Resting-state functional magnetic resonance imaging (RS-fMRI) has been widely used to investigate temporally correlated fluctuations between distributed brain areas, as well as to characterize local synchronization of low frequency (<0.1 Hz) spontaneous fMRI signal. Regional homogeneity (ReHo) was proposed as a voxel-wise measure of the synchronization of the timecourses of neighboring voxels and has been used in many studies of brain disorders. However, the interpretation of ReHo remains challenging because the effect of high frequency task on ReHo is still not clear. In order to investigate the effect of a high-frequency task on the modulation of local synchronization of resting-state activity, we employed three right-finger movement scanning sessions: slow-event related ('Slow'), fast-event related ('Fast'), and continuous finger pressure ('Tonic'), from 21 healthy participants and compared the ReHo of the three task states with that of resting-state ('Rest'). In the contralateral sensorimotor cortex, 'Slow' task state showed greater ReHo than 'Rest' in low frequency band (0-0.08Hz) fMRI signal, but lower ReHo in high frequency band (0.08-1.67 Hz); 'Fast' task state showed lower ReHo than 'Rest' in both the low and high frequency band; 'Tonic' state did not show any significant difference compared to 'Rest'. The results in the contralateral sensorimotor cortex suggest that local synchronization of BOLD signal varies with different finger tapping speed. In the ipsilateral sensorimotor cortex, all the three task states had lower ReHo than the 'Rest' state both in the low and high frequency, suggesting a similar effect of fast and slow finger tapping frequencies on local synchronization of BOLD signal in the ipsilateral motor cortex.

We aimed to elucidate the dACC laterality in typically developing children and their sex/age-related differences with a sample of 84 right-handed children (6-16 years, 42 boys). We first replicated the previous finding observed in adults that gray matter density asymmetry in the dACC was region-specific: leftward (left > right) in its superior part, rightward (left < right) in its inferior part. Intrinsic connectivity analysis of these regions further revealed region-specific asymmetric connectivity profiles in dACC as well as their sex and age differences. Specifically, the superior dACC connectivity with frontoparietal network and the inferior dACC connectivity with visual network are rightward. The superior dACC connectivity with the default network (lateral temporal cortex) was more involved in the left hemisphere. In contrast, the inferior dACC connectivity with the default network (anterior medial prefrontal cortex) was more lateralized towards the right hemisphere. The superior dACC connectivity with lateral visual cortex was more distinct across two hemispheres in girls than that in boys. This connection in boys changed with age from right-prominent to left-prominent asymmetry whereas girls developed the connection from left-prominent to no asymmetry. These findings not only highlight the complexity and laterality of the dACC but also provided insights into dynamical structure-function relationships during the development.

Children with rolandic epilepsy (RE) are often associated with cognitive deficits and behavioral problems. Findings from neurophysiological and neuroimaging studies in RE have now demonstrated dysfunction not only in rolandic focus, but also in distant neuronal circuits. Little is known, however, about whether there is distributed abnormal spontaneous brain activity in RE. Using resting-state functional magnetic resonance imaging (RS-fMRI), the present study aimed to determine whether children with RE show abnormal local synchronization during resting state and, if so, whether these changes could be associated with the behavioral/clinical characteristics of RE. Regional homogeneity (ReHo) in children with RE (n = 30) and healthy children (n = 20) was computed on resting-state functional MRI data. In comparison with healthy children, children with RE showed increased ReHo in the central, premotor, and prefrontal regions, while they showed decreased ReHo in bilateral orbitofrontal cortex and temporal pole. In addition, the ReHo value in the left orbitofrontal cortex negatively was corrected with performance intelligence quotient in the children with RE. The aberrant local synchronization, not strictly related to primary site of the typical rolandic focus, indicates the neuropathophysiological mechanism of RE. The study findings may shed new light on the understanding of neural correlation of neuropsychological deficiencies in the children with RE.

