EEG Desynchronization Research Articles

ВИВЧЕННЯ ФУНКЦІОНАЛЬНО-РЕГУЛЮЮЧОГО ЕФЕКТУ РІЗНИХ МЕТОДИК ПАЛЬМІНГУ

Relevance of the research topic. The prevalence of myopia associated with visual system strain necessitates the improvement of existing methods and the search for new effective methods of treatment and prevention for this condition. The active inclusion of physical rehabilitation methods in the complex therapy of myopia requires alignment with the pathogenetic rationale for their intended application. Objective: This study aims to identify the specific functional-regulatory effects of different palming techniques. Methods: The research was conducted using electroencephalography in three different palming variants. Results: Discrepancies were found in brain bioelectropotential indicators, confirming different mechanisms of effect: a relaxing effect in Bates' method and a stimulating effect in Norbekov’s method. Conclusions: 1.Preventive measures for eye strain and the development of myopia should align with the principles of overall physical conditioning for each individual. 2. A logical collaboration between ophthalmologists and physical therapists in the prevention and treatment of myopia forms a basis for defining this direction as opto-physical rehabilitation. 3. In developing protocols involving physical therapy methods for myopia prevention and treatment, it is advisable to evaluate their effectiveness using appropriate objective methods. 4. During palming according to Bates, brain biopotential changes indicate a reduction in α-rhythm and an increase in β1-rhythm, showing an EEG desynchronization type. 5. During neutral-condition palming, an increase in α-rhythm activity indicates an EEG hypersynchronization type. 6. A comparative increase in the brain bioelectropotential indicators for Δ and Ӫ rhythms during Bates' palming suggests reduced brain activity, while brain activity increases in neutral and Norbekov palming conditions. 7. The results of electroencephalographic studies confirm the functional directionality of Bates’ (relaxing type) and Norbekov’s (stimulating type) palming techniques, which should be considered in their application.

EEG-Characteristics of Aesthetic Perception and Evaluation of Artworks During a Museum Visit: А Neuroaesthetic Study

Twenty-eight people (30–70 years old, 12 men, 16 women, artists and non-artists) participated in a comparative neuroaesthetic study in the conditions of real-life visit to M. Vrubel mono-exhibition (Russian Museum, St. Petersburg). During the visit to the exhibition (usually lasted for around 60 min), EEG of participants was recorded. The subjects were looking at the paintings for 30 seconds to 3 min and evaluated the subjective aesthetic “attractiveness” of the paintings by a series of button presses (from 1 to 10). Were analyzed EEG spectral power in the α1 (8–10 Hz)-, α2 (10–13 Hz)-, β1 (13–18 Hz)-, β2 (13–30 Hz)-frequency bands during viewing the most famous Vrubel paintings (“Bogatyr”, “Swan Princess”, “Swan”, “Sitting Demon”, “Flying Demon”, “Pan”, etc.) and event-related EEG synchronization/desynchronization in relation to the subjective emotional and aesthetic evaluation of these paintings. Professional artists showed lower spectral power values in α1 (leads F3, C3, T4, Pz) and α2 (F3, Fz, F4, C3, Cz, C4, P3, Pz, P4)-frequency bands in frontal, central, and parietal regions. The artists were also found to have lower power values in β1,2-frequency bands in frontal (F3, F4, C3) regions and higher power values in occipital (O1, O2 – β1, β2) and posterior temporal (β2) cortical regions compared to the group of subjects with no special artistic education. Moreover, artists decision-making about the high emotional-aesthetic attractiveness of paintings was accompanied by an increase in event-related EEG synchronization for 11.5–27 Hz in frontal and central cortical areas over 580–360 ms before giving the response, compared to non-artists, whereas low emotional-aesthetic evaluation was characterized by 9–27 Hz EEG desynchronization, which started 60 ms before the giving the response and lasted up to 440 ms after it, in the posterior temporal and parietal regions. The differences in frontal cortical areas may indicate a higher engagement of the reward system during the perception of aesthetically pleasing paintings, and the differences in parietal and posterior temporal areas may indicate a continuing visual synthesis (more sustained visual attention) during the perception of subjectively less attractive paintings in artists compared to non-artists.

