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.

Co-activation patterns during viewing of different video game genres.

Past research has revealed cognitive improvements resulting from engagement with both traditional action video games and newer action-like video games, such as action real-time strategy games (ARSG). However, the cortical dynamics elicited by different video gaming genres remain unclear. This study explored the temporal dynamics of cortical networks in response to different gaming genres. Functional magnetic resonance imaging (fMRI) data were obtained during eye-closed resting and passive viewing of gameplay videos of three genres: life simulation games (LSG), first-person shooter games (FPS), and ARSG. Data analysis used a seed-free Co-Activation Pattern (CAP) based on Regions of Interest (ROIs). When comparing the viewing of action-like video games (FPS and ARSG) to LSG viewing, significant dynamic distinctions were observed in both primary and higher-order networks. Within action-like video games, compared to FPS viewing, ARSG viewing elicited a more pronounced increase in the Fraction of Time and Counts of attentional control-related CAPs, along with an increased Transition Probability from sensorimotor-related CAPs to attentional control-related CAPs. Compared to ARSG viewing, FPS viewing elicited a significant increase in the Fraction of Time of sensorimotor-related CAPs, when gaming experience was considered as a covariate. Thus, different video gaming genres, including distinct action-like video gaming genres, elicited unique dynamic patterns in whole-brain CAPs, potentially influencing the development of various cognitive processes.

A neurofunctional signature of subjective disgust generalizes to oral distaste and socio-moral contexts.

While disgust originates in the hard-wired mammalian distaste response, the conscious experience of disgust in humans strongly depends on subjective appraisal and may even extend to socio-moral contexts. Here, in a series of studies, we combined functional magnetic resonance imaging with machine-learning-based predictive modelling to establish a comprehensive neurobiological model of subjective disgust. The developed neurofunctional signature accurately predicted momentary self-reported subjective disgust across discovery (n = 78) and pre-registered validation (n = 30) cohorts and generalized across core disgust (n = 34 and n = 26), gustatory distaste (n = 30) and socio-moral (unfair offers; n = 43) contexts. Disgust experience was encoded in distributed cortical and subcortical systems, and exhibited distinct and shared neural representations with subjective fear or negative affect in interoceptive-emotional awareness and conscious appraisal systems, while the signatures most accurately predicted the respective target experience. We provide an accurate functional magnetic resonance imaging signature for disgust with a high potential to resolve ongoing evolutionary debates.

Behavioral state-dependent associations between EEG temporal correlations and depressive symptoms.

Previous studies have shown abnormal long-range temporal correlations in neuronal oscillations among individuals with Major Depressive Disorders, occurring during both resting states and transitions between resting and task states. However, the understanding of this effect in preclinical individuals with depression remains limited. This study investigated the association between temporal correlations of neuronal oscillations and depressive symptoms during resting and task states in preclinical individuals, specifically focusing on male action video gaming experts. Detrended fluctuation analysis (DFA), Lifetimes, and Waitingtimes were employed to explore temporal correlations across long-range and short-range scales. The results indicated widespread changes from the resting state to the task state across all frequency bands and temporal scales. Rest-task DFA changes in the alpha band exhibited a negative correlation with depressive scores at most electrodes. Significant positive correlations between DFA values and depressive scores were observed in the alpha band during the resting state but not in the task state. Similar patterns of results emerged concerning maladaptive negative emotion regulation strategies. Additionally, short-range temporal correlations in the alpha band echoed the DFA results. These findings underscore the state-dependent relationships between temporal correlations of neuronal oscillations and depressive symptoms, as well as maladaptive emotion regulation strategies, in preclinical individuals.

A new model for dynamic mapping of effective connectivity in task fMRI.

Whole-brain dynamic functional connectivity is a growing area in neuroimaging research, encompassing data-driven methods for investigating how large-scale brain networks dynamically reorganize during resting states. However, this approach has been rarely applied to functional magnetic resonance imaging (fMRI) data acquired during task performance. In this study, we first combined the psychophysiological interactions (PPI) and sliding-window methods to analyze dynamic effective connectivity of fMRI data obtained from subjects performing the N-back task within the Human Connectome Project dataset. We then proposed a hypothetical model called Condition Activated Specific Trajectory (CAST) to represent a series of spatiotemporal synchronous changes in significantly activated connections across time windows, which we refer to as a trajectory. Our finding demonstrate that the CAST model outperforms other models in terms of intra-group consistency of individual spatial pattern of PPI connectivity, overall representational ability of temporal variability and hierarchy for individual task performance and cognitive traits. This dynamic view afforded by the CAST model reflects the intrinsic nature of coherent brain activities.

