Objective We aimed to explore the feasibility of using scalp‐recorded high‐frequency oscillations (HFOs) to evaluate the efficacy and prognosis of adrenocorticotropic hormone (ACTH) treatment in patients with infantile spasms. Methods Thirty‐nine children with infantile spasms were enrolled and divided into seizure‐free and non–seizure‐free groups after ACTH treatment. Patients who were seizure‐free were further divided into relapse and non‐relapse subgroups based on the observations made during a 6‐month follow‐up period. Scalp ripples were detected and compared during the interictal periods before and after 2 weeks of treatment. Results After ACTH treatment, the number and channels of ripples were significantly lower, whereas the percentage decrease in the number, spectral power, and channels of ripples was significantly higher in the seizure‐free group than in the non–seizure‐free group. In addition, the relapse subgroup showed higher number and spectral power and wider distribution of ripples than did the non‐relapse subgroup. Changes in HFOs in terms of number, spectral power, and channel of ripples were closely related to the severity of epilepsy and can indicate disease susceptibility. Significance Scalp HFOs can be used as an effective biomarker to monitor the effect and evaluate the prognosis of ACTH therapy in patients with infantile spasms.

: Epilepsy is a network disease caused by aberrant neocortical large-scale connectivity spanning regions on the scale of several centimeters. High-frequency oscillations, characterized by the 80–600 Hz signals in electroencephalography, have been proven to be a promising biomarker of epilepsy that can be used in assessing the severity and susceptibility of epilepsy as well as the location of the epileptogenic zone. However, the presence of a high-frequency oscillation network remains a topic of debate as high-frequency oscillations have been previously thought to be incapable of propagation, and the relationship between high-frequency oscillations and the epileptogenic network has rarely been discussed. Some recent studies reported that high-frequency oscillations may behave like networks that are closely relevant to the epileptogenic network. Pathological high-frequency oscillations are network-driven phenomena and elucidate epileptogenic network development; high-frequency oscillations show different characteristics coincident with the epileptogenic network dynamics, and cross-frequency coupling between high-frequency oscillations and other signals may mediate the generation and propagation of abnormal discharges across the network.

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ObjectiveAltered expression patterns of Na+-K+-2Cl– (NKCC1) and K+-Cl– (KCC2) co-transporters have been implicated in the pathogenesis of epilepsy. Here, we assessed the effects of imbalanced NKCC1 and KCC2 on γ-aminobutyric acidergic (GABAergic) neurotransmission in certain brain regions involved in human focal cortical dysplasia (FCD).Materials and methodsWe sought to map a micro-macro neuronal network to better understand the epileptogenesis mechanism. In patients with FCD, we resected cortical tissue from the seizure the onset zone (SOZ) and the non-seizure onset zone (non-SOZ) inside the epileptogenic zone (EZ). Additionally, we resected non-epileptic neocortical tissue from the patients with mesial temporal lobe epilepsy (MTLE) as control. All of tissues were analyzed using perforated patch recordings. NKCC1 and KCC2 co-transporters expression and distribution were analyzed by immunohistochemistry and western blotting.ResultsResults revealed that depolarized GABAergic signals were observed in pyramidal neurons in the SOZ and non-SOZ groups compared with the control group. The total number of pyramidal neurons showing GABAergic spontaneous postsynaptic currents was 11/14, 7/17, and 0/12 in the SOZ, non-SOZ, and control groups, respectively. The depolarizing GABAergic response was significantly dampened by the specific NKCC1 inhibitor bumetanide (BUM). Patients with FCD exhibited higher expression and internalized distribution of KCC2, particularly in the SOZ group.ConclusionOur results provide evidence of a potential neurocircuit underpinning SOZ epileptogenesis and non-SOZ seizure susceptibility. Imbalanced function of NKCC1 and KCC2 may affect chloride ion homeostasis in neurons and alter GABAergic inhibitory action, thereby contributing to epileptogenesis in FCDs. Maintaining chloride ion homeostasis in the neurons may represent a new avenue for the development of novel anti-seizure medications (ASMs).

We aim to explore the microscopic neurophysiology of focal cortical dysplasia (FCD) induced epileptogenesis in specific macroscopic brain regions, therefore mapping a micro–macro neuronal network that potentially indicates the epileptogenic mechanism. Epileptic and relatively non-epileptic temporal neocortex specimens were resected from FCD and mesial temporal lobe epilepsy (mTLE) patients, respectively. Whole-cell patch-clamping was performed on cells from the seizure onset zone (SOZ) and non-SOZ inside the epileptogenic zone (EZ) of FCD patients, as well as the non-epileptic neocortex of mTLE patients. Microscopic data were recorded, including membrane characteristics, spontaneous synaptic activities, and evoked action potentials. Immunohistochemistry was also performed on parvalbumin-positive (PV+) interneurons. We found that SOZ interneurons exhibited abnormal neuronal expression and distribution as well as reduced overall function compared with non-SOZ and mTLE interneurons. The SOZ pyramidal cells experienced higher excitation but lower inhibition than the mTLE controls, whereas the non-SOZ pyramidal cells exhibited intermediate excitability. Action potential properties of both types of neurons also suggested more synchronized neuronal activity inside the EZ, particularly inside the SOZ. Together, our research provides evidence for a potential neurocircuit underlying SOZ epileptogenesis and non-SOZ seizure susceptibility. Further investigation of this microscopic network may promote understanding of the mechanism of FCD-induced epileptogenesis.