Microstates in resting-state EEG: Current status and future directions

Electroencephalography (EEG) is a powerful method of studying the electrophysiology of the brain with high temporal resolution. Several analytical approaches to extract information from the EEG signal have been proposed. One method, termed microstate analysis, considers the multichannel EEG recording as a series of quasi-stable “microstates” that are each characterized by a unique topography of electric potentials over the entire channel array. Because this technique simultaneously considers signals recorded from all areas of the cortex, it is capable of assessing the function of large-scale brain networks whose disruption is associated with several neuropsychiatric disorders. In this review, we first introduce the method of EEG microstate analysis. We then review studies that have discovered significant changes in the resting-state microstate series in a variety of neuropsychiatric disorders and behavioral states. We discuss the potential utility of this method in detecting neurophysiological impairments in disease and monitoring neurophysiological changes in response to an intervention. Finally, we discuss how the resting-state microstate series may reflect rapid switching among neural networks while the brain is at rest, which could represent activity of resting-state networks described by other neuroimaging modalities. We conclude by commenting on the current and future status of microstate analysis, and suggest that EEG microstates represent a promising neurophysiological tool for understanding and assessing brain network dynamics on a millisecond timescale in health and disease.     

全部睡眠剥夺对健康男性青年脑电功率谱的影响

目的 探讨全部睡眠剥夺对健康男性青年脑电功率谱的影响。方法 选身体健康男性青年（１９￣２２岁）自愿受试者２０名,剥夺全部睡眠５０ｈ,定时记录脑电图共８次（间隔６ｈ）,分析各脑区各频段脑电功率。结果 睡眠剥夺５０ｈ后所有脑区（双侧枕区除外）的δ频段（Ｐ〈０．０５￣Ｐ〈０．００１）、θ频段（Ｐ〈０．０１￣Ｐ〈０．００１）功率升高,α２频段功率降低（Ｐ〈０．００１）,并与睡眠剥夺时间呈线性相关（Ｐ〈０．０１￣Ｐ〈０．００１）。例如,Ｆ３区δ、θ和α２频段脑电功率在睡眠剥夺前后分别为３．７８、４．１７;３．６５、４．３４;４．６４和３．９１ｌｎ（μＶ＾２）。脑电功率出现显著变化的时间由早以晚依次为α２频段、θ频段和δ频段。额前区、中央区、顶区和颞中区的改变较早,左半球比右半球早。脑电功率具有显著的随时间变化现象。快波频     

Inter-hemispheric functional coupling of eyes-closed resting EEG rhythms in adolescents with Down syndrome

ObjectiveWe tested the hypothesis that inter-hemispheric directional functional coupling of eyes-closed resting EEG rhythms is abnormal in adolescents with Down syndrome (DS).MethodsEyes-closed resting EEG data were recorded in 38 DS adolescents (18.7 years ±0.67 SE, IQ = 49 ± 1.9 SE) and in 17 matched normal control subjects (NYoung = 19.1 years ±0.39 SE). The EEG data were recorded from 8 electrodes (Fp1, Fp2, C3, C4, T3, T4, O1, O2) referenced to vertex. EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). Power of EEG rhythms was evaluated by FFT for control purposes, whereas inter-hemispheric directional EEG functional coupling was computed by directed transfer function (DTF).ResultsAs expected, alpha, beta, and gamma power was widely higher in NYoung than DS subjects, whereas the opposite was true for delta power. As a novelty, DTF (directionality) values globally prevailed from right to left occipital areas in NYoung subjects and in the opposite direction in DS patients. A control experiment showed that this DTF difference could not be observed in the comparison between DS adults with mild cognitive impairment and normal age-matched adults.ConclusionsThese results indicate a peculiar abnormal directional inter-hemispheric interplay in visual occipital areas of DS adolescents.SignificanceDirection of inter-hemispheric EEG functional coupling unveils a new abnormal brain network feature in DS adolescents.     

