Phenotypic analysis of multielectrode array EEG biomarkers in developing and adult male Fmr1 KO mice.

Fragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety and social and sensory processing deficits. Recent electroencephalographic (EEG) studies in humans with FXS have identified neural oscillation deficits that include increased resting state gamma power, increased amplitude of auditory evoked potentials, and reduced phase locking of sound-evoked gamma oscillations. Similar EEG phenotypes are present in mouse models of FXS, but very little is known about the development of such abnormal responses. In the current study, we employed a 30-channel mouse multielectrode array (MEA) system to record and analyze resting and stimulus-evoked EEG signals in male P21 and P91 WT and Fmr1 KO mice. This led to several novel findings. First, P91, but not P21, Fmr1 KO mice have significantly increased resting EEG power in the low- and high-gamma frequency bands. Second, both P21 and P91 Fmr1 KO mice have markedly attenuated inter-trial phase coherence (ITPC) to spectrotemporally dynamic auditory stimuli as well as to 40 Hz and 80 Hz auditory steady-state response (ASSR) stimuli. This suggests abnormal temporal processing from early development that may lead to abnormal speech and language function in FXS. Third, we found hemispheric asymmetry of fast temporal processing in the mouse auditory cortex in WT but not Fmr1 KO mice. Together, these findings define a set of EEG phenotypes in young and adult mice that can serve as translational targets for genetic and pharmacological manipulation in phenotypic rescue studies.

Clinical, behavioral, and electrophysiological profiles along a continuum of suicide risk: evidence from an implicit association task.

BACKGROUND: An urgent need exists to identify neural correlates associated with differing levels of suicide risk and develop novel, rapid-acting therapeutics to modulate activity within these neural networks. METHODS: Electrophysiological correlates of suicide were evaluated using magnetoencephalography (MEG) in 75 adults with differing levels of suicide risk. During MEG scanning, participants completed a modified Life-Death Implicit Association Task. MEG data were source-localized in the gamma (30-58 Hz) frequency, a proxy measure of excitation-inhibition balance. Dynamic causal modeling was used to evaluate differences in connectivity estimates between risk groups. A proof-of-concept, open-label, pilot study of five high risk participants examined changes in gamma power after administration of ketamine (0.5 mg/kg), an NMDAR antagonist with rapid anti-suicide ideation effects. RESULTS: Implicit self-associations with death were stronger in the highest suicide risk group relative to all other groups, which did not differ from each other. Higher gamma power for self-death compared to self-life associations was found in the orbitofrontal cortex for the highest risk group and the insula and posterior cingulate cortex for the lowest risk group. Connectivity estimates between these regions differentiated the highest risk group from the full sample. Implicit associations with death were not affected by ketamine, but enhanced gamma power was found for self-death associations in the left insula post-ketamine compared to baseline. CONCLUSIONS: Differential implicit cognitive processing of life and death appears to be linked to suicide risk, highlighting the need for objective measures of suicidal states. Pharmacotherapies that modulate gamma activity, particularly in the insula, may help mitigate risk.Clinicaltrials.gov identifier: NCT02543983, NCT00397111.

Beta-triggered adaptive deep brain stimulation during reaching movement in Parkinson's disease.

