Adolescent alcohol consumption predicted by differences in electrophysiological functional connectivity and neuroanatomy.

Alcohol consumption during adolescence has been associated with neuroanatomical abnormalities and the appearance of future disorders. However, the latest advances in this field point to the existence of risk profiles which may lead to some individuals into an early consumption. To date, some studies have established predictive models of consumption based on sociodemographic, behavioral, and anatomical-functional variables using MRI. However, the neuroimaging variables employed are usually restricted to local and hemodynamic phenomena. Given the potential of connectome approaches, and the high temporal dynamics of electrophysiology, we decided to explore the relationship between future alcohol consumption and electrophysiological connectivity measured by MEG in a cohort of 83 individuals aged 14 to 16. As a result, we found a positive correlation between alcohol consumption and the functional connectivity in frontal, parietal, and frontoparietal connections. Once this relationship was described, multivariate linear regression analyses were used to evaluate the predictive capacity of functional connectivity in conjunction with other neuroanatomical and behavioral variables described in the literature. Finally, the multivariate linear regression analysis determined the importance of anatomical and functional variables in the prediction of alcohol consumption but failed to find associations with impulsivity, sensation seeking, and executive function scales. In conclusion, the predictive traits obtained in these models were closely associated with changes occurring during adolescence, suggesting the existence of different paths in neurodevelopment that have the potential to influence adolescents' relationship with alcohol consumption.

Functional connectivity across the lifespan: a cross-sectional analysis of changes.

In the era of functional brain networks, our understanding of how they evolve across life in a healthy population remains limited. Here, we investigate functional connectivity across the human lifespan using magnetoencephalography in a cohort of 792 healthy individuals, categorized into young (13 to 30 yr), middle (31 to 54 yr), and late adulthood (55 to 80 yr). Employing corrected imaginary phase-locking value, we map the evolving landscapes of connectivity within delta, theta, alpha, beta, and gamma classical frequency bands among brain areas. Our findings reveal significant shifts in functional connectivity patterns across all frequency bands, with certain networks exhibiting increased connectivity and others decreased, dependent on the frequency band and specific age groups, showcasing the dynamic reorganization of neural networks as age increases. This detailed exploration provides, to our knowledge, the first all-encompassing view of how electrophysiological functional connectivity evolves at different life stages, offering new insights into the brain's adaptability and the intricate interplay of cognitive aging and network connectivity. This work not only contributes to the body of knowledge on cognitive aging and neurological health but also emphasizes the need for further research to develop targeted interventions for maintaining cognitive function in the aging population.

How to make calibration less painful-A proposition for an automatic, reliable and time-efficient procedure.

In behavioral and neurophysiological pain studies, multiple types of calibration methods are used to quantify the individual pain sensation stimuli. Often, studies lack a detailed calibration procedure description, data linearity, and quality quantification and omit required control for sex pain differences. This hampers study repetition and interexperimental comparisons. Moreover, typical calibration procedures require a high number of stimulations, which may cause discomfort and stimuli habituation among participants. To overcome those shortcomings, we present an automatic calibration procedure with a novel stimuli estimation method for intraepidermal stimulation. We provide an in-depth data analysis of the collected self-reports from 70 healthy volunteers (37 males) and propose a method based on a dynamic truncated linear regression model (tLRM). We compare its estimates for the sensation (t) and pain (T) thresholds and mid-pain stimulation (MP), with those calculated using traditional estimation methods and standard linear regression models. Compared to the other methods, tLRM exhibits higher R2 and requires 36% fewer stimuli applications and has significantly higher t intensity and lower T and MP intensities. Regarding sex differences, t and T were found to be lower for females compared to males, regardless of the estimation method. The proposed tLRM method quantifies the calibration procedure quality, minimizes its duration and invasiveness, and provides validation of linearity between stimuli intensity and subjective scores, making it an enabling technique for further studies. Moreover, our results highlight the importance of control for sex in pain studies.

When Maturation is Not Linear: Brain Oscillatory Activity in the Process of Aging as Measured by Electrophysiology.