Although mesial temporal lobe epilepsy (mTLE) is characterized by the pathological changes in mesial temporal lobe, function alteration was also found in extratemporal regions. Our aim is to investigate the information flow between the epileptogenic zone (EZ) and other brain regions. Resting-state functional magnetic resonance imaging (RS-fMRI) data were recorded from 23 patients with left mTLE and matched controls. We first identified the potential EZ using the amplitude of low-frequency fluctuation (ALFF) of RS-fMRI signal, then performed voxel-wise Granger causality analysis between EZ and the whole brain. Relative to controls, patients demonstrated decreased driving effect from EZ to thalamus and basal ganglia, and increased feedback. Additionally, we found an altered causal relation between EZ and cortical networks (default mode network, limbic system, visual network and executive control network). The influence from EZ to right precuneus and brainstem negatively correlated with disease duration, whereas that from the right hippocampus, fusiform cortex, and lentiform nucleus to EZ showed positive correlation. These findings demonstrate widespread brain regions showing abnormal functional interaction with EZ. In addition, increased ALFF in EZ was positively correlated with the increased driving effect on EZ in patients, but not in controls. This finding suggests that the initiation of epileptic activity depends not only on EZ itself, but also on the activity emerging in large-scale macroscopic brain networks. Overall, this study suggests that the causal topological organization is disrupted in mTLE, providing valuable information to understand the pathophysiology of this disorder.

Recent studies employing rapid sampling techniques have demonstrated that the resting state fMRI (rs-fMRI) signal exhibits synchronized activities at frequencies much higher than the conventional frequency range (<0.1 Hz). However, little work has investigated the changes in the high-frequency fluctuations between different resting states. Here, we acquired rs-fMRI data at a high sampling rate (TR = 400 ms) from subjects with both eyes open (EO) and eyes closed (EC), and compared the amplitude of fluctuation (AF) between EO and EC for both the low- and high-frequency components. In addition to robust AF differences in the conventional low frequency band (<0.1 Hz) in visual cortex, primary auditory cortex and primary sensorimotor cortex (PSMC), we also detected high-frequency (primarily in 0.1-0.35 Hz) differences. The high-frequency results without covariates regression exhibited noisy patterns. For the data with nuisance covariates regression, we found a significant and reproducible reduction in high-frequency AF between EO and EC in the bilateral PSMC and the supplementary motor area (SMA), and an increase in high-frequency AF in the left middle occipital gyrus (MOG). Furthermore, we investigated the effect of sampling rate by down-sampling the data to effective TR = 2 s. Briefly, by using the rapid sampling rate, we were able to detect more regions with significant differences while identifying fewer artifactual differences in the high-frequency bands as compared to the down-sampled dataset. We concluded that (1) high-frequency fluctuations of rs-fMRI signals can be modulated by different resting states and thus may be of physiological importance; and (2) the regression of covariates and the use of fast sampling rates are superior for revealing high-frequency differences in rs-fMRI signals.

Neuroimaging studies have revealed that the task-related functional brain activities are impaired in internet gaming disorder (IGD) subjects. However, little is known about the alternations in spontaneous brain activities about them. Recent studies have proposed that the brain activities of different frequency ranges are generated by different nervous activities and have different physiological and psychological functions. Thus, in this study, we set to explore the spontaneous brain activities in IGD subjects by measuring the fractional amplitude of low-frequency fluctuation (fALFF), to investigate band-specific changes of resting-state fALFF. We subdivided the frequency range into five bands based on literatures. Comparing to healthy controls, the IGD group showed decreased fALFF values in the cerebellum posterior lobe and increased fALFF values in superior temporal gyrus. Significant interactions between frequency bands and groups were found in the cerebellum, the anterior cingulate, the lingual gyrus, the middle temporal gyrus, and the middle frontal gyrus. Those brain regions are proved related to the executive function and decision-making. These results revealed the changed spontaneous brain activity of IGD, which contributed to understanding the underlying pathophysiology of IGD.

