High Gamma Oscillations Research Articles

Pilot Trial of Perampanel on Peritumoral Hyperexcitability in Newly Diagnosed High-grade Glioma.

Glutamatergic neuron-glioma synaptogenesis and peritumoral hyperexcitability promote glioma growth in a positive feedback loop. The objective of this study was to evaluate the feasibility and estimated effect sizes of the targeted AMPA receptor antagonist perampanel on peritumoral hyperexcitability. An open-label trial was performed comparing perampanel with standard of care (SOC) in patients undergoing resection of newly diagnosed radiologic high-grade glioma. Perampanel was administered as a preoperative loading dose followed by maintenance therapy until progressive disease or up to 12 months. SOC treatment involved levetiracetam for 7 days or as clinically indicated. The primary outcome of hyperexcitability was defined by intraoperative electrocorticography high-frequency oscillation (HFO) rates. Seizure freedom and overall survival were estimated by the Kaplan-Meier method. Tissue concentrations of perampanel, levetiracetam, and correlative biomarkers were measured by mass spectrometry. HFO rates were similar between patients treated with perampanel and levetiracetam. The trial was terminated early after a planned interim analysis, and outcomes assessed in 11 patients (seven perampanel treated; four treated with SOC). Over a median 281 days of postenrollment follow-up, 27% of patients had seizures, including 14% maintained on perampanel and 50% treated with SOC. Overall survival in perampanel-treated patients was similar to that in a glioblastoma reference cohort. Glutamate concentrations in surface biopsies were positively correlated with HFO rates in adjacent electrode contacts and were not significantly associated with treatment assignment or drug concentrations. Glioma peritumoral glutamate concentrations correlated with high-gamma oscillation rates. Targeting glutamatergic activity with perampanel achieved similar electrocorticographic hyperexcitability levels as in levetiracetam-treated patients.

Effectiveness of perampanel for focal seizures determined by interictal gamma oscillation regularity analysis.

Although perampanel (PER) has received approval as an antiseizure medication, reports quantifying its antiseizure effects using electroencephalography (EEG) remain scarce. In a previous study, we demonstrated that the interictal high gamma oscillation regularity (GOR) on scalp EEG is an excellent marker of epileptogenicity. Herein, we investigated whether the antiseizure effect of PER could be quantified through interictal GOR analysis of scalp EEG data. To investigate this, we examined the interictal GOR from 20 s of scalp EEG data before and after PER administration collected from five patients with epilepsy with focal seizures. Prior to PER administration, each patient presented with localized areas with high GOR consistent with brain lesions or seizure semiology. In all patients, the seizures improved following PER administration, and the localized high GOR, which is considered an epileptogenic focus, disappeared. These results indicate that interictal GOR analysis may be a useful tool for the quantitative assessments of the antiseizure effects of PER in focal epilepsy. PLAIN LANGUAGE SUMMARY: This study explored whether perampanel (PER)'s antiseizure effects can be quantified using interictal high gamma oscillation regularity (GOR) analysis from scalp EEG data. Analyzing 20-second EEG segments before and after PER administration in five patients with focal epilepsy, we found that high GOR areas, indicative of epileptogenic foci, disappeared following PER administration. The results suggest that interictal GOR analysis could effectively quantify the antiseizure effects of PER.

Effects of Phasic Activation of Locus Ceruleus on Cortical Neural Activity and Auditory Discrimination Behavior.

Although the locus ceruleus (LC) is recognized as a crucial modulator for attention and perception by releasing norepinephrine into various cortical regions, the impact of LC-noradrenergic (LC-NE) modulation on auditory discrimination behavior remains elusive. In this study, we firstly recorded local field potential and single-unit activity in multiple cortical regions associated with auditory-motor processing, including the auditory cortex, posterior parietal cortex, secondary motor cortex, anterior cingulate cortex, prefrontal cortex, and orbitofrontal cortex (OFC), in response to optogenetic activation (40 Hz and 0.5 s) of the LC-NE neurons in awake mice (male). We found that phasic LC stimulation induced a persistent high gamma oscillation (50-80 Hz) in the OFC. Phasic activation of LC-NE neurons also resulted in a corresponding increase in norepinephrine levels in the OFC, accompanied by a pupillary dilation response. Furthermore, when mice were performing a go/no-go auditory discrimination task, we optogeneticaly activated the neural projections from LC to OFC and revealed a shortened latency in behavioral responses to sound stimuli and an increased false alarm rate. These impulsive behavioral responses may be associated with the gamma neural activity in the OFC. These findings have broadened our understanding of the neural mechanisms involved in the role of LC in auditory-motor processing.

