Search bioRxiv⌕ Search

bioRxiv · 10.1101/2025.09.19.677437

Elevated Thalamic Blood Flow in Self-Limited Epilepsy with Centrotemporal Spikes

Abstract

Children with self-limited epilepsy syndrome with centrotemporal spikes (SeLECTS) exhibit altered thalamocortical connectivity, but whether thalamic function itself is abnormal remains unclear. We investigated whether thalamic blood flow, a marker of metabolism, differs between children with SeLECTS and controls, and examined the effects of spike distribution and antiseizure medications (ASMs) on thalamic perfusion. In this retrospective cohort study, we identified consecutive children with SeLECTS who underwent magnetic resonance imaging (MRI) for epilepsy evaluation (n = 44) and age- and sex-matched children who underwent MRI for non-epilepsy indications (n = 35). We quantified thalamic blood flow via manual segmentation of cerebral blood flow (CBF) sequences obtained from arterial spin labeling MRI. Clinical variables including sedation use during MRI, daily ASM use, and spike distribution (unilateral or bilateral) were extracted from medical records. Children with SeLECTS demonstrated elevated thalamic blood flow compared to controls, with the most pronounced differences in specific subgroups. Children with unilateral spikes showed the highest CBF, particularly in the thalamus contralateral to spike activity. ASM use significantly modulated thalamic blood flow: children taking oxcarbazepine showed the highest CBF, while those on levetiracetam had CBF similar to controls. Unmedicated children showed intermediate elevations. These findings demonstrate that elevated thalamic blood flow may be intrinsic to SeLECTS pathophysiology, with different ASMs producing distinct neurobiological effects. The differential medication effects may relate to their clinical efficacy and provide neurobiological rationale for treatment selection in this common childhood epilepsy syndrome.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Iasinovschi, N., Tong, E., Bicknell, L., Baumer, F. M.. 2025-09-20. Elevated Thalamic Blood Flow in Self-Limited Epilepsy with Centrotemporal Spikes. https://doi.org/10.1101/2025.09.19.677437

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Different hippocampal subfield volumes predict source memory performance and general cognitive ability in an adult lifespan sample

Modest positive associations between episodic memory performance and whole hippocampal and hippocampal subfield volumes have been reported in numerous prior studies. A smaller number of studies have reported associations between hippocampal volume and performance on tests of non-mnemonic cognition. The present study examined whether these associations were evident in a lifespan sample of cognitively healthy adults. Of particular interest was whether any identified associations were sensitive to age, and whether associations between subfield volumes and mnemonic and non-mnemonic performance were subfield dependent. We acquired high-resolution T1- and T2-weighted structural images from 163 adults (18-87 years of age). Participants also undertook a comprehensive neuropsychological test battery and an in-scanner test of source memory. Principal components analysis was employed to reduce the neuropsychological test scores to 5 cognitive components. Two components reflected memory performance while the other three reflected different aspects of non-mnemonic cognition. Hippocampal subfields (Cornu Ammonis (CA)1, CA2-3, dentate gyrus (DG) and subiculum) were segmented and measured with the Automated Segmentation of Hippocampus Subfields (ASHS) package. Source memory performance was selectively associated across participants with CA2-3 volume. By contrast, both mnemonic and non-mnemonic component scores derived from the test battery were associated exclusively with the volume of the DG. All associations were age-invariant. The findings indicate that different cognitive domains can be dissociated by virtue of their associations with different hippocampal subfields. Of importance, these associations appear to be life-long and hence are unlikely to reflect individual differences in age-related decline in structural integrity.

neuroscience↗

Cell type specific astrocytic feedback regulates excitation inhibition balance and cortical network dynamics

Astrocytes actively regulate synaptic transmission and neuronal excitability, yet their role in orchestrating macroscopic cortical network regimes and slow-wave oscillations remains an active area of reasearch. This study investigates how bidirectional neuron astrocyte interactions shape emergent population dynamics using a computational network model of excitatory and inhibitory neurons coupled to an astrocyte. The results identify astrocytic feedback topology, rather than astrocytic coupling strength alone, as a key determinant of emergent cortical network dynamics. By systematically dissecting pathway-specific connectivity, it has been shown that the neuronal population driving astrocytic activation and the neuronal population receiving gliotransmission jointly determine whether the network occupies asynchronous irregular (AI), synchronous irregular (SI), synchronous regular(SR), asynchronous regular(AR) or quiescent regimes.Directing gliotransmission selectively onto excitatory neurons consistently promotes population synchrony regardless of the population influencing astrocytic dynamics, whereas selective modulation of inhibitory interneurons induces network quiescence via strong suppression. Under dual-target gliotransmission, network synchrony is dictated by the population driving astrocytic dynamics: excitatory-only drive promotes synchrony, while combined or inhibitory-specific drive preserves asynchronous states. Furthermore, the model reveals that astrocytic signaling kinetics provide an additional temporal control mechanism that regulates the frequency and persistence of self sustained up states.

neuroscience↗

VCP inhibition prevents cone photoreceptor degeneration in the cpfl1 mouse model of achromatopsia

Achromatopsia (ACHM) is a rare autosomal recessive retinal disorder characterized by absent cone photoreceptor function from early life, leading to severe visual impairment. Mutations in genes involved in the cone phototransduction cascade frequently result in elevated cyclic guanosine monophosphate (cGMP) levels and activation of stress pathways, including endoplasmic reticulum (ER) stress and the unfolded protein response. Targeting common downstream mechanisms rather than individual mutations may provide a broadly applicable therapeutic strategy. Here, we investigated whether pharmacological inhibition of valosin-containing protein (VCP), a key regulator of ER and protein homeostasis, can prevent cone degeneration in the spontaneous cone photoreceptor function loss 1 (cpfl1) mouse model of ACHM. Organotypic culture of retinal explants from cpfl1 mice were treated with the selective VCP inhibitor ML240. Cone survival, cell death, opsin expression and localization were assessed by TUNEL assay, immunohistochemistry, and quantitative image analysis. ML240 treatment significantly increased cone density and improved cone opsin expression and trafficking to the outer segments (OSs) in cpfl1 explants compared to controls. Importantly, rhodopsin trafficking in rod photoreceptors was unaffected, indicating that VCP inhibition did not impair normal rod phototransduction. These findings demonstrate that VCP inhibition by ML240 effectively preserves cone photoreceptors and improves cone-specific functional markers in the cpfl1 model. Targeting VCP may represent a mutation-independent therapeutic strategy for preventing cone death in ACHM.

neuroscience↗