Publications

16 Mar

Language network disruption in patients with Lewy body diseases

Lewy body diseases, including Parkinson’s disease and dementia with Lewy bodies, are marked by neuronal α‑synuclein aggregation, motor parkinsonism, cognitive impairment and diverse non‑motor symptoms including communication impairments. Compared to other symptoms, non‑motor communication impairments remain under-explored, especially outside English‑speaking cohorts. The aim of this study was to elucidate the neural underpinnings of linguistic deficits as assessed by fMRI in Czech-speaking patients diagnosed with neuronal Lewy body disease and mild cognitive impairment (LBD-MCI). Scores from the Short Neuropsychological Battery and resting‑state functional MRI data were analyzed in 26 Czech‑speaking patients with LBD‑MCI and 24 healthy controls. Analyses targeted regions of interest within the dorsal and ventral language networks. We applied graph theory metrics, within‑network connectivity and seed‑based functional connectivity analysis. Graph analysis revealed dorsal‑stream disruption in LBD‑MCI: reduced clustering coefficient, increased path length, and diminished node strength, each correlating with language functions; ventral‑stream topology remained intact. Within‑network analyses showed impaired connectivity across both pathways, but weaker coupling between the opercular inferior frontal gyrus and posterior superior temporal gyrus predicted behavioral scores in language functioning, further highlighting dorsal vulnerability. Seed‑based analysis identified reduced frontotemporal connectivity in the dorsal stream and decreased fronto‑occipital and temporo-cerebellar connections in the ventral stream. 

16 Mar

Intracranial electroencephalographic connectivity analysis to localize epileptogenic networks: Systematic review and meta-analysis from ILAE Epilepsy Surgery Networks Task Force

Intracranial electroencephalographic (iEEG) connectivity analysis is a promising method to localize epileptic networks and guide surgical planning in focal drug-resistant epilepsy. Despite numerous studies exploring its utility, the added value of iEEG connectivity over standard clinical presurgical evaluation remains unclear. We assess the current evidence on the efficacy of iEEG connectivity analyses to improve seizure outcomes following epilepsy surgery through a systematic review and meta-analysis. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) reporting guidelines, we searched PubMed and Embase for studies (2006-2024) of adult focal drug-resistant epilepsy patients who underwent surgical resection or ablation, reported outcomes at least 1 year postsurgery, and used iEEG connectivity analysis to localize networks. Reviews, nonhuman studies, and studies lacking iEEG connectivity analysis or network localization were excluded. We derived classification metrics (true/false positives/negatives) based on concordance between iEEG findings, clinical localization, and outcome. Subgroup meta-analyses and meta-regressions determined differences by seizure type, lesion status, and analysis approach. Of 2881 studies screened, 25 met criteria (n = 909). The pooled odds ratio comparing seizure outcome prediction using iEEG connectivity versus standard clinical evaluation was 1.36 (95% confidence interval = 1.10-1.69, p = .004), indicating a significant overall benefit. 

16 Mar

PRPF8-associated retinitis pigmentosa variant induces human neural retina-autonomous photoreceptor defects

Retinitis pigmentosa (RP) is an inherited retinal disorder characterized by the progressive loss of photoreceptors that currently lacks effective treatment. Here, we investigated the effects of the PRPF8-Y2334N variant on neural retina cells using human induced pluripotent stem cell (hiPSC)-derived retinal organoids. Expression of PRPF8-Y2334N variant resulted in photoreceptor defects, including thinning of the outer segment layer. This indicates that the neural retina is impacted independently of retinal pigment epithelium (RPE). At the molecular level, we observed relatively minor changes in mRNA expression in multiple retinal cells. We also found splicing alterations in genes associated with neural and retinal diseases, including those involved in intraflagellar transport, suggesting that these genes may represent common targets of splicing factor mutations. Finally, we detected the misexpression of several circular RNAs (circRNAs), which could serve as early biomarkers of splicing defects caused by RP mutations. Together, we present a model of RP that recapitulates photoreceptor degeneration and demonstrates that these defects are independent of RPE degeneration.

16 Mar

Local Field Aperiodic Spectral Power Modulated by Deep Brain Stimulation in Parkinson's Disease

Background: Aperiodic spectral broadband power has been described recently as reflecting Parkinson's disease (PD) severity. It has therefore become an increasing focus of research interest in the context of the new adaptive deep brain stimulation (DBS) approach.

Objective: We aimed to study the influence of DBS on the main parameters of the aperiodic spectral component of local field potentials (LFPs).

