Publications

9 Feb 2023

A preliminary choroid plexus volumetric study in individuals with psychosis

The choroid plexus (ChP) is part of the blood-cerebrospinal fluid barrier, regulating brain homeostasis and the brain's response to peripheral events. Its upregulation and enlargement are considered essential in psychosis. However, the timing of the ChP enlargement has not been established. This study introduces a novel magnetic resonance imaging-based segmentation method to examine ChP volumes in two cohorts of individuals with psychosis. The first sample consists of 41 individuals with early course psychosis (mean duration of illness = 1.78 years) and 30 healthy individuals. The second sample consists of 30 individuals with chronic psychosis (mean duration of illness = 7.96 years) and 34 healthy individuals. We utilized manual segmentation to measure ChP volumes. We applied ANCOVAs to compare normalized ChP volumes between groups and partial correlations to investigate the relationship between ChP, LV volumes, and clinical characteristics. Our segmentation demonstrated good reliability (.87).

9 Feb 2023

Glioblastoma and cerebral organoids: development and analysis of an in vitro model for glioblastoma migration

It is currently challenging to adequately model the growth and migration of glioblastoma using two-dimensional (2D) in vitro culture systems as they quickly lose the original, patient-specific identity and heterogeneity. However, with the advent of three-dimensional (3D) cell cultures and human induced pluripotent stem cell (iPSC)-derived cerebral organoids (COs), studies demonstrate that the glioblastoma-CO (GLICO) co-culture model helps to preserve the phenotype of the patient-specific tissue. Here, we aimed to set up such a model using mature COs and develop a pipeline for subsequent analysis of co-cultured glioblastoma. Our data demonstrates that the growth and migration of the glioblastoma cell line within the mature COs are significantly increased in the presence of extracellular matrix proteins, shortening the time needed for glioblastoma to initiate migration. We also describe in detail the method for the visualization and quantification of these migrating cells within the GLICO model.

24 Jan 2023

Utilization of temporal autoencoder for semi-supervised intracranial EEG clustering and classification

Manual visual review, annotation and categorization of electroencephalography (EEG) is a time-consuming task that is often associated with human bias and requires trained electrophysiology experts with specific domain knowledge. This challenge is now compounded by development of measurement technologies and devices allowing large-scale heterogeneous, multi-channel recordings spanning multiple brain regions over days, weeks. Currently, supervised deep-learning techniques were shown to be an effective tool for analyzing big data sets, including EEG. However, the most significant caveat in training the supervised deep-learning models in a clinical research setting is the lack of adequate gold-standard annotations created by electrophysiology experts. Here, we propose a semi-supervised machine learning technique that utilizes deep-learning methods with a minimal amount of gold-standard labels. The method utilizes a temporal autoencoder for dimensionality reduction and a small number of the expert-provided gold-standard labels used for kernel density estimating (KDE) maps.

24 Jan 2023

Shadows of very high-frequency oscillations can be detected in lower frequency bands of routine stereoelectroencephalography

Very high-frequency oscillations (VHFOs, > 500 Hz) are more specific in localizing the epileptogenic zone (EZ) than high-frequency oscillations (HFOs, < 500 Hz). Unfortunately, VHFOs are not visible in standard clinical stereo-EEG (SEEG) recordings with sampling rates of 1 kHz or lower.

Here we show that "shadows" of VHFOs can be found in frequencies below 500 Hz and can help us to identify SEEG channels with a higher probability of increased VHFO rates.

Subsequent analysis of Logistic regression models on 141 SEEG channels from thirteen patients shows that VHFO "shadows" provide additional information to gold standard HFO analysis and can potentially help in precise EZ delineation in standard clinical recordings.

