Whole-brain Network Research Articles

Normative Temporal Dynamics of Resting EEG Microstates.

The large-scale electrophysiological events known as electroencephalographic microstates provide an important window into the intrinsic activity of whole-brain neuronal networks. The spontaneous activity of coordinated brain networks, including the ongoing temporal dynamics expressed by microstates, are thought to reflect individuals' neurocognitive functioning, and predict development, disease progression, and psychological differences among varied populations. A comprehensive understanding of human brain function therefore requires characterizing typical and atypical patterns in the temporal dynamics of microstates. But population-level estimates of normative microstate temporal dynamics are still unknown. To address this gap, I conducted a systematic search of the literature and accompanying meta-analysis of the average dynamics of microstates obtained from studies investigating spontaneous brain activity in individuals during periods of eyes-closed and eyes-open rest. Meta-analyses provided estimates of the average temporal dynamics of microstates across 93 studies totaling 6583 unique individual participants drawn from diverse populations. Results quantified the expected range of plausible estimates of average microstate dynamics across study samples, as well as characterized heterogeneity resulting from sampling variability and systematic differences in development, clinical diagnoses, or other study methodological factors. Specifically, microstate dynamics significantly differed for samples with specific developmental differences or clinical diagnoses, relative to healthy, typically developing samples. This research supports the notion that microstates and their dynamics reflect functionally relevant properties of large-scale brain networks, encoding typical and atypical neurocognitive functioning.

Segmented spin-echo echo-planar imaging improves whole-brain BOLD functional MRI in awake pigeon brains.

Functional magnetic resonance imaging (fMRI) in awake small animals such as pigeons or songbirds opens a new window into the neural fundaments of cognitive behavior. However, high-field fMRI in the avian brain is challenging due to strong local magnetic field inhomogeneities caused by air cavities in the skull. A spoiled gradient-echo fMRI sequence has already been used to map the auditory network in songbirds, but due to susceptibility artifacts only 50% of the whole brain could be recorded. Since whole-brain fMRI coverage is vital to reveal whole-brain networks, an MRI sequence that is less susceptible to these artifacts was required. This was recently achieved in various bird species by using a rapid acquisition with relaxation enhancement (RARE) sequence. Weak blood oxygen level-dependent (BOLD) sensitivity, low temporal resolution, and heat caused by the long train of RF refocusing pulses are the main limits of RARE fMRI at high magnetic fields. To go beyond some of these limitations, we here describe the implementation of a two-segmented spin-echo echo-planar imaging (SE-EPI). The proposed sequence covers the whole brain of awake pigeons. The sequence was applied to investigate the auditory network in awake pigeons and assessed the relative merits of this method in comparison with the single-shot RARE sequence. At the same imaging resolution but with a volume acquisition of 3 s versus 4 s for RARE, the two-segmented SE-EPI provided twice the strength of BOLD activity compared with the single-shot RARE sequence, while the image signal-to-noise ratio (SNR) and in particular the temporal SNR were very similar for the two sequences. In addition, the activation patterns in two-segmented SE-EPI data are more symmetric and larger than single-shot RARE results. Two-segmented SE-EPI represents a valid alternative to the RARE sequence in avian fMRI research since it yields more than twice the BOLD sensitivity per unit of time with much less energy deposition and better temporal resolution, particularly for event-related experiments.

Abnormal white matter structural network topological property in patients with temporal lobe epilepsy.

