Evaluating cortical excitatory and inhibitory activity through interictal intracranial electroencephalography in mesial temporal lobe epilepsy.

Gamma oscillation regularity (GOR) indicates the synchronization of inhibitory interneurons, while the reactivity of cortico-cortical evoked potentials (CCEPs) is supposed to reflect local cortical excitability. Under the assumption that the early response of CCEP near the stimulation site also indicates excitatory activity primarily mediated by pyramidal cells, we aimed to visualize the cortical inhibitory and excitatory activities using GOR and CCEP in combination and to use them to predict the epileptogenic zone (EZ) in mesial temporal lobe epilepsy (MTLE). In five patients who underwent intracranial electrode implantation, GOR and CCEP reactivity in the vicinity of the stimulation site was quantified. The interictal GOR was calculated using multiscale entropy (MSE), the decrease of which was related to the enhanced GOR. These parameters were compared on an electrode-and-electrode basis, and spatially visualized on the brain surface. As a result, elevated GOR and CCEP reactivities, indicative of enhanced inhibitory and excitatory activities, were observed in the epileptogenic regions. Elevated CCEP reactivity was found to be localized to a restricted area centered on the seizure onset region, whereas GOR elevation was observed in a broader region surrounding it. Although these parameters independently predicted the EZ with high specificity, we combined the two to introduce a novel parameter, the excitatory and inhibitory (EI) index. The EI index predicted EZ with increased specificity compared with GOR or CCEP reactivity alone. Our results demonstrate that GOR and CCEP reactivity provided a quantitative visualization of the distribution of cortical inhibitory and excitatory activities and highlighted the relationship between the two parameters. The combination of GOR and CCEP reactivities are expected to serve as biomarkers for localizing the epileptogenic zone in MTLE from interictal intracranial electroencephalograms.

Analyzing top-down visual attention in the context of gamma oscillations: a layer- dependent network-of- networks approach.

Top-down visual attention is a fundamental cognitive process that allows individuals to selectively attend to salient visual stimuli in the environment. Recent empirical findings have revealed that gamma oscillations participate in the modulation of visual attention. However, computational studies face challenges when analyzing the attentional process in the context of gamma oscillation due to the unstable nature of gamma oscillations and the complexity induced by the layered fashion in the visual cortex. In this study, we propose a layer-dependent network-of-networks approach to analyze such attention with gamma oscillations. The model is validated by reproducing empirical findings on orientation preference and the enhancement of neuronal response due to top-down attention. We perform parameter plane analysis to classify neuronal responses into several patterns and find that the neuronal response to sensory and attention signals was modulated by the heterogeneity of the neuronal population. Furthermore, we revealed a counter-intuitive scenario that the excitatory populations in layer 2/3 and layer 5 exhibit opposite responses to the attentional input. By modification of the original model, we confirmed layer 6 plays an indispensable role in such cases. Our findings uncover the layer-dependent dynamics in the cortical processing of visual attention and open up new possibilities for further research on layer-dependent properties in the cerebral cortex.

TRanscranial AlterNating current stimulation FOR patients with mild Alzheimer's Disease (TRANSFORM-AD): a randomized controlled clinical trial.

