Slow EEG Research Articles

Working Memory in Children with Learning Disorders: An EEG Power Spectrum Analysis.

Learning disorders (LDs) are diagnosed in children whose academic skills of reading, writing or mathematics are impaired and lagging according to their age, schooling and intelligence. Children with LDs experience substantial working memory (WM) deficits, even more pronounced if more than one of the academic skills is affected. We compared the task-related electroencephalogram (EEG) power spectral density of children with LDs (n = 23) with a control group of children with good academic achievement (n = 22), during the performance of a WM task. sLoreta was used to estimate the current distribution at the sources, and 18 brain regions of interest (ROIs) were chosen with an extended version of the eigenvector centrality mapping technique. In this way, we lessened some drawbacks of the traditional EEG at the sensor space by an analysis at the brain-sources level over data-driven selected ROIs. Results: The LD group showed fewer correct responses in the WM task, an overall slower EEG with more delta and theta activity, and less high-frequency gamma activity in posterior areas. We explain these EEG patterns in LD children as indices of an inefficient neural resource management related with a delay in neural maturation.

Coupling of gamma band activity to sleep spindle oscillations – a combined EEG/MEG study

Sleep spindles are crucial to memory consolidation. Cortical gamma oscillations (30–100 Hz) are considered to reflect processing of memory in local cortical networks. The temporal and regulatory relationship between spindles and gamma activity might therefore provide clues into how sleep strengthens cortical memory representations. Here, combining EEG with MEG recordings during sleep in healthy humans (n = 12), we investigated the temporal relationships of cortical gamma band activity, always measured by MEG, during fast (12–16 Hz) and slow (8–12 Hz) sleep spindles detected in the EEG or MEG. Time-frequency distributions did not show a consistent coupling of gamma to the spindle oscillation, although activity in the low gamma (30–40 Hz) and neighboring beta range (<30 Hz) was generally increased during spindles. However, more fine-grained analyses of cross-frequency interactions revealed that both low and high gamma power (30–100 Hz) was coupled to the phase of slow and fast EEG spindles, importantly, with this coupling at a fixed phase only for the oscillations within an individual spindle, but with variable phase across spindles. We did not observe any coupling of gamma activity for spindles detected solely in the MEG and not in parallel EEG recordings, raising the possibility that these are more local spindles of different quality. Similar to fast spindle activity, low gamma band power followed a ~0.025 Hz infraslow rhythm during sleep whose frequency, however, was significantly faster than that of spindle activity. Our findings suggest a general function of fast and slow spindles that by spanning larger cortical networks might serve to synchronize gamma band activity occurring in more local but distributed networks. Thereby, spindles might help linking local memory processing between distributed networks.

Loss of frontal regulator of vigilance during sleep inertia: A simultaneous EEG-fMRI study.

Sleep inertia refers to a distinct physiological state of waking up from sleep accompanied by performance impairments and sleepiness. The neural substrates of sleep inertia are unknown, but growing evidence suggests that this inertia state maintains certain sleep features. To investigate the neurophysiological mechanisms of sleep inertia, a comparison of pre‐sleep and post‐sleep wakefulness with eyes‐open resting‐state was performed using simultaneous EEG‐fMRI, which has the potential to reveal the dynamic details of neuroelectric and hemodynamic responses with high temporal resolution. Our data suggested sleep‐like features of slow EEG power and decreased BOLD activity were persistent during sleep inertia. In the pre‐sleep phase, participants with stronger EEG vigilance showed stronger activity in the fronto‐parietal network (FPN), but this phenomenon disappeared during sleep inertia. A time course analysis confirmed a decreased correlation between EEG vigilance and the FPN activity during sleep inertia. This simultaneous EEG‐fMRI study advanced our understanding of sleep inertia and revealed the importance of the FPN in maintaining awareness. This is the first study to reveal the dynamic brain network changes from multi‐modalities perspective during sleep inertia.

Lack of antidepressant effects of burst-suppressing isoflurane anesthesia in adult male Wistar outbred rats subjected to chronic mild stress.

