Spectral exponent assessment and neurofilament light chain: a comprehensive approach to describe recovery patterns in stroke.

Introduction: Understanding the residual recovery potential in stroke patients is crucial for tailoring effective neurorehabilitation programs. We propose using EEG and plasmatic Neurofilament light chain (NfL) levels as a model to depict longitudinal patterns of stroke recovery. Methods: We enrolled 13 patients (4 female, mean age 74.7 ± 8.8) who underwent stroke in the previous month and were hospitalized for 2-months rehabilitation. Patients underwent blood withdrawal, clinical evaluation and high-definition EEG at T1 (first week of rehabilitation) and at T2 (53 ± 10 days after). We assessed the levels of NfL and we analyzed the EEG signal extracting Spectral Exponent (SE) values. We compared our variables between the two timepoint and between cortical and non-cortical strokes. Results: We found a significant difference in the symmetry of SE values between cortical and non-cortical stroke at both T1 (p = 0.005) and T2 (p = 0.01). SE in the affected hemisphere showed significantly steeper values at T1 when compared with T2 (p = 0.001). EEG measures were consistently related to clinical scores, while NfL at T1 was related to the volume of ischemic lesions (r = 0.75; p = 0.003). Additionally, the combined use of NfL and SE indicated varying trends in longitudinal clinical recovery. Conclusion: We present proof of concept of a promising approach for the characterization of different recovery patterns in stroke patients.

EEG Microstates Indicate Heightened Somatic Awareness in Insomnia: Toward Objective Assessment of Subjective Mental Content.

People with Insomnia Disorder (ID) not only experience abundant nocturnal mentation, but also report altered spontaneous mental content during daytime wakefulness, such as an increase in bodily experiences (heightened somatic awareness). Previous studies have shown that resting-state EEG can be temporally partitioned into quasi-stable microstates, and that these microstates form a small number of canonical classes that are consistent across people. Furthermore, the microstate classes have been associated with individual differences in resting mental content including somatic awareness. To address the hypothesis that altered resting mental content in ID would be reflected in an altered representation of the corresponding EEG microstates, we analyzed resting-state high-density EEG of 32 people with ID and 32 age- and sex-matched controls assessed during 5-min eyes-closed wakefulness. Using data-driven topographical k-means clustering, we found that 5 microstate classes optimally explained the EEG scalp voltage map sequences across participants. For each microstate class, 3 dynamic features were obtained: mean duration, frequency of occurrence, and proportional coverage time. People with ID had a shorter mean duration of class C microstates, and more frequent occurrence of class D microstates. The finding is consistent with previously established associations of these microstate properties with somatic awareness, and increased somatic awareness in ID. EEG microstate assessment could provide objective markers of subjective experience dimensions in studies on consciousness during the transition between wake and sleep, when self-report is not possible because it would interfere with the very process under study. Addressing somatic awareness may benefit psychotherapeutic treatment of insomnia.

Sleep Stage Transition Dynamics Reveal Specific Stage 2 Vulnerability in Insomnia.

Study Objectives: Objective sleep impairments in insomnia disorder (ID) are insufficiently understood. The present study evaluated whether whole-night sleep stage dynamics derived from polysomnography (PSG) differ between people with ID and matched controls and whether sleep stage dynamic features discriminate them better than conventional sleep parameters. Methods: Eighty-eight participants aged 21-70 years, including 46 with ID and 42 age- and sex-matched controls without sleep complaints, were recruited through www.sleepregistry.nl and completed two nights of laboratory PSG. Data of 100 people with ID and 100 age- and sex-matched controls from a previously reported study were used to validate the generalizability of findings. The second night was used to obtain, in addition to conventional sleep parameters, probabilities of transitions between stages and bout duration distributions of each stage. Group differences were evaluated with nonparametric tests. Results: People with ID showed higher empirical probabilities to transition from stage N2 to the lighter sleep stage N1 or wakefulness and a faster decaying stage N2 bout survival function. The increased transition probability from stage N2 to stage N1 discriminated people with ID better than any of their deviations in conventional sleep parameters, including less total sleep time, less sleep efficiency, more stage N1, and more wake after sleep onset. Moreover, adding this transition probability significantly improved the discriminating power of a multiple logistic regression model based on conventional sleep parameters. Conclusions: Quantification of sleep stage dynamics revealed a particular vulnerability of stage N2 in insomnia. The feature characterizes insomnia better than-and independently of-any conventional sleep parameter.

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.

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

STUDY OBJECTIVES: Whereas 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 one's heartbeat (heartbeat-evoked potential, HEP). We here investigated whether insomnia is associated with increased interoceptive sensitivity as indexed by the HEP amplitude. METHODS: Sixty-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. RESULTS: In 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. CONCLUSIONS: People 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 OBJECTIVES: Although 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. METHODS: A 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. RESULTS: As 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. CONCLUSIONS: The 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.