BACKGROUND: The mechanistic effects of gamma transcranial alternating current stimulation (tACS) on hippocampal gamma oscillation activity in Alzheimer's Disease (AD) remains unclear. This study aimed to clarify beneficial effects of gamma tACS on cognitive functioning in AD and to elucidate effects on hippocampal gamma oscillation activity. METHODS: This is a double-blind, randomized controlled single-center trial. Participants with mild AD were randomized to tACS group or sham group, and underwent 30 one-hour sessions of either 40 Hz tACS or sham stimulation over consecutive 15 days. Cognitive functioning, structural magnetic resonance imaging (MRI), and simultaneous electroencephalography-functional MRI (EEG-fMRI) were evaluated at baseline, the end of the intervention and at 3-month follow-up from the randomization. RESULTS: A total of 46 patients were enrolled (23 in the tACS group, 23 in the sham group). There were no group differences in the change of the primary outcome, 11-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-Cog) score after intervention (group*time, p = 0.449). For secondary outcomes, compared to the control group, the intervention group showed significant improvement in MMSE (group*time, p = 0.041) and MoCA scores (non-parametric test, p = 0.025), which were not sustained at 3-month follow-up. We found an enhancement of theta-gamma coupling in the hippocampus, which was positively correlated with improvements of MMSE score and delayed recall. Additionally, fMRI revealed increase of the local neural activity in the hippocampus. CONCLUSION: Effects on the enhancement of theta-gamma coupling and neural activity within the hippocampus suggest mechanistic models for potential therapeutic mechanisms of tACS. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03920826; Registration Date: 2019-04-19.

Auditory entrainment coordinates cortical-BNST-NAc triple time locking to alleviate the depressive disorder.

Listening to music is a promising and accessible intervention for alleviating symptoms of major depressive disorder. However, the neural mechanisms underlying its antidepressant effects remain unclear. In this study on patients with depression, we used auditory entrainment to evaluate intracranial recordings in the bed nucleus of the stria terminalis (BNST) and nucleus accumbens (NAc), along with temporal scalp electroencephalogram (EEG). We highlight music-induced synchronization across this circuit. The synchronization initiates with temporal theta oscillations, subsequently inducing local gamma oscillations in the BNST-NAc circuit. Critically, the incorporated external entrainment induced a modulatory effect from the auditory cortex to the BNST-NAc circuit, activating the antidepressant response and highlighting the causal role of physiological entrainment in enhancing the antidepressant response. Our study explores the pivotal role of the auditory cortex and proposes a neural oscillation triple time-locking model, emphasizing the capacity of the auditory cortex to access the BNST-NAc circuit.

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.

Impaired 40-Hz and intact hierarchical organization mode of auditory steady-state responses among individuals with clinical high-risk for psychosis.

BACKGROUND: Impaired gamma band oscillation, specifically 40-Hz auditory steady state response (ASSR) has been robustly found in schizophrenia, while there is relatively little evidence characterizing the ASSR before full-blown psychosis. OBJECTIVE: To characterize gamma-band ASSR in populations at clinical high-risk for psychosis (CHR). METHODS: One hundred and seven CHR subjects and sixty-five healthy control (HC) subjects were included and completed clinical assessments, the ASSR paradigm of electroencephalography (EEG) and cognitive assessments. Both indices of event-related spectrum perturbation (ERSP) and intertrial coherence (ITC) in response to 20-Hz, 30-Hz and 40-Hz click sounds were respectively qualified and compared between these two groups, as well as the relationship to clinical psychopathology and cognitive function was assessed. RESULTS: At 40-Hz click sounds, ERSP in HC group (1.042 ± 0.047) was statistical significantly increased than that in CHR group (0.873 ± 0.036) (p = 0.005)；at 30-Hz, ERSP in HC group (0.536 ± 0.024) was increased than that in CHR group (0.483 ± 0.019), but the difference was trend statistical significance (p = 0.083)；at 20-Hz, ERSP in HC group (0.452 ± 0.017) was not different significantly from CHR group (0.418 ± 0.013) (p = 0.104). ERSP of the HC group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of the three ERSP showed statistical significance (30-Hz vs. 40-Hz: p < 0.001; 20-Hz vs. 40-Hz: p < 0.001；20-Hz vs. 30-Hz: p = 0.003). Similarly, ERSP of the CHR group was the highest at 40-Hz click sounds, followed by 30-Hz, and the lowest at 20-Hz. The difference between any two of these three ERSP showed statistical significance (30-Hz vs. 40-Hz: p < 0.001; 20-Hz vs. 40-Hz: p < 0.001；20-Hz vs. 30-Hz: p = 0.002). A statistically significant small positive correlation of 40-Hz ERSP with signal processing speed score was observed in the HC group (ρ = 0.27, p = 0.029). A statistically significant small negative correlation of 40-Hz ERSP with visual learning score was observed in the CHR group (ρ = -0.22, p = 0.023). CONCLUSION: Impaired 40-Hz but undamaged hierarchical organization mode of auditory steady state presented in the CHR populations. Abnormal 40 Hz ASSR for CHR might be associated with cognitive functions, such as information processing speed and visual memory.

