In this essay, we examine the use of resting state fMRI data for psychological inferences. We argue that resting state studies hold the paired promises of discovering novel functional brain networks, and of avoiding some of the limitations of task-based fMRI. However, we argue that the very features of experimental design that enable resting state fMRI to support exploratory science also generate a novel confound. We argue that seemingly key features of (...) resting state functional connectivity networks may be artefacts resulting from sampling a ‘mixture distribution’ of diverse brain networks active at different times during the scan. We explore the consequences of this ‘mixture view’ for attempts to theorize about the cognitive or psychological functions of resting state networks, as well as the value of exploratory experiments. (shrink)

Background and objectivesThe study of brain functional connectivity alterations in children with Attention-Deficit/Hyperactivity Disorder has been the subject of considerable investigation, but the biological mechanisms underlying these changes remain poorly understood. Here, we aim to investigate the brain alterations in patients with ADHD and Typical Development children and accurately classify ADHD children from TD controls using the graph-theoretical measures obtained from resting-state fMRI.Materials and methodsWe investigated the performances of rs-fMRI data for classifying drug-naive children with ADHD (...) from TD controls. Fifty six drug-naive ADHD children and 56 age matched TD controls were included in this study. The graph measures extracted from rs-fMRI functional connectivity were used as features. Extracted network-based features were fed to the RFE feature selection algorithm to select the most discriminating subset of features. We trained and tested Support Vector Machine, Random Forest, and Gradient Boosting using Peking center data from ADHD-200 database to classify ADHD and TD children using discriminative features. In addition to the machine learning approach, the statistical analysis was conducted on graph measures to discover the differences in the brain network of patients with ADHD.ResultsAn accuracy of 78.2% was achieved for classifying drug-naive children with ADHD from TD controls employing the optimal features and the GB classifier. We also performed a hub node analysis and found that the number of hubs in TD controls and ADHD children were 8 and 5, respectively, indicating that children with ADHD have disturbance of critical communication regions in their brain network. The findings of this study provide insight into the neurophysiological mechanisms underlying ADHD.ConclusionPattern recognition and graph measures of the brain networks, based on the rs-fMRI data, can efficiently assist in the classification of ADHD children from TD controls. (shrink)

Objectives: Autism spectrum disorder (ASD) is a juvenile onset neurodevelopmental disorder with social impairment and stereotyped behavior as the main symptoms. Unaffected relatives may also exhibit similar ASD features due to genetic factors. Although previous studies have demonstrated atypical brain morphological features as well as task-state brain function abnormalities in unaffected parents with ASD children, it remains unclear the pattern of brain function in the resting state.Methods: A total of 42 unaffected parents of ASD children (pASD) and (...) 39 age-, sex-, and handedness-matched controls were enrolled. Multiple resting-state fMRI (rsfMRI) analyzing methods were applied, including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), degree centrality (DC), and functional connectivity (FC), to reveal the functional abnormalities of unaffected parents in ASD-related brain regions. Spearman Rho correlation analysis between imaging metric values and the severity of ASD traits were evaluated as well.Results: ALFF, ReHo, and DC methods all revealed abnormal brain regions in the pASD group, such as the left medial orbitofrontal cortex (mOFC) and rectal gyrus (ROI-1), bilateral supplementary motor area (ROI-2), right caudate nucleus head and right amygdala/para-hippocampal gyrus (ROI-3). FC decreasing was observed between ROI-1 and right anterior cingulate cortex (ACC), ROI-2, and bilateral precuneus. FC enhancing was observed between ROI-3 and right anterior cerebellar lobe, left medial temporal gyrus, left superior temporal gyrus, left medial frontal gyrus, left precentral gyrus, right postcentral gyrus in pASD. In addition, ALFF values in ROI-1, DC values in ROI-3 were positively correlated with AQ scores in pASD (ρ1 = 0.298, P1 = 0.007; ρ2 = 0.220, P2 = 0.040), while FC values between ROI-1 and right ACC were negatively correlated with AQ scores (ρ3 = −0.334, P3 = 0.002).Conclusion: rsfMRI metrics could be used as biomarkers to reveal the underlying neurobiological feature of ASD for unaffected parents. (shrink)