As the multi-center studies with resting-state functional magnetic resonance imaging (RS-fMRI) have been more and more applied to neuropsychiatric studies, both intra- and inter-scanner reliability of RS-fMRI are becoming increasingly important. The amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) are 3 main RS-fMRI metrics in a way of voxel-wise whole-brain (VWWB) analysis. Although the intra-scanner reliability (i.e., test-retest reliability) of these metrics has been widely investigated, few studies has investigated their inter-scanner reliability. In the current study, 21 healthy young subjects were enrolled and scanned with blood oxygenation level dependent (BOLD) RS-fMRI in 3 visits (V1 - V3), with V1 and V2 scanned on a GE MR750 scanner and V3 on a Siemens Prisma. RS-fMRI data were collected under two conditions, eyes open (EO) and eyes closed (EC), each lasting 8 minutes. We firstly evaluated the intra- and inter-scanner reliability of ALFF, ReHo, and DC. Secondly, we measured systematic difference between two scanning visits of the same scanner as well as between two scanners. Thirdly, to account for the potential difference of intra- and inter-scanner local magnetic field inhomogeneity, we measured the difference of relative BOLD signal intensity to the mean BOLD signal intensity of the whole brain between each pair of visits. Last, we used percent amplitude of fluctuation (PerAF) to correct the difference induced by relative BOLD signal intensity. The inter-scanner reliability was much worse than intra-scanner reliability; Among the VWWB metrics, DC showed the worst (both for intra-scanner and inter-scanner comparisons). PerAF showed similar intra-scanner reliability with ALFF and the best reliability among all the 4 metrics. PerAF reduced the influence of BOLD signal intensity and hence increase the inter-scanner reliability of ALFF. For multi-center studies, inter-scanner reliability should be taken into account.

Conventional functional magnetic resonance imaging (fMRI) studies on motor feedback employ periodical blocked paradigm which does not allow frequency analysis of brain activity. Here, we carried out an fMRI study by using a continuous paradigm, that is, continuous (8 min) feedback of finger force. Borrowing an analytic method widely used in resting-state fMRI studies, that is, regional homogeneity (ReHo), we compared the local synchronization in some subfrequency bands between real and sham feedback, and the subbands were defined as Slow-6 (0.0-0.01 Hz), Slow-5 (0.01-0.027 Hz), Slow-4 (0.027-0.073 Hz), Slow-3 (0.073-0.198 Hz), and Slow-2 (0.198-0.25 Hz). Our results revealed that the five subfrequency bands of brain activity contributed to the changes of ReHo between real and sham feedback differently, and, more importantly, the changes in basal ganglia were only manifested in Slow-6, implicating the fact that ReHo in ultraslow band may be associated with the functional significance of BG, that is, motor control. These findings provide novel insights into the neural substrate underlying motor feedback, and properties of the ultraslow band of local synchronization deserve more attention in future explorations.

The amplitude of low-frequency fluctuation (ALFF) measures low-frequency oscillations of the blood-oxygen-level-dependent signal, characterizing local spontaneous activity during the resting state. ALFF is a commonly used measure for resting-state functional magnetic resonance imaging (rs-fMRI) in numerous basic and clinical neuroscience studies. Using a test-retest rs-fMRI dataset consisting of 21 healthy subjects and three repetitive scans, we found that several key brain regions with high ALFF intensities (or magnitude) had poor reliability. Such regions included the posterior cingulate cortex, the medial prefrontal cortex in the default mode network, parts of the right and left thalami, and the primary visual and motor cortices. The above finding was robust with regard to different sample sizes (number of subjects), different scanning parameters (repetition time) and variations of test-retest intervals (i.e., intra-scan, intra-session, and inter-session reliability), as well as with different scanners. Moreover, the qualitative, map-wise results were validated further with a region-of-interest-based quantitative analysis using "canonical" coordinates as reported previously. Therefore, we suggest that the reliability assessments be incorporated in future ALFF studies, especially for the brain regions with a large ALFF magnitude as listed in our paper. Splitting single data into several segments and assessing within-scan "test-retest" reliability is an acceptable alternative if no "real" test-retest datasets are available. Such evaluations might become more necessary if the data are collected with clinical scanners whose performance is not as good as those that are used for scientific research purposes and are better maintained because the lower signal-to-noise ratio may further dampen ALFF reliability.