24 Jan 2023

Transient Reflexive Pain Responses and Chronic Affective Nonreflexive Pain Responses Associated with Neuroinflammation Processes in Both Spinal and Supraspinal Structures in Spinal Cord-Injured Female Mice

Central neuropathic pain is not only characterized by reflexive pain responses, but also emotional or affective nonreflexive pain responses, especially in women. Some pieces of evidence suggest that the activation of the neuroimmune system may be contributing to the manifestation of mood disorders in patients with chronic pain conditions, but the mechanisms that contribute to the development and chronicity of CNP and its associated disorders remain poorly understood. This study aimed to determine whether neuroinflammatory factor over-expression in the spinal cord and supraspinal structures may be associated with reflexive and nonreflexive pain response development from acute SCI phase to 12 weeks post-injury in female mice. The results show that transient reflexive responses were observed during the SCI acute phase associated with transient cytokine overexpression in the spinal cord.

12 Jan 2023

Small RNA Sequencing Identifies a Six-MicroRNA Signature Enabling Classification of Brain Metastases According to their Origin

Background/aim: Brain metastases (BMs) are the most frequent intracranial tumors in adults and one of the greatest challenges for modern oncology. Most are derived from lung, breast, renal cell, and colorectal carcinomas and melanomas. Up to 14% of patients are diagnosed with BMs of unknown primary, which are commonly characterized by an early and aggressive metastatic spread. It is important to discover novel biomarkers for early identification of BM origin, allowing better management of patients with this disease. Our study focused on microRNAs (miRNAs), which are very stable in frozen native and FFPE tissues and have been shown to be sensitive and specific diagnostic biomarkers of cancer. We aimed to identify miRNAs with significantly different expression in the five most frequent groups of BMs and develop a diagnostic classifier capable of sensitive and specific classification of BMs.

6 Jan 2023

White matter alterations in MR-negative temporal and frontal lobe epilepsy using fixel-based analysis

This study focuses on white matter alterations in pharmacoresistant epilepsy patients with no visible lesions in the temporal and frontal lobes on clinical MRI (i.e. MR-negative) with lesions confirmed by resective surgery. The aim of the study was to extend the knowledge about group-specific neuropathology in MR-negative epilepsy. We used the fixel-based analysis (FBA) that overcomes the limitations of traditional diffusion tensor image analysis, mainly within-voxel averaging of multiple crossing fibres. Group-wise comparisons of fixel parameters between healthy controls (N = 100) and: (1) frontal lobe epilepsy (FLE) patients (N = 9); (2) temporal lobe epilepsy (TLE) patients (N = 13) were performed. A significant decrease of the cross-section area of the fixels in the superior longitudinal fasciculus was observed in the FLE. Results in TLE reflected widespread atrophy of limbic, thalamic, and cortico-striatal connections and tracts directly connected to the temporal lobe (such as the anterior commissure, inferior fronto-occipital fasciculus, uncinate fasciculus, splenium of corpus callosum, and cingulum bundle). 

6 Jan 2023

The decline in stroke hospitalization due to COVID-19 is unrelated to COVID-19 intensity

Background and purpose: During the coronavirus disease 2019 (COVID-19) pandemic many countries reported a decline in stroke volumes. The aim of this study was to analyze if the decline was related to the intensity of the COVID-19 pandemic.

Methods: The first pandemic year (1 March 2020 to 28 February 2021) overall and during the three COVID-19 waves were compared with the preceding year. Volumes of acute ischaemic stroke (AIS), subarachnoid hemorrhage, intracerebral hemorrhage and recanalization treatments (intravenous thrombolysis [IVT] and mechanical thrombectomy [MT]) were obtained from the National Register of Reimbursed Health Services. Door-to-needle time, onset-to-door time and National Institutes of Health Stroke Scale at admission were obtained from the Registry of Stroke Care Quality.

Results: During the pandemic year compared to the preceding year there were 26,453 versus 28,771 stroke admissions, representing an 8.8% decline (p < 0.001). 

6 Jan 2023

Repetitive transcranial magnetic stimulation for hypokinetic dysarthria in Parkinson's disease enhances white matter integrity of the auditory-motor loop

Background and purpose: In our previous study, repeated sessions of repetitive transcranial magnetic stimulation (rTMS) over the auditory feedback area were shown to improve hypokinetic dysarthria (HD) in Parkinson's disease (PD) and led to changes in functional connectivity within the left-sided articulatory networks. We analyzed data from this previous study and assessed the effects of rTMS for HD in PD on the diffusion parameters of the left anterior arcuate fasciculus (AAF), which connects the auditory feedback area with motor regions involved in articulation.

