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The purpose of this study was to determine whether white matter microstructure measured by diffusion magnetic resonance imaging (dMRI) provides independent information about baseline level or change in executive function (EF) or memory (MEM) in older adults with and without cognitive impairment. Longitudinal data was acquired from the Alzheimer's Disease Neuroimaging Initiative (ADNI) study from phases GO and 2 (2009–2015). ADNI participants included were diagnosed as cognitively normal (n = 46), early mild cognitive impairment (MCI) (n = 48), late MCI (n = 29), and dementia (n = 39) at baseline. We modeled the association between dMRI-based global white matter mean diffusivity (MD) and baseline level and change in EF and MEM composite scores, in models controlling for baseline bilateral hippocampal volume, regional cerebral FDG PET metabolism and global cerebral AV45 PET uptake. EF and MEM composite scores were measured at baseline, 6, 12, 24 and 36 months. In the baseline late MCI and dementia groups, greater global MD was associated with lesser baseline EF, but not EF change nor MEM baseline or change. As expected, lesser hippocampal volume and lesser FDG PET metabolism was associated with greater rates of EF and MEM decline. In ADNI-GO/2 participants, white matter integrity provided independent information about current executive function, but was not sensitive to future cognitive change. Since individuals experiencing executive function declines progress to dementia more rapidly than those with only memory impairment, better biomarkers of future executive function decline are needed. Highlights • In the ADNI cohort, MRI and PET predictors of baseline and change in executive function were tested. • Global mean diffusivity was associated with baseline, but not change in, executive function. • Diffusion MRI provides independent information on current executive function in older adults.

Auditory evoked potentials were recorded from 47 subjects ranging in age from 6 to 76 years in order to assess the effects of maturation and aging on the evoked (N1 and P2) and event-related (N2 and P3) components. Because of clear differences in the effects of age on the event-related components between children (less than 15 years of age) and adults the subjects were divided into two populations for analysis. For adults there was a systematic increase in the latency and decrease in amplitude of each component with age. Also the rate of the age-related increase in latency was proportional to the latency of the component. The scalp distributions of both the stimulus-evoked and event-related components were found to vary with age yielding a more nearly equipotential distribution for older subjects. For children the latencies of the event-related components decreased with age. The stimulus-evoked components had latencies which were not significantly different from those predicted from the adult data. In contrast to the adult data, age affected the scalp distributions of the stimulus-evoked components differently than the event-related components. These results suggest an aging process is reflected in the auditory evoked potential which is not the simple inverse of maturational processes. © 1978.

© 2016 The Authors Adolescence is a developmental period characterized by a greater tendency to take risks. While the adult literature has shown that sex steroids influence reward-related brain functioning and risk taking, research on the role of these hormones during puberty is limited. In this study, we examined the relation between pubertal hormones and adolescent risk taking using a probabilistic decision-making task. In this task, participants could choose on each trial to play or pass based on explicit information about the risk level and stakes involved in their decision. We administered this task to 58 11-to-13-year-old girls while functional MRI images were obtained to examine reward-related brain processes associated with their risky choices. Results showed that higher testosterone levels were associated with increased risk taking, which was mediated by increased medial orbitofrontal cortex activation. Furthermore, higher estradiol levels were associated with increased nucleus accumbens activation, which in turn related to decreased risk taking. These findings offer potential neuroendocrine mechanisms that can explain why some adolescent girls might engage in more risk taking compared to others.

Although chronic pain is one of the most important medical problems facing society, there has been very limited progress in the development of novel therapies for this condition. Here, we discuss high-impact research priorities to reduce the number of people transitioning from acute to chronic intractable pain.

Nanobodies (nAbs) are small, minimal antibodies that have distinct attributes that make them uniquely suited for certain biomedical research, diagnostic and therapeutic applications. Prominent uses include as intracellular antibodies or intrabodies to bind and deliver cargo to specific proteins and/or subcellular sites within cells, and as nanoscale immunolabels for enhanced tissue penetration and improved spatial imaging resolution. Here, we report the generation and validation of nAbs against a set of proteins prominently expressed at specific subcellular sites in mammalian brain neurons. We describe a novel hierarchical validation pipeline to systematically evaluate nAbs isolated by phage display for effective and specific use as intrabodies and immunolabels in mammalian cells including brain neurons. These nAbs form part of a robust toolbox for targeting proteins with distinct and highly spatially-restricted subcellular localization in mammalian brain neurons, allowing for visualization and/or modulation of structure and function at those sites.

Mood and anxiety disorders are complex heterogeneous syndromes that manifest in dysfunctions across multiple brain regions, cell types, and circuits. Biomarkers using brain-wide activity patterns in humans have proven useful in distinguishing between disorder subtypes and identifying effective treatments. In order to improve biomarker identification, it is crucial to understand the basic circuitry underpinning brain-wide activity patterns. Leveraging a large repertoire of techniques, animal studies have examined roles of specific cell types and circuits in driving maladaptive behavior. Recent advances in multiregion recording techniques, data-driven analysis approaches, and machine-learning-based behavioral analysis tools can further push the boundary of animal studies and bridge the gap with human studies, to assess how brain-wide activity patterns encode and drive emotional behavior. Together, these efforts will allow identifying more precise biomarkers to enhance diagnosis and treatment.

How does a lack of sleep affect our brains? In contrast to the benefits of sleep, frameworks exploring the impact of sleep loss are relatively lacking. Importantly, the effects of sleep deprivation (SD) do not simply reflect the absence of sleep and the benefits attributed to it; rather, they reflect the consequences of several additional factors, including extended wakefulness. With a focus on neuroimaging studies, we review the consequences of SD on attention and working memory, positive and negative emotion, and hippocampal learning. We explore how this evidence informs our mechanistic understanding of the known changes in cognition and emotion associated with SD, and the insights it provides regarding clinical conditions associated with sleep disruption.

AbstractMicroglia shape the synaptic environment in health and disease, but synapses do not exist in a vacuum. Instead, pre- and postsynaptic terminals are surrounded by extracellular matrix (ECM), which together with glia comprise the four elements of the contemporary tetrapartite synapse model. While research in this area is still just beginning, accumulating evidence points toward a novel role for microglia in regulating the ECM during normal brain homeostasis, and such processes may, in turn, become dysfunctional in disease. As it relates to synapses, microglia are reported to modify the perisynaptic matrix, which is the diffuse matrix that surrounds dendritic and axonal terminals, as well as perineuronal nets (PNNs), specialized reticular formations of compact ECM that enwrap neuronal subsets and stabilize proximal synapses. The interconnected relationship between synapses and the ECM in which they are embedded suggests that alterations in one structure necessarily affect the dynamics of the other, and microglia may need to sculpt the matrix to modify the synapses within. Here, we provide an overview of the microglial regulation of synapses, perisynaptic matrix, and PNNs, propose candidate mechanisms by which these structures may be modified, and present the implications of such modifications in normal brain homeostasis and in disease.