Biology subjects

Kalviainen, R.

Publications and source records attributed to Kalviainen, R..

4 recordsLinked to original sources

bioRxiv2025

Multimodal approach to characterize surgically removed epileptogenic zone from patients with focal drug-resistant epilepsy: from operating room to wet lab

ObjectiveWe have established a comprehensive sample handling protocol designed for the multiscale assessment of epileptogenic tissue. This protocol aims to identify novel therapeutic targets and enhance the diagnosis and stratification of patients with drug-resistant epilepsy, thereby optimizing their treatment with anti-seizure medications and surgical interventions. MethodsPatients with drug-resistant focal epilepsy, recommended for surgical treatment, are recruited after detailed multidisciplinary preoperative evaluation at the Epilepsy Center at Kuopio University Hospital in Finland. A day before the resective surgery, patients undergo magnetic resonance imaging (MRI) including advanced methodologies. During the surgery, each piece of resected tissue is placed under oxygenation on ice-cold artificial cerebral spinal fluid-solution. The pieces are then immediately transported to the laboratory, assessed by a neuropathologist, and sliced for both clinical diagnosis and research. Two adjacent slices are provided for research and are sent to the University of Eastern Finland. ResultsThe developed sample handling protocol provides the opportunity for detailed characterization of the tissue from the same patient using emerging imaging, electrophysiology, and molecular biology technologies. We have optimized the conditions for preserving the resected tissue alive for electrophysiological measurements and simultaneously making possible ex vivo studies including multi-omics acquisition, electron microscopy, histology, and MRI. Our protocol enables the mapping of functional readouts to structural and molecular alterations in human tissue. Our goal is to integrate multimodal data and co-register the resected tissues within the whole brains in vivo MRI space. This approach aims to enhance the characterization and localization of epileptogenic zones and refine surgical treatment targets by identifying abnormalities in global connectivity and structural patterns. SignificanceWe have successfully developed a systematic protocol for the collection and analysis of multimodal data. This protocol aims to elucidate the structural, functional, and molecular characteristics that render tissue epileptogenic, thereby enhancing the diagnosis and subsequent care of patients with epilepsy. Key pointsO_LIIntroducing a systematic sample handling protocol to assess tissue epileptogenicity at structural, functional and molecular levels. C_LIO_LIA multimodal approach integrating advanced technology with detailed characterization of epileptogenic tissue properties to obtain patient-specific data. C_LIO_LICorrelation of data from preoperative MRI and resected tissue to predict tissue pathology from clinical MRI. C_LI

neuroscience↗

bioRxiv2025

Microelectrode array scaled for recording human hippocampal slices

Temporal lobe epilepsy (TLE) is a prevalent neurological disorder characterized by recurrent seizures originating from the cortex, amygdala and especially hippocampus. While two-thirds of TLE patients achieve seizure control through medication, approximately one-third remain refractory to pharmacological interventions. For these individuals, surgical resection offers a potential curative option, with approximately 70% achieving seizure freedom. However, the pathogenesis of TLE remains incompletely understood, necessitating further investigation. Therefore, resected brain tissue obtained during the surgery provides a valuable resource for ex vivo study of pathological neuronal activity. Currently, microelectrode array (MEA) technology is widely used for electrophysiological studies. However, commercially available MEAs are limited in their ability to record from large tissue samples, such as an entire hippocampal section. To address this limitation, we have developed a custom MEA and sample chamber compatible with commercially available headstages. This system enables recording of extracellular action potentials (EAPs) and local field potentials (LFPs) across human hippocampal tissue, providing a valuable tool for investigating the neurophysiological mechanisms underlying TLE. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=71 SRC="FIGDIR/small/640534v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@188e42corg.highwire.dtl.DTLVardef@3c10c6org.highwire.dtl.DTLVardef@17145a5org.highwire.dtl.DTLVardef@19369eb_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIA custom microelectrode array and chamber created for human hippocampal slices C_LIO_LIThe custom array recorded action potentials from human hippocampal slices C_LIO_LIThe custom array recorded local field potentials from human hippocampal slices C_LI

neuroscience↗

bioRxiv2021

Structural network alterations in focal and generalized epilepsy follow axes of epilepsy risk gene expression: An ENIGMA study

Epilepsy is associated with genetic risk factors and cortico-subcortical network alterations, but associations between neurobiological mechanisms and macroscale connectomics remain unclear. This multisite ENIGMA-Epilepsy study examined whole-brain structural covariance networks in patients with epilepsy and related findings to postmortem co-expression patterns of epilepsy risk genes. Brain network analysis included 578 adults with temporal lobe epilepsy (TLE), 288 adults with idiopathic generalized epilepsy (IGE), and 1,328 healthy controls from 18 centres worldwide. Graph theoretical analysis of structural covariance networks revealed increased clustering and path length in orbitofrontal and temporal regions in TLE, suggesting a shift towards network regularization. Conversely, people with IGE showed decreased clustering and path length in fronto-temporo-parietal cortices, indicating a random network configuration. Syndrome-specific topological alterations reflected expression patterns of risk genes for hippocampal sclerosis in TLE and for generalized epilepsy in IGE. These imaging-genetic signatures could guide diagnosis, and ultimately, tailor therapeutic approaches to specific epilepsy syndromes.

neuroscience↗

bioRxiv2021

Topographic divergence of atypical cortical asymmetry and regional atrophy patterns in temporal lobe epilepsy: a worldwide enigma study

AO_SCPLOWBSTRACTC_SCPLOWTemporal lobe epilepsy (TLE), a common drug-resistant epilepsy in adults, is primarily a limbic network disorder associated with predominant unilateral hippocampal pathology. Structural MRI has provided an in vivo window into whole-brain grey matter pathology in TLE relative to controls, by either mapping (i) atypical inter-hemispheric asymmetry or (ii) regional atrophy. However, similarities and differences of both atypical asymmetry and regional atrophy measures have not been systematically investigated. Here, we addressed this gap using the multi-site ENIGMA-Epilepsy dataset comprising MRI brain morphological measures in 732 TLE patients and 1,418 healthy controls. We compared spatial distributions of grey matter asymmetry and atrophy in TLE, contextualized their topographies relative to spatial gradients in cortical microstructure and functional connectivity, and examined clinical associations using machine learning. We identified a marked divergence in the spatial distribution of atypical inter-hemispheric asymmetry and regional atrophy mapping. The former revealed a temporo-limbic disease signature while the latter showed diffuse and bilateral patterns. Our findings were robust across individual sites and patients. Cortical atrophy was significantly correlated with disease duration and age at seizure onset, while degrees of asymmetry did not show a significant relationship to these clinical variables. Our findings highlight that the mapping of atypical inter-hemispheric asymmetry and regional atrophy tap into two complementary aspects of TLE-related pathology, with the former revealing primary substrates in ipsilateral limbic circuits and the latter capturing bilateral disease effects. These findings refine our notion of the neuropathology of TLE and may inform future discovery and validation of complementary MRI biomarkers in TLE.

neuroscience↗