Resting State Network Dynamics Across Wakefulness and Sleep

The function of sleep is a longstanding mystery of the brain. By contrast, the function of resting state networks (RSNs) is one of its most recent mysteries. The relationship between RSNs and neuronal activity has been unclear since RSNs were discovered during the advent of functional magnetic resonance imaging (fMRI). Somewhat paradoxically, investigating these enigmatic phenomena in parallel can help to illuminate the function of both. The three studies described as part of this thesis all involve an evaluation of RSN dynamics across wakefulness and sleep. They are all based on the same dataset, derived from an experimental paradigm in which healthy, non sleep-deprived participants (N=36, 21 female) slept in an MRI scanner, as their brain activity was recorded using simultaneous electroencephalography (EEG)-fMRI. An independent component analysis (ICA) was performed in the first study. Spatial boundaries of components in each sleep stage were compared with those of wakefulness, in the first attempt to catalogue RSNs across all healthy alternate functional modes of the brain. Against expectations, all non-wake-RSN components were positively identified as noise. This indicated that sleep is supported by much the same RSN architecture as wakefulness, despite the unique operations performed during sleep. In the second study, between-RSN functional connectivity (FC) dynamics were evaluated across wakefulness and sleep, in order to determine whether they reflect known cortical neurophysiological dynamics. This was confirmed, highlighting the connection between RSNs and neuronal activity. Moreover, the dynamic pattern suggested that one of the functions of sleep may be to homeostatically counterbalance wakefulness RSN FC. A further pattern, indicating increased FC of “higher-order” RSNs (e.g., default mode network), suggested that slow wave sleep might manifest an altered, rather than a reduced state of awareness, in contrast to historical depictions. Finally, the third study correlated frequency-banded oscillatory activity, as measured by EEG, with RSN activity, as measured with fMRI. This was done in order to track changes in representations of frequency-banded neuronal activity in each RSN across stages. It was discovered that the pattern of frequency band representation dynamics reflects the aforementioned cortical neurophysiological dynamics, further strengthening the connection between RSNs and neuronal activity

The relationship between cognitive ability and BOLD activation across sleep–wake states

The sleep spindle, a waxing and waning oscillation in the sigma frequency range, has been shown to correlate with fluid intelligence; i.e. the ability to use logic, learn novel rules/patterns, and solve problems. Using simultaneous EEG and fMRI, we previously identified the neural correlates of this relationship, including activation of the thalamus, bilateral putamen, medial frontal gyrus, middle cingulate cortex, and precuneus. However, research to date has focussed primarily on non-rapid eye movement (NREM) sleep, and spindles per se, thus overlooking the possibility that brain activity that occurs in other sleep–wake states might also be related to cognitive abilities. In our current study, we sought to investigate whether brain activity across sleep/wake states is also related to human intelligence in N = 29 participants. During NREM sleep, positive correlations were observed between fluid intelligence and blood oxygen level dependent (BOLD) activations in the bilateral putamen and the paracentral lobule/precuneus, as well as between short-term memory (STM) abilities and activity in the medial frontal cortex and inferior frontal gyrus. During wake, activity in bilateral postcentral gyri and occipital lobe was positively correlated with short-term memory abilities. In participants who experienced REM sleep in the scanner, fluid intelligence was positively associated with midbrain activation, and verbal intelligence was associated with right postcentral gyrus activation. These findings provide evidence that the relationship between sleep and intellectual abilities exists beyond sleep spindles

Reversed and increased functional connectivity in non-REM sleep suggests an altered rather than reduced state of consciousness relative to wake

Sleep resting state network (RSN) functional connectivity (FC) is poorly understood, particularly for rapid eye movement (REM), and in non-sleep deprived subjects. REM and non-REM (NREM) sleep involve competing drives; towards hypersynchronous cortical oscillations in NREM; and towards wake-like desynchronized oscillations in REM. This study employed simultaneous electroencephalography-functional magnetic resonance imaging (EEG-fMRI) to explore whether sleep RSN FC reflects these opposing drives. As hypothesized, this was confirmed for the majority of functional connections modulated by sleep. Further, changes were directional: e.g., positive wake correlations trended towards negative correlations in NREM and back towards positive correlations in REM. Moreover, the majority did not merely reduce magnitude, but actually either reversed and strengthened in the opposite direction, or increased in magnitude during NREM. This finding supports the notion that NREM is best expressed as having altered, rather than reduced FC. Further, as many of these functional connections comprised “higher-order” RSNs (which have been previously linked to cognition and consciousness), such as the default mode network, this finding is suggestive of possibly concomitant alterations to cognition and consciousness