Source localization of mu-rhythm event related desynchronization in EEG during tactile imagery

Tactile imagery remains a relatively understudied phenomenon in the field of mental imagery research. However, alongside motor imagery, this technique holds promise as an effective tool for sensorimotor rehabilitation following stroke and spinal cord injuries. In this study, conducted with 22 healthy volunteers, we investigated the source localization of mu-rhythm event related desynchronization (Event-Related Desynchronization, ERD) using multi-channel electroencephalogram recordings and subsequent inverse problem solution with the sLORETA method. All participants exhibited ERD during tactile imagery task, as well as under vibrotactile stimulation. It was demonstrated that mu-rhythm ERD during vibrotactile stimulation, as well as tactile imagery, was localized in the sensorimotor areas of the contralateral hemisphere. Within the source space, ERD in the postcentral gyrus was significantly stronger compared to the precentral gyrus. These findings indicate that tactile imagery, akin to the perception of real tactile stimuli, leads to prominent activation of sensorimotor cortical areas, consistent with the general understanding of the shared neural substrate during mental imagery and perception.

Dynamics of EEG Synchronization and Desynchronization on Execution of Real and Imaginary Hand Movements Towards a Visible Target

Dynamics of EEG Synchronization and Desynchronization on Execution of Real and Imaginary Hand Movements Towards a Visible Target

Dynamics of EEG synchronization and desynchronization when performing real and imagined hand reaching

The work investigates spatial and temporal EEG patterns during real and imagined execution of hand reaching. Six independent sources of electrical activity were identified in the EEG recordings. The sources corresponded to the premotor areas, supplementary motor area, primary motor areas, and posterior parietal cortex. Their activation patterns in the alpha and beta range were studied using a continuous wavelet transform. The main differences between real and imagined movement are found in the activation of primary motor and premotor areas. Asymmetry in activation of primary motor areas was observed only during the imaginary movements. Desynchronization in premotor areas of both the alpha and beta ranges, suggesting their activation, accompanied the imaginary movements throughout their course. On the other hand, hypersynchronization was observed in premotor areas during real movement, which likely corresponds to inhibition, while desynchronization was observed in the latent period, 1.5 seconds before the start of movement. Thus, an imaginary movement bears the features of planning a real movement.

High-definition transcranial direct current stimulation desynchronizes refractory status epilepticus

Recently, we showed that high-definition transcranial direct current stimulation (hd-tDCS) can acutely reduce epileptic spike rates during and after stimulation in refractory status epilepticus (RSE), with a greater likelihood of patient discharge from the intensive care unit compared to historical controls. We investigate whether electroencephalographic (EEG) desynchronization during hd-tDCS can help account for observed anti-epileptic effects. Defining desynchronization as greater power in higher frequencies such as above 30 ​Hz (“gamma”) and lesser power in frequency bands lower than 30 ​Hz, we analyzed 27 EEG sessions from 10 RSE patients who had received 20-minute session(s) of 2-milliamperes of transcranial direct current custom-targeted at the epileptic focus as previously determined by a clinical EEGer monitoring the EEG in real-time. During hd-tDCS, median relative power change over the EEG electrode chains in which power changes were maximal was +4.84%, −5.25%, −1.88%, −1.94%, and +4.99% for respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p ​= ​0.0001); and +4.13%, −5.44%, −1.81%, −3.23%, and +5.41% in the referential Laplacian montage (p ​= ​0.0012). After hd-tDCS, median relative power changes reversed over the EEG electrode chains in which power changes were maximal: −2.74%, +4.20%, +1.74%, +1.75%, and −4.68% for the respective delta, theta, alpha, beta, and gamma frequency bands in the bipolar longitudinal montage (p ​= ​0.0001); and +1.59%, +5.07%, +1.74%, +2.40%, and −5.12% in the referential Laplacian montage (p ​= ​0.0004). These findings are consistent with EEG desynchronization through theta-alpha-beta-gamma bands during hd-tDCS, helping account for the efficacy of hd-tDCS as an emerging novel anti-epileptic therapy against RSE.