Globus pallidus interna (GPi) is an effective deep brain stimulation site for the treatment of Tourette syndrome (TS), and plays a crucial role in the pathophysiology of TS. To investigate the functional network feature of GPi in TS patients, we retrospectively studied 24 boys with 'pure' TS and 32 age-/education-matched healthy boys by resting state functional magnetic resonance images. Amplitude of low-frequency fluctuation (ALFF) and functional connectivity were used to estimate the local activity in GPi and its functional coordinate with the whole brain regions, respectively. We found decreased ALFF in patients' bilateral GPi, which was also negatively correlated with clinical symptoms. Functional connectivity analysis indicated abnormal regions within motor and motor-control networks in patients (inferior part of sensorimotor area, cerebellum, prefrontal cortex, cingulate gyrus, caudate nucleus, and brain stem). Transcranial magnetic stimulation sites defined by previous studies ("hand knob" area, premotor area, and supplementary motor area) did not show significantly different functional connectivity with GPi between groups. In summary, this study characterized the disrupted functional network of GPi and provided potential regions-of-interest for further basic and clinical studies on TS.

As mesial temporal lobe epilepsy (mTLE) has been recognized as a network disorder, a longitudinal connectome investigation may shed new light on the understanding of the underlying pathophysiology related to distinct surgical outcomes. Resting-state functional MRI data was acquired from mTLE patients before (n = 37) and after (n = 24) anterior temporal lobectomy. According to surgical outcome, patients were classified as seizure-free (SF, n = 14) or non-seizure-free (NSF, n = 10). First, we found higher network resilience to targeted attack on topologically central nodes in the SF group compared to the NSF group, preoperatively. Next, a two-way mixed analysis of variance with between-subject factor 'outcome' (SF vs. NSF) and within-subject factor 'treatment' (pre-operation vs. post-operation) revealed divergent dynamic reorganization in nodal topological characteristics between groups, in the temporoparietal junction and its connection with the ventral prefrontal cortex. We also correlated the network damage score (caused by surgical resection) with postsurgical brain function, and found that the damage score negatively correlated with postoperative global and local parallel information processing. Taken together, dynamic connectomic architecture provides vital information for selecting surgical candidates and for understanding brain recovery mechanisms following epilepsy surgery.

Many studies have shown abnormal functional connectivity in children with attention deficit hyperactivity disorder (ADHD) by using resting-state functional magnetic resonance imaging (rs-fMRI). However, few studies illustrated that to what extent these findings were consistent across different datasets. The present study aimed to assess the consistency of abnormal functional connectivity in children with ADHD across the four datasets from a public-assess rs-fMRI ADHD cohort, namely, ADHD-200. We employed the identical analysis process of previous studies and examined a few factors, including connectivity with the seed regions of the bilateral dorsal anterior cingulate cortex, bilateral inferior frontal gyrus, and bilateral middle frontal gyrus; connectivity between default mode network and executive control network; stringent and lenient statistical thresholds; and the ADHD subtypes. Our results revealed a high inconsistency of abnormal seed-based connectivity in children with ADHD across all datasets, even across three datasets from the same research site. This inconsistency could also be observed with a lenient statistical threshold. Besides, each dataset did not show abnormal connectivity between default mode network and executive control network for ADHD, albeit this abnormal connectivity between networks was intensively reported in previous studies. Importantly, the ADHD combined subtype showed greater consistency than did the inattention subtype. These findings provided methodological insights into the studies on spontaneous brain activity of ADHD, and the ADHD subtypes deserve more attention in future studies.

