Electrophysiological Brain Activity Research Articles

F191. Electrophysiological brain activity during motor imagery enhanced by brain–computer interface in healthy volunteers and post-stroke patients

Introduction Motor imagery (MI) has been shown to be an effective tool in rehabilitation of post-stroke patients. MI can be enhanced by kinesthetic feedback provided by brain-computer-exoskeleton interfaces. Description and analysis of brain activity during the kinesthetic imagery of movements in healthy subjects and post-stroke patients with the subcortical location of the damage was performed in the current study. Methods Seven right-handed healthy volunteers (age 29 [22.0; 35.0] years) and nine post-stroke patients (age 52.0 [36.0; 58.0] years, time since stroke 6.0 [4.0; 13.0] months) were enrolled. They were trained in kinesthetic motor imagery using brain-computer interface (BCI) and a controllable exoskeleton. All participants had 20 training sessions with a duration of up to 15 min. The BCI was controlled using a Bayessian classifier, which was preset to recognize the imagery of left or right hand extension and the rest state. Processing of EEG recordings was performed using the independent component analysis. The digitization of EEG-electrode positions for obtaining their coordinates in the MRI-related system was made using an NBS Eximia Nexstim device for navigational transcranial magnetic stimulation. This study used the AMICA method to find the sources of electrophysiological brain activity during motor imagery. For each component determined, the EEG inverse problem was solved according to the sLORETA method. Results Components that are most frequently identified by the AMICA method were revealed in the same areas in both groups: SIL (the primary somatosensory left cortex), SIR (the primary somatosensory right cortex), PRC (the precuneus), PRM (the premotor left cortex), and SMA (the supplementary motor area). There were differences in the activity characteristics when comparing healthy controls and patients: the μ -rhythm in the somatosensory area was characterized by a lower frequency in the studied poststroke patients than in the healthy subjects; it had a poorly pronounced peak in all mental states and was only slightly suppressed during contralateral hand motor imagery. The rhythm in the α -band was also characterized by a low frequency with a poorly pronounced peak in the precuneus and premotor area; however, unlike in the healthy subjects, this rhythm increased, i.e., was synchronized, during motor imagery. Conclusion This study is an extension of previous investigations of EEGs during motor imagery in healthy subjects. Only two symmetrical sources in the primary somatosensory cortex were previously discussed. This study revealed three more sources: the premotor area, precuneus, and supplementary motor area. The characteristics of the EEG sources during motor imagery are fundamentally different in post-stroke patients comparing to healthy controls. Funding was provided by grant RFMEF N I60715X0128.

Differential electrophysiological correlates of panic disorder in non-pulsatile tinnitus

AimsThe prevalence of panic disorder (PD) reportedly is up to fivefold higher in people with tinnitus than it is in the general population. The brain networks in the two conditions overlap but the pathophysiological link remains unclear. In this study the electrophysiological brain activity is investigated in adults with non-pulsatile tinnitus with and without concurrent PD. MethodsResting-state EEGs of 16 participants with non-pulsatile tinnitus and PD were compared with those of 16 peers with non-pulsatile tinnitus without PD and as many healthy controls. The sLORETA technique was used to identify group-specific electrophysiological frequencies in the brain and to approximate the brain regions where differences occurred. The influence of distress was investigated and functional connectivity charted using the Region-of-Interest (ROI) approach (amygdala, anterior cingulate cortex (ACC), insula, precuneus). ResultsThe comorbid group showed significantly diminished theta activity (p < 0.05) in the precuneus (BA7) compared to the tinnitus group without PD as well as in another region of the precuneus (BA31) as compared to the controls. Higher levels of distress influenced results in the tinnitus group without PD, while in those with PD a diminished connectivity was observed between the dorsal ACC and the other three ROIs as contrasted to the controls. ConclusionsAdults with non-pulsatile tinnitus and concurrent PD show differential brain activity patterns to tinnitus only sufferers and healthy controls. Higher levels of distress may modulate brain activity in the absence of PD. Screening for distress is recommended in both clinical and research settings.