Post-ictal emergence of slow wave EEG (electroencephalogram) activity and burst-suppression has been associated with the therapeutic effects of the electroconvulsive therapy (ECT), indicating that mere “cerebral silence” may elicit antidepressant actions. Indeed, brief exposures to burst-suppressing anesthesia has been reported to elicit antidepressant effects in a subset of patients, and produce behavioral and molecular alterations, such as increased expression of brain-derived neurotrophic factor (BDNF), connected with antidepressant responses in rodents. Here, we have further tested the cerebral silence hypothesis by determining whether repeated exposures to isoflurane anesthesia reduce depressive-like symptoms or influence BDNF expression in male Wistar outbred rats (Crl:WI(Han)) subjected to chronic mild stress (CMS), a model which is responsive to repeated electroconvulsive shocks (ECS, a model of ECT). Stress-susceptible, stress-resilient, and unstressed rats were exposed to 5 doses of isoflurane over a 15-day time period, with administrations occurring every third day. Isoflurane dosing is known to reliably produce rapid EEG burst-suppression (4% induction, 2% maintenance; 15 min). Antidepressant and anxiolytic effects of isoflurane were assessed after the first, third, and fifth drug exposure by measuring sucrose consumption, as well as performance on the open field and the elevated plus maze tasks. Tissue samples from the medial prefrontal cortex and hippocampus were collected, and levels of BDNF (brain-derived neurotrophic factor) protein were assessed. We find that isoflurane anesthesia had no impact on the behavior of stress-resilient or anhedonic rats in selected tests; findings which were consistent—perhaps inherently related—with unchanged levels of BDNF.

EEG Slowing and Axial Motor Impairment Are Independent Predictors of Cognitive Worsening in a Three-Year Cohort of Patients With Parkinson's Disease.

Objective: We aimed to determine whether the combination of two parameters: (a) score of axial impairment and limb rigidity (SAILR) with (b) EEG global relative median power in the frequency range theta 4–8 Hz (GRMPT) predicted cognitive outcome in patients with Parkinson's disease (PD) better than each of these measures alone.Methods: 47 non-demented patients with PD were examined and re-examined after 3 years. At both time-points, the patients underwent a comprehensive neuropsychological and neurological assessment and EEG in eyes-closed resting-state condition. The results of cognitive tests were normalized and individually summarized to obtain a “global cognitive score” (GCS). Change of GCS was used to represent cognitive changes over time. GRMPT and SAILR was used for further analysis. Linear regression models were calculated.Results: GRMPT and SAILR independently predicted cognitive change. Combination of GRMPT and SAILR improved the significance of the regression model as compared to using each of these measures alone. GRMPT and SAILR only slightly correlate between each other.Conclusion: The combination of axial signs and rigidity with quantitative EEG improves early identification of patients with PD prone to severe cognitive decline. GRMPT and SAILR seem to reflect different disease mechanisms.Significance Combination of EEG and axial motor impairment assessment may be a valuable marker in the cognitive prognosis of PD.

Dual Tasks as an Indicator of the Characteristics of Cognitive Deficit in Patients after Craniocerebral Trauma

Objectives. To study the characteristics of impairments to brain activity in patients after craniocerebral trauma (CCT) on performing double tasks as compared with normal subjects. Materials and methods. Clinical electroencephalographic (EEG) and stabilographic investigations were run in nine patients (mean age 25.0 ± 1.2 years) within three months of moderate CCT. The control group consisted of 18 healthy subjects (mean age 26.6 ± 0.07 years). All subjects performed two motor and two cognitive tasks separately and simultaneously, i.e., dual tasks. Results. Patients with CCT had cognitive deficit with retention of posture control. EEG data showed that performance of the cognitive components of dual tasks was accompanied by decreases in the coherence of the slow rhythms in the left hemisphere and frontal areas. Healthy subjects showed increases in coherence in the slow EEG rhythms in these parts of the brain. Conclusions. Dual tasks provided an informative method for evaluating the predominance of cognitive deficit after moderate CCT and use of this approach as a rehabilitation measure promoted clinical improvements.

