Variability Of Resting-state Functional Connectivity Research Articles

Effects of repetitive transcranial magnetic stimulation on individual variability of resting-state functional connectivity in major depressive disorder.

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for major depressive disorder (MDD), but substantial heterogeneity in outcomes remains. We examined a potential mechanism of action of rTMS to normalize individual variability in resting-state functional connectivity (rs-fc) before and after a course of treatment. Variability in rs-fc was examined in healthy controls (baseline) and individuals with MDD (baseline and after 4-6 weeks of rTMS). Seed-based connectivity was calculated to 4 regions associated with MDD: left dorsolateral prefrontal cortex (DLPFC), right subgenual anterior cingulate cortex (sgACC), bilateral insula, and bilateral precuneus. Individual variability was quantified for each region by calculating the mean correlational distance of connectivity maps relative to the healthy controls; a higher variability score indicated a more atypical/idiosyncratic connectivity pattern. We included data from 66 healthy controls and 252 individuals with MDD in our analyses. Patients with MDD did not show significant differences in baseline variability of rs-fc compared with controls. Treatment with rTMS increased rs-fc variability from the right sgACC and precuneus, but the increased variability was not associated with clinical outcomes. Interestingly, higher baseline variability of the right sgACC was significantly associated with less clinical improvement (p = 0.037, uncorrected; did not survive false discovery rate correction).Limitations: The linear model was constructed separately for each region of interest. This was, to our knowledge, the first study to examine individual variability of rs-fc related to rTMS in individuals with MDD. In contrast to our hypotheses, we found that rTMS increased the individual variability of rs-fc. Our results suggest that individual variability of the right sgACC and bilateral precuneus connectivity may be a potential mechanism of rTMS.

Dissociation of Reliability, Heritability, and Predictivity inCoarse- and Fine-Scale Functional Connectomes duringDevelopment.

The functional connectome supports information transmission through the brain at various spatial scales, from exchange between broad cortical regions to finer-scale, vertex-wise connections that underlie specific information processing mechanisms. In adults, while both the coarse- and fine-scale functional connectomes predict cognition, the fine scale can predict up to twice the variance as the coarse-scale functional connectome. Yet, past brain-wide association studies, particularly using large developmental samples, focus on the coarse connectome to understand the neural underpinnings of individual differences in cognition. Using a large cohort of children (age 9-10 years; n = 1,115 individuals; both sexes; 50% female, including 170 monozygotic and 219 dizygotic twin pairs and 337 unrelated individuals), we examine the reliability, heritability, and behavioral relevance of resting-state functional connectivity computed at different spatial scales. We use connectivity hyperalignment to improve access to reliable fine-scale (vertex-wise) connectivity information and compare the fine-scale connectome with the traditional parcel-wise (coarse scale) functional connectomes. Though individual differences in the fine-scale connectome are more reliable than those in the coarse-scale, they are less heritable. Further, the alignment and scale of connectomes influence their ability to predict behavior, whereby some cognitive traits are equally well predicted by both connectome scales, but other, less heritable cognitive traits are better predicted by the fine-scale connectome. Together, our findings suggest there are dissociable individual differences in information processing represented at different scales of the functional connectome which, in turn, have distinct implications for heritability and cognition.

An examination of the reliability of seed-to-seed resting state functional connectivity in tinnitus patients

Resting state functional connectivity (RS-FC) studies of tinnitus over the years have produced inconsistent results. While findings can be organized into broad categories, such as increased correlations between auditory and limbic areas in tinnitus patients and a disrupted default mode network, there has been little one-to-one correspondence of results across RS-FC studies of tinnitus. While some of this variation can be explained by the heterogeneity of the tinnitus population, including tinnitus severity, the sources of variability in RS-FC of tinnitus patients are unclear. To directly assess the reliability of RS-FC measures in tinnitus, both tinnitus and control participants from two different sites (University of Illinois at Urbana-Champaign, or UIUC, and the Wilford Hall Ambulatory Surgical Center, or WHASC, at the Lackland Airforce Base in San Antonio, Texas) participated in two resting state MRI scans separated by exactly one week. Seed-to-seed analysis assessing correlations between the fMRI activity of 27 regions in the default mode, dorsal attention, auditory, visual, salience, and emotional processing networks were examined in control and tinnitus participants separately for each site. Additionally, heart rate and respiration measures were collected at UIUC, and the effect of extra physiological corrections using these measures on reliability was examined within the UIUC participants. Intra-class correlation coefficients (ICCs) were used as the measure of reliability. Overall, RS-FC in a seed-to-seed analysis was as reliable in tinnitus participants as it was in control participants in the seed regions examined. As previously shown in studies of participants with normal hearing sensitivity, intra-network reliability was higher than inter-network reliability. Related to this, stronger correlations between two seed regions were predictive of stronger reliability of the connectivity between those regions. These effects were seen in both control and tinnitus populations. Additional physiological corrections did not have a significant impact on the ICC values. The current study demonstrates that, on a whole-brain level, RS-FC assessed via seed-to-seed analysis is reliable in tinnitus participants. We therefore must look to other sources as potential causes of discrepancies across studies, such as variability within analysis techniques or within the behavioral characteristics of tinnitus participants.

