Jennifer R. Ramautar

Individual Differences in White Matter Diffusion Affect Sleep Oscillations

The characteristic oscillations of the sleeping brain, spindles and slow waves, show trait-like, within-subject stability and a remarkable interindividual variability that correlates with functionally relevant measures such as memory performance and intelligence. Yet, the mechanisms underlying these interindividual differences are largely unknown. Spindles and slow waves are affected by the recent history of learning and neuronal activation, indicating sensitivity to changes in synaptic strength and thus to the connectivity of the neuronal network. Because the structural backbone of this network is formed by white matter tracts, we hypothesized that individual differences in spindles and slow waves depend on the white matter microstructure across a distributed network. We recorded both diffusion-weighted magnetic resonance images and whole-night, high-density electroencephalography and investigated whether individual differences in sleep spindle and slow wave parameters were associated with diffusion tensor imaging metrics; white matter fractional anisotropy and axial diffusivity were quantified using tract-based spatial statistics. Individuals with higher spindle power had higher axial diffusivity in the forceps minor, the anterior corpus callosum, fascicles in the temporal lobe, and the tracts within and surrounding the thalamus. Individuals with a steeper rising slope of the slow wave had higher axial diffusivity in the temporal fascicle and frontally located white matter tracts (forceps minor, anterior corpus callosum). These results indicate that the profiles of sleep oscillations reflect not only the dynamics of the neuronal network at the synaptic level, but also the localized microstructural properties of its structural backbone, the white matter tracts.

Do sleep complaints contribute to age-related cognitive decline?

The cognitive changes that occur with ageing are usually referred to as age-related cognitive decline. The most pronounced changes may be found in the executive functions that require integrity of the prefrontal cortical circuitry. With age, sleep also changes profoundly, with more sleep fragmentation, earlier awakenings and less slow wave sleep as its main features. Interestingly, experimental sleep deprivation studies in healthy young adults showed a particularly consistent effect on executive functions, suggesting that sleep problems might contribute to the cognitive changes accompanying older age. We here investigate this possibility by reviewing reports on age-related and insomnia-related changes in cognition and brain function and structure, as found in studies investigating subjective complaints, objective functioning in everyday life, neuropsychological assessment, psychometry, structural and functional magnetic resonance imaging, electroencephalography, positron emission tomography and transcranial magnetic stimulation. The chapter focuses on the normal age-related sleep changes that are experienced as insomnia - that is, fragmentation of sleep, more superficial sleep, more wake after sleep onset and earlier awakenings - rather than on specific sleep disturbances as sleep-disordered breathing, restless legs or periodic limb movements during sleep, for all of which the risk increases with age. It turned out that relatively few studies directly addressed the question whether elderly with different degrees of sleep complaints are differentially affected by age-related cognitive decline. Still, several similarities between age-related and insomnia-related cognitive and brain changes are apparent, notably with respect to performance requiring integrity of the prefrontal cortical system. We suggest that at least part of what we regard as age-related changes may, in fact, be due to poor sleep, which is in some cases a treatable condition. Further research directly comparing aged good sleepers versus aged insomniacs will need to elucidate how sleep disturbances are involved in the cognitive, structural and functional changes observed with increasing age. The findings suggest that discrimination of subtypes of poor sleep at high age will aid in understanding the mechanisms by which it affects cognition and brain function.

Carbon-wire loop based artifact correction outperforms post-processing EEG/fMRI corrections--A validation of a real-time simultaneous EEG/fMRI correction method.

