Hyperbolic graph embedding of MEG brain networks to study brain alterations in individuals with subjective cognitive decline.

An expansive area of research focuses on discerning patterns of alterations in functional brain networks from the early stages of Alzheimer's disease, even at the subjective cognitive decline (SCD) stage. Here, we developed a novel hyperbolic MEG brain network embedding framework for transforming high-dimensional complex MEG brain networks into lower-dimensional hyperbolic representations. Using this model, we computed hyperbolic embeddings of the MEG brain networks of two distinct participant groups: individuals with SCD and healthy controls. We demonstrated that these embeddings preserve both local and global geometric information, presenting reduced distortion compared to rival models, even when brain networks are mapped into low-dimensional spaces. In addition, our findings showed that the hyperbolic embeddings encompass unique SCD-related information that improves the discriminatory power above and beyond that of connectivity features alone. Notably, we introduced a unique metric-the radius of the node embeddings-which effectively proxies the hierarchical organization of the brain. Using this metric, we identified subtle hierarchy organizational differences between the two participant groups, suggesting increased hierarchy in the dorsal attention, frontoparietal, and ventral attention subnetworks among the SCD group. Last, we assessed the correlation between these hierarchical variations and cognitive assessment scores, revealing associations with diminished performance across multiple cognitive evaluations in the SCD group. Overall, this study presents the first evaluation of hyperbolic embeddings of MEG brain networks, offering novel insights into brain organization, cognitive decline, and potential diagnostic avenues of Alzheimer's disease.

Hyperbolic graph embedding of MEG brain networks to study brain alterations in individuals with subjective cognitive decline.

An expansive area of research focuses on discerning patterns of alterations in functional brain networks from the early stages of Alzheimer's disease, even at the subjective cognitive decline (SCD) stage. Here, we developed a novel hyperbolic MEG brain network embedding framework for transforming high-dimensional complex MEG brain networks into lower-dimensional hyperbolic representations. Using this model, we computed hyperbolic embeddings of the MEG brain networks of two distinct participant groups: individuals with SCD and healthy controls. We demonstrated that these embeddings preserve both local and global geometric information, presenting reduced distortion compared to rival models, even when brain networks are mapped into low-dimensional spaces. In addition, our findings showed that the hyperbolic embeddings encompass unique SCD-related information that improves the discriminatory power above and beyond that of connectivity features alone. Notably, we introduced a unique metric-the radius of the node embeddings-which effectively proxies the hierarchical organization of the brain. Using this metric, we identified subtle hierarchy organizational differences between the two participant groups, suggesting increased hierarchy in the dorsal attention, frontoparietal, and ventral attention subnetworks among the SCD group. Last, we assessed the correlation between these hierarchical variations and cognitive assessment scores, revealing associations with diminished performance across multiple cognitive evaluations in the SCD group. Overall, this study presents the first evaluation of hyperbolic embeddings of MEG brain networks, offering novel insights into brain organization, cognitive decline, and potential diagnostic avenues of Alzheimer's disease.

Cognitive Training Modulates Brain Hypersynchrony in a Population at Risk for Alzheimer's Disease.

BACKGROUND: Recent studies demonstrated that brain hypersynchrony is an early sign of dysfunction in Alzheimer's disease (AD) that can represent a proxy for clinical progression. Conversely, non-pharmacological interventions, such as cognitive training (COGTR), are associated with cognitive gains that may be underpinned by a neuroprotective effect on brain synchrony. OBJECTIVE: To study the potential of COGTR to modulate brain synchrony and to eventually revert the hypersynchrony phenomenon that characterizes preclinical AD. METHODS: The effect of COGTR was examined in a sample of healthy controls (HC, n = 41, 22 trained) and individuals with subjective cognitive decline (SCD, n = 49, 24 trained). Magnetoencephalographic activity and neuropsychological scores were acquired before and after a ten-week COGTR intervention aimed at improving cognitive function and daily living performance. Functional connectivity (FC) was analyzed using the phase-locking value. A mixed-effects ANOVA model with factors time (pre-intervention/post-intervention), training (trained/non-trained), and diagnosis (HC/SCD) was used to investigate significant changes in FC. RESULTS: We found an average increase in alpha-band FC over time, but the effect was different in each group (trained and non-trained). In the trained group (HC and SCD), we report a reduction in the increase in FC within temporo-parietal and temporo-occipital connections. In the trained SCD group, this reduction was stronger and showed a tentative correlation with improved performance in different cognitive tests. CONCLUSION: COGTR interventions could mitigate aberrant increases in FC in preclinical AD, promoting brain synchrony normalization in groups at a higher risk of developing dementia.

Ongoing Oscillatory Electrophysiological Alterations in Frail Older Adults: A MEG Study.