Multimodal Technologies for Closed-Loop Neural Modulation and Sensing.

Existing methods for studying neural circuits and treating neurological disorders are typically based on physical and chemical cues to manipulate and record neural activities. These approaches often involve predefined, rigid, and unchangeable signal patterns, which cannot be adjusted in real time according to the patient's condition or neural activities. With the continuous development of neural interfaces, conducting in vivo research on adaptive and modifiable treatments for neurological diseases and neural circuits is now possible. In this review, current and potential integration of various modalities to achieve precise, closed-loop modulation, and sensing in neural systems are summarized. Advanced materials, devices, or systems that generate or detect electrical, magnetic, optical, acoustic, or chemical signals are highlighted and utilized to interact with neural cells, tissues, and networks for closed-loop interrogation. Further, the significance of developing closed-loop techniques for diagnostics and treatment of neurological disorders such as epilepsy, depression, rehabilitation of spinal cord injury patients, and exploration of brain neural circuit functionality is elaborated.

Brain activation and connection across resting and motor-task states in patients with generalized tonic-clonic seizures.

AIMS: Motor abnormalities have been identified as one common symptom in patients with generalized tonic-clonic seizures (GTCS) inspiring us to explore the disease in a motor execution condition, which might provide novel insight into the pathomechanism. METHODS: Resting-state and motor-task fMRI data were collected from 50 patients with GTCS, including 18 patients newly diagnosed without antiepileptic drugs (ND_GTCS) and 32 patients receiving antiepileptic drugs (AEDs_GTCS). Motor activation and its association with head motion and cerebral gradients were assessed. Whole-brain network connectivity across resting and motor states was further calculated and compared between groups. RESULTS: All patients showed over-activation in the postcentral gyrus and the ND_GTCS showed decreased activation in putamen. Specifically, activation maps of ND_GTCS showed an abnormal correlation with head motion and cerebral gradient. Moreover, we detected altered functional network connectivity in patients within states and across resting and motor states by using repeated-measures analysis of variance. Patients did not show abnormal connectivity in the resting state, while distributed abnormal connectivity in the motor-task state. Decreased across-state network connectivity was also found in all patients. CONCLUSION: Convergent findings suggested the over-response of activation and connection of the brain to motor execution in GTCS, providing new clues to uncover motor susceptibility underlying the disease.

Simultaneous EEG-fMRI Investigation of Rhythm-Dependent Thalamo-Cortical Circuits Alteration in Schizophrenia.

Schizophrenia is accompanied by aberrant interactions of intrinsic brain networks. However, the modulatory effect of electroencephalography (EEG) rhythms on the functional connectivity (FC) in schizophrenia remains unclear. This study aims to provide new insight into network communication in schizophrenia by integrating FC and EEG rhythm information. After collecting simultaneous resting-state EEG-functional magnetic resonance imaging data, the effect of rhythm modulations on FC was explored using what we term "dynamic rhythm information." We also investigated the synergistic relationships among three networks under rhythm modulation conditions, where this relationship presents the coupling between two brain networks with other networks as the center by the rhythm modulation. This study found FC between the thalamus and cortical network regions was rhythm-specific. Further, the effects of the thalamus on the default mode network (DMN) and salience network (SN) were less similar under alpha rhythm modulation in schizophrenia patients than in controls ([Formula: see text]). However, the similarity between the effects of the central executive network (CEN) on the DMN and SN under gamma modulation was greater ([Formula: see text]), and the degree of coupling was negatively correlated with the duration of disease ([Formula: see text], [Formula: see text]). Moreover, schizophrenia patients exhibited less coupling with the thalamus as the center and greater coupling with the CEN as the center. These results indicate that modulations in dynamic rhythms might contribute to the disordered functional interactions seen in schizophrenia.

Identification of four biotypes in temporal lobe epilepsy via machine learning on brain images.