Hybrid framework of fatigue: connecting motivational control and computational moderators to gamma oscillations.

There is a need to develop a comprehensive account of time-on-task fatigue effects on performance (i.e., the vigilance decrement) to increase predictive accuracy. We address this need by integrating three independent accounts into a novel hybrid framework. This framework unites (1) a motivational system balancing goal and comfort drives as described by an influential cognitive-energetic theory with (2) accumulating microlapses from a recent computational model of fatigue, and (3) frontal gamma oscillations indexing fluctuations in motivational control. Moreover, the hybrid framework formally links brief lapses (occurring over milliseconds) to the dynamics of the motivational system at a temporal scale not otherwise described in the fatigue literature. EEG and behavioral data was collected from a brief vigilance task. High frequency gamma oscillations were assayed, indexing effortful controlled processes with motivation as a latent factor. Binned and single-trial gamma power was evaluated for changes in real- and lagged-time and correlated with behavior. Functional connectivity analyses assessed the directionality of gamma power in frontal-parietal communication across time-on-task. As a high-resolution representation of latent motivation, gamma power was scaled by fatigue moderators in two computational models. Microlapses modulated transitions from an effortful controlled state to a minimal-effort default state. The hybrid models were compared to a computational microlapse-only model for goodness-of-fit with simulated data. Findings suggested real-time high gamma power exhibited properties consistent with effortful motivational control. However, gamma power failed to correlate with increases in response times over time, indicating electrophysiology and behavior relations are insufficient in capturing the full range of fatigue effects. Directional connectivity affirmed the dominance of frontal gamma activity in controlled processes in the frontal-parietal network. Parameterizing high frontal gamma power, as an index of fluctuating relative motivational control, produced results that are as accurate or superior to a previous microlapse-only computational model. The hybrid framework views fatigue as a function of a energetical motivational system, managing the trade-space between controlled processes and competing wellbeing needs. Two gamma computational models provided compelling and parsimonious support for this framework, which can potentially be applied to fatigue intervention technologies and related effectiveness measures.

Functional interaction of abnormal beta and gamma oscillations on bradykinesia in parkinsonian rats

Bradykinesia, a debilitating symptom characterized by impaired movement initiation and reduced speed in Parkinson’s disease (PD), is associated with abnormal oscillatory activity in the motor cortex-basal ganglia circuit. We investigated the interplay between abnormal beta and gamma oscillations in relation to bradykinesia in parkinsonian rats. Our findings showed reduced movement activities in parkinsonian rats, accompanied by enhanced high beta oscillations in the motor cortex, which are closely associated with movement transitional difficulties. Additionally, gamma oscillations correlated with movement velocity in control rats but not in parkinsonian rats. We observed selective coupling between high beta oscillation phase and gamma oscillation amplitude in PD, as well as cortical high beta-broadband gamma phase-amplitude coupling (PAC) negatively influencing locomotor activities in control and PD rats. These findings suggest a collaborative role of cortical beta and gamma oscillations in facilitating movement execution, with beta oscillations being linked to movement initiation and gamma oscillations associated with movement speed. Importantly, the aberrant alterations of these oscillations are closely related to the development of bradykinesia. Furthermore, PAC hold promise as a biomarker for comprehensive assessment of movement performance in PD.

AMPK-mediated autophagy pathway activation promotes ΔFosB degradation to improve levodopa-induced dyskinesia

