Functional Connectivity Scores Research Articles

Aberrant Correlation Between the Default Mode and Salience Networks in Mild Traumatic Brain Injury

Objectives: The specific intrinsic network coupling abnormalities in mild traumatic brain injury (mTBI) patients are poorly understood. Our objective is to compare the correlations among the default mode, salience, and central executive networks in patients with mTBI and healthy controls.Methods: This 2-year prospective study included 32 acute mTBI patients and 37 healthy comparisons. We calculated the functional connectivity scores among the default mode, salience, and central executive networks. Then we conducted multilevel correlation analysis to investigate component correlations, global graph, and local functional connectivity changes.Results: Patients with mTBI showed significant increased functional connectivity between the anterior part of the default mode network and the salience network compared with controls (p = 0.013, false discovery rate correction). Hyper-connectivity between the default mode and salience network was significantly positively correlated with the dimensional change card sort score in patients with mTBI (r = 0.40, p = 0.037). The average path length of mTBI patients was significantly higher than that of controls (p = 0.028).Conclusions: Aberrant functional coupling between the default mode and salience networks were identified in acute mTBI patients. Our finding has great potential to improve our understanding of the network architecture of mTBI.

Default mode network functional connectivity after multiple concussions in children and adolescents

Abstract The default mode network (DMN), a set of brain regions, has been shown to be affected post-concussion. Objective This cross-sectional study aims to elucidate if children and adolescents with multiple concussions demonstrate long-term alterations in DMN functional connectivity (FC). Method Participants (N = 57, 27 girls and 30 boys; 8-19 years old, M age = 14.7, SD = 2.8) were divided into three groups (orthopedic injury [OI] n = 20; one concussion n = 16; multiple concussions n = 21, M = 3.2 concussions, SD = 1.7) and seen on average 31.6 months post-injury (range 4.3-130.7 months; SD = 19.4). They underwent a resting-state functional magnetic resonance imaging scan. Parents completed the ADHD rating scale-5 for children and adolescents. Children and parents completed the post-concussion symptom inventory (PCSI). Results Anterior and posterior DMN components were extracted from the fMRI data for each participant using FSL’s MELODIC and dual regression. We tested for pairwise group differences within each DMN component in FSL’s Randomize (5000 permutations) using threshold-free cluster enhancement to estimate cluster activation, controlling for age, sex, and symptoms of inattention. FC of the anterior DMN was significantly reduced in the group with multiple concussions compared to the two other groups, whereas there were no significant group differences on FC of the posterior DMN. There were no significant associations between DMN FC and PCSI scores. Conclusions These results suggest reduced FC in the anterior DMN in youth with multiple concussions, but no linear association with post-concussive symptoms.

Structural and functional reorganization following unilateral internal capsule infarction contribute to neurological function recovery.

To investigate proliferative reorganization in the bilateral corticospinal tract (CST) and functional reorganization in the sensorimotor network (SMN) after internal capsule stroke, and to examine the significance of this reorganization. We recruited 17 patients with first-onset acute stroke (16 male, 1 female, mean age 52 ± 10years) and 17 age- and sex-matched healthy controls. We excluded patients aged < 18 or > 65years and those with lesions outside the unilateral internal capsule. All subjects underwent diffusion tensor imaging and resting-state functional MRI on days 7, 30, and 90 from symptom onset. We measured fractional anisotropy (FA) in the CST, interhemispheric functional connectivity (FC) within the SMN, and pre-MRI clinical scores, including the National Institutes of Health Stroke Scale (NIHSS), Barthel Index (BI), and Fugl-Meyer (FM). Correlations among the changes in FA, FC, and clinical scores were analyzed. From day 7 to 90 after stroke, FA in the bilateral CST increased (ipsilesional side, Pinternal capsule = 0.009, Pcentrum semiovale = 0.001; contralesional side, Pinternal capsule = 0.006, Pcentrum semiovale = 0.017), as did FC (P < 0.05); NIHSS scores decreased (P < 0.05), while FM and BI progressively increased (P < 0.05). Increased FA in bilateral CST was negatively correlated with decreased NIHSS scores. Increased FA in only the ipsilesional side was positively correlated with increased FM. Increased FC was positively correlated only with increased BI. Proliferative reorganization in the CST and functional reorganization in the SMN support and promote neurological functional recovery after internal capsule infarction.