Theta-band Oscillations in the Middle Temporal Gyrus Reflect Novel Word Consolidation.

Like many other types of memory formation, novel word learning benefits from an offline consolidation period after the initial encoding phase. A previous EEG study has shown that retrieval of novel words elicited more word-like-induced electrophysiological brain activity in the theta band after consolidation [Bakker, I., Takashima, A., van Hell, J. G., Janzen, G., & McQueen, J. M. Changes in theta and beta oscillations as signatures of novel word consolidation. Journal of Cognitive Neuroscience, 27, 1286-1297, 2015]. This suggests that theta-band oscillations play a role in lexicalization, but it has not been demonstrated that this effect is directly caused by the formation of lexical representations. This study used magnetoencephalography to localize the theta consolidation effect to the left posterior middle temporal gyrus (pMTG), a region known to be involved in lexical storage. Both untrained novel words and words learned immediately before test elicited lower theta power during retrieval than existing words in this region. After a 24-hr consolidation period, the difference between novel and existing words decreased significantly, most strongly in the left pMTG. The magnitude of the decrease after consolidation correlated with an increase in behavioral competition effects between novel words and existing words with similar spelling, reflecting functional integration into the mental lexicon. These results thus provide new evidence that consolidation aids the development of lexical representations mediated by the left pMTG. Theta synchronization may enable lexical access by facilitating the simultaneous activation of distributed semantic, phonological, and orthographic representations that are bound together in the pMTG.

Electrophysiological Measurement of Noxious-evoked Brain Activity in Neonates Using a Flat-tip Probe Coupled to Electroencephalography.

Pain is an unpleasant sensory and emotional experience. In non-verbal patients, it is very difficult to measure pain, even with pain assessment tools. Those tools are subjective or determine secondary physiological indicators which also have certain limitations particularly when exploring the effectiveness of analgesia. As cortical processing is essential for pain perception, brain activity measures may provide a useful approach to assess pain in infants. Here we present a method to assess nociception with electrophysiological brain activity recordings optimized for the use in newborn infants. To produce highly standardized and reproducible noxious stimuli we applied mechanical stimulation with a flat-tip probe, e.g., PinPrick, which is not skin-breaking and does not cause behavioral distress. The noxious-evoked potential allows the objective measurement of nociception in non-verbal patients. This method can be used in newborn infants as early as 34 weeks of gestational age. Moreover, it could be applied in different situations such as measuring the efficacy of analgesic or anesthetic drugs.

An objective neural signature of rapid perspective taking.

The frequency-tagging approach has generally been confined to study low-level sensory processes and always found related activation over the occipital region. Here for the first time, we investigated with it, high-level socio-cognitive functions, i.e. the processing of what other people are looking at which is referred to as level 1 visual perspective taking (VPT). Sixteen participants were presented with visual scenes alternating at 2.5 Hz which were depicting a person and an object in a room, while recording electrophysiological brain activity. The person orientation and object position changed at every stimulus but the person in the room always faced the object, except on every fifth stimulus. We found responses in the electroencephalography (EEG) spectrum exactly at the frequency corresponding to the presentation of the scenes where the person could not see the object, i.e. 0.5 Hz. While the 2.5 Hz stimulation rate response focused on typical medial occipital sites, the specific 0.5 Hz response was found mainly over a centro-parietal region. Besides a robust group effect, these responses were significant and quantifiable for most individual participants. Overall, these observations reveal a clear measure of level 1-VPT representation, highlighting the potential of EEG frequency-tagging to capture high-level socio-cognitive functions in the brain.

Electrophysiological Anomalies in Face-Name Memory Encoding in Young Binge Drinkers.