Artificial intelligence provides an opportunity to try to redefine disease subtypes based on similar pathobiology. Using a machine-learning algorithm (Subtype and Stage Inference) with cross-sectional MRI from 296 individuals with focal epilepsy originating from the temporal lobe (TLE) and 91 healthy controls, we show phenotypic heterogeneity in the pathophysiological progression of TLE. This study was registered in the Chinese Clinical Trials Registry (number: ChiCTR2200062562). We identify two hippocampus-predominant phenotypes, characterized by atrophy beginning in the left or right hippocampus; a third cortex-predominant phenotype, characterized by hippocampus atrophy after the neocortex; and a fourth phenotype without atrophy but amygdala enlargement. These four subtypes are replicated in the independent validation cohort (109 individuals). These subtypes show differences in neuroanatomical signature, disease progression and epilepsy characteristics. Five-year follow-up observations of these individuals reveal differential seizure outcomes among subtypes, indicating that specific subtypes may benefit from temporal surgery or pharmacological treatment. These findings suggest a diverse pathobiological basis underlying focal epilepsy that potentially yields to stratification and prognostication - a necessary step for precise medicine.

Discrepant changes in structure-function coupling in dancers and musicians.

Dance and music are well known to improve sensorimotor skills and cognitive functions. To reveal the underlying mechanism, previous studies focus on the brain plastic structural and functional effects of dance and music training. However, the discrepancy training effects on brain structure-function relationship are still blurred. Thus, proficient dancers, musicians, and controls were recruited in this study. The graph signal processing framework was employed to quantify the region-level and network-level relationship between brain function and structure. The results showed the increased coupling strength of the right ventromedial putamen in the dance and music groups. Distinctly, enhanced coupling strength of the ventral attention network, increased coupling strength of the right inferior frontal gyrus opercular area, and increased function connectivity of coupling function signal between the right and left middle frontal gyrus were only found in the dance group. Besides, the dance group indicated enhanced coupling function connectivity between the left inferior parietal lobule caudal area and the left superior parietal lobule intraparietal area compared with the music groups. The results might illustrate dance and music training's discrepant effect on the structure-function relationship of the subcortical and cortical attention networks. Furthermore, dance training seemed to have a greater impact on these networks.

A neural signature for the subjective experience of threat anticipation under uncertainty.

Uncertainty about potential future threats and the associated anxious anticipation represents a key feature of anxiety. However, the neural systems that underlie the subjective experience of threat anticipation under uncertainty remain unclear. Combining an uncertainty-variation threat anticipation paradigm that allows precise modulation of the level of momentary anxious arousal during functional magnetic resonance imaging (fMRI) with multivariate predictive modeling, we train a brain model that accurately predicts subjective anxious arousal intensity during anticipation and test it across 9 samples (total n = 572, both gender). Using publicly available datasets, we demonstrate that the whole-brain signature specifically predicts anxious anticipation and is not sensitive in predicting pain, general anticipation or unspecific emotional and autonomic arousal. The signature is also functionally and spatially distinguishable from representations of subjective fear or negative affect. We develop a sensitive, generalizable, and specific neuroimaging marker for the subjective experience of uncertain threat anticipation that can facilitate model development.

Exploring resting-state EEG oscillations in patients with Neuromyelitis Optica Spectrum Disorder.