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.

Inter-subject gamma oscillation synchronization as a biomarker of abnormal processing of social interaction in ADHD.

Children with attention-deficit hyperactivity disorder (ADHD) have difficulties in social interactions. Studying brain activity during social interactions is difficult with conventional artificial stimuli. This pioneering study examined the neural correlates of social perception in children with ADHD and matched controls using naturalistic stimuli. We presented 20 children with ADHD and 20 age-and-sex-matched controls with tailored movies featuring high- or low-level social interactions while recording electroencephalographic signals. Both groups exhibited synchronized gamma-band oscillations, but controls demonstrated greater inter-subject correlations. Additionally, the difference in inter-subject correlations between high- and low-interaction movies was significantly larger in controls compared to ADHD patients. Between 55 and 75 Hz comparing viewing high interaction movies with low interaction moves, controls had a significantly larger weighting in the right parietal lobe, while ADHD patients had a significantly smaller weighting in the left occipital lobe. These findings reveal distinct spatiotemporal neural signatures in social interaction processing among children with ADHD and controls using naturalistic stimuli. These neural markers offer potential for group differentiation and assessing intervention efficacy, advancing our understanding ADHD-related social interaction mechanisms.

Firing rate models for gamma oscillations in I-I and E-I networks.

Firing rate models for describing the mean-field activities of neuronal ensembles can be used effectively to study network function and dynamics, including synchronization and rhythmicity of excitatory-inhibitory populations. However, traditional Wilson-Cowan-like models, even when extended to include an explicit dynamic synaptic activation variable, are found unable to capture some dynamics such as Interneuronal Network Gamma oscillations (ING). Use of an explicit delay is helpful in simulations at the expense of complicating mathematical analysis. We resolve this issue by introducing a dynamic variable, u, that acts as an effective delay in the negative feedback loop between firing rate (r) and synaptic gating of inhibition (s). In effect, u endows synaptic activation with second order dynamics. With linear stability analysis, numerical branch-tracking and simulations, we show that our r-u-s rate model captures some key qualitative features of spiking network models for ING. We also propose an alternative formulation, a v-u-s model, in which mean membrane potential v satisfies an averaged current-balance equation. Furthermore, we extend the framework to E-I networks. With our six-variable v-u-s model, we demonstrate in firing rate models the transition from Pyramidal-Interneuronal Network Gamma (PING) to ING by increasing the external drive to the inhibitory population without adjusting synaptic weights. Having PING and ING available in a single network, without invoking synaptic blockers, is plausible and natural for explaining the emergence and transition of two different types of gamma oscillations.

Circuit dynamics of superficial and deep CA1 pyramidal cells and inhibitory cells in freely moving macaques.

Diverse neuron classes in hippocampal CA1 have been identified through the heterogeneity of their cellular/molecular composition. How these classes relate to hippocampal function and the network dynamics that support cognition in primates remains unclear. Here, we report inhibitory functional cell groups in CA1 of freely moving macaques whose diverse response profiles to network states and each other suggest distinct and specific roles in the functional microcircuit of CA1. In addition, pyramidal cells that were grouped by their superficial or deep layer position differed in firing rate, burstiness, and sharp-wave ripple-associated firing. They also showed strata-specific spike-timing interactions with inhibitory cell groups, suggestive of segregated neural populations. Furthermore, ensemble recordings revealed that cell assemblies were preferentially organized according to these strata. These results suggest that hippocampal CA1 in freely moving macaques bears a sublayer-specific circuit organization that may shape its role in cognition.

