Brain communications最新文献

The clinical hallmark of episodic ataxia type 2 (EA2) consists of episodes of recurrent severe vestibulo-cerebellar dysfunction, characterized by marked postural unsteadiness and oscillopsia. Triggering factors of EA2 attacks, such as physical exertion and sensory stimulation, the high comorbidity with migraine, and the increased risk of epilepsy in EA2 suggest abnormal brain excitability. To investigate this, we assessed brain excitability in response to visual (checkerboard) and visual motion (optic flow) stimuli using interictal functional magnetic resonance imaging. Visual stimulation elicited strong bilateral neural activity in the primary visual cortex (V1-V3) and in motion-sensitive visual areas (V5) in 21 EA2 patients and 21 age-matched healthy participants (HP). Compared to HP, EA2 patients revealed decreased activity in the primary visual cortex (V1), cerebellar Crus I and II and caudal vermis but increased activation of multisensory vestibular processing areas (posterior insula, superior temporal and supramarginal gyrus, inferior parietal lobe). Interestingly, the abnormal excitability in the vestibular processing cortex areas was primarily found in patients without medication (4-aminopyridine, acetazolamide) but hardly seen in patients on medication. Our findings in treatment-naïve patients reflect disease-inherent changes in visual cortical excitability in EA2, which may be reversible through anti-episodic medication. As excitability by visual motion stimuli in multi-sensory vestibular processing cortical areas was largely found in patients on medication it may also indicate an inhibitory effect on the physiological reciprocal inhibitory visual-vestibular interaction as a multisensory mechanism for self-motion perception: the annoying oscillopsia of EA2 patients is counterbalanced by decreased visual cortex activity and hence smaller inhibition of the vestibular cortex.

Reports of associations between bradycardia and elevated resting heart rate with cognitive decline are inconsistent, and the underlying mechanisms unclear. Resting heart rate was recorded in a prospective cohort of memory clinic subjects, and the associations of resting heart rate with cross-sectional cognition, brain magnetic resonance imaging and circulating biomarkers (pTau-181 and neurofilament light chain), and longitudinal cognitive decline were investigated. Subjects with atrial fibrillation were excluded. Among 643 subjects (mean age 72.8 ± 8.0 years, 57% female, 39% dementia), 35% had resting heart rate between 60 and 69 bpm, 23% had bradycardia (<60 bpm) and 42% had elevated resting heart rate (≥70 bpm). Compared to 60-69 bpm, both bradycardia (<60 bpm) and elevated resting heart rate ≥70 bpm were associated with worse baseline global cognition (P < 0.05), and elevated resting heart rate additionally with worse Clinical Dementia Rating-Sum of boxes scores (P < 0.05) and executive function on multivariable adjustment (P = 0.001). Longitudinally, resting heart rate ≥70 bpm was associated with accelerated global cognitive decline, and bradycardia with accelerated functional decline (P _interaction < 0.05). Regarding neuroimaging and circulating biomarkers, bradycardia was associated with reduced grey matter volume, and higher levels of circulating pTau-181 and neurofilament light chain when compared to resting heart rate 60-69 bpm (P < 0.05). Conversely, elevated resting heart rate ≥70 bpm was associated with higher burden of cortical infarcts, cerebral microbleeds and lacunes compared to resting heart rate 60-69 bpm, and higher white matter hyperintensity volume ratio and cerebral microbleeds compared to bradycardia (P < 0.05). Resting heart rate displayed a U-shaped association with cognitive impairment and structural cerebral abnormalities, and may be underpinned by distinct mechanisms. Further study of the mechanisms underlying resting heart rate and cognitive trajectories are warranted. Trial registration: National Healthcare Group Domain Specific Review Board 2018/01098 and 2010/00017.

Functional neuroimaging studies have shown that a set of cortical brain regions is typically engaged during noxious stimulation and pain perception in humans. Other studies have focused on cortical brain activation patterns in patients suffering from chronic pain conditions such as fibromyalgia. Recent work has shown that functional MRI signals are also present in white matter. In this study, we present an analysis of white and grey matter functional MRI activation during a block-designed pain stimulus task in cohorts of fibromyalgia patients and healthy controls. Task data and resting-state functional MRI data were collected from female fibromyalgia patients (N = 54) and controls (N = 56). Pain-stimulation task-based functional MRI included noxious pressure of the left shin as well as an appraisal of pain intensity. White and grey matter brain activities related to pain stimulation were analysed in 29 white matter and 200 grey matter regions-of-interest using time-locked activation analysis. In the healthy cohort, we present evidence of functional MRI brain activity in response to processing painful stimuli for a large majority of cerebral white fibre tracts investigated. In contrast, white matter functional MRI activity in the fibromyalgia cohort was limited to the contralateral posterior and anterior limb of the internal capsule as well as the bilateral cerebral peduncles. Pain stimulation and appraisal of pain intensity also resulted in widespread time-locked functional MRI activity in grey matter, such as visual, somatomotor, fronto-parietal attention and frontal networks as well as in the insular cortex. We have shown that white matter functional MRI signal changes localized to thalamocortical projection fibres, which are attributed to sensory and motor neuronal processing, are related to the perception and appraisal of pain in both fibromyalgia patients and healthy controls. Our results suggest that functional MRI of white matter projection fibres provide additional information that goes beyond task-induced functional MRI responses in cerebral grey matter, with a potential to become clinically useful in the future.

