52. The only imaging analysis steps required in the proposed framework are brain extraction and linear registration, hence robust results are obtained with a low computational cost. In addition, the network model provides a novel insight on aging patterns within the brain and specific information about anatomical districts displaying relevant changes with aging.Here we present a method for the simultaneous segmentation of white matter lesions and normal-appearing neuroanatomical structures from multi-contrast brain MRI scans of multiple sclerosis patients. The method integrates a novel model for white matter lesions into a previously validated generative model for whole-brain segmentation. By using separate models for the shape of anatomical structures and their appearance in MRI, the algorithm can adapt to data acquired with different scanners and imaging protocols without retraining. We validate the method using four disparate datasets, showing robust performance in white matter lesion segmentation while simultaneously segmenting dozens of other brain structures. We further demonstrate that the contrast-adaptive method can also be safely applied to MRI scans of healthy controls, and replicate previously documented atrophy patterns in deep gray matter structures in MS. The algorithm is publicly available as part of the open-source neuroimaging package FreeSurfer.While a recent upsurge in the application of neuroimaging methods to creative cognition has yielded encouraging progress toward understanding the neural underpinnings of creativity, the neural basis of barriers to creativity are as yet unexplored. Here, we report the first investigation into the neural correlates of one such recently identified barrier to creativity anxiety specific to creative thinking, or creativity anxiety (Daker et al., 2019). We employed a machine-learning technique for exploring relations between functional connectivity and behavior (connectome-based predictive modeling; CPM) to investigate the functional connections underlying creativity anxiety. Using whole-brain resting-state functional connectivity data, we identified a network of connections or "edges" that predicted individual differences in creativity anxiety, largely comprising connections within and between regions of the executive and default networks and the limbic system. We then found that the edges related to creativity anxiety identified in one sample generalize to predict creativity anxiety in an independent sample. We additionally found evidence that the network of edges related to creativity anxiety were largely distinct from those found in previous work to be related to divergent creative ability (Beaty et al., 2018). In addition to being the first work on the neural correlates of creativity anxiety, this research also included the development of a new Chinese-language version of the Creativity Anxiety Scale, and demonstrated that key behavioral findings from the initial work on creativity anxiety are replicable across cultures and languages.Hierarchy is a major organizational principle of the cortex and underscores modern computational theories of cortical function. The local microcircuit amplifies long-distance inter-areal input, which show distance-dependent changes in their laminar profiles. Statistical modeling of these changes in laminar profiles demonstrates that inputs from multiple hierarchical levels to their target areas show remarkable consistency, allowing the construction of a cortical hierarchy based on a principle of hierarchical distance. The statistical modeling that is applied to structure can also be applied to laminar differences in the oscillatory coherence between areas thereby determining a functional hierarchy of the cortex. Close examination of the anatomy of inter-areal connectivity reveals a dual counterstream architecture with well-defined distance-dependent feedback and feedforward pathways in both the supra- and infragranular layers, suggesting a multiplicity of feedback pathways with well-defined functional properties. These findings are consistent with feedback connections providing a generative network involved in a wide range of cognitive functions. A dynamical model constrained by connectivity data sheds insight into the experimentally observed signatures of frequency-dependent Granger causality for feedforward versus feedback signaling. Concerted experiments capitalizing on recent technical advances and combining tract-tracing, high-resolution fMRI, optogenetics and mathematical modeling hold the promise of a much improved understanding of lamina-constrained mechanisms of neural computation and cognition. However, because inter-areal interactions involve cortical layers that have been the target of important evolutionary changes in the primate lineage, these investigations will need to include human and non-human primate comparisons.Speech-in-noise (SIN) understanding often becomes difficult for older adults because of impaired hearing and aging-related changes in central auditory processing. Central auditory processing depends on a fine balance between excitatory and inhibitory neural mechanisms, which may be upset in older age by a change in the level of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In this study, we used MEGA-PRESS magnetic resonance spectroscopy (MRS) to estimate GABA levels in both the left and right auditory cortices of young and older adults. Cl-amidine We found that total auditory GABA levels were lower in older compared to young adults. To understand the relationship between GABA and hearing function, we correlated GABA levels with hearing loss and SIN performance. In older adults, the GABA level in the right auditory cortex was correlated with age and SIN performance. The relationship between chronological age and SIN loss was partially mediated by the GABA level in the right auditory cortex. These findings support the hypothesis that inhibitory mechanisms in the auditory system are reduced in aging, and this reduction relates to functional impairments.Lipid peroxidation results in generation of a variety of lipid hydroperoxides and other highly reactive species that covalently modify proteins, nucleic acids, and other lipids, thus resulting in lipotoxicity. Although biological relevance of 4-hydroxynonenal (4-HNE) and malondialdehyde (MDA) is well studied, the existing data on the role of isolevuglandins (isoLGs) in pathology are insufficient. Therefore, the objective of the present study was to review the existing data on biological effects of isoLG and isoLG adducts and their role in multiple diseases. Sixty four highly reactive levuglandin-like γ-ketoaldehyde (γ-KA, or isoketals, IsoK, or isolevuglandins, IsoLG) regio- and stereo-isomers are formed as products of arachidonic acid oxidation. IsoLGs react covalently with lysyl residues of proteins to form a stable adduct and intramolecular aminal, bispyrrole, and trispyrrole cross-links. Phosphatidylethanolamine was also shown to be the target for isoLG binding as compared to proteins and DNA. Free IsoLGs are not detectable in vivo, although isolevuglandin adduction to amino acid residues of particular proteins may be evaluated with liquid chromatography-tandem mass spectrometry.