The zebrafish model has attracted much attention due to its strong reproductive ability, short research cycle, and ease of maintenance. It has always been an important vertebrate model system, often used to carry out human disease research. Its motor behavior features have the advantages of being simpler, more intuitive, and quantifiable. In recent years, it has received widespread attention in the study of traditional Chinese medicine(TCM)for the treatment of sleep disorders, neurodegenerative diseases, fatigue, epilepsy, and other diseases. This paper reviews the characteristics of zebrafish motor behavior and its applications in the pharmacodynamic verification and mechanism research of TCM extracts, active ingredients, and TCM compounds, as well as in active ingredient screening and safety evaluation. The paper also analyzes its advantages and disadvantages, with the aim of improving the breadth and depth of zebrafish and its motor behavior applications in the field of TCM research.
Zebrafish/physiology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/therapeutic use* ; Disease Models, Animal ; Drug Evaluation, Preclinical/methods* ; Animals ; Sleep Wake Disorders/physiopathology* ; Epilepsy/physiopathology* ; Neurodegenerative Diseases/physiopathology* ; Fatigue/physiopathology* ; Behavior, Animal/physiology* ; Motor Activity/physiology*

The existing epilepsy seizure detection algorithms have problems such as overfitting and poor generalization ability due to high reliance on manual labeling of electroencephalogram's data and data imbalance between seizure and interictal periods. An unsupervised learning detection method for epileptic seizure that jointed graph attention network (GAT) and Transformer framework (GAT-T) was proposed. In this method, channel correlations were adaptively learned by GAT encoder. Temporal information was captured by one-dimensional convolution decoder. Combining outputs of the two mentioned above, predicted values for electroencephalogram were generated. The collective anomaly score was calculated and the detection threshold was determined. The results demonstrated that GAT-T achieved the average performance exceeding 90% (or 99%) with a 0.25 s (or 2 s) time segment length, which could effectively detect epileptic seizures. Moreover, the channel association probability matrix was expected to assist clinicians in the initial screening of the epileptogenic zone, and ablation experiments also reflected the significance of each module in GAT-T. This study may assist clinicians in making more accurate diagnostic and therapeutic decisions for epilepsy patients.
Humans ; Electroencephalography/methods* ; Epilepsy/physiopathology* ; Algorithms ; Seizures/physiopathology* ; Neural Networks, Computer ; Signal Processing, Computer-Assisted

Current epilepsy prediction methods are not effective in characterizing the multi-domain features of complex long-term electroencephalogram (EEG) data, leading to suboptimal prediction performance. Therefore, this paper proposes a novel multi-scale sparse adaptive convolutional network based on multi-head attention mechanism (MS-SACN-MM) model to effectively characterize the multi-domain features. The model first preprocesses the EEG data, constructs multiple convolutional layers to effectively avoid information overload, and uses a multi-layer perceptron and multi-head attention mechanism to focus the network on critical pre-seizure features. Then, it adopts a focal loss training strategy to alleviate class imbalance and enhance the model's robustness. Experimental results show that on the publicly created dataset (CHB-MIT) by MIT and Boston Children's Hospital, the MS-SACN-MM model achieves a maximum accuracy of 0.999 for seizure prediction 10 ~ 15 minutes in advance. This demonstrates good predictive performance and holds significant importance for early intervention and intelligent clinical management of epilepsy patients.
Humans ; Electroencephalography/methods* ; Epilepsy/physiopathology* ; Neural Networks, Computer ; Seizures/physiopathology* ; Signal Processing, Computer-Assisted ; Algorithms