Diffusion tensor imaging (DTI) studies have demonstrated white matter (WM) abnormalities in patients with temporal lobe epilepsy (TLE). However, alterations in the topological properties of the WM structural network in patients with TLE remain unclear. Graph theoretical analysis provides a new perspective for evaluating the connectivity of WM structural networks. DTI was used to map the structural networks of 18 patients with TLE (10 males and 8 females) and 29 (17 males and 12 females) age- and gender-matched normal controls (NC). Graph theory was used to analyze the whole-brain networks and their topological properties between the two groups. Finally, partial correlation analyses were performed on the weighted network properties and clinical characteristics, namely, duration of epilepsy, verbal intelligence quotient (IQ), and performance IQ. Patients with TLE exhibited reduced global efficiency and increased characteristic path length. A total of 31 regions with nodal efficiency alterations were detected in the fractional anisotropy_ weighted network of the patients. Communication hubs, such as the middle temporal gyrus, right inferior temporal gyrus, left calcarine, and right superior parietal gyrus, were also differently distributed in the patients compared with the NC. Several node regions showed close relationships with duration of epilepsy, verbal IQ, and performance IQ. Our results demonstrate the disruption of the WM structural network in TLE patients. This study may contribute to the further understanding of the pathological mechanism of TLE.

Functional disruptions of the brain network in low back pain: a graph-theoretical study.

The aim of this study was to investigate alterations in the topological organization of whole-brain functional networks in patients with chronic low back pain (CLBP) and characterize the relationship of these alterations with pain characteristics. Thirty-three CLBP patients and 34 matched healthy controls (HCs) underwent fMRI scans. A graph-theoretical approach was applied to identify brain network changes in patients suffering from chronic low back pain given its nonspecific etiology and complexity. Graph theory-based analysis was used to construct functional connectivity matrices and extract the features of small-world networks of the brain in both groups. Then, the whole-brain functional connectivity differences were characterized by network-based statistics (NBS) analysis, and the relationship between the altered brain features and clinical measures was explored. At the global level, patients with CLBP showed significantly decreased gamma, sigma, global efficiency, and local efficiency and increased lambda and shortest path length compared with HCs. At the regional level, there were deficits in nodal efficiency within the default mode network and salience network. NBS analysis demonstrated that decreased functional connectivity was present in the CLBP patients, mainly in the frontolimbic circuit and temporal regions. Furthermore, aspects of topological dysfunctions in CLBP were correlated with pain severity. This study highlighted the aberrant topological organization of functional brain networks in CLBP, which may shed light on the pathophysiology of CLBP and support the development of pain management approaches.

Disconnection of Network Hubs Underlying the Executive Function Deficit in Patients with Ischemic Leukoaraiosis.

Cognitive impairment is the most common clinical manifestation of ischemic leukoaraiosis (ILA), but the underlying neurobiological pathways have not been well elucidated. Recently, it was thought that ILA is a "disconnection syndrome". Disorganized brain connectome were considered the key neuropathology underlying cognitive deficits in ILA patients. We aimed to detect the disruption of network hubs in ILA patients using a new analytical method called voxel-based eigenvector centrality (EC) mapping. Subjects with moderate to severe white matters hyperintensities (Fazekas score ≥3) and healthy controls (HCs) (Fazekas score = 0) were included in the study. The resting-state functional magnetic resonance imaging and the EC mapping approach were performed to explore the alteration of whole-brain network connectivity in ILA patients. Relative to the HCs, the ILA patients exhibited poorer cognitive performance in episodic memory, information processing speed, and executive function (all ps < 0.0125). Additionally, compared with HCs, the ILA patients had lower functional connectivity (i.e., EC values) in the medial parts of default-mode network (i.e., bilateral posterior cingulate gyrus and ventral medial prefrontal cortex [vMPFC]). Intriguingly, the functional connectivity strength at the right vMPFC was positively correlated with executive function deficit in the ILA patients. The findings suggested disorganization of the hierarchy of the default-mode regions within the whole-brain network in patients with ILA and advanced our understanding of the neurobiological mechanism underlying executive function deficit in ILA.