0327 NREM Sleep EEG in Typically Developing and Drug-Naïve ADHD Adolescents: Data from a Longitudinal Study

Abstract Introduction Structural MRI studies suggest delayed brain maturation in children with attention deficit hyperactivity disorder (ADHD). The steep adolescent decline in sleep slow wave EEG activity provides an opportunity to investigate brain electrophysiological evidence for this maturational delay. Most ADHD sleep EEG studies have been cross-sectional. Here we present data from an ongoing longitudinal study of the maturational trajectories of sleep EEG in drug-naïve ADHD and typically developing adolescents. Methods Nine children diagnosed with ADHD (combined subtype, DSM-V criteria, mean age 12.39±0.61 years), and nine typically developing controls (12.07±0.35 years) were recruited. Subjects underwent an adaptation night and all night polysomnography twice yearly at the Laboratory. Sleep EEG was analyzed using fast Fourier transform. NREM delta and theta EEG activity were compared across first two recordings. Results Group effects (ADHD vs. control) on all night delta and theta energy, and delta power were not significant (p&amp;gt;0.2 for all). All night theta power was lower (p=0.035) for the ADHD group, and all night NREM sleep duration trended (p=0.060) toward being lower for the ADHD group. Controlling for sleep duration differences by examining only the first 5 h of NREM sleep showed no group effect on delta power (p=0.77) and a trend toward lower theta power (p=0.057) for the ADHD group. Conclusion At age 12 to 13 years, NREM sleep delta EEG did not differ between ADHD and control subjects. Theta power, which declines at a younger age than delta, was lower in control subjects. The two recordings thus far differ only by 6 months. The entire study will provide 5 semiannual recordings and allow us to determine if the higher theta power in the ADHD group will hold and if delta power will be greater as well, and thus provide electrophysiological support for the delayed brain maturation suggested by MRI findings. Support Shota Rustaveli National Science Foundation Grant FR17_94; Subjects Recruitment Support - Mental Health Service in Tbilisi “Kamara”.

High-voltage, diffuse delta rhythms coincide with wakeful consciousness and complexity in Angelman syndrome.

Abundant evidence from slow wave sleep, anesthesia, coma, and epileptic seizures links high-voltage, slow electroencephalogram (EEG) activity to loss of consciousness. This well-established correlation is challenged by the observation that children with Angelman syndrome (AS), while fully awake and displaying volitional behavior, display a hypersynchronous delta (1–4 Hz) frequency EEG phenotype typical of unconsciousness. Because the trough of the delta oscillation is associated with down-states in which cortical neurons are silenced, the presence of volitional behavior and wakefulness in AS amidst diffuse delta rhythms presents a paradox. Moreover, high-voltage, slow EEG activity is generally assumed to lack complexity, yet many theories view functional brain complexity as necessary for consciousness. Here, we use abnormal cortical dynamics in AS to assess whether EEG complexity may scale with the relative level of consciousness despite a background of hypersynchronous delta activity. As characterized by multiscale metrics, EEGs from 35 children with AS feature significantly greater complexity during wakefulness compared with sleep, even when comparing the most pathological segments of wakeful EEG to the segments of sleep EEG least likely to contain conscious mentation and when factoring out delta power differences across states. These findings (i) warn against reverse inferring an absence of consciousness solely on the basis of high-amplitude EEG delta oscillations, (ii) corroborate rare observations of preserved consciousness under hypersynchronization in other conditions, (iii) identify biomarkers of consciousness that have been validated under conditions of abnormal cortical dynamics, and (iv) lend credence to theories linking consciousness with complexity.

Resting anxiety increases EEG delta–beta correlation: Relationships with the Reinforcement Sensitivity Theory Personality traits

Research has shown that the coupling between slow and fast EEG frequency oscillations reflects cortico-subcortical interaction. Specifically, the between-subject delta-beta amplitude-amplitude correlation is found to increase in some hypothetically anxiogenic conditions. We tested whether cortical-subcortical coupling would increase as a function of decreased delta (theta) or higher beta (gamma) activity. EEG recording was obtained from a group of 59 students during a resting anxiogenic situation (Anxiety) and from another group of 66 during a relaxation situation (Relaxation). Participants filled out the State Anxiety and the Reinforcement Sensitivity Theory Personality Questionnaire. Between-subjects cross-frequency correlations were calculated between power values in the delta (theta) and beta (gamma) frequency bands and compared between Anxiety and Relaxation groups. A significant positive between-subject delta-beta correlation was observed in the resting Anxiety, and this association was significantly higher than that observed in the Relaxation group. In the Anxiety, but not Relaxation group, we observed a delta-beta coupling for the low delta activity. In the Anxiety group, BIS trait was significantly associated with higher strength of within-subject delta-beta coupling, while in the Relaxation group BIS was positively associated with delta-theta coupling. Interesting, in both resting Anxiety and Relaxation groups, BAS-GDP was positively associated with higher delta-gamma coupling.