Objective: The role of the central nervous system in the pathophysiology of frailty is controversial. We used magnetoencephalography (MEG) to search for abnormalities in the ongoing oscillatory neural activity of frail individuals without global cognitive impairment. Methods: Fifty four older (≥70 years) and cognitively healthy (Mini-Mental State Examination ≥24) participants were classified as robust (0 criterion, n = 34) or frail (≥ 3 criteria, n = 20) following Fried's phenotype. Memory, language, attention, and executive function were assessed through well-validated neuropsychological tests. Every participant underwent a resting-state MEG and a T1-weighted magnetic resonance imaging scan. We performed MEG power spectral analyses to compare the electrophysiological profiles of frail and robust individuals. We used an ensemble learner to investigate the ability of MEG spectral power to discriminate frail from robust participants. Results: We identified increased relative power in the frail group in the mu (p < 0.05) and sensorimotor (p < 0.05) frequencies across right sensorimotor, posterior parietal, and frontal regions. The ensemble learner discriminated frail from robust participants [area under the curve = 0.73 (95% CI = 0.49-0.98)]. Frail individuals performed significantly worse in the Trail Making Test, Digit Span Test (forward), Rey-Osterrieth Complex Figure, and Semantic Fluency Test. Interpretation: Frail individuals without global cognitive impairment showed ongoing oscillatory alterations within brain regions associated with aspects of motor control, jointly to failures in executive function. Our results suggest that some physical manifestations of frailty might partly arise from failures in central structures relevant to sensorimotor and executive processing.

Abnormal organization of inhibitory control functional networks in future binge drinkers.

BACKGROUND AND AIMS: Adolescent Binge drinking has become an increasing health and social concern, which cause several detrimental consequences for brain integrity. However, research on neurophysiological traits of vulnerability for binge drinking predisposition is limited at this time. In this work, we conducted a two-year longitudinal study with magnetoencephalography (MEG) over a cohort of initially alcohol-naive adolescents with the purpose of characterize inhibitory cortical networks' anomalies prior to alcohol consumption onset in those youths who will transit into binge drinkers years later. METHODS: Sixty-seven participant's inhibitory functional networks, and dysexecutive/impulsivity traits were measured by means of inhibitory task (go/no-go) and questionnaires battery. After a follow-up period of two years, we evaluated their alcohol consumption habits, sub-dividing them in two groups according to their alcohol intake patterns: future binge drinkers (fBD): n = 22; future Light/non-drinkers (fLD): n = 17. We evaluated whole-brain and seed-based functional connectivity profiles, as well as its correlation with impulsive and dysexecutive behaviours, searching for early abnormalities before consumption onset. RESULTS: For the first time, abnormalities in MEG functional networks and higher dysexecutive and impulsivity profiles were detected in alcohol-naïve adolescents who two years later became binge drinkers. Concretely, fBD exhibit a distinctive pattern of beta band hyperconnectivity among crucial regions of inhibitory control networks, positively correlated with behavioral traits and future alcohol intake rate. CONCLUSIONS: These findings strongly support the idea of early neurobiological vulnerabilities for substances consumption initiation, with inhibitory functional networks' abnormalities as a relevant neurophysiological marker of subjects at risk- we hypothesize this profile is due to neurodevelopmental and neurobiological differences involving cognitive control networks and neurotransmission pathways.

Functional Connectivity Disruption in Frail Older Adults Without Global Cognitive Deficits.

Frailty is a common representation of cumulative age-related decline that may precede disability in older adults. In our study, we used magnetoencephalography (MEG) to explore the existence of abnormalities in the synchronization patterns of frail individuals without global cognitive impairment. Fifty-four older (≥70 years) and cognitively healthy (Mini-Mental State Examination ≥24) adults, 34 robust (not a single positive Fried criterion) and 20 frail (≥3 positive Fried criteria) underwent a resting-state MEG recording and a T1-weighted magnetic resonance imaging scan. Seed-based functional connectivity (FC) analyses were used to explore group differences in the synchronization of fronto-parietal areas relevant to motor function. Additionally, we performed group comparisons of intra-network FC for key resting-state networks such as the sensorimotor, fronto-parietal, default mode, and attentional (dorsal and ventral) networks. Frail participants exhibited reduced FC between posterior regions of the parietal cortex (bilateral supramarginal gyrus, right superior parietal lobe, and right angular gyrus) and widespread clusters spanning mainly fronto-parietal regions. Frail participants also demonstrated reduced intra-network FC within the fronto-parietal, ventral attentional, and posterior default mode networks. All the FC results concerned the upper beta band, a frequency range classically linked to motor function. Overall, our findings reveal the existence of abnormalities in the synchronization patterns of frail individuals within central structures important for accurate motor control. This study suggests that alterations in brain connectivity might contribute to some motor impairments associated with frailty.

Scoping Review of Neuroimaging Studies Investigating Frailty and Frailty Components.

Background: Neuroimaging techniques are a cornerstone for diagnosing and investigating cognitive decline and dementia in the elderly. In frailty research, the physical as opposed to the cognitive domain of the aging process, neuroimaging studies are less common. Here we systematically review the use of neuroimaging techniques in frailty research. Methods: We searched PUBMED for any publication reporting the association between neuroimaging markers and frailty, following Fried's original definition, as well as its determining phenotypes: gait speed, grip strength, fatigue and recent weight loss in the non-diseased population older than 65 years. Results: The search returned a total of 979 abstracts which were independently screened by 3 reviewers. In total, 17 studies met the inclusion criteria. Of these, 12 studies evaluated gait speed, 2 grip strength, and 3 frailty (2 Fried Frailty, 1 Frailty Index). An association between increased burden of white matter lesions, lower fractional anisotropy, and higher diffusivity has been associated consistently to frailty and worse performance in the different frailty components. Conclusions: White matter lesions were significantly associated to frailty and frailty components thus highlighting the potential utility of neuroimaging in unraveling the underlying mechanisms of this state. However, considering small sample size and design effects, it is not possible to completely rule out reverse causality between frailty and neuroimaging findings. More studies are needed to clarify this important clinical question.