Functional connectivity impairment of postcentral gyrus in relapsing-remitting multiple sclerosis with somatosensory disorder

PurposeTo characterize the spatial patterns of functional connectivity(FC) changes of whole brain in RRMS with somatosensory disorder(RRMS-SS) and to investigate the correlation between abnormal FC and clinical scores. MethodsTwenty-six RRMS-SS patients and 23 healthy controls(HC) underwent resting-state functional magnetic resonance imaging(RS-fMRI) scanning. The clinical scores were collected including Expanded Disability Status Scores(EDSS), Disease Duration and Somatosensory Evaluation by the Fugl-Meyer sensory score(FMSS). With the voxel-wise methods, RS-fMRI data were analyzed using REST software, to assess the FC of the postcentral gyrus(PoCG). Correlation between clinical variables and the strength of FC was analyzed. ResultsCompared with HC, the left postcentral-based FC showed decreased FC of the right cerebellum_8, lingual lobe and Rolandic operculum gyrus, and increased FC of the left middle frontal lobe. The right postcentral-based FC revealed decreased FC with the right Heschl's gyrus lobule, and increased FC with bilateral middle frontal lobe (p < 0.001, AlphaSim corrected). Correlation analysis revealed that the FC of altered brain regions was associated with FMSS, EDSS and disease duration. ConclusionThe functional connectivity of PoCG at RS-fMRI has multi-network changes in patients with RRMS-SS. This suggests a complex pattern of abnormal connections between the somatosensory network regions and the whole brain. Moreover, the correlation between the FC and the FMSS, such as the left middle frontal lobe and the right PoCG, indicate that these two brain regions play an important role in RRMS-SS.

Altered functional connectivity of dentate nucleus in parkinsonian and cerebellar variants of multiple system atrophy.

The cerebellum is known to influence cerebral cortical activity via cerebello-thalamo-cortical (CTC) circuits and thereby may be implicated in the pathophysiology of multiple system atrophy (MSA). As the aim of this study, we investigated the abnormalities of corticocerebellar functional connectivity (FC) in patients with two variants of MSA. Resting-state functional magnetic resonance imaging (rs-fMRI) studies were obtained from 55 patients with MSA, including Parkinsonian (MSAp, n = 29) and cerebellar (MSAc, n = 26) variants. We also examined a similar number of healthy controls (HC, n = 51). Seed-based connectivity analysis was performed to assess alterations in CTC circuits. Relations between FC and clinical scores were assessed as well. Compared with the HC group, diminished FC was evident from bilateral dentate nucleus (DN) to motor cortex, bilateral basal ganglia, right cerebellum, default mode network (DMN), and limbic system in patients with MSAc. Patients with MSAp (vs HC subjects) showed less FC from left DN to right putamen, DMN, and limbic systems. Reduced FC was also demonstrated from left DN to DMN in patients with MSAc (vs MSAp), as well as from right DN to right cerebellum, DMN, basal ganglia, motor cortex, and limbic systems. In addition, the extent of FC from right DN to right cerebellum negatively correlated with Unified Parkinson's Disease Rating Scale-III scores in patients with MSA, while showing a positive association with Montreal Cognitive Assessment scores. The FC of DN was similarly altered in patients with MSAc and MSAp, although right cerebellar and motor cortical changes were more widespread in the MSAc group. There may be differing mechanisms of cerebellar functional activity responsible for motor and cognitive impairment, which should be further investigated.