Functional diversity of brain networks supports consciousness and verbal intelligence

© 2018, The Author(s). How are the myriad stimuli arriving at our senses transformed into conscious thought? To address this question, in a series of studies, we asked whether a common mechanism underlies loss of information processing in unconscious states across different conditions, which could shed light on the brain mechanisms of conscious cognition. With a novel approach, we brought together for the first time, data from the same paradigm—a highly engaging auditory-only narrative—in three independent domains: anesthesia-induced unconsciousness, unconsciousness after brain injury, and individual differences in intellectual abilities during conscious cognition. During external stimulation in the unconscious state, the functional differentiation between the auditory and fronto-parietal systems decreased significantly relatively to the conscious state. Conversely, we found that stronger functional differentiation between these systems in response to external stimulation predicted higher intellectual abilities during conscious cognition, in particular higher verbal acuity scores in independent cognitive testing battery. These convergent findings suggest that the responsivity of sensory and higher-order brain systems to external stimulation, especially through the diversification of their functional responses is an essential feature of conscious cognition and verbal intelligence

Behavioral, Functional Imaging, and Neurophysiological Outcomes of Transcranial Direct Current Stimulation and Speech-Language Therapy in an Individual with Aphasia

Speech-language therapy (SLT) is the most effective technique to improve language performance in persons with aphasia. However, residual language impairments remain even after intensive SLT. Recent studies suggest that combining transcranial direct current stimulation (tDCS) with SLT may improve language performance in persons with aphasia. However, our understanding of how tDCS and SLT impact brain and behavioral relation in aphasia is poorly understood. We investigated the impact of tDCS and SLT on a behavioral measure of scripted conversation and on functional connectivity assessed with multiple methods, both resting-state functional magnetic resonance imaging (rs–fMRI) and resting-state electroencephalography (rs–EEG). An individual with aphasia received 15 sessions of 20-min cathodal tDCS to the right angular gyrus concurrent with 40 min of SLT. Performance during scripted conversation was measured three times at baseline, twice immediately post-treatment, and at 4- and 8-weeks post-treatment. rs–fMRI was measured pre-and post-3-weeks of treatment. rs–EEG was measured on treatment days 1, 5, 10, and 15. Results show that both communication performance and left hemisphere functional connectivity may improve after concurrent tDCS and SLT. Results are in line with aphasia models of language recovery that posit a beneficial role of left hemisphere perilesional areas in language recovery

Sleep spindle-dependent functional connectivity correlates with cognitive abilities

© 2019 Massachusetts Institute of Technology. EEG studies have shown that interindividual differences in the electrophysiological properties of sleep spindles (e.g., density, amplitude, duration) are highly correlated with trait-like “reasoning” abilities (i.e., “fluid intelligence”; problem-solving skills; the ability to employ logic or identify complex patterns), but not interindividual differences in STM or “verbal” intellectual abilities. Previous simultaneous EEG-fMRI studies revealed brain activations time-locked to spindles. Our group has recently demonstrated that the extent of activation in a subset of these regions was related to interindividual differences in reasoning intellectual abilities, specifically. However, spindles reflect communication between spatially distant and functionally distinct brain areas. The functional communication among brain regions related to spindles and their relationship to reasoning abilities have yet to be investigated. Using simultaneous EEG-fMRI sleep recordings and psychophysiological interaction analysis, we identified spindle-related functional communication among brain regions in the thalamo-cortical-BG system, the salience network, and the default mode network. Furthermore, the extent of the functional connectivity of the cortical–striatal circuitry and the thalamo-cortical circuitry was specifically related to reasoning abilities but was unrelated to STM or verbal abilities, thus suggesting that individuals with higher fluid intelligence have stronger functional coupling among these brain areas during spontaneous spindle events. This may serve as a first step in further understanding the function of sleep spindles and the brain network functional communication, which support the capacity for fluid intelligence