Detecting the Information of Functional Connectivity Networks in Normal Aging Using Deep Learning From a Big Data Perspective.

BackgroundPatients with amnestic mild cognitive impairment (aMCI) and Alzheimer’s disease (AD) show functional and structural connectivity alterations in the default mode network (DMN) while cerebrovascular disease (CeVD) shows functional and structural connectivity changes in the executive control network (ECN). Such disruptions are associated with memory and executive function impairment, respectively. Concurrent AD and CeVD pathology is associated with a higher rate of cognitive decline and differential neurodegenerative patterns. Together, such findings are likely reflective of different underlying pathology in AD with and without CeVD. However, few studies have examined the effect of CeVD on network functional connectivity (task-free functional magnetic resonance imaging (fMRI)) and structural connectivity (diffusion MRI) of the DMN and ECN in aMCI and AD using a hypothesis-driven multiple seed-based approach.MethodsWe examined functional and structural connectivity network changes in 39 aMCI, 50 aMCI+CeVD, 47 AD, 47 AD+CeVD, and 65 healthy controls (HCs) and their associations with cognitive impairment in the executive/attention and memory domains.ResultsWe demonstrate divergent DMN and ECN functional connectivity changes in CeVD and non-CeVD subjects. Compared with controls, intra-DMN hippocampal functional connectivity reductions were observed in both AD and AD+CeVD, while intra-DMN parietal and medial prefrontal-parietal functional connectivity was higher in AD+CeVD and aMCI+CeVD, but lower in AD. Intra-ECN frontal functional connectivity increases and fronto-parietal functional connectivity decreases occurred in CeVD but not non-CeVD subjects. Such functional connectivity alterations were related with cognitive impairment in a dissociative manner: intra-DMN functional connectivity changes were associated with worse cognition primarily in non-CeVD groups, while intra-ECN functional connectivity changes were associated with worse cognition primarily in CeVD groups. Additionally, CeVD and non-CeVD groups showed overlapping and distinct alterations in inter-network DMN-ECN functional connectivity depending on disease severity. In contrast to functional connectivity, CeVD groups had greater network structural connectivity damage compared with non-CeVD groups in both aMCI and AD patients. Network structural connectivity damage was associated with worse cognition.ConclusionsWe demonstrate differential functional and structural network changes between aMCI and AD patients with and without CeVD through diverging and deleterious network-based degeneration underlying domain-specific cognitive impairment.

ObjectiveChildren’s motor development is closely related to the development of their brain functions. Currently, the central neural mechanisms in children with developmental coordination disorder (DCD) are poorly understood. This study investigated the changes of EEG patterns in DCD boys.MethodsIn this study, 15 boys with DCD were screened via the Movement Assessment Battery for Children 2nd Edition (MABC-2), and 15 boys with typical development (TD) at the same age were matched as the control group. The electroencephalographic (EEG) signals of the boys were recorded in the resting state and during the visual motor integration (VMI) task, and the relative power, sample entropy (SampEn), phase lag index (PLI), and lateralization of functional connectivity were analyzed.ResultsIn the resting state, no abnormal changes were found in the relative power of the EEG or SampEn of the DCD boys (p > 0.05), and the PLI of each frequency band in the DCD boys was significantly lower than that in the TD boys (p < 0.001). During the VMI task, the θ power of the DCD boys decreased significantly at the right frontal central border (FC2: p < 0.05), the β power decreased significantly at the right frontal central border (FC2: p < 0.001), and the midline of the parietal region (Pz: p < 0.001), and there was no abnormal change in SampEn. The PLIs of the α, β, and γ frequency bands in DCD boys were significantly lower than those in TD boys (p < 0.001), and the functional connectivity of the β band around the cerebral motor cortex was significantly lateralized right hemispheric acceleration (p < 0.05).ConclusionThe brain functional network connectivity of DCD boys may have developmental defects, and the abnormal changes in brain activation, functional connectivity, and lateralization of functional connectivity during movement may be important brain mechanisms for their poor motor coordination. These findings provide a new perspective for analyzing and evaluating the brain function of DCD children.

Unprecedented 4D spatiotemporal infant regional cerebral blood flow framework and region-specific physiology–function coupling across infancy were elucidated, highlighting strong physiology–function coupling specifically at the default-mode network to meet extraneuronal metabolic demand for network emergence.