A focal ischemic lesion is thought to alter neuronal activity beyond the area of structural damage, thereby interfering with the whole network architecture. Here, we used a combination of transcranial magnetic stimulation and electroencephalography in conjunction with dynamic connectivity analyses and graph theory to study alterations and reorganization of cortical connectivity in a cohort of 41 patients longitudinally after stroke. We found a link between an increase in low-frequency coupling in the delta band and alterations in neural information processing in the first weeks after stroke and their relevance for motor outcome >3 months later. We demonstrated that stroke enhances slow activity and delta coupling between frontocentral and parietal regions. In addition, we observed a loss of the physiological network architecture with a decrease in small-worldness and modularity in the delta frequency, implying that a focal ischemic lesion interferes with both cortical information integration and functional segregation within the first weeks after stroke. While we found a link between bifrontal coupling in the alpha spectrum and the degree of the motor deficit in the early post-acute phase, the amount of small-worldness disruption early after stroke indicated the motor outcome in the follow-up session. In contrast, recovery of motor function and cortical reorganization after >3 months post-stroke were paralleled by the normalization of increased low-frequency coupling and a reinstatement of the complex network structure featuring a modular and small-world topology.

Aggression is a prevalent concern among adolescents with Internet Gaming Disorder (IGD), especially those with a history of childhood trauma. While IGD and childhood trauma are linked to aggression, the underlying neurobiological mechanisms remain poorly understood. This study aims to investigate how childhood trauma influences aggressive behaviour in adolescents with IGD through brain functional network alterations. A total of 108 adolescents with varying levels of IGD and childhood trauma were recruited and divided into IGD-with-trauma, IGD-without-trauma and healthy controls. Resting-state functional connectivity and graph theory analyses were used to investigate the global and nodal topological disruptions between groups. Then, correlation and mediation analyses were conducted to assess the relationship between functional network alterations, childhood trauma (Childhood Trauma Questionnaire-Short Form score) and aggression scores. Although all groups showed small-world topology in functional networks, compared to controls, both IGD groups exhibited significantly decreased normalized clustering coefficient (γ) and small-world index (σ). For regional topology, IGD with trauma group exhibited significantly reduced efficiency in bilateral superior parietal gyrus, left hippocampus, pallidum and thalamus compared with IGD without trauma group. Furthermore, γ, σ and nodal efficiency of left superior parietal gyrus not only showed significant correlations with Childhood Trauma Questionnaire-Short Form and Reactive Aggression scores, but also significantly mediated the correlation between Childhood Trauma Questionnaire and Reactive Aggression scores. These findings highlight both local brain dysfunctions and global topological disruptions contribute to aggressive behaviour, and provide valuable guidance for future intervention strategies that improving the integration and efficiency of brain functional networks may help reduce aggression in at-risk youths with IGD and trauma histories.

Glaucoma patients often have higher injurious fall rates compared to healthy older adults. However, little is known about the underlying neural mechanisms. Recent evidence shows cerebral changes beyond the visual pathway of glaucoma patients, yet it remains unclear whether the cerebellum, which plays an important role in balance and motor control, is involved in glaucoma. In this study, we sought to investigate cerebellar functional connectivity changes in glaucoma by comparing 32 glaucoma subjects and 10 age-matched healthy control subjects who underwent resting-state functional magnetic resonance imaging at 3 Tesla with eyes closed. After conducting both regions-of-interest and seed-to-voxel analyses, we found that the functional connectivity within the cerebellum tended to be weakened in glaucoma patients compared to healthy controls, whereas the functional connectivity between some cerebral and cerebellar regions showed opposite changes in the same glaucoma subjects. Our findings underscore the potential role of cerebellar and cerebro-cerebellar dysfunction in postural and cognitive control in glaucoma patients. Taken together, these observations implicate the widespread brain changes in glaucoma beyond the cerebral regions into the cerebellum that may underlie the neural underpinnings of impaired balance control in this disease.

