An electrophysiological marker of arousal level in humans

Abstract:

Deep non-rapid eye movement sleep (NREM) and general anesthesia with propofol are prominent states of reduced arousal linked to the occurrence of synchronized oscillations in the electroencephalogram (EEG). Although rapid eye movement (REM) sleep is also associated with diminished arousal levels, it is characterized by a desynchronized, ‘wake-like’ EEG. This observation implies that reduced arousal states are not necessarily only defined by synchronous oscillatory activity. Using intracranial and surface EEG recordings in four independent data sets, we demonstrate that the 1/f spectral slope of the electrophysiological power spectrum, which reflects the non-oscillatory, scale-free component of neural activity, delineates wakefulness from propofol anesthesia, NREM and REM sleep. Critically, the spectral slope discriminates wakefulness from REM sleep solely based on the neurophysiological brain state. Taken together, our findings describe a common electrophysiological marker that tracks states of reduced arousal, including different sleep stages as well as anesthesia in humans.

Authors:

• Janna D Lendner

• Randolph F Helfrich

• Bryce A Mander

• Luis Romundstad

• Jack J Lin

• Matthew P Walker

• Pal G Larsson

• Robert T Knight

Date: 2020

DOI: https://doi.org/10.7554/eLife.55092

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Coupling between slow-waves and sharp-wave ripples organizes distributed neural activity during sleep in humans

Abstract:

Hippocampal-dependent memory consolidation during sleep is hypothesized to depend on the synchronization of distributed neuronal ensembles, organized by the hippocampal sharp-wave ripples (SWRs, 80-150 Hz) and subcortical/cortical slow-waves (0.5-4 Hz). However, the precise role of SWR-slow-wave interactions in synchronizing subcortical/cortical neuronal activity is unclear. Here, we leverage intracranial electrophysiological recordings from the human hippocampus, amygdala, temporal and frontal cortices, to examine activity modulation and cross-regional coordination during SWRs. Hippocampal SWRs are associated with widespread modulation of high frequency activity (HFA; 70-200 Hz) a measure of local neuronal activation. This peri-SWR HFA modulation is predicted by the coupling between hippocampal SWRs and local subcortical/cortical slow-waves. Finally, local cortical slow-wave phase offsets during SWRs predicted functional connectivity between the frontal and temporal cortex. These findings suggest a selection mechanism wherein hippocampal SWR and cortical slow-wave synchronization governs the transient engagement of distributed neuronal populations supporting hippocampal-dependent memory consolidation.

Authors:

• Ivan Skelin

• Haoxin Zhang

• Jie Zheng

• Shiting Ma

• Bryce A Mander

• Olivia Kim Mcmanus

• Sumeet Vadera

• Robert T Knight

• Bruce L McNaughton

• Jack J Lin

Date: 2020

DOI: https://doi.org/10.1101/2020.05.24.113480

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Bidirectional prefrontal-hippocampal dynamics organize information transfer during sleep in humans

Abstract:

How are memories transferred from short-term to long-term storage? Systems-level memory consolidation is thought to be dependent on the coordinated interplay of cortical slow waves, thalamo-cortical sleep spindles and hippocampal ripple oscillations. However, it is currently unclear how the selective interaction of these cardinal sleep oscillations is organized to support information reactivation and transfer. Here, using human intracranial recordings, we demonstrate that the prefrontal cortex plays a key role in organizing the ripple-mediated information transfer during non-rapid eye movement (NREM) sleep. We reveal a temporally precise form of coupling between prefrontal slow-wave and spindle oscillations, which actively dictates the hippocampal-neocortical dialogue and information transfer. Our results suggest a model of the human sleeping brain in which rapid bidirectional interactions, triggered by the prefrontal cortex, mediate hippocampal activation to optimally time subsequent information transfer to the neocortex during NREM sleep.

Authors:

• Randolph F Helfrich

• Janna D Lendner

• Bryce A Mander

• Heriberto Guillen

• Michelle Paff

• Lilit Mnatsakanyan

• Sumeet Vadera

• Matthew P Walker

• Jack J Lin

• Robert T Knight

Date: 2019

DOI: https://doi.org/10.1038/s41467-019-11444-x

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Sleep as a potential biomarker of tau and β-amyloid burden in the human brain

Abstract:

Recent proposals suggest that sleep may be a factor associated with accumulation of two core pathological features of Alzheimer's disease (AD): tau and β-amyloid (Aβ). Here we combined PET measures of Aβ and tau, electroencephalogram sleep recordings, and retrospective sleep evaluations to investigate the potential utility of sleep measures in predicting in vivo AD pathology in male and female older adults. Regression analyses revealed that the severity of impaired slow oscillation-sleep spindle coupling predicted greater medial temporal lobe tau burden. Aβ burden was not associated with coupling impairment but instead predicted the diminished amplitude of <1 Hz slow-wave-activity, results that were statistically dissociable from each other. Additionally, comparisons of AD pathology and retrospective, self-reported changes in sleep duration demonstrated that changes in sleep across the lifespan can predict late-life Aβ and tau burden. Thus, quantitative and qualitative features of human sleep represent potential noninvasive, cost-effective, and scalable biomarkers (current and future forecasting) of AD pathology, and carry both therapeutic and public health implications.

Authors:

• Joseph R Winer

• Bryce A Mander

• Randolph F Helfrich

• Anne Maass

• Theresa M Harrison

• Suzanne L Baker

• Robert T Knight

• William J Jagust

• Matthew P Walker

Date: 2019

DOI: https://doi.org/10.1523/JNEUROSCI.0503-19.2019

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