ObjectiveRetinal vein occlusion (RVO) is the second most common retinal vascular disorder after diabetic retinopathy, which is the main cause of vision loss. Retinal vein occlusion might lead to macular edema, causing severe vision loss. Previous neuroimaging studies of patients with RVO demonstrated that RVO was accompanied by cerebral changes, and was related to stroke. The purpose of the study is to investigate synchronous neural activity changes in patients with RVO.MethodsA total of 50 patients with RVO and 48 healthy subjects (...) with matched sex, age, and education were enrolled in the study. The ReHo method was applied to investigate synchronous neural activity changes in patients with RVO.ResultsCompared with HC, patients with RVO showed increased ReHo values in the bilateral cerebellum_4_5. On the contrary, patients with RVO had decreased ReHo values in the bilateral middle occipital gyrus, right cerebelum_crus1, and right inferior temporal gyrus.ConclusionOur study demonstrated that patients with RVO were associated with abnormal synchronous neural activities in the cerebellum, middle occipital gyrus, and inferior temporal gyrus. These findings shed new insight into neural mechanisms of vision loss in patients with RVO. (shrink)

ObjectiveThe effects and possible mechanisms of cerebellar high-frequency repetitive transcranial magnetic stimulation on swallowing-related neural networks were studied using resting-state functional magnetic resonance imaging.MethodA total of 23 healthy volunteers were recruited, and 19 healthy volunteers were finally included for the statistical analysis. Before stimulation, the cerebellar hemisphere dominant for swallowing was determined by the single-pulse TMS. The cerebellar representation of the suprahyoid muscles of this hemisphere was selected as the target for stimulation with 10 Hz rTMS, 100% (...) class='Hi'>resting motor threshold, and 250 pulses, with every 1 s of stimulation followed by an interval of 9 s. The motor evoked potential amplitude of the suprahyoid muscles in the bilateral cerebral cortex was measured before and after stimulation to evaluate the cortical excitability. Forty-eight hours after elution, rTMS was reapplied on the dominant cerebellar representation of the suprahyoid muscles with the same stimulation parameters. Rs-fMRI was performed before and after stimulation to observe the changes in amplitude of low-frequency fluctuation and regional homology at 0.01–0.08 Hz, 0.01–0.027 Hz, and 0.027–0.073 Hz.ResultsAfter cerebellar high-frequency rTMS, MEP recorded from swallowing-related bilateral cerebral cortex was increased. The results of rs-fMRI showed that at 0.01–0.08 Hz, ALFF was increased at the pons, right cerebellum, and medulla and decreased at the left temporal lobe, and ReHo was decreased at the left insular lobe, right temporal lobe, and corpus callosum. At 0.01–0.027 Hz, ALFF was decreased at the left temporal lobe, and ReHo was decreased at the right temporal lobe, left putamen, and left supplementary motor area.ConclusionRepetitive transcranial magnetic stimulation of the swallowing cortex in the dominant cerebellar hemisphere increased the bilateral cerebral swallowing cortex excitability and enhanced pontine, bulbar, and cerebellar spontaneous neural activity, suggesting that unilateral high-frequency stimulation of the cerebellum can excite both brainstem and cortical swallowing centers. These findings all provide favorable support for the application of cerebellar rTMS in the clinical practice. (shrink)

The idea that intelligence is embedded not only in a single brain network, but instead in a complex, well-optimized system of complementary networks, has led to the development of whole brain network analysis. Using graph theory to analyze resting-state functional MRI data, we investigated the brain graph networks (or brain networks) of high intelligence quotient (HIQ) children. To this end, we computed the “hub disruption index κ”, an index sensitive to graph network modifications. We found significant topological differences (...) in the integration and segregation properties of brain networks in HIQ compared to standard IQ children, not only for the whole brain graph, but also for each hemispheric graph, and for the homotopic connectivity. Moreover, two profiles of HIQ children, homogenous and heterogeneous, based on the differences between the two main IQ subscales (verbal comprehension index (VCI) and perceptual reasoning index (PRI)), were compared. Brain networks changes were more pronounced in the heterogeneous HIQ than in the homogeneous HIQ subgroups. Finally, we found significant correlations between the graph networks’ changes and the full-scale IQ (FSIQ), as well as the subscales VCI and PRI. Specifically, the higher the FSIQ the greater was the brain organization modification in the whole brain, the left hemisphere, and the homotopic connectivity. These results shed new light on the relation between functional connectivity topology and high intelligence, as well as on different intelligence profiles. (shrink)

