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).