Abnormal EEG Power Spectrum in Individuals with High Autistic Personality Traits: an eLORETA Study

Autistic traits lie on a continuously distributed spectrum ranging from non-clinical to clinical conditions. Indeed, autistic traits have been observed in general population at sub-threshold levels. Here, the main aim was to investigate differences in resting state (RS) electroencephalographic (EEG) power spectrum in individuals with high vs. low autistic traits. Fifty undergraduates completed the Autism-Spectrum Quotient (AQ) and the Empathy Quotient (EQ). For each participant five minutes of RS-EEG were recorded and analysed by means of the exact Low-Resolution Electromagnetic Tomography software (eLORETA). A Two-Step Cluster Analysis revealed two groups: high autistic traits (AT+) and low autistic traits (AT−) group. Compared to AT−, AT+ individuals showed an increase of delta power in parietal/occipital and cortico-limbic areas. No alterations were observed in other frequency bands. Furthermore, both AQ and EQ total scores were positively correlated with delta EEG power after controlling for sex, age, and subclinical psychopathological traits. Results show that AT+ individuals exhibit an increase in slow RS EEG power in regions involved in self-referential processes, suggesting a reduction in these internally directed mental activities and adding new evidence on the existence of a continuum in the autistic spectrum which spreads from clinical to non-clinical significance.

Slow frequency EEG activity in obesity hypoventilation syndrome

Slow frequency EEG activity in obesity hypoventilation syndrome

Localizing non-epileptiform abnormal brain function in children using high density EEG: Electric Source Imaging of focal slowing

BackgroundElectric Source Imaging (ESI) of interictal epileptiform discharges (IED) is increasingly validated for localizing epileptic activity. In children, IED can be absent or multifocal even in cases of a focal epileptogenic zone and additional electrophysiological markers are needed. Here, we investigated ESI of pathological focal slowing (FS) recorded on EEG as a new localizing marker in children with drug-resistant epilepsy. MethodsWe selected 15 children (median: 12; range: 4-18yrs), with high-density EEG (hdEEG), presurgical evaluation and surgical resection. One patient had a non-lesional MRI. ESI of patient-specific focal slow activity was performed (distributed linear inverse solution and individual head model). The maximal average power in the band of interest was considered as the source of focal slowing (ESI-FS). The Euclidian distance between ESI-FS and the resection (5 mm margin) was compared to the localization of maximal ESI of interictal epileptiform discharges (ESI-IED), interictal FDG-PET and ictal SPECT/SISCOM. ResultsIn 9/15 patients (60%), ESI of focal slowing (ESI-FS) was inside or ≤5 mm from resection margins. The remaining 6/15 cases had distances ≤15 mm. In 9/15 patients with interictal spikes, the ESI-IED was concordant with the resection. 6/15 patients with concordant ESI-FS showed also interictal concordant ESI of IED; in 3/15 patients, ESI-FS but not ESI-IED was concordant with the resection. In 10/15 patients, ESI-FS was concordant with MRI lesion and for ESI-IED this concordance was on 8/15 patients. Maximal hypometabolism and SISCOM were concordant with the resection for 7/15 and 7/12, respectively. ConclusionThese findings suggest that “non-epileptiform” EEG activity, such as focal slowing, could be a complementary useful marker to localize the epileptogenic zone. ESI-FS may notably be applied in young patients without focal interictal spikes or multifocal spikes. This potential new marker of brain dysfunction has potential applications to other neurological disorders associated with slow EEG activity.

Do readiness potentials happen all the time?