ObjectiveStatic regional homogeneity based on the resting-state functional magnetic resonance imaging has been used to study intrinsic brain activity in Alzheimer’s disease. However, few studies have examined dynamic ReHo in AD. In this study, we used rs-fMRI and dReHo to investigate the alterations in dynamic IBA in patients with AD to uncover dynamic imaging markers of AD.MethodIn total, 111 patients with AD, 29 patients with mild cognitive impairment, and 73 healthy controls were recruited for this study ultimately. (...) After the rs-fMRI scan, we calculated the dReHo values using the sliding window method. ANOVA and post hoc two-sample t-tests were used to detect the differences among the three groups. We used the mini-mental state examination and Montreal Cognitive Assessment to evaluate the cognitive function of the subjects. The associations between the MMSE score, MoCA score, and dReHo were assessed by the Pearson correlation analysis.ResultsSignificant dReHo variability in the right middle frontal gyrus and right posterior cingulate gyrus was detected in the three groups through ANOVA. In post hoc analysis, the AD group exhibited significantly greater dReHo variability in the right MFG than the MCI group. Compared with the HC group, the AD group exhibited significantly increased dReHo variability in the right PCG. Furthermore, dReHo variability in the right PCG was significantly negatively correlated with the MMSE and MoCA scores of patients with AD.ConclusionDisrupted dynamic IBA in the DMN might be an important characteristic of AD and could be a potential biomarker for the diagnosis or prognosis of AD. (shrink)

IntroductionTranscranial direct current stimulation is a noninvasive brain stimulation technique that applied to modulate brain activity and enhance motor recovery. However, the neurobiological substrates underlying the effects of tDCS on brain function remain poorly understood. This study aimed to investigate the central mechanisms of tDCS on improving the athletic performance of male rowing athletes.MethodsTwelve right-handed male professional rowing athletes received tDCS over the left primary motor cortex while undergoing regular training. The resting-state functional magnetic resonance imaging data were (...) acquired before and after tDCS. Measures of amplitude of low-frequency fluctuation and regional homogeneity were calculated and compared between baseline and follow-up, as well as topological measures including global and local efficiency of functional brain networks constructed by graph theoretical analysis.ResultsMale rowing athletes showed increased isokinetic muscle strength of the left knee and left shoulder after tDCS. Increased ALFF values were found in the right precentral gyrus of male rowing athletes after tDCS when compared with those before tDCS. In addition, male rowing athletes showed increased ReHo values in the left paracentral lobule following tDCS. Moreover, increased nodal global efficiency was identified in the left inferior frontal gyrus of male rowing athletes after tDCS.ConclusionThe findings suggested that simultaneous tDCS-induced excitation over the primary motor cortex might potentially improve the overall athletic performance in male rowing athletes through the right precentral gyrus and left paracentral lobule, as well as left inferior frontal gyrus. (shrink)

Music-based interventions (MBI) have become increasingly widely adopted for dementia and related disorders. Previous research shows that music engages reward-related regions through functional connectivity with the auditory system, but evidence for the effectiveness of MBI is mixed in older adults with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). This underscores the need for a unified mechanistic understanding to motivate MBIs. The main objective of the present study is to characterize the intrinsic connectivity of the auditory and reward systems in (...) healthy aging individuals with MCI, and those with AD. Using resting-state fMRI data from the Alzheimer’s Database Neuroimaging Initiative, we tested resting-state functional connectivity within and between auditory and reward systems in older adults with MCI, AD, and age-matched healthy controls (N = 105). Seed-based correlations were assessed from regions of interest (ROIs) in the auditory network (i.e., anterior superior temporal gyrus, posterior superior temporal gyrus, Heschl’s Gyrus), and the reward network (i.e., nucleus accumbens, caudate, putamen, and orbitofrontal cortex). AD individuals were lower in both within-network and between-network functional connectivity in the auditory network and reward networks compared to MCI and controls. Furthermore, graph theory analyses showed that the MCI group had higher clustering and local efficiency than both AD and control groups, whereas AD individuals had lo... (shrink)