The relationship between age-related changes in brain structural connectivity (SC) and functional connectivity (FC) with cognition is not well understood. Furthermore, it is not clear whether cognition is represented via a similar spatial pattern of FC and SC or instead is mapped by distinct sets of distributed connectivity patterns. To this end, we used a longitudinal, within-subject, multimodal approach aiming to combine brain data from diffusion-weighted MRI (DW-MRI), and functional MRI (fMRI) with behavioral evaluation, to better understand how changes in FC and SC correlate with changes in cognition in a sample of older adults. FC and SC measures were derived from the multimodal scans acquired at two time points. Change in FC and SC was correlated with 13 behavioral measures of cognitive function using Partial Least Squares Correlation (PLSC). Two of the measures indicate an age-related change in cognition and the rest indicate baseline cognitive performance. FC and SC—cognition correlations were expressed across several cognitive measures, and numerous structural and functional cortical connections, mainly cingulo-opercular, dorsolateral prefrontal, somatosensory and motor, and temporo-parieto-occipital, contributed both positively and negatively to the brain-behavior relationship. Whole-brain FC and SC captured distinct and independent connections related to the cognitive measures. Overall, we examined age-related function-structure associations of the brain in a comprehensive and integrated manner, using a multimodal approach. We pointed out the behavioral relevance of age-related changes in FC and SC. Taken together, our results highlight that the heterogeneity in distributed FC and SC connectivity patterns provide unique information about the variable nature of healthy cognitive aging.

Previous studies showed alterations of brain function in the ventromedial prefrontal cortex of schizophrenia patients. Also, neurochemical changes, especially GABA level alteration, have been found in the medial prefrontal cortex of schizophrenia patients. However, the relationship between GABA level in the ventromedial prefrontal cortex and brain functional activity in schizophrenia patients remains unexplored. In total, 23 drug-naïve, first-episode psychosis patients and 26 matched healthy controls completed the study. The single voxel proton magnetic resonance spectroscopy data were acquired in ventromedial prefrontal cortex region, which was used as the seed region for resting-state functional connectivity analysis. The proton magnetic resonance spectroscopy data were processed to quantify the concentrations of GABA+, glutamine and glutamate, and N-acetylaspartate in ventromedial prefrontal cortex. Spearman correlation analysis was used to examine the relationship between metabolite concentration, functional connectivity and clinical variables. Pearson correlation analysis was used to examine the relationship between GABA+ concentration and functional connectivity value. In first-episode psychosis patients, GABA+ level in ventromedial prefrontal cortex was higher and was positively correlated with ventromedial prefrontal cortex-left middle orbital frontal cortex functional connectivity. N-acetylaspartate level was positively correlated with positive symptoms, and the functional connectivity between ventromedial prefrontal cortex and left precuneus was negatively associated with negative symptoms of first-episode psychosis patients. Our results indicated that ventromedial prefrontal cortex functional connectivity changes were positively correlated with higher local GABA+ level in first-episode psychosis patients. The altered neurochemical concentration and functional connectivity provide insights into the pathology of schizophrenia.

Altered resting-state functional network connectivity is associated with suicide attempt in young depressed patients

Several imaging studies have identified localized anatomical and functional brain changes in medication-overuse headache (MOH). The objective of this article is to evaluate whole-brain functional connectivity at rest together with voxel-based morphometry in MOH patients, in comparison with episodic migraine (EM) patients and healthy controls (HCs). Anatomical MRI and resting-state functional MRI scans were obtained in MOH patients (n = 17 and 9, respectively), EM patients (n = 18 and 15, respectively) and HCs (n = 17 and 17). SPM8 was used to analyze voxel-based morphometry and seed (left precuneus) to voxel connectivity data in the whole brain. Functional connectivity at rest was altered in MOH patients. Connectivity was decreased between precuneus and regions of the default-mode network (frontal and parietal cortices), but increased between precuneus and hippocampal/temporal areas. These functional modifications were not accompanied by significant gross morphological changes. Furthermore, connectivity between precuneus and frontal areas in MOH was negatively correlated with migraine duration and positively correlated with self-evaluation of medication dependence. Gray matter volumes of frontal regions, precuneus and hippocampus were also negatively related to migraine duration. Functional connectivity within the default-mode network appeared to predict anxiety scores of MOH patients while gray matter volumes in this network predicted their depression scores. Our data suggest that MOH is associated with functional alterations within intrinsic brain networks rather than with macrostructural changes. They also support the view that dependence-related processes might play a prominent role in its development and maintenance.