Subthalamic nucleus (STN) beta-triggered adaptive deep brain stimulation (ADBS) has been shown to provide clinical improvement comparable to conventional continuous DBS (CDBS) with less energy delivered to the brain and less stimulation induced side effects. However, several questions remain unanswered. First, there is a normal physiological reduction of STN beta band power just prior to and during voluntary movement. ADBS systems will therefore reduce or cease stimulation during movement in people with Parkinson's disease and could therefore compromise motor performance compared to CDBS. Second, beta power was smoothed and estimated over a time period of 400 ms in most previous ADBS studies, but a shorter smoothing period could have the advantage of being more sensitive to changes in beta power, which could enhance motor performance. In this study, we addressed these two questions by evaluating the effectiveness of STN beta-triggered ADBS using a standard 400 ms and a shorter 200 ms smoothing window during reaching movements. Results from 13 people with Parkinson's disease showed that reducing the smoothing window for quantifying beta did lead to shortened beta burst durations by increasing the number of beta bursts shorter than 200 ms and more frequent switching on/off of the stimulator but had no behavioural effects. Both ADBS and CDBS improved motor performance to an equivalent extent compared to no DBS. Secondary analysis revealed that there were independent effects of a decrease in beta power and an increase in gamma power in predicting faster movement speed, while a decrease in beta event related desynchronization (ERD) predicted quicker movement initiation. CDBS suppressed both beta and gamma more than ADBS, whereas beta ERD was reduced to a similar level during CDBS and ADBS compared with no DBS, which together explained the achieved similar performance improvement in reaching movements during CDBS and ADBS. In addition, ADBS significantly improved tremor compared with no DBS but was not as effective as CDBS. These results suggest that STN beta-triggered ADBS is effective in improving motor performance during reaching movements in people with Parkinson's disease, and that shortening of the smoothing window does not result in any additional behavioural benefit. When developing ADBS systems for Parkinson's disease, it might not be necessary to track very fast beta dynamics; combining beta, gamma, and information from motor decoding might be more beneficial with additional biomarkers needed for optimal treatment of tremor.

The mitigation of the executive vigilance decrement via HD-tDCS over the right posterior parietal cortex and its association with neural oscillations.

Vigilance-maintaining a prolonged state of preparation to detect and respond to specific yet unpredictable environmental changes-usually decreases across prolonged tasks, causing potentially severe real-life consequences, which could be mitigated through transcranial direct current stimulation (tDCS). The present study aimed at replicating previous mitigatory effects observed with anodal high-definition tDCS (HD-tDCS) over the right posterior parietal cortex (rPPC) while extending the analyses on electrophysiological measures associated with vigilance. In sum, 60 participants completed the ANTI-Vea task while receiving anodal (1.5 mA, n = 30) or sham (0 mA, n = 30) HD-tDCS over the rPPC for ~ 28 min. EEG recordings were completed before and after stimulation. Anodal HD-tDCS specifically mitigated executive vigilance (EV) and reduced the alpha power increment across time-on-task while increasing the gamma power increment. To further account for the observed behavioral and physiological outcomes, a new index of Alphaparietal/Gammafrontal is proposed. Interestingly, the increment of this Alphaparietal/Gammafrontal Index with time-on-task is associated with a steeper EV decrement in the sham group, which was mitigated by anodal HD-tDCS. We highlight the relevance of replicating mitigatory effects of tDCS and the need to integrate conventional and novel physiological measures to account for how anodal HD-tDCS can be used to modulate cognitive performance.

The hippocampus as the switchboard between perception and memory.

Adaptive memory recall requires a rapid and flexible switch from external perceptual reminders to internal mnemonic representations. However, owing to the limited temporal or spatial resolution of brain imaging modalities used in isolation, the hippocampal-cortical dynamics supporting this process remain unknown. We thus employed an object-scene cued recall paradigm across two studies, including intracranial electroencephalography (iEEG) and high-density scalp EEG. First, a sustained increase in hippocampal high gamma power (55 to 110 Hz) emerged 500 ms after cue onset and distinguished successful vs. unsuccessful recall. This increase in gamma power for successful recall was followed by a decrease in hippocampal alpha power (8 to 12 Hz). Intriguingly, the hippocampal gamma power increase marked the moment at which extrahippocampal activation patterns shifted from perceptual cue toward mnemonic target representations. In parallel, source-localized EEG alpha power revealed that the recall signal progresses from hippocampus to posterior parietal cortex and then to medial prefrontal cortex. Together, these results identify the hippocampus as the switchboard between perception and memory and elucidate the ensuing hippocampal-cortical dynamics supporting the recall process.

Early Family Experiences and Neural Activity in Rural Pakistani Children: The Differential Role of Gender.