Exploring the impact of 40 Hz multi-luminaire light exposure in Alzheimer's dementia: insights from a convenient sampling, non-randomized case-control study.

BACKGROUND: Recent studies propose 40 Hz neural activity induction as a promising approach for managing Alzheimer's dementia (AD). However, traditional flickering light is suboptimal in addressing cognitive and neuropsychiatric symptoms (NPS) of AD. This study aims to investigate the clinical efficacy of a novel multi-luminaire lighting technology, with reduced perceptible flickering, for treating AD NPS. METHODS: This study is a prospective, convenient sampling, non-randomized case-control investigation involving seventy-eight clinically diagnosed AD patients from 7 daycare centers. Thirty-five were exposed to 40 Hz light through Delta M + BrainCare Light (M +), 4 h daily, 5 days/week, for 12 weeks. The other 43 patients served as controls. Sum of boxes of the Clinical Dementia Rating (CDR-SB) scale, Neuropsychiatric Inventory (NPI), and Zarit Burden Interview (ZBI) were assessed at baseline and the 13th week. RESULTS: At baseline, the cases had worse cognitive function, lower cognitive score (Mini-Mental State Examination, p = 0.04; Cognitive Abilities Screening Instrument, p = 0.04), and advanced caregiver burden with higher ZBI scores (p < 0.01) than the controls. After the intervention, the cases had significant improvements in NPS as assessed using the NPI (p = 0.02), especially depression and euphoria symptoms (p = 0.04 and < 0.01, respectively) and less caregiver burden (ZBI score, p < 0.01). In global function, the control group showed a significant decline in CDR-SB score (p < 0.01), while the cases did not. CONCLUSIONS: Results suggest M + may slow global function decline, preserve cognitive function, improve NPS, and reduce caregiver burden in AD patients. Larger studies with biomarkers are needed to explore underlying mechanisms.

Sensitivity to and Control of Distraction: Distractor-Entrained Oscillation and Frontoparietal EEG Gamma Synchronization.

While recent advancements have been made towards a better understanding of the involvement of the prefrontal cortex (PFC) in the context of cognitive control, the exact mechanism is still not fully understood. Successful behavior requires the correct detection of goal-relevant cues and resisting irrelevant distractions. Frontal parietal networks have been implicated as important for maintaining cognitive control in the face of distraction. The present study investigated the role of gamma-band power in distraction resistance and frontoparietal networks, as its increase is linked to cholinergic activity. We examined changes in gamma activity and their relationship to frontoparietal top-down modulation for distractor challenges and to bottom-up distractor processing. Healthy young adults were tested using a modified version of the distractor condition sustained attention task (dSAT) while wearing an EEG. The modified distractor was designed so that oscillatory activities could be entrained to it, and the strength of entrainment was used to assess the degree of distraction. Increased top-down control during the distractor challenge increased gamma power in the left parietal regions rather than the right prefrontal regions predicted from rodent studies. Specifically, left parietal gamma power increased in response to distraction where the amount of this increase was negatively correlated with the neural activity reflecting bottom-up distractor processing in the visual area. Variability in gamma power in right prefrontal regions was associated with increased response time variability during distraction. This may suggest that the right prefrontal region may contribute to the signaling needed for top-down control rather than its implementation.

A large-scale neuronal network modelling study: Stimulus size modulates gamma oscillations in the primary visual cortex by long-range connections.