The Readiness Potential (RP) is a slow negative EEG potential found in the seconds preceding voluntary actions. Here, we explore whether the RP is found only at this time, or if it also occurs when no action is produced. Recent theories suggest the RP reflects the average of accumulated stochastic fluctuations in neural activity, rather than a specific signal related to self-initiated action: RP-like events should then be widely present, even in the absence of actions. We investigated this hypothesis by searching for RP-like events in background EEG of an appropriate dataset for which the action-locked EEG had previously been analysed to test other hypotheses [Khalighinejad, N., Brann, E., Dorgham, A., Haggard, P. Dissociating cognitive and motoric precursors of human self-initiated action. Journal of Cognitive Neuroscience. 2019, 1-14]. We used the actual mean RP as a template, and searched the entire epoch for similar neural signals, using similarity metrics that capture the temporal or spatial properties of the RP. Most EEG epochs contained a number of events that were similar to the true RP, but did not lead directly to any voluntary action. However, these RP-like events were equally common in epochs that eventually terminated in voluntary actions as in those where voluntary actions were not permitted. Events matching the temporal profile of the RP were also a poor match for the spatial profile, and vice versa. We conclude that these events are false positives, and do not reflect the same mechanism as the RP itself. Finally, applying the same template-search algorithm to simulated EEG data synthesized from different noise distributions showed that RP-like events will occur in any dataset containing the 1⁄f noise ubiquitous in EEG recordings. To summarise, we found no evidence of genuinely RP-like events at any time other than immediately prior to self-initiated actions. Our findings do not support a purely stochastic model of RP generation, and suggest that the RP may be a specific precursor of self-initiated voluntary actions.

Comparation between slow frequency quantitative eeg and nihss in acute ischaemic stroke

Background In acute phase of stroke, the severity is one of the important output predictors. There is a high correlation between patient clinical improvement and tissue volume surviving in functional tissue (ischemic penumbra). In some studies show that NIHSS is a good predictor of stroke output whereas quantitative EEG is a tool that can be used to assess functional brain that reflects evolution of penumbra. Purpose To determine the quantitative EEG suitability with severity of acute ischemic stroke (NIHSS) patient in Sardjito hospital Method This study was conducted using observational cross sectional design with Spearman test. The subjects of this study were taken from patients at RSUP Dr Sardjito Yogyakarta in January 2018 – March 2018 that has been diagnosed ischemic stroke through anamnesis, physical examination and head CT scan and has been assessed the degree of stroke severity with NIHSS. Performed an absolute power and relative power assessment of qEEG against NIHSS on the subject and for secondary outcomes, we also performed delta alpha ratio (DAR) and delta tetha alpha betha ratio (DTABR). Result and conclusion The value of delta and tetha band were not significant but delta alpha ratio (r = 0,419) and delta tetha alpha betha ratio (r = 0,453) were positively correlated with sufficient strength with NIHSS in acute ischaemic stroke patients.

Slow-frequency electroencephalography activity during wake and sleep in obesity hypoventilation syndrome.

Neurophysiological activity during wake and sleep states in obesity hypoventilation (OHS) and its relationship with neurocognitive function is not well understood. This study compared OHS with equally obese obstructive sleep apnea (OSA) patients, with similar apnea-hypopnea indices. Resting wake and overnight sleep electroencephalography (EEG) recordings, neurocognitive tests, and sleepiness, depression and anxiety scores were assessed before and after 3 months of positive airway pressure (PAP) therapy in 15 OHS and 36 OSA patients. Pretreatment, greater slow frequency EEG activity during wake and sleep states (increased delta-alpha ratio during sleep, and theta power during awake) was observed in the OHS group compared to the OSA group. EEG slowing was correlated with poorer performance on the psychomotor vigilance task (slowest 10% of reciprocal reaction times, psychomotor vigilance test [PVT SRRT], primary outcome), and worse sleep-related hypoxemia measures in OHS. There was no between-group significant difference in PVT performance at pre or post-treatment. Similarly, despite both groups demonstrating improved sleepiness, anxiety and depression scores with PAP therapy, there were no differences in treatment response between the OSA and OHS groups. Patients with OHS have greater slow frequency EEG activity during sleep and wake than equally obese patients with OSA. Greater EEG slowing was associated with worse vigilance and lower oxygenation during sleep. This trial was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12615000122550).

Predictive Value of Slow and Fast EEG Oscillations for Methylphenidate Response in ADHD.

