15 Jul

Multifocal Noninvasive Deep Brain Stimulation to Enhance Cognition in Mild Cognitive Impairment: A Crossover Trial

Importance: Impairment of working memory (WM), which relies on distributed cortical and subcortical structures, including cerebello-striatal pathways, is a core contributor to functional decline in patients with mild cognitive impairment (MCI) and dementia. Because the striatum is affected early in dementia, whereas the cerebellum remains relatively preserved, the cerebellum may offer support for maintaining striatal function in neurodegenerative diseases.

Objective: To evaluate whether sequential cerebellar transcranial magnetic stimulation (TMS) and striatal transcranial temporal interference stimulation (tTIS) enhances WM in patients with MCI, especially those with early striatal degeneration, like MCI with Lewy bodies (MCI-LB).

Design, setting, and participants: This randomized, quadruple-blind, placebo-controlled, crossover trial was conducted from August 2023 to October 2024 at 1 site in Switzerland and 1 in Czech Republic. Participants included individuals with MCI-LB or amnestic MCI (aMCI) and age-matched healthy controls (HCs).

15 Jul

Relative entropy as a biomarker for vagus nerve stimulation response in epilepsy: Insights from intracerebral electroencephalography

Objective: This study aims to analyze differences in pre-implantation invasive electroencephalographic (IEEG) data between vagus nerve stimulation (VNS) responders (>50% seizure reduction) and VNS nonresponders (<50% seizure reduction).

Methods: We retrospectively identified 19 patients with drug-resistant focal epilepsy who underwent IEEG followed by VNS implantation instead of resective brain surgery. Resting-state IEEG recordings (30 min) were selected for all patients. Three biomarkers were analyzed in the IEEG data: (1) the number of interictal epileptiform discharges (IEDs), (2) the number of high-frequency oscillations (HFOs; ripples: 80-250 Hz, fast ripples: 250-600 Hz), and (3) relative entropy (all frequency bands, 80-250 Hz, and 250-600 Hz). Analyses were performed in three regions of interest: (1) the all contact zones (ACZ), (2) the seizure-onset zones (SOZ), and (3) the non-seizure onset zones (NON SOZ). Differences between VNS responders and nonresponders were then evaluated. Finally, a statistical classifier was constructed to predict VNS efficacy based on all three biomarkers in the ACZ, SOZ, and non-SOZ.

15 Jul

Ultrafast oscillations in the human brain and their functional significance

Objective: The upper frequency limit of human brain activity remains unknown. Using ultrahigh sampling rate (≥20 kHz) intracranial microelectroencephalography, this study aimed to systematically explore and quantitatively characterize brain field oscillations beyond the established high-frequency oscillation range (>2 kHz), and to determine their relationship to epileptogenic tissue.

Methods: We analyzed intracranial electroencephalographic recordings from 15 patients with drug-resistant epilepsy, comprising 466 microcontacts and 434 macrocontacts implanted in mesiotemporal structures across four international epilepsy centers. A custom spectrogram-based detector optimized for ultrahigh frequencies was developed to identify ultrafast oscillations (UFOs; >2 kHz). UFO rates were assessed in epileptic (successfully resected) and nonepileptic hippocampi and compared with established electrophysiological biomarkers, including interictal epileptiform discharges, ripples, and fast ripples. Statistical comparisons were performed using mixed-effects models to account for intersubject and interelectrode variability.

15 Jul

Real-world effectiveness of cenobamate in drug-resistant and ultra-refractory epilepsy: A multicenter study

Objective: To evaluate the real-world effectiveness, safety, and treatment retention of cenobamate (CNB) in patients with drug-resistant epilepsy (DRE), including ultra-refractory epilepsy (URE), high seizure burden, and extensive prior treatment history.

Methods: We conducted a retrospective, multicenter study of 500 adults with DRE (focal or combined epilepsy) who were treated with CNB at three Czech tertiary epilepsy centers. Among these patients, 83.4% met criteria for URE. Seizure outcomes, treatment retention, and adverse events were analyzed, with stratification by treatment duration and cumulative ASM exposure (number of previous and concomitant anti-seizure medications). Primary outcomes were ≥ 50% responder rate and seizure freedom at 12 months.