A growing body of evidence indicates that the intake of large amounts of alcohol during one session may have structural and functional effects on the still-maturing brains of young people. These effects are particularly pronounced in prefrontal and hippocampal regions, which appear to be especially sensitive to the neurotoxic effects of alcohol. However, to date, few studies have used the event-related potentials (ERPs) technique to analyze the relationship between binge drinking (BD) and associative memory. The objective of this study was to examine brain activity during memory encoding using the Subsequent memory paradigm in subjects who have followed a BD pattern of alcohol consumption for at least 2 years. A total of 50 undergraduate students (mean age = 20.6 years), i.e., 25 controls (12 females) and 25 binge drinkers (BDs; 11 females), with no personal or family history of alcoholism or psychopathological disorders, performed a visual face–name association memory task. The task used enables assessment of the Difference due to memory effect (Dm), a measure of memory encoding based on comparison of the neural activity associated with subsequent successful and unsuccessful retrieval. In ERP studies, study items that are subsequently remembered elicit larger positive amplitudes at midline parieto-frontal sites than those items that are subsequently forgotten. The Dm effect generally appears in the latency range of about 300–800 ms. The results showed a Dm effect in posterior regions in the 350–650 ms latency range in the Control group. However, in the BD group, no significant differences were observed in the electrophysiological brain activity between remembered and forgotten items during the encoding process. No differences between groups were found in behavioral performance. These findings show that young BDs display abnormal pattern of ERP brain activity during the encoding phase of a visual face–name association task, possibly suggesting a different neural signature of successful memory encoding.

Electrophysiological brain activity during the control of a motor imagery-based brain–computer interface

This article considers the features of five electroencephalogram patterns that are most frequently extracted by the independent component analysis when subjects imagine the movement of their hands during the control of a brain–computer interface (BCI). The solution of the EEG inverse problem using the individual geometrical head model shows that the sources of the revealed patterns are located at the bottom of the left and right central sulci, as well as in the left premotor cortex, supplementary motor area, and precuneus. The functional value of the patterns is discussed by comparing the location results with the results of the metaanalysis of the published data that were obtained using a functional magnetic resonance imaging. The source locations are the same for seven healthy subjects and four poststroke patients with subcortical damage location. However, despite the same locations, the two groups of subjects significantly differed in the frequency characteristics of the revealed patterns; in particular, the patients had no clearly pronounced activity in the upper α-band and were characterized by a much lower level of inhibition of rates in the primary somatosensory areas during motor imagery.

The combined use of virtual reality and EEG to study language processing in naturalistic environments

When we comprehend language, we often do this in rich settings where we can use many cues to understand what someone is saying. However, it has traditionally been difficult to design experiments with rich three-dimensional contexts that resemble our everyday environments, while maintaining control over the linguistic and nonlinguistic information that is available. Here we test the validity of combining electroencephalography (EEG) and virtual reality (VR) to overcome this problem. We recorded electrophysiological brain activity during language processing in a well-controlled three-dimensional virtual audiovisual environment. Participants were immersed in a virtual restaurant while wearing EEG equipment. In the restaurant, participants encountered virtual restaurant guests. Each guest was seated at a separate table with an object on it (e.g., a plate with salmon). The restaurant guest would then produce a sentence (e.g., “I just ordered this salmon.”). The noun in the spoken sentence could either match (“salmon”) or mismatch (“pasta”) the object on the table, creating a situation in which the auditory information was either appropriate or inappropriate in the visual context. We observed a reliable N400 effect as a consequence of the mismatch. This finding validates the combined use of VR and EEG as a tool to study the neurophysiological mechanisms of everyday language comprehension in rich, ecologically valid settings.

The impact of hyperoxia on brain activity: A resting-state and task-evoked electroencephalography (EEG) study.

A better understanding of the effect of oxygen on brain electrophysiological activity may provide a more mechanistic insight into clinical studies that use oxygen treatment in pathological conditions, as well as in studies that use oxygen to calibrate functional magnetic resonance imaging (fMRI) signals. This study applied electroencephalography (EEG) in healthy subjects and investigated how high a concentration of oxygen in inhaled air (i.e., normobaric hyperoxia) alters brain activity under resting-state and task-evoked conditions. Study 1 investigated its impact on resting EEG and revealed that hyperoxia suppressed α (8-13Hz) and β (14-35Hz) band power (by 15.6±2.3% and 14.1±3.1%, respectively), but did not change the δ (1-3Hz), θ (4-7Hz), and γ (36-75Hz) bands. Sham control experiments did not result in such changes. Study 2 reproduced these findings, and, furthermore, examined the effect of hyperoxia on visual stimulation event-related potentials (ERP). It was found that the main peaks of visual ERP, specifically N1 and P2, were both delayed during hyperoxia compared to normoxia (P = 0.04 and 0.02, respectively). In contrast, the amplitude of the peaks did not show a change. Our results suggest that hyperoxia has a pronounced effect on brain neural activity, for both resting-state and task-evoked potentials.

