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.

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.

The effects of white matter hyperintensities on MEG power spectra in cognitively healthy aging.

Objective: This study sought to identify magnetoencephalography (MEG) power spectra patterns associated with cerebrovascular damage (white matter hyperintensities - WMH) and their relationship with cognitive performance and brain structure integrity in aging individuals without cognitive impairment. Methods: We hypothesized a "slowness" pattern characterized by increased power in δ and θ bands and decreased power in the ß band associated with the severity of vascular damage. MEG signals were analyzed in cognitively healthy older adults to investigate these associations. Results: Contrary to expectations, we did not observe an increase in δ and θ power. However, we found a significant negative correlation between ß band power and WMH volume. This ß power reduction was linked to structural brain changes, such as larger lateral ventricles, reduced white matter volume, and decreased fractional anisotropy in critical white matter tracts, but not to cognitive performance. This suggests that ß band power reduction may serve as an early marker of vascular damage before the onset of cognitive symptoms. Conclusion: Our findings partially confirm our initial hypothesis by demonstrating a decrease in ß band power with increased vascular damage but not the anticipated increase in slow band power. The lack of correlation between the ßpow marker and cognitive performance suggests its potential utility in early identification of at-risk individuals for future cognitive impairment due to vascular origins. These results contribute to understanding the electrophysiological signatures of preclinical vascular damage and highlight the importance of MEG in detecting subtle brain changes associated with aging.

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.

Correlation between autistic traits and brain functional connectivity in preschoolers with autism spectrum disorder: a resting state MEG study.

BACKGROUND: Neurophysiological studies recognized that Autism Spectrum Disorder (ASD) is associated with altered patterns of over- and under-connectivity. However, little is known about network organization in children with ASD in the early phases of development and its correlation with the severity of core autistic features. METHODS: The present study aimed at investigating the association between brain connectivity derived from MEG signals and severity of ASD traits measured with different diagnostic clinical scales, in a sample of 16 children with ASD aged 2 to 6 years. RESULTS: A significant correlation emerged between connectivity strength in cortical brain areas implicated in several resting state networks (Default mode, Central executive, Salience, Visual and Sensorimotor) and the severity of communication anomalies, social interaction problems, social affect problems, and repetitive behaviors. Seed analysis revealed that this pattern of correlation was mainly caused by global rather than local effects. CONCLUSIONS: The present evidence suggests that altered connectivity strength in several resting state networks is related to clinical features and may contribute to neurofunctional correlates of ASD. Future studies implementing the same method on a wider and stratified sample may further support functional connectivity as a possible biomarker of the condition.

Correction: Epigenetic, psychological, and EEG changes after a 1-week retreat based on mindfulness and compassion for stress reduction in healthy adults: Study protocol of a cross-over randomized controlled trial.

[This corrects the article DOI: 10.1371/journal.pone.0283169.].

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.

Q fever, a rare cause of secondary hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome in which Coxiella burnetii is a very infrequent etiology. We present the case of a 62-year-old male with progressive pulmonary infiltrates, fever, hepatitis, and bicytopenia despite broad spectrum antibiotics. A thorough clinical evaluation led to a high suspicion of Coxiella burnetii infection, subsequently confirmed through a positive serum polymerase chain reaction (PCR) analysis. HLH diagnosis was established based on the fulfillment of 5/8 diagnostic criteria, obviating the need for a bone marrow biopsy. Targeted antibiotic treatment and dexamethasone led to full recovery within two weeks, eliminating the need for stronger immunosuppressive therapy.

Epigenetic, psychological, and EEG changes after a 1-week retreat based on mindfulness and compassion for stress reduction in healthy adults: Study protocol of a cross-over randomized controlled trial.