Resting State Individual Variability in Youth and Young Adults With Autism Spectrum Disorder: Insights From a Transcranial Magnetic Stimulation Trial

Individuals with autism spectrum disorder (ASD) exhibit greater variability of resting-state functional connectivity than typically developing controls (TDC). Here, we employed two approaches to characterize individual variability of resting state connectivity in youth and young adults with ASD, and examined the effect of a 4-week (20-session) clinical trial of active vs. sham repetitive Transcranial Magnetic Stimulation (rTMS) to the dorsolateral prefrontal cortex (DLPFC).

Atypical Resting-State Functional Connectivity Dynamics Correlate With Early Cognitive Dysfunction in HIV Infection.

Purpose: Previous studies have shown that HIV affects striato-cortical regions, leading to persisting cognitive impairment in 30–70% of the infected individuals despite combination antiretroviral therapy. This study aimed to investigate brain functional dynamics whose deficits might link to early cognitive decline or immunologic deterioration.Methods: We applied sliding windows and K-means clustering to fMRI data (HIV patients with asymptomatic neurocognitive impairment and controls) to construct dynamic resting-state functional connectivity (RSFC) maps and identify states of their reoccurrences. The average and variability of dynamic RSFC, and the dwelling time and state transitioning of each state were evaluated.Results: HIV patients demonstrated greater variability in RSFC between the left pallidum and regions of right pre-central and post-central gyri, and between the right supramarginal gyrus and regions of the right putamen and left pallidum. Greater variability was also found in the frontal RSFC of pars orbitalis of the left inferior frontal gyrus and right superior frontal gyrus (medial). While deficits in learning and memory recall of HIV patients related to greater striato-sensorimotor variability, deficits in attention and working memory were associated with greater frontal variability. Greater striato-parietal variability presented a strong link with immunologic function (CD4+/CD8+ ratio). Furthermore, HIV-infected patients exhibited longer time and reduced transitioning in states typified by weaker connectivity in specific networks. CD4+T-cell counts of the HIV-patients were related to reduced state transitioning.Conclusion: Our findings suggest that HIV alters brain functional connectivity dynamics, which may underlie early cognitive impairment. These findings provide novel insights into our understanding of HIV pathology, complementing the existing knowledge.

Phenotypic Variability in Resting-State Functional Connectivity: Current Status

We reviewed the extant literature with the goal of assessing the extent to which resting-state functional connectivity is associated with phenotypic variability in healthy and disordered populations. A large corpus of work has accumulated to date (125 studies), supporting the association between intrinsic functional connectivity and individual differences in a wide range of domains-not only in cognitive, perceptual, motoric, and linguistic performance, but also in behavioral traits (e.g., impulsiveness, risky decision making, personality, and empathy) and states (e.g., anxiety and psychiatric symptoms) that are distinguished by cognitive and affective functioning, and in neurological conditions with cognitive and motor sequelae. Further, intrinsic functional connectivity is sensitive to remote (e.g., early-life stress) and enduring (e.g., duration of symptoms) life experience, and it exhibits plasticity in response to recent experience (e.g., learning and adaptation) and pharmacological treatment. The most pervasive associations were observed with the default network; associations were also widespread between the cingulo-opercular network and both cognitive and affective behaviors, while the frontoparietal network was associated primarily with cognitive functions. Associations of somatomotor, frontotemporal, auditory, and amygdala networks were relatively restricted to the behaviors linked to their respective putative functions. Surprisingly, visual network associations went beyond visual function to include a variety of behavioral traits distinguished by affective function. Together, the reviewed evidence sets the stage for testing causal hypothesis about the functional role of intrinsic connectivity and augments its potential as a biomarker for healthy and disordered brain function.