Epileptic seizures and the interictal epileptiform discharges both have similar waveforms. And a method to effectively extract features that can be used to distinguish seizures is of crucial importance both in theory and clinical practice. We constructed state transfer networks by using visibility graphlet at multiple sampling intervals and analyzed network features. We found that the characteristics waveforms in ictal periods were more robust with various sampling intervals, and those feature network structures did not change easily in the range of the smaller sampling intervals. Inversely, the feature network structures of interictal epileptiform discharges were stable in range of relatively larger sampling intervals. Furthermore, the feature nodes in networks during ictal periods showed long-term correlation along the process, and played an important role in regulating system behavior. For stereo-electroencephalography at around 500 Hz, the greatest difference between ictal and the interictal epileptiform occurred at the sampling interval around 0.032 s. In conclusion, this study effectively reveals the correlation between the features of pathological changes in brain system and the multiple sampling intervals, which holds potential application value in clinical diagnosis for identifying, classifying, and predicting epilepsy.
Humans ; Electroencephalography/methods* ; Epilepsy/diagnosis* ; Signal Processing, Computer-Assisted ; Brain/physiopathology* ; Seizures/diagnosis* ; Algorithms

OBJECTIVE: To investigate the effects of acid-sensing ion channels (ASICs) on electrophysiological epileptic activities of mouse hippocampal pyramidal neurons in the extracellular acidotic condition. METHODS: We investigated effects of extracellular acidosis on epileptic activities induced by elevated extracellular K concentration or the application of an antagonist of GABA receptors in perfusate of mouse hippocampal slices under field potential recordings. We also tested the effects of extracellular acidosis on neuronal excitability under field potential recording and evaluated the changes in epileptic activities of the neurons in response to pharmacological inhibition of ASICs using a specific inhibitor of ASICs. RESULTS: Extracellular acidosis significantly suppressed epileptic activities of the hippocampal neurons by converting ictal-like epileptic activities to non-ictal-like epileptic activities in both high [K ]o and disinhibition models, and also suppressed the intrinsic excitability of the neurons. ASICs inhibitor did not antagonize the inhibitory effect of extracellular acidosis on ictal epileptic activities and intrinsic neuronal excitability, but exacerbated non-ictal epileptic activities of the neurons in extracellular acidotic condition in both high [K]o and disinhibition models. CONCLUSIONS ASICs can differentially modulate ictal-like and non-ictallike epileptic activities via its direct actions on excitatory neurons.
Acid Sensing Ion Channels ; metabolism ; Acidosis ; Animals ; Epilepsy ; physiopathology ; Hydrogen-Ion Concentration ; Mice ; Pyramidal Cells ; pathology ; physiology

OBJECTIVE: To observe the expressions of sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate receptor 2 (S1PR2) in hippocampus of epileptic rats and to investigate the pathogenesis of SphK1 and S1PR2 in epilepsy. METHODS: One hundred and eight male Sprague-Dawley (SD) rats were randomly divided into control group (n=48) and pilocarpine (PILO) group (n=60). A robust convulsive status epilepticus (SE) was induced in PILO group rats by the application of pilocarpine. Control group rats were injected with respective of physiological saline. Pilocarpine group was randomly divided into 6 subgroups (n=8): acute group (E6 h, E1 d, E3 d), latent group (E7 d) and chronic group (E30 d, E56 d). Each subgroup has 8 control rats and 8 epileptic rats. Hippocampal tissue and brain slices were obtained from control rats and rats subjected to the Li-PILO model of epilepsy at 6 h, 1 d, 3 d,7 d,30 d and 56 d after status epilepticus (SE). Western blot technique was used to determine the expressions of SphK1 and S1PR2 in hippocampus at different point of time after pilocarpine treatment. Immunofluorescence was applied to detect the activation and proliferation of hippocampal astrocytes and the localization of SphK1 and S1PR2 in rat hippocampal astrocytes. RESULTS: Compared with control group, the levels of SphK1 in acute phase (E3 d), latent phase (E7 d) and chronic phase (E30 d, E56 d) were significantly increased while the expressions of S1PR2 were decreased in acute phase (E3 d), latent phase (E7 d) and chronic phase (E30 d, E56 d)(P＜0.05 or P＜0.01). Immunofluorescence results showed astrocyte activation and proliferation in hippocampus of epileptic (E7 d) rats (P＜0.05). Confocal microscopy confirmed the preferential expressions of SphK1 and S1PR2 in epileptic rat(E7 d)hippocampal astrocytes. CONCLUSION The results indicate that SphK1 and S1PR2 may play an important role in the pathogenesis of epilepsy by regulating the activation and proliferation of hippocampal astrocytes and altering neuronal excitability.
Animals ; Astrocytes ; enzymology ; Epilepsy ; enzymology ; physiopathology ; Hippocampus ; cytology ; enzymology ; Male ; Phosphotransferases (Alcohol Group Acceptor) ; metabolism ; Pilocarpine ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, Lysosphingolipid ; metabolism