BACKGROUND AND OBJECTIVE: Quantitative resting-state electroencephalography (rs-EEG) is a convenient method for characterizing the functional impairments and adaptations of the brain that has been shown to be valuable for assessing many neurological and psychiatric disorders, especially in monitoring disease status and assisting neuromodulation treatment. However, it has not yet been explored in patients with neuromyelitis optica spectrum disorder (NMOSD). This study aimed to investigate the rs-EEG features of NMOSD patients and explore the rs-EEG features related to disease characteristics and complications (such as anxiety, depression, and fatigue). METHODS: A total of 32 NMOSD patients and 20 healthy controls (HCs) were recruited; their demographic and disease information were collected, and their anxiety, depression, and fatigue symptoms were evaluated. The rs-EEG power spectra of all the participants were obtained. After excluding the participants with low-quality rs-EEG data during processing, statistical analysis was conducted based on the clinical information and rs-EEG data of 29 patients and 19 HCs. The rs-EEG power (the mean spectral energy (MSE) of absolute power and relative power in all frequency bands, as well as the specific power for all electrode sites) of NMOSD patients and HCs was compared. Furthermore, correlation analyses were performed between rs-EEG power and other variables for NMOSD patients (including the disease characteristics and complications). RESULTS: The distribution of the rs-EEG power spectra in NMOSD patients was similar to that in HCs. The dominant alpha-peaks shifted significantly towards a lower frequency for patients when compared to HCs. The delta and theta power was significantly increased in the NMOSD group compared to that in the HC group. The alpha oscillation power was found to be significantly negatively associated with the degree of anxiety (reflected by the anxiety subscore of hospital anxiety and depression scale (HADS)) and the degree of depression (reflected by the depression subscore of HADS). The gamma oscillation power was revealed to be significantly positively correlated with the fatigue severity scale (FSS) score, while further analysis indicated that the electrode sites of almost the whole brain region showing correlations with fatigue. Regarding the disease variables, no statistically significant rs-EEG features were related to the main disease features in NMOSD patients. CONCLUSION: The results of this study suggest that the rs-EEG power spectra of NMOSD patients show increased slow oscillations and are potential biomarkers of widespread white matter microstructural damage in NMOSD. Moreover, this study revealed the rs-EEG features associated with anxiety, depression, and fatigue in NMOSD patients, which might help in the evaluation of these complications and the development of neuromodulation treatment. Quantitative rs-EEG analysis may play an important role in the management of NMOSD patients, and future studies are warranted to more comprehensively understand its application value.

A brief real-time fNIRS-informed neurofeedback training of the prefrontal cortex changes brain activity and connectivity during subsequent working memory challenge.

Working memory (WM) represents a building-block of higher cognitive functions and a wide range of mental disorders are associated with WM impairments. Initial studies have shown that several sessions of functional near-infrared spectroscopy (fNIRS) informed real-time neurofeedback (NF) allow healthy individuals to volitionally increase activity in the dorsolateral prefrontal cortex (DLPFC), a region critically involved in WM. For the translation to therapeutic or neuroenhancement applications, however, it is critical to assess whether fNIRS-NF success transfers into neural and behavioral WM enhancement in the absence of feedback. We therefore combined single-session fNIRS-NF of the left DLPFC with a randomized sham-controlled design (N = 62 participants) and a subsequent WM challenge with concomitant functional MRI. Over four runs of fNIRS-NF, the left DLPFC NF training group demonstrated enhanced neural activity in this region, reflecting successful acquisition of neural self-regulation. During the subsequent WM challenge, we observed no evidence for performance differences between the training and the sham group. Importantly, however, examination of the fMRI data revealed that - compared to the sham group - the training group exhibited significantly increased regional activity in the bilateral DLPFC and decreased left DLPFC - left anterior insula functional connectivity during the WM challenge. Exploratory analyses revealed a negative association between DLPFC activity and WM reaction times in the NF group. Together, these findings indicate that healthy individuals can learn to volitionally increase left DLPFC activity in a single training session and that the training success translates into WM-related neural activation and connectivity changes in the absence of feedback. This renders fNIRS-NF as a promising and scalable WM intervention approach that could be applied to various mental disorders.

Evaluating the depression state during perinatal period by non-invasive scalp EEG.

Perinatal depression, with a prevalence of 10 to 20% in United States, is usually missed as multiple symptoms of perinatal depression are common in pregnant women. Worse, the diagnosis of perinatal depression still largely relies on questionnaires, leaving the objective biomarker being unveiled yet. This study suggested a safe and non-invasive technique to diagnose perinatal depression and further explore its underlying mechanism. Considering the non-invasiveness and clinical convenience of electroencephalogram for mothers-to-be and fetuses, we collected the resting-state electroencephalogram of pregnant women at the 38th week of gestation. Subsequently, the difference in network topology between perinatal depression patients and healthy mothers-to-be was explored, with related spatial patterns being adopted to achieve the classification of pregnant women with perinatal depression from those healthy ones. We found that the perinatal depression patients had decreased brain network connectivity, which indexed impaired efficiency of information processing. By adopting the spatial patterns, the perinatal depression could be accurately recognized with an accuracy of 87.88%; meanwhile, the depression severity at the individual level was effectively predicted, as well. These findings consistently illustrated that the resting-state electroencephalogram network could be a reliable tool for investigating the depression state across pregnant women, and will further facilitate the clinical diagnosis of perinatal depression.

Multimodal Covariance Network Reflects Individual Cognitive Flexibility.

