Hongyi Ye

The thalamus coordinates sleep-dependent brain function including memory consolidation, sensory gating, and network stability through spindle oscillations. Thalamocortical circuits are also affected in many neurological and neuropsychiatric disorders. Yet how human thalamocortical circuits respond to pathological disruptions remain poorly understood. Here, we leveraged interictal epileptiform discharges (IEDs) as spontaneous perturbations to probe spindle-generating circuits and thalamocortical dynamics in vivo. Using multi-night intracranial recordings spanning multiple thalamic nuclei and cortical regions in 55 individuals with epilepsy, we investigated interactions between sleep spindles and epileptic activity across timescales from milliseconds to days. Sleep spindles were associated with IED suppression, whereas IEDs increased subsequent spindle probability, revealing bidirectional interactions between physiological and pathological activity. Nights with lower IEDs corresponded to increased spindle occurrence, longer duration, and faster frequency, reflecting a more stable thalamocortical state. These findings propose sleep spindles as potential regulators of thalamocortical networks that actively respond to and regulate pathological activity.

Reward expectancy engages the anterior insular cortex (AIC) to coordinate cognitive allocation. Using intracranial electroencephalographic data from epilepsy patients navigating a virtual T-maze, we identified reward-specific brain patterns (RBPs) that were preactivated in the AIC prior to reward onset. This pre-activation was followed by phase-amplitude coupling (PAC) between theta oscillations and gamma activity, with coupling strength positively correlated with the pre-activation level across contacts. Furthermore, this PAC exhibited a phase-precession-like effect (PPLE), characterized by a progressive shift of peak gamma activity to earlier theta phases across successive navigation rounds. Participants exhibiting stronger PPLE in the AIC showed greater trial-by-trial improvements in reward-collection performance. Taken together, these findings reveal a precise phase-tuned timing mechanism in the AIC that supports reward-directed behavior. Specifically, oscillatory coordination initiated by representational pre-activation, is dynamically refined through PPLE across successive exposures to the same reward. This mechanism accelerates responses to impending rewards, thereby optimizing adaptive behavior.

Objective: Tapering of the antiseizure medication dosage in the epilepsy monitoring unit can provoke seizures, but its effects on seizure dynamics remain poorly characterized. This study addresses three questions: (1) Does antiseizure medication tapering influence spatiotemporal dynamics of seizures? (2) Does the tapering rate affect these dynamics? (3) Does tapering have a similar effect on interictal epileptic discharges as it does on seizures? Methods: Patients with drug‐resistant epilepsy undergoing stereoelectroencephalographic (stereo‐EEG) presurgical evaluations at Duke University Medical Center ( n = 104) and the Montreal Neurological Institute and Hospital ( n = 80) were screened. We included patients in whom the antiseizure medication dosage was tapered from the highest daily dosage (high dosage) to ≤ 50% (low dosage) during stereo‐EEG monitoring, and at least one seizure from the same focus was recorded in both conditions. Using an intrapatient design, we compared seizure onset‐zone, onset pattern, and propagation dynamics between the two conditions. Given the intrinsic seizure variability, comparisons were made between same‐dosage and cross‐dosage seizure pairs. We further assessed effects of tapering rates and examined the characteristics of interictal epileptiform discharges. Results: Among 30 patients, the proportion of channels in the seizure onset zone did not differ between high‐dosage and low‐dosage conditions (7.25% vs. 8.95%, p = .50, d = −.04). Similarly, no differences were observed in the overlap ratio of seizure‐onset regions (62% vs. 64%, p = .72, d = −.01), or the cross‐correlation of seizure‐onset patterns (.36 vs. .35, p = .54, d = .04) when comparing same‐dosage versus cross‐dosage seizure pairs. Conversely, seizures at low dosage involved more channels (40.71% vs. 81.49%, p = .001, d = −.39) and lasted longer (33.36 s vs. 74.30 s, p < .01, d = −.47). Tapering rate did not affect seizure dynamics. The mean interictal epileptiform discharge rate and number of propagation channels also remained unchanged. Significance: Despite seizure exacerbation during antiseizure medication tapering, seizure‐onset location remained stable. This supports the robustness of seizure‐based localization even under reduced medication levels and rapid tapering regimens.