BackgroundParkinson's disease patients on chronic levodopa often suffer from motor complications, which tend to reduce their quality of life. Levodopa-induced dyskinesia (LID) is one of the most prevalent motor complications, often characterized by abnormal involuntary movements, and the pathogenesis of LID is still unclear but recent studies have suggested the involvement of autophagy. MethodsThe onset of LID was mimicked by chronic levodopa treatment in a unilateral 6-hydroxydopamine (6-OHDA) -lesion rat model. Overexpression of ΔFosB in HEK293 cells to mimic the state of ΔFosB accumulation. The modulation of the AMP-activated protein kinase (AMPK)-mediated autophagy pathway using by metformin, AICAR (an AMPK activator), Compound C (an AMPK inhibitor) and chloroquine (an autophagy pathway inhibitor). The severity of LID was assessed by axial, limb, and orofacial (ALO) abnormal involuntary movements (AIMs) score and in vivo electrophysiology. The activity of AMPK pathway as well as autophagy markers and FosB-ΔFosB levels were detected by western blotting. RT-qPCR was performed to detect the transcription level of FosB-ΔFosB. The mechanism of autophagy dysfunction was further explored by immunofluorescence and transmission electron microscopy. ResultsIn vivo experiments demonstrated that chronic levodopa treatment reduced AMPK phosphorylation, impaired autophagosome-lysosomal fusion and caused FosB-ΔFosB accumulation in the striatum of PD rats. Long-term metformin intervention improved ALO AIMs scores as well as reduced the mean power of high gamma (hγ) oscillations and the proportion of striatal projection neurons unstable in response to dopamine for LID rats. Moreover, the intervention of metformin promoted AMPK phosphorylation, ameliorated the impairment of autophagosome-lysosomal fusion, thus, promoting FosB-ΔFosB degradation to attenuate its accumulation in the striatum of LID rats. However, the aforementioned roles of metformin were reversed by Compound C and chloroquine. The results of in vitro studies demonstrated the ability of metformin and AICAR to attenuate ΔFosB levels by promoting its degradation, while Compound C and chloroquine could block this effect. ConclusionsIn conclusion, our results suggest that long-term metformin treatment could promote ΔFosB degradation and thus attenuate the development of LID through activating the AMPK-mediated autophagy pathway. Overall, our results support the AMPK-mediated autophagy pathway as a novel therapeutic target for LID and also indicate that metformin is a promising therapeutic candidate for LID.

Study on Improving the Modulatory Effect of Rhythmic Oscillations by Transcranial Magneto-Acoustic Stimulation.

In hippocampus, synaptic plasticity and rhythmic oscillations reflect the cytological basis and the intermediate level of cognition, respectively. Transcranial ultrasound stimulation (TUS) has demonstrated the ability to elicit changes in neural response. However, the modulatory effect of TUS on synaptic plasticity and rhythmic oscillations was insufficient in the present studies, which may be attributed to the fact that TUS acts mainly through mechanical forces. To enhance the modulatory effect on synaptic plasticity and rhythmic oscillations, transcranial magneto-acoustic stimulation (TMAS) which induced a coupled electric field together with TUS's ultrasound field was applied. The modulatory effect of TMAS and TUS with a pulse repetition frequency of 100 Hz were compared. TMAS/TUS were performed on C57 mice for 7 days at two different ultrasound intensities (3 W/cm2 and 5 W/cm [Formula: see text]. Behavioral tests, long-term potential (LTP) and local field potentials in vivo were performed to evaluate TUS/TMAS modulatory effect on cognition, synaptic plasticity and rhythmic oscillations. Protein expression based on western blotting were used to investigate the under- lying mechanisms of these beneficial effects. At 5 W/cm2, TMAS-induced LTP were 113.4% compared to the sham group and 110.5% compared to TUS. Moreover, the relative power of high gamma oscillations (50-100Hz) in the TMAS group ( 1.060±0.155 %) was markedly higher than that in the TUS group ( 0.560±0.114 %) and sham group ( 0.570±0.088 %). TMAS significantly enhanced the synchronization of theta and gamma oscillations as well as theta-gamma cross-frequency coupling. Whereas, TUS did not show relative enhancements. TMAS provides enhanced effect for modulating the synaptic plasticity and rhythmic oscillations in hippocampus.

