, and behavioral levels. The examples in this article cover different periods of neurocognitive development—early childhood, adolescence, and adulthood—and focus on studies in which researchers have used a variety of methodologies to illustrate the early effects of socioeconomic status and stress on brain function, as well as how allelic differences explain why some individuals respond to intervention and others do not. These studies highlight how similar behaviors can be driven by different underlying neural processes and show how a neurocomputational model of early development can account for neurodevelopmental syndromes, such as autism spectrum disorders, with novel implications for intervention. Finally, these studies illustrate the importance of the timing of environmental and genetic factors on development, consistent with our view that phenotypes are emergent, not predetermined
The Structural and Functional Connectome and Prediction of Risk for Cognitive Impairment in Older Adults
The human connectome refers to a comprehensive description of the brain's structural and functional connections in terms of brain networks. As the field of brain connectomics has developed, data acquisition, subsequent processing and modeling, and ultimately the representation of the connectome have become better defined and integrated with network science approaches. In this way, the human connectome has provided a way to elucidate key features of not only the healthy brain but also diseased brains. The field has quickly evolved, offering insights into network disruptions that are characteristic for specific neurodegenerative disorders. In this paper, we provide a brief review of the field of brain connectomics, as well as a more in-depth survey of recent studies that have provided new insights into brain network pathologies, including those found in Alzheimer's disease (AD), patients with mild cognitive impairment (MCI), and finally in people classified as being "at risk". Until the emergence of brain connectomics, most previous studies had assessed neurodegenerative diseases mainly by focusing on specific and dispersed locales in the brain. Connectomics-based approaches allow us to model the brain as a network, which allows for inferences about how dynamic changes in brain function would be affected in relation to structural changes. In fact, looking at diseases using network theory gives rise to new hypotheses on mechanisms of pathophysiology and clinical symptoms. Finally, we discuss the future of this field and how understanding both the functional and structural connectome can aid in gaining sharper insight into changes in biological brain networks associated with cognitive impairment and dementia
Low smoking-exposure, the adolescent brain, and the modulating role of CHRNA5 polymorphisms
© 2019 Background: Studying the neural consequences of tobacco smoking during adolescence, including those associated with early light use, may help expose the mechanisms that underlie the transition from initial use to nicotine dependence in adulthood. However, only a few studies in adolescents exist, and they include small samples. In addition, the neural mechanism, if one exists, that links nicotinic receptor genes to smoking behavior in adolescents is still unknown. Methods: Structural and diffusion tensor magnetic resonance imaging data were acquired from a large sample of 14-year-old adolescents who completed an extensive battery of neuropsychological, clinical, personality, and drug-use assessments. Additional assessments were conducted at 16 years of age. Results: Exposure to smoking in adolescents, even at low doses, is linked to volume changes in the ventromedial prefrontal cortex and to altered neuronal connectivity in the corpus callosum. The longitudinal analyses strongly suggest that these effects are not preexisting conditions in those who progress to smoking. There was a genetic contribution wherein the volume reduction effects were magnified in smokers who were carriers of the high-risk genotype of the alpha 5 nicotinic receptor subunit gene, rs16969968. Conclusions: These findings give insight into a mechanism involving genes, brain structure, and connectivity underlying why some adolescents find nicotine especially addictive
- …