Methods: LFPs were recorded from the subthalamic nucleus (STN) in patients with PD (n = 22) during a simple experimental paradigm that included 5 minutes of resting state and a short gait task during DBS OFF and ON conditions (off medication). Classical spectral analysis was performed using fast Fourier transform; the analysis of the aperiodic component was performed by fitting oscillations and a one-over-F approach. In a subset of the patients (n = 14), it was possible to evaluate the symptom progression over time after 1 year by analyzing the control measurement.

Results: The severity of hypokinetic/rigid symptomatology, measured by International Parkinson and Movement Disorders Society Unified Parkinson's Disease Rating Scale, correlated significantly with both of the aperiodic components characteristics of the STN LFPs: the slope and the offset. These parameters were significantly modified by DBS, as evaluated with a Wilcoxon signed-rank test during the resting state and during the gait task. 

13 Feb

Complex multi-echo fMRI dataset: New strategies in processing of multi-echo data

This publication introduces a novel, publicly available dataset designed to support the development and evaluation of advanced algorithms and processing workflows for complex multi-echo functional magnetic resonance imaging (fMRI) data.

The dataset comprises multi-echo fMRI and electrophysiological recordings collected from 83 healthy, right-handed adult participants.

Data was acquired with two 3 T MR scanners and is available on OpenNeuro under the title "Complex multi-echo fMRI dataset: New strategies in processing of multi-echo data".

13 Feb

Effectiveness of brief semiological training in distinguishing functional/dissociative seizures from epileptic seizures

Objective: Functional/dissociative seizures are seizures that mimic epileptic seizures in their presentation and are often mistaken for them. Clinical recognition of these seizures presents a challenge and misdiagnosis can lead to inappropriate treatment, increasing the risk of complications. To address this, we conducted a study involving 45 young neurology residents from the Czech Republic and Slovakia who had no specialized training in epilepsy or functional neurological disorders. Our goal was to determine whether a brief training in selected semiological features of functional/dissociative seizures (FDS) would efficiently teach them to differentiate between FDS and epileptic seizures (ES) in a clinical setting.

Methods: A set of 10 clinical signs characteristic of FDS was selected based on Evidence-Based Practice for the Clinical Assessment of Psychogenic Nonepileptic Seizures (Baslet et al., 2021). Initially, participants identified epileptic seizures and FDS in 30 video recordings without any prior instruction. Subsequently, they received a 15-minute educational session focused on selected semiological features of FDS. Then the same 30 seizure videos were shown again to assess their recognition abilities. No EEG recordings were shown.

Results: Following this educational intervention, participants' accuracy in distinguishing FDS from ES significantly improved from 77% before training to 89% after training (p < 0.001).

13 Feb

Timing for Starting Antiseizure Medication Withdrawal After Epilepsy Surgery in Adults

Background and objectives: More than half of people undergoing epilepsy surgery become seizure-free and may consider withdrawing antiseizure medications (ASMs). Withdrawal practices vary, and the optimal timing remains unclear. We aim to compare seizure relapse risk among individuals initiating ASM withdrawal at different time points after epilepsy surgery.

Methods: We conducted a multicenter observational cohort study of adults who underwent resective epilepsy surgery between 1990 and 2016 at 12 tertiary centers. Participants were seizure-free before medication withdrawal and had at least 1 year of follow-up. Seizure relapse risk was compared among those initiating withdrawal 1, 2, 3, 4, or 5 years postoperatively vs later. We used propensity score matching for each comparison to adjust for treatment selection bias.

Results: Of the 964 people included (51% female; median age at surgery 34 years [interquartile range 26-44]), 446 (46%) began ASM withdrawal in the first year after surgery, 255 (26%) in the second, 110 (11%) in the third, 58 (6%) in the fourth, 29 (3%) in the fifth, and 66 (7%) after the fifth year. After matching, those starting withdrawal in the first (hazard ratio [HR] 1.4; p = 0.003) or second (HR 1.18; p < 0.001) year had a higher risk of relapse than those who withdrew later. Starting withdrawal in the third (HR 1.7; p = 0.12), fourth (HR 1.3; p = 0.45), or fifth (HR 0.17; p = 0.82) year after surgery showed no increase in risk compared with later withdrawal. 

22 Jan

GLP-1 Receptor Agonists for Secondary Prevention After Myocardial Infarction and Stroke in Type 2 Diabetes: Nationwide Real-World Evidence

Aims: Glucagon-like peptide-1 receptor agonists (GLP-1RA) reduce cardiovascular risk in patients with type 2 diabetes (T2D) and established atherosclerotic cardiovascular disease and are recommended in guidelines. We evaluated the real-world effectiveness of GLP-1RA therapy on cardiovascular outcomes in patients with T2D after myocardial infarction (MI) or ischemic stroke and examined trends and disparities.