Gamma oscillations in the mPFC: A potential predictive biomarker of depression and antidepressant effects

Gamma oscillations have attracted much attention in the field of mood disorders, but their role in depression remains poorly understood. This study aimed to investigate whether gamma oscillations in the medial prefrontal cortex (mPFC) could serve as a predictive biomarker of depression. Chronic restraint stress (CRS) or lipopolysaccharide (LPS) were used to induce depression-like behaviors in mice; local field potentials (LFPs) in the mPFC were recorded by electrophysiological techniques; We found that both CRS and LPS induced significant depression-like behaviors in mice, including increasing immobility durations in the forced swimming test (FST) and tail suspension test (TST) and increasing the latency to feed in the novelty-suppressed feeding test (NSFT). Electrophysiological results suggested that CRS and LPS significantly reduced low and high gamma oscillations in the mPFC. Furthermore, a single injection of ketamine or scopolamine for 24 h significantly increased gamma oscillations and elicited rapid-acting antidepressant-like effects. In addition, fluoxetine treatment for 21 days significantly increased gamma oscillations and elicited antidepressant-like effects. Taken together, our findings suggest that gamma oscillations are strongly associated with depression, yielding new insights into investigating the predictive biomarkers of depression and the time course of antidepressant effects.

Spatiotemporal dynamics across visual cortical laminae support a predictive coding framework for interpreting mismatch responses.

Context modulates neocortical processing of sensory data. Unexpected visual stimuli elicit large responses in primary visual cortex (V1)-a phenomenon known as deviance detection (DD) at the neural level, or "mismatch negativity" (MMN) when measured with EEG. It remains unclear how visual DD/MMN signals emerge across cortical layers, in temporal relation to the onset of deviant stimuli, and with respect to brain oscillations. Here we employed a visual "oddball" sequence-a classic paradigm for studying aberrant DD/MMN in neuropsychiatric populations-and recorded local field potentials in V1 of awake mice with 16-channel multielectrode arrays. Multiunit activity and current source density profiles showed that although basic adaptation to redundant stimuli was present early (50ms) in layer 4 responses, DD emerged later (150-230ms) in supragranular layers (L2/3). This DD signal coincided with increased delta/theta (2-7Hz) and high-gamma (70-80Hz) oscillations in L2/3 and decreased beta oscillations (26-36Hz) in L1. These results clarify the neocortical dynamics elicited during an oddball paradigm at a microcircuit level. They are consistent with a predictive coding framework, which posits that predictive suppression is present in cortical feed-back circuits, which synapse in L1, whereas "prediction errors" engage cortical feed-forward processing streams, which emanate from L2/3.

Balance between pallidal neural oscillations correlated with dystonic activity and severity

Background and objectiveThe balance between neural oscillations provides valuable insights into the organisation of neural oscillations related to brain states, which may play important roles in dystonia. We aim to investigate the relationship of the balance in the globus pallidus internus (GPi) with the dystonic severity under different muscular contraction conditions. MethodsTwenty-one patients with dystonia were recruited. All of them underwent bilateral GPi implantation, and local field potentials (LFPs) from the GPi were recorded via simultaneous surface electromyography. The power spectral ratio between neural oscillations was computed as the measure of neural balance. This ratio was calculated under high and low dystonic muscular contraction conditions, and its correlation with the dystonic severity was assessed using clinical scores. ResultsThe power spectral of the pallidal LFPs peaked in the theta and alpha bands. Within participant comparison showed that the power spectral of the theta oscillations significantly increased during high muscle contraction compared with that during low contraction. The power spectral ratios between the theta and alpha, theta and low beta, and theta and high gamma oscillations were significantly higher during high contraction than during low contraction. The total score and motor score were associated with the power spectral ratio between the low and high beta oscillations, which was correlated with the dystonic severity both during high and low contractions. The power spectral ratios between the low beta and low gamma and between the low beta and high gamma oscillations showed a significantly positive correlation with the total score during both high and low contractions; a correlation with the motor scale score was found only during high contraction. Meanwhile, the power spectral ratio between the theta and alpha oscillations during low contraction showed a significantly negative correlation with the total score. The power spectral ratios between the alpha and high beta, alpha and low gamma, and alpha and high gamma oscillations were significantly correlated with the dystonic severity only during low contraction. ConclusionThe balance between neural oscillations, as quantified by the power ratio between specific frequency bands, differed between the high and low muscular contraction conditions and was correlated with the dystonic severity. The balance between the low and high beta oscillations was correlated with the dystonic severity during both conditions, making this parameter a new possible biomarker for closed-loop deep brain stimulation in patients with dystonia.

