Victoria Ho | PubMed Health

PubMed2026

Single-nucleus transcriptomics reveals cell type-specific remodeling and epilepsy-associated microglia.

Temporal lobe epilepsy (TLE) is the most common acquired epilepsy, causing refractory seizures and cognitive deficits. We performed single-nucleus RNA sequencing on hippocampal tissue from mice 3 and 6 weeks following pilocarpine-induced status epilepticus, a robust model of TLE. Epilepsy samples showed reductions in Cck and Lamp5-Lhx6 interneuron subclusters, alongside increases in Cajal-Retzius cells, dentate granule (DG) cell precursors, and a mature DG cell subcluster. Among glia, an astrocyte subcluster and a markedly expanded microglia sublcuster were increased. We term this microglia population epilepsy-associated microglia (EAM). The transcriptomic profile of EAM overlaps with microglia described in models of Alzheimer's disease and traumatic brain injury, including enrichment of Myo1e and Igf1. EAM display amoeboid morphology, can be found in clumps around pyramidal and granule cell body layers, and exhibit enlarged vesicles and mitochondria. Cell-cell interaction analysis predicts DG cells as their primary interaction partners. This dataset defines transcriptomic programs underlying key cellular alterations in TLE, enabling mechanistic dissection of epileptogenesis.

TLE↗

PubMed2026

Altered EEG microstate dynamics reflect depressive symptoms in temporal lobe epilepsy.

BACKGROUND: Depressive symptoms are a common and disabling comorbidity in temporal lobe epilepsy (TLE), yet the neural mechanisms linking seizure networks to affective symptoms remain unclear. Although limbic network dysfunction has been implicated in both epilepsy and depressive disorders, it is unknown whether the time-varying dynamics of large-scale electrophysiological brain states reflect depressive symptom severity in TLE. In this study, we examined whether EEG microstate dynamics capture network alterations associated with depressive symptoms in individuals with unilateral TLE. METHODS: We analyzed resting-state, visually normal scalp EEG from 26 individuals with unilateral TLE. EEG microstates were identified by clustering global field power peaks into four canonical classes, with electrode positions mirrored to align the ictal hemisphere across subjects. Microstate dwell time, fractional occupancy, global transition entropy, and Markov transition probabilities were quantified and related to Beck Depression Inventory-II (BDI) scores. RESULTS: Individuals with high depressive symptoms (BDI ≥ 13; N = 12) exhibited longer mean dwell time in the ictal hemisphere-aligned microstate compared with individuals with low depressive symptom burden (BDI < 13; N = 14). Across subjects, dwell time in this microstate correlated with depressive symptom severity (r = 0.57, p = 0.002). TLE individuals with higher depressive symptoms exhibited reduced global transition entropy (p = 0.02), which also correlated with depressive symptom severity (r = -0.54, p = 0.004), indicating decreased flexibility of microstate transitions. Despite similar fractional occupancy of this state between groups, individuals with higher depressive symptoms were less likely to transition into the ictal hemisphere-aligned microstate from non-ictal or posterior configurations. Once engaged, however, the ictal-aligned microstate showed increased persistence, indicating prolonged stabilization of this network configuration. CONCLUSION: Higher depressive symptom burden in unilateral TLE is associated with increased temporal rigidity of the ictal hemisphere-aligned brain microstate, reflecting impaired disengagement of epileptogenic network configurations. These findings suggest that depressive symptoms in TLE may be associated with epilepsy-related disruptions in large-scale neural dynamics.

Humans↗