Objective: This study aims to evaluate the glymphatic system (GS) in different temporal lobe epilepsy (TLE) subtypes using diffusion tensor imaging analysis along the perivascular space (DTI‐ALPS) and to explore its correlation with clinical factors and memory performance. Methods: The study encompassed 112 TLE patients with hippocampal sclerosis (TLE‐HS), 73 TLE patients with no lesions on magnetic resonance imaging (TLE‐NL), and 55 healthy controls. The DTI‐ALPS index was calculated based on 3.0T diffusion tensor image sequences, and the memory performance was assessed using the Wechsler Memory Scale‐Revised. The DTI‐ALPS index was compared among the three groups, and its relationships with clinical characteristics and memory performance were explored. Results: TLE‐HS group showed a significantly lower DTI‐ALPS index compared with healthy controls in both hemispheres (ipsilateral: p < 0.001; contralateral: p = 0.002). By contrast, TLE‐NL group exhibited a reduced DTI‐ALPS index solely in the ipsilateral hemisphere ( p < 0.001). Within TLE‐NL cohort, those with a history of focal to bilateral tonic–clonic seizures showed reduced DTI‐ALPS indices in both hemispheres (ipsilateral: p = 0.037; contralateral: p = 0.004). In the TLE‐HS group, DTI‐ALPS index positively correlated with memory performance ( p s < 0.05). A multiple regression analysis indicated that the average DTI‐ALPS index was significantly associated with memory quotient ( β = 0.309, p < 0.001; R ² = 0.226), independent of the ipsilateral hippocampal volume. Significance: The patterns of reduced DTI‐ALPS index differed between TLE‐HS and TLE‐NL patients. The extent of GS impairment in TLE‐HS patients correlated with memory decline, suggesting its potential as a therapeutic target for memory enhancement. Plain Language Summary: This study employed the DTI‐ALPS index, a neuroimaging marker, to assess glymphatic system function in distinct subtypes of temporal lobe epilepsy (TLE). Glymphatic impairment was observed in both TLE with hippocampal sclerosis (TLE‐HS) and nonlesional TLE (TLE‐NL), exhibiting distinct patterns. Notably, this dysfunction was associated with memory deficits, suggesting that targeting glymphatic clearance may represent a novel therapeutic strategy for memory improvement in epilepsy.

Objective: This study evaluated the association between temporal piriform cortex (tPC) resection and long‐term postoperative outcomes in temporal lobe epilepsy (TLE). Methods: We conducted a retrospective analysis of patients with TLE undergoing surgery between 2012 and 2022, with a minimum follow‐up of 2 years. The extent of resection, including the tPC, hippocampal head/body, and amygdala, was assessed using magnetic resonance imaging scans. These measurements, along with demographic data and other presurgical evaluations, were analyzed for their associations with Engel class postoperative outcomes and antiseizure medications (ASMs) withdrawal across different TLE subtypes. Results: Among 216 included patients, 158 had mesial TLE (MTLE). At the final follow‐up, 131 MTLE and 35 neocortical TLE (NTLE) patients were seizure‐free. Multivariable logistic regression revealed that unresected tPC significantly predicted seizure recurrence ( p < .001, odds ratio [OR] = 4.415, 95% confidence interval [CI] = 2.032–9.594), along with older age at surgery ( p = .018, OR = 1.034, 95% CI = 1.006–1.063) and nonspecific pathology ( p = .017, OR = 3.899, 95% CI = 1.278–11.894). In NTLE, tPC resection did not significantly affect outcomes. However, in MTLE, unresected tPC was strongly associated with poorer seizure outcomes at both 2‐year ( p = .012, OR = 3.362, 95% CI = 1.311–8.621) and 5‐year ( p = .014, OR = 5.750, 95% CI = 1.423–23.242) follow‐ups. Among seizure‐free MTLE patients, those with tPC resection had higher rates of ASMs reduction and withdrawal after 5 years ( p < .05). In hippocampal sclerosis (HS) patients, unresected tPC correlated with seizure recurrence ( p < .05), whereas no such association was observed in non‐HS cases. Significance: Our findings suggest that tPC involvement in the epileptogenic zone varies by TLE subtype, with tPC resection strongly linked to favorable outcomes in MTLE, particularly in HS patients. These results reinforce the understanding of the hippocampus–amygdala–piriform complex as crucial to the epileptogenic zone in MTLE.