GABA and cortical inhibition in motor and non-motor regions using combined TMS–EEG: A time analysis

ObjectiveThe induction of long interval cortical inhibition (LICI) in motor cortex with paired pulse transcranial magnetic stimulation (ppTMS) is an established paradigm for the assessment of cortical inhibition, proposed to be related to GABA_B receptor inhibitory neurotransmission. This study aimed to further evaluate recent methods of the assessment of LICI in non motor regions with ppTMS and electroencephalography (EEG).MethodsppTMS was applied using a single coil to the motor and dorsolateral prefrontal cortex (DLPFC) in 14 healthy subjects, and in the parietal lobe in 5 of those subjects.ResultsIn the motor cortex, LICI resulted in significant suppression in mean cortical evoked activity on EEG between 75 and 250 ms following delivery of the test stimulus. Maximal inhibition was seen from 50 to 250 ms in DLPFC, and between 50 and 175 ms in the parietal lobe.ConclusionsppTMS may be used to produce LICI in several cortical regions with a time course similar to known GABA_B activity.SignificanceppTMS induction of LICI can be recorded by combining TMS with EEG and seems to relate to GABA_B activity.     

The implication of functional connectivity strength in predicting treatment response of major depressive disorder: A resting EEG study

Predicting treatment response in major depressive disorder (MDD) has been an important clinical issue given that the initial intent-to-treat response rate is only 50 to 60%. This study was designed to examine whether functional connectivity strengths of resting EEG could be potential biomarkers in predicting treatment response at 8 weeks of treatment. Resting state 3-min eyes-closed EEG activity was recorded at baseline and compared in 108 depressed patients. All patients were being treated with selective serotonin-reuptake inhibitors. Baseline coherence and power series correlation were compared between responders and non-responders evaluated at the 8th week by Hamilton Depression Rating Scale. Pearson correlation and receiver operating characteristic (ROC) analyses were applied to evaluate the performance of connectivity strengths in predicting/classifying treatment responses. The connectivity strengths of right fronto-temporal network at delta/theta frequencies differentiated responders and non-responders at the 8th week of treatment, such that the stronger the connectivity strengths, the poorer the treatment response. ROC analyses supported the value of these measures in classifying responders/non-responders. Our results suggest that fronto-temporal connectivity strengths could be potential biomarkers to differentiate responders and slow responders or non-responders in MDD.     

Exteroceptive suppression of masseter muscle: assessment of two methods for quantitating suppression periods

Objectives – The late exteroceptive suppression period (ES2) of the masseter muscle is conventionally quantified by a combination of measures of duration, amplitude, or mean activity. The combination of measures makes it difficult to compare ES2s obtained from different set-ups. An unbiased method for quantitating ES2 is introduced allowing ranking of ES2s. The introduced method is utilized to evaluate stimulus and recording conditions under which ES2 is maximal. Material and methods – Fifteen male volunteers participated in 3 experiments designed to determine the effect of level of teeth clenching, stimulus intensity, and perceived pain intensity on the ES2. Results – Coefficients of variance (1 h/1 month) were: duration: 11%/43%, latency: 9%/12%, and magnitude of suppression: 11%/12%. A level of teeth clenching of 66% of maximal voluntary bite force, and a stimulus intensity below pain detection threshold was associated with maximal magnitude of suppression of ES2. Conclusion – The introduced method is reproducible and allows ranking and stimulus-response estimations of ES2. It is suggested that ES2 does not reflect activity along the nociceptive pathways in the trigeminal region.     

Separate ipsilateral and contralateral corticospinal projections in congenital mirror movements: Neurophysiological evidence and significance for motor rehabilitation.

The neurophysiological hallmark of congenital mirror movements (MM) are fast-conducting corticospinal projections from the hand area of one primary motor cortex to both sides of the spinal cord. It is still unclear whether the abnormal ipsilateral projection originates through branching fibres from the normal contralateral projection or constitutes a separate ipsilateral projection. To clarify this question, we used focal paired-pulse transcranial magnetic stimulation to test task-related modulation of short-interval intracortical inhibition (SICI) in the abductor pollicis brevis (APB) muscles of a 15-year-old girl (Patient 1) and a 40-year-old woman (Patient 2) with congenital MM. In both patients, during intended unilateral APB contraction, SICI decreased markedly in the "task" APB but remained unchanged in the "mirror" APB when compared to muscle rest. In contrast, spinal excitability as tested with H reflexes increased similarly in the task and mirror flexor carpi radialis muscles. This dissociation of task-related SICI modulation strongly supports the existence of a separate ipsilateral fast-conducting corticospinal projection. In Patient 1, we tested the functional significance of this separate ipsilateral projection during 7 months of motor rehabilitation training, which was designed to facilitate unilateral finger movements. A marked reduction of MM was observed after training, suggesting that unwanted mirror activity in the ipsilateral pathway can be suppressed by learning.     

