Publications by authors named "Laura D Lewis"

Cerebrospinal fluid (CSF) flow in the brain is tightly regulated and essential for brain health, and imaging techniques are needed to quantitatively establish the properties of this flow system. Flow-sensitive fMRI has recently emerged as a tool to measure large scale CSF flow dynamics with high sensitivity and temporal resolution; however, the measured signal is not quantitative. Here, we developed a dynamic model to simulate fMRI inflow signals based on time-varying flow velocities.

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The ability to detect fast responses with functional MRI depends on the speed of hemodynamic responses to neural activity, because hemodynamic responses act as a temporal low-pass filter which blurs rapid changes. However, the shape and timing of hemodynamic responses are highly variable across the brain and across stimuli. This heterogeneity of responses implies that the temporal specificity of functional MRI (fMRI) signals, or the ability of fMRI to preserve fast information, could also vary substantially across the cortex.

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Cerebrospinal fluid (CSF) flow in the brain is tightly regulated and essential for brain health, and imaging techniques are needed to quantitatively establish the properties of this flow system. Flow-sensitive fMRI has recently emerged as a tool to measure large scale CSF flow dynamics with high sensitivity and temporal resolution; however, the measured signal is not quantitative. Here, we developed a dynamic model to simulate fMRI inflow signals based on time-varying flow velocities.

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Cerebrospinal fluid (CSF) flow is a key component of the brain's waste clearance system. However, our understanding of CSF flow in the human brain, particularly within the brain-wide subarachnoid space (SAS), is limited due to a lack of non-invasive tools for measuring slow flow. Here, we propose a CSF flowmetry technique using phase-contrast MRI combined with a slow-flow-sensitized acquisition.

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Ascending neuromodulatory projections from deep brain nuclei generate internal brain states that differentially engage specific neuronal cell types. Because neurovascular coupling is cell-type specific and neuromodulatory transmitters have vasoactive properties, we hypothesized that the impulse response function (IRF) linking spontaneous neuronal activity with hemodynamics would depend on neuromodulation. To test this hypothesis, we used optical imaging to measure (1) release of neuromodulatory transmitters norepinephrine (NE) or acetylcholine (ACh), (2) Ca activity of local cortical neurons, and (3) changes in hemoglobin concentration and oxygenation across the dorsal surface of cerebral cortex during spontaneous neuronal activity in awake mice.

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Aging reduces the quality and quantity of sleep, and greater sleep loss over the lifespan is predictive of neurodegeneration and cognitive decline. One mechanism by which sleep loss could contribute to impaired brain health is through disruption of cerebrospinal fluid (CSF) circulation. CSF is the primary waste transport system of the brain, and in young adults, CSF waves are largest during NREM sleep.

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Sleep research has evolved considerably since the first sleep electroencephalography recordings in the 1930s and the discovery of well-distinguishable sleep stages in the 1950s. While electrophysiological recordings have been used to describe the sleeping brain in much detail, since the 1990s neuroimaging techniques have been applied to uncover the brain organization and functional connectivity of human sleep with greater spatial resolution. The combination of electroencephalography with different neuroimaging modalities such as positron emission tomography, structural magnetic resonance imaging and functional magnetic resonance imaging imposes several challenges for sleep studies, for instance, the need to combine polysomnographic recordings to assess sleep stages accurately, difficulties maintaining and consolidating sleep in an unfamiliar and restricted environment, scanner-induced distortions with physiological artefacts that may contaminate polysomnography recordings, and the necessity to account for all physiological changes throughout the sleep cycles to ensure better data interpretability.

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Sleep entails significant changes in cerebral hemodynamics and metabolism. Yet, the way these processes evolve throughout wakefulness and sleep and their spatiotemporal dependence remain largely unknown. Here, by integrating a novel functional PET technique with simultaneous EEG-fMRI, we reveal a tightly coupled temporal progression of global hemodynamics and metabolism during the descent into NREM sleep, with large hemodynamic fluctuations emerging as global glucose metabolism declines, both of which track EEG arousal dynamics.

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Over the past two decades, rapid advancements in magnetic resonance technology have significantly enhanced the imaging resolution of functional Magnetic Resonance Imaging (fMRI), far surpassing its initial capabilities. Beyond mapping brain functional architecture at unprecedented scales, high-spatial-resolution acquisitions have also inspired and enabled several novel analytical strategies that can potentially improve the sensitivity and neuronal specificity of fMRI. With small voxels, one can sample from different levels of the vascular hierarchy within the cerebral cortex and resolve the temporal progression of hemodynamic changes from parenchymal to pial vessels.