Methods: Patients were assigned to 10 sessions of real or sham 1-Hz stimulation over the right posterior superior temporal gyrus. Stimulation effects were evaluated using magnetic resonance diffusion tensor imaging and by a speech therapist using a validated tool (Phonetics score of the Dysarthric Profile) at baseline, immediately after 2 weeks of stimulation, and at follow-up visits at Weeks 6 and 10 after the baseline.

6 Jan 2023

Prolonged survival in patients with local chronic infection after high-grade glioma treatment: Two case reports

Keywords: anaplastic astrocytoma; glioblastoma; high-grade glioma; prolonged survival; wound infection.

23 Dec 2022

rTMS treatment for hypokinetic dysarthria in Parkinson's disease enhances white matter integrity of the auditory-motor loop

Background: In our previous study, repeated sessions of repetitive transcranial magnetic stimulation (rTMS) over the auditory feedback area were shown to improve hypokinetic dysarthria (HD) in Parkinson's disease (PD) and led to changes in functional connectivity within the left-sided articulatory networks.

Objectives: We analyzed data from this previous study and assessed the effects of rTMS for HD in PD on the diffusion parameters of the left anterior arcuate fasciculus (AAF), which connects the auditory feedback area with motor regions involved in articulation.

Methods: Patients were assigned to ten sessions of real or sham 1 Hz stimulation over the right posterior superior temporal gyrus (STG). Stimulation effects were evaluated using magnetic resonance diffusion tensor imaging and by speech therapist using a validated tool (Phonetics score of the Dysarthric Profile) at baseline, immediately after 2 weeks of stimulation, and at follow-up visits at week 6 and 10 after the baseline.

19 Dec 2022

Impact of analgesic regimen on patient outcome following subarachnoid hemorrhage: positive adjuvant effects of metamizole

Introduction: Various analgesics are used to control intense headaches in patients following subarachnoid hemorrhage. In addition to pain control, it has been shown that some analgesics can affect various pathophysiological cascades. Therefore, we devised a study to assess whether the use of metamizole has a significant impact on the development of ischemic complications, hydrocephalus, and the overall outcome in patients following aneurysmal subarachnoid hemorrhage in the context of the other non-opioids and opioids effects.

Methods: In our retrospective, single-center cohort study, we enrolled 192 patients diagnosed with subarachnoid hemorrhage. We recorded their initial clinical status, comorbidities, and the daily dosage of analgesics over 14 days of hospitalization after the onset of subarachnoid hemorrhage. Using univariate and subsequent multivariate logistic regression analysis, we assessed the influence of various factors, including analgesics, on the development of delayed cerebral ischemia and hydrocephalus, as well as on 2-week and 6-month outcomes.

19 Dec 2022

The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location

Histone 3 lysine27-to-methionine (H3-K27M) mutations most frequently occur in diffuse midline gliomas (DMGs) of the childhood pons but are also increasingly recognized in adults. Their potential heterogeneity at different ages and midline locations is vastly understudied. Here, through dissecting the single-cell transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs, we delineate how age and anatomical location shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. We show that stem-like oligodendroglial precursor-like cells, present across all clinico-anatomical groups, display varying levels of maturation dependent on location. We reveal a previously underappreciated relationship between mesenchymal cancer cell states and age, linked to age-dependent differences in the immune microenvironment. Further, we resolve the spatial organization of H3-K27M DMG cell populations and identify a mitotic oligodendroglial-lineage niche.