Fast responders have blinders on: ERP correlates of response inhibition in competition

Recent studies have demonstrated that individuals acting in a social context form shared representations, resulting in incorporating another person's action plan into their own. The present study investigated the extent to which shared representations are formed in a competitive task. Specifically, it was tested whether in competition the process of response inhibition is affected by explicit knowledge of another's task. Event-related potential (ERP) correlates of response inhibition were measured while pairs of participants competed with each other on a speeded go/no-go task. Participants were instructed to always try to respond faster than their direct competitor. No-go stimuli requiring an inhibitory response of the other person as well (compatible action) or no-go stimuli to which the other person should respond (incompatible action) were directly compared. Behavioral performance measures and response inhibition, as reflected in the no-go P3, were decreased on incompatible actions compared to compatible ones. Interestingly, both the behavioral and the ERP effects were caused by the slow responding and thus unsuccessful competitors. These findings indicate that shared representations are formed in competitive tasks, but differently for successful and unsuccessful competitors. Only the slow responders are impeded by incompatible actions. The present study therefore demonstrates that the formation of shared representations is not a fully automatic process. People can differ in the extent to which they incorporate the other's action plan into their own and this may be closely related to successful performance in competitive action.     

Left temporal low‐frequency rTMS for the treatment of tinnitus: clinical predictors of treatment outcome – a retrospective study

Background: There is increasing evidence that repetitive transcranial magnetic stimulation (rTMS) can reduce chronic tinnitus. However, treatment results are characterized by high interindividual variability. Therefore, the identification of predictors for treatment response is of high clinical relevance. Methods: Clinical data of 194 patients with tinnitus were evaluated. All patients were treated with a standardized rTMS procedure (1 Hz, 10 days, 2000 stimuli/day, over the left temporal cortex). A potential influence on the outcome was analysed for the following parameters: age, gender, depression scores in Beck Depression Inventory (BDI) and tinnitus severity (TQ) before rTMS, lateralization, frequency and duration of tinnitus and extent of hearing loss. Results: An effect of tinnitus laterality was observed. In patients with left‐sided or bilateral tinnitus, rTMS resulted in a statistically significant reduction of TQ scores, whereas patients with right‐sided tinnitus did not show a significant improvement after rTMS treatment. However, in correlation analyses, we found a trend which did not reach statistical significance that in the subgroup of treatment responders tinnitus duration influenced rTMS outcome. In addition, a multiple regression analysis identified the TQ score at baseline as a significant predictor for treatment outcome. For all other investigated parameters, no statistically significant effects were found. Conclusions: This study suggests that left temporal low‐frequency rTMS has beneficial effects in left‐sided and bilateral tinnitus, but not in right‐sided tinnitus. In line with the results from earlier studies involving smaller samples, tinnitus duration was found to influence rTMS outcome.     

The effect of waiting: A meta-analysis of wait-list control groups in trials for tinnitus distress

Objective

The response rates and effects of being placed on a wait-list control condition are well documented in psychiatric populations. Despite the usefulness of such estimates and the frequent use of no-treatment controls in clinical trials for tinnitus, the effect of waiting in a tinnitus trial has not been investigated systematically. The aim of the present study was to quantify the overall effect of wait-list control groups on tinnitus distress.

Methods

Studies were retrieved via a systematic review of randomised controlled trials of cognitive behaviour therapy for tinnitus distress. Outcomes of psychometrically robust tinnitus-specific measures (Tinnitus Handicap Inventory, Tinnitus Questionnaire, Tinnitus Reaction Questionnaire) from wait-list control groups were quantified using meta-analytic techniques. Percentage of change and standard mean difference effect sizes were calculated using the pre and post wait period.

Results

Eleven studies involving 314 wait-list subjects with tinnitus were located. The analysis for a waiting period of 6 to 12 weeks revealed a mean decrease in scores on tinnitus-specific measures of 3% to 8%. Across studies, a statically significant small mean within-group effect size was obtained (Hedges' g=.17). The effects were moderated by methodological quality of the trial, sample characteristics (i.e., age, tinnitus duration), time of the wait-list and how diagnosis was established.

Conclusion

Subjects in a tinnitus trial improve in tinnitus distress over a short waiting phase. The effects of waiting are highly variable and depend on the characteristics of the sample and of the trial.     