Simultaneous EEG-fMRI combines two powerful neuroimaging techniques, but the EEG signal suffers from severe artifacts in the MRI environment that are difficult to remove. These are the MR scanning artifact and the blood-pulsation artifact--strategies to remove them are a topic of ongoing research. Additionally large, unsystematic artifacts are produced across the full frequency spectrum by the magnets helium pump (and ventilator) systems which are notoriously hard to remove. As a consequence, experimenters routinely deactivate the helium pump during simultaneous EEG-fMRI acquisitions which potentially risks damaging the MRI system and necessitates more frequent and expensive helium refills. We present a novel correction method addressing both helium pump and ballisto-cardiac (BCG) artifacts, consisting of carbon-wire loops (CWL) as additional sensors to accurately track unpredictable artifacts related to subtle movements in the scanner, and an EEGLAB plugin to perform artifact correction. We compare signal-to-noise metrics of EEG data, corrected with CWL and three conventional correction methods, for helium pump off and on measurements. Because the CWL setup records signals in real-time, it fits requirements of applications where immediate correction is necessary, such as neuro-feedback applications or stimulation time-locked to specific sleep oscillations. The comparison metrics in this paper relate to: (1) the EEG signal itself, (2) the eyes open vs. eyes closed effect, and (3) an assessment of how the artifact corrections impacts the ability to perform meaningful correlations between EEG alpha power and the BOLD signal. Results show that the CWL correction corrects for He pump artifact and also produces EEG data more comparable to EEG obtained outside the magnet than conventional post-processing methods.

Cognitive Control and Individual Differences in Economic Ultimatum Decision-Making

Much publicity has been given to the fact that peoples economic decisions often deviate from the rational predictions of standard economic models. In the classic ultimatum game, for example, most people turn down financial gains by rejecting unequal monetary splits. The present study points to neglected individual differences in this debate. After participants played the ultimatum game we tested for individual differences in cognitive control capacity of the most and least economic responders. The key finding was that people who were higher in cognitive control, as measured by behavioral (Go/No-Go performance) and neural (No-Go N2 amplitude) markers, did tend to behave more in line with the standard models and showed increased acceptance of unequal splits. Hence, the cognitively highest scoring decision-makers were more likely to maximize their monetary payoffs and adhere to the standard economic predictions. Findings question popular claims with respect to the rejection of standard economic models and the irrationality of human economic decision-making.

I Keep a Close Watch on This Heart of Mine: Increased Interoception in Insomnia.

STUDY OBJECTIVESnWhereas both insomnia and altered interoception are core symptoms in affective disorders, their neural mechanisms remain insufficiently understood and have not previously been linked. Insomnia Disorder (ID) is characterized by sensory hypersensitivity during wakefulness and sleep. Previous studies on sensory processing in ID addressed external stimuli only, but not interoception. Interoceptive sensitivity can be studied quantitatively by measuring the cerebral cortical response to ones heartbeat (heartbeat-evoked potential, HEP). We here investigated whether insomnia is associated with increased interoceptive sensitivity as indexed by the HEP amplitude.nnnMETHODSnSixty-four participants aged 21-70 years were recruited through www.sleepregistry.nl including 32 people suffering from ID and 32 age- and sex-matched controls without sleep complaints. HEPs were obtained from resting-state high-density electroencephalography (HD-EEG) recorded during evening wakeful rest in eyes-open (EO) and eyes-closed (EC) conditions of 5-minute duration each. Significance of group differences in HEP amplitude and their topographical distribution over the scalp were assessed by means of cluster-based permutation tests.nnnRESULTSnIn particular during EC, and to a lesser extent during EO, people with ID had a larger amplitude late HEP component than controls at frontal electrodes 376-500 ms after the R-wave peak. Source localization suggested increased neural activity time-locked to heartbeats in people with ID mainly in anterior cingulate/medial frontal cortices.nnnCONCLUSIONSnPeople with insomnia show insufficient adaptation of their brain responses to the ever-present heartbeats. Abnormalities in the neural circuits involved in interoceptive awareness including the salience network may be of key importance to the pathophysiology of insomnia.

Wake High-Density Electroencephalographic Spatiospectral Signatures of Insomnia.