Changes in brain oscillatory activity are commonly used as biomarkers both in cognitive neuroscience and in neuropsychiatric conditions. However, little is known about how its profile changes across maturation. Here we use regression models to characterize magnetoencephalography power changes within classical frequency bands in a sample of 792 healthy participants, covering the range 13 to 80 years old. Our findings unveil complex, non-linear power trajectories that defy the traditional linear paradigm, with notable cortical region variations. Interestingly, slow wave activity increases correlate with improved cognitive performance throughout life and larger gray matter volume in the elderly. Conversely, fast wave activity diminishes in adulthood. Elevated low-frequency activity during aging, traditionally seen as compensatory, may also signify neural deterioration. This dual interpretation, highlighted by our study, reveals the intricate dynamics between brain oscillations, cognitive performance, and aging. It advances our understanding of neurodevelopment and aging by emphasizing the regional specificity and complexity of brain rhythm changes, with implications for cognitive and structural integrity.

An Analytical Approach for Naturalistic Cooperative and Competitive EEG-Hyperscanning Data: A Proof-of-Concept Study.

Investigating the neural mechanisms underlying both cooperative and competitive joint actions may have a wide impact in many social contexts of human daily life. An effective pipeline of analysis for hyperscanning data recorded in a naturalistic context with a cooperative and competitive motor task has been missing. We propose an analytical pipeline for this type of joint action data, which was validated on electroencephalographic (EEG) signals recorded in a proof-of-concept study on two dyads playing cooperative and competitive table tennis. Functional connectivity maps were reconstructed using the corrected imaginary part of the phase locking value (ciPLV), an algorithm suitable in case of EEG signals recorded during turn-based competitive joint actions. Hyperbrain, within-, and between-brain functional connectivity maps were calculated in three frequency bands (i.e., theta, alpha, and beta) relevant during complex motor task execution and were characterized with graph theoretical measures and a clustering approach. The results of the proof-of-concept study are in line with recent findings on the main features of the functional networks sustaining cooperation and competition, hence demonstrating that the proposed pipeline is promising tool for the analysis of joint action EEG data recorded during cooperation and competition using a turn-based motor task.

Tactile expectancy modulates occipital alpha oscillations in early blindness.

Alpha oscillatory activity is thought to contribute to visual expectancy through the engagement of task-relevant occipital regions. In early blindness, occipital alpha oscillations are systematically reduced, suggesting that occipital alpha depends on visual experience. However, it remains possible that alpha activity could serve expectancy in non-visual modalities in blind people, especially considering that previous research has shown the recruitment of the occipital cortex for non-visual processing. To test this idea, we used electroencephalography to examine whether alpha oscillations reflected a differential recruitment of task-relevant regions between expected and unexpected conditions in two haptic tasks (texture and shape discrimination). As expected, sensor-level analyses showed that alpha suppression in parieto-occipital sites was significantly reduced in early blind individuals compared with sighted participants. The source reconstruction analysis revealed that group differences originated in the middle occipital cortex. In that region, expected trials evoked higher alpha desynchronization than unexpected trials in the early blind group only. Our results support the role of alpha rhythms in the recruitment of occipital areas in early blind participants, and for the first time we show that although posterior alpha activity is reduced in blindness, it remains sensitive to expectancy factors. Our findings therefore suggest that occipital alpha activity is involved in tactile expectancy in blind individuals, serving a similar function to visual anticipation in sighted populations but switched to the tactile modality. Altogether, our results indicate that expectancy-dependent modulation of alpha oscillatory activity does not depend on visual experience. SIGNIFICANCE STATEMENT: Are posterior alpha oscillations and their role in expectancy and anticipation dependent on visual experience? Our results show that tactile expectancy can modulate posterior alpha activity in blind (but not sighted) individuals through the engagement of occipital regions, suggesting that in early blindness, alpha oscillations maintain their proposed role in visual anticipation but subserve tactile processing. Our findings bring a new understanding of the role that alpha oscillatory activity plays in blindness, contrasting with the view that alpha activity is task unspecific in blind populations.