Stimulus size modulation of neuronal firing activity is a fundamental property of the primary visual cortex. Numerous biological experiments have shown that stimulus size modulation is affected by multiple factors at different spatiotemporal scales, but the exact pathways and mechanisms remain incompletely understood. In this paper, we establish a large-scale neuronal network model of primary visual cortex with layer 2/3 to study how gamma oscillation properties are modulated by stimulus size and especially how long-range connections affect the modulation as realistic neuronal properties and spatial distributions of synaptic connections are considered. It is shown that long-range horizontal synaptic connections are sufficient to produce dimensional modulation of firing rates and gamma oscillations. In particular, with increasing grating stimulus size, the firing rate increases and then decreases, the peak frequency of gamma oscillations decreases and the spectral power increases. These are consistent with biological experimental observations. Furthermore, we explain in detail how the number and spatial distribution of long-range connections affect the size modulation of gamma oscillations by using the analysis of neuronal firing activity and synaptic current fluctuations. Our results provide a mechanism explanation for size modulation of gamma oscillations in the primary visual cortex and reveal the important and unique role played by long-range connections, which contributes to a deeper understanding of the cognitive function of gamma oscillations in visual cortex.

The influence of electrode types to the visually induced gamma oscillations in mouse primary visual cortex.

The local field potential (LFP) is an extracellular electrical signal associated with neural ensemble input and dendritic signaling. Previous studies have linked gamma band oscillations of the LFP in cortical circuits to sensory stimuli encoding, attention, memory, and perception. Inconsistent results regarding gamma tuning for visual features were reported, but it remains unclear whether these discrepancies are due to variations in electrode properties. Specifically, the surface area and impedance of the electrode are important characteristics in LFP recording. To comprehensively address these issues, we conducted an electrophysiological study in the V1 region of lightly anesthetized mice using two types of electrodes: one with higher impedance (1 MΩ) and a sharp tip (10 µm), while the other had lower impedance (100 KΩ) but a thicker tip (200 µm). Our findings demonstrate that gamma oscillations acquired by sharp-tip electrodes were significantly stronger than those obtained from thick-tip electrodes. Regarding size tuning, most gamma power exhibited surround suppression at larger gratings when recorded from sharp-tip electrodes. However, the majority showed enhanced gamma power at larger gratings when recorded from thick-tip electrodes. Therefore, our study suggests that microelectrode parameters play a significant role in accurately recording gamma oscillations and responsive tuning to sensory stimuli.

Safety, tolerability, and efficacy estimate of evoked gamma oscillation in mild to moderate Alzheimer's disease.

Background: Alzheimer's Disease (AD) is a multifactorial, progressive neurodegenerative disease that disrupts synaptic and neuronal activity and network oscillations. It is characterized by neuronal loss, brain atrophy and a decline in cognitive and functional abilities. Cognito's Evoked Gamma Therapy System provides an innovative approach for AD by inducing EEG-verified gamma oscillations through sensory stimulation. Prior research has shown promising disease-modifying effects in experimental AD models. The present study (NCT03556280: OVERTURE) evaluated the feasibly, safety and efficacy of evoked gamma oscillation treatment using Cognito's medical device (CogTx-001) in participants with mild to moderate AD. Methods: The present study was a randomized, double blind, sham-controlled, 6-months clinical trial in participants with mild to moderate AD. The trial enrolled 76 participants, aged 50 or older, who met the clinical criteria for AD with baseline MMSE scores between 14 and 26. Participants were randomly assigned 2:1 to receive self-administered daily, one-hour, therapy, evoking EEG-verified gamma oscillations or sham treatment. The CogTx-001 device was use at home with the help of a care partner, over 6 months. The primary outcome measures were safety, evaluated by physical and neurological exams and monthly assessments of adverse events (AEs) and MRI, and tolerability, measured by device use. Although the trial was not statistically powered to evaluate potential efficacy outcomes, primary and secondary clinical outcome measures included several cognitive and functional endpoints. Results: Total AEs were similar between groups, there were no unexpected serious treatment related AEs, and no serious treatment-emergent AEs that led to study discontinuation. MRI did not show Amyloid-Related Imaging Abnormalities (ARIA) in any study participant. High adherence rates (85-90%) were observed in sham and treatment participants. There was no statistical separation between active and sham arm participants in primary outcome measure of MADCOMS or secondary outcome measure of CDR-SB or ADAS-Cog14. However, some secondary outcome measures including ADCS-ADL, MMSE, and MRI whole brain volume demonstrated reduced progression in active compared to sham treated participants, that achieved nominal significance. Conclusion: Our results demonstrate that 1-h daily treatment with Cognito's Evoked Gamma Therapy System (CogTx-001) was safe and well-tolerated and demonstrated potential clinical benefits in mild to moderate AD.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03556280.