Adversity within low- and middle-income countries (LMICs) poses severe threats to neurocognitive development, which can be partially mitigated by high-quality early family experiences. Specifically, maternal scaffolding and home stimulation can buffer cognitive development in LMIC, possibly by protecting underlying neural functioning. However, the association between family experiences and neural activity remains largely unexplored in LMIC contexts. This study explored the relation of early family experiences to later cognitive skills and absolute gamma power (21-45 Hz), a neural marker linked to higher-order cognitive skills. Drawing data from the PEDS trial, a longitudinal study in rural Pakistan, we examined maternal scaffolding at 24 months and home stimulation quality at 18 months as predictors of verbal IQ, executive functions, and absolute gamma at 48 months for 105 mother-child dyads (52 girls). Maternal scaffolding interacted with gender to predict absolute gamma power, such that higher maternal scaffolding was related to higher gamma more strongly for girls. Maternal scaffolding also interacted with absolute gamma to predict executive functions, such that higher gamma was related to better executive functions only when maternal scaffolding was average to high. Individual differences in early family experiences may partially buffer the neural underpinnings of cognitive skills from adversity in LMIC.

Anesthesia-induced loss of consciousness disrupts auditory responses beyond primary cortex.

Despite its ubiquitous use in medicine, and extensive knowledge of its molecular and cellular effects, how anesthesia induces loss of consciousness (LOC) and affects sensory processing remains poorly understood. Specifically, it is unclear whether anesthesia primarily disrupts thalamocortical relay or intercortical signaling. Here we recorded intracranial electroencephalogram (iEEG), local field potentials (LFPs), and single-unit activity in patients during wakefulness and light anesthesia. Propofol infusion was gradually increased while auditory stimuli were presented and patients responded to a target stimulus until they became unresponsive. We found widespread iEEG responses in association cortices during wakefulness, which were attenuated and restricted to auditory regions upon LOC. Neuronal spiking and LFP responses in primary auditory cortex (PAC) persisted after LOC, while responses in higher-order auditory regions were variable, with neuronal spiking largely attenuated. Gamma power induced by word stimuli increased after LOC while its frequency profile slowed, thus differing from local spiking activity. In summary, anesthesia-induced LOC disrupts auditory processing in association cortices while relatively sparing responses in PAC, opening new avenues for future research into mechanisms of LOC and the design of anesthetic monitoring devices.

Atypical resting-state gamma band trajectory in adult attention deficit/hyperactivity disorder.

Decreased gamma activity has been reported both in children and adults with attention deficit/hyperactivity disorder (ADHD). However, while ADHD is a lifelong neurodevelopmental disorder, our insight into the associations of spontaneous gamma band activity with age is limited, especially in adults. Therefore, we conducted an explorative study to investigate trajectories of resting gamma activity in adult ADHD patients (N = 42) versus matched healthy controls (N = 59). We investigated the relationship of resting gamma activity (30-48 Hz) with age in four right hemispheric electrode clusters where diminished gamma power in ADHD had previously been demonstrated by our group. We found significant non-linear association between resting gamma power and age in the lower frequency gamma1 range (30-39 Hz) in ADHD as compared to controls in all investigated locations. Resting gamma1 increased with age and was significantly lower in ADHD than in control subjects from early adulthood. We found no significant association between gamma activity and age in the gamma2 range (39-48 Hz). Alterations of gamma band activity might reflect altered cortical network functioning in adult ADHD relative to controls. Our results reveal that abnormal gamma power is present at all ages, highlighting the lifelong nature of ADHD. Nonetheless, longitudinal studies are needed to confirm our results.

Sexually dimorphic patterns in electroencephalography power spectrum and autism-related behaviors in a rat model of fragile X syndrome.