Impaired prefrontal cortex-thalamus pathway in intractable temporal lobe epilepsy with aberrant executive control function: MRI evidence

ObjectivesThis study aimed to assess structural and functional connectivity alterations of the prefrontal cortex (PFC)-thalamus axis in individuals with unilateral intractable temporal lobe epilepsy (TLE) showing executive control function (ECF) impairment and to explore the potential mechanism. MethodsThirty-eight individuals with intractable left TLE and twenty-nine healthy controls (HCs) were recruited for diffusion tensor imaging (DTI) and resting-state fMRI (rs-fMRI) scanning. According to the ECF state, patients were assigned to normal and impaired ECF groups. Functional connectivity (FC) and probabilistic diffusion tractography of the PFC- thalamus pathway were assessed. The general linear model (GLM) was employed for comparing fiber number (FN) and FC between groups. Pearson correlation analysis of FC, FN and ECF test scores was performed. ResultsFC and FN of left DLPFC-thalamus pathway were significantly increased in the impaired ECF group compared with the normal ECF and HC groups. However, FC and FN were not correlated with ECF score. ConclusionsThese findings indicated increased connectivity between DLPFC and the ipsilateral thalamus might reflect nonfunctional nerve remodeling along the seizure pathway. SignificanceThe present findings suggest that the DLPFC-thalamus pathway may be an important structure for exploring the mechanisms of TLE with ECF dysfunction.

Alterations of static functional connectivity and dynamic functional connectivity in motor execution regions after stroke

The aims of this study were to examine both static functional connectivity (FC) and dynamic FC alterations in motor execution regions after stroke and to investigate whether the altered static or dynamic FC was associated with the clinical behaviors in stroke patients. Seventy-six stroke patients and 55 healthy controls (HC) were recruited. Static FC and dynamic FC maps were computed based on the seeds of six core regions in motor execution network. Correlation analyses were performed between static or dynamic FC and clinical behavioral scores in stroke patients. Compared with the HC, the stroke patients had significantly higher static FC between the seeds and the precentral or postcentral gyrus, frontal gyrus, inferior parietal lobule, thalamus and insula, and lower static FC between the seeds and the cerebellum and middle temporal gyrus. There were significant differences in dynamic FC between the seeds and precuneus, calcarine gyrus, insula, inferior parietal lobule, precentral gyrus, and middle temporal, frontal or occipital gyrus between the stroke patients and HC. Furthermore, a significant negative correlation was found between the Fugl-Meyer assessment scores and dynamic FC of the ipsilesional primary motor cortex and contralesional precentral gyrus in patients. The current study shows that the patterns of both static FC and dynamic FC changed after stroke, and correlation between motor function and temporal variability in the FC of the precentral gyrus was significant in stroke patients. Our findings indicate that dynamic FC might be a potential indicator for evaluating motor function after stroke.

Brain network alteration in patients with temporal lobe epilepsy with cognitive impairment

The aims of this study were to investigate the brain network alternation in patients with temporal lobe epilepsy (TLE) with and without cognitive impairment (CI) using functional magnetic resonance imaging (fMRI) and to further explore the potential mechanisms of epilepsy-induced CI. Forty patients with TLE and nineteen healthy controls (HCs) were recruited for this study. All participants received the Montreal Cognitive Assessment (MoCA) test, and the patients were divided into CI (n=21) and cognitive nonimpairment (CNI) groups (n=19) according to MoCA performance. Functional connectivity (FC) differences of resting state networks (RSNs) were compared among the CI, CNI, and HC groups. Correlation between FC and MoCA scores was also observed. When compared with the HC group, significantly decreased FC between medial visual network (mVN) and left frontoparietal network (lFPN) as well as between visuospatial network (VSN) and the anterior default mode network (aDMN) were revealed in both CI and CNI groups. In addition, significantly decreased FC between lFPN and executive control network (ECN) and increased FC between ECN and sensorimotor-related network (SMN) were found in CNI and CI groups, respectively. When compared with the CNI group, the CI group exhibited significant increased FC between ECN and lFPN as well as between ECN and SMN. Moreover, in the CI group, FC between ECN and lFPN showed negative correlation with attention scores. Our findings suggested that cognitive networks are different from epileptic networks, and the increased FC between RSNs closely related to cognitive function changes may help us to further understand the mechanism of CI in TLE.