Electric activity of the brain at early and late clinical stages of experimental modeling of Parkinson's disease, an impact of hemantane

S. To study an influence of the adamantane derivative hemantane on the electrical activity of the brain structures of mice at the early and late (severe) stages of experimental modeling of Parkinson's disease (PD). For experimental modeling of PD in C57BL/6J mice, 30 male C57BL/6J mice weighing 25-32 g were systemically (intraperitoneally) administered proneurotoxin MPTP in two modes corresponding to different clinical stages of the disease: 1-methyl-4-phenyl-1.2.3.6-tetrahydropyridine (MPTP) at a dose of 12 mg/kg, 4 times and 20 mg/kg, 4 times with an interval of 2 hours, respectively. At the early and late clinical stages of experimental modeling of PD in the brain structures of mice (sensorimotor cortex, substantia nigra, caudate nucleus), EEG desynchronization, an increase in wave amplitude, and an increase in the power spectrum in the range of delta frequencies and beta frequencies are observed at the late symptomatic stage experimental model of PD along with a decrease in electrical activity in the range of 4-12 Hz. Preliminary application of the adamantane derivative hemantane at a dose of 20 mg/kg, both in the early and late clinical stages of PD, prevented an excessive increase in the amplitudes of all groups of waves, normalized theta activity in the range of 4-12 Hz, reduced pathological slowing and dysregulation activity in the ranges delta and beta waves, with the prevalence of these effects in the substantia nigra of the brain of animals. The effect of hemantane is more pronounced at the early clinical stage of experimental modeling of PD than at the later (full-scale) stage.

Missing Puzzle Pieces in Dementia Research: HCN Channels and Theta Oscillations.

Increasing evidence indicates a role of hyperpolarization activated cation (HCN) channels in controlling the resting membrane potential, pacemaker activity, memory formation, sleep, and arousal. Their disfunction may be associated with the development of epilepsy and age-related memory decline. Neuronal hyperexcitability involved in epileptogenesis and EEG desynchronization occur in the course of dementia in human Alzheimer's Disease (AD) and animal models, nevertheless the underlying ionic and cellular mechanisms of these effects are not well understood. Some suggest that theta rhythms involved in memory formation could be used as a marker of memory disturbances in the course of neurogenerative diseases, including AD. This review focusses on the interplay between hyperpolarization HCN channels, theta oscillations, memory formation and their role(s) in dementias, including AD. While individually, each of these factors have been linked to each other with strong supportive evidence, we hope here to expand this linkage to a more inclusive picture. Thus, HCN channels could provide a molecular target for developing new therapeutic agents for preventing and/or treating dementia.

Event-Related EEG Desynchronization Reveals Enhanced Motor Imagery From the Third Person Perspective by Manipulating Sense of Body Ownership With Virtual Reality for Stroke Patients.

Virtual reality (VR)-based rehabilitation training holds great potential for post-stroke motor recovery. Existing VR-based motor imagery (MI) paradigms mostly focus on the first-person perspective, and the benefit of the third-person perspective (3PP) remains to be further exploited. The 3PP is advantageous for movements involving the back or those with a large range because of its field coverage. Some movements are easier to imagine from the 3PP. However, the 3PP training efficiency may be unsatisfactory, which may be attributed to the difficulty encountered when generating a strong sense of ownership (SOO). In this work, we attempt to enhance a visual-guided 3PP MI in stroke patients by eliciting the SOO over a virtual avatar with VR. We propose to achieve this by inducing the so-called out-of-body experience (OBE), which is a full-body illusion (FBI) that people misperceive a 3PP virtual body as his/her own (i.e., generating the SOO to the virtual body). Electroencephalography signals of 13 stroke patients are recorded while MI of the affected upper limb is being performed. The proposed paradigm is evaluated by comparing event-related desynchronization (ERD) with a control paradigm without FBI induction. The results show that the proposed paradigm leads to a significantly larger ERD during MI, indicating a bilateral activation pattern consistent with that in previous studies. In conclusion, 3PP MI can be enhanced in stroke patients by eliciting the SOO through induction of the "OBE" FBI. This study offers more possibilities for virtual rehabilitation in stroke patients and can further facilitate VR application in rehabilitation.

