Centeno, M. | Search bioRxiv

bioRxiv2025

Emergence of high-connectivity states before epileptic seizures: Multi-patient validation, physiological correlates, and network modeling

Objective.Epilepsy affects around 50 million people worldwide, and reliable pre-seizure biomarkers could significantly improve neuromodulation therapies for drug-resistant patients. Recent research using stereo-electroencephalography (sEEG) has revealed transient changes in network dynamics preceding seizures. In particular, our previous work showed that these alterations are driven by recurrent, short-lasting (0.6 s) high-connectivity network configurations--termed High-Connectivity States (HCS). Here, we aim to replicate and further characterize HCS as a biomarker in a multicentric patient cohort, assess its robustness across recording modalities and montages, explore its relationship with interpretable physiological variables, and examine its network-level association with seizure-onset zone (SOZ) dynamics. Approach.We analyzed long-term intracranial EEG (iEEG) recordings from 12 patients with sEEG and electrocorticography (ECoG). In two patients with extensive clinical information, we examined the interplay between HCS and SOZ dynamics. We also developed a low-dimensional stochastic network model to investigate mechanistic rationales of HCS emergence. Additionally, we compared HCS dynamics with gamma-band activity and heart rate, and tested robustness across different montage configurations. Main Results.In most patients, HCS probability reliably increased hours before seizure onset. In the two deeply characterized patients, this increase was specifically linked to an increased network centrality within the SOZ. The network model revealed that changes in HCS probability stem primarily from topological reconfigurations rather than changes in mean connectivity, underscoring the importance of dynamic interactions between epileptogenic and non-epileptogenic regions. Significance.These results support HCS probability as a promising biomarker for early seizure prediction and offer mechanistic insights into pre-seizure brain network dynamics.

neuroscience↗

bioRxiv2018

Dorsal Hippocampal Activation Suppresses Neuropathic Pain Behaviors: Chronic pain as extinction-resistant pain-related memory traces

Accumulating evidence suggests the hippocampus being involved in, and modified with, chronic neuropathic pain. However, it is still not clear whether hippocampal activity has direct control over neuropathic behaviors. Here we show that activation of the dorsal, but not ventral, hippocampus, by glutamate microinjection or by chemogenetically increasing excitability (PSAM/PSEM), completely or partially reversed neuropathic behaviors: tactile allodynia and thermal hyperalgesia in the models of spared nerve injury and lumbar spinal nerve ligation. Using a new methodology (chemo-fMRI), where we combine awake resting state brain imaging with viral vector mediated chemogenetic activation (PSAM/PSEM), we could demonstrate that increased excitability of dorsal hippocampus neurons altered resting state functional connectivity within circuitry specifically related to the extent of diminution of neuropathic behavior (tactile allodynia). The identified circuitry most reliably (survived a validation procedure) identified dorsal hippocampal connections to the somatosensory cortex and the thalamus. Moreover, anterograde tracing indicated non-overlapping projections from dorsal and ventral hippocampus. Thus, the present study exhibits a novel causal role for the dorsal hippocampus, and mediating circuitry, controlling neuropathic pain-related behaviors. Altogether, these results imply downregulation of dorsal hippocampus circuitry in chronic neuropathic pain; the activation of which reverses pain behaviors either through disruption of accumulated memories and/or by enhancing extinction circuitry.

neuroscience↗