Investigations of brain-wide functional and structural networks of dopaminergic and CamKIIα-positive neurons in VTA with DREADD-fMRI and neurotropic virus tracing technologies

BackgroundThe ventral tegmental area (VTA) contains heterogeneous cell populations. The dopaminergic neurons in VTA play a central role in reward and cognition, while CamKIIα-positive neurons, composed mainly of glutamatergic and some dopaminergic neurons, participate in the reward learning and locomotor activity behaviors. The differences in brain-wide functional and structural networks between these two neuronal subtypes were comparatively elucidated.MethodsIn this study, we applied a method combining Designer Receptors Exclusively Activated by Designer Drugs (DREADD) and fMRI to assess the cell type-specific modulation of whole-brain neural networks. rAAV encoding the cre-dependent hM3D was injected into the right VTA of DAT-cre or CamKIIα-cre transgenic rats. The global brain activities elicited by DREADD stimulation were then detected using BOLD-fMRI. Furthermore, the cre-dependent antegrade transsynaptic viral tracer H129ΔTK-TT was applied to label the outputs of VTA neurons.ResultsWe found that DREADD stimulation of dopaminergic neurons induced significant BOLD signal changes in the VTA and several VTA-related regions including mPFC, Cg and Septum. More regions responded to selective activation of VTA CamKIIα-positive neurons, resulting in increased BOLD signals in VTA, Insula, mPFC, MC_R (Right), Cg, Septum, Hipp, TH_R, PtA_R, and ViC_R. Along with DREADD-BOLD analysis, further neuronal tracing identified multiple cortical (MC, mPFC) and subcortical (Hipp, TH) brain regions that are structurally and functionally connected by VTA dopaminergic and CamKIIα-positive neurons.ConclusionsOur study dissects brain-wide structural and functional networks of two neuronal subtypes in VTA and advances our understanding of VTA functions.

Functional network segregation is associated with higher functional connectivity in endurance runners

Neuroimaging studies have identified significant differences in brain structure, function, and connectivity between endurance runners and healthy controls. However, the topological organization of large-scale functional brain networks remains unexplored in endurance runners. Using resting-state functional magnetic resonance imaging data, this study examined the differences in the topological organization of functional networks between endurance runners (n = 22) and healthy controls (n = 20). Endurance runners had significantly higher clustering coefficients in the whole-brain functional network than healthy controls, but the two did not differ regarding the shortest path length or small-world index. Using network-based statistics, we identified one subnetwork in endurance runners with higher functional connectivity than healthy controls, and the mean functional connectivity of the subnetwork significantly correlated with the three aforementioned small-world parameters. In this subnetwork, the mean clustering coefficient of nodes associated with short-range connections was higher in endurance runners than in healthy controls, but the mean clustering coefficient of nodes associated with long-range connections did not differ between the two groups. In conclusion, using graph theoretical approaches, we revealed significant differences in the topological organization of the whole-brain functional network and functional connectivity between endurance runners and healthy controls. The relationship between these two features suggests that a more segregated network may arise from the optimization of the identified subnetwork in endurance runners. These findings are possibly the neural basis underlying the good performance of endurance runners in endurance running.

Mild traumatic brain injury history is associated with lower brain network resilience in soldiers.