Objective: To investigate how etiology and seizure localization influence ictal scalp electroencephalographic (EEG) patterns in temporal lobe epilepsy (TLE).Methods: We retrospectively analyzed ictal EEG features from 504 focal seizures recorded in 189 TLE patients with various etiologies who underwent resective surgery.Results: For seizure onset patterns (SOPs), α/β onset was more common in the low‐grade tumor group (38.4%) than in the hippocampal sclerosis (HS) group (14.1%, p < 0.001). The ictal EEG duration was shorter in the tumor group compared to the focal cortical dysplasia (FCD), HS, and non‐specific groups (p < 0.05). Among mesial TLE patients, SOPs varied depending on the etiology. Within both the tumor and non‐specific groups, SOPs and the spreading time to the contralateral hemisphere differed between mesial and neocortical origins. Ictal pattern (87.7%) and ictal theta activity (83.9%) correctly lateralized the seizure in most cases.Significance: The ictal scalp pattern in TLE is influenced by both etiology and seizure localization. TLE associated with low‐grade tumors exhibits distinct ictal EEG characteristics. Furthermore, ictal pattern and ictal theta activity are equally effective in lateralizing seizures, regardless of etiology.Plain Language Summary: This research examined how brain activity during seizures in people with temporal lobe epilepsy can be different based on what caused the epilepsy and where in the brain the seizure starts. We found that seizures caused by brain tumors have unique patterns in the brain's electrical activity. Additionally, we discovered that specific patterns and types of brain waves can help determine which side of the brain the seizure is occurring on, regardless of its cause.

High-frequency oscillations (HFOs) encompass ripples (80 Hz–200 Hz) and fast ripples (200 Hz–600 Hz), serving as a promising biomarker for localizing the epileptogenic zone in epilepsy. Spontaneous fast ripples are always pathological, while ripples may be physiological or pathological. Distinguishing physiological from pathological ripples is important not only for designating epileptogenic brain regions, but also for investigations that study ripples in the context of memory encoding, consolidation, and recall in patients with epilepsy. Many studies have sought to identify distinguishing features between pathological and physiological ripples over the past two decades. Physiological and pathological ripples differ with respect to their spatial location, cellular mechanisms, morphology, and coupling with background electroencephalographic activity. Retrospective studies have demonstrated that differentiating between pathological and physiological ripples can improve surgical outcome prediction. In this review, we summarize the characteristics, differences, and applications of pathological and physiological HFOs and discuss strategies for their clinical translation.

Reward expectancy shapes behavioral performance by coordinating the allocation of cognitive resources, which incorporates the involvement of the anterior insular cortex (AIC). To investigate the electrophysiological mechanisms of the AIC during reward expectancy, we collected intracranial electroencephalographic data from epilepsy patients undergoing clinical monitoring. Subjects navigated a virtual T-maze containing rewards at three predetermined locations. We focused on the period immediately before entering the reward zone, termed the reward expectancy stage. During this stage, we identified the reward-specific brain patterns (RBPs) that were preactivated in the AIC. This pre-activation preceded the emergence of robust phase-amplitude coupling (PAC), where theta oscillations (5-7 Hz) modulated gamma activities (75–110 Hz). The PAC strength correlated positively with the pre-activation level of RBPs, implying the potential role of oscillatory coordination in amplifying preactivated reward representations. Strikingly, this PAC effect exhibited a specific temporal structure that peak gamma activity became progressively coupled to earlier theta phases as reward approached, mirroring the theta phase precession phenomenon previously observed in frontal and temporal lobes. We refer to this dynamic as phase-precession-like effect (PPLE). Moreover, subjects exhibiting PPLE in the AIC presented greater trial-by-trial improvements in response latency. Taken together, these findings shed light on the electrophysiological mechanisms of the AIC underlying reward expectancy.