9 Dec 2022

A new approach to the determination of tubular membrane capacitance: passive membrane electrical properties under reduced electrical conductivity of the extracellular solution

The transverse-axial tubular system (tubular system) of cardiomyocytes plays a key role in excitation-contraction coupling. To determine the area of the tubular membrane in relation to the area of the surface membrane, indirect measurements through the determination of membrane capacitances are currently used in addition to microscopic methods. Unlike existing electrophysiological methods based on an irreversible procedure (osmotic shock), the proposed new approach uses a reversible short-term intermittent increase in the electrical resistance of the extracellular medium. The resulting increase in the lumen resistance of the tubular system makes it possible to determine separate capacitances of the tubular and surface membranes. Based on the analysis of the time course of the capacitive current, computational relations were derived to quantify the elements of the electrical equivalent circuit of the measured cardiomyocyte including both capacitances. 

9 Dec 2022

Use of free radial forearm and pronator quadratus muscle flap: Anatomical study and clinical application

The authors present an anatomical study and clinical experience with radial forearm flap (RFF) and pronator quadratus muscle (PQM) application in the reconstruction of various body areas. The aim was to describe the anatomical placement and proportions of the PQM, the anatomical location of the major arterial branch of the radial artery supplying the PQM, and the application of this knowledge in clinical practice. The anatomical study was based upon an analysis of 13 fresh adult cadaver upper extremities, of which nine were female and four male; both arms from the same donors were used in four cases. The study of the PQM was performed using a dye-containing intraarterial injection, standard macro- and micro-preparation techniques, and chemical digestion. The data on the PQM size in males and females, thickness of the radial artery branch (the principal artery nourishing the muscle), and its position were analysed. The radial artery branch nourishing the PQM was identified in all cadaveric specimens of the anatomical study.

9 Dec 2022

Immune system disorders in the early post-injury period in patients after severe brain injury from the perspective of the severity of the injury

Background: Brain injuries are the most common cause of death in productive age. Besides the extent of the injury, other systemic factors can also affect the outcome. Patients suffering from severe brain injury often experience extracranial inflammatory complications during the early period of treatment. Here, we investigate the changes in immunity in patients with brain injury.

Methods: 121 patients and 92 healthy controls were included in the research. Blood samples were collected on admission and analyzed by flow cytometry and biochemical methods. Multiple clusters of differentiation (CD) and antibody levels were investigated. The results were compared between patients and controls. In addition, results of two classes of severity (Glasgow Coma Scale, GCS, of 3-5 vs. 6-8) were also compared.

9 Dec 2022

Model-informed unsupervised deep learning approaches to frequency and phase correction of MRS signals

Purpose: A supervised deep learning (DL) approach for frequency and phase correction (FPC) of MRS data recently showed encouraging results, but obtaining transients with labels for supervised learning is challenging. This work investigates the feasibility and efficiency of unsupervised deep learning-based FPC.

Methods: Two novel deep learning-based FPC methods (deep learning-based Cr referencing and deep learning-based spectral registration), which use a priori physics domain knowledge, are presented. The proposed networks were trained, validated, and evaluated using simulated, phantom, and publicly accessible in vivo MEGA-edited MRS data. The performance of our proposed FPC methods was compared with other generally used FPC methods, in terms of precision and time efficiency. A new measure was proposed in this study to evaluate the FPC method performance. 

9 Dec 2022

Perinatal maternal mental health and amygdala morphology in young adulthood

The pre- and perinatal environment is thought to play a critical role in shaping brain development. Specifically, maternal mental health and maternal care have been shown to influence offspring brain development in regions implicated in emotional regulation such as the amygdala. In this study, we used data from a neuroimaging follow-up of a prenatal birth-cohort, the European Longitudinal Study of Pregnancy and Childhood, to investigate the impact of early postnatal maternal anxiety/co-dependence, and prenatal and early-postnatal depression and dysregulated mood on amygdala volume and morphology in young adulthood (n = 103). We observed that in typically developing young adults, greater maternal anxiety/co-dependence after birth was significantly associated with lower volume (right: t = -2.913, p = 0.0045, β = -0.523; left: t = -1.471, p = 0.144, β = -0.248) and non-significantly associated with surface area (right: t = -3.502, q = 0.069, <10%FDR, β = -0.090, left: t = -3.137, q = 0.117, <10%FDR, = -0.088) of the amygdala in young adulthood.