Perinatal brain injury is a significant cause of adverse neurodevelopmental outcomes. The objective of this systematic review was to identify patterns of altered brain function, quantified using functional connectivity (FC) changes in resting-state fMRI (rs-fMRI) data, that were associated with motor and language outcomes in individuals with a history of perinatal brain injury. A systematic search using electronic databases was conducted to identify relevant studies. A total of 10 studies were included in the systematic review, representing 260 individuals with a history of perinatal brain injury. Motor and language outcomes were measured at time points ranging from 4 months to 29 years 1 month. Relations between FC and motor measures revealed increased intra-hemispheric FC, reduced inter-hemispheric FC and impaired lateralization of motor-related brain regions associated with motor outcomes. Altered FC within sensorimotor, visual, cerebellum and frontoparietal networks, and between sensorimotor, visual, auditory and higher-order networks, including cerebellum, frontoparietal, default-mode, salience, self-referential and attentional networks were also associated with motor outcomes. In studies assessing the relationship between rs-fMRI and language outcome, reduced intra-hemispheric FC, increased inter-hemispheric FC and right-hemisphere lateralization of language-related brain regions correlated with language outcomes. Evidence from this systematic review suggests a possible association between diaschisis and motor and language impairments in individuals after perinatal brain lesions. These findings support the need to explore the contributions of additional brain regions functionally connected but remote from the primary lesioned brain area for targeted treatments and appropriate intervention, though more studies with increased standardization across neuroimaging and neurodevelopmental assessments are needed.

Tinnitus severity is related to changes in functional connectivity between precuneus and inferior temporal gyrus.

Brain functional connectivity (FC) changes and microstructural abnormalities are reported in infants born moderate and late preterm (MLPT). We evaluated the effect of low-grade (grades I, II) intraventricular hemorrhage (IVH) in MLPT babies on brain structural connectivity (SC) and FC. Babies born MLPT between January 2014 and May 2017 underwent brain ultrasound (US) at 72h and 7days after birth, and MRI at around term equivalent. The MRI protocol comprised T1- and T2-weighted sequences, diffusion tensor imaging (DTI), and resting-state functional MRI (fMRI). SC and FC were assessed using graph analysis. Of 350 MLPT neonates, 15 showed low-grade IVH on US at 72h, for which brain MRI was available in 10. These 10 infants, with mean gestational age (GA) 34.0 ± 0.8weeks, comprised the study group, and 10 MLPT infants of mean GA 33.9 ± 1.1weeks, with no abnormalities on brain US and MRI, were control subjects. All study subjects presented modularity, small world topology, and rich club organization for both SC and FC. The patients with low-grade IVH had lower FC rich club coefficient and lower SC betweenness centrality in the left frontoparietal operculum, and lower SC rich club coefficient in the right superior orbitofrontal cortex than the control subjects. Topological and functional properties of mature brain connectivity are present in MLPT infants. IVH in these infants was associated with structural and functional abnormalities in the left frontoparietal operculum and right orbitofrontal cortex, regions related to language and cognition.

Functional network topology associated with apathy in Alzheimer's disease

Introduction To evaluate resting state functional connectivity and topological properties of brain network in narcolepsy compared with healthy controls. Methods Resting state fMRI was performed in 26 adult narcolepsy patients and 30 matched healthy controls. MRI data was first analyzed by group independent component analysis, then a graph theoretical method was applied to evaluate topological properties within whole brain. Small-world network parameters and nodal topological properties were measured. Altered topological properties in brain areas between groups were selected as ROI-seeds, then functional connectivity among these ROI-seeds were compared between groups. Partial correlation analysis was performed to evaluate the relationship between sleepiness severity and functional connectivity or topological properties in the narcolepsy. Results 21 independent components out of 48 components were obtained. Compared with healthy controls, narcolepsy exhibited a significant decreased functional connectivity within the executive and salience network, while increased functional connectivity in bilateral frontal lobe within executive network can be detected in narcolepsy. There were no differences in small-world network properties between narcolepsy and healthy controls. The altered brain areas in nodal topological properties were mainly located in inferior frontal cortex, basal ganglia, anterior cingulate, sensory cortex, supplementary motor cortex and visual cortex between groups. In the partial correlation analysis, nodal topological properties in putamen, anterior cingulate and sensory cortex as well as functional connectivity between these brain regions were correlated with the severity of sleepiness (sleep latency, REM sleep latency and ESS) among narcolepsy. Conclusion Altered connectivity within executive network and salience network were found in narcolepsy. Functional connection changes between left frontal cortex and left caudate nucleus may be one of the parameters describing the severity of narcolepsy. Nodal topological properties alterations in left putamen and left posterior cingulate, changes in functional connectivity between left supplementary motor area and right occipital as well as changes in functional connectivity between left anterior cingulate gyrus and bilateral postcentral gyrus can be considered to be a specific indicator for evaluating the severity of narcolepsy. Support National Natural Science Foundation of China (81700088)National Program on Key Basic Research Project of China (973 Program, 2015CB856405)