Methods: Using nationwide Czech registry data (2015-2024), we identified patients with incident nonfatal MI or ischemic stroke and confirmed T2D. GLP-1RA users-initiating therapy within 12 months post-event-were propensity score-matched to non-users. The primary outcome was major adverse cardiovascular events (MACE: nonfatal MI, nonfatal stroke, cardiovascular death); secondary outcomes included individual components and all-cause mortality.

Results: GLP-1RA therapy was initiated in only ∼2% of MI and stroke survivors with T2D. Among 126,845 MI survivors, 28,206 had T2D; the matched cohort comprised 2,271 patients (401 GLP-1RA; median follow-up 35 months). GLP-1RA use was associated with lower risk of MACE (HR:0.7; 95%CI:0.52-0.93), all-cause (HR:0.61;95%CI:0.47-0.80) and cardiovascular death (HR:0.54, 95%CI:0.36-0.80). Among 177,115 stroke survivors, 73,750 had T2D; the matched cohort comprised 2,235 patients (385 GLP-1RA; median follow-up 27 months). 

22 Jan

The Assessment of RAB32 p.Ser71Arg Variant Prevalence in Parkinson's Disease Across Selected African, European, and South American Cohorts

Monogenic forms of Parkinson's disease (PD) have demonstrated a heterogeneous disorder involving multiple biological pathways.¹ Familial forms of PD have been linked to variants in LRRK2, SNCA, VPS35, PARKIN, and PINK1.¹ Heterozygous GBA mutation carriers are associated with higher disease risk, earlier onset, and accelerated clinical progression.¹

Recently, RAB32 has emerged as a nominated PD gene. It encodes a Rab GTPase involved in mitochondrial and vesicular trafficking pathways. A rare substitution, p.Ser71Arg (rs200251693), has been proposed as a potential susceptibility factor.^2, 3 Reported carriers exhibit late-onset, levodopa-responsive parkinsonism with familial clustering; the only available autopsy case lacked Lewy bodies.^1-3 Across published studies, RAB32 c.213C>G was detected in 0.22% to 2.3% of patients, primarily within Mediterranean and North American cohorts, and was absent in large East Asian datasets. This pattern suggests regional specificity and a possible shared Mediterranean haplotype.^2-6 Limited data exist from several regions, including Eastern Europe, Ireland, sub-Saharan Africa, and South America.

22 Jan

Influence of hypokinetic dysarthria severity level on the long-term outcome of repetitive transcranial magnetic stimulation therapy

Introduction: Hypokinetic dysarthria (HD) is a common and disabling symptom of Parkinson's disease (PD) for which established pharmacological and surgical treatments bring only limited, often short-term improvement in speech. The aim of this study was to investigate whether the long-term acoustic effects of repetitive transcranial magnetic stimulation (rTMS) over the right superior temporal gyrus (STG) depend on the baseline severity of HD.

Methods: 26 PD patients were randomized to active STG-targeted rTMS (n = 15) or sham stimulation (n = 11) and followed across five recording sessions over 14 weeks, alongside one session of matched healthy controls. HD severity at baseline was quantified using 3F test subscores and used to stratify patients into milder (0) and more severe (1) subgroups. The STG 1 subgroup combined greater motor and speech impairment with shorter disease duration. Multiple acoustic features from sustained phonation and free monologue were extracted, normalized to controls, adjusted for sex, and analyzed using non-parametric statistics and descriptive visualisations.

Results: Patients with more severe HD receiving active stimulation (STG 1) showed consistent, long-lasting improvements in phonation-related parameters, whereas milder HD (STG 0) and sham groups (SHAM 0, SHAM 1) exhibited only limited or transient changes.

5 Jan

Network hubs supporting memory encoding: Implications for cognitive preservation in epilepsy surgery

Objective: Memory impairments are common in neurological disorders, especially drug-resistant epilepsy, where cognitive deficits such as accelerated long-term forgetting may occur before surgery due to interictal/ictal discharges, antiseizure medications, and disease progression. Postsurgical memory decline affects 40%-60% of patients. Understanding the neural mechanisms of memory encoding is essential for identifying critical network hubs and guiding surgical interventions that preserve cognitive function.

Methods: We analyzed intracranial electroencephalographic recordings from epilepsy patients (n = 15) performing a verbal memory encoding task to identify key structures involved in successful memory formation. Functional connectivity was computed using multiple features across several frequency bands. Temporal dynamics of connectivity were examined to characterize pre-encoding and encoding phases.