Between alpha and gamma oscillations: Neural signatures of linguistic predictions and listener's attention to speaker's communication intention

When listeners hear a message produced by their interlocutor, they can predict upcoming words thanks to the sentential context and their attention can be focused on the speaker's communication intention. In two electroencephalographical (EEG) studies, we investigated the oscillatory correlates of prediction in spoken-language comprehension and how they are modulated by the listener’s attention. Sentential contexts which were strongly predictive of a particular word were ended by a possessive adjective either matching the gender of the predicted word or not. Alpha, beta and gamma oscillations were studied as they were considered to play a crucial role in the predictive process. While evidence of word prediction was related to alpha fluctuations when listeners focused their attention on sentence meaning, changes in high-gamma oscillations were triggered by word prediction when listeners focused their attention on the speaker's communication intention. Independently of the endogenous attention to a level of linguistic information, the oscillatory correlates of word predictions in language comprehension were sensitive to the prosodic emphasis produced by the speaker at a late stage. These findings thus bear major implications for understanding the neural mechanisms that support predictive processing in spoken-language comprehension.

Bilateral ablation of the vomeronasal organs produces dramatic changes in the EEG of the main olfactory system during paradoxical sleep

Background: The vomeronasal organ (VNO) plays an important role in reproductive physiology, behavior, sexual behavior and aggression. Objective: The aim is to report a surprising effect of the removal of the VNO on the cortical electrical activity of the olfactory bulb, piriform lobe and frontal cortex exclusively during paradoxical sleep (PS). Methodology: Seventeen adult armadillos chronically prepared for electrographic recordings were employed. Some animals were subjected to VNO bilateral remove. They were studied during wakefulness and sleep phases. Results: An outstanding phenomenon occurs during PS of armadillos submitted to bilateral ablation of the VNO. There is a dramatic change in the oscillations of the olfactory bulb electrical activity strictly confined to PS. The change consists of the sudden appearance, as soon as PS initiates, of high amplitude gamma oscillations during the whole duration of each PS episode. They disappear as soon as PS comes to an end. The oscillations are also seen in the paleocortex and the frontal neocortex. They disappear after the transverse section of the olfactory peduncles. Conclusions: Our results show the absence of VNO deeply modifies the electrophysiological expression of PS in the olfactory bulb and other extensive brain areas. They are elicited by the centrifugal input to the olfactory bulb. From there they propagate to the piriform and frontal neocortex. These results show a new and subtle role for the organs. Some hypotheses related to the effects of bilateral removal of the VNO are presented.

Altered Odor-Evoked Electrophysiological Responses in the Anterior Piriform Cortex of Conscious APP/PS1 Mice.

Olfactory decline is an indicator of early-stage Alzheimer's disease (AD). Although the anterior piriform cortex (aPC) is an important brain area involved in processing olfactory input, little is known about how its neuronal activity is affected in early-stage AD. To elucidate whether odor-induced electrophysiological responses are altered in the aPC of 3-5-month-old APP/PS1 mice. Using head-fixed multi-channel recording techniques in APP/PS1 AD mouse model to uncover potential aberrance of the aPC neuronal firing and local field potential (LFP) in response to vanillin. We show that the firing rate of aPC neurons evoked by vanillin is significantly reduced in conscious APP/PS1 mice. LFP analysis demonstrates reduced low- and high-gamma (γlow,γhigh) oscillations during both the baseline and odor stimulation periods in APP/PS1 mice. Moreover, according to spike-field coherence (SFC) analysis, APP/PS1 mice show decreased coherence between odor-evoked spikes and γlow rhythms, while the coherence with γhigh rhythms and the ΔSFC of the oscillations is unaffected. Furthermore, APP/PS1 mice show reduced phase-locking strength in the baseline period, such that there is no difference between baseline and odor-stimulation conditions. This contrasts markedly with wild type mice, where phase-locking strength decreases on stimulation. The abnormalities in both the neuronal and oscillatory activities of the aPC may serve as electrophysiological indicators of underlying olfactory decline in early AD.