Cognitive flexibility refers to the capacity to shift between patterns of mental function and relies on functional activity supported by anatomical structures. However, how the brain's structural-functional covarying is preconfigured in the resting state to facilitate cognitive flexibility under tasks remains unrevealed. Herein, we investigated the potential relationship between individual cognitive flexibility performance during the trail-making test (TMT) and structural-functional covariation of the large-scale multimodal covariance network (MCN) using magnetic resonance imaging (MRI) and electroencephalograph (EEG) datasets of 182 healthy participants. Results show that cognitive flexibility correlated significantly with the intra-subnetwork covariation of the visual network (VN) and somatomotor network (SMN) of MCN. Meanwhile, inter-subnetwork interactions across SMN and VN/default mode network/frontoparietal network (FPN), as well as across VN and ventral attention network (VAN)/dorsal attention network (DAN) were also found to be closely related to individual cognitive flexibility. After using resting-state MCN connectivity as representative features to train a multi-layer perceptron prediction model, we achieved a reliable prediction of individual cognitive flexibility performance. Collectively, this work offers new perspectives on the structural-functional coordination of cognitive flexibility and also provides neurobiological markers to predict individual cognitive flexibility.

Striatum- and Cerebellum-Modulated Epileptic Networks Varying Across States with and without Interictal Epileptic Discharges.

Idiopathic generalized epilepsy (IGE) is characterized by cryptogenic etiology and the striatum and cerebellum are recognized as modulators of epileptic network. We collected simultaneous electroencephalogram and functional magnetic resonance imaging data from 145 patients with IGE, 34 of whom recorded interictal epileptic discharges (IEDs) during scanning. In states without IEDs, hierarchical connectivity was performed to search core cortical regions which might be potentially modulated by striatum and cerebellum. Node-node and edge-edge moderation models were constructed to depict direct and indirect moderation effects in states with and without IEDs. Patients showed increased hierarchical connectivity with sensorimotor cortices (SMC) and decreased connectivity with regions in the default mode network (DMN). In the state without IEDs, striatum, cerebellum, and thalamus were linked to weaken the interactions of regions in the salience network (SN) with DMN and SMC. In periods with IEDs, overall increased moderation effects on the interaction between regions in SN and DMN, and between regions in DMN and SMC were observed. The thalamus and striatum were implicated in weakening interactions between regions in SN and SMC. The striatum and cerebellum moderated the cortical interaction among DMN, SN, and SMC in alliance with the thalamus, contributing to the dysfunction in states with and without IEDs in IGE. The current work revealed state-specific modulation effects of striatum and cerebellum on thalamocortical circuits and uncovered the potential core cortical targets which might contribute to develop new clinical neuromodulation techniques.

The central renin-angiotensin system: A genetic pathway, functional decoding, and selective target engagement characterization in humans.

Accumulating evidence suggests that the brain renin angiotensin system (RAS) plays a pivotal role in the regulation of cognition and behavior as well as in the neuropathology of neurological and mental disorders. The angiotensin II type 1 receptor (AT1R) mediates most functional and neuropathology-relevant actions associated with the central RAS. However, an overarching comprehension to guide translation and utilize the therapeutic potential of the central RAS in humans is currently lacking. We conducted a comprehensive characterization of the RAS using an innovative combination of transcriptomic gene expression mapping, image-based behavioral decoding, and pre-registered randomized controlled discovery-replication pharmacological resting-state functional magnetic resonance imaging (fMRI) trials (N = 132) with a selective AT1R antagonist. The AT1R exhibited a particular dense expression in a subcortical network encompassing the thalamus, striatum, and amygdalo-hippocampal formation. Behavioral decoding of the AT1R gene expression brain map showed an association with memory, stress, reward, and motivational processes. Transient pharmacological blockade of the AT1R further decreased neural activity in subcortical systems characterized by a high AT1R expression, while increasing functional connectivity in the cortico-basal ganglia-thalamo-cortical circuitry. Effects of AT1R blockade on the network level were specifically associated with the transcriptomic signatures of the dopaminergic, opioid, acetylcholine, and corticotropin-releasing hormone signaling systems. The robustness of the results was supported in an independent pharmacological fMRI trial. These findings present a biologically informed comprehensive characterization of the central AT1R pathways and their functional relevance on the neural and behavioral level in humans.