Special Operations Forces combat soldiers sustain frequent blast and blunt neurotrauma, most often classified as mild traumatic brain injuries. Exposure to repetitive mild traumatic brain injuries is associated with persistent behavioural, cognitive, emotional and neurological symptoms later in life. Identifying neurophysiological changes associated with mild traumatic brain injury exposure, in the absence of present-day symptoms, is necessary for detecting future neurological risk. Advancements in graph theory and functional MRI have offered novel ways to analyse complex whole-brain network connectivity. Our purpose was to determine how mild traumatic brain injury history, lifetime incidence and recency affected whole-brain graph theoretical outcome measures. Healthy male Special Operations Forces combat soldiers (age = 33.2 ± 4.3 years) underwent multimodal neuroimaging at a biomedical research imaging centre using 3T Siemens Prisma or Biograph MRI scanners in this cross-sectional study. Anatomical and functional scans were preprocessed. The blood-oxygen-level-dependent signal was extracted from each functional MRI time series using the Big Brain 300 atlas. Correlations between atlas regions were calculated and Fisher z-transformed to generate subject-level correlation matrices. The Brain Connectivity Toolbox was used to obtain functional network measures for global efficiency (the average inverse shortest path length), local efficiency (the average global efficiency of each node and its neighbours), and assortativity coefficient (the correlation coefficient between the degrees of all nodes on two opposite ends of a link). General linear models were fit to compare mild traumatic brain injury lifetime incidence and recency. Nonparametric ANOVAs were used for tests on non-normally distributed data. Soldiers with a history of mild traumatic brain injury had significantly lower assortativity than those who did not self-report mild traumatic brain injury (t148 = 2.44, P = 0.016). The assortativity coefficient was significantly predicted by continuous mild traumatic brain injury lifetime incidence [F1,144 = 6.51, P = 0.012]. No differences were observed between recency groups, and no global or local efficiency differences were observed between mild traumatic brain injury history and lifetime incidence groups. Brain networks with greater assortativity have more resilient, interconnected hubs, while those with lower assortativity indicate widely distributed, vulnerable hubs. Greater lifetime mild traumatic brain injury incidence predicted lower assortativity in our study sample. Less resilient brain networks may represent a lack of physiological recovery in mild traumatic brain injury patients, who otherwise demonstrate clinical recovery, more vulnerability to future brain injury and increased risk for accelerated age-related neurodegenerative changes. Future longitudinal studies should investigate whether decreased brain network resilience may be a predictor for long-term neurological dysfunction.

Disrupted topological organization of white matter structural networks in high myopia patients revealed by diffusion kurtosis imaging and tractography.

High myopia (HM) is a public health issue that can lead to severe visual impairment. Previous studies have exhibited widespread white matter (WM) integrity damage in HM patients. However, how these WM damages are topologically related, and the network-level structural disruptions underlying HM has not been fully defined. We aimed to assess the alterations of brain WM structural networks in HM patients using diffusion kurtosis imaging (DKI) and tractography in the present study. Individual whole-brain and ROI-level WM networks were constructed using DKI tractography in 30 HM patients and 33 healthy controls. Graph theory analysis was then applied to explore the altered global and regional network topological properties. Pearson correlations between regional properties and disease duration in the HM group were also assessed. For global topology, although both groups showed a small-world network organization, HM patients exhibited significant decreased local efficiency and clustering coefficient compared with controls. For regional topology, HM patients and controls showed highly similar hub distributions, except for three additional hub regions in HM patients including left insula, anterior cingulate and paracingulate gyri (ACG), and median cingulate and paracingulate gyri (DCG). In addition, HM patients showed significantly altered nodal betweenness centrality (BC) mainly in the bilateral inferior occipital gyrus (IOG), left superior occipital gyrus (SOG), caudate nucleus, rolandic operculum and right putamen, pallidum, and gyrus rectus compared with controls. Intriguingly, the nodal BC of left IOG was negatively correlated with disease duration in HM patients. Our findings suggest that HM exhibited alterations in WM structural networks as indicated by decreased local specialization. This study may advance the current understanding of the pathophysiological mechanisms underlying HM.

Application of the wholebrain calculation interactive framework to map whole-brain neural connectivity networks

The aim of this work was to develop a simple and feasible method of mapping the neural network topology of the mouse brain. Wild-type C57BL/6 J mice (n = 10) aged 8–10 weeks were injected with the cholera toxin subunit B (CTB) tracer in the anterior (NAcCA) and posterior (NAcCP) parts of the nucleus accumbens (NAc) core and in the medial (NAcSM) and lateral (NAcSL) parts of the NAc shell. The labeled neurons were reconstructed using the WholeBrain Calculation Interactive Framework. The NAcCA receives neuronal projections from the olfactory areas (OLF) and isocortex; the thalamus and isocortex project more fibers to the NAcSL, and the hypothalamus send more fiber projections to the NAcSM. Cell resolution can be automatically annotated, analyzed, and visualized using the WholeBrain Calculation Interactive Framework, making large-scale mapping of mouse brains at cellular and subcellular resolutions easier and more accurate.