Beneficial effects of repetitive transcranial magnetic stimulation (rTMS) on left dorsolateral prefrontal cortex (DLPFC) have been consistently shown for treating various neuropsychiatrical or neuropsychological disorders, but relatively little is known about its neural mechanisms. Here we conducted a randomized, double-blind, SHAM-controlled study to assess the effects of high-frequency left DLPFC rTMS on resting-state activity. Thirty-eight young healthy subjects received two sessions of either real rTMS (N = 18, 90% motor-threshold; left DLPFC at 20 Hz) or SHAM TMS (N = 20) and functional magnetic resonance imaging scan during rest in 2 days separated by 48 h. Resting-state bran activity was measured with the fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC). Increased fALFF was found in rostral anterior cingulate cortex (rACC) after 20 Hz rTMS, while no changes were observed after SHAM stimulation. Using the suprathreshold rACC cluster as the seed, increased FC was found in left temporal cortex (stimulation vs. group interaction). These data suggest that high-frequency rTMS on left DLPFC enhances low-frequency resting-state brain activity in the target site and remote sites as reflected by fALFF and FC.

Spontaneous brain activity or off-line activity after memory encoding is associated with memory consolidation. A few recent resting-state functional magnetic resonance imaging (RS-fMRI) studies indicate that the RS-fMRI could map off-line memory consolidation effects. However, the gene effects on memory consolidation process remain largely unknown. Here we collected two RS-fMRI sessions, one before and another after an episodic memory encoding task, from two groups of healthy young adults, one with apolipoprotein E (APOE) ε2/ε3 and the other with APOE ε3/ε4. The ratio of regional homogeneity (ReHo), a measure of local synchronization of spontaneous RS-fMRI signal, of the two sessions was used as an index of memory-consolidation. APOE ε3/ε4 group showed greater ReHo ratio within the medial temporal lobe (MTL). The ReHo ratio in MTL was significantly correlated with the recognition memory performance in the APOE ε3/ε4 group but not in ε2/ε3 group. Additionally, APOE ε3/ε4 group showed lower ReHo ratio in the occipital and parietal picture-encoding areas. Our results indicate that APOE ε3/ε4 group may have a different off-line memory consolidation process compared to ε2/ε3 group. These results may help generate future hypotheses that the off-line memory consolidation might be impaired in Alzheimer's disease.

High-frequency oscillations (HFOs, >0.1 Hz) of resting-state fMRI (rs-fMRI) signals have received much attention in recent years. Denoising is critical for HFO studies. Previous work indicated that head motion (HM) has remarkable influences on a variety of rs-fMRI metrics, but its influences on rs-fMRI HFOs are still unknown. In this study, we investigated the impacts of HM regression (HMR) on HFO results using a fast sampling rs-fMRI dataset. We demonstrated that apparent high-frequency (∼0.2-0.4 Hz) components existed in the HM trajectories in almost all subjects. In addition, we found that individual-level HMR could robustly reveal more between-condition (eye-open vs. eye-closed) amplitude differences in high-frequency bands. Although regression of mean framewise displacement (FD) at the group level had little impact on the results, mean FD could significantly account for inter-subject variance of HFOs even after individual-level HMR. Our findings suggest that HM artifacts should not be ignored in HFO studies, and HMR is necessary for detecting HFO between-condition differences.

Prior research has shown that the amygdala of carriers of the short allele (s) of the serotonin transporter (5-HTT) gene (5-HTTLPR) have a larger response to negative emotional stimuli and higher spontaneous activity during the resting state than non-carriers. However, recent studies have suggested that the effects of 5-HTTLPR may be specific to different ethnic groups. Few studies have been conducted to address this issue.