Objective: The dopamine hypothesis is one of the most influential theories of the neurobiological background of schizophrenia (SCZ). However, direct evidence for abnormal dopamine-related subcortical-cortical circuitry disconnectivity is still lacking. The aim of this study was therefore to test dopamine-related substantia nigra (SN)-based striato-thalamo-cortical resting-state functional connectivity (FC) in SCZ. Method: Based on our a priori hypothesis, we analyzed a large sample resting-state functional magnetic resonance imaging (fMRI) dataset from first-episode drug-naïve SCZ patients (n = (...) 112) and healthy controls (n = 82) using the SN as the seed region for an investigation of striato-thalamo-cortical FC. This was done in the standard band of slow frequency oscillations and then in its subfrequency bands (Slow4 and Slow5). Results: The analysis showed in SCZ: (1) reciprocal functional hypo-connectivity between SN and striatum, with differential patterns for Slow5 and Slow4; (2) functional hypo-connectivity between striatum and thalamus, as well as functional hyper-connectivity between thalamus and sensorimotor cortical areas, specifically in Slow4; (3) correlation of thalamo-sensorimotor functional hyper-connectivity with psychopathological symptoms. Conclusions: We demonstrate abnormal dopamine-related SN-based striato-thalamo-cortical FC in slow frequency oscillations in first-episode drug-naive SCZ. This suggests that altered dopaminergic function in the SN leads to abnormal neuronal synchronization (as indexed by FC) within subcortical-cortical circuitry, complementing the dopamine hypothesis in SCZ on the regional level of resting-state activity. (shrink)

Optic neuropathy refers to disease of the optic nerve and can result in loss of visual acuity and/or visual field defects. Combining findings from multiple fMRI modalities can offer valuable information for characterizing and managing optic neuropathies. In this article, we review a subset of resting-state functional magnetic resonance imaging (RS-fMRI) studies of optic neuropathies. We consider glaucoma, acute optic neuritis (ON), discuss traumatic optic neuropathy (TON), and explore consistency between findings from RS and visually driven (...) fMRI studies. Consistent with visually driven studies, glaucoma studies at rest also indicated reduced activation in the visual cortex and dorsal visual stream. RS-fMRI further reported varying levels of functional connectivity in the ventral stream depending on disease severity. ON patients show alterations within the visual cortex in both fMRI techniques. Particularly, higher-than-normal RS activity is observed in the acute phase and decreases as the disease progresses. A similar pattern is observed in the visual cortex of TON-like, open globe injury (OGI), patients. Additionally, visually driven and RS-fMRI studies of ON patients show recovery of brain activity in the visual cortex. RS-fMRI suggests recovery of signals in higher-tier visual areas MT and LOC as well. Finally, RS-fMRI has not yet been applied to TON, although reviewing OGI studies suggests that it is feasible. Future RS-fMRI studies of optic neuropathies could prioritize studying the fine scale RS activity of brain areas that visually driven studies have identified. We suggest that a more systematic longitudinal comparison of optic neuropathies with advanced fMRI would provide improved diagnostic and prognostic information. (shrink)

Introduction: Electroconvulsive therapy is a commonly used brain stimulation treatment for treatment-resistant or severe depression. This study was planned to find the effects of ECT on brain connectivity by conducting a systematic review and coordinate-based meta-analysis of the studies performing resting state fMRI in patients with depression receiving ECT.Methods: We systematically searched the databases published up to July 31, 2020, for studies in patients having depression that compared resting-state functional connectivity before and after a course (...) of pulse wave ECT. Meta-analysis was performed using the activation likelihood estimation method after extracting details about coordinates, voxel size, and method for correction of multiple comparisons corresponding to the significant clusters and the respective rsFC analysis measure with its method of extraction.Results: Among 41 articles selected for full-text review, 31 articles were included in the systematic review. Among them, 13 articles were included in the meta-analysis, and a total of 73 foci of 21 experiments were examined using activation likelihood estimation in 10 sets. Using the cluster-level interference method, one voxel-wise analysis with the measure of amplitude of low frequency fluctuations and one seed-voxel analysis with the right hippocampus showed a significant reduction in the left cingulate gyrus and a significant increase in the right hippocampus with the right parahippocampal gyrus, respectively. Another analysis with the studies implementing network-wise resting state functional connectivity showed a significant increase in bilateral posterior cingulate cortex. There was considerable variability as well as a few key deficits in the preprocessing and analysis of the neuroimages and the reporting of results in the included studies. Due to lesser studies, we could not do further analysis to address the neuroimaging variability and subject-related differences.Conclusion: The brain regions noted in this meta-analysis are reasonably specific and distinguished, and they had significant changes in resting state functional connectivity after a course of ECT for depression. More studies with better neuroimaging standards should be conducted in the future to confirm these results in different subgroups of depression and with varied aspects of ECT. (shrink)