Nonlinear changes in delayed functional network topology in Alzheimer’s disease: relationship with amyloid and tau pathology

BackgroundAlzheimer’s disease is a neurodegenerative disorder associated with the abnormal deposition of pathological processes, such as amyloid-ß and tau, which produces nonlinear changes in the functional connectivity patterns between different brain regions across the Alzheimer’s disease continuum. However, the mechanisms underlying these nonlinear changes remain largely unknown. Here, we address this question using a novel method based on temporal or delayed correlations and calculate new whole-brain functional networks to tackle these mechanisms.MethodsTo assess our method, we evaluated 166 individuals from the ADNI database, including amyloid-beta negative and positive cognitively normal subjects, patients with mild cognitive impairment, and patients with Alzheimer’s disease dementia. We used the clustering coefficient and the global efficiency to measure the functional network topology and assessed their relationship with amyloid and tau pathology measured by positron emission tomography, as well as cognitive performance using tests measuring memory, executive function, attention, and global cognition.ResultsOur study found nonlinear changes in the global efficiency, but not in the clustering coefficient, showing that the nonlinear changes in functional connectivity are due to an altered ability of brain regions to communicate with each other through direct paths. These changes in global efficiency were most prominent in early disease stages. However, later stages of Alzheimer’s disease were associated with widespread network disruptions characterized by changes in both network measures. The temporal delays required for the detection of these changes varied across the Alzheimer’s disease continuum, with shorter delays necessary to detect changes in early stages and longer delays necessary to detect changes in late stages. Both global efficiency and clustering coefficient showed quadratic associations with pathological amyloid and tau burden as well as cognitive decline.ConclusionsThis study suggests that global efficiency is a more sensitive indicator of network changes in Alzheimer’s disease when compared to clustering coefficient. Both network properties were associated with pathology and cognitive performance, demonstrating their relevance in clinical settings. Our findings provide an insight into the mechanisms underlying nonlinear changes in functional network organization in Alzheimer’s disease, suggesting that it is the lack of direct connections that drives these functional changes.

Contributions of Lower Structures to Higher Cognition: Towards a Dynamic Network Model.

Researchers often attribute higher cognition to the enlargement of cortical regions throughout evolution, reflecting the belief that humans sit at the top of the cognitive pyramid. Implicitly, this approach assumes that the subcortex is of secondary importance for higher-order cognition. While it is now recognized that subcortical regions can be involved in various cognitive domains, it remains unclear how they contribute to computations essential for higher-level cognitive processes such as endogenous attention and numerical cognition. Herein, we identify three models of subcortical-cortical relations in these cognitive processes: (i) subcortical regions are not involved in higher cognition; (ii) subcortical computations support elemental forms of higher cognition mainly in species without a developed cortex; and (iii) higher cognition depends on a whole-brain dynamic network, requiring integrated cortical and subcortical computations. Based on evolutionary theories and recent data, we propose the SEED hypothesis: the Subcortex is Essential for the Early Development of higher cognition. According to the five principles of the SEED hypothesis, subcortical computations are essential for the emergence of cognitive abilities that enable organisms to adapt to an ever-changing environment. We examine the implications of the SEED hypothesis from a multidisciplinary perspective to understand how the subcortex contributes to various forms of higher cognition.

Effect of transcranial direct current stimulation on the functionality of 40 Hz auditory steady state response brain network: graph theory approach.