The antidepressant effect of nucleus accumbens deep brain stimulation is mediated by parvalbumin-positive interneurons in the dorsal dentate gyrus

The nucleus accumbens (NAc) is a crucial region in the reward circuit and is related to anhedonia, the pivotal symptom of major depression disorder (MDD). Deep brain stimulation (DBS) of NAc has been identified as an effective treatment for severe refractory major depression; however, the underlying mechanism of NAc-DBS in MDD treatment remains elusive. Using the chronic unpredictable mild stress (CUMS) mouse model, we found NAc-DBS rescued depression-like behaviors, and reversed high gamma oscillation reduction and neurogenesis impairment in the dorsal dentate gyrus. Inactivation of parvalbumin (PV)-positive interneurons (PVI) in the dorsal DG led to depression-like behavior and decreased adult neurogenesis. Further investigation elucidated the VTA-DG GABAergic projection and CA1-NAc projection might jointly participate in NAc-DBS therapeutic mechanism. Disinhibition of the VTA-DG GABAergic projection had an antidepressant effect, and inhibition of the CA1-NAc projection reduced the antidepressant effect of DBS-NAc. Moreover, disinhibiting the VTA-DG GABAergic projection or activating the CA1-NAc projection could increase PVI activity in the dorsal DG. These results showed PVI in the dorsal DG as an essential target in depression and NAc-DBS antidepressant mechanisms.

Altered gamma oscillations and beta–gamma coupling in drug-naive first-episode major depressive disorder: Association with sleep and cognitive disturbance

ObjectiveGamma oscillations contribute to the pathogenesis mechanisms of major depressive disorder (MDD) have been proposed, but gamma activity is not well characterized. This study is the first attempt to investigate the altered gamma oscillations in first-episode MDD, particularly the beta–gamma coupling, and to determine the potential symptomatic relationship with the identified gamma dysregulation. MethodsResting electroencephalography was recorded for 43 drug-naive first-episode MDD and 57 healthy control (HC) subjects. Integrated analysis of relative spectral power, weighted phase lag index, and phase–amplitude coupling (PAC) were utilized to reveal the alterations of gamma activities. Pearson's correlation was implemented to identify the relationship between altered gamma activities and the clinical depressive symptoms, which were categorized into four factors: anxiety somatization, retardation, cognitive disturbance, and sleep disturbance. ResultsCompared with HC subjects, MDD patients showed not only significantly decreased gamma powers in the left temporal and the bilateral occipital regions but also weakened gamma connectivity between the left hemisphere and the right frontal region. Furthermore, attenuated beta–gamma PAC of MDD patients was observed in the left temporal regions. Importantly, the suppression of left occipital mid- and high gamma oscillations were negatively correlated with sleep disturbance, while the deficits in left temporal beta–mid-gamma PAC and beta–high gamma PAC showed negative correlations with cognitive disturbance. LimitationsImportant limitations are the small sample size and the possible inclusion of bipolar depression in the MDD group. ConclusionsOur findings provide the first evidence that in first-episode MDD, aberrant gamma powers and beta–gamma coupling are associated with sleep and cognitive impairments, respectively, deepening our understanding of the physiological mechanisms underlying sleep and cognitive symptoms in first-episode MDD. Altered gamma oscillations emerge as promising biomarkers for diagnosing MDD.

Odor-induced modification of oscillations and related theta-higher gamma coupling in olfactory bulb neurons of awake and anesthetized rats.

Olfactory gamma oscillations (40–100 Hz) are generated spontaneously in animals and represent the activity of local olfactory bulb (OB) networks, which play important roles in cognitive mechanisms. In addition, high-frequency oscillations (HFO, 130–180 Hz) have attracted widespread attention and are novel neuronal oscillations with a frequency range closer to high gamma oscillations (60–100 Hz, HGOs). Both HGOs and HFOs are distinctly regulated by θ rhythm in the hippocampus. To understand their mediation mechanisms in the OB, we investigated whether local field potential (LFP) oscillations including HGOs and HFOs and even their coupling with theta rhythm are modified by odor stimulation in both freely moving and anesthetized rats. Therefore, we combined electrophysiological technology and cross-frequency coupling analysis approaches to determine the difference in the odor-modulated LFP oscillations between awake and anesthetized rats. The obtained results indicate that LFP oscillations including HGOs and HFOs were differently modified by odor stimulation in animals of both states. However, θ-HGO and θ-HFO coupling were modified in only awake animals. It is suggested that these oscillations and their interactions with theta oscillations may play crucial roles in olfactory network activity. This could pave the way for further understanding the underlying mechanisms of oscillations in OB neurons towards odor sensation.