Fragile X syndrome (FXS), a neurodevelopmental disorder with autistic features, is caused by the loss of the fragile X mental retardation protein. Sex-specific differences in the clinical profile have been observed in FXS patients, but few studies have directly compared males and females in rodent models of FXS. To address this, we performed electroencephalography (EEG) recordings and a battery of autism-related behavioral tasks on juvenile and young adult Fmr1 knockout (KO) rats. EEG analysis demonstrated that compared to wild-type, male Fmr1 KO rats showed an increase in gamma frequency band power in the frontal cortex during the sleep-like immobile state, and both male and female KO rats failed to show an increase in delta frequency power in the sleep-like state, as observed in wild-type rats. Previous studies of EEG profiles in FXS subjects also reported abnormally increased gamma frequency band power, highlighting this parameter as a potential translatable biomarker. Both male and female Fmr1 KO rats displayed reduced exploratory behaviors in the center zone of the open field test, and increased distance travelled in an analysis of 24-h home cage activity, an effect that was more prominent during the nocturnal phase. Reduced wins against wild-type opponents in the tube test of social dominance was seen in both sexes. In contrast, increased repetitive behaviors in the wood chew test was observed in male but not female KO rats, while increased freezing in a fear conditioning test was observed only in the female KO rats. Our findings highlight sex differences between male and female Fmr1 KO rats, and indicate that the rat model of FXS could be a useful tool for the development of new therapeutics for treating this debilitating neurodevelopmental disorder.

Multielectrode array analysis of EEG biomarkers in a mouse model of Fragile X Syndrome.

Fragile X Syndrome (FXS) is a leading known genetic cause of intellectual disability with symptoms that include increased anxiety and social and sensory processing deficits. Recent EEG studies in humans with FXS have identified neural oscillation deficits that include increased resting state gamma power, increased amplitude of auditory evoked potentials, and reduced inter-trial phase coherence of sound-evoked gamma oscillations. Identification of comparable EEG biomarkers in mouse models of FXS could facilitate the pre-clinical to clinical therapeutic pipeline. However, while human EEG studies have involved 128-channel scalp EEG acquisition, no mouse studies have been performed with more than three EEG channels. In the current study, we employed a recently developed 30-channel mouse multielectrode array (MEA) system to record and analyze resting and stimulus-evoked EEG signals in WT vs. Fmr1 KO mice. Using this system, we now report robust MEA-derived phenotypes including higher resting EEG power, altered event-related potentials (ERPs) and reduced inter-trial phase coherence to auditory chirp stimuli in Fmr1 KO mice that are remarkably similar to those reported in humans with FXS. We propose that the MEA system can be used for: (i) derivation of higher-level EEG parameters; (ii) EEG biomarkers for drug testing; and (ii) mechanistic studies of FXS pathophysiology.

Status Epilepticus Dynamics Predicts Latency to Spontaneous Seizures in the Kainic Acid Model.

BACKGROUND/AIMS: Status epilepticus (SE) might be followed by temporal lobe epilepsy (TLE), a common neurologic disorder characterized by spontaneous recurrent seizures (SRSs). However, the relationship between SE and TLE is still incompletely characterized. For this reason, in a model of TLE we evaluated the lesion extent and the onset of SRSs to determine if they were influenced by the SE dynamics. METHODS: Sixty-two adult male Sprague-Dawley rats were implanted for video-electrocorticographic (v-ECoG) monitoring and intraperitoneally treated with saline or kainic acid (KA, 15 mg/kg) at 8 weeks of age. v-ECoG recordings were obtained during SE, in the following 9 weeks, and assessed by amplitude or power band spectrum. Rats were euthanized 3 or 64 days after SE to evaluate the lesion. RESULTS: SE lasted about 10 h during which the mean duration of convulsive seizures (CSs) increased from 39 s, at 30 min, to 603 s at 4 h. The gamma power peaked 30 min after the SE onset and its peak was correlated (r²=0.13, p=0.042) with the overall SE duration. Subsequently, the gamma power was reduced under the baseline until the end of SE. The theta power increased at approximately 150% of basal levels 3 h after KA injection, but it went back to basal levels with the full development of CSs. Interestingly, the timing of the first SRS in chronic epilepsy was correlated with the latency to develop the first CS with loss of posture during SE (r²=0.60, p<0.001). Additionally, the overall duration of CSs observed during SE was related to the number of damaged brain regions (r²=0.60, p=0.005), but it did not influence the timing of the first SRS in chronic epilepsy. CONCLUSION: Overall, our results show that the onset of chronic epilepsy is modulated by SE dynamics, whereas brain damage is related to prolonged convulsions in SE.

