Variability in the analysis of a single neuroimaging dataset by many teams.

Data analysis workflows in many scientific domains have become increasingly complex and flexible. Here we assess the effect of this flexibility on the results of functional magnetic resonance imaging by asking 70 independent teams to analyse the same dataset, testing the same 9 ex-ante hypotheses1. The flexibility of analytical approaches is exemplified by the fact that no two teams chose identical workflows to analyse the data. This flexibility resulted in sizeable variation in the results of hypothesis tests, even for teams whose statistical maps were highly correlated at intermediate stages of the analysis pipeline. Variation in reported results was related to several aspects of analysis methodology. Notably, a meta-analytical approach that aggregated information across teams yielded a significant consensus in activated regions. Furthermore, prediction markets of researchers in the field revealed an overestimation of the likelihood of significant findings, even by researchers with direct knowledge of the dataset2-5. Our findings show that analytical flexibility can have substantial effects on scientific conclusions, and identify factors that may be related to variability in the analysis of functional magnetic resonance imaging. The results emphasize the importance of validating and sharing complex analysis workflows, and demonstrate the need for performing and reporting multiple analyses of the same data. Potential approaches that could be used to mitigate issues related to analytical variability are discussed.

The significance and limited influence of cerebrovascular reactivity on age and sex effects in task- and resting-state brain activity.

Functional MRI measures the blood-oxygen-level dependent signals, which provide an indirect measure of neural activity mediated by neurovascular responses. Cerebrovascular reactivity affects both task-induced and resting-state blood-oxygen-level dependent activity and may confound inter-individual effects, such as those related to aging and biological sex. We examined a large dataset containing breath-holding, checkerboard, and resting-state tasks. We used the breath-holding task to measure cerebrovascular reactivity, used the checkerboard task to obtain task-based activations, and quantified resting-state activity with amplitude of low-frequency fluctuations and regional homogeneity. We hypothesized that cerebrovascular reactivity would be correlated with blood-oxygen-level dependent measures and that accounting for these correlations would result in better estimates of age and sex effects. We found that cerebrovascular reactivity was correlated with checkerboard task activations in the visual cortex and with amplitude of low-frequency fluctuations and regional homogeneity in widespread fronto-parietal regions, as well as regions with large vessels. We also found significant age and sex effects in cerebrovascular reactivity, some of which overlapped with those observed in amplitude of low-frequency fluctuations and regional homogeneity. However, correcting for the effects of cerebrovascular reactivity had very limited influence on the estimates of age and sex. Our results highlight the limitations of accounting for cerebrovascular reactivity with the current breath-holding task.

Network-wise analysis of movie-specific information in dynamic functional connectivity using COBE.

Movie watching during functional magnetic resonance imaging has emerged as a promising tool to measure the complex behavior of the brain in response to a stimulus similar to real-life situations. It has been observed that presenting a movie (sequence of events) as a stimulus will lead to a unique time course of dynamic functional connectivity related to movie stimuli that can be compared across the participants. We assume that the observed dynamic functional connectivity across subjects can be divided into following 2 components: (i) specific to a movie stimulus (depicting group-level behavior in functional connectivity) and (ii) individual-specific behavior (not necessarily common across the subjects). In this work, using the dynamic time warping distance measure, we have shown the extent of similarity between the temporal sequences of functional connectivity while the underlying movie stimuli were same and different. Further, the temporal sequence of functional connectivity patterns related to a movie is enhanced by suppressing the subject-specific components of dynamic functional connectivity using common and orthogonal basis extraction. Quantitative analysis using the F-ratio measure reveals significant differences in dynamic functional connectivity within the somatomotor network and default mode network, as well as between the occipital network and somatomotor networks.

Altered white matter functional pathways in Alzheimer's disease.