INTRODUCTION: The main objective of the study will be to evaluate the effects of two widely used standardized mindfulness-based programs [Mindfulness-Based Stress Reduction (MBSR) and Compassion Cultivation Training (CCT)], on epigenetic, neurobiological, psychological, and physiological variables. METHODS: The programs will be offered in an intensive retreat format in a general population sample of healthy volunteer adults. During a 7-day retreat, participants will receive MBSR and CCT in a crossover design where participants complete both programs in random order. After finishing their first 3-day training with one of the two programs, participants will be assigned to the second 3-day training with the second program. The effects of the MBSR and CCT programs, and their combination, will be measured by epigenetic changes (i.e., DNA methylation biomarkers), neurobiological and psychophysiological measures (i.e., EEG resting state, EKG, respiration patterns, and diurnal cortisol slopes), self-report questionnaires belonging to different psychological domains (i.e., mindfulness, compassion, well-being, distress, and general functioning), and stress tasks (i.e., an Arithmetic Stress Test and the retrieval of negative autobiographical memories). These measures will be collected from both groups on the mornings of day 1 (pre-program), day 4 (after finishing the first program and before beginning the second program), and day 7 (post-second program). We will conduct a 3-month and a 12-month follow-up using only the set of self-report measures. DISCUSSION: This study aims to shed light on the neurobiological and psychological mechanisms linked to meditation and compassion in the general population. The protocol was registered at clinicaltrials.gov (Identifier: NCT05516355; August 23, 2022).

An individual data-driven virtual resection model based on epileptic network dynamics in children with intractable epilepsy: a magnetoencephalography interictal activity application.

Epilepsy surgery continues to be a recommended treatment for intractable (medication-resistant) epilepsy; however, 30-70% of epilepsy surgery patients can continue to have seizures. Surgical failures are often associated with incomplete resection or inaccurate localization of the epileptogenic zone. This retrospective study aims to improve surgical outcome through in silico testing of surgical hypotheses through a personalized computational neurosurgery model created from individualized patient's magnetoencephalography recording and MRI. The framework assesses the extent of the epileptic network and evaluates underlying spike dynamics, resulting in identification of one single brain volume as a candidate for resection. Dynamic-locked networks were utilized for virtual cortical resection. This in silico protocol was tested in a cohort of 24 paediatric patients with focal drug-resistant epilepsy who underwent epilepsy surgery. Of 24 patients who were included in the analysis, 79% (19 of 24) of the models agreed with the patient's clinical surgery outcome and 21% (5 of 24) were considered as model failures (accuracy 0.79, sensitivity 0.77, specificity 0.82). Patients with unsuccessful surgery outcome typically showed a model cluster outside of the resected cavity, while those with successful surgery showed the cluster model within the cavity. Two of the model failures showed the cluster in the vicinity of the resected tissue and either a functional disconnection or lack of precision of the magnetoencephalography-MRI overlapping could explain the results. Two other cases were seizure free for 1 year but developed late recurrence. This is the first study that provides in silico personalized protocol for epilepsy surgery planning using magnetoencephalography spike network analysis. This model could provide complementary information to the traditional pre-surgical assessment methods and increase the proportion of patients achieving seizure-free outcome from surgery.

Effects of spaceflight on the EEG alpha power and functional connectivity.

Electroencephalography (EEG) can detect changes in cerebral activity during spaceflight. This study evaluates the effect of spaceflight on brain networks through analysis of the Default Mode Network (DMN)'s alpha frequency band power and functional connectivity (FC), and the persistence of these changes. Five astronauts' resting state EEGs under three conditions were analyzed (pre-flight, in-flight, and post-flight). DMN's alpha band power and FC were computed using eLORETA and phase-locking value. Eyes-opened (EO) and eyes-closed (EC) conditions were differentiated. We found a DMN alpha band power reduction during in-flight (EC: p < 0.001; EO: p < 0.05) and post-flight (EC: p < 0.001; EO: p < 0.01) when compared to pre-flight condition. FC strength decreased during in-flight (EC: p < 0.01; EO: p < 0.01) and post-flight (EC: ns; EO: p < 0.01) compared to pre-flight condition. The DMN alpha band power and FC strength reduction persisted until 20 days after landing. Spaceflight caused electrocerebral alterations that persisted after return to earth. Periodic assessment by EEG-derived DMN analysis has the potential to become a neurophysiologic marker of cerebral functional integrity during exploration missions to space.

The effects of white matter hyperintensities on MEG power spectra in population with mild cognitive impairment.