Event-related EEG synchronization and desynchronization in patients with obsessive-compulsive disorder.

Symptoms in patients with obsessive-compulsive disorder (OCD) are associated with impairment in cognitive control, attention, and action inhibition. We investigated OCD group differences relative to healthy subjects in terms of event-related alpha and beta range synchronization (ERS) and desynchronization (ERD) during a visually cued Go/NoGo task. Subjects were 62 OCD patients and 296 healthy controls (HC). The OCD group in comparison with HC, showed a changed value of alpha/beta oscillatory power over the central cortex, in particular, an increase in the alpha/beta ERD over the central-parietal cortex during the interstimulus interval (Cue condition) as well as changes in the postmovement beta synchronization topography and frequency. Over the frontal cortex, the OCD group showed an increase in magnitude of the beta ERS in NoGo condition. Within the parietal-occipital ERS/ERD modulations, the OCD group showed an increase in the alpha/beta ERD over the parietal cortex after the presentation of the visual stimuli as well as a decrease in the beta ERD over the occipital cortex after the presentation of the Cue and Go stimuli. The specific properties in the ERS/ERD patterns observed in the OCD group may reflect high involvement of the frontal and central cortex in action preparation and action inhibition processes and, possibly, in maintaining the motor program, which might be a result of the dysfunction of the cortico-striato-thalamo-cortical circuits involving prefrontal cortex. The data about enhanced involvement of the parietal cortex in the evaluation of the visual stimuli are in line with the assumption about overfocused attention in OCD.

The challenge of measuring physiological parameters during motor imagery engagement in patients after a stroke.

It is suggested that eye movement recordings could be used as an objective evaluation method of motor imagery (MI) engagement. Our investigation aimed to evaluate MI engagement in patients after stroke (PaS) compared with physical execution (PE) of a clinically relevant unilateral upper limb movement task of the patients' affected body side. In total, 21 PaS fulfilled the MI ability evaluation [Kinaesthetic and Visual Imagery Questionnaire (KVIQ-10), body rotation task (BRT), and mental chronometry task (MC)]. During the experiment, PaS moved a cup to distinct fields while wearing smart eyeglasses (SE) with electrooculography electrodes integrated into the nose pads and electrodes for conventional electrooculography (EOG). To verify MI engagement, heart rate (HR) and oxygen saturation (SpO2) were recorded, simultaneously with electroencephalography (EEG). Eye movements were recorded during MI, PE, and rest in two measurement sessions to compare the SE performance between conditions and SE's psychometric properties. MI and PE correlation of SE signals varied between r = 0.12 and r = 0.76. Validity (cross-correlation with EOG signals) was calculated for MI (r = 0.53) and PE (r = 0.57). The SE showed moderate test-retest reliability (intraclass correlation coefficient) with r = 0.51 (95% CI 0.26-0.80) for MI and with r = 0.53 (95% CI 0.29 - 0.76) for PE. Event-related desynchronization and event-related synchronization changes of EEG showed a large variability. HR and SpO2 recordings showed similar values during MI and PE. The linear mixed model to examine HR and SpO2 between conditions (MI, PE, rest) revealed a significant difference in HR between rest and MI, and between rest and PE but not for SpO2. A Pearson correlation between MI ability assessments (KVIQ, BRT, MC) and physiological parameters showed no association between MI ability and HR and SpO2. The objective assessment of MI engagement in PaS remains challenging in clinical settings. However, HR was confirmed as a reliable parameter to assess MI engagement in PaS. Eye movements measured with the SE during MI did not resemble those during PE, which is presumably due to the demanding task. A re-evaluation with task adaptation is suggested.