Enhancement of low gamma oscillations by volitional conditioning of local field potential in the primary motor and visual cortex of mice.

Volitional control of local field potential oscillations in low gamma band via brain machine interface can not only uncover the relationship between low gamma oscillation and neural synchrony but also suggest a therapeutic potential to reverse abnormal local field potential oscillation in neurocognitive disorders. In nonhuman primates, the volitional control of low gamma oscillations has been demonstrated by brain machine interface techniques in the primary motor and visual cortex. However, it is not clear whether this holds in other brain regions and other species, for which gamma rhythms might involve in highly different neural processes. Here, we established a closed-loop brain-machine interface and succeeded in training mice to volitionally elevate low gamma power of local field potential in the primary motor and visual cortex. We found that the mice accomplished the task in a goal-directed manner and spiking activity exhibited phase-locking to the oscillation in local field potential in both areas. Moreover, long-term training made the power enhancement specific to direct and adjacent channel, and increased the transcriptional levels of NMDA receptors as well as that of hypoxia-inducible factor relevant to metabolism. Our results suggest that volitionally generated low gamma rhythms in different brain regions share similar mechanisms and pave the way for employing brain machine interface in therapy of neurocognitive disorders.

Utilizing Excitatory and Inhibitory Activity Derived from Interictal Intracranial Electroencephalography as Potential Biomarkers for Epileptogenicity.

Epileptogenic zones (EZs), where epileptic seizures cease after resection, are localized by assessing the seizure-onset zone using ictal electroencephalography (EEG). Owing to the difficulty in capturing unpredictable seizures, biomarkers capable of identifying EZs from interictal EEG are anticipated. Recent studies using intracranial EEG have identified several potential candidate biomarkers for epileptogenicity. High-frequency oscillation (HFO) was initially expected to be a robust biomarker of abnormal excitatory activity in the ictogenic region. However, HFO-guided resection failed to improve seizure prognosis. Meanwhile, the regularity of low-gamma oscillations (30-80 Hz) indicates inhibitory interneurons' hypersynchronization, which could be used to localize the EZ. Besides resting-state EEG assessments, evoked potentials elicited by single-pulse electrical stimulation, such as corticocortical evoked potentials (CCEP), became valuable tools for assessing epileptogenic regions. CCEP responses recorded in the cortex remote from the stimulation site indicate functional connectivity, revealing increased internal connectivity within the ictogenic region and elevated inhibitory input from the non-involved regions to the ictogenic region. Conversely, large responses close to the stimulation site reflect local excitability, manifesting as an increased N1 amplitude and overriding HFO. Further research is required to establish whether these novel electrophysiological methods, either individually or in combination, can function as robust biomarkers of epileptogenicity and hold promise for improving seizure prognosis.

Temporal hyper-connectivity and frontal hypo-connectivity within gamma band in schizophrenia: A resting state EEG study.