Analysis of the Relation Between Balance Control Subsystems: A Structural Equation Modeling Approach.

Balance plays a crucial role in human life and social activities. Maintaining balance is a relatively complex process that requires the participation of various balance control subsystems (BCSes). However, previous studies have primarily focused on evaluating an individual's overall balance ability or the ability of each BCS in isolation, without considering how they influence (or interact with) each other. The first study used clinical scales to evaluate the functions of the four BCSes, namely Reactive Postural Control (RPC), Anticipatory Postural Adjustment (APA), Dynamic Gait (DG), and Sensory Orientation (SO), and psychological factors such as fear of falling (FOF). A hierarchical structural equation modeling (SEM) was used to investigate the relationship between the BCSes and their association with FOF. The second study involved using posturography to measure and extract parameters from the center of pressure (COP) signal. SEM with sparsity constraint was used to analyze the relationship between vision, proprioception, and vestibular sense on balance based on the extracted COP parameters. The first study revealed that the RPC, APA, DG and SO indirectly influenced each other through their overall balance ability, and their association with FOF was not the same. APA has the strongest association with FOF, while RPC has the least association with FOF. The second study revealed that sensory inputs, such as vision, proprioception, and vestibular sensing, directly affected each other, but their associations were not identical. Among them, proprioception plays the most important role in the three sensory subsystems. This study provides the first numerical evidence that the BCSes are not independent of each other and exist in direct or indirect interplay. This approach has important implications for the diagnosis and management of balance-related disorders in clinical settings and improving our understanding of the underlying mechanisms of balance control.

A Unified and Biologically Plausible Relational Graph Representation of Vision Transformers.

Vision transformer (ViT) and its variants have achieved remarkable success in various tasks. The key characteristic of these ViT models is to adopt different aggregation strategies of spatial patch information within the artificial neural networks (ANNs). However, there is still a key lack of unified representation of different ViT architectures for systematic understanding and assessment of model representation performance. Moreover, how those well-performing ViT ANNs are similar to real biological neural networks (BNNs) is largely unexplored. To answer these fundamental questions, we, for the first time, propose a unified and biologically plausible relational graph representation of ViT models. Specifically, the proposed relational graph representation consists of two key subgraphs: an aggregation graph and an affine graph. The former considers ViT tokens as nodes and describes their spatial interaction, while the latter regards network channels as nodes and reflects the information communication between channels. Using this unified relational graph representation, we found that: 1) model performance was closely related to graph measures; 2) the proposed relational graph representation of ViT has high similarity with real BNNs; and 3) there was a further improvement in model performance when training with a superior model to constrain the aggregation graph.

Disruption of TLE epileptiform activity retarded the seizure and reduced pathological HFOs.

In temporal lobe epilepsy (TLE), the epileptogenic zones, such as the temporal lobe structure, could generate pathological high-frequency oscillations (pHFOs, 250-500 Hz) before the ictal period. These pHFOs have also been observed during the process of seizures in both TLE patients and animals, exhibiting a critical role as promising biomarkers for TLE seizures. TLE seizures could be modulated via regulating the neural excitability in epileptogenic zones, for that TLE is primarily associated with the excitation-inhibition imbalance. However, whether these kinds of modulations could also impact the pHFOs characteristics during TLE seizures is still unclear. For this purpose, we pharmaco-genetically inhibited the principal cells (PCs) in the mouse CA3 region and tracked the difference in the behavioral and electrophysiological features during LiCl-pilocarpine-induced TLE seizure between the hM4Di+CNO (experimental) mice and mCherry+CNO (control) mice. Delayed latency, decreased averaged duration, and reduced counts of the generalized seizure were observed in the experimental mice. Besides, the electrophysiological characteristics, such as the firing rate of PCs and the count of pHFO, exhibited significant decline in the CA3 and CA1 regions. During TLE seizure, there existed strong phase-coupling between pHFO and PCs spike timing in the control mice, while it was abolished in the experimental mice. In addition, we also found that the counts of pHFO were significantly associated with the behavioral features, indicating the close relationships within them. Collectively, our findings suggested that alterations in pHFO and the retardation of seizures may be attributed to disruptions in neuronal excitability, and the variations of electrophysiological features were related to seizure severity during TLE seizures. These results provide valuable insights into the role of pHFOs in TLE and shed light on the underlying mechanisms involved.