Attention-deficit/hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder and is characterized by symptoms of inattention and/or hyperactivity and impulsivity. In the current study, we obtained quantitative EEG (QEEG) recordings of 51 children aged between 6 and 12 years before the initiation of methylphenidate treatment. The relationship between changes in the scores of ADHD symptoms and initial QEEG features (power/power ratios values) were assessed. In addition, the children were classified as responder and nonresponder according to the ratio of their response to the medication (>25% improvement after medication). Logistic regression analyses were performed to analyze the accuracy of QEEG features for predicting responders. The findings indicate that patients with increased delta power at F8, theta power at Fz, F4, C3, Cz, T5, and gamma power at T6 and decreased beta powers at F8 and P3 showed more improvement in ADHD hyperactivity symptoms. In addition, increased delta/beta power ratio at F8 and theta/beta power ratio at F8, F3, Fz, F4, C3, Cz, P3, and T5 showed negative correlations with Conners' score difference of hyperactivity as well. This means, those with greater theta/beta and delta/beta powers showed more improvement in hyperactivity following medication. Theta power at Cz and T5 and theta/beta power ratios at C3, Cz, and T5 have significantly classified responders and nonresponders according to the logistic binary regression analysis. The results show that slow and fast oscillations may have predictive value for treatment response in ADHD. Future studies should seek for more sensitive biomarkers.

A hypothesis regarding how sleep can calibrate neuronal excitability in the central nervous system and thereby offer stability, sensitivity and the best possible cognitive function

The function of sleep in mammal and other vertebrates is one of the great mysteries of biology. Many hypotheses have been proposed, but few of these have made even the slightest attempt to explain the essence of sleep – the uncompromising need for reversible unconsciousness. During sleep, epiphenomena – often of a somatic character – occur, but these cannot explain the core function of sleep. One answer could be hidden in the observations made for long periods of time of the function of the central nervous system (CNS). The CNS is faced with conflicting requirements on stability and excitability. A high level of excitability is desirable, and is also a prerequisite for sensitivity and quick reaction times; however, it can also lead to instability and the risk of feedback, with life-threatening epileptic seizures. Activity-dependent negative feedback in neuronal excitability improves stability in the short term, but not to the degree that is required. A hypothesis is presented here demonstrating how calibration of individual neurons – an activity which occurs only during sleep – can establish the balanced and highest possible excitability while also preserving stability in the CNS. One example of a possible mechanism is the observation of slow oscillations in EEGs made on birds and mammals during slow wave sleep. Calibration to a genetically determined level of excitability could take place in individual neurons during the slow oscillation. This is only possible offline, which explains the need for sleep. The hypothesis can explain phenomena such as the need for unconsciousness during sleep, with the disconnection of sensory stimuli, slow EEG oscillations, the relationship of sleep and epilepsy, age, the effects of sleep on neuronal firing rate and the effects of sleep deprivation and sleep homeostasis. This is with regard primarily to mammals, including humans, but also all other vertebrates.

CT perfusion and EEG patterns in patients with acute isolated aphasia in seizure-related stroke mimics

PurposeIsolated speech impairment is one of the most challenging clinical manifestations of stroke mimic (SM). We aimed to investigate perfusional and EEG pattern of isolated aphasia to better differentiate between vascular and epileptic etiology in emergency settings. MethodWe retrospectively analyzed 481 cases with acute focal neurological symptoms admitted to our Stroke Unit. The patients showing isolated aphasia and confirmed ischemic infarction or SM with seizure etiology on follow-up were included for subsequent analysis of clinical, neuroimaging, and EEG data. We investigated differences in CT Perfusion maps between ROI in the anatomical area compatible with clinical presentation, contralateral ROI and EEG in order to evaluate perfusion and brain oscillatory activity abnormalities. Results45 patients presented isolated aphasia as principal neurological symptom: 27 cases due to acute ischemic event, 11 due to seizure SM, while 7 were SM due to other etiologies. Out of 11 SM patients with seizure etiology, significant hyperperfusion on CTP maps (MTT AI%<-10%) and sharp EEG waves were observed in 8 patients, while in 3 patients slight hypoperfusion (MTT AI%<20%) and slow EEG rhythms were detected. 24 out of 27 ischemic stroke patients presented severe hypoperfusion with MTT AI above the stroke threshold (MTT AI > 45%). All ischemic stroke patients presented slower EEG rhythms. ConclusionsThe main finding of this study is the identification of different clinical and neuroimaging patterns of isolated aphasia with epileptic or ischemic etiology in emergency settings.