Neurophysiological correlates of suicidal ideation in major depressive disorder: Hyperarousal during sleep

BackgroundSuicide is a major public health concern, and a barrier to reducing the suicide rate is the lack of objective predictors of risk. The present study considers whether quantitative sleep electroencephalography (EEG) may be a neurobiological correlate of suicidal ideation. MethodsParticipants included 84 (45 female, mean age=26.6) adults diagnosed with major depressive disorder (MDD). The item that measures thoughts of death or suicide on the Quick Inventory of Depressive Symptomatology (QIDS) was used to classify 47 participants as low suicidal ideation (24 females, mean age=26.1) and 37 as high suicidal ideation (21 females, mean age=27.3). Data were obtained from archival samples collected at the University of Michigan and University of Texas Southwestern Medical Center between 2004 and 2012. Sleep EEG was quantified using power spectral analysis, and focused on alpha, beta, and delta frequencies. ResultsResults indicated that participants with high compared to low suicidal ideation experienced 1) increased fast frequency activity, 2) decreased delta activity, and 3) increased alpha-delta sleep after adjusting for age, sex, depression, and insomnia symptoms. LimitationsLimitations include the exclusion of imminent suicidal intent, a single suicidal ideation item, and cross-sectional archival data. ConclusionsThis is one of the first studies to provide preliminary support that electrophysiological brain activity during sleep is associated with increased suicidal ideation in MDD, and may point toward central nervous system (CNS) hyperarousal during sleep as a neurobiological correlate of suicidal ideation.

Variability in functional brain networks predicts expertise during action observation

Observing an action performed by another individual activates, in the observer, similar circuits as those involved in the actual execution of that action. This activation is modulated by prior experience; indeed, sustained training in a particular motor domain leads to structural and functional changes in critical brain areas. Here, we capitalized on a novel graph-theory approach to electroencephalographic data (Fraiman et al., 2016) to test whether variability in functional brain networks implicated in Tango observation can discriminate between groups differing in their level of expertise. We found that experts and beginners significantly differed in the functional organization of task-relevant networks. Specifically, networks in expert Tango dancers exhibited less variability and a more robust functional architecture. Notably, these expertise-dependent effects were captured within networks derived from electrophysiological brain activity recorded in a very short time window (2s). In brief, variability in the organization of task-related networks seems to be a highly sensitive indicator of long-lasting training effects. This finding opens new methodological and theoretical windows to explore the impact of domain-specific expertise on brain plasticity, while highlighting variability as a fruitful measure in neuroimaging research.

On the Potential of a New Generation of Magnetometers for MEG: A Beamformer Simulation Study.

Magnetoencephalography (MEG) is a sophisticated tool which yields rich information on the spatial, spectral and temporal signatures of human brain function. Despite unique potential, MEG is limited by a low signal-to-noise ratio (SNR) which is caused by both the inherently small magnetic fields generated by the brain, and the scalp-to-sensor distance. The latter is limited in current systems due to a requirement for pickup coils to be cryogenically cooled. Recent work suggests that optically-pumped magnetometers (OPMs) might be a viable alternative to superconducting detectors for MEG measurement. They have the advantage that sensors can be brought to within ~4 mm of the scalp, thus offering increased sensitivity. Here, using simulations, we quantify the advantages of hypothetical OPM systems in terms of sensitivity, reconstruction accuracy and spatial resolution. Our results show that a multi-channel whole-head OPM system offers (on average) a fivefold improvement in sensitivity for an adult brain, as well as clear improvements in reconstruction accuracy and spatial resolution. However, we also show that such improvements depend critically on accurate forward models; indeed, the reconstruction accuracy of our simulated OPM system only outperformed that of a simulated superconducting system in cases where forward field error was less than 5%. Overall, our results imply that the realisation of a viable whole-head multi-channel OPM system could generate a step change in the utility of MEG as a means to assess brain electrophysiological activity in health and disease. However in practice, this will require both improved hardware and modelling algorithms.