Motor learning-induced changes in functional brain connectivity as revealed by means of graph-theoretical network analysis

Sacral neuromodulation is widely used for refractory overactive bladder; however, its mechanism of action remains unclear. This study aims to investigate real-time changes in brain activity and functional connectivity (FC) during neuromodulation in an overactive bladder (OAB) rat model using functional magnetic resonance imaging. Twelve female Sprague Dawley rats were implanted with fine bipolar electrodes adjacent to the L6 nerve root. Cystometry was performed on normal rats, acetic acid-induced OAB rats, and during spinal nerve stimulation (SNS) to confirm efficacy. Task-based functional magnetic resonance imaging (fMRI) was acquired using a 20-second rest-stimulus cycle, followed by T2-weighted anatomical imaging on a 9.4T MRI scanner. Comparative analyses examined changes in the amplitude of low-frequency fluctuations (ALFF) and FC between normal and OAB rats. Brain activity during SNS was further assessed using the general linear model (GLM) and FC analysis. Statistical significance was defined as P<0.05 (family-wise error-corrected). Compared with normal rats, OAB rats exhibited increased ALFF in the left prefrontal cortex, periaqueductal gray (PAG), and left primary somatosensory cortex. In addition, FC between the PAG and pons was enhanced (P=0.002). GLM analysis revealed that the left primary somatosensory cortex, left prefrontal cortex, corpus callosum, left secondary motor area, and right brainstem exhibited decreased activity during SNS (P<0.05). Significant FC changes were observed between several regions: the left cerebellum and left caudal zona incerta (P=0.024), right fasciculus retroflexus and left ventral orbital area (P=0.025), and between the pons and PAG (P=0.004). Seed-to-voxel analysis indicated altered FC between clusters identified in the GLM analysis and regions including the PAG, left cingulate area, left prefrontal cortex, left caudate putamen, and right granular insular cortex. Our fMRI study identified several alterations in brain activity during SNS in rats. Specifically, activity in the left prefrontal cortex decreased during SNS, and FC between the PAG and pons was reduced. These changes may represent central mechanisms underlying sacral neuromodulation in OAB patients.

Motor-cognitive interactive interventions, such as action observation training (AOT), have shown great potential in restoring cognitive function and motor behaviors. It is expected that an advanced AOT incorporating specific Tai Chi movements with continuous and spiral characteristics can facilitate the shift from automatic to intentional actions and thus enhance motor control ability for early-stage PD. Nonetheless, the underlying neural mechanisms remain unclear. The study aimed to investigate changes in brain functional connectivity (FC) and clinical improvement after 12 weeks of Tai Chi-based action observation training (TC-AOT) compared to traditional physical therapy (TPT). Thirty early-stage PD patients were recruited and randomly assigned to the TC-AOT group (N = 15) or TPT group (N = 15). All participants underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans before and after 12 weeks of training and clinical assessments. The FCs were evaluated by seed-based correlation analysis based on the default mode network (DMN). The rehabilitation effects of the two training methods were compared while the correlations between significant FC changes and clinical improvement were investigated. The results showed that the TC-AOT group exhibited significantly increased FCs between the dorsal medial prefrontal cortex and cerebellum crus I, between the posterior inferior parietal lobe and supramarginal gyrus, and between the temporal parietal junction and clusters of middle occipital gyrus and superior temporal. Moreover, these FC changes had a positive relationship with patients' improved motor and cognitive performance. The finding supported that the TC-AOT promotes early-stage PD rehabilitation outcomes by promoting brain neuroplasticity where the FCs involved in the integration of sensorimotor processing and motor learning were strengthened.