Effects of Diazepam on Low-Frequency and High-Frequency Electrocortical γ-Power Mediated by α1- and α2-GABAA Receptors.

Patterns of spontaneous electric activity in the cerebral cortex change upon administration of benzodiazepines. Here we are testing the hypothesis that the prototypical benzodiazepine, diazepam, affects spectral power density in the low (20-50 Hz) and high (50-90 Hz) γ-band by targeting GABAA receptors harboring α1- and α2-subunits. Local field potentials (LFPs) and action potentials were recorded in the barrel cortex of wild type mice and two mutant strains in which the drug exclusively acted via GABAA receptors containing either α1- (DZα1-mice) or α2-subunits (DZα2-mice). In wild type mice, diazepam enhanced low γ-power. This effect was also evident in DZα2-mice, while diazepam decreased low γ-power in DZα1-mice. Diazepam increased correlated local LFP-activity in wild type animals and DZα2- but not in DZα1-mice. In all genotypes, spectral power density in the high γ-range and multi-unit action potential activity declined upon diazepam administration. We conclude that diazepam modifies low γ-power in opposing ways via α1- and α2-GABAA receptors. The drug's boosting effect involves α2-receptors and an increase in local intra-cortical synchrony. Furthermore, it is important to make a distinction between high- and low γ-power when evaluating the effects of drugs that target GABAA receptors.

Decomposing Tool-Action Observation: A Stereo-EEG Study.

A description of the spatiotemporal dynamics of human cortical activity during cognitive tasks is a fundamental goal of neuroscience. In the present study, we employed stereo-EEG in order to assess the neural activity during tool-action observation. We recorded from 49 epileptic patients (5502 leads) implanted with intracerebral electrodes, while they observed tool and hand actions. We deconstructed actions into 3 events-video onset, action onset, and tool-object contact-and assessed how different brain regions respond to these events. Video onset, with actions not yet visible, recruited only visual areas. Aligning the responses at action onset, yielded activity in the parietal-frontal manipulation circuit and, selectively for tool actions, in the left anterior supramarginal gyrus (aSMG). Finally, by aligning to the tool-object contact that signals the achievement of the main goal of the observed action, activations were found in SII and dorsal premotor cortex. In conclusion, our data show that during tool-action observation, in addition to the general action observation network there is a selective activation of aSMG, which exhibits internally different patterns of responsiveness. In addition, neural responses selective for the contact between the tool and the object were also observed.

Tuning face perception with electrical stimulation of the fusiform gyrus.

The fusiform gyrus (FG) is an important node in the face processing network, but knowledge of its causal role in face perception is currently limited. Recent work demonstrated that high frequency stimulation applied to the FG distorts the perception of faces in human subjects (Parvizi et al. []: J Neurosci 32:14915-14920). However, the timing of this process in the FG relative to stimulus onset and the spatial extent of FG's role in face perception are unknown. Here, we investigate the causal role of the FG in face perception by applying precise, event-related electrical stimulation (ES) to higher order visual areas including the FG in six human subjects undergoing intracranial monitoring for epilepsy. We compared the effects of single brief (100 µs) electrical pulses to the FG and non-face-selective visual areas on the speed and accuracy of detecting distorted faces. Brief ES applied to face-selective sites did not affect accuracy but significantly increased the reaction time (RT) of detecting face distortions. Importantly, RT was altered only when ES was applied 100ms after visual onset and in face-selective but not place-selective sites. Furthermore, ES applied to face-selective areas decreased the amplitude of visual evoked potentials and high gamma power over this time window. Together, these results suggest that ES of face-selective regions within a critical time window induces a delay in face perception. These findings support a temporally and spatially specific causal role of face-selective areas and signify an important link between electrophysiology and behavior in face perception. Hum Brain Mapp 38:2830-2842, 2017. © 2017 Wiley Periodicals, Inc.

Long-latency reductions in gamma power predict hemodynamic changes that underlie the negative BOLD signal.