Response inhibition results in the emotional devaluation of faces: neural correlates as revealed by fMRI

Although it is well established that prior experience with faces determines their subsequent social-emotional evaluation, recent work shows that top-down inhibitory mechanisms, including response inhibition, can lead to social devaluation after even a single, brief exposure. These rapidly induced effects indicate interplay among perceptual, attentional, response-selection and social-emotional networks; yet, the brain mechanisms underlying this are not well understood. This study used functional magnetic resonance imaging (fMRI) to investigate the neural mechanism mediating the relationship between inhibitory control and emotional devaluation. Participants performed two tasks: (i) a Go/No-Go task in response to faces and (ii) a trustworthiness rating task involving the previously seen faces. No-Go faces were rated as significantly less trustworthy than Go faces. By examining brain activations during Task 1, behavioral measures and brain activations obtained in Task 2 could be predicted. Specifically, activity in brain areas during Task 1 associated with (i) executive control and response suppression (i.e. lateral prefrontal cortex) and (ii) affective responses and value representation (i.e. orbitofrontal cortex), systematically covaried with behavioral ratings and amygdala activity obtained during Task 2. The present findings offer insights into the neural mechanisms linking inhibitory processes to affective responses.     

Transcranial magnetic stimulation as a tool for understanding neurophysiology in Huntington's disease: A review

Structural and functional magnetic resonance imaging modalities have been critical in advancing our understanding of the neuroanatomical and pathophysiological changes that emerge during the premanifest and symptomatic stages of Huntington's disease (HD). However, the relationship between underlying neuropathology and the motor, cognitive and behavioural changes associated with the disorder still remain poorly understood. Less conventional technologies, such as transcranial magnetic stimulation (TMS) and electroencephalography (EEG), provide a unique opportunity to further investigate the causal relationships between targeted neural circuits and objective neurophysiological responses together with overt behaviours. In this review, we discuss previous successful applications of TMS in other neurological disorders and its prospective use in HD. We also address the added value of multimodal TMS techniques, such as TMS–EEG, in investigating the integrity of neural networks in non-motor regions in HD. We conclude that neurophysiological outcome measures are likely to contribute towards characterising further the trajectory of decline across functional domains in HD, enhance understanding of underlying neural mechanisms, and offer new avenues for elucidating sensitive endophenotypic biomarkers of disease progression.     

Finding a way in: A review and practical evaluation of fMRI and EEG for detection and assessment in disorders of consciousness

Diagnoses and assessments of cognitive function in disorders of consciousness (DOC) are notoriously prone to error due to their reliance on behavioural measures. As a result, researchers have turned to functional neuroimaging and electrophysiological techniques with the goal of developing more effective methods of detecting awareness and assessing cognition in these patients. This article reviews functional magnetic resonance imaging (fMRI) and electroenchphalography (EEG)-based studies of cognition and consciousness in DOC, including assessment of basic sensory, perceptual, language, and emotional processing; studies for detection of conscious awareness; paradigms for the establishment of communication in the absence of behaviour; and functional connectivity studies. The advantages and limitations of fMRI and EEG-based measures are examined as research and clinical tools in this population and an explanation offered for the rediscovery of the unique advantages of EEG in the study of DOC.     

Glycine receptors in the caudal pontine reticular formation: are they important for the inhibition of the acoustic startle response?

The present paper sought to test the hypothesis that inhibitory glycine receptors (GlyRs) on giant neurons of the caudal pontine reticular formation (PnC) are involved in the inhibition of the acoustic startle response (ASR) in rats. First we provided evidence for the presence of the strychnine-sensitive inhibitory GlyR on PnC neurons by immunocytochemical labeling using an antibody against the α₁ subunit of the GlyR. We then measured the ASR as well as two ASR inhibiting phenomena, short-term habituation and prepulse inhibition, after microinjections of the glycine antagonist strychnine (0, 5 or 10 nmol) or the glycine agonist β-alanine (0, 50 or 100 nmol) into the PnC. Neither strychnine nor β-alanine had a measurable influence on any of the parameters of the ASR investigated (amplitude, short-term habituation, prepulse inhibition). In contrast, systemic injection of strychnine (1 mg/kg) markedly increased the ASR amplitude. The systemic administration of strychnine did not impair prepulse inhibition. The human ‘startle disease’ (hyperekplexia), an exaggerated startle response, is caused by a defect of the α₁ subunit of the inhibitory GlyR, but it is unclear at which site in the central nervous system this defect ultimately leads to the symptoms of hyperekplexia. Our data indicate that a blockade of the inhibitory GlyRs in the PnC does not affect the ASR of rats, suggesting that deficient GlyRs in the PnC might not be involved in the etiology of the human ‘startle disease’. We conclude that the inhibitory GlyRs on PnC neurons are not necessary for the inhibition of the ASR and believe that they are involved in another behavioral context.     