One Definition to Join Them All: The N-Spherical Solution for the EEG Lead Field.

Albeit its simplicity, the concentric spheres head model is widely used in EEG. The reason behind this is its simple mathematical definition, which allows for the calculation of lead fields with negligible computational cost, for example, for iterative approaches. Nevertheless, the literature shows contradictory formulations for the electrical solution of this head model. In this work, we study several different definitions for the electrical lead field of a four concentric spheres conduction model, finding that their results are contradictory. A thorough exploration of the mathematics used to build these formulations, provided in the original works, allowed for the identification of errors in some of the formulae, which proved to be the reason for the discrepancies. Moreover, this mathematical review revealed the iterative nature of some of these formulations, which allowed us to develop a formulation to solve the lead field in a head model built from an arbitrary number of concentric, homogeneous, and isotropic spheres.

A multi-site, multi-participant magnetoencephalography resting-state dataset to study dementia: The BioFIND dataset.

Early detection of Alzheimer's Disease (AD) is vital to reduce the burden of dementia and for developing effective treatments. Neuroimaging can detect early brain changes, such as hippocampal atrophy in Mild Cognitive Impairment (MCI), a prodromal state of AD. However, selecting the most informative imaging features by machine-learning requires many cases. While large publically-available datasets of people with dementia or prodromal disease exist for Magnetic Resonance Imaging (MRI), comparable datasets are missing for Magnetoencephalography (MEG). MEG offers advantages in its millisecond resolution, revealing physiological changes in brain oscillations or connectivity before structural changes are evident with MRI. We introduce a MEG dataset with 324 individuals: patients with MCI and healthy controls. Their brain activity was recorded while resting with eyes closed, using a 306-channel MEG scanner at one of two sites (Madrid or Cambridge), enabling tests of generalization across sites. A T1-weighted MRI is provided to assist source localisation. The MEG and MRI data are formatted according to international BIDS standards and analysed freely on the DPUK platform (https://portal.dementiasplatform.uk/Apply). Here, we describe this dataset in detail, report some example (benchmark) analyses, and consider its limitations and future directions.

Electrophysiological resting-state hyperconnectivity and poorer behavioural regulation as predisposing profiles of adolescent binge drinking.

Adolescent Binge Drinking (BD) has become an increasing health and social concern, with detrimental consequences for brain development and functional integrity. However, research on neurophysiological and neuropsychological traits predisposing to BD are limited at this time. In this work, we conducted a 2-year longitudinal magnetoencephalography (MEG) study over a cohort of initially alcohol-naïve adolescents with the purpose of exploring anomalies in resting-state electrophysiological networks, impulsivity, sensation-seeking, and dysexecutive behaviour able to predict future BD patterns. In a sample of 67 alcohol-naïve adolescents (age = 14.5 ± 0.9), we measured resting-state activity using MEG. Additionally, we evaluated their neuropsychological traits using self-report ecological scales (BIS-11, SSS-V, BDEFS, BRIEF-SR and DEX). In a second evaluation, 2 years later, we measured participant's alcohol consumption, sub-dividing the original sample in two groups: future binge drinkers (22 individuals, age 14.6 ± 0.8; eight females) and future light/no drinkers (17 individuals, age 14.5 ± 0.8; eight females). Then, we searched for differences predating alcohol BD intake. We found abnormalities in MEG resting state, in a form of gamma band hyperconnectivity, in those adolescents who transitioned into BD years later. Furthermore, they showed higher impulsivity, dysexecutive behaviours and sensation seeking, positively correlated with functional connectivity (FC). Sensation seeking and impulsivity mainly predicted BD severity in the future, while the relationship between dysexecutive trait and FC with future BD was mediated by sensation seeking. These findings shed light to electrophysiological and neuropsychological traits of vulnerability towards alcohol consumption. We hypothesise that these differences may rely on divergent neurobiological development of inhibitory neurotransmission pathways and executive prefrontal circuits.