Exploring the transition from inter-ictal to ictal epileptiform discharges (IDs) and how GABA receptor-mediated action affects the onset of IDs will enrich our understanding of epileptogenesis and epilepsy treatment. We used Mg-free artificial cerebrospinal fluid (ACSF) to induce epileptiform discharges in juvenile mouse hippocampal slices and used a micro-electrode array to record the discharges. After the slices were exposed to Mg-free ACSF for 10 min-20 min, synchronous recurrent seizure-like events were recorded across the slices, and each event evolved from inter-ictal epileptiform discharges (IIDs) to pre-ictal epileptiform discharges (PIDs), and then to IDs. During the transition from IIDs to PIDs, the duration of discharges increased and the inter-discharge interval decreased. After adding 3 μmol/L of the GABA receptor agonist muscimol, PIDs and IDs disappeared, and IIDs remained. Further, the application of 10 μmol/L muscimol abolished all the epileptiform discharges. When the GABA receptor antagonist bicuculline was applied at 10 μmol/L, IIDs and PIDs disappeared, and IDs remained at decreased intervals. These results indicated that there are dynamic changes in the hippocampal network preceding the onset of IDs, and GABA receptor activity suppresses the transition from IIDs to IDs in juvenile mouse hippocampus.
Animals ; Animals, Newborn ; Bicuculline ; pharmacology ; Disease Models, Animal ; Epilepsy ; pathology ; GABA-A Receptor Agonists ; pharmacology ; GABA-A Receptor Antagonists ; therapeutic use ; Hippocampus ; drug effects ; metabolism ; physiopathology ; In Vitro Techniques ; Magnesium ; metabolism ; pharmacology ; Male ; Membrane Potentials ; drug effects ; Mice ; Mice, Inbred C57BL ; Muscimol ; pharmacology ; Nerve Net ; drug effects ; Receptors, GABA-A ; metabolism

OBJECTIVE: To investigate the clinical significance of high-frequency oscillations (HFOs) on scalp electroencephalography (EEG) in patients with epileptic encephalopathy with continuous spike-and-wave during sleep (CSWS). METHODS: Twenty-one CSWS patients treated for epilepsy from January 2006 to December 2016 in Pediatric Department of Peking University First Hospital were enrolled into the study. Selected clinical variables including gender, age parameters, seizure frequencies and antiepileptic drugs were compared between (a). HFO-positive group and HFO-negative group before methylprednisolone treatment and (b). excellent seizure outcome group and not-excellent seizure outcome group after methylprednisolone treatment. Interictal HFOs and spikes in pre- and post-methylprednisolone scalp EEG were measured and analyzed. RESULTS: Before methylprednisolone treatment, there were 12 of 21 (57%) CSWS patients had HFOs, with a mean value 43.17 per 60 s per patient. The 12 patients with HFOs tended to have more frequent epileptic negative myoclonus/atonic/myoclonus/atypical absences than those without HFOs in a month before methylprednisolone treatment. A total of 518 HFOs and 22 592 spikes were found in the pre-methylprednisolone EEG data of 21 patients, and 441 HFOs (86%) were associated with spikes. The highest amplitudes of HFOs were significantly positively correlated with that of spikes (r=0.279, P<0.001). Rates reduced by methylprednisolone treatment were statistically significant for both HFOs (P=0.002) and spikes (P=0.006). The percentage of reduction was 91% (473/518) and 39% (8 905/22 592) for spikes and HFOs, respectively. The percentage of spike and HFOs changes was respectively 100% decrease and 47% decrease in the excellent seizure outcome group, and they were 79% decrease and 18% increase in the not-excellent seizure outcome group. CONCLUSION Prevalence of HFOs might reflect some aspect of epileptic activity. HFOs were more sensitive to methylprednisolone treatment than spikes and had a good correlation with the prognosis of seizures, and HFOs could be applied to assess epilepsy severity and antiepileptic therapy.
Anticonvulsants/therapeutic use* ; Child ; Electroencephalography/methods* ; Epilepsy/physiopathology* ; Epilepsy, Absence ; Humans ; Methylprednisolone ; Scalp ; Seizures ; Sleep

