Biology subjects

Grohn, O.

Publications and source records attributed to Grohn, O..

7 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↗

bioRxiv2024

Whisker stimulation with different frequencies reveals non-uniform modulation of functional magnetic resonance imaging signal across sensory systems in awake rats

Primary sensory systems are classically considered to be separate units, however there is current evidence that there are notable interactions between them. We examined the cross-sensory interplay by applying a quiet and motion-tolerant zero echo time functional magnetic resonance imaging (fMRI) technique to elucidate the evoked brain-wide responses to whisker pad stimulation in awake and anesthetized rats. Specifically, characterized the brain-wide responses in core and non-core regions to whisker pad stimulation by the varying stimulation-frequency, and determined whether isoflurane-medetomidine anesthesia, traditionally used in preclinical imaging, confounded investigations related to sensory integration. We demonstrated that unilateral whisker pad stimulation not only elicited robust activity along the whisker-mediated tactile system, but also in auditory, visual, high-order, and cerebellar regions, indicative of brain-wide cross-sensory and associative activity. By inspecting the response profiles to different stimulation frequencies and temporal signal characteristics, we observed that the non-core regions responded to stimulation in a very different way compared to the primary sensory system, likely reflecting different encoding modes between the primary sensory, cross-sensory, and integrative processing. Lastly, while the activity evoked in low-order sensory structures could be reliably detected under anesthesia, the activity in high-order processing and the complex differences between primary, cross-sensory, and associative systems were visible only in the awake state. We conclude that our study reveals novel aspects of the cross-sensory interplay of whisker-mediated tactile system, and importantly, that these would be difficult to observe in anesthetized rats.

neuroscience↗

bioRxiv2023

A multi-channel TMS system enabling accurate stimulus orientation control during concurrent ultra-high-field MRI for preclinical applications

Monitoring cortical responses to neuromodulation protocols on preclinical models can elucidate fundamental mechanisms of brain function. Concurrent brain stimulation and imaging is challenging, usually compromising spatiotemporal resolution, accuracy, and versatility. Here we report a non-invasive brain stimulation system with electronic control of neuromodulation parameters in a 9.4-T magnetic resonance imaging (MRI) environment. In the imaging scanner, transcranial magnetic stimulation is delivered with a set of two coils and the MRI signals are recorded with a radiofrequency coil. The coil set provides millisecond-scale electronic control of the stimulus orientation with 1{degrees} resolution. Without physically rotating the coils, we evoked orientation-specific muscle responses after cortical stimulation on an anesthetized rat. We show that the stimulation pulses do not affect the anatomical imaging quality, and imaging signals are disrupted only if recorded before 10 ms after pulse delivery. Concurrent electronically targeted brain stimulation and neuroimaging sets the stage for the causal investigation of whole-brain network functions, endorsing more efficient treatment protocols.

neuroscience↗

bioRxiv2021

Automatic segmentation of the rat brain hippocampus in MRI after traumatic brain injury

AO_SCPLOWBSTRACTC_SCPLOWRegistration-based methods are commonly used in the anatomical segmentation of magnetic resonance (MR) brain images. However, they are sensitive to the presence of deforming brain pathologies that may interfere with the alignment of the atlas image with the target image. Our goal was to develop an algorithm for automated segmentation of the normal and injured rat hippocampus. We implemented automated segmentation using a U-Net-like Convolutional Neural Network (CNN). of sham-operated experimental controls and rats with lateral-fluid-percussion induced traumatic brain injury (TBI) on MR images and trained ensembles of CNNs. Their performance was compared to three registration-based methods: single-atlas, multi-atlas based on majority voting and Similarity and Truth Estimation for Propagated Segmentations (STEPS). Then, the automatic segmentations were quantitatively evaluated using six metrics: Dice score, Hausdorff distance, precision, recall, volume similarity and compactness using cross-validation. Our CNN and multi-atlas -based segmentations provided excellent results (Dice scores > 0.90) despite the presence of brain lesions, atrophy and ventricular enlargement. In contrast, the performance of singe-atlas registration was poor (Dice scores < 0.85). Unlike registration-based methods, which performed better in segmenting the contralateral than the ipsilateral hippocampus, our CNN-based method performed equally well bilaterally. Finally, we assessed the progression of hippocampal damage after TBI by applying our automated segmentation tool. Our data show that the presence of TBI, time after TBI, and whether the location of the hippocampus was ipsilateral or contralateral to the injury explained hippocampal volume (p = 0.029, p < 0.001, and p < 0.001 respectively).