The organization of functional neurocognitive networks in focal epilepsy correlates with domain-specific cognitive performance.

Understanding and diagnosing cognitive impairment in epilepsy remains a prominent challenge. New etiological models suggest that cognitive difficulties might not be directly linked to seizure activity, but are rather a manifestation of a broader brain pathology. Consequently, treating seizures is not sufficient to alleviate cognitive symptoms, highlighting the need for novel diagnostic tools. Here, we investigated whether the organization of three intrinsic, resting-state functional connectivity networks was correlated with domain-specific cognitive test performance. Using individualized EEG source reconstruction and graph theory, we examined the association between network small worldness and cognitive test performance in 23 patients with focal epilepsy and 17 healthy controls, who underwent a series of standardized pencil-and-paper and digital cognitive tests. We observed that the specific networks robustly correlated with test performance in distinct cognitive domains. Specifically, correlations were evident between the default mode network and memory in patients, the central-executive network and executive functioning in controls, and the salience network and social cognition in both groups. Interestingly, the correlations were evident in both groups, but in different domains, suggesting an alteration in these functional neurocognitive networks in focal epilepsy. The present findings highlight the potential clinical relevance of functional brain network dysfunction in cognitive impairment.

Hypersynchronization in mild cognitive impairment: the 'X' model.

Hypersynchronization has been proposed as a synaptic dysfunction biomarker in the Alzheimer's disease continuum, reflecting the alteration of the excitation/inhibition balance. While animal models have verified this idea extensively, there is still no clear evidence in humans. Here we test this hypothesis, evaluating the risk of conversion from mild cognitive impairment (MCI) to Alzheimer's disease in a longitudinal study. We compared the functional resting state eyes-closed magnetoencephalographic networks of 54 patients with MCI who were followed-up every 6 months. According to their clinical outcome, they were split into: (i) the 'progressive' MCI (n = 27) group; and (ii) the 'stable' MCI group (n = 27). They did not differ in gender or educational level. For all participants, two magnetoencephalographic recordings were acquired. Functional connectivity was evaluated using the phase locking value. To extract the functional connectivity network with significant changes between both magnetoencephalographic recordings, we evaluated the functional connectivity ratio, defined as functional connectivity post-/pre-condition, in a network-based statistical model with an ANCOVA test with age as covariate. Two significant networks were found in the theta and beta bands, involving fronto-temporal and fronto-occipital connections, and showing a diminished functional connectivity ratio in the progressive MCI group. These topologies were then evaluated at each condition showing that at baseline, patients with progressive MCI showed higher synchronization than patients with stable MCI, while in the post-condition this pattern was reversed. These results may be influenced by two main factors in the post-condition: the increased synchrony in the stable MCI patients and the network failure in the progressive MCI patients. These findings may be explained as an 'X' form model where the hypersynchrony predicts conversion, leading subsequently to a network breakdown in progressive MCI. Patients with stable MCI showed an opposite phenomenon, which could indicate that they were a step beyond in the Alzheimer's disease continuum. This model would be able to predict the risk for the conversion to dementia in MCI patients.

Sex Differences in the Complexity of Healthy Older Adults' Magnetoencephalograms.

The analysis of resting-state brain activity recording in magnetoencephalograms (MEGs) with new algorithms of symbolic dynamics analysis could help obtain a deeper insight into the functioning of the brain and identify potential differences between males and females. Permutation Lempel-Ziv complexity (PLZC), a recently introduced non-linear signal processing algorithm based on symbolic dynamics, was used to evaluate the complexity of MEG signals in source space. PLZC was estimated in a broad band of frequencies (2-45 Hz), as well as in narrow bands (i.e., theta (4-8 Hz), alpha (8-12 Hz), low beta (12-20 Hz), high beta (20-30 Hz), and gamma (30-45 Hz)) in a sample of 98 healthy elderly subjects (49 males, 49 female) aged 65-80 (average age of 72.71 ± 4.22 for males and 72.67 ± 4.21 for females). PLZC was significantly higher for females than males in the high beta band at posterior brain regions including the precuneus, and the parietal and occipital cortices. Further statistical analyses showed that higher complexity values over highly overlapping regions than the ones mentioned above were associated with larger hippocampal volumes only in females. These results suggest that sex differences in healthy aging can be identified from the analysis of magnetoencephalograms with novel signal processing methods.