Results: Among 436 patients with evaluable seizure data after ≥ 3 months of CNB treatment, 55.7% achieved ≥ 50% seizure reduction and 16.5% became seizure-free. At 12 months (n = 331), ≥ 50% response was achieved in 61.6%, and 18.1% became seizure-free. 

15 Jul

Comparison of bi- and tri-component approaches for the analysis of short-T2* tissues in the presence of fat: application to the Achilles tendon

Objective: To evaluate how data acquisition and post-processing choices influence ultrashort echo time (UTE)-based characterization of the short-T₂^* compositional structure of the Achilles tendon.

Methods: Ten healthy volunteers (33.3 ± 6.9 years) underwent Achilles tendon MRI using a multi-echo, time-interleaved UTE sequence. T₂^* data were analyzed with and without fat suppression using two models: (i) a bi-component decay with two water pools and (ii) a tri-component decay including two water components and one fat component. The effect of magnitude versus complex fitting on compositional estimates was also assessed. Three Achilles tendon regions were analyzed: insertion (INS), mid-portion (MID), and muscle-tendon junction (MTJ).

Results: Estimated short vs. long T₂^* components differed significantly depending on the use of fat suppression (p < 0.001 for all tendon regions) and fitting method (magnitude vs. complex) (p_INS = 0.002, p_MID < 0.001, p_MTJ < 0.001). T₂^* time constants were comparatively stable, particularly in the MID part (p > 0.05). 

9 Jun

The correlates of hyperechogenicity of the substantia nigra in subjects at risk of dementia with Lewy bodies

Substantia nigra hyperechogenicity (SN+) detected by transcranial sonography (TCS) has been proposed as a risk marker for synucleinopathies, particularly Parkinson's disease. Its role in prodromal dementia with Lewy bodies (DLB) remains insufficiently explored. To examine clinical, cognitive, genetic, EEG, and plasma biomarker differences between SN+ and normal echogenicity (SN-) individuals in a well-characterized at-risk-of-DLB cohort, with additional sex-stratified analyses. A total of 121 participants aged 55-70 years from an at-risk-of-DLB cohort underwent TCS, neurological and neuropsychological assessment, nighttime wrist actigraphy, high-density EEG, genetic testing for APOE allelic variants, and plasma biomarker analysis (NfL, GFAP, pTau181). SN status was defined using laboratory-specific cut-offs. Group differences were assessed using non-parametric statistics with relevant corrections for multiple comparisons and adjustment for age. SN+ status as compared to SN- status was associated with poorer verbal memory performance and altered visuo-constructive performance (driven mostly by males), and significant differences in distinct actigraphy-derived sleep parameters. 

21 Apr

Global coincident bursts of high frequency oscillations across the human cortex coordinate large-scale memory processing

Oscillations in the high gamma and ripple frequency ranges are known to coordinate local hippocampal and neocortical neuronal assemblies during memory encoding and recall. Here, we explored spatiotemporal dynamics and the role of global coordination of these fast oscillatory discharges across the sensory and associational cortical areas in distinct phases of memory processing. Individual bursts of high frequency oscillations were detected in intracranial recordings from epilepsy patients remembering word lists for immediate free recall. We found constant coincident bursting across visual and higher order processing areas, peaking before recall and elevated during encoding of words. This global co-bursting was modulated by memory processing, engaged approximately half of the recorded electrode contact sites, and clustered into a sequence of multiple consecutive bursting events. Our results suggest a general role of global coincident high frequency oscillations in organizing large-scale information processing across the brain necessary especially, but not exclusively, for memory functions.

21 Apr

Dynamic functional connectivity is related to cognitive performance of prodromal Lewy body dementia

Keywords: Cognitive domains; Dynamic connectivity states; Dynamic functional connectivity; Fast eigenvector centrality; Prodromal Lewy body dementia; Resting state fMRI.