Recurrently and abnormally hypersynchronous discharge is a striking feature of idiopathic generalized epilepsy (IGE). Resting-state functional magnetic resonance imaging has revealed aberrant spontaneous brain synchronization, predominately in low-frequency range (<0.1 Hz), in individuals with IGE. Little is known, however, about these changes in local synchronization across different frequency bands. We examined alterations to frequency-specific local synchronization in terms of spontaneous blood oxygen level-dependent (BOLD) fluctuations across 5 bands, spanning 0 to 0.25 Hz. Specifically, we compared brain activity in a large cohort of IGE patients (n = 86) to age- and sex-matched normal controls (n = 86). IGE patients showed decreased local synchronization in low frequency (<0.073 Hz), primarily in the default mode network (DMN). IGE patients also exhibited increased local synchronization in high-frequency (>0.073 Hz) in a "conscious perception network," which is anchored by the pregenual and dorsal anterior cingulate cortex, as well as the bilateral insular cortices, possibly contributing to impaired consciousness. Furthermore, we found frequency-specific alternating local synchronization in the posterior portion of the DMN relative to the anterior part, suggesting an interaction between the disease and frequency bands. Importantly, the aberrant high-frequency local synchronization in the middle cingulate cortex was associated with disease duration, thus linking BOLD frequency changes to disease severity. These findings provide an overview of frequency-specific local synchronization of BOLD fluctuations, and may be helpful in uncovering abnormal synchronous neuronal activity in patients with IGE at specific frequency bands.

Sustained attention involves two distinct processes, i.e., external focus and internal focus. Some recent neuroimaging studies employed the instruction of experimenters or the self-report from participants to generate the two attentional processes, and observed that the default mode network (DMN) was also responding to the external focus. These observations challenged the general view that the DMN accounts for the internally directed cognition, e.g., unfocused mind wandering, task independent-thoughts and internally focused events. Notably, the instruction or self-report may not effectively ensure the participants engage in the external focus/internal focus, and thus, the functional significance of the DMN for the externally focused process remains to be verified. In the present study, a new task paradigm, i.e., real/sham continuous feedback of finger force, was employed to generate the attentional process of external focus/internal focus, and the functional connectivity among the node regions of the DMN was further investigated in the two processes respectively. We found that two regions of the DMN, posterior cingulate cortex and left inferior parietal cortex/angular gyrus showed stronger inter-regional connectivity in the externally focused process than it in the internally focused process. Intriguingly, this functional connectivity was closely related to the behavioral performance in the process of external focus. These findings implicated that the functional significance of the DMN in sustained attention was more than responding to the internally directed cognition, and the task paradigm of continuous finger force feedback could benefit for the future studies on the externally focused/internally focused process of sustained attention.

The amplitude of low-frequency fluctuation (ALFF) measures resting-state functional magnetic resonance imaging (RS-fMRI) signal of each voxel. However, the unit of blood oxygenation level-dependent (BOLD) signal is arbitrary and hence ALFF is sensitive to the scale of raw signal. A well-accepted standardization procedure is to divide each voxel's ALFF by the global mean ALFF, named mALFF. Although fractional ALFF (fALFF), a ratio of the ALFF to the total amplitude within the full frequency band, offers possible solution of the standardization, it actually mixes with the fluctuation power within the full frequency band and thus cannot reveal the true amplitude characteristics of a given frequency band. The current study borrowed the percent signal change in task fMRI studies and proposed percent amplitude of fluctuation (PerAF) for RS-fMRI. We firstly applied PerAF and mPerAF (i.e., divided by global mean PerAF) to eyes open (EO) vs. eyes closed (EC) RS-fMRI data. PerAF and mPerAF yielded prominently difference between EO and EC, being well consistent with previous studies. We secondly performed test-retest reliability analysis and found that (PerAF ≈ mPerAF ≈ mALFF) > (fALFF ≈ mfALFF). Head motion regression (Friston-24) increased the reliability of PerAF, but decreased all other metrics (e.g. mPerAF, mALFF, fALFF, and mfALFF). The above results suggest that mPerAF is a valid, more reliable, more straightforward, and hence a promising metric for voxel-level RS-fMRI studies. Future study could use both PerAF and mPerAF metrics. For prompting future application of PerAF, we implemented PerAF in a new version of REST package named RESTplus.

No abstract available