Ictal EEG desynchronization during low-voltage fast activity for prediction of surgical outcomes in focal epilepsy.

The authors investigated alterations in functional connectivity (FC) and EEG power during ictal onset patterns of low-voltage fast activity (LVFA) in drug-resistant focal epilepsy. They hypothesized that such changes would be useful to classify epilepsy surgical outcomes. In a cohort of 79 patients with drug-resistant focal epilepsy who underwent stereoelectroencephalography (SEEG) evaluation as well as resective surgery, FC changes during the peri-LVFA period were measured using nonlinear regression (h2) and power spectral properties within/between three regions: the seizure onset zone (SOZ), early propagation zone (PZ), and noninvolved zone (NIZ). Desynchronization and power desynchronization h2 indices were calculated to assess the degree of EEG desynchronization during LVFA. Multivariate logistic regression was employed to control for confounding factors. Finally, receiver operating characteristic curves were generated to evaluate the performance of desynchronization indices in predicting surgical outcome. Fifty-three patients showed ictal LVFA and distinct zones of the SOZ, PZ, and NIZ. Among them, 39 patients (73.6%) achieved seizure freedom by the final follow-up. EEG desynchronization, measured by h2 analysis, was found in the seizure-free group during LVFA: FC decreased within the SOZ and between regions compared with the pre-LVFA and post-LVFA periods. In contrast, the non-seizure-free group showed no prominent EEG desynchronization. The h2 desynchronization index, but not the power desynchronization index, enabled classification of seizure-free versus non-seizure-free patients after resective surgery. EEG desynchronization during the peri-LVFA period, measured by within-zone and between-zone h2 analysis, may be helpful for identifying patients with favorable postsurgical outcomes and also may potentially improve epileptogenic zone identification in the future.

Underlying pharmacological mechanisms of psilocin-induced broadband desynchronization and disconnection of EEG in rats.

Psilocybin is one of the most extensively studied psychedelic drugs with a broad therapeutic potential. Despite the fact that its psychoactivity is mainly attributed to the agonism at 5-HT2A receptors, it has high binding affinity also to 5-HT2C and 5-HT1A receptors and indirectly modulates the dopaminergic system. Psilocybin and its active metabolite psilocin, as well as other serotonergic psychedelics, induce broadband desynchronization and disconnection in EEG in humans as well as in animals. The contribution of serotonergic and dopaminergic mechanisms underlying these changes is not clear. The present study thus aims to elucidate the pharmacological mechanisms underlying psilocin-induced broadband desynchronization and disconnection in an animal model. Selective antagonists of serotonin receptors (5-HT1A WAY100635, 5-HT2A MDL100907, 5-HT2C SB242084) and antipsychotics haloperidol, a D2 antagonist, and clozapine, a mixed D2 and 5-HT receptor antagonist, were used in order to clarify the underlying pharmacology. Psilocin-induced broadband decrease in the mean absolute EEG power was normalized by all antagonists and antipsychotics used within the frequency range 1-25 Hz; however, decreases in 25-40 Hz were influenced only by clozapine. Psilocin-induced decrease in global functional connectivity and, specifically, fronto-temporal disconnection were reversed by the 5-HT2A antagonist while other drugs had no effect. These findings suggest the involvement of all three serotonergic receptors studied as well as the role of dopaminergic mechanisms in power spectra/current density with only the 5-HT2A receptor being effective in both studied metrics. This opens an important discussion on the role of other than 5-HT2A-dependent mechanisms underlying the neurobiology of psychedelics.