Adults with Down syndrome carry high risk of developing Alzheimer's disease and efforts to include this population in clinical trials remain limited. A barrier to recruitment for anti-amyloid trials includes the availability of the same amyloid PET radiotracer to multiple treatment centres. The objective of the study is to compare longitudinal rates of change between different amyloid PET radiotracers, particularly Pittsburgh compound B and florbetapir, in Down syndrome and to compare the estimated age at amyloid-positivity derived from these radiotracers. Two hundred thirty-seven adults with Down syndrome from the Trial Ready Cohort-Down syndrome and Alzheimer's Biomarker Consortium-Down syndrome studies were imaged using T₁-weighted MRI and using PET images of Pittsburgh compound B, florbetapir, NAV4694 or flutemetamol to screen for amyloid plaque burden. Currently, Pittsburgh compound B and florbetapir have longitudinal data from these cohorts, while NAV4694 has one individual with longitudinal scans and flutemetamol has no available longitudinal data. Pittsburgh compound B displayed a greater effect size to measure amyloid change compared to florbetapir. NAV4694 and Pittsburgh compound B, which are structurally similar compounds, displayed similar sensitivity to measure longitudinal amyloid increase. The estimated age at amyloid onset showed no significant difference between Pittsburgh compound B, florbetapir, NAV4694 or flutemetamol. The findings suggest that different amyloid PET radiotracers provide consistent estimates of amyloid onset age for adults with Down syndrome. Multicentre studies of Alzheimer's disease therapeutics can utilize multiple amyloid PET radiotracers to facilitate recruitment; however, these radiotracers have different sensitivity to detect longitudinal change.

There have been reports of altered functional connectivity in Alzheimer's disease, which is associated with the buildup of pathogenic proteins in the brain, including neurofibrillary tau tangles and amyloid-beta plaques. It is believed that the tau aggregates are the main driver of functional disconnection and resulted in cognitive decline in Alzheimer's disease. Tau propagates through connected neurons, a phenomenon often described as the 'prion-like' properties of tau, which can locally result in functional connectivity disruption. Apolipoprotein E gene allele 4 status and amyloid-beta are accelerating factors for tau-related pathological changes in Alzheimer's disease. However, the potential role of apolipoprotein E gene allele 4 and amyloid-beta in mediating the tau-related functional disconnection is not clear. I aimed to investigate the mediating effect of apolipoprotein E gene allele 4 and amyloid-beta on the local association of tau spreading on functional connections. I analysed follow-up resting-state functional MRI (fMRI) (non-baseline visit) and longitudinal tau-PET data from 211 subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and 138 healthy elderly individuals from the Harvard Aging Brain Study (HABS). The follow-up resting-state fMRI (non-baseline visit) was studied in order to study the time needed effect of tau pathology. The top 10 regions with the highest probability-weighted SUVR values using Gaussian mixture models were selected as individual-level tau-PET epicentres. I looked at how the relationship between functional connectivity to epicentres and individualized connectivity-related tau spreading was mediated by amyloid-beta status and the apolipoprotein E gene allele 4 genotype. Higher rates of tau aggregation accumulation were seen in areas with stronger connectedness (shorter distance-based connectivity) to the baseline-defined tau epicentres. Moreover, the association between functional connectivity to epicentres and tau spreading through functional connections was mediated by apolipoprotein E gene allele 4 and amyloid-beta status in both dataset's participants. Tau aggregates spread through functional connections and locally disrupt connectivity between tau epicentre and non-epicentre regions, which is mediated in apolipoprotein E gene allele 4 carriers and amyloid-beta-positive participants. These findings have implications for trial designs, proposing that apolipoprotein E gene allele 4 carriers and amyloid-beta-positive participants might need earlier intervention to attenuate tau spreading and tau relative functional disconnection.

Freezing of gait is a debilitating motor symptom in Parkinson's disease that significantly increases fall risk and impairs quality of life. The poorly understood pathophysiology of freezing of gait presents challenges for early prediction and therapeutic intervention. This prospective study investigated whether eye movement abnormalities, specifically in the anti-saccade paradigm, could predict freezing of gait onset in Parkinson's disease patients over a two-year follow-up period. We analysed longitudinal data from the Ontario Neurodegenerative Disease Research Initiative, focusing on Parkinson's disease patients without freezing of gait at baseline who underwent comprehensive clinical evaluations and eye movement recordings. Anti-saccade reaction time and error ratio, combined with clinical measures including right upper extremity rigidity, demonstrated significant predictive value for freezing of gait development within two years. These findings suggest that eye movement deficits and upper limb rigidity emerge years before freezing of gait onset, indicating a prodromal phase in freezing of gait pathogenesis. The predictive relationship between these measures supports the hypothesis of shared neural substrates, potentially involving the mesencephalic locomotor region, in the development of both oculomotor dysfunction and gait freezing episodes.