bioRxiv Science⌕ Search

bioRxiv · 10.1101/2023.08.22.553552

Cerebral perfusion alterations in temporal lobe epilepsy: Structural underpinnings and network disruptions

Abstract

AO_SCPLOWBSTRACTC_SCPLOWO_ST_ABSOO_SCPLOWBJECTIVEC_SCPLOWC_ST_ABSNeuroimaging has been the prevailing method to study brain networks in temporal lobe epilepsy (TLE), showing widespread alterations beyond the mesiotemporal lobe. Despite the critical role of the cerebrovascular system in maintaining whole-brain structure and function, changes in cerebral blood flow (CBF) remain incompletely understood in the disease. MO_SCPLOWETHODSC_SCPLOWWe studied 24 individuals with pharmaco-resistant TLE and 38 healthy adults using multimodal 3T magnetic resonance imaging. We compared regional CBF changes in patients relative to controls and related our perfusion findings to morphological and microstructural metrics. We further probed inter-regional vascular networks in TLE, using graph theoretical CBF covariance analysis. Finally, we assessed the effects of disease duration to study progressive changes. RO_SCPLOWESULTSC_SCPLOWCompared to controls, individuals with TLE showed widespread CBF reductions, predominantly in fronto-temporal regions, with 83% of patients showing more marked decreases ipsilateral than contralateral to the seizure focus. Parallel structural profiling and network-based models showed that cerebral hypoperfusion may be partly constrained by grey and white matter changes and topologically segregated from whole-brain perfusion networks. Negative effects of progressive disease duration further targeted regional CBF profiles in patients. Findings were confirmed in a subgroup of patients who remained seizure-free after surgery. IO_SCPLOWNTERPRETATIONC_SCPLOWOur multimodal findings provide insights into vascular contributions to TLE pathophysiology and highlight their clinical potential in seizure lateralization.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ngo, A., Royer, J., Rodriguez-Cruces, R., Xie, K., DeKraker, J., Auer, H., Tavakol, S., Lam, J., Schrader, D., Dudley, R. W. R., Bernasconi, A., Ladbon-Bernasconi, N., Frauscher, B., Lariviere, S., Bernhardt, B. C.. 2023-08-24. Cerebral perfusion alterations in temporal lobe epilepsy: Structural underpinnings and network disruptions. https://doi.org/10.1101/2023.08.22.553552

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

KEEP EXPLORING

Related preprints

Rab10 and Arhgef7 interact to promote axon extension by linking vesicle supply and exocytosis

The formation of functional neural circuits begins with the extension of a single axon by immature neurons. Axon elongation requires an expansion of the plasma membrane that depends on the polarization of vesicle trafficking and exocytosis. It is not completely understood how the increased transport of vesicles into the growing axon is linked to their subsequent insertion into the plasma membrane. An analysis of early stages of neuronal differentiation indicates that an asymmetry in neurite length precedes axon specification and the accumulation of PPVs in the nascent axon. We show that increasing the transport of vesicles in unpolarized neurons is sufficient to promote the extension of additional axons. This effect indicates that an increased supply of vesicles stimulates their subsequent insertion into the membrane to allow neurite growth. The link between vesicle transport and exocytosis is mediated by the interaction of Rab10 with Arhgef7. Rab10 stimulates Arhgef7 activity on PPVs as a GEF for Cdc42b to promote axon extension through exocyst-dependent exocytosis, suggesting that their interaction links the increased supply of PPVs to their exocytosis.

neuroscience↗

Subcellular Spatial Profiling Unveils Links Between Neuritic Plaques with Selective Tau Vulnerability in Alzheimer's Disease

Alzheimer's disease (AD) features widespread extracellular amyloid-{beta} plaques but selective intraneuronal tau accumulation in cortical layers II/III and V, while layer IV remains relatively resistant. Here, we combined subcellular spatial transcriptomics with co-registered A{beta} and pTau immunohistochemistry to determine why neurons exposed to comparable plaque-associated pathology differ in somatic pTau accumulation. Plaque-associated neuritic stress occurred similarly across layers, but layer IV neurons showed attenuated pTau accumulation and reduced somatic expression of a shared neurite-soma stress program involving DCTN1, CALM3, NORAD, and PIN1. Trajectory analysis within layers identified tau-vulnerable and resistant neuronal states implicating calcium signaling, retrograde transport, and lysosomal function. Notably, astrocytic APOE-neuronal LRP1 co-expression increased significantly along the pTau-vulnerable trajectory, and APOE {epsilon}4 was associated with stronger coupling of local plaque pathology to pTau-associated molecular programs. These findings reveal neuronal programs and neuron-glia interactions underlying selective tau vulnerability and resistance in AD, highlighting potential tau-targeting therapeutics.

neuroscience↗

Widespread oscillatory suppression in autism persists in the absence of psychotropic medication.

Purpose: Investigate the neural oscillatory activity associated with autism spectrum disorder (ASD) using electroencephalographic (EEG) recordings in children and adolescents. Compare the corresponding oscillatory power between ASD patients taking psychotropic medication with a drug-naive group. Methods: ASD diagnosis was done using DSM-IV and CARS (Childhood Autism Rating Scale). EEG recordings employed 22 scalp electrodes (10/20 system). ASD vs. neurotypical groups were matched for sex and age (5 females; average age: ~10 years old). We analyzed the resting state (eyes open) EEG power spectrum during ~2-minute recordings. The multitaper FFT method was used to estimate spectral power for the delta, theta, alpha, beta and gamma frequency bands. We pooled together data from several electrodes to compute comprehensive power spectra and assess the oscillatory behavior of macro brain regions. Results: We observed widespread (~4Hz - 20Hz) oscillatory suppression comprising the theta, alpha and beta frequency bands. The most widespread and robust ASD-associated power suppression was in the high theta and alpha bands. Delta and gamma bands showed no significant power change for any of the brain regions studied. Results from a subgroup of patients (N = 9) who never used psychotropics confirmed these findings, indicating that they are not an artifact of medication. Conclusion: Suppression in theta, alpha and beta oscillations may offer insights into the neurophysiological underpinnings of autism and could be used as an accessible and comprehensive tool in ASD diagnosis, regardless of the patients being or not on medication.

neuroscience↗