Alzheimer's disease (AD) is associated with functional disruption in gray matter (GM) and structural damage to white matter (WM), but the relationship to functional signal in WM is unknown. We performed the functional connectivity (FC) and graph theory analysis to investigate abnormalities of WM and GM functional networks and corpus callosum among different stages of AD from a publicly available dataset. Compared to the controls, AD group showed significantly decreased FC between the deep WM functional network (WM-FN) and the splenium of corpus callosum, between the sensorimotor/occipital WM-FN and GM visual network, but increased FC between the deep WM-FN and the GM sensorimotor network. In the clinical groups, the global assortativity, modular interaction between occipital WM-FN and visual network, nodal betweenness centrality, degree centrality, and nodal clustering coefficient in WM- and GM-FNs were reduced. However, modular interaction between deep WM-FN and sensorimotor network, and participation coefficients of deep WM-FN and splenium of corpus callosum were increased. These findings revealed the abnormal integration of functional networks in different stages of AD from a novel WM-FNs perspective. The abnormalities of WM functional pathways connect downward to the corpus callosum and upward to the GM are correlated with AD.

Boosting interpersonal emotion regulation through facial imitation: functional neuroimaging foundations.

Empathic function, which is primarily manifested by facial imitation, is believed to play a pivotal role in interpersonal emotion regulation for mood reinstatement. To explore this association and its neural substrates, we performed a questionnaire survey (study l) to identify the relationship between empathy and interpersonal emotion regulation; and a task-mode fMRI study (study 2) to explore how facial imitation, as a fundamental component of empathic processes, promotes the interpersonal emotion regulation effect. Study 1 showed that affective empathy was positively correlated with interpersonal emotion regulation. Study 2 showed smaller negative emotions in facial imitation interpersonal emotion regulation (subjects imitated experimenter's smile while followed the interpersonal emotion regulation guidance) than in normal interpersonal emotion regulation (subjects followed the interpersonal emotion regulation guidance) and Watch conditions. Mirror neural system (e.g. inferior frontal gyrus and inferior parietal lobe) and empathy network exhibited greater activations in facial imitation interpersonal emotion regulation compared with normal interpersonal emotion regulation condition. Moreover, facial imitation interpersonal emotion regulation compared with normal interpersonal emotion regulation exhibited increased functional coupling from mirror neural system to empathic and affective networks during interpersonal emotion regulation. Furthermore, the connectivity of the right orbital inferior frontal gyrus-rolandic operculum lobe mediated the association between the accuracy of facial imitation and the interpersonal emotion regulation effect. These results show that the interpersonal emotion regulation effect can be enhanced by the target's facial imitation through increased functional coupling from mirror neural system to empathic and affective neural networks.

The critical mediating roles of the middle temporal gyrus and ventrolateral prefrontal cortex in the dynamic processing of interpersonal emotion regulation.

Interpersonal emotion regulation (IER) is a crucial ability for effectively recovering from negative emotions through social interaction. It has been emphasized that the empathy network, cognitive control network, and affective generation network sustain the deployment of IER. However, the temporal dynamics of functional connectivity among these networks of IER remains unclear. This study utilized IER task-fMRI and sliding window approach to examine both the stationary and dynamic functional connectivity (dFC) of IER. Fifty-five healthy participants were recruited for the present study. Through clustering analysis, four distinct brain states were identified in dFC. State 1 demonstrated situation modification stage of IER, with strong connectivity between affective generation and visual networks. State 2 exhibited pronounced connectivity between empathy network and both cognitive control and affective generation networks, reflecting the empathy stage of IER. Next, a 'top-down' pattern is observed between the connectivity of cognitive control and affective generation networks during the cognitive control stage of state 3. The affective response modulation stage of state 4 mainly involved connections between empathy and affective generation networks. Specifically, the degree centrality of the left middle temporal gyrus (MTG) mediated the association between one's IER tendency and the regulatory effects in state 2. The betweenness centrality of the left ventrolateral prefrontal cortex (VLPFC) mediated the association between one's IER efficiency and the regulatory effects in state 3. Altogether, these findings revealed that dynamic connectivity transitions among empathy, cognitive control, and affective generation networks, with the left VLPFC and MTG playing dominant roles, evident across the IER processing.