OBJECTIVE: The brain network serves as the physiological foundation for information processing of the brain. Many studies have reported abnormalities of gamma oscillations in Schizophrenia. The aim of this study was to investigate the gamma-band connectivity in Schizophrenia patients. METHODS: We recorded the resting state electroencephalogram (EEG) for 15 schizophrenia patients with refractory auditory hallucinations and 14 healthy controls, with eyes open and closed. The brain network was constructed based on weighted phase lag index for gamma band. Whole scalp metrics (clustering coefficient, global efficiency and local efficiency) and local region metrics (degree and betweenness centrality) in the frontal and temporal lobes were computed. Correlation analyses between network metrics and symptom scales were examined to find associations with symptom severity. RESULTS: Schizophrenia patients had larger global efficiency and local efficiency (p < 0.05) with eyes closed, probably representing greater brain activity and information exchange. For degree and betweenness centrality, schizophrenia patients showed an increase (p < 0.05) in the temporal lobe but a decrease (p < 0.05) in the frontal lobe with eyes closed and open, potentially account for the patients' symptoms such as hallucinations and thought disorders. Local efficiency and frontal lobe degree were positively and negatively correlated with the scales, respectively (both p < 0.05). CONCLUSIONS: Altered connectivity of the resting state brain network has been revealed and may be associated with the core symptoms of schizophrenia. Our study provides promising evidence for the investigation of the pathological basis of Schizophrenia and could aid in objective diagnosis.

The Thalamocortical Mechanism Underlying the Generation and Regulation of the Auditory Steady-State Responses in Awake Mice.

The auditory steady-state response (ASSR) is a cortical oscillation induced by trains of 40 Hz acoustic stimuli. While the ASSR has been widely used in clinic measurement, the underlying neural mechanism remains poorly understood. In this study, we investigated the contribution of different stages of auditory thalamocortical pathway-medial geniculate body (MGB), thalamic reticular nucleus (TRN), and auditory cortex (AC)-to the generation and regulation of 40 Hz ASSR in C57BL/6 mice of both sexes. We found that the neural response synchronizing to 40 Hz sound stimuli was most prominent in the GABAergic neurons in the granular layer of AC and the ventral division of MGB (MGBv), which were regulated by optogenetic manipulation of TRN neurons. Behavioral experiments confirmed that disrupting TRN activity has a detrimental effect on the ability of mice to discriminate 40 Hz sounds. These findings revealed a thalamocortical mechanism helpful to interpret the results of clinical ASSR examinations.Significance Statement Our study contributes to clarifying the thalamocortical mechanisms underlying the generation and regulation of the auditory steady-state response (ASSR), which is commonly used in both clinical and neuroscience research to assess the integrity of auditory function. Combining a series of electrophysiological and optogenetic experiments, we demonstrate that the generation of cortical ASSR is dependent on the lemniscal thalamocortical projections originating from the ventral division of medial geniculate body to the GABAergic interneurons in the granule layer of the auditory cortex. Furthermore, the thalamocortical process for ASSR is strictly regulated by the activity of thalamic reticular nucleus (TRN) neurons. Behavioral experiments confirmed that dysfunction of TRN would cause a disruption of mice's behavioral performance in the auditory discrimination task.

Gamma-band harmonic responses for beta-band auditory steady-state response are intact in patients with early stage schizophrenia.

Gamma oscillations, thought to arise from the activity of ɣ-aminobutyric acid (GABA)ergic interneurons, have potential as a biomarker for schizophrenia. Gamma-band auditory steady-state responses (ASSRs) are notably reduced in both chronic and early-stage schizophrenia patients. Furthermore, alterations in gamma-band ASSRs have been demonstrated in animal models through translational research. However, the 40-Hz harmonic responses of the 20-Hz ASSR are not as well-characterized, despite the possibility that these harmonic oscillatory responses may reflect resonant activity in neural circuits. In this study, we investigated the 40-Hz harmonic response to the 20-Hz ASSR in the early stages of schizophrenia. The study recruited 49 participants, including 15 individuals at ultra-high-risk (UHR) for psychosis, 13 patients with first-episode schizophrenia (FES), and 21 healthy controls (HCs). The 40-Hz harmonic responses of the 20-Hz ASSR were evident in all groups. Interestingly, while previous report observed reduced 40-Hz ASSRs, the 40-Hz harmonic responses of the 20-Hz ASSR were not reduced in the UHR or FES groups. These findings suggest that the gamma-band ASSR and its harmonic responses may represent distinct aspects of pathophysiology in the early stages of schizophrenia.