Results: The middle temporal gyrus (MTG) consistently emerged as a verbal memory hub across features and frequency bands. The inferior frontal gyrus (IFG) was identified as a beta-band-specific hub via phase synchrony. Temporal analyses revealed that MTG exhibited stable and widespread connectivity differences across all encoding phases, suggesting a role in pre-encoding network priming. 

5 Jan

Functional Impact Score of Mitochondrial Variants and Its Relationship With Functional Connectivity of the Brain: Potential Origins of Premature Aging in Young Adulthood

Alterations in mitochondrial DNA (mtDNA) have been associated with worse cognitive abilities in older adults and premature epigenetic aging in young adulthood. However, it is not clear how mitochondrial dysfunction affects brain function in young adulthood and whether cognition-related networks might be most affected. We tested whether mtDNA functional impact (FI) score might map onto specific patterns of between-network functional connectivity in young adults from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC). We also tested whether these relationships might be mediated by accelerated epigenetic aging, calculated using Horvath's epigenetic clock, CheekAge clock, and AltumAge clock. General connectivity method was used as a reliable marker of individual differences in brain function. We showed that a greater mtDNA FI score was associated with lower connectivity between the dorsal attention and language networks (beta = -0.41, p = 0.0007, AdjR² = 0.15) and that there was suggestive evidence that this relationship might be mediated by accelerated epigenetic aging calculated using Horvath's epigenetic clock in young adulthood (ab = -0.061, SE = 0.04, 95% CI [-0.163; 0.001], 90% CI [-0.142; -0.002]). These findings were independent of sex, current BMI, and current substance use. 

10 Dec 2025

Limitations of multiexponential T1 mapping of cortical myeloarchitecture

Neuropsychiatric malignancies frequently manifest at the level of individual cortical layers. The resolutions currently available for medical magnetic resonance imaging (MRI) prevent the study of these pathologies at clinically available field strengths of 3 T. Previous studies have claimed to have overcome these issues by extensions of quantitative MRI. Following this, the feasibility of multiexponential T1 relaxometry was assessed as a basis for in vivo delineation of cortical lamination. Three methods of non-linear least-squares-based multiexponential analysis were examined across key degrees of freedom identified in the literature. The methods employ a wide variety of ways to overcome the common pitfalls of multiexponential analysis, such as regularization, bound constraints, and repeated optimization from multiple starting points. A custom MRI phantom was 3D-printed and filled with various MnCL2 mixtures that represent the spin-lattice relaxation times that commonly occur in neocortical gray and white matter at 3 T. A 96 × 96-voxel image consisting of a single slice was acquired using a FLASH sequence and used to create 10 composite datasets with known distributions of T1 decay constants. The results showed that lowest relative error achieved across multiexponential models was approximately 20%. 

10 Dec 2025

Ultra-refractory epilepsy: The newly described entity

Objective: Drug-resistant epilepsy (DRE) is defined as the failure of two antiseizure medications (ASMs) to achieve complete seizure control, affecting approximately 30% of epilepsy patients. In some cases, additional ASMs and surgical approaches are also unsuccessful. Ultra-Refractory Epilepsy (URE) is a newly described entity, characterized by the failure of six distinct epilepsy treatment strategies, including ASMs, surgical resection, and neurostimulation techniques. This study aimed to analyze demographic and clinical data of URE patients managed at the Brno Epilepsy Center, a member of the European Reference Network (ERN)-EpiCARE.

Methods: We conducted a retrospective cohort study with a prospective follow-up component. Adult patients hospitalized for epilepsy at the Brno Epilepsy Center between 2017 and 2023 were retrospectively identified, and their outcomes were prospectively assessed in February 2025 through medical record review and structured telephone interviews. URE patients were identified, and their demographic and clinical data were analyzed.

Results: In this study, 1034 patients' charts were reviewed, and 62 patients (6%) met the criteria for URE. In the URE cohort, the median age of epilepsy onset was 9 years (range 1-60 years), and the median age at the time of evaluation was 35 years (range 21-67 years).