To optimize the monitoring time of interictal epileptiform discharges (IED) in patients with epilepsy by long-term video electroencephalogram (VEEG).The cumulative percentages of IED detected by VEEG in 346 epilepsy patients (349 times) with different purposes, different waking sleep states and different MRI findings were retrospectively analyzed. According to the purposes, there were 164 patients (165 times) for clarifying diagnosis, 124 patients (124 times) for preoperative evaluation and 58 patients (60 times) for adjustment of medications. According to MRI results, there were responsible lesions in 98 patients (98 times) and no responsible lesions in 173 patients (174 times).Among 346 patients (349 times), IED was detected within 24 h in 231 patients (times). The percentage of detection in patients with purpose of preoperative evaluation was higher than those with purpose of diagnosis and medication adjustment. The detection of LED was gradually increased in first 8 h with 59.0%, then stably in 24 h. 46.8% IED was recorded during sleep time, particularly in the second stage of sleep. The cumulative percentage of IED in patients with abnormal MRI findings was higher in all periods. It reached 83.7% within 8 h, and then tended to be stable.The study shows that LED should be monitored by VEEG at least 8 hours and should include the second stage of sleep in patients with epilepsy. Patients with refractory epilepsy and with abnormal lesions on MRI should record IED more frequently.
Brain ; diagnostic imaging ; pathology ; Brain Waves ; Electroencephalography ; methods ; statistics & numerical data ; Epilepsy ; pathology ; physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; statistics & numerical data ; Male ; Retrospective Studies ; Sleep ; physiology ; Time Factors

Temporal lobe epilepsy (TLE) is a common and severe neurological disorder which is often intractable. It can not only damage the normal structure and function of hippocampus, but also affect the neurogenesis in dentate gyrus (DG). It is well documented from researches on the animal models of TLE that after a latent period of several days, prolonged seizure activity leads to a dramatic increase in mitotic activity in the hippocampal DG. However, cell proliferation returns to baseline levels within 3-4 weeks after status epilepticus (SE). Meanwhile, there are two major abnormalities of DG neurogenesis, including the formation of hilar basal dendrites and the ectopic migration of newborn granule cells into the polymorphic cell layer, which may affect epileptogenesis and seizure onset. However, the specific contribution of these abnormalities to seizures is still unknown. In other words, whether they are anti-epileptic or pro-epileptic is still under heated discussion. This article systematically reviews current knowledge on neurogenesis and epilepsy based on the results of studies in recent years and discusses the possible roles of neurogenesis in epileptogenesis and pathologic mechanisms, so as to provide information for the potential application of neurogenesis as a new clinical therapeutic target for temporal lobe epilepsy.
Animals ; Brain ; Cell Movement ; physiology ; Cell Proliferation ; physiology ; Dendrites ; pathology ; Dentate Gyrus ; growth & development ; pathology ; Epilepsy, Temporal Lobe ; etiology ; pathology ; physiopathology ; Hippocampus ; growth & development ; pathology ; Humans ; Mitosis ; physiology ; Neurogenesis ; physiology ; Neurons ; pathology ; Seizures ; etiology ; physiopathology ; Status Epilepticus ; physiopathology