Mapping of human brain function has revolutionized systems neuroscience. However, traditional functional neuroimaging by positron emission tomography or functional magnetic resonance imaging cannot be used when applications require portability, or are contraindicated because of ionizing radiation (positron emission tomography) or implanted metal (functional magnetic resonance imaging). Optical neuroimaging offers a non-invasive alternative that is radiation free and compatible with implanted metal and electronic devices (for example, pacemakers). However, optical imaging technology has heretofore lacked the combination of spatial resolution and wide field of view sufficient to map distributed brain functions. Here, we present a high-density diffuse optical tomography imaging array that can map higher-order, distributed brain function. The system was tested by imaging four hierarchical language tasks and multiple resting-state networks including the dorsal attention and default mode networks. Finally, we imaged brain function in patients with Parkinson’s disease and implanted deep brain stimulators that preclude functional magnetic resonance imaging.
Brain aging is associated with diminished circadian clock output and decreased expression of the core clock proteins, which regulate many aspects of cellular biochemistry and metabolism. The genes encoding clock proteins are expressed throughout the brain, though it is unknown whether these proteins modulate brain homeostasis. We observed that deletion of circadian clock transcriptional activators aryl hydrocarbon receptor nuclear translocator-like (Bmal1) alone, or circadian locomotor output cycles kaput (Clock) in combination with neuronal PAS domain protein 2 (Npas2), induced severe age-dependent astrogliosis in the cortex and hippocampus. Mice lacking the clock gene repressors period circadian clock 1 (Per1) and period circadian clock 2 (Per2) had no observed astrogliosis. Bmal1 deletion caused the degeneration of synaptic terminals and impaired cortical functional connectivity, as well as neuronal oxidative damage and impaired expression of several redox defense genes. Targeted deletion of Bmal1 in neurons and glia caused similar neuropathology, despite the retention of intact circadian behavioral and sleep-wake rhythms. Reduction of Bmal1 expression promoted neuronal death in primary cultures and in mice treated with a chemical inducer of oxidative injury and striatal neurodegeneration. Our findings indicate that BMAL1 in a complex with CLOCK or NPAS2 regulates cerebral redox homeostasis and connects impaired clock gene function to neurodegeneration.
Functional neuroimaging is a vital element of neuroscience and cognitive research and, increasingly, is an important clinical tool. Diffuse optical imaging is an emerging, noninvasive technique with unique portability and hemodynamic contrast capabilities for mapping brain function in young subjects and subjects in enriched or clinical environments. We have developed a high-performance, high-density diffuse optical tomography (DOT) system that overcomes previous limitations and enables superior image quality. We show herein the utility of the DOT system by presenting functional hemodynamic maps of the adult human visual cortex. The functional brain images have a high contrast-to-noise ratio, allowing visualization of individual activations and highly repeatable mapping within and across subjects. With the improved spatial resolution and localization, we were able to image functional responses of 1.7 cm in extent and shifts of <1 cm. Cortical maps of angle and eccentricity in the visual field are consistent with retinotopic studies using functional MRI and positron-emission tomography. These results demonstrate that high-density DOT is a practical and powerful tool for mapping function in the human cortex. functional brain mapping ͉ near-infrared spectroscopy ͉ neuroimaging ͉ retinotopy F unctional mapping of the human brain is an important aspect of cognitive neuroscience that is used to study brain organization and development. Increasingly, functional neuroimaging is being used as a diagnostic and prognostic tool in the clinical setting. Its expanding application in the study of disease and development necessitates new, flexible functional neuroimaging tools. Many situations are not amenable to scanner logistics, such as subjects who are in the intensive care unit, who are performing complex tasks, or who might otherwise require sedation for imaging, such as infants and young children. Additionally, there are imaging situations in which the neurovascular coupling either is not mature, such as in neonates and very young infants (1-3), or is altered due to injury or illness (4, 5). Diffuse optical imaging (DOI) is a methodology uniquely suited to such tasks, because it is a mobile system that uses a small, flexible imaging cap (6, 7). DOI images hemodynamic contrasts similar to functional MRI (fMRI) with blood oxygen-level dependent (BOLD) signals (fMRI-BOLD); however, DOI can measure changes in oxygenated hemoglobin (⌬HbO 2 ), deoxygenated hemoglobin (⌬Hb R ), and total hemoglobin (⌬Hb T ), whereas the BOLD signal is mainly dependent on ⌬Hb R (8). The ability to simultaneously image these contrasts allows DOI to distinguish differences in their magnitude (3, 4, 9), timing (3, 10-12), and localization (13-15), forming a more complete picture of neurovascular function. In contrast to positron emission tomography (PET), which uses ionizing radiation, DOI uses safe, infrared light for imaging. Despite unique strengths, however, DOI as a standard tool for functional mapping has been limited by low spatial resolution...
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