Alpha-band hypersynchronization in progressive mild cognitive impairment: a magnetoencephalography study.

People with mild cognitive impairment (MCI) show a high risk to develop Alzheimer's disease (AD; Petersen et al., 2001). Nonetheless, there is a lack of studies about how functional connectivity patterns may distinguish between progressive (pMCI) and stable (sMCI) MCI patients. To examine whether there were differences in functional connectivity between groups, MEG eyes-closed recordings from 30 sMCI and 19 pMCI subjects were compared. The average conversion time of pMCI was 1 year, so they were considered as fast converters. To this end, functional connectivity in different frequency bands was assessed with phase locking value in source space. Then the significant differences between both groups were correlated with neuropsychological scores and entorhinal, parahippocampal, and hippocampal volumes. Both groups did not differ in age, gender, or educational level. pMCI patients obtained lower scores in episodic and semantic memory and also in executive functioning. At the structural level, there were no differences in hippocampal volume, although some were found in left entorhinal volume between both groups. Additionally, pMCI patients exhibit a higher synchronization in the alpha band between the right anterior cingulate and temporo-occipital regions than sMCI subjects. This hypersynchronization was inversely correlated with cognitive performance, both hippocampal volumes, and left entorhinal volume. The increase in phase synchronization between the right anterior cingulate and temporo-occipital areas may be predictive of conversion from MCI to AD.

A Fuzzy Inference System for Closed-Loop Deep Brain Stimulation in Parkinson's Disease.

Parkinsons disease is a complex neurodegenerative disorder for which patients present many symptoms, tremor being the main one. In advanced stages of the disease, Deep Brain Stimulation is a generalized therapy which can significantly improve the motor symptoms. However despite its beneficial effects on treating the symptomatology, the technique can be improved. One of its main limitations is that the parameters are fixed, and the stimulation is provided uninterruptedly, not taking into account any fluctuation in the patients state. A closed-loop system which provides stimulation by demand would adjust the stimulation to the variations in the state of the patient, stimulating only when it is necessary. It would not only perform a more intelligent stimulation, capable of adapting to the changes in real time, but also extending the devices battery life, thereby avoiding surgical interventions. In this work we design a tool that learns to recognize the principal symptom of Parkinsons disease and particularly the tremor. The goal of the designed system is to detect the moments the patient is suffering from a tremor episode and consequently to decide whether stimulation is needed or not. For that, local field potentials were recorded in the subthalamic nucleus of ten Parkinsonian patients, who were diagnosed with tremor-dominant Parkinsons disease and who underwent surgery for the implantation of a neurostimulator. Electromyographic activity in the forearm was simultaneously recorded, and the relation between both signals was evaluated using two different synchronization measures. The results of evaluating the synchronization indexes on each moment represent the inputs to the designed system. Finally, a fuzzy inference system was applied with the goal of identifying tremor episodes. Results are favourable, reaching accuracies of higher 98.7% in 70% of the patients.

Guiding functional connectivity estimation by structural connectivity in MEG: an application to discrimination of conditions of mild cognitive impairment.

Whole brain resting state connectivity is a promising biomarker that might help to obtain an early diagnosis in many neurological diseases, such as dementia. Inferring resting-state connectivity is often based on correlations, which are sensitive to indirect connections, leading to an inaccurate representation of the real backbone of the network. The precision matrix is a better representation for whole brain connectivity, as it considers only direct connections. The network structure can be estimated using the graphical lasso (GL), which achieves sparsity through l1-regularization on the precision matrix. In this paper, we propose a structural connectivity adaptive version of the GL, where weaker anatomical connections are represented as stronger penalties on the corresponding functional connections. We applied beamformer source reconstruction to the resting state MEG recordings of 81 subjects, where 29 were healthy controls, 22 were single-domain amnestic Mild Cognitive Impaired (MCI), and 30 were multiple-domain amnestic MCI. An atlas-based anatomical parcellation of 66 regions was obtained for each subject, and time series were assigned to each of the regions. The fiber densities between the regions, obtained with deterministic tractography from diffusion-weighted MRI, were used to define the anatomical connectivity. Precision matrices were obtained with the region specific time series in five different frequency bands. We compared our method with the traditional GL and a functional adaptive version of the GL, in terms of log-likelihood and classification accuracies between the three groups. We conclude that introducing an anatomical prior improves the expressivity of the model and, in most cases, leads to a better classification between groups.