Studies that use prolonged periods of sensory stimulation report associations between regional reductions in neural activity and negative blood oxygenation level-dependent (BOLD) signaling. However, the neural generators of the negative BOLD response remain to be characterized. Here, we use single-impulse electrical stimulation of the whisker pad in the anesthetized rat to identify components of the neural response that are related to "negative" hemodynamic changes in the brain. Laminar multiunit activity and local field potential recordings of neural activity were performed concurrently with two-dimensional optical imaging spectroscopy measuring hemodynamic changes. Repeated measurements over multiple stimulation trials revealed significant variations in neural responses across session and animal datasets. Within this variation, we found robust long-latency decreases (300 and 2000 ms after stimulus presentation) in gamma-band power (30-80 Hz) in the middle-superficial cortical layers in regions surrounding the activated whisker barrel cortex. This reduction in gamma frequency activity was associated with corresponding decreases in the hemodynamic responses that drive the negative BOLD signal. These findings suggest a close relationship between BOLD responses and neural events that operate over time scales that outlast the initiating sensory stimulus, and provide important insights into the neurophysiological basis of negative neuroimaging signals.

Transcranial direct-current stimulation of the prefrontal cortex enhances working memory and suppresses pathological gamma power elevation in schizophrenia.

BACKGROUND: This investigation examines the clinical benefits of prefrontal cortex transcranial direct current stimulation (tDCS) treatment of working memory (WM) dysfunction in chronic schizophrenia patients. RESEARCH DESIGN AND METHODS: 34 schizophrenia (SZ) patients were evaluated at baseline, and 29 patients were randomly assigned to either active tDCS intervention or sham tDCS intervention. tDCS intervention applied 10 consecutive sessions (20 minutes, 2 mA, two sessions a day) over 5 days. WM performance (N = 25), symptom severity (N = 29), and resting EEG (N = 17) were assessed from pre- to post-tDCS intervention. Additionally, symptom severity was noted over a 12-week follow-up period. RESULTS: WM accuracy significantly improved in the active tDCS group while WM accuracy in the sham tDCS group was unchanged. Significant symptom-severity reduction was sustained for one week after active tDCS intervention. Sustained resting gamma stability (RGS) was noted from baseline to post tDCS in the active-treatment group versus a significant elevation in pathological gamma power in the sham-tDCS group. CONCLUSIONS: Examining treatment effects on RGS in SZ could be critical in identifying effective novel treatment strategies that promote left-DLPFC excitability and enhance WM functioning. Further empirical support is warranted to support the clinical benefits over longer periods of time. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04637724. ETHICS APPROVAL REGISTRATION NO: 337-19.

Intracranial EEGs evidenced visual object processing in the human medial temporal lobe subregions.

The perirhinal cortex (PRC) and parahippocampal cortex (PHC) are core regions along the visual dual-stream. The specific functional roles of the PRC and PHC and their interactions with the downstream hippocampus cortex (HPC) are crucial for understanding visual memory. Our research used human intracranial EEGs to study the neural mechanism of the PRC, PHC, and HPC in visual object encoding. Single-regional function analyses found evidence that the PRC, PHC, and HPC are activated ∼100 ms within the broad-gamma band and that the PRC was more strongly activated than either the PHC or the HPC after an object stimulus. Inter-regional analyses showed strong bidirectional interactions of the PRC with both the PHC and HPC in the low-frequency band, whereas the interactions between the PHC and HPC were not significant. These findings demonstrated the core role of the PRC in encoding visual object information and supported the hypothesis of PRC-HPC-ventral object pathway. The recruitment of the PHC and its interaction with the PRC in visual object encoding also provide new insights beyond the traditional dorsal-stream hypothesis.

The relationship between gamma-band neural oscillations and language skills in youth with Autism Spectrum Disorder and their first-degree relatives.