Ketamine-induced regulation of TrkB-GSK3β signaling is accompanied by slow EEG oscillations and sedation but is independent of hydroxynorketamine metabolites

Subanesthetic rather than anesthetic doses are thought to bring the rapid antidepressant effects of the NMDAR (N-methyl-d-aspartate receptor) antagonist ketamine. Among molecular mechanisms, activation of BDNF receptor TrkB along with the inhibition of GSK3β (glycogen synthase kinase 3β) are considered as critical molecular level determinants for ketamine's antidepressant effects. Hydroxynorketamines (2R,6R)-HNK and (2S,6S)–HNK), non-anesthetic metabolites of ketamine, have been proposed to govern the therapeutic effects of ketamine through a mechanism not involving NMDARs. However, we have shown that nitrous oxide, another NMDAR blocking anesthetic and a putative rapid-acting antidepressant, evokes TrkB-GSK3β signaling alterations during rebound slow EEG (electroencephalogram) oscillations. We investigated here the acute effects of ketamine, 6,6-d2-ketamine (a ketamine analogue resistant to metabolism) and cis-HNK that contains (2R,6R) and (2S,6S) enantiomers in 1:1 ratio, on TrkB-GSK3β signaling and concomitant electroencephalographic (EEG) alterations in the adult mouse cortex. Ketamine dose-dependently increased slow oscillations and phosphorylations of TrkBY816 and GSK3βS9 in crude brain homogenates (i.e. sedative/anesthetic doses (>50 mg/kg, i.p.) produced more prominent effects than a subanesthetic dose (10 mg/kg, i.p.)). Similar, albeit less obvious, effects were seen in crude synaptosomes. A sedative dose of 6,6-d2-ketamine (100 mg/kg, i.p.) recapitulated the effects of ketamine on TrkB and GSK3β phosphorylation while cis-HNK at a dose of 20 mg/kg produced negligible acute effects on TrkB-GSK3β signaling or slow oscillations. These findings suggest that the acute effects of ketamine on TrkB-GSK3β signaling are by no means restricted to subanesthetic (i.e. antidepressant) doses and that cis-HNK is not responsible for these effects.

Synchronization of Slow Cortical Rhythms During Motor Imagery-Based Brain-Machine Interface Control.

Modulation of sensorimotor rhythm (SMR) power, a rhythmic brain oscillation physiologically linked to motor imagery, is a popular Brain-Machine Interface (BMI) paradigm, but its interplay with slower cortical rhythms, also involved in movement preparation and cognitive processing, is not entirely understood. In this study, we evaluated the changes in phase and power of slow cortical activity in delta and theta bands, during a motor imagery task controlled by an SMR-based BMI system. In Experiment I, EEG of 20 right-handed healthy volunteers was recorded performing a motor-imagery task using an SMR-based BMI controlling a visual animation, and during task-free intervals. In Experiment II, 10 subjects were evaluated along five daily sessions, while BMI-controlling same visual animation, a buzzer, and a robotic hand exoskeleton. In both experiments, feedback received from the controlled device was proportional to SMR power (11-14 Hz) detected by a real-time EEG-based system. Synchronization of slow EEG frequencies along the trials was evaluated using inter-trial-phase coherence (ITPC). Results: cortical oscillations of EEG in delta and theta frequencies synchronized at the onset and at the end of both active and task-free trials; ITPC was significantly modulated by feedback sensory modality received during the tasks; and ITPC synchronization progressively increased along the training. These findings suggest that phase-locking of slow rhythms and resetting by sensory afferences might be a functionally relevant mechanism in cortical control of motor function. We propose that analysis of phase synchronization of slow cortical rhythms might also improve identification of temporal edges in BMI tasks and might help to develop physiological markers for identification of context task switching and practice-related changes in brain function, with potentially important implications for design and monitoring of motor imagery-based BMI systems, an emerging tool in neurorehabilitation of stroke.