Dynamic functional connectivity is modulated by the amount of p-Tau231 in blood in cognitively intact participants.

INTRODUCTION: Electrophysiology and plasma biomarkers are early and non-invasive candidates for Alzheimer's disease detection. The purpose of this paper is to evaluate changes in dynamic functional connectivity measured with magnetoencephalography, associated with the plasma pathology marker p-tau231 in unimpaired adults. METHODS: 73 individuals were included. Static and dynamic functional connectivity were calculated using leakage corrected amplitude envelope correlation. Each source's strength entropy across trials was calculated. A data-driven statistical analysis was performed to find the association between functional connectivity and plasma p-tau231 levels. Regression models were used to assess the influence of other variables over the clusters' connectivity. RESULTS: Frontotemporal dynamic connectivity positively associated with p-tau231 levels. Linear regression models identified pathological, functional and structural factors that influence dynamic functional connectivity. DISCUSSION: These results expand previous literature on dynamic functional connectivity in healthy individuals at risk of AD, highlighting its usefulness as an early, non-invasive and more sensitive biomarker.

EEG electrodes and where to find them: automated localization from 3D scans.

Objective.The accurate localization of electroencephalography (EEG) electrode positions is crucial for accurate source localization. Recent advancements have proposed alternatives to labor-intensive, manual methods for spatial localization of the electrodes, employing technologies such as 3D scanning and laser scanning. These novel approaches often integrate magnetic resonance imaging (MRI) as part of the pipeline in localizing the electrodes. The limited global availability of MRI data restricts its use as a standard modality in several clinical scenarios. This limitation restricts the use of these advanced methods.Approach.In this paper, we present a novel, versatile approach that utilizes 3D scans to localize EEG electrode positions with high accuracy. Importantly, while our method can be integrated with MRI data if available, it is specifically designed to be highly effective even in the absence of MRI, thus expanding the potential for advanced EEG analysis in various resource-limited settings. Our solution implements a two-tiered approach involving landmark/fiducials localization and electrode localization, creating an end-to-end framework.Main results.The efficacy and robustness of our approach have been validated on an extensive dataset containing over 400 3D scans from 278 subjects. The framework identifies pre-auricular points and achieves correct electrode positioning accuracy in the range of 85.7% to 91.0%. Additionally, our framework includes a validation tool that permits manual adjustments and visual validation if required.Significance.This study represents, to the best of the authors' knowledge, the first validation of such a method on a substantial dataset, thus ensuring the robustness and generalizability of our innovative approach. Our findings focus on developing a solution that facilitates source localization, without the need for MRI, contributing to the critical discussion on balancing cost effectiveness with methodological accuracy to promote wider adoption in both research and clinical settings.

Sex differences in the progression to Alzheimer's disease: a combination of functional and structural markers.