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Article Synopsis
  • * Researchers used fast fMRI-EEG techniques to study how sleep deprivation affects brain function and discovered that cerebrospinal fluid (CSF) flow mimicking sleep patterns disrupts cognitive processes while awake.
  • * The study suggests that CSF flow is linked to attention levels, with increased flow during attention lapses, indicating a complex relationship between fluid dynamics and brain function, which implies the need for recovery periods in the brain when sleep-deprived.
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Article Synopsis
  • Combining MRI and EEG offers a comprehensive way to study brain function, but existing EEG nets limit the quality of simultaneous imaging due to radiofrequency interference.
  • The study tested the Inknet2, a new high-resistance EEG net using conductive ink, which showed potential to minimize artifacts and maintain image quality across various MRI sequences.
  • Results indicated that Inknet2 produced fewer artifacts than traditional nets and achieved comparable image quality to scans without any net, making it a promising tool for high-quality brain imaging.
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Article Synopsis
  • Significant advancements have been made in understanding cortical networks related to conscious awareness, but research on subcortical arousal networks is still underdeveloped due to challenges in accurately defining brainstem arousal nuclei.
  • Researchers created a probabilistic atlas of brainstem arousal nuclei using high-resolution diffusion MRI scans of five ex vivo human brain samples, with annotations based on specific immunostaining.
  • A Bayesian segmentation algorithm was developed to automatically identify these nuclei across different MRI techniques, showing high accuracy and reliability, with applications in detecting changes related to disorders like Alzheimer's disease and traumatic coma.
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Closing our eyes largely shuts down our ability to see. That said, our eyelids still pass some light, allowing our visual system to coarsely process information about visual scenes, such as changes in luminance. However, the specific impact of eye closure on processing within the early visual system remains largely unknown.

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The ability to detect fast responses with functional MRI depends on the speed of hemodynamic responses to neural activity, because hemodynamic responses act as a temporal low-pass filter which blurs rapid changes. However, the shape and timing of hemodynamic responses are highly variable across the brain and across stimuli. This heterogeneity of responses implies that the temporal specificity of fMRI signals, or the ability of fMRI to preserve fast information, could also vary substantially across the cortex.

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The brain exhibits rich oscillatory dynamics that play critical roles in vigilance and cognition, such as the neural rhythms that define sleep. These rhythms continuously fluctuate, signaling major changes in vigilance, but the brainwide dynamics underlying these oscillations are unknown. Using simultaneous EEG and fast fMRI in humans drifting between sleep and wakefulness, we developed a machine learning approach to investigate which brainwide fMRI networks predict alpha (8-12 Hz) and delta (1-4 Hz) fluctuations.

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Closing our eyes largely shuts down our ability to see. That said, our eyelids still pass some light, allowing our visual system to coarsely process information about visual scenes, such as changes in luminance. However, the specific impact of eye closure on processing within the early visual system remains largely unknown.

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Functional magnetic resonance imaging (fMRI) has proven to be a powerful tool for noninvasively measuring human brain activity; yet, thus far, fMRI has been relatively limited in its temporal resolution. A key challenge is understanding the relationship between neural activity and the blood-oxygenation-level-dependent (BOLD) signal obtained from fMRI, generally modeled by the hemodynamic response function (HRF). The timing of the HRF varies across the brain and individuals, confounding our ability to make inferences about the timing of the underlying neural processes.

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The thalamus is a small, bilateral structure in the diencephalon that integrates signals from many areas of the CNS. This critical anatomical position allows the thalamus to influence whole-brain activity and adaptive behaviour. However, traditional research paradigms have struggled to attribute specific functions to the thalamus, and it has remained understudied in the human neuroimaging literature.

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A workshop titled "Beyond the Symptom: The Biology of Fatigue" was held virtually September 27-28, 2021. It was jointly organized by the Sleep Research Society and the Neurobiology of Fatigue Working Group of the NIH Blueprint Neuroscience Research Program. For access to the presentations and video recordings, see: https://neuroscienceblueprint.

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Neurofluids is a term introduced to define all fluids in the brain and spine such as blood, cerebrospinal fluid, and interstitial fluid. Neuroscientists in the past millennium have steadily identified the several different fluid environments in the brain and spine that interact in a synchronized harmonious manner to assure a healthy microenvironment required for optimal neuroglial function. Neuroanatomists and biochemists have provided an incredible wealth of evidence revealing the anatomy of perivascular spaces, meninges and glia and their role in drainage of neuronal waste products.

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Unlabelled: We introduce a new electroencephalogram (EEG) net, which will allow clinicians to monitor EEG while tracking head motion. Motion during MRI limits patient scans, especially of children with epilepsy. EEG is also severely affected by motion-induced noise, predominantly ballistocardiogram (BCG) noise due to the heartbeat.

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Simultaneous EEG-fMRI is a powerful multimodal technique for imaging the brain, but its use in neurofeedback experiments has been limited by EEG noise caused by the MRI environment. Neurofeedback studies typically require analysis of EEG in real time, but EEG acquired inside the scanner is heavily contaminated with ballistocardiogram (BCG) artifact, a high-amplitude artifact locked to the cardiac cycle. Although techniques for removing BCG artifacts do exist, they are either not suited to real-time, low-latency applications, such as neurofeedback, or have limited efficacy.

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Cerebrospinal fluid (CSF) flow maintains healthy brain homeostasis, facilitating solute transport and the exchange of brain waste products. CSF flow is thus important for brain health, but the mechanisms that control its large-scale movement through the ventricles are not well understood. While it is well established that CSF flow is modulated by respiratory and cardiovascular dynamics, recent work has also demonstrated that neural activity is coupled to large waves of CSF flow in the ventricles during sleep.

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Ketamine produces antidepressant effects in patients with treatment-resistant depression, but its usefulness is limited by its psychotropic side effects. Ketamine is thought to act via NMDA receptors and HCN1 channels to produce brain oscillations that are related to these effects. Using human intracranial recordings, we found that ketamine produces gamma oscillations in prefrontal cortex and hippocampus, structures previously implicated in ketamine's antidepressant effects, and a 3 Hz oscillation in posteromedial cortex, previously proposed as a mechanism for its dissociative effects.

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