STUDY OBJECTIVESnAlthough daytime complaints are a defining characteristic of insomnia, most EEG studies evaluated sleep only. We used high-density electroencephalography to investigate wake resting state oscillations characteristic of insomnia disorder (ID) at a fine-grained spatiospectral resolution.nnnMETHODSnA case-control assessment during eyes open (EO) and eyes closed (EC) was performed in a laboratory for human physiology. Participants (n = 94, 74 female, 21-70 y) were recruited through www.sleepregistry.nl: 51 with ID, according to DSM-5 and 43 matched controls. Exclusion criteria were any somatic, neurological or psychiatric condition. Group differences in the spectral power topographies across multiple frequencies (1.5 to 40 Hz) were evaluated using permutation-based inference with Threshold-Free Cluster-Enhancement, to correct for multiple comparisons.nnnRESULTSnAs compared to controls, participants with ID showed less power in a narrow upper alpha band (11-12.7 Hz, peak: 11.7 Hz) over bilateral frontal and left temporal regions during EO, and more power in a broad beta frequency range (16.3-40 Hz, peak: 19 Hz) globally during EC. Source estimates suggested global rather than cortically localized group differences.nnnCONCLUSIONSnThe widespread high power in a broad beta band reported previously during sleep in insomnia is present as well during eyes closed wakefulness, suggestive of a round-the-clock hyperarousal. Low power in the upper alpha band during eyes open is consistent with low cortical inhibition and attentional filtering. The fine-grained HD-EEG findings suggest that, while more feasible than PSG, wake EEG of short duration with a few well-chosen electrodes and frequency bands, can provide valuable features of insomnia.

More Severe Insomnia Complaints in People with Stronger Long-Range Temporal Correlations in Wake Resting-State EEG

The complaints of people suffering from Insomnia Disorder (ID) concern both sleep and daytime functioning. However, little is known about wake brain temporal dynamics in people with ID. We therefore assessed possible alterations in Long-Range Temporal Correlations (LRTC) in the amplitude fluctuations of band-filtered oscillations in electroencephalography (EEG) recordings. We investigated whether LRTC differ between cases with ID and matched controls. Within both groups, we moreover investigated whether individual differences in subjective insomnia complaints are associated with LRTC. Resting-state high-density EEG (256-channel) was recorded in 52 participants with ID and 43 age- and sex-matched controls, during Eyes Open (EO) and Eyes Closed (EC). Detrended fluctuation analysis was applied to the amplitude envelope of band-filtered EEG oscillations (theta, alpha, sigma, beta-1, beta-2) to obtain the Hurst exponents (H), as measures of LRTC. Participants rated their subjective insomnia complaints using the Insomnia Severity Index (ISI). Through general linear models, we evaluated whether H, aggregated across electrodes and frequencies, differed between cases and controls, or showed within-group associations with individual differences in ISI. Additionally, we characterized the spatio-spectral profiles of group differences and associations using non-parametric statistics. H did not differ between cases with ID and controls in any of the frequency bands, neither during EO nor EC. During EO, however, within-group associations between H and ISI indicated that individuals who experienced worse sleep quality had stronger LRTC. Spatio-spectral profiles indicated that the associations held most prominently for the amplitude fluctuations of parietal theta oscillations within the ID group, and of centro-frontal beta-1 oscillations in controls. While people suffering from insomnia experience substantially worse sleep quality than controls, their brain dynamics express similar strength of LRTC. In each group, however, individuals experiencing worse sleep quality tend to have stronger LRTC during eyes open wakefulness, in a spatio-spectral range specific for each group. Taken together, the findings indicate that subjective insomnia complaints involve distinct dynamical processes in people with ID and controls. The findings are in agreement with recent reports on decreasing LRTC with sleep depth, and with the hypothesis that sleep balances brain excitability.

Coupling of infraslow fluctuations in autonomic and central vigilance markers: Skin temperature, EEG beta power and ERP P300 latency

Even under thermoneutral conditions, skin temperature fluctuates spontaneously, most prominently at distal parts of the body. These fluctuations were shown to be associated with fluctuations in vigilance: mild manipulation of skin temperature during nocturnal sleep affects sleep depth and the power spectral density of the electroencephalogram (EEG), and fluctuations in skin temperature during daytime wakefulness are related to sleep propensity and task performance. The association of daytime skin temperature fluctuations with EEG markers of vigilance has not previously been investigated. Therefore, the present study aimed to evaluate the association between daytime fluctuations in skin temperature with those in two quantitative EEG measures: the power spectral density of background EEG, and the event related potential (ERP) elicited by visual stimuli. High-density EEG and skin temperature were obtained in eight healthy adults five times a day while they performed a visual sustained-attention task. Assessments were made after a night of normal sleep and after the challenge of a night of total sleep deprivation. Fluctuations in the distal-to-proximal skin temperature gradient measured from the earlobe and mastoid were associated with fluctuations in parieto-occipital high beta band (20-40 Hz) power of the pre-stimulus background EEG, but only after sleep deprivation. The temperature fluctuations were moreover associated with fluctuations in the latency of the P300 elicited by the stimulus. The findings demonstrate close association between fluctuations in an autonomic correlate of the vigilance state (i.e. the distal-to-proximal skin temperature gradient), and fluctuations in central nervous system correlates of the vigilance state (i.e. background EEG and ERP). The findings are of theoretical and practical relevance for the assessment and manipulation of vigilance.