Neural correlates of attention biases,behavioral inhibition,and social anxiety in children: An ERP study

Behavioral inhibition (BI) is a biologically-based temperament characterized by vigilance toward threat. Over time, many children with BI increasingly fear social circumstances and display maladaptive social behavior. BI is also one of the strongest individual risk factors for developing social anxiety disorder. Although research has established a link between BI and anxiety, its causal mechanism remains unclear. Attention biases may underlie this relation. The current study examined neural markers of the BI-attention-anxiety link in children ages 9–12 years (N = 99, Mean = 9.97, SD = 0.97). ERP measures were collected as children completed an attention-bias (dot-probe) task with neutral and angry faces. P2 and N2 amplitudes were associated with social anxiety and attention bias, respectively. Specifically, augmented P2 was related to decreased symptoms of social anxiety and moderated the relation between BI and social anxiety, suggesting that increasing attention mobilization may serve as a compensatory mechanism that attenuates social anxiety in individuals with high BI. The BI by N2 interaction found that larger N2 related to threat avoidance with increasing levels of BI, consistent with over-controlled socio-emotional functioning. Lastly, children without BI (BN) showed an augmented P1 to probes replacing angry faces, suggesting maintenance of attentional resources in threat-related contexts.     

Methodology of photic stimulation revisited: updated European algorithm for visual stimulation in the EEG laboratory

Intermittent photic stimulation (IPS) is a common procedure performed in the electroencephalography (EEG) laboratory in children and adults to detect abnormal epileptogenic sensitivity to flickering light (i.e., photosensitivity). In practice, substantial variability in outcome is anecdotally found due to the many different methods used per laboratory and country. We believe that standardization of procedure, based on scientific and clinical data, should permit reproducible identification and quantification of photosensitivity. We hope that the use of our new algorithm will help in standardizing the IPS procedure, which in turn may more clearly identify and assist monitoring of patients with epilepsy and photosensitivity. Our algorithm goes far beyond that published in 1999 (Epilepsia, 1999a, 40, 75; Neurophysiol Clin, 1999b, 29, 318): it has substantially increased content, detailing technical and logistical aspects of IPS testing and the rationale for many of the steps in the IPS procedure. Furthermore, our latest algorithm incorporates the consensus of repeated scientific meetings of European experts in this field over a period of 6 years with feedback from general neurologists and epileptologists to improve its validity and utility. Accordingly, our European group has provided herein updated algorithms for two different levels of methodology: (1) requirements for defining photosensitivity in patients and in family members of known photosensitive patients and (2) requirements for tailored studies in patients with a clear history of visually induced seizures or complaints, and in those already known to be photosensitive.     

Development of brain networks for social functions: Confirmatory analyses in a large open source dataset

Human observers show robust activity in distinct brain networks during movie-viewing. For example, scenes that emphasize characters’ thoughts evoke activity in the “Theory of Mind” (ToM) network, whereas scenes that emphasize characters’ bodily sensations evoke activity in the “Pain Matrix.” A prior exploratory fMRI study used a naturalistic movie-viewing stimulus to study the developmental origins of this functional dissociation, and the links between cortical and cognitive changes in children’s social development (Richardson et al., 2018). To replicate and extend this work, the current study utilized a large publicly available dataset (n = 241, ages 5–20 years) (Alexander et al., 2017) who viewed “The Present” (Frey, 2014) and completed a resting state scan (n = 200) while undergoing fMRI. This study provides confirmatory evidence that 1) ToM and pain networks are functionally dissociated early in development, 2) selectivity increases with age, and in ToM regions, with a behavioral index of social reasoning. Additionally, while inter-region correlations are similar when measured during the movie and at rest, only inter-region correlations measured during movie-viewing correlated with functional maturity. This study demonstrates the scientific benefits of open source data in developmental cognitive neuroscience, and provides insight into the relationship between functional and intrinsic properties of the developing brain.