ERP Correlates of Simulated Purchase Decisions.

Decision making in economic context is an everyday activity but its neuronal correlates are poorly understood. The present study aimed at investigating the electrophysiological brain activity during simulated purchase decisions of technical products for a lower or higher price relative to a mean price estimated in a pilot study. Expectedly, participants mostly decided to buy a product when it was cheap and not to buy when it was expensive. However, in some trials they made counter-conformity decisions to buy a product for a higher than the average price or not to buy it despite an attractive price. These responses took more time and the variability of the response latency was enhanced relative to conformity responses. ERPs showed enhanced conflict related fronto-central N2 during both types of counter-conformity compared to conformity decisions. A reverse pattern was found for the P3a and P3b. The response-locked P3 (r-P3) was larger and the subsequent CNV smaller for counter-conformity than conformity decisions. We assume that counter-conformity decisions elevate the response threshold (larger N2), intensify response evaluation (r-P3) and attenuate the preparation for the next trial (CNV). These effects were discussed in the framework of the functional role of the fronto-parietal cortex in economic decision making.

Time-Frequency Spatial Wavelet Phase Coherence Analysis of EEG in EC and EO During Resting State

The electrophysiological brain activities are nonlinear in nature as measured by Electroencephalography (EEG). There are coherent activities in brain not only seen during explicit tasks but also during rest. This article aims to investigate the Wavelet based Phase coherence of oscillations of eye closed and eye open signals during resting states. The wavelet coherence is computed for selected 19 electrodes according to 10-20 system from 129 channel EEG signals. The significance was obtained using Wilcoxon Signed Rank test and pairwise wavelet coherence was computed for each possible combination. The Wavelet Phase Coherence using Wavelet Transform gives significantly high results (P<0.05) in EC and EO signals during resting states in frequency interval 0.5-50Hz overall as well as in the band intervals such as delta (05-4Hz), theta (4-7Hz), alpha (7-13Hz), beta (13-22Hz) and gamma (22-50Hz).

Symptômes négatifs de la schizophrénie : de l’électrophysiologie à l’électrothérapie

The aim of this review of the literature is to summarize the state of the knowledge concerning the relationship between negative symptoms in schizophrenia, electrophysiology and electrotherapy. The scientific literature search of international articles was performed during August and September 2015 using the PubMed electronic database. We used the following MeSH terms: “Negative symptoms”, “Schizophrenia”, “Electrophysiology”, “Neurophysiology”, “EEG power”, “Alpha rhythm”, “Transcranial magnetic stimulation”, “Transcranial direct current stimulation”, “Electroconvulsive therapy”, “Neurofeedback”, “Vagus Nerve Stimulation”, “Deep Brain Stimulation”, and “State dependent”. Negative symptoms in schizophrenia are associated with altered activity in prefrontal cortex in functional neuroimaging studies. This is in line with electrophysiological measurements that found a change in EEG spectral power in the alpha frequency band over prefrontal brain regions. The notion of functional hypofrontality has led to hypotheses that electrotherapy applied to the prefrontal cortex may be an effective treatment of negative symptoms in schizophrenia. Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) were used to increase cortical activity in schizophrenia and achieve a clinical effect on negative symptoms. Three meta-analyses confirmed, with a moderate effect size, that rTMS is an effective treatment option for negative symptoms in schizophrenia. The two subsequently published prospective multicenter studies, however, found opposite results from each other. Two randomized controlled studies suggested that tDCS is an effective treatment option for negative symptoms. There is no study on the efficacy of neurofeedback, vagal nerve stimulation or deep brain stimulation on negative symptoms in schizophrenia. Additional studies are needed to confirm the efficacy of rTMS and tDCS on negative symptoms in schizophrenia. Influencing factors, related to clinical and stimulation parameters, of rTMS and tDCS on negative symptoms should be better investigated. Effects related to electrophysiological brain activity of the patient, especially in the alpha band, during the stimulation should also be better investigated. The action of electrotherapy may be state dependent, and a better understanding of electrophysiological effects of electrotherapy techniques could enable their optimization.