BACKGROUND: Most children with Autism Spectrum Disorder (ASD) have co-occurring language impairments and some of these autism-specific language difficulties are also present in their non-autistic first-degree relatives. One of the possible neural mechanisms associated with variability in language functioning is alterations in cortical gamma-band oscillations, hypothesized to be related to neural excitation and inhibition balance. METHODS: We used a high-density 128-channel electroencephalography (EEG) to register brain response to speech stimuli in a large sex-balanced sample of participants: 125 youth with ASD, 121 typically developing (TD) youth, and 40 unaffected siblings (US) of youth with ASD. Language skills were assessed with Clinical Evaluation of Language Fundamentals. RESULTS: First, during speech processing, we identified significantly elevated gamma power in ASD participants compared to TD controls. Second, across all youth, higher gamma power was associated with lower language skills. Finally, the US group demonstrated an intermediate profile in both language and gamma power, with nonverbal IQ mediating the relationship between gamma power and language skills. LIMITATIONS: We only focused on one of the possible neural contributors to variability in language functioning. Also, the US group consisted of a smaller number of participants in comparison to the ASD or TD groups. Finally, due to the timing issue in EEG system we have provided only non-phase-locked analysis. CONCLUSIONS: Autistic youth showed elevated gamma power, suggesting higher excitation in the brain in response to speech stimuli and elevated gamma power was related to lower language skills. The US group showed an intermediate pattern of gamma activity, suggesting that the broader autism phenotype extends to neural profiles.

Effects of optogenetic and visual stimulation on gamma activity in the visual cortex.

Studying brain functions and activity during gamma oscillations can be a challenge because it requires careful planning to create the necessary conditions for a controlled experiment. Such an experiment consists of placing the brain into a gamma state and investigating cognitive processing with a careful design. Cortical oscillations in the gamma frequency range (30-80 Hz) play an essential role in a variety of cognitive processes, including visual processing and cognition. The present study aims to investigate the effects of a visual stimulus on the primary visual cortex under gamma oscillations. Specifically, we sought to explore the behavior of gamma oscillations triggered by optogenetic stimulation in the II and IV layers of the visual cortex, both with and without concurrent visual stimulation. Our results show that optogenetic stimulation increases the power of gamma oscillation in both layers of the visual cortex. However, the combined stimuli resulted in a reduction of gamma power in layer II and an increase and reinforcement in gamma power in layer IV. Modelling the results with the Wilson-Cowan model suggests changes in the input of the excitatory population due to the combined stimuli. In addition, our analysis of the data using the Lempel-Ziv complexity method supports our interpretations from the modeling. Thus, our results suggest that optogenetic stimulation enhances low gamma power in both layers of the visual cortex, while simultaneous visual stimulation has differing effects on the two layers, reducing gamma power in layer II and increasing it in layer IV.

Ketamine supresses REM sleep and markedly increases EEG gamma oscillations in the Wistar Kyoto rat model of treatment-resistant depression.

Wistar-Kyoto (WKY) rats exhibit depression-like characteristics and decreased sensitivity to monoamine-based antidepressants, making them a suitable model of treatment-resistant depression (TRD). Ketamine has emerged recently as a rapidly acting antidepressant with high efficacy in TRD. Our aim was to determine whether subanaesthetic doses of ketamine can correct sleep and electroencephalogram (EEG) alterations in WKY rats and whether any ketamine-induced changes differentially affect WKY rats compared to Sprague-Dawley (SD) rats. Thus, we surgically implanted 8 SD and 8 WKY adult male rats with telemetry transmitters and recorded their EEG, electromyogram, and locomotor activity after vehicle or ketamine (3, 5 or 10 mg/kg, s.c.) treatment. We also monitored the plasma concentration of ketamine and its metabolites, norketamine and hydroxynorketamine in satellite animals. We found that WKY rats have an increased amount of rapid eye movement (REM) sleep, fragmented sleep-wake pattern, and increased EEG delta power during non-REM sleep compared to SD rats. Ketamine suppressed REM sleep and increased EEG gamma power during wakefulness in both strains, but the gamma increase was almost twice as large in WKY rats than in SD rats. Ketamine also increased beta oscillations, but only in WKY rats. These differences in sleep and EEG are unlikely to be caused by dissimilarities in ketamine metabolism as the plasma concentrations of ketamine and its metabolites were similar in both strains. Our data suggest an enhanced antidepressant-like response to ketamine in WKY rats, and further support the predictive validity of acute REM sleep suppression as a measure of antidepressant responsiveness.