Words Listening Related Electroencephalography Spectrum Perturbations in Normally Developing Children and Sensory Alalia Children

The analysis of electroencephalography (EEG) event related spectrum perturbations in 23 normally developing and 23 sensory alalia children of age between 4 and 10 years old during listening to nouns is conducted. In EEG θ-frequency range of healthy children, synchronization was detected in the frontal, central, and temporal leads, and desynchronization was found in most leads in children with sensory alalia. Intergroup differences in the reactivity of the EEG θ-range reached the level of statistical significance in C4 lead. In the α‑range, EEG desynchronization was observed in typically developing children, and synchronization was observed in children with sensory alalia. Differences in the α-activity power reached the level of statistical significance in leads C3, F3, P3, O1. An EEG θ-band synchronization decrease during words listening in children with sensory alalia may reflect an impairment of retrieving words from memory and less emotional involvement in the speech perception process, while the absence of α-activity desynchronization in the central leads is a impairment of the functioning of sensorimotor neural networks, involved in the speech perception and generation. The revealed features of EEG reactivity are important for understanding the central speech perception mechanisms in normal children, as well as in children with disorders such as sensory alalia.

Особенности реактивности μ-ритма ЭЭГ у детей с расстройствами аутистического спектра в ситуациях помогающего поведения

One of the subjects being discussed by the professional community currently is the role possibly played by the mirror neuron system (MNS) in the violation of social behavior of children with autism spectrum disorders (ASD). The MNS is known to shape the perception of emotions of others and understanding and imitation of their actions. Mu rhythm desynchronization in EEG is considered to be the indicator of the MNS activation. The purpose of this study was to identify the features of reactivity of the EEG mu rhythm within an individually determined frequency range in preschoolers with ASD in situations requiring instrumental, emotional and altruistic helping behavior (HB). The study involved children 4–7 years old with ASD (n = 26) and their normally developing peers without the condition (n = 37). Although in most cases, HB was more pronounced in the group of normally developing children, the differences between the groups are significant only for altruistic HP (p < 0.01), and for the situation requiring complex altruistic and emotional HP it approaches significance (p = 0.09). Evaluation of the mu rhythm reactivity indices showed that the tasks invoking complex altruistic and emotional HB bring this indicator down significantly in children with ASD compared to the group of normally developing participants, as shown by the central leads of the left and right hemispheres and the parietal lead of the right hemisphere (C3: p = 0.02 ; C4: p = 0.03; P4: p = 0.03). It is assumed that the detected features stem from the impaired functioning of the MNS and the downstream regulation to the MNS from prefrontal cortex and other areas of the neocortex. The data obtained can be used in development of EEG biofeedback training protocols for children with ASD.

Intact memory storage but impaired retrieval in visual memory in autism: New insights from an electrophysiological study.

In a recent study on visual episodic memory (Desaunay, Clochon, et al., 2020), we have shown event-related potentials (ERPs) differences associated with priming (150-300 msec), familiarity (350-470 msec), and recollection (600-700 msec), in young people with autism spectrum disorders (ASD) compared with typical development (TD). To go further into the study of the processes of storage and retrieval of the memory trace, we re-analyzed Desaunay, Clochon, et al's data using time-frequency analysis, that is, event-related synchronization and desynchronization (ERS/ERD). This allows a decomposition of the spectral power within frequency bands associated with these ERPs. We focused both on the same time windows and the same regions of interest as previously published. We mainly identified, in ASD compared with TD, reduced ERS in low-frequencies (delta, theta) in early time-windows, and non-significant differences in ERD in higher frequencies (alpha, beta1) in all time-windows. Reduced ERS during recognition confirmed previously reported diminution of priming effects and difficulties in manipulation and retrieval of both semantic and episodic information. Conversely, preserved ERD corroborates a preservation of memory storage processes. These observations are consistent with a cognitive model of memory in ASD, that suggests difficulties in cognitive operations or executive demand at retrieval, subsequent to successful long-term storage of information. LAY SUMMARY: We assessed the EEG synchronization and desynchronization, during visual episodic recognition. We observed, in youth with Autism, reduced synchronization in low-frequencies (delta, theta), suggesting reduced access to and manipulation of long-term stored information. By contrast, non-significant differences in desynchronization at higher frequencies (alpha, beta frequency bands), that support long-term stored semantic and episodic information, suggested preserved memory traces.