Estimation of static and dynamic functional connectivity in resting-state fMRI using zero-frequency resonator.

Resting-state functional magnetic resonance imaging (rs-fMRI) is increasingly being used to infer the functional organization of the brain. Blood oxygen level-dependent (BOLD) features related to spontaneous neuronal activity, are yet to be clearly understood. Prior studies have hypothesized that rs-fMRI is spontaneous event-related and these events convey crucial information about the neuronal activity in estimating resting state functional connectivity (FC). Attempts have been made to extract these temporal events using a predetermined threshold. However, the thresholding methods in addition to being very sensitive to noise, may consider redundant events or exclude the low-valued inflection points. Here, we extract the event-related temporal onsets from the rs-fMRI time courses using a zero-frequency resonator (ZFR). The ZFR reflects the transient behavior of the BOLD events at its output. The conditional rate (CR) of the BOLD events occurring in a time course with respect to a seed time course is used to derive static FC. The temporal activity around the estimated events called high signal-to-noise ratio (SNR) segments are also obtained in the rs-fMRI time course and are then used to compute static and dynamic FCs during rest. Coactivation pattern (CAP) is the dynamic FC obtained using the high SNR segments driven by the ZFR. The static FC demonstrates that the ZFR-based CR distinguishes the coactivation and non-coactivation scores well in the distribution. CAP analysis demonstrated the stable and longer dwell time dominant resting state functional networks with high SNR segments driven by the ZFR. Static and dynamic FC analysis underpins that the ZFR-driven temporal onsets of BOLD events derive reliable and consistent FCs in the resting brain using a subset of the time points.

Cerebrovascular reactivity increases across development in multiple networks as revealed by a breath-holding task: A longitudinal fMRI study.

Functional magnetic resonance imaging (fMRI) has been widely used to understand the neurodevelopmental changes that occur in cognition and behavior across childhood. The blood-oxygen-level-dependent (BOLD) signal obtained from fMRI is understood to be comprised of both neuronal and vascular information. However, it is unclear whether the vascular response is altered across age in studies investigating development in children. Since the breath-hold (BH) task is commonly used to understand cerebrovascular reactivity (CVR) in fMRI studies, it can be used to account for developmental differences in vascular response. This study examines how the cerebrovascular response changes over age in a longitudinal children's BH data set from the Nathan Kline Institute (NKI) Rockland Sample (aged 6-18 years old at enrollment). A general linear model approach was applied to derive CVR from BH data. To model both the longitudinal and cross-sectional effects of age on BH response, we used mixed-effects modeling with the following terms: linear, quadratic, logarithmic, and quadratic-logarithmic, to find the best-fitting model. We observed increased BH BOLD signals in multiple networks across age, in which linear and logarithmic mixed-effects models provided the best fit with the lowest Akaike information criterion scores. This shows that the cerebrovascular response increases across development in a brain network-specific manner. Therefore, fMRI studies investigating the developmental period should account for cerebrovascular changes that occur with age.

Compressed cerebro-cerebellar functional gradients in children and adolescents with attention-deficit/hyperactivity disorder.

Both cortical and cerebellar developmental differences have been implicated in attention-deficit/hyperactivity disorder (ADHD). Recently accumulating neuroimaging studies have highlighted hierarchies as a fundamental principle of brain organization, suggesting the importance of assessing hierarchy abnormalities in ADHD. A novel gradient-based resting-state functional connectivity analysis was applied to investigate the cerebro-cerebellar disturbed hierarchy in children and adolescents with ADHD. We found that the interaction of functional gradient between diagnosis and age was concentrated in default mode network (DMN) and visual network (VN). At the same time, we also found that the opposite gradient changes of DMN and VN caused the compression of the cortical main gradient in ADHD patients, implicating the co-occurrence of both low- (visual processing) and high-order (self-related thought) cognitive dysfunction manifesting in abnormal cerebro-cerebellar organizational hierarchy in ADHD. Our study provides a neurobiological framework to better understand the co-occurrence and interaction of both low-level and high-level functional abnormalities in the cortex and cerebellum in ADHD.