Investigating the relationship between multiple grip forces and BOLD signal in the Cerebellum and dentate nuclei of MS subjects

Investigating the relationship between multiple grip forces and BOLD signal in the Cerebellum and dentate nuclei of MS subjects

EP 29. Resting-state test-retest reliability over different preprocessing steps

Functional magnetic resonance imaging (fMRI) plays a vital role in understanding normal and clinical brain function and relies on detecting changes in blood oxygenation (i.e., BOLD). Synchronized signal fluctuations can be observed even when the subject is at rest, i.e., without performing any task. Therefore, analyzing resting-state data has become one way of studying ongoing brain activity and interrelation of brain regions. Apparent brain activity can be influenced by unwanted signals including system noise, thermal noise and noise induced by non-neuronal physiological processes. The latter induced noise is mostly the unwanted noise that affects the BOLD signal. Globally influencing nuisance regressors are derived from either whole brain or specific tissues types and removed from the main signal ( Behzadi et al., 2007 , Murphy et al., 2009 ). Removal of various global nuisance regressors alters the variance of the residual signal. Functional connectivity (FC) in general measures, how well different regions in the brain relate to each other. It estimates the common variance of the signal fluctuations within these regions by linear correlation. In this study, we tested the reliability of FC after removing confounding noise regressors. Here we focused on the effects of various commonly used confound removals in the resting state studies, such as PCA de-noising, global mean signal regression including white matter (WM) and CSF mean signal regression, tissue signal regression (Grey matter (GM), WM and CSF). Additionally, we examined GM specific time series extraction from seed regions. We conducted a seed based FC analysis on 42 subjects scanned twice with an interval of 100–250 day and tested the reliability between scans. In order to compute the seed based functional connectivity, a priori defined networks were analyzed (extended socioaffective default mode network and the working-memory network). Both these networks show robust within network resting state connectivity, as well as anti-correlation between each other. The reliability of functional connectivity is measured using two different measures i.e., by computing the spearman correlations and the absolute differences of the functional connectivity scores. Our results ( Fig. 1 ) showed that GM masking of the seed regions based on the group-average GM probabilities is advisable. Also, PCA de-noising reduces the reliability of connectivity estimates. Finally, with respect to global signal regression, we observed that refraining from this approach enhances test-retest reliability but comes at the expense of potentially poorer biological validity, indicated by missing anti-correlations between what has been previously described as antagonistic networks. Here removal of global WM and CSF signals seems to provide a good compromise, as this approach yielded reliable and meaningful estimates of within and between-network connections. Importantly, reliability showed correlation with the retained variance, presumably including structured noise. Consequently, noise removal from fMRI data requires a compromise between maximizing the test-retest reliability and removing variance that may be attributable to non-neuronal sources.

Amygdala functional connectivity as a longitudinal biomarker of symptom changes in generalized anxiety.

Generalized anxiety disorder (GAD) is characterized by excessive worry, autonomic dysregulation and functional amygdala dysconnectivity, yet these illness markers have rarely been considered together, nor their interrelationship tested longitudinally. We hypothesized that an individual’s capacity for emotion regulation predicts longer-term changes in amygdala functional connectivity, supporting the modification of GAD core symptoms. Sixteen patients with GAD (14 women) and individually matched controls were studied at two time points separated by 1 year. Resting-state fMRI data and concurrent measurement of vagally mediated heart rate variability were obtained before and after the induction of perseverative cognition. A greater rise in levels of worry following the induction predicted a stronger reduction in connectivity between right amygdala and ventromedial prefrontal cortex, and enhanced coupling between left amygdala and ventral tegmental area at follow-up. Similarly, amplified physiological responses to the induction predicted increased connectivity between right amygdala and thalamus. Longitudinal shifts in a distinct set of functional connectivity scores were associated with concomitant changes in GAD symptomatology over the course of the year. Results highlight the prognostic value of indices of emotional dysregulation and emphasize the integral role of the amygdala as a critical hub in functional neural circuitry underlying the progression of GAD symptomatology.

Alteration of Resting-State Brain Sensorimotor Connectivity following Spinal Cord Injury: A Resting-State Functional Magnetic Resonance Imaging Study.