bioinformatics↗

bioRxiv2021

Whole-brain studies of spontaneous behavior in head-fixed rats enabled by zero echo time MB-SWIFT fMRI

Understanding the link between the brain activity and behavior is a key challenge in modern neuroscience. Behavioral neuroscience, however, lacks tools to record whole-brain activity in complex behavioral settings. Here we demonstrate that a novel Multi-Band SWeep Imaging with Fourier Transformation (MB-SWIFT) functional magnetic resonance imaging (fMRI) approach enables whole-brain studies in spontaneously behaving head-fixed rats. First, we show anatomically relevant functional parcellation. Second, we show sensory, motor, exploration, and stress-related brain activity in relevant networks during corresponding spontaneous behavior. Third, we show odor-induced activation of olfactory system with high correlation between the fMRI and behavioral responses. We conclude that the applied methodology enables novel behavioral study designs in rodents focusing on tasks, cognition, emotions, physical exercise, and social interaction. Importantly, novel zero echo time and large bandwidth approaches, such as MB-SWIFT, can be applied for human behavioral studies, allowing more freedom as body movement is dramatically less restricting factor.

neuroscience↗

bioRxiv2020

Automated skull-stripping and segmentation with Multi-Task U-Net in large mouse brain MRI databases

Skull-stripping and region segmentation are fundamental steps in preclinical magnetic resonance imaging (MRI) studies, and these common procedures are usually performed manually. We present Multi-task U-Net (MU-Net), a convolutional neural network designed to accomplish both tasks simultaneously. MU-Net achieved higher segmentation accuracy than state-of-the-art multi-atlas segmentation methods with an inference time of 0.35 seconds and no pre-processing requirements. We evaluated the performance of our network in the presence of skip connections and recently proposed framing connections, finding the simplest network to be the most effective. We tested MU-Net with an unusually large dataset combining several independent studies consisting of 1,782 mouse brain MRI volumes of both healthy and Huntington animals, and measured average Dice scores of 0.906 (striati), 0.937 (cortex), and 0.978 (brain mask). These high evaluation scores demonstrate that MU-Net is a powerful tool for segmentation and skull-stripping, decreasing inter and intra-rater variability of manual segmentation. The MU-Net code and the trained model are publicly available at https://github.com/Hierakonpolis/MU-Net.

bioinformatics↗

bioRxiv2019

Individual head models for estimating the TMS-induced electric field in rat brain

In transcranial magnetic stimulation (TMS), the initial cortical activation due to stimulation is determined by the state of the brain and the magnitude, waveform, and direction of the induced electric field (E-field) in the cortex. The E-field distribution depends on the conductivity geometry of the head. The effects of deviations from a spherically symmetric conductivity profile have been studied in detail in humans. In small mammals, such as rats, these effects are more pronounced due to their smaller and less spherical heads. In this study, we describe a simple method for building individual realistically shaped head models for rats from high-resolution X-ray tomography images. We computed the TMS-induced E-field with the boundary element method and assessed the effect of head-model simplifications on the estimated E-field. The deviations from spherical symmetry have large, non-trivial effects on the E-field distribution: in some cases, even the direction of the E-field in the cortex cannot be reliably predicted by the coil orientation unless these deviations are properly considered.

neuroscience↗