Effects of VNS stimulation on electrocorticography in patients with dual neuro- stimulation devices

BackgroundOne-third of epilepsy patients become refractory to anti-epileptic medications. In these patients neurostimulation devices are considered as potential treatment options. The FDA has approved vagal nerve stimulation (VNS) and responsive neurostimulation (RNS system) for the treatment of focal epilepsy. There is limited data on interaction between the two devices and their mechanism of action is actively being researched. Limited prior evidence suggests that acute VNS stimulation may reduce epileptiform activity and cause EEG desynchronization. Our study aims to isolate the effects of VNS on electrocorticography (ECoG) as recorded by the RNS system.MethodsECoG from 20 patients were obtained. For each patient, five pairs of ‘on’ recordings of 60-second VNS stimulation on ECoGs were compared to ‘off’ baseline 60s recordings. ECoGs were analyzed for differences in spectral content.ResultsPreliminary results show that acute VNS stimulation is associated with significant decrease in power (i.e. desynchronization) in the theta, beta, and (50–70 Hz) gamma bands.ConclusionThis study demonstrates desynchronization as a mechanism of action of VNS, as recorded by the RNS system. As more patients receive dual neurostimulators, it will be crucial to understand isolated effects of each device to optimize programming and improve therapeutic efficacy.navya.joseph@unmc.edu

Psilocin, LSD, mescaline, and DOB all induce broadband desynchronization of EEG and disconnection in rats with robust translational validity

Serotonergic psychedelics are recently gaining a lot of attention as a potential treatment of several neuropsychiatric disorders. Broadband desynchronization of EEG activity and disconnection in humans have been repeatedly shown; however, translational data from animals are completely lacking. Therefore, the main aim of our study was to assess the effects of tryptamine and phenethylamine psychedelics (psilocin 4 mg/kg, LSD 0.2 mg/kg, mescaline 100 mg/kg, and DOB 5 mg/kg) on EEG in freely moving rats. A system consisting of 14 cortical EEG electrodes, co-registration of behavioral activity of animals with subsequent analysis only in segments corresponding to behavioral inactivity (resting-state-like EEG) was used in order to reach a high level of translational validity. Analyses of the mean power, topographic brain-mapping, and functional connectivity revealed that all of the psychedelics irrespective of the structural family induced overall and time-dependent global decrease/desynchronization of EEG activity and disconnection within 1–40 Hz. Major changes in activity were localized on the large areas of the frontal and sensorimotor cortex showing some subtle spatial patterns characterizing each substance. A rebound of occipital theta (4–8 Hz) activity was detected at later stages after treatment with mescaline and LSD. Connectivity analyses showed an overall decrease in global connectivity for both the components of cross-spectral and phase-lagged coherence. Since our results show almost identical effects to those known from human EEG/MEG studies, we conclude that our method has robust translational validity.

Vagus Nerve Stimulation Elicits Sleep EEG Desynchronization and Network Changes in Responder Patients in Epilepsy.