Electroencephalography during general anaesthesia differs between term-born and premature-born children

ObjectivesPremature birth is associated with a wide range of complications in later life, including structural and functional neurological abnormalities and altered pain sensitivity. We investigated whether during anaesthesia premature-born children display different patterns of background EEG activity and exhibit increased responses to nociceptive stimuli. MethodsWe examined background EEG and time-locked responses to clinical cannulation in 45 children (mean age (±SD) at study: 4.9(±3.0)years) under sevoflurane monoanaesthesia maintained at a steady-state end-tidal concentration of 2.5%. 15 were born prematurely (mean gestational age at birth: 29.2±3.9weeks) and 30 were age-matched term-born children. ResultsBackground levels of alpha and beta power were significantly lower in the premature-born children compared to term-born controls (p=0.048). Clinical cannulation evoked a significant increase in delta activity (p=0.032), which was not significantly different between the two groups (p=0.44). ConclusionsThe results indicate that whilst under anaesthesia premature-born children display different patterns of background brain activity compared to term-born children. SignificanceAs electrophysiological techniques are increasingly used by anaesthetists to gauge anaesthetic depth, differences in background levels of electrophysiological brain activity between premature and term-born children may be relevant when considering titration of anaesthetic dose.

Targeting Adenosine Monophosphate-Activated Protein Kinase by Metformin Adjusts Post-Ischemic Hyperemia and Extracellular Neuronal Discharge in Transient Global Cerebral Ischemia.

I/R and its subsequent reactive hyperemia results in different adverse effects such as brain edema and BBB disruption. AMPK activation has been perceived as one of the target factors for I/R treatment. We investigated the effect of Met (an AMPK activator) on some physiological parameters including vascular responses, hyperemia, BBB disruption, and electrophysiological activity following tGCI. Rats were pretreated with Met for two weeks and CC was administered half an hour before tGCI. Brain vascular responses, hyperemia, BBB disruption, and electrophysiological activity were evaluated following the ischemia. Met attenuated BBB disruption and reactive hyperemia in tGCI rats compared with the untreated I/R rats (p<0.001). Met administration along with CC in the ischemic rats reversed the beneficial effects of Met on BBB disruption and reactive hyperemia (p<0.001). Electrophysiological records indicated that Met increased spike rates in the ischemic rats comparing with I/R rats (p<0.001), whereas, CC administration blocked the beneficial effects of Met on the neuronal discharges (p<0.05). We established a regulatory role for AMPK in vascular and electrophysiological responses to tGCI. Studies are ongoing to determine if activation of AMPK in the reperfusion period would offer similar protection.

Time-Frequency Wavelet Based Coherence Analysis of EEG in EC and EO during Resting State