Measuring whole-brain networks of the 40 Hz auditory steady state response (ASSR) is a promising approach to describe the after-effects of transcranial direct current stimulation (tDCS). The main objective of this study was to evaluate the effect of tDCS on the brain network of 40 Hz ASSR in healthy adult males using graph theory. The second objective was to identify a population in which tDCS effectively modulates the brain network of 40 Hz ASSR. This study used a randomized, sham-controlled, double-blinded crossover approach. Twenty-five adult males (20-24 years old) completed two sessions at least 1 month apart. The participants underwent cathodal or sham tDCS of the dorsolateral prefrontal cortex, after which 40 Hz ASSR was measured using magnetoencephalography. After the signal sources were mapped onto the Desikan-Killiany brain atlas, the statistical relationships between localized activities were evaluated in terms of the debiased weighted phase lag index (dbWPLI). Weighted and undirected graphs were constructed for the tDCS and sham conditions based on the dbWPLI. Weighted characteristic path lengths and clustering coefficients were then measured and compared between the tDCS and sham conditions using mixed linear models. The characteristic path length was significantly lower post-tDCS simulation (p = 0.04) than after sham stimulation. This indicates that after tDCS simulation, the whole-brain networks of 40 Hz ASSR show a significant functional integration. Simple linear regression showed a higher characteristic path length at baseline, which was associated with a larger reduction in characteristic path length after tDCS. Hence, a pronounced effect of tDCS is expected for those who have a less functionally integrated network of 40 Hz ASSR. Given that the healthy brain is functionally integrated, we conclude that tDCS could effectively normalize less functionally integrated brain networks rather than enhance functional integration.

Altered topological properties and their relationship to cognitive functions in unilateral temporal lobe epilepsy

ObjectiveTo investigate abnormalities in topological properties in unilateral temporal lobe epilepsy (TLE) with hippocampal sclerosis and their correlations with cognitive functions. MethodsThirty-eight patients with TLE and 19 age- and sex-matched healthy controls (HCs) were enrolled in this research and underwent resting-state functional magnetic resonance imaging (fMRI) examinations. Whole-brain functional networks of participants were constructed based on the fMRI data. Topological characteristics of the functional network were compared between patients with left and right TLE and HCs. Correlations between altered topological properties and cognitive measurements were explored. ResultsCompared with the HCs, patients with left TLE showed decreased clustering coefficient, global efficiency, and local efficiency (Eloc), and patients with right TLE showed decreased Eloc. We found altered nodal centralities in six regions related to the basal ganglia (BG) network or default mode network (DMN) in patients with left TLE and those in three regions related to reward/emotion network or ventral attention network in patients with right TLE. Patients with right TLE showed higher integration (reduced nodal shortest path length) in four regions related to the DMN and lower segregation (reduced nodal local efficiency and nodal clustering coefficient) in the right middle temporal gyrus. When comparing left TLE with right TLE, no significant differences were detected in global parameters, but the nodal centralities in the left parahippocampal gyrus and the left pallidum were decreased in left TLE. The Eloc and several nodal parameters were significantly correlated with memory functions, duration, national hospital seizure severity scale (NHS3), or antiseizure medications (ASMs) in patients with TLE. ConclusionsThe topological properties of whole-brain functional networks were disrupted in TLE. Networks of left TLE were characterized by lower efficiency; right TLE was preserved in global efficiency but disrupted in fault tolerance. Several nodes with abnormal topological centrality in the basal ganglia network beyond the epileptogenic focus in the left TLE were not found in the right TLE. Right TLE had some nodes with reduced shortest path length in regions of the DMN as compensation. These findings provide new insights into the effect of lateralization on TLE and help us to understand the cognitive impairment of patients with TLE.

Aging brain shows joint declines in brain within-network connectivity and between-network connectivity: a large-sample study (N > 6,000).

Numerous studies have shown that aging has important effects on specific functional networks of the brain and leads to brain functional connectivity decline. However, no studies have addressed the effect of aging at the whole-brain level by studying both brain functional networks (i.e., within-network connectivity) and their interaction (i.e., between-network connectivity) as well as their joint changes. In this work, based on a large sample size of neuroimaging data including 6300 healthy adults aged between 49 and 73 years from the UK Biobank project, we first use our previously proposed priori-driven independent component analysis (ICA) method, called NeuroMark, to extract the whole-brain functional networks (FNs) and the functional network connectivity (FNC) matrix. Next, we perform a two-level statistical analysis method to identify robust aging-related changes in FNs and FNCs, respectively. Finally, we propose a combined approach to explore the synergistic and paradoxical changes between FNs and FNCs. Results showed that the enhanced FNCs mainly occur between different functional domains, involving the default mode and cognitive control networks, while the reduced FNCs come from not only between different domains but also within the same domain, primarily relating to the visual network, cognitive control network, and cerebellum. Aging also greatly affects the connectivity within FNs, and the increased within-network connectivity along with aging are mainly within the sensorimotor network, while the decreased within-network connectivity significantly involves the default mode network. More importantly, many significant joint changes between FNs and FNCs involve default mode and sub-cortical networks. Furthermore, most synergistic changes are present between the FNCs with reduced amplitude and their linked FNs, and most paradoxical changes are present in the FNCs with enhanced amplitude and their linked FNs. In summary, our study emphasizes the diversity of brain aging and provides new evidence via novel exploratory perspectives for non-pathological aging of the whole brain.

Impaired rich-club connectivity in childhood absence epilepsy.

Childhood absence epilepsy (CAE) is a well-known pediatric epilepsy syndrome. Recent evidence has shown the presence of a disrupted structural brain network in CAE. However, little is known about the rich-club topology. This study aimed to explore the rich-club alterations in CAE and their association with clinical characteristics. Diffusion tensor imaging (DTI) datasets were acquired in a sample of 30 CAE patients and 31 healthy controls. A structural network was derived from DTI data for each participant using probabilistic tractography. Then, the rich-club organization was examined, and the network connections were divided into rich-club connections, feeder connections, and local connections. Our results confirmed a less dense whole-brain structural network in CAE with lower network strength and global efficiency. In addition, the optimal organization of small-worldness was also damaged. A small number of highly connected and central brain regions were identified to form the rich-club organization in both patients and controls. However, patients exhibited a significantly reduced rich-club connectivity, while the other class of feeder and local connections was relatively spared. Moreover, the lower levels of rich-club connectivity strength were statistically correlated with disease duration. Our reports suggest that CAE is characterized by abnormal connectivity concentrated to rich-club organizations and might contribute to understanding the pathophysiological mechanism of CAE.

Does emotion regulation network mediate the effect of social network on psychological distress among older adults?

ABSTRACT Socio-emotional interactions are integral for regulating emotions and buffering psychological distress. Social neuroscience perspectives on aging suggest that empathetic interpersonal interactions are supported by the activation of brain regions involved in regulating negative affect. The current study tested whether resting state functional connectivity of a network of brain regions activated during cognitive emotion regulation, i.e., emotion regulation network (ERN), statistically mediates the frequency of social contact with friends or family on psychological distress. Here, a 10-min resting-state functional MRI scan was collected along with self-reported anxiety/depressive, somatic, and thought problems and social networking from 90 community-dwelling older adults (aged 65–85 years). The frequency of social interactions with family, but not friends and neighbors, was associated with lower psychological distress. The magnitude of this effect was reduced by 33.34% to non-significant upon adding resting state ERN connectivity as a mediator. Follow-up whole-brain graph network analyses revealed that efficiency and centrality of the left inferior frontal gyrus and the right middle temporal gyrus relate to greater family interactions and lower distress. These hubs may help to buffer psychological problems in older adults through interactions involving empathetic and cognitive emotion regulation with close family.

Whole-brain network transitions within the framework of ignition and transfer entropy following VIM-MRgFUS in essential tremor patients

Magnetic resonance-guided focused ultrasound (MRgFUS) lesioning of the ventralis intermedius nucleus (VIM) has shown promise in treating drug-refractory essential tremor (ET). It remains unknown whether focal VIM lesions by MRgFUS have broader restorative effects on information flow within the whole-brain network of ET patients. We applied an information-theoretical approach based on intrinsic ignition and the concept of transfer entropy (TE) to assess the spatiotemporal dynamics after VIM-MRgFUS. Eighteen ET patients (mean age 71.44 years) underwent repeated 3T resting-state functional magnetic resonance imaging combined with Clinical Rating Scale for Tremor (CRST) assessments one day before (T0) and one month (T1) and six months (T2) post-MRgFUS, respectively. We observed increased whole brain ignition-driven mean integration (IDMI) at T1 (p < 0.05), along with trend increases at T2. Further, constraining to motor network nodes, we identified significant increases in information-broadcasting (bilateral supplementary motor area (SMA) and left cerebellar lobule III) and information-receiving (right precentral gyrus) at T1. Remarkably, increased information-broadcasting in bilateral SMA was correlated with relative improvement of the CRST in the treated hand. In addition, causal TE-based effective connectivity (EC) at T1 showed an increase from right SMA to left cerebellar lobule crus II and from left cerebellar lobule III to right thalamus. In conclusion, results suggest a change in information transmission capacity in ET after MRgFUS and a shift towards a more integrated functional state with increased levels of global and directional information flow.

Parkinson's disease speech production network as determined by graph-theoretical network analysis.

Parkinson's disease (PD) can affect speech as well as emotion processing. We employ whole-brain graph-theoretical network analysis to determine how the speech-processing network (SPN) changes in PD, and assess its susceptibility to emotional distraction. Functional magnetic resonance images of 14 patients (aged 59.6 ± 10.1 years, 5 female) and 23 healthy controls (aged 64.1 ± 6.5 years, 12 female) were obtained during a picture-naming task. Pictures were supraliminally primed by face pictures showing either a neutral or an emotional expression. PD network metrics were significantly decreased (mean nodal degree, p < 0.0001; mean nodal strength, p < 0.0001; global network efficiency, p < 0.002; mean clustering coefficient, p < 0.0001), indicating an impairment of network integration and segregation. There was an absence of connector hubs in PD. Controls exhibited key network hubs located in the associative cortices, of which most were insusceptible to emotional distraction. The PD SPN had more key network hubs, which were more disorganized and shifted into auditory, sensory, and motor cortices after emotional distraction. The whole-brain SPN in PD undergoes changes that result in (a) decreased network integration and segregation, (b) a modularization of information flow within the network, and (c) the inclusion of primary and secondary cortical areas after emotional distraction.

Hub structure in functional network of EEG signals supporting high cognitive functions in older individuals.

Maintaining high cognitive functions is desirable for "wellbeing" in old age and is particularly relevant to a super-aging society. According to their individual cognitive functions, optimal intervention for older individuals facilitates the maintenance of cognitive functions. Cognitive function is a result of whole-brain interactions. These interactions are reflected in several measures in graph theory analysis for the topological characteristics of functional connectivity. Betweenness centrality (BC), which can identify the "hub" node, i.e., the most important node affecting whole-brain network activity, may be appropriate for capturing whole-brain interactions. During the past decade, BC has been applied to capture changes in brain networks related to cognitive deficits arising from pathological conditions. In this study, we hypothesized that the hub structure of functional networks would reflect cognitive function, even in healthy elderly individuals. To test this hypothesis, based on the BC value of the functional connectivity obtained using the phase lag index from the electroencephalogram under the eyes closed resting state, we examined the relationship between the BC value and cognitive function measured using the Five Cognitive Functions test total score. We found a significant positive correlation of BC with cognitive functioning and a significant enhancement in the BC value of individuals with high cognitive functioning, particularly in the frontal theta network. The hub structure may reflect the sophisticated integration and transmission of information in whole-brain networks to support high-level cognitive function. Our findings may contribute to the development of biomarkers for assessing cognitive function, enabling optimal interventions for maintaining cognitive function in older individuals.