Motor and sensory deficits after spinal cord injury (SCI) result in functional reorganization of the sensorimotor network. While several task-evoked functional magnetic resonance imaging (fMRI) studies demonstrated functional alteration of the sensorimotor network in SCI, there has been no study of the possible alteration of resting-state functional connectivity using resting-state fMRI. The aim of this study was to investigate the changes of brain functional connectivity in the sensorimotor cortex of patients with SCI. We evaluated the functional connectivity scores between brain areas within the sensorimotor network in 18 patients with SCI and 18 controls. Our findings demonstrated that, compared with control subjects, patients with SCI showed increased functional connectivity between primary motor cortex and other motor areas, such as the supplementary motor area and basal ganglia. However, decreased functional connectivity between primary somatosensory cortex and secondary somatosensory cortex also was found in patients with SCI, compared with controls. These findings therefore demonstrated alteration of the resting-state sensorimotor network in patients with SCI, who showed increased connectivity between motor components, and decreased connectivity between sensory components, within the sensorimotor network, suggesting that motor components within the motor network increased in functional connectivity in order to compensate for motor deficits, whereas the sensory network did not show any such increases or compensation for sensory deficits.

Functional connectivity pattern during rest within the episodic memory network in association with episodic memory performance in bipolar disorder

In this study, we sought to examine the intrinsic functional organization of the episodic memory network during rest in bipolar disorder (BD). The previous work suggests that deficits in intrinsic functional connectivity may account for impaired memory performance. We hypothesized that regions involved in episodic memory processing would reveal aberrant functional connectivity in patients with bipolar disorder. We examined 21 patients with BD and 21 healthy matched controls who underwent functional magnetic resonance imaging (fMRI) during a resting condition. We did a seed-based functional connectivity analysis (SBA), using the regions of the episodic memory network that showed a significantly different activation pattern during task-related fMRI as seeds. The functional connectivity scores (FC) were further correlated with episodic memory task performance. Our results revealed decreased FC scores within frontal areas and between frontal and temporal/hippocampal/limbic regions in BD patients in comparison with controls. We observed higher FC in BD patients compared with controls between frontal and limbic regions. The decrease in fronto-frontal functional connectivity in BD patients showed a significant positive association with episodic memory performance. The association between task-independent dysfunctional frontal-limbic FC and episodic memory performance may be relevant for current pathophysiological models of the disease.

Contralateral interictal spikes are related to tapetum damage in left temporal lobe epilepsy.

In temporal lobe epilepsy (TLE), the epileptogenic focus is focal and unilateral in the majority of patients. A key characteristic of focal TLE is the presence of subclinical epileptiform activity in both the ictal and contralateral "healthy" hemisphere. Such interictal activity is clinically important, as it may reflect the spread of pathology, potentially leading to secondary epileptogenesis. The role played by white matter pathways in this process is unknown. We compared three interhemispheric white matter tracts (anterior commissure, fornix, and tapetum) to determine the pathway most associated with the presence of contralateral interictal spikes. Forty patients with unilateral left or right TLE were categorized based on the presence or absence of contralateral interictal spikes. Analyses of variance (ANOVAs) were run on diffusion properties from each tract. The analyses revealed that patients with left TLE and with bilateral interictal spikes had lower fractional anisotropy (FA) and higher mean diffusivity (MD) in the tapetum. Patients with right TLE did not show this effect. No significant associations with bilateral activity were observed for the other tracts. Blood oxygen level-dependent (BOLD) functional connectivity data revealed that homotopic lateral, not mesial, temporal areas were reliably correlated in bilateral patients, independent of ictal side. Our results indicate that, among the tracts investigated, only the tapetum was associated with contralateral epileptiform activity, implicating this structure in seizures and possible secondary epileptogenesis. We describe two mechanisms that might explain this association (the interruption of inhibitory signals or the toxic effect of carrying epileptiform signals toward the healthy hemisphere), but also acknowledge other rival factors that may be at work. We also report that patients with TLE with bilateral spikes had increased lateral bitemporal lobe connectivity. Our current results can be seen as bringing together important functional and structural data to elucidate the basis of contralateral interictal activity in focal, unilateral epilepsy. A PowerPoint slide summarizing this article is available for download in the Supporting Information section here.