The electrophysiological brain activities are nonlinear in nature as measured by Electroencephalography (EEG). There are coherent activities in brain not only seen during explicit tasks but also during rest. This article aims to employ most robust nonlinear dynamics Time Frequency representation (TFR) techniques such as wavelet phase coherence to investigate brain activity in different frequency bands at temporal and spatial scale dynamics in form of topographic maps in resting state networks. The TFR has the advantages to study the combined effect of time and frequency domains simultaneously. The wavelet coherence computed in this way exhibit high precision to detect the phase coherence in different frequency intervals to analyze highly complex non-autonomous and non-stationary EEG signals. The spatiotemporal dynamics of resting state networks are investigated by computing coherence. We have investigated the Wavelet based Phase coherence of oscillations of eye closed and eye open signals during resting states. The wavelet coherence is computed for selected 19 electrodes according to 10-20 system from 129 channel EEG signals. The significance was obtained using Wilcoxon Signed Rank test and pairwise wavelet coherence was computed for each possible combination. The Wavelet Phase Coherence using Wavelet Transform gives significantly high results (P<0.05) in EC and EO signals during resting states in frequency interval 0.5-50 Hz overall as well as in the band intervals such as delta (05-4 Hz), theta (4-7 Hz), alpha (7-13 Hz), beta (13-22 Hz) and gamma (22-50 Hz). By computing the spatial wavelet phase coherence, we observed significant pathways including sagittal factor (anterior-posterior interhemispheric) and lateral factor (perpendicular to anterior-posterior axis). The lateral factor differences have less affect than the sagittal factor. Each band was involved in different activities in some way, however alpha band showed distinct anteriorposterior activity when the eye-closed coherence was higher than the eye open coherence.

Phase-clustering bias in phase–amplitude cross-frequency coupling and its removal

BackgroundCross-frequency coupling methods allow for the identification of non-linear interactions across frequency bands, which are thought to reflect a fundamental principle of how electrophysiological brain activity is temporally orchestrated. In this paper we uncover a heretofore unknown source of bias in a commonly used method that quantifies cross-frequency coupling (phase–amplitude-coupling, or PAC). New methodWe demonstrate that non-uniform phase angle distributions – a phenomenon that can readily occur in real data – can under some circumstances produce statistical errors and uninterpretable results when using PAC. We propose a novel debiasing procedure that, through a simple linear subtraction, effectively ameliorates this phase clustering bias. ResultsSimulations showed that debiased PAC (dPAC) accurately detected the presence of coupling. This was true even in the presence of moderate noise levels, which inflated the phase clustering bias. Finally, dPAC was applied to intracranial sleep recordings from a macaque monkey, and to hippocampal LFP data from a freely moving rat, revealing robust cross-frequency coupling in both data sets. Comparison with existing methodsCompared to dPAC, regular PAC showed inflated or deflated estimations and statistically negative coupling values, depending on the strength of the bias and the angle of coupling. Noise increased these unwanted effects. Two other frequently used phase–amplitude coupling methods (the Modulation Index and Phase Locking Value) were also affected by the bias, though allowed for statistical inferences that were similar to dPAC. ConclusionWe conclude that dPAC provides a simple modification of PAC, and thereby offers a cleaner and possibly more sensitive alternative method, to more accurately assess phase–amplitude coupling.

Trajectory of frequency stability in typical development.

This work explores a feature of brain dynamics, metastability, by which transients are observed in functional brain data. Metastability is a balance between static (stable) and dynamic (unstable) tendencies in electrophysiological brain activity. Furthermore, metastability is a theoretical mechanism underlying the rapid synchronization of cell assemblies that serve as neural substrates for cognitive states, and it has been associated with cognitive flexibility. While much previous research has sought to characterize metastability in the adult human brain, few studies have examined metastability in early development, in part because of the challenges of acquiring adequate, noise free continuous data in young children. To accomplish this endeavor, we studied a new method for characterizing the stability of EEG frequency in early childhood, as inspired by prior approaches for describing cortical phase resets in the scalp EEG of healthy adults. Specifically, we quantified the variance of the rate of change of the signal phase (i.e., frequency) as a proxy for phase resets (signal instability), given that phase resets occur almost simultaneously across large portions of the scalp. We tested our method in a cohort of 39 preschool age children (age =53 ± 13.6months). We found that our outcome variable of interest, frequency variance, was a promising marker of signal stability, as it increased with the number of phase resets in surrogate (artificial) signals. In our cohort of children, frequency variance decreased cross-sectionally with age (r = -0.47, p = 0.0028). EEG signal stability, as quantified by frequency variance, increases with age in preschool age children. Future studies will relate this biomarker with the development of executive function and cognitive flexibility in children, with the overarching goal of understanding metastability in atypical development.