Neural desynchronization was shown as a key mechanism of vagus nerve stimulation (VNS) action in epilepsy, and EEG synchronization measures are explored as possible response biomarkers. Since brain functional organization in sleep shows different synchrony and network properties compared to wakefulness, we aimed to explore the effects of acute VNS on EEG-derived measures in the two different states of vigilance. EEG epochs were retrospectively analyzed from twenty-four VNS-treated epileptic patients (11 responders, 13 non-responders) in calm wakefulness and stage N2 sleep. Weighted Phase Lag Index (wPLI) was computed as connectivity measure of synchronization, for VNS OFF and VNS ON conditions. Global efficiency (GE) was computed as a network measure of integration. Ratios OFF/ON were obtained as desynchronization/de-integration index. Values were compared between responders and non-responders, and between EEG states. ROC curve and area-under-the-curve (AUC) analysis was performed for response classification. In responders, stronger VNS-induced theta desynchronization (p < 0.05) and decreased GE (p < 0.05) were found in sleep, but not in wakefulness. Theta sleep wPLI Ratio OFF/ON yielded an AUC of 0.825, and 79% accuracy as a response biomarker if a cut-off value is set at 1.05. Considering all patients, the VNS-induced GE decrease was significantly more important in sleep compared to awake EEGstate (p < 0.01). In conclusion, stronger sleep EEG desynchronization in theta band distinguishes responders to VNS therapy from non-responders. VNS-induced reduction of network integration occurs significantly more in sleep than in wakefulness.

FoxP2 cells in the lateral parabrachial area may drive respiratory responses to hypercapnia

We have previously reported that CGRP neurons in the external lateral parabrachial nucleus (PBCGRP) play a critical role in transmitting the arousal signal to cause EEG desynchronization in response to hypercapnia. A second population of neurons adjacent to the PBCGRP group, which projects to respiratory control areas in the medulla, are marked by expression of the transcription factor FoxP2. We hypothesize that while the PBCGRP neurons wake up the forebrain during apneas, the adjacent PBFoxP2 neurons may trigger sudden activation of the airway dilators and other components of the respiratory system during apnea. We first exposed mice (n=4) to 2h of 10% CO2, and tested if PBFoxP2 cells can be activated by such exposure, by double- immunostaining the brain tissue for both FoxP2 and cFos. We found that PBFoxP2 neurons showed cFos activation during CO2 exposure, but that none of them also stained for CGRP. Second, we investigated the response of either optogenetic inhibition or activation of PBFoxP2 neurons on respiration. We injected FoxP2Cre mice, that express Cre-recombinase enzyme in all the FoxP2 cells, bilaterally in the PB with adeno-associated virus containing the gene for either channel rhodopsin2 (AAV-FLEX-ChR2-mCherry; n=3, for neuronal activation) or archaerhodopsin T TP009 (AAV-FLEX-ArchT-GFP ArchT; n=2, for neuronal inhibition) in a Cre-inducible FLEX cassette that expressed either ChR2 or ArchT only in the PBFoxP2 cells. These mice were prepared for sleep recordings and were implanted with bilateral optic fiber targeting the PB. Blue laser (473nm) light targeted to the PB, activated ChR2 expressing neurons with 10ms pulses of 473nm given at 5, 10 and 20Hz, for 5s every 5 minutes, without any hypercapnia stimulus and then respiration was measured. Photo-stimulation of ChR2 expressing PBFoxP2 at 10Hz for 5s significantly increased the respiratory rate (RR) (F2, 12= 6.35, P=0.013) and the tidal volume (TV) compared to the pre-stimulation period (F2, 12= 3.20, P=0.04), with no effect at 5 Hz. At 20 Hz for 5s, RR increased by 63% and VT by 62%. Animals woke-up in most trials towards the end of the 5s stimulation period. We also investigated the respiratory response to10% CO2 given for 30s every 300s, with and without photo-inhibition of the PBFoxP2 neurons with 593 nm laser light. Laser light was on for 60s beginning 20s prior and extending 10s after the CO2 stimulus. Inhibition of the PBFoxP2 cells caused 27% reduction in the ventilatory effort as calculated by the minute ventilation (MV) during the time the animals were exposed to CO2 both before (F1,11=3.68; P= 0.026) and after EEG arousal (F1,11=3.68; P<0.001), without affecting the latency of arousal from CO2. Finally, the GCaMP fiber photometry recordings suggested that the firing of the PBFoxP2 neurons as seen by the increase in GCaMP fluorescence correlates positively with respiratory rate and tidal volume (R2= 0.36; P<0.001), thus corroborating the role of PBFoxP2 neurons in regulating respiratory response to hypercapnia.