Mild cognitive impairment (MCI) has been frequently interpreted as a transitional phase between healthy cognitive aging and dementia, particularly of the Alzheimer's disease (AD) type. Of note, few studies explored that transition from a multifactorial perspective, taking into consideration the effect of basic factors such as biological sex. In the present study 96 subjects with MCI (37 males and 59 females) were followed-up and divided into two subgroups according to their clinical outcome: "progressive" MCI (pMCI = 41), if they fulfilled the diagnostic criteria for AD at the end of follow-up; and "stable" MCI (sMCI = 55), if they remained with the initial diagnosis. Different markers were combined to characterize sex differences between groups, including magnetoencephalography recordings, cognitive performance, and brain volumes derived from magnetic resonance imaging. Results indicated that the pMCI group exhibited higher low-frequency activity, lower scores in neuropsychological tests and reduced brain volumes than the sMCI group, being these measures significantly correlated. When sex was considered, results revealed that this pattern was mainly due to the influence of the females' sample. Overall, females exhibited lower cognitive scores and reduced brain volumes. More interestingly, females in the pMCI group showed an increased theta activity that correlated with a more abrupt reduction of cognitive and volumetric scores as compared with females in the sMCI group and with males in the pMCI group. These findings suggest that females' brains might be more vulnerable to the effects of AD pathology, since regardless of age, they showed signs of more pronounced deterioration than males.

Decoding the Best Automated Segmentation Tools for Vascular White Matter Hyperintensities in the Aging Brain: A Clinician's Guide to Precision and Purpose.

Cerebrovascular damage from small vessel disease (SVD) occurs in healthy and pathological aging. SVD markers, such as white matter hyperintensities (WMH), are commonly found in individuals over 60 and increase in prevalence with age. WMHs are detectable on standard MRI by adhering to the STRIVE criteria. Currently, visual assessment scales are used in clinical and research scenarios but is time-consuming and has rater variability, limiting its practicality. Addressing this issue, our study aimed to determine the most precise WMH segmentation software, offering insights into methodology and usability to balance clinical precision with practical application. This study employed a dataset comprising T1, FLAIR, and DWI images from 300 cognitively healthy older adults. WMHs in this cohort were evaluated using four automated neuroimaging tools: Lesion Prediction Algorithm (LPA) and Lesion Growth Algorithm (LGA) from Lesion Segmentation Tool (LST), Sequence Adaptive Multimodal Segmentation (SAMSEG), and Brain Intensity Abnormalities Classification Algorithm (BIANCA). Additionally, clinicians manually segmented WMHs in a subsample of 45 participants to establish a gold standard. The study assessed correlations with the Fazekas scale, algorithm performance, and the influence of WMH volume on reliability. Results indicated that supervised algorithms were superior, particularly in detecting small WMHs, and can improve their consistency when used in parallel with unsupervised tools. The research also proposed a biomarker for moderate vascular damage, derived from the top 95th percentile of WMH volume in healthy individuals aged 50 to 60. This biomarker effectively differentiated subgroups within the cohort, correlating with variations in brain structure and behavior.

Decoding the best automated segmentation tools for vascular white matter hyperintensities in the aging brain: a clinician's guide to precision and purpose.

White matter hyperintensities of vascular origin (WMH) are commonly found in individuals over 60 and increase in prevalence with age. The significance of WMH is well-documented, with strong associations with cognitive impairment, risk of stroke, mental health, and brain structure deterioration. Consequently, careful monitoring is crucial for the early identification and management of individuals at risk. Luckily, WMH are detectable and quantifiable on standard MRI through visual assessment scales, but it is time-consuming and has high rater variability. Addressing this issue, the main aim of our study is to decipher the utility of quantitative measures of WMH, assessed with automatic tools, in establishing risk profiles for cerebrovascular deterioration. For this purpose, first, we work to determine the most precise WMH segmentation open access tool compared to clinician manual segmentations (LST-LPA, LST-LGA, SAMSEG, and BIANCA), offering insights into methodology and usability to balance clinical precision with practical application. The results indicated that supervised algorithms (LST-LPA and BIANCA) were superior, particularly in detecting small WMH, and can improve their consistency when used in parallel with unsupervised tools (LST-LGA and SAMSEG). Additionally, to investigate the behavior and real clinical utility of these tools, we tested them in a real-world scenario (N = 300; age > 50 y.o. and MMSE > 26), proposing an imaging biomarker for moderate vascular damage. The results confirmed its capacity to effectively identify individuals at risk comparing the cognitive and brain structural profiles of cognitively healthy adults above and below the resulted threshold.