Frequency-dependent alterations of global signal topography in patients with major depressive disorder.

BACKGROUND: Major depressive disorder (MDD) is associated not only with disorders in multiple brain networks but also with frequency-specific brain activities. The abnormality of spatiotemporal networks in patients with MDD remains largely unclear. METHODS: We investigated the alterations of the global spatiotemporal network in MDD patients using a large-sample multicenter resting-state functional magnetic resonance imaging dataset. The spatiotemporal characteristics were measured by the variability of global signal (GS) and its correlation with local signals (GSCORR) at multiple frequency bands. The association between these indicators and clinical scores was further assessed. RESULTS: The GS fluctuations were reduced in patients with MDD across the full frequency range (0-0.1852 Hz). The GSCORR was also reduced in the MDD group, especially in the relatively higher frequency range (0.0728-0.1852 Hz). Interestingly, these indicators showed positive correlations with depressive scores in the MDD group and relative negative correlations in the control group. CONCLUSION: The GS and its spatiotemporal effects on local signals were weakened in patients with MDD, which may impair inter-regional synchronization and related functions. Patients with severe depression may use the compensatory mechanism to make up for the functional impairments.

Distinct neurofunctional alterations during motivational and hedonic processing of natural and monetary rewards in depression - a neuroimaging meta-analysis.

Reward processing dysfunctions are considered a candidate mechanism underlying anhedonia and apathy in depression. Neuroimaging studies have documented that neurofunctional alterations in mesocorticolimbic circuits may neurally mediate these dysfunctions. However, common and distinct neurofunctional alterations during motivational and hedonic evaluation of monetary and natural rewards in depression have not been systematically examined. Here, we capitalized on pre-registered neuroimaging meta-analyses to (1) establish general reward-related neural alterations in depression, (2) determine common and distinct alterations during the receipt and anticipation of monetary v. natural rewards, and, (3) characterize the differences on the behavioral, network, and molecular level. The pre-registered meta-analysis (https://osf.io/ay3r9) included 633 depressed patients and 644 healthy controls and revealed generally decreased subgenual anterior cingulate cortex and striatal reactivity toward rewards in depression. Subsequent comparative analyses indicated that monetary rewards led to decreased hedonic reactivity in the right ventral caudate while natural rewards led to decreased reactivity in the bilateral putamen in depressed individuals. These regions exhibited distinguishable profiles on the behavioral, network, and molecular level. Further analyses demonstrated that the right thalamus and left putamen showed decreased activation during the anticipation of monetary reward. The present results indicate that distinguishable neurofunctional alterations may neurally mediate reward-processing alterations in depression, in particular, with respect to monetary and natural rewards. Given that natural rewards prevail in everyday life, our findings suggest that reward-type specific interventions are warranted and challenge the generalizability of experimental tasks employing monetary incentives to capture reward dysregulations in everyday life.

Structural and functional network analysis of twins using fMRI data.

Similarities between twins have been widely demonstrated, underscoring the remarkable influence of genetics across numerous traits. In this study, we explore the genetic underpinnings of the human brain by examining MRI data from the Queensland Twin Imaging study. Specifically, this study seeks to compare brain structure and function between twins and unrelated subjects, with an emphasis on describing the effects of genetic factors. To achieve these goals, we employed the source-based morphometry method to extract intrinsic components and elucidate recognizable patterns. Our results show that twins exhibit a higher degree of similarity in gray and white matter density compared with unrelated individuals. In addition, four distinct states of brain activity were identified using coactivation patterns analysis. Furthermore, twins demonstrated a greater degree of similarity in the temporal and spatial features of each state compared with unrelated subjects. Taken together, these results support the hypothesis that twins show greater similarity in both brain structure and dynamic functional brain activity. Further exploration of these methods may advance our understanding of the complex interplay between genes, environment, and brain networks.