Cerebrovascular disease is responsible for up to 20% of cases of dementia worldwide, but also it is a major comorbid contributor to the progression of other neurodegenerative diseases, like Alzheimer's disease. White matter hyperintensities (WMH) are the most prevalent imaging marker in cerebrovascular disease. The presence and progression of WMH in the brain have been associated with general cognitive impairment and the risk to develop all types of dementia. The aim of this piece of work is the assessment of brain functional differences in an MCI population based on the WMH volume. One-hundred and twenty-nine individuals with mild cognitive impairment (MCI) underwent a neuropsychological evaluation, MRI assessment (T1 and Flair), and MEG recordings (5 min of eyes closed resting state). Those participants were further classified into vascular MCI (vMCI; n = 61, mean age 75 ± 4 years, 35 females) or non-vascular MCI (nvMCI; n = 56, mean age 72 ± 5 years, 36 females) according to their WMH total volume, assessed with an automatic detection toolbox, LST (SPM12). We used a completely data-driven approach to evaluate the differences in the power spectra between the groups. Interestingly, three clusters emerged: One cluster with widespread larger theta power and two clusters located in both temporal regions with smaller beta power for vMCI compared to nvMCI. Those power signatures were also associated with cognitive performance and hippocampal volume. Early identification and classification of dementia pathogenesis is a crucially important goal for the search for more effective management approaches. These findings could help to understand and try to palliate the contribution of WMH to particular symptoms in mixed dementia progress.

Noise characteristics in spaceflight multichannel EEG.

The cognitive performance of the crew has a major impact on mission safety and success in space flight. Monitoring of cognitive performance during long-duration space flight therefore is of paramount importance and can be performed using compact state-of-the-art mobile EEG. However, signal quality of EEG may be compromised due to the vicinity to various electronic devices and constant movements. We compare noise characteristics between in-flight extraterrestrial microgravity and ground-level terrestrial electroencephalography (EEG) recordings. EEG data recordings from either aboard International Space Station (ISS) or on earth's surface, utilizing three EEG amplifiers and two electrode types, were compared. In-flight recordings showed noise level of an order of magnitude lower when compared to pre- and post-flight ground-level recordings with the same EEG system. Noise levels between ground-level recordings with actively shielded cables, and in-flight recordings without shielded cables, were similar. Furthermore, noise level characteristics of shielded ground-level EEG recordings, using wet and dry electrodes, and in-flight EEG recordings were similar. Actively shielded mobile dry EEG systems will support neuroscientific research and neurocognitive monitoring during spaceflight, especially during long-duration space missions.

Episodic memory dysfunction and hypersynchrony in brain functional networks in cognitively intact subjects and MCI: a study of 379 individuals.

Delayed recall (DR) impairment is one of the most significant predictive factors in defining the progression to Alzheimer's disease (AD). Changes in brain functional connectivity (FC) could accompany this decline in the DR performance even in a resting state condition from the preclinical stages to the diagnosis of AD itself, so the characterization of the relationship between the two phenomena has attracted increasing interest. Another aspect to contemplate is the potential moderator role of the APOE genotype in this association, considering the evidence about their implication for the disease. 379 subjects (118 mild cognitive impairment (MCI) and 261 cognitively intact (CI) individuals) underwent an extensive evaluation, including MEG recording. Applying cluster-based permutation test, we identified a cluster of differences in FC and studied which connections drove such an effect in DR. The moderation effect of APOE genotype between FC results and delayed recall was evaluated too. Higher FC in beta band in the right occipital region is associated with lower DR scores in both groups. A significant anteroposterior link emerged in the seed-based analysis with higher values in MCI. Moreover, APOE genotype appeared as a moderator between beta FC and DR performance only in the CI group. An increased beta FC in the anteroposterior brain region appears to be associated with lower memory performance in MCI. This finding could help discriminate the pattern of the progression of healthy aging to MCI and the relation between resting state and memory performance.

Sex specific EEG signatures associated with cerebrospinal fluid biomarkers in mild cognitive impairment.

OBJECTIVE: The use of the electroencephalography (EEG) technique in Alzheimer's disease (AD) diagnosis is scarce due to a lack of validation of its neurophysiological information with current biomarkers. Therefore, our goal was to assess correlations between brain spectral power signatures and cerebrospinal fluid markers (CSF) such as amyloid-ß 42 load (Aß-42), total tau (t-tau), and phosphorylated tau (p-tau) in a mild cognitive impairment (MCI) population. Furthermore, given the AD sex-dependent vulnerability related to CSF biomarkers, we went a little forward looking for different electrophysiological correlations for males and females independently. METHODS: A data-driven approach was employed to determine bidimensional spectral power signatures (space-frequency) that correlated (Spearman) significantly with any of the three CSF markers in 27 patients with MCI in any of the two sex-dependent subsamples (i.e., 12 females and 15 males). RESULTS: Our main significant outcomes evidenced 1) a negative correlation of Aß-42 load with central-posterior theta power and a negative correlation of t-tau with widespread alpha power within the male subsample, and 2) a significant negative correlation between t-tau and widespread beta power in the female subgroup. CONCLUSIONS: There is a distinctive profile of correlations between resting-state electrophysiological signatures and CSF markers in male and female individuals. SIGNIFICANCE: The combination of these two measures would be pointing out the need of a more personalized approach to promote early AD diagnosis.

Alpha-band power increases in posterior brain regions in attention deficit hyperactivity disorder after digital cognitive stimulation treatment: randomized controlled study.

The changes triggered by pharmacological treatments in resting-state alpha-band (8-14 Hz) oscillations have been widely studied in attention deficit hyperactivity disorder. However, to date, there has been no evidence regarding the possible changes in cognitive stimulation treatments on these oscillations. This paper sets out to verify whether cognitive stimulation treatments based on progressive increases in cognitive load can be effective in triggering changes in alpha-band power in attention deficit hyperactivity disorder. With this objective, we compared a cognitive stimulation treatment (n = 12) to a placebo treatment (n = 14) for 12 weeks (36 sessions of 15 min) in child patients (8-11 years old) with attention deficit hyperactivity disorder. Two magnetoencephalographic recordings were acquired for all participants. In order to extract the areas with changes in alpha power between both magnetoencephalographic recordings, the differences in the power ratio (pre/post-condition) were calculated using an analysis of covariance test adjusted for the age variable. The results show an increase in the post-treatment alpha power in the experimental group versus the placebo group (P < 0.01) in posterior regions. In addition, these changes were related to measures of attention, working memory and flexibility. The results seem to indicate that cognitive stimulation treatment based on progressive increases in cognitive load triggers alpha-band power changes in children diagnosed with attention deficit hyperactivity disorder in the direction of their peers without this disorder.

Gamma band functional connectivity reduction in patients with amnestic mild cognitive impairment and epileptiform activity.

There is growing evidence for neuronal hyperexcitability in Alzheimer's disease. Hyperexcitability is associated with an increase in epileptiform activity and the disruption of inhibitory activity of interneurons. Interneurons fire at a high rate and are frequently associated with high-frequency oscillations in the gamma frequency band (30-150 Hz). It is unclear how hyperexcitability affects the organization of functional brain networks. A sample of 63 amnestic mild cognitive impairment patients underwent a magnetoencephalography resting-state recording with eyes closed. Twenty (31.75%) mild cognitive impairment patients had epileptiform activity. A cluster-based analysis of the magnetoencephalography functional connectivity revealed a region within the right temporal cortex whose global connectivity in the gamma frequency band was significantly reduced in patients with epileptiform activity relative to those without epileptiform activity. A subsequent seed-based analysis showed that this was largely due to weaker gamma band connectivity of this region with ipsilateral frontal and medial regions, and the upper precuneus area. In addition, this reduced functional connectivity was associated with higher grey matter atrophy across several cortical regions in the patients with epileptiform activity. These functional network disruptions and changes in brain physiology and morphology have important clinical implications as they may contribute to cognitive decline in mild cognitive impairment and Alzheimer's disease.

Electrophysiological Brain Changes Associated With Cognitive Improvement in a Pediatric Attention Deficit Hyperactivity Disorder Digital Artificial Intelligence-Driven Intervention: Randomized Controlled Trial.

BACKGROUND: Cognitive stimulation therapy appears to show promising results in the rehabilitation of impaired cognitive processes in attention deficit hyperactivity disorder. OBJECTIVE: Encouraged by this evidence and the ever-increasing use of technology and artificial intelligence for therapeutic purposes, we examined whether cognitive stimulation therapy implemented on a mobile device and controlled by an artificial intelligence engine can be effective in the neurocognitive rehabilitation of these patients. METHODS: In this randomized study, 29 child participants (25 males) underwent training with a smart, digital, cognitive stimulation program (KAD_SCL_01) or with 3 commercial video games for 12 weeks, 3 days a week, 15 minutes a day. Participants completed a neuropsychological assessment and a preintervention and postintervention magnetoencephalography study in a resting state with their eyes closed. In addition, information on clinical symptoms was collected from the child´s legal guardians. RESULTS: In line with our main hypothesis, we found evidence that smart, digital, cognitive treatment results in improvements in inhibitory control performance. Improvements were also found in visuospatial working memory performance and in the cognitive flexibility, working memory, and behavior and general executive functioning behavioral clinical indexes in this group of participants. Finally, the improvements found in inhibitory control were related to increases in alpha-band power in all participants in the posterior regions, including 2 default mode network regions of the interest: the bilateral precuneus and the bilateral posterior cingulate cortex. However, only the participants who underwent cognitive stimulation intervention (KAD_SCL_01) showed a significant increase in this relationship. CONCLUSIONS: The results seem to indicate that smart, digital treatment can be effective in the inhibitory control and visuospatial working memory rehabilitation in patients with attention deficit hyperactivity disorder. Furthermore, the relation of the inhibitory control with alpha-band power changes could mean that these changes are a product of plasticity mechanisms or changes in the neuromodulatory dynamics. TRIAL REGISTRATION: ISRCTN Registry ISRCTN71041318; https://www.isrctn.com/ISRCTN71041318.

Compensatory neuroadaptation to binge drinking: Human evidence for allostasis.

Animal studies have established that acute alcohol increases neural inhibition and that frequent intoxication episodes elicit neuroadaptive changes in the excitatory/inhibitory neurotransmission balance. To compensate for the depressant effects of alcohol, neural hyperexcitability develops in alcohol use disorder and is manifested through withdrawal symptoms. It is unclear, however, whether neuroadaptive changes can be observed in young, emerging adults at lower levels of consumption in the absence of withdrawal symptoms. Here, we used an anatomically constrained magnetoencephalography method to assess cortical excitability in two independent sets of experiments. We measured early visual activity (1) in social drinkers during alcohol intoxication versus placebo conditions and (2) in parallel cohorts of sober binge drinkers (BDs) and light drinkers (LDs). Acute alcohol intoxication attenuated early sensory activity in the visual cortex in social drinkers, confirming its inhibitory effects on neurotransmission. In contrast, sober BDs showed greater neural responsivity compared with a matched group of LDs. A positive correlation between alcohol consumption and neural activity in BDs is indicative of cortical hyperexcitability associated with hazardous drinking. Furthermore, neural responsivity was positively correlated with alcohol intake in social drinkers whose drinking did not reach binge levels. This study provides novel evidence of compensatory imbalance reflected in the downregulation of inhibitory and upregulation of excitatory signaling associated with binge drinking in young, emerging adults. By contrasting acute effects and a history of BD, these results support the mechanistic model of allostasis. Direct neural measures are sensitive to synaptic currents and could serve as biomarkers of neuroadaptation.

Age and APOE genotype affect the relationship between objectively measured physical activity and power in the alpha band, a marker of brain disease.

BACKGROUND: Electrophysiological studies show that reductions in power within the alpha band are associated with the Alzheimer's disease (AD) continuum. Physical activity (PA) is a protective factor that has proved to reduce AD risk and pathological brain burden. Previous research has confirmed that exercise increases power in the alpha range. However, little is known regarding whether other non-modifiable risk factors for AD, such as increased age or APOE ε4 carriage, alter the association between PA and power in the alpha band. METHODS: The relationship between PA and alpha band power was examined in a sample of 113 healthy adults using magnetoencephalography. Additionally, we explored whether ε4 carriage and age modulate this association. The correlations between alpha power and gray matter volumes and cognition were also investigated. RESULTS: We detected a parieto-occipital cluster in which PA positively correlated with alpha power. The association between PA and alpha power remained following stratification of the cohort by genotype. Younger and older adults were investigated separately, and only younger adults exhibited a positive relationship between PA and alpha power. Interestingly, when four groups were created based on age (younger-older adult) and APOE (E3/E3-E3/E4), only younger E3/E3 (least predicted risk) and older E3/E4 (greatest predicted risk) had associations between greater alpha power and higher PA. Among older E3/E4, greater alpha power in these regions was associated with improved memory and preserved brain structure. CONCLUSION: PA could protect against the slowing of brain activity that characterizes the AD continuum, where it is of benefit for all individuals, especially E3/E4 older adults.