Increased hippocampal-prefrontal functional connectivity in insomnia

HighlightsHigh hippocampal functional connectivity with left middle frontal gyrus in insomnia.Insomnia severity increases with strength of hippocampal‐MFG connectivity.Sleep efficiency decreases with strength of hippocampal‐MFG connectivity.No differences in hippocampal volume between people with insomnia and controls. Abstract Insomnia Disorder (ID) is the second‐most common mental disorder and has a far‐reaching impact on daytime functioning. A meta‐analysis indicates that, of all cognitive domains, declarative memory involving the hippocampus is most affected in insomnia. Hippocampal functioning has consistently been shown to be sensitive to experimental sleep deprivation. Insomnia however differs from sleep deprivation in many aspects, and findings on hippocampal structure and function have been equivocal. The present study used both structural and resting‐state functional Magnetic Resonance Imaging in a larger sample than previously reported to evaluate hippocampal volume and functional connectivity in ID. Included were 65 ID patients (mean age = 48.3 y ± 14.0, 17 males) and 65 good sleepers (mean age = 44.1 y ± 15.2, 23 males). Insomnia severity was assessed with the Insomnia Severity Index (ISI), subjective sleep with the Consensus Sleep Diary (CSD) and objective sleep by two nights of polysomnography (PSG). Seed‐based analysis showed a significantly stronger connectivity of the bilateral hippocampus with the left middle frontal gyrus in ID than in controls (p = .035, cluster based correction for multiple comparisons). Further analyses across all participants moreover showed that individual differences in the strength of this connectivity were associated with insomnia severity (ISI, r = 0.371, p = 9.3e−5) and with subjective sleep quality (CSD sleep efficiency, r = −0.307, p = .009) (all p FDR‐corrected). Hippocampal volume did not differ between ID and controls. The findings indicate more severe insomnia and worse sleep quality in people with a stronger functional connectivity between the bilateral hippocampus and the left middle frontal gyrus, part of a circuit that characteristically activates with maladaptive rumination and deactivates with sleep.

“Eyes open – Eyes closed” EEG/fMRI data set including dedicated “carbon wire loop” motion detection channels

This data set contains electroencephalography (EEG) data as well as simultaneous EEG with functional magnetic resonance imaging (EEG/fMRI) data. During EEG/fMRI, the EEG cap was outfitted with a hardware-based add-on consisting of carbon-wire loops (CWL). These yielded six extra׳CWL׳ signals related to Faraday induction of these loops in the main magnetic field “Measurement and reduction of motion and ballistocardiogram artefacts from simultaneous EEG and fMRI recordings” (Masterton et al., 2007) [1]. In this data set, the CWL data make it possible to do a direct regression approach to deal with the BCG and specifically He artifact. The CWL-EEG/fMRI data in this paper has been recorded on two MRI scanners with different Helium pump systems (4 subjects on a 3 T TIM Trio and 4 subjects on a 3T VERIO). Separate EEG/fMRI data sets have been recorded for the helium pump ON as well as the helium pump OFF conditions. The EEG-only data (same subjects) has been recorded for a motion artifact-free reference EEG signal outside of the scanner. This paper also links to an EEGlab “EEGLAB: an open source toolbox for analysis of single-trial EEG dynamics including independent component analysis” (Delorme and Makeig, 2004) [2] plugin to perform a CWL regression approach to deal with the He pump artifact, as published in the main paper “Carbon-wire loop based artifact correction outperforms post-processing EEG/fMRI corrections-A validation of a real-time simultaneous EEG/fMRI correction method” (van der Meer et al., 2016) [3].