Multifractal long-range dependence pattern of functional magnetic resonance imaging in the human brain at rest.

Long-range dependence is a prevalent phenomenon in various biological systems that characterizes the long-memory effect of temporal fluctuations. While recent research suggests that functional magnetic resonance imaging signal has fractal property, it remains unknown about the multifractal long-range dependence pattern of resting-state functional magnetic resonance imaging signals. The current study adopted the multifractal detrended fluctuation analysis on highly sampled resting-state functional magnetic resonance imaging scans to investigate long-range dependence profile associated with the whole-brain voxels as specific functional networks. Our findings revealed the long-range dependence's multifractal properties. Moreover, long-term persistent fluctuations are found for all stations with stronger persistency in whole-brain regions. Subsets with large fluctuations contribute more to the multifractal spectrum in the whole brain. Additionally, we found that the preprocessing with band-pass filtering provided significantly higher reliability for estimating long-range dependence. Our validation analysis confirmed that the optimal pipeline of long-range dependence analysis should include band-pass filtering and removal of daily temporal dependence. Furthermore, multifractal long-range dependence characteristics in healthy control and schizophrenia are different significantly. This work has provided an analytical pipeline for the multifractal long-range dependence in the resting-state functional magnetic resonance imaging signal. The findings suggest differential long-memory effects in the intrinsic functional networks, which may offer a neural marker finding for understanding brain function and pathology.

Temporal dynamic patterns of the ventromedial prefrontal cortex underlie the association between rumination and depression.

As a major contributor to the development of depression, rumination has proven linked with aberrant default-mode network (DMN) activity. However, it remains unclear how the spontaneous spatial and temporal activity of DMN underlie the association between rumination and depression. To illustrate this issue, behavioral measures and resting-state functional magnetic resonance images were connected in 2 independent samples (NSample1 = 100, NSample2 = 95). Fractional amplitude of low-frequency fluctuations (fALFF) and regional homogeneity (ReHo) were used to assess spatial characteristic patterns, while voxel-wise functional concordance (across time windows) (VC) and Hurst exponent (HE) were used to assess temporal dynamic patterns of brain activity. Results from both samples consistently show that temporal dynamics but not spatial patterns of DMN are associated with rumination. Specifically, rumination is positively correlated with HE and VC (but not fALFF and ReHo) values, reflecting more consistent and regular temporal dynamic patterns in DMN. Moreover, subregion analyses indicate that temporal dynamics of the ventromedial prefrontal cortex (VMPFC) reliably predict rumination scores. Furthermore, mediation analyses show that HE and VC of VMPFC mediate the association between rumination and depression. These findings shed light on neural mechanisms of individual differences in rumination and corresponding risk for depression.

Structural-functional connectivity mapping of the insular cortex: a combined data-driven and meta-analytic topic mapping.

In this study, we examined structural and functional profiles of the insular cortex and mapped associations with well-described functional networks throughout the brain using diffusion tensor imaging (DTI) and resting-state functional connectivity (RSFC) data. We used a data-driven method to independently estimate the structural-functional connectivity of the insular cortex. Data were obtained from the Human Connectome Project comprising 108 adult participants. Overall, we observed moderate to high associations between the structural and functional mapping scores of 3 different insular subregions: the posterior insula (associated with the sensorimotor network: RSFC, DTI = 50% and 72%, respectively), dorsal anterior insula (associated with ventral attention: RSFC, DTI = 83% and 83%, respectively), and ventral anterior insula (associated with the frontoparietal: RSFC, DTI = 42% and 89%, respectively). Further analyses utilized meta-analytic decoding maps to demonstrate specific cