Reorganization Of Functional Connectivity Research Articles

Biophysical models applied to dementia patients reveal links between geographical origin, gender, disease duration, and loss of neural inhibition

BackgroundThe hypothesis of decreased neural inhibition in dementia has been sparsely studied in functional magnetic resonance imaging (fMRI) data across patients with different dementia subtypes, and the role of social and demographic heterogeneities on this hypothesis remains to be addressed.MethodsWe inferred regional inhibition by fitting a biophysical whole-brain model (dynamic mean field model with realistic inter-areal connectivity) to fMRI data from 414 participants, including patients with Alzheimer’s disease, behavioral variant frontotemporal dementia, and controls. We then investigated the effect of disease condition, and demographic and clinical variables on the local inhibitory feedback, a variable related to the maintenance of balanced neural excitation/inhibition.ResultsDecreased local inhibitory feedback was inferred from the biophysical modeling results in dementia patients, specific to brain areas presenting neurodegeneration. This loss of local inhibition correlated positively with years with disease, and showed differences regarding the gender and geographical origin of the patients. The model correctly reproduced known disease-related changes in functional connectivity.ConclusionsResults suggest a critical link between abnormal neural and circuit-level excitability levels, the loss of grey matter observed in dementia, and the reorganization of functional connectivity, while highlighting the sensitivity of the underlying biophysical mechanism to demographic and clinical heterogeneities in the patient population.

Structural-and-dynamical similarity predicts compensatory brain areas driving the post-lesion functional recovery mechanism.

The focal lesion alters the excitation-inhibition (E-I) balance and healthy functional connectivity patterns, which may recover over time. One possible mechanism for the brain to counter the insult is global reshaping functional connectivity alterations. However, the operational principles by which this can be achieved remain unknown. We propose a novel equivalence principle based on structural and dynamic similarity analysis to predict whether specific compensatory areas initiate lost E-I regulation after lesion. We hypothesize that similar structural areas (SSAs) and dynamically similar areas (DSAs) corresponding to a lesioned site are the crucial dynamical units to restore lost homeostatic balance within the surviving cortical brain regions. SSAs and DSAs are independent measures, one based on structural similarity properties measured by Jaccard Index and the other based on post-lesion recovery time. We unravel the relationship between SSA and DSA by simulating a whole brain mean field model deployed on top of a virtually lesioned structural connectome from human neuroimaging data to characterize global brain dynamics and functional connectivity at the level of individual subjects. Our results suggest that wiring proximity and similarity are the 2 major guiding principles of compensation-related utilization of hemisphere in the post-lesion functional connectivity re-organization process.

Serum neurofilament light chain is associated with disturbed limbic-based functional connectivity in patients with anti-NMDAR encephalitis.

Anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis shows a predilection for affecting the limbic system, but structural MRI in most patients is usually unremarkable. However, the functional connectivity reorganization of limbic nodes remains unknown. Serum neurofilament light chains (sNfL) are clinically linked with the disease severity and neurological disability of anti-NMDAR encephalitis. However, the relationship between sNfL and limbic-based functional architecture has not been explored. We consecutively recruited 20 convalescent patients with anti-NMDAR encephalitis and 24 healthy controls from March 2018 to March 2021. Resting-state functional MRI metrics, including fractional amplitude of low-frequency fluctuation (fALFF), regional homogeneity (ReHo), and atlas-based seed functional connectivity, were analyzed to investigate regional activities and functional connectivity alterations. Correlation analysis among functional connectivity, sNfL, Mini-Mental State Examination (MMSE), and Montreal cognitive assessment outcomes were explored in patients. Compared with those of healthy controls, the fALFF and ReHo were consistently increased in regions of the posterior default mode network (DMN) hub, mainly the bilateral supramarginal gyrus and precuneus, in patients with anti-NMDAR encephalitis (FWE-corrected p< 0.05). Patients demonstrated disturbed functional organization characterized by reduced connectivity of the posterior DMN hub with the sensorimotor cortex and hypoconnectivity of the parahippocampal gyrus (PHG) with the right fusiform gyrus but extensively enhanced thalamocortical connectivity (FWE-corrected p< 0.05). Furthermore, convalescent sNfL showed a positive correlation with enhanced thalamocortical connectivity (r= 0.4659, p= 0.0384). Onset sNfL with an independent linear correlation to convalescent MMSE performance (B coefficient, -0.013, 95% CI, -0.025 ~ -0.002, p= 0.0260) was positively correlated with intra-DMN connectivity (r= 0.8969, p< 0.0001) and limbic-sensory connectivity (r= 0.4866, p= 0.0346 for hippocampus seed and r= 0.5218, p= 0.0220 for PHG seed). Patients with anti-NMDAR encephalitis demonstrated disturbed functional organization with substantial thalamocortical hyperconnectivity, that was positively correlated with convalescent sNfL. Onset sNfL showed a positive correlation with intra-DMN connectivity and limbic-sensory connectivity.

Regional Neural Activity Abnormalities and Whole-Brain Functional Connectivity Reorganization in Bulimia Nervosa: Evidence From Resting-State fMRI.

The management of eating behavior in bulimia nervosa (BN) patients is a complex process, and BN involves activity in multiple brain regions that integrate internal and external functional information. This functional information integration occurs in brain regions involved in reward, cognition, attention, memory, emotion, smell, taste, vision and so on. Although it has been reported that resting-state brain activity in BN patients is different from that of healthy controls, the neural mechanisms remain unclear and need to be further explored. The fractional amplitude of low-frequency fluctuation (fALFF) analyses are an important data-driven method that can measure the relative contribution of low-frequency fluctuations within a specific frequency band to the whole detectable frequency range. The fALFF is well suited to reveal the strength of interregional cooperation at the single-voxel level to investigate local neuronal activity power. FC is a brain network analysis method based on the level of correlated dynamics between time series, which establishes the connection between two spatial regions of interest (ROIs) with the assistance of linear temporal correlation. Based on the psychological characteristics of patients with BN and the abnormal brain functional activities revealed by previous neuroimaging studies, in this study, we investigated alterations in regional neural activity by applying fALFF analysis and whole-brain functional connectivity (FC) in patients with BN in the resting state and to explore correlations between brain activities and eating behavior. We found that the left insula and bilateral inferior parietal lobule (IPL), as key nodes in the reorganized resting-state neural network, had altered FC with other brain regions associated with reward, emotion, cognition, memory, smell/taste, and vision-related functional processing, which may have influenced restrained eating behavior. These results could provide a further theoretical basis and potential effective targets for neuropsychological treatment in patients with BN.

The Correlation between Functional Connectivity of the Primary Somatosensory Cortex and Cervical Spinal Cord Microstructural Injury in Patients with Cervical Spondylotic Myelopathy.

Objectives To explore functional connectivity reorganization of the primary somatosensory cortex, the chronic microstructure damage of the cervical spinal cord, and their relationship in cervical spondylotic myelopathy (CSM) patients. Methods Thirty-three patients with CSM and 23 healthy controls (HCs) were recruited for rs-fMRI and cervical spinal cord diffusion tensor imaging (DTI) scans. Six subregions (including leg, back, chest, hand, finger and face) of bilateral primary somatosensory cortex (S1) were selected for seed-based whole-brain functional connectivity (FC). Then, we calculated the apparent diffusion coefficient (ADC) and fractional anisotropy (FA) values of the cervical spinal cord. Correlation analysis was conducted between FC values of brain regions and DTI parameters of cervical spinal cord (ADC, FA), and their relationship with each other and clinical parameters. Results Compared with the HC group, the CSM group showed decreased FC between areas of the left S1hand, the left S1leg, the right S1chest, and the right S1leg with brain regions. The mean FA values of the cervical spinal cord in CSM patients were positively correlated with JOA scores. Especially, the FApos values of bilateral posterior funiculus were positively correlated with JOA scores. The ADC and FA values of bilateral posterior funiculus in the cervical spinal cord were also positively correlated with the FC values. Conclusions There was synchronization between chronic cervical spinal cord microstructural injury and cerebral cortex sensory function compensatory recombination. DTI parameters of the posterior cervical spinal cord could objectively reflect the degree of cerebral cortex sensory function impairment to a certain extent.

Dynamic Reorganization of Functional Connectivity During Post-Break Task Reengagement.

Because of the undesired fatigue-related consequences, accumulating efforts have been made to find an effective intervention to alleviate the suboptimal cognitive function caused by mental fatigue. Nonetheless, limitations of intervention and evaluation methods may hinder the revealing of underlying neural mechanisms of fatigue recovery. Through the newly-developed dynamic functional connectivity (FC) analysis framework, this study aims to investigate the effects of two types of mid-task interventions (i.e., rest-break and moderate-intensity exercise-break) on the dynamic reorganization of FC during the execution of psychomotor vigilance test (PVT). Using a sliding window approach, temporal brain networks within each frequency band (i.e., δ , θ , α , & β ) were estimated before and immediately after the intervention, and towards the end of the task to investigate the immediate and delayed effects respectively during post-break task reengagement. Behaviourally, similar beneficial effects of exercise- and rest-break on performance were observed, manifested by the immediate improvements after both interventions and a long-lasting influence towards the end of tasks. Moreover, temporal brain networks assessment showed significant immediate decreases of fluctuability, which was followed by an increase of fluctuability towards the end of intervention tasks. Furthermore, the temporal nodal measure revealed the channels with significant differences across tasks were mainly resided in the fronto-parietal areas that exhibited interesting frequency-dependent distribution. The observations of immediate and delayed dynamic FC reorganizations extend previous fatigue-related intervention and static FC studies, and provide new insight into the dynamic characteristics of FC during post-break task reengagement.

Resting-state Functional Connectivity After Occipital Stroke

Background Resting-state functional magnetic resonance imaging (rsfMRI) reflects spontaneous activation of cortical networks. After stroke, these networks reorganize, both due to structural lesion and reorganization of functional connectivity (FC). Objective We studied FC in chronic phase occipital stroke patients with homonymous visual field defects before and after repetitive transorbital alternating current stimulation (rtACS). Methods This spin-off study, embedded in the randomized, sham-controlled REVIS trial, comprised 16 chronic occipital stroke patients with visual field defect and 12 healthy control subjects. The patients underwent rsfMRI at baseline, after two weeks of rtACS or sham treatment, and after two months of treatment-free follow-up, whereas the control subjects were measured once. We used a multivariate regression connectivity model to determine mutual prediction accuracy between 74 cortical regions of interest. Additionally, the model parameters were included into a graph to analyze average path length, centrality eigenvector, centrality degree, and clustering of the network. The patients and controls at baseline and the two treatment groups were compared with multilevel modeling. Results Before treatment, the patients and controls had similar whole-network prediction accuracy and network parameters, whereas centrality eigenvector differed in perilesional regions, indicating local modification in connectivity. In line with behavioral results, neither prediction accuracy nor any network parameter changed systematically as a result of rtACS rehabilitation compared to sham. Conclusions Whole-network FC showed no difference between occipital stroke patients and healthy population, congruent with the peripheral location of the visual network in relation to the high-density cortical core. rtACS treatment in the given setting did not affect FC.

Functional connectome reorganization relates to post-stroke motor recovery and structural and functional disconnection

Motor recovery following ischemic stroke is contingent on the ability of surviving brain networks to compensate for damaged tissue. In rodent models, sensory and motor cortical representations have been shown to remap onto intact tissue around the lesion site, but remapping to more distal sites (e.g. in the contralesional hemisphere) has also been observed. Resting state functional connectivity (FC) analysis has been employed to study compensatory network adaptations in humans, but mechanisms and time course of motor recovery are not well understood. Here, we examine longitudinal FC in 23 first-episode ischemic pontine stroke patients and utilize a graph matching approach to identify patterns of functional connectivity reorganization during recovery. We quantified functional reorganization between several intervals ranging from 1 week to 6 months following stroke, and demonstrated that the areas that undergo functional reorganization most frequently are in cerebellar/subcortical networks. Brain regions with more structural and functional connectome disruption due to the stroke also had more remapping over time. Finally, we show that functional reorganization is correlated with the extent of motor recovery in the early to late subacute phases, and furthermore, individuals with greater baseline motor impairment demonstrate more extensive early subacute functional reorganization (from one to two weeks post-stroke) and this reorganization correlates with better motor recovery at 6 months. Taken together, these results suggest that our graph matching approach can quantify recovery-relevant, whole-brain functional connectivity network reorganization after stroke.

Compensatory functional connectome changes in a rat model of traumatic brain injury.

Penetrating cortical impact injuries alter neuronal communication beyond the injury epicentre, across regions involved in affective, sensorimotor and cognitive processing. Understanding how traumatic brain injury reorganizes local and brain wide nodal interactions may provide valuable quantitative parameters for monitoring pathological progression and recovery. To this end, we investigated spontaneous fluctuations in the functional MRI signal obtained at 11.1 T in rats sustaining controlled cortical impact and imaged at 2- and 30-days post-injury. Graph theory-based calculations were applied to weighted undirected matrices constructed from 12 879 pairwise correlations between functional MRI signals from 162 regions. Our data indicate that on Days 2 and 30 post-controlled cortical impact there is a significant increase in connectivity strength in nodes located in contralesional cortical, thalamic and basal forebrain areas. Rats imaged on Day 2 post-injury had significantly greater network modularity than controls, with influential nodes (with high eigenvector centrality) contained within the contralesional module and participating less in cross-modular interactions. By Day 30, modularity and cross-modular interactions recover, although a cluster of nodes with low strength and low eigenvector centrality remain in the ipsilateral cortex. Our results suggest that changes in node strength, modularity, eigenvector centrality and participation coefficient track early and late traumatic brain injury effects on brain functional connectivity. We propose that the observed compensatory functional connectivity reorganization in response to controlled cortical impact may be unfavourable to brain wide communication in the early post-injury period.

Drinking coffee enhances neurocognitive function by reorganizing brain functional connectivity

The purpose of this study was to identify the mechanisms underlying effects of coffee on cognition in the context of brain networks. Here we investigated functional connectivity before and after drinking coffee using graph-theoretic analysis of electroencephalography (EEG). Twenty-one healthy adults voluntarily participated in this study. The resting-state EEG data and results of neuropsychological tests were consecutively acquired before and 30 min after coffee consumption. Graph analyses were performed and compared before and after coffee consumption. Correlation analyses were conducted to assess the relationship between changes in graph measures and those in cognitive function tests. Functional connectivity (FC) was reorganized toward more efficient network properties after coffee consumption. Performance in Digit Span tests and Trail Making Test Part B improved after coffee consumption, and the improved performance in executive function was correlated with changes in graph measures, reflecting a shift toward efficient network properties. The beneficial effects of coffee on cognitive function might be attributed to the reorganization of FC toward more efficient network properties. Based on our findings, the patterns of network reorganization could be used as quantitative markers to elucidate the mechanisms underlying the beneficial effects of coffee on cognition, especially executive function.

Connectivity Measures Differentiate Cortical and Subcortical Sub-Acute Ischemic Stroke Patients.

Brain lesions caused by cerebral ischemia lead to network disturbances in both hemispheres, causing a subsequent reorganization of functional connectivity both locally and remotely with respect to the injury. Quantitative electroencephalography (qEEG) methods have long been used for exploring brain electrical activity and functional connectivity modifications after stroke. However, results obtained so far are not univocal. Here, we used basic and advanced EEG methods to characterize how brain activity and functional connectivity change after stroke. Thirty-three unilateral post stroke patients in the sub-acute phase and ten neurologically intact age-matched right-handed subjects were enrolled. Patients were subdivided into two groups based on lesion location: cortico-subcortical (CS, n = 18) and subcortical (S, n = 15), respectively. Stroke patients were evaluated in the period ranging from 45 days since the acute event (T0) up to 3 months after stroke (T1) with both neurophysiological (resting state EEG) and clinical assessment (Barthel Index, BI) measures, while healthy subjects were evaluated once. Brain power at T0 was similar between the two groups of patients in all frequency bands considered (δ, θ, α, and β). However, evolution of θ-band power over time was different, with a normalization only in the CS group. Instead, average connectivity and specific network measures (Integration, Segregation, and Small-worldness) in the β-band at T0 were significantly different between the two groups. The connectivity and network measures at T0 also appear to have a predictive role in functional recovery (BI T1-T0), again group-dependent. The results obtained in this study showed that connectivity measures and correlations between EEG features and recovery depend on lesion location. These data, if confirmed in further studies, on the one hand could explain the heterogeneity of results so far observed in previous studies, on the other hand they could be used by researchers as biomarkers predicting spontaneous recovery, to select homogenous groups of patients for the inclusion in clinical trials.

Distinction of High- and Low-Frequency Repetitive Transcranial Magnetic Stimulation on the Functional Reorganization of the Motor Network in Stroke Patients.

Objective To investigate the functional reorganization of the motor network after repetitive transcranial magnetic stimulation (rTMS) in stroke patients with motor dysfunction and the distinction between high-frequency rTMS (HF-rTMS) and low-frequency rTMS (LF-rTMS). Methods Thirty-three subcortical stroke patients were enrolled and assigned to the HF-rTMS group, LF-rTMS group, and sham group. Each patient of rTMS groups received either 10.0 Hz rTMS over the ipsilesional primary motor cortex (M1) or 1.0 Hz rTMS over the contralesional M1 for 10 consecutive days. A resting-state functional magnetic resonance imaging (fMRI) scan and neurological examinations were performed at baseline and after rTMS. The motor network and functional connectivities intramotor network with the core brain regions including the bilateral M1, premotor area (PMA), and supplementary motor area (SMA) were calculated. Comparisons of functional connectivities and Pearson correlation analysis between functional connectivity changes and behavioral improvement were calculated. Results Significant motor improvement was found after rTMS in all groups which was larger in two rTMS groups than in the sham group. The functional connectivities of the motor network were significantly increased in bilateral M1, SMA, and contralesional PMA after real rTMS. These changes were only detected in the regions of the ipsilesional hemisphere in the HF-rTMS group and in the regions of the contralesional hemisphere in the LF-rTMS group. Significantly changed functional connectivities of the intramotor network were found between the ipsilesional M1 and SMA and contralesional PMA, between contralesional M1 and contralesional SMA, between contralesional SMA and ipsilesional SMA and contralesional PMA in the HF-rTMS group in which the changed connectivity between ipsilesional M1 and contralesional PMA was obviously correlated with the motor improvement. In addition, the functional connectivity of the intramotor network between ipsilesional M1 and contralesional PMA was significantly higher in the HF-rTMS group than in the LF-rTMS group. Conclusion Both HF-rTMS and LF-rTMS have a positive effect on motor recovery in patients with subcortical stroke and could promote the reorganization of the motor network. HF-rTMS may contribute more to the functional connectivity reorganization of the ipsilesional motor network and realize greater benefit to the motor recovery.

Subacute functional connectivity correlates with cognitive recovery six months after stroke

Background and purposeCognitive impairment is a common consequence of stroke, and the rewiring of the surviving brain circuits might contribute to cognitive recovery. Studies investigating how the functional connectivity of networks change across time and whether their remapping relates to cognitive recovery in stroke patients are scarce. We aimed to investigate whether resting-state functional connectivity was associated with cognitive performance in stroke patients and if any alterations in these networks were correlated with cognitive recovery. MethodsUsing an fMRI ROI-ROI approach, we compared the ipsilesional, contralesional and interhemispheric functional connectivity of three resting-state networks involved in cognition – the Default Mode (DMN), Salience (SN) and Central Executive Networks (CEN), in subacute ischemic stroke patients (time 1, n = 37, stroke onset: 24.32 ± 7.44 days, NIHSS: 2.66 ± 3.45) with cognitively healthy controls (n = 20). Patients were reassessed six months after the stroke event (time 2, n = 20, stroke onset: 182.05 ± 8.17 days) to verify the subsequent reorganization of functional connections and whether such reorganization was associated with cognitive recovery. ResultsAt time 1, patients had weaker interhemispheric connectivity in the DMN than controls; better cognitive performance at time 1 was associated with stronger interhemispheric and ipsilesional DMN connectivity, and weaker contralesional SN connectivity. At time 2, there were no changes in functional connectivity in stroke patients, compared to time 1. Better cognitive recovery measured at time 2 (time 2 – time 1) was associated with stronger functional connectivity in the DMN, and weaker interhemispheric subacute connectivity in the SN, both from time 1. ConclusionsStroke disrupts the functional connectivity of the DMN, not only at the lesioned hemisphere but also between hemispheres. Six months after the stroke event, we could not detect the remapping of networks. Cognitive recovery was associated with the connectivity of both the DMN and SN of time 1. Our findings may be helpful for facilitating further understanding of the potential mechanisms underlying post-stroke cognitive performance.

Self‐reported quality of sleep is related to frontoparietal network connectivity in mild cognitive impairment

AbstractBackgroundSleep has been identified as a modifiable factor involved in both the development and progression of Alzheimer’s disease (AD). Previous findings have suggested that poor sleep may be associated with increased risk of AD. Conversely, higher quality of sleep may slow progression of pathophysiological mechanisms in mild cognitive impairment (MCI) through functional connectivity reorganization of neural networks underlying higher cognitive functions.MethodIn clinic, 38 MCI patients and 38 age‐matched controls completed structural magnetic resonance imaging (MRI), resting‐state functional MRI (rs‐fMRI), and a cognitive test battery, covering memory, executive functions, and language. The Sleep Continuity in Alzheimer’s Disease Scale (SCADS) was used to assess sleep quality. Patients were stratified into “good” (n=20) and “poor” (n=18) sleepers, using the median SCADS score as a cut‐point. Default mode (DMN) and left and right frontoparietal (FPN) networks were reconstructed through an independent component analysis approach. Differences in network connectivity across MCI groups were investigated with non‐parametric inference using FSL randomize (n=5000 permutations), corrected at a threshold‐free‐cluster enhancement level of pFWE &lt; 0.025. Grey matter and sex were inserted as covariates in the analysis. The same model was implemented to investigate associations between connectivity and cognition in MCI. Finally, between‐network connectivity was assessed through partial correlation with sex as covariate.ResultMCI good sleepers showed increased FPN connectivity compared to MCI poor sleepers. Increased FPN connectivity was positively associated with language performance in the former group. Finally, we found a positive coupling connectivity between DMN and FPN and between left and right FPN in MCI good sleepers, while this pattern was disrupted in MCI patients with lower quality of sleep.ConclusionThese findings suggest a relationship between sleep quality and FPN connectivity in MCI, highlighting possible sleep‐induced compensatory mechanisms. Future studies in larger samples using longitudinal methods and objective measures of sleep will be necessary to confirm this finding. However, these results further support the concept that better sleep may be protective on the pathway to AD.

Effects of childhood trauma experience and COMT Val158Met polymorphism on brain connectivity in a multimodal MRI study.

Childhood adversity may act as a stressor to produce a cascade of neurobiological effects that irreversibly alter neural development, setting the stage for developing psychopathology in adulthood. The catechol‐O‐methyltransferase (COMT) Val158Met polymorphism has received much attention as a candidate gene associated with environmental adversity, modifying risk for psychopathology. In this study, we aim to see how gene × brain × environment models give a more integrative understanding of brain modifications that contribute to predicting psychopathology related to childhood adversity. A large nonclinical sample of young adults completed Childhood Trauma Questionnaire (CTQ), behavioral scores, multimodal magnetic resonance imaging (MRI) scans, and genotyping. We utilized graph‐based connectivity analysis in morphometric similarity mapping and resting‐state functional MRI to investigate brain alterations. Relationships among COMT genotypes, CTQ score, imaging phenotypes, and behavioral scores were identified by multiple regression and mediation effect analysis. Significant main effect of CTQ score was found in anatomic connectivity of orbitofrontal cortex that was an outstanding mediator supporting the relationship between CTQ score and anxiety/harm‐avoiding personality. We also noted the main effect of childhood trauma on reorganization of functional connectivity within the language network. Additionally, we found genotype × CTQ score interactions on functional connectivity of the right frontoparietal network as well as anatomic connectivity of motor and limbic regions. Our data demonstrate childhood adversity and COMT genotypes are associated with abnormal brain connectivity, structurally and functionally. Early identification of individuals at risk, assessment of brain abnormality, and cognitive interventions may help to prevent or limit negative outcomes.

Breastfeeding improves dynamic reorganization of functional connectivity in preterm infants: a temporal brain network study.

Substantial evidences have shown the benefits of breastfeeding to infants in terms of better nutrition and neurodevelopmental outcome. However, the relationship between brain development and feeding in preterm infants, who are physiologically and developmentally immature at birth, is only beginning to be quantitatively assessed, coinciding with the recent advent of neuroimaging techniques. In the current work, we studied a sample of 50 preterm infants-born between 29 and 33 weeks (32.20 ± 0.89 weeks) of gestational age, where 30 of them were breastfed and the remaining 20 were formula-fed. Resting-state functional magnetic resonance imaging (fMRI) was recorded around term-equivalent age (40.00 ± 1.31 weeks, range 39-44 weeks) using a 1.5-T scanner under sedation condition. Temporal brain networks were estimated by the correlation of sliding time-window time courses among regions of a predefined atlas. Through our newly introduced temporal efficiency approach, we examined, for the first time, the 3D spatiotemporal architecture of the temporal brain network. We found prominent temporal small-world properties in both groups, suggesting the arrangement of dynamic functional connectivity permits effective coordination of various brain regions for efficient information transfer over time at both local and global levels. More importantly, we showed that breastfed preterm infants exhibited greater temporal global efficiency in comparison with formula-fed preterm infants. Specifically, we found localized elevation of temporal nodal properties in the right temporal gyrus and bilateral caudate. Taken together, these findings provide new evidence to support the notion that breast milk promotes early brain development and cognitive function, which may have neurobiological and public health implications for parents and pediatricians.Breastfeeding has long been recognized to have beneficial effect on early neurodevelopment in infants. However, the influence of breastfeeding on reorganization of functional connectivity in preterm infants are largely unknown. To this end, we utilized our recently developed temporal brain network analysis framework to investigate the dynamic reorganization of brain functional connectivity in preterm infants fed with breast milk. We found that beyond an optimal temporal small-world topology, breastfed preterm infants exhibited improved network efficiency at both global and regional levels in comparisons with those of formula-fed infants. Graphical abstract: Breastfeeding has long been recognized to have beneficial effect on early neurodevelopment in infants. However, the influence of breastfeeding on reorganization of brain functional connectivity in preterm infants are largely unknown. To this end, we utilized our recently developed temporal brain network analysis framework to investigate the dynamic reorganization of functional connectivity in preterm infants fed with breast milk. We found that beyond an optimal temporal small-world topology, breastfed preterm infants exhibited improved network efficiency at both global and regional levels in comparisons with those of formula-fed infants.

Quality of sleep predicts increased frontoparietal network connectivity in patients with mild cognitive impairment

High quality of sleep may mitigate the impact of pathophysiological mechanisms in mild cognitive impairment (MCI) through functional connectivity reorganization of neural networks underlying higher cognitive functions. Thirty-eight patients with MCI stratified into high and low quality of sleep in accordance with a self-reported questionnaire for sleep habits, and 38 controls underwent resting-state functional magnetic resonance imaging. Independent component analysis was used to reconstruct the default mode network and frontoparietal network (FPN). High quality of sleep was associated with increased FPN connectivity among patients with MCI. Moreover, a positive coupling of connectivity between networks was found in MCI reporting high quality of sleep, congruently with the pattern observed in controls, whereas this coupling was disrupted in MCI with low quality of sleep. An association between FPN connectivity and language scores was observed in MCI. These findings suggest a relationship between sleep quality and FPN connectivity in MCI that may underlie compensatory mechanisms to overcome advancing neurodegeneration.

Working memory training increases neural efficiency in Parkinson's disease: a randomized controlled trial.

Impairment of working memory and executive functions is already frequently observed in early stages of Parkinson’s disease. Improvements in working memory performance in this cohort could potentially be achieved via working memory training. However, the specific neural mechanisms underlying different working memory processes such as maintenance as opposed to manipulation are largely under-investigated in Parkinson’s disease. Moreover, the plasticity of these correlates as a function of working memory training is currently unknown in this population. Thus, the working memory subprocesses of maintenance and manipulation were assessed in 41 cognitively healthy patients with Parkinson’s disease using a newly developed working memory paradigm and functional MRI. Nineteen patients were randomized to a 5-week home-based digital working memory training intervention while the remaining patients entered a control, wait list condition. Working memory task-related activation patterns and context-dependent functional connectivity, as well as the change of these neural correlates as a function of training, were assessed. While both working memory processes activated an extended frontoparietal–cerebellar network, only the manipulation of items within working memory also recruited the anterior striatum. The intervention effect on the neural correlates was small, but decreased activation in areas relevant for working memory could be observed, with activation changes correlating with behavioural change. Moreover, training seemed to result in decreased functional connectivity when pure maintenance was required, and in a reorganization of functional connectivity when items had to be manipulated. In accordance with the neural efficacy hypothesis, training resulted in overall reduced activation and reorganized functional connectivity, with a differential effect on the different working memory processes under investigation. Now, larger trials including follow-up examinations are needed to further explore the long-term effects of such interventions on a neural level and to estimate the clinical relevance to potentially delay cognitive decline in cognitively healthy patients with Parkinson’s disease.

Dynamic Reorganization of Functional Connectivity Unmasks Fatigue Related Performance Declines in Simulated Driving.

Although driving fatigue has long been recognized as one of the leading causes of fatal accidents worldwide, the underlying neural mechanisms remain largely unknown that impedes the developments of automatic detection techniques. This study investigated the effects of driving fatigue on the reorganization of dynamic functional connectivity (FC) through our newly developed temporal brain network analysis framework. EEG data were recorded from 20 healthy subjects (male/female = 15/5, age = 22.2 ± 3.2 years) using a remote wireless cap with 24 channels. Temporal brain networks in the theta, alpha and beta were estimated using a sliding window approach and quantitatively compared between the most vigilant and fatigue states during a 90-min simulated driving experiment. Behaviorally, subjects demonstrated a salient driving fatigue effect as reflected by a monotonic increase of reaction time and speed variation. Furthermore, we found a significantly disintegrated spatiotemporal topology of dynamic FC as shown in reduced temporal global efficiency and increased temporal local efficiency at fatigue state. Specifically, we found localized changes of temporal closeness centrality mainly resided in the frontal and parietal areas. Finally, the changes of temporal network measures were associated with those of behavioral metrics. Our findings provide new insights into dynamic characteristics of functional connectivity during driving fatigue and demonstrate the potential for using temporal network metrics as reliable biomarkers for driving fatigue detection.

Abstract WP474: Improvement of Cognitive Function and Reorganization of Brain Networks Following Carotid Endarterectomy and Carotid Artery Stenting

Background: Internal carotid artery stenosis (ICS) can lead to cognitive impairment as well as ischemic stroke. Although carotid revascularization surgery, such as carotid endarterectomy (CEA) and carotid artery stenting (CAS), can prevent future strokes, the effect of revascularization on cognitive function is controversial. In this study, we examined the resting-state functional connectivity (FC) in ICS patients undergoing revascularization surgery, with a special focus on the Default Mode Network (DMN). Methods: We prospectively enrolled 24 ICS patients, who were expecting the intervention of CEA (14 cases) or CAS (10 cases). Cognitive assessment, including the Mini-Mental State Examination (MMSE), the Frontal Assessement Battery (FAB), and the Japanese version of the Montreal Cognitive Assessment (MoCA-J) and rs-fMRI were administered ≤ 1 week preoperatively and postoperatively at 1 week. For the analysis of FC, a seed was placed in the region associated with DMN. Results: After revascularization surgery, significant improvement in the score of MMSE (27.4 vs 28.4, P = 0.03) and MoCA-J (23.1 vs 25.0, P = 0.0001) was found. As for the analysis of the CAS and CEA groups, the MoCA-J score of the CEA group (24.1 vs 26.1, P = 0.001) and the MMSE score of the CAS group (26.0 vs 28.4, P = 0.01) showed statistically significant improvements. In both CAS and CEA groups, Seed-to-Voxel focusing on DMN revealed increased connectivity between medial prefrontal cortex and precuneus. Conclusion: Both CEA and CAS are associated with an improvement in neurocognitive performance and reorganization of functional connectivity, including DMN.