Psilocybin reduces low frequency oscillatory power and neuronal phase-locking in the anterior cingulate cortex of awake rodents

Psilocybin is a hallucinogenic compound that is showing promise in the ability to treat neurological conditions such as depression and post-traumatic stress disorder. There have been several investigations into the neural correlates of psilocybin administration using non-invasive methods, however, there has yet to be an invasive study of the mechanism of action in awake rodents. Using multi-unit extracellular recordings, we recorded local field potential and spiking activity from populations of neurons in the anterior cingulate cortex of awake mice during the administration of psilocybin (2 mg/kg). The power of low frequency bands in the local field potential was found to significantly decrease in response to psilocybin administration, whilst gamma band activity trended towards an increase. The population firing rate was found to increase overall, with just under half of individual neurons showing a significant increase. Psilocybin significantly decreased the level of phase modulation of cells with each neural frequency band except high-gamma oscillations, consistent with a desynchronization of cortical populations. Furthermore, bursting behavior was altered in a subset of cells, with both positive and negative changes in the rate of bursting. Neurons that increased their burst firing following psilocybin administration were highly likely to transition from a phase-modulated to a phase unmodulated state. Taken together, psilocybin reduces low frequency oscillatory power, increases overall firing rates and desynchronizes local neural activity. These findings are consistent with dissolution of the default mode network under psilocybin, and may be indicative of disruption of top-down processing in the acute psychedelic state.

Evaluating the Effect of Increasing Working Memory Load on EEG-Based Functional Brain Networks

Purpose: Working Memory (WM) plays a crucial role in many cognitive functions of the human brain. Examining how the inter-regional connectivity and characteristics of functional brain networks modulate with increasing WM load could lead to a more in-depth understanding of the WM system.
 Materials and Methods: To investigate the effect of WM load alterations on the inter-regional synchronization and functional network characteristics, we used Electroencephalogram (EEG) data recorded from 21 healthy participants during an n-back task with three load levels (0-back, 2-back, and 3-back). The networks were constructed based on the weighted Phase Lag Index (wPLI) in the theta, alpha, beta, low-gamma, and high-gamma frequency bands. After constructing the fully connected, weighted, and undirected networks, the node-to-node connections, graph-theory metrics consisting of mean Clustering coefficient (C), characteristic path Length (L), and node strength were analyzed by statistical tests.
 Results: It was revealed that in the presence of WM load (2- and 3-back tasks) compared with the WM-free condition (0-back task) within the alpha range, the Inter-Regional Functional Connectivity (IRFC), functional integration, functional segregation, and node strength in channels located at the frontal, parietal and occipital regions were significantly reduced. In the high-gamma band, IRFC was significantly higher in the difficult task (3-back) compared to the easy and moderate tasks (0- and 2-back). Besides, locally clustered connections were significantly increased in 3-back relative to the 2-back task.
 Conclusion: Inter-regional alpha synchronization and alpha-band network metrics can distinguish between the WM and WM-free tasks. In contrast, phase synchronization of high-gamma oscillations can differentiate between the levels of WM load, which demonstrates the potential of the phase-based functional connectivity and brain network metrics for predicting the WM load level.

Commentary: Interictal High Gamma Oscillation Regularity as a Marker for Presurgical Epileptogenic Zone Localization.

Commentary: Interictal High Gamma Oscillation Regularity as a Marker for Presurgical Epileptogenic Zone Localization.

Ictal Electroencephalographic Characteristics of Nodding Syndrome: A Comparative Case-Series from South Sudan, Tanzania, and Uganda.

Nodding syndrome (NS) is a poorly understood form of childhood‐onset epilepsy that is characterized by the pathognomonic ictal phenomenon of repetitive vertical head drops. To evaluate the underlying ictal neurophysiology, ictal EEG features were evaluated in nine participants with confirmed NS from South Sudan, Tanzania, and Uganda and ictal presence of high frequency gamma oscillations on scalp EEG were assessed. Ictal EEG during the head nodding episode predominantly showed generalized slow waves or sharp‐and‐slow wave complexes followed by electrodecrement. Augmentation of gamma activity (30–70 Hz) was seen during the head nodding episode in all the participants. We confirm that head nodding episodes in persons with NS from the three geographically distinct regions in sub‐Saharan Africa share the common features of slow waves with electrodecrement and superimposed gamma activity. ANN NEUROL 2022;92:75–80