Functional connectivity of negative emotional processing in adolescent depression

BackgroundThe subgenual anterior cingulate cortex (sgACC) and its connected circuitry have been heavily implicated in emotional functioning in adolescent-onset major depressive disorder (MDD). While several recent studies have examined sgACC functional connectivity (FC) in depressed youth at rest, no studies to date have investigated sgACC FC in adolescent depression during negative emotional processing. MethodsNineteen medication-naïve adolescents with MDD and 19 matched healthy controls (HCL) performed an implicit fear facial affect recognition task during functional magnetic resonance imaging (fMRI). We defined seeds in bilateral sgACC and assessed FC using the psychophysiological interaction method. We also applied cognitive behavioral modeling to estimate group differences in perceptual sensitivity in this task. Finally, we correlated connectivity strength with clinical data and perceptual sensitivity. ResultsDepressed adolescents showed increased sgACC-amygdala FC and decreased sgACC-fusiform gyrus, sgACC-precuneus, sgACC-insula, and sgACC-middle frontal gyrus FC compared to HCL (p<0.05, corrected). Among the MDD, sgACC-precuneus FC negatively correlated with depression severity (p<0.05, corrected). Lastly, MDD adolescents exhibited poorer perceptual sensitivity in the task than HCL, and individual differences in perceptual sensitivity significantly correlated with sgACC FC and depression scores (p<0.05, corrected). LimitationsSubjects were clinically homogenous, possibly limiting generalizability of the findings. ConclusionsAdolescent depression is associated with biased processing of negative stimuli that may be driven by sgACC dysregulation and may possibly lead to an imbalance among intrinsic functional brain networks. This work also establishes the use of combining neuroimaging and cognitive behavioral modeling methods to investigate cognitive and neural differences between psychiatric and healthy populations.

Inferring task-related networks using independent component analysis in magnetoencephalography

A novel framework for analysing task-positive data in magnetoencephalography (MEG) is presented that can identify task-related networks. Techniques that combine beamforming, the Hilbert transform and temporal independent component analysis (ICA) have recently been applied to resting-state MEG data and have been shown to extract resting-state networks similar to those found in fMRI. Here we extend this approach in two ways. First, we systematically investigate optimisation of time-frequency windows for connectivity measurement. This is achieved by estimating the distribution of functional connectivity scores between nodes of known resting-state networks and contrasting it with a distribution of artefactual scores that are entirely due to spatial leakage caused by the inverse problem. We find that functional connectivity, both in the resting-state and during a cognitive task, is best estimated via correlations in the oscillatory envelope in the 8–20 Hz frequency range, temporally down-sampled with windows of 1–4 s. Second, we combine ICA with the general linear model (GLM) to incorporate knowledge of task structure into our connectivity analysis. The combination of ICA with the GLM helps overcome problems of these techniques when used independently: namely, the interpretation and separation of interesting independent components from those that represent noise in ICA and the correction for multiple comparisons when applying the GLM. We demonstrate the approach on a 2-back working memory task and show that this novel analysis framework is able to elucidate the functional networks involved in the task beyond that which is achieved using the GLM alone. We find evidence of localised task-related activity in the area of the hippocampus, which is difficult to detect reliably using standard methods. Task-positive ICA, coupled with the GLM, has the potential to be a powerful tool in the analysis of MEG data.

Alteration of functional connectivity in tinnitus brain revealed by resting-state fMRI?: A pilot study

Objective: We report a case study on possible alterations in resting-state functional connectivity between the auditory network and non-auditory brain regions in tinnitus patients. Design: Independent component analyses were performed to evaluate coherent spontaneous activity in distributed brain networks. The resting-state functional connectivity scores between the right and left auditory networks were measured. Direct comparison of resting-state connectivity between tinnitus patients and controls was made using a two-sample t-test. Study sample: Four patients (three male, one female; mean age 45 ± 3.92 years) with chronic tinnitus lateralized to the left ear, and six age-matched controls (four male, two female; mean age 45 ± 2.76 years) participated in this case study. Results: The average resting-state functional connectivity (FC) score between the left and right auditory cortical regions was significantly lower in tinnitus patients than in controls (P < 0.05). Direct comparison between patients and controls showed that increased functional connectivity caused by tinnitus occurred predominantly in the left amygdala and in the dorsomedial prefrontal cortex. Conclusions: Our pilot study suggested that resting state functional magnetic resonance imaging (fMRI) could be useful to investigate possible alterations in resting-state neuronal activity between the auditory and non-auditory networks in tinnitus patients.