28 Nov 2025

Sentence comprehension in Lewy body diseases: a functional magnetic resonance imaging study

Lewy body diseases, including Parkinson's disease and dementia with Lewy bodies, often involve mild cognitive impairment at diagnosis (mild cognitive impairment with Lewy bodies (MCI-LB). Language dysfunction in MCI-LB patients is often unrecognized. This study aimed to assess syntactic comprehension deficits in MCI-LB patients and to explore their neural correlates. A total of 25 MCI-LB patients (mean ± sd: 72 ± 5.6 years old, 10 women) and 25 healthy controls (HC, mean ± sd: 66 ± 4.0 years old, 12 women) performed task functional MRI Test of Sentence Comprehension (ToSC). Functional connectivity was analysed using psychophysiological interaction (PPI) method, focusing on the striatum and language networks. MCI-LB patients had lower ToSC scores than HC (MCI-LB: 74.7 ± 15.7, HC: 88.5 ± 9.0, P < 0.001) and their PPI analysis revealed decreased connectivity from the striatum to the cuneus, precuneus, and left supramarginal gyrus, and reduced connectivity particularly in the dorsal pathway during noncanonical (syntactically more complex) sentence processing. Taken together, in this cross-sectional study MCI-LB patients showed impaired sentence comprehension related to decreased subcortical-cortical and dorsal language network connectivity. 

28 Nov 2025

The Pattern Glare Test: Further Exploration of Methodological and Demographic Factors

Purpose: The Pattern Glare Test (PGT) is a widely used tool for assessing visual discomfort and perceptual distortions elicited by repetitive, high-contrast patterns. It has been applied across diverse populations and research fields, including neuroscience, cognitive psychology, optometry, orthoptics, and ophthalmology. Despite its broad use, considerable variation exists in how the PGT is implemented, particularly regarding stimulus parameters, participant characteristics, and scoring methods. Such variability introduces potential confounding factors that may obscure the psychological and neurological mechanisms underlying pattern-induced visual discomfort.

Methods: We analyzed PGT data from 184 neurotypical young adults (72 males and 112 female; mean age = 24.29 years, SD = 4.75) to examine methodological influences on reports of associated visual distortions (AVDs) and discomfort. Our main analyses utilized cumulative link mixed models and cluster analysis of intraindividual responses.

Results: Significant effects of trial progression and sex (biological; male/female) on subjective responses have been revealed, with the effect of sex not accounted for by migraine occurrence. Substantial overlap among color-related AVDs supported their consolidation into a single category. 

19 Nov 2025

Digital speech biomarkers for assessing cognitive decline across neurodegenerative conditions

This study investigates speech impairments in individuals with mild cognitive impairment due to Alzheimer's disease (MCI-AD), mild cognitive impairment with Lewy bodies (MCI-LB), and Parkinson's disease with mild cognitive impairment (PD-MCI), compared to healthy controls (HC), aiming to identify linguistic and acoustic digital biomarkers that differentiate these groups. Monologue recordings were collected from 68 HC, 42 MCI-AD, 50 MCI-LB, and 47 PD-MCI participants (ON state). Participants were instructed to speak spontaneously for one and a half minutes. Speech was automatically transcribed, manually corrected, and analyzed using natural language processing to extract eight linguistic (lexical/syntactic) and four acoustic (prosodic) biomarkers. Group differences were assessed using the Mann-Whitney U test, with Spearman's correlation used to examine associations with clinical and MRI measures (FDR-corrected). Machine learning models (XGBoost) were applied to evaluate the classificatory and predictive potential of speech features. Distinct speech patterns were observed across groups: MCI-AD participants exhibited reduced use of function words, resulting in increased content density, PD-MCI participants used shorter sentences and fewer coordinating conjunctions with longer pauses, and MCI-LB participants exhibited greater lexical repetition than MCI-AD. 

19 Nov 2025

Non-invasive Temporal Interference Stimulation of the Hippocampus Suppresses Epileptic Biomarkers in Patients with Epilepsy: Biophysical Differences between Kilohertz and Amplitude Modulated Stimulation

Introduction: Medication-refractory focal epilepsy creates a significant clinical challenge, with approximately 30% of patients deemed ineligible for surgery due to involvement of eloquent cortical regions within the epileptogenic network. For these patients, electrical neuromodulation represents a promising alternative therapy. We investigated the potential of non-invasive temporal interference (TI) electrical stimulation in reducing epileptic biomarkers in patients with mesiotemporal epilepsy (MTLE) MATERIAL AND METHOD: Thirteen patients implanted with stereoelectroencephalography (sEEG) depth electrodes received TI stimulation with an amplitude modulation (AM) frequency of 130 Hz (Δf), delivered through either low-frequency (1 kHz + 1.13 kHz) or high-frequency (9 kHz + 9.13 kHz) carrier waves, specifically targeting the hippocampus-a common epileptic focus in MTLE. Intracerebral recordings before, during, and after TI stimulation were compared to recordings during sham stimulation at varying high-frequency (HF) carrier frequencies (1, 2, 5, and 9 kHz).