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Svalina, M.

Publications and source records attributed to Svalina, M..

2 recordsLinked to original sources

Stable Network Motifs with Divergent Engagement Across Memory Outcomes

Visual recognition memory depends on coordinated interactions across distributed medial temporal, prefrontal, and limbic networks, yet the sub-second large-scale network dynamics distinguishing successful from unsuccessful recognition remain poorly understood. Here we used intracranial EEG recordings from seven patients (4 female, 3 male) with medically refractory epilepsy performing a new-old visual recognition memory task to characterize time-resolved directed functional connectivity and dynamic network organization. Directed effective connectivity was estimated using bivariate Granger causality in a sliding-window framework, and dynamic community structure was identified using the Louvain modularity algorithm. Successful recognition (Hits) was associated with a qualitatively distinct network configuration: low modularity (Q = 0.05 vs. 0.09-0.15 in other conditions), a cross-hemispheric community structure integrating left medial temporal lobe (MTL) with right prefrontal cortex, and sustained network integration throughout the post-stimulus period. Right-hemisphere nodes within this cross-hemispheric community showed stronger within-community directed connectivity than left-hemisphere nodes (mean asymmetry index = 0.33, p < 0.001), consistent with right prefrontal dominance in driving network integration during successful retrieval. In contrast, Correct Rejections were characterized by early transient network segregation (onset 32 ms) dominated by right-hemisphere activity. Hub regions were non-overlapping across conditions--left-lateralized during Hits, right-lateralized during Correct Rejections. These findings imply that successful visual recognition is distinguished not by stronger connectivity per se, but by a reorganization of large-scale network topology that transiently integrates left MTL with right prefrontal cortex into a unified functional community.

neuroscience↗

Developmental Characterization of Neuronal Migration Anomalies and Axon Proliferation in mTOR pathway-associated Malformations of Cortical Development

Drug-resistant epilepsy (DRE) is a prevalent problem in children that can lead to abnormal development and various psychiatric comorbidities. Malformations of cortical development (MCD) include focal cortical dysplasia, tuberous sclerosis complex and hemimegalencephaly, which are the most common pathologies among children who undergo surgical resection for treatment of DRE. These disorders share many histopathological features, including dyslamination of the cerebral cortex and enlarged neuronal somata. Recently, genetic mutations in the mammalian target of rapamycin (mTOR) signaling cascade have been shown to underpin most MCDs. Rodent models, including the RhebCA model, recapitulate histologic and physiologic aspects of human DRE. However, there have been few studies characterizing the developmental time point of the histological changes seen in MCDs. In this study, we use in utero electroporation to upregulate the Rheb protein (directly upstream of mTOR) in a focal area of the neocortex. We demonstrate that mTOR dysregulation leads to focal dyslamination and increased neuronal size that is histologically similar to MCD, which correlates to spontaneous recurrent seizures. We used immunohistochemistry to investigate neuronal lamination at several time points during development between E18 and P21 and show early differences in lamination that persisted through development. Furthermore, the increased axonal length associated with mTOR upregulation occurs early in development. Our study provides a time frame for the initial development of abnormal neuronal migration and cellular growth that occurs in MCDs, and our data supports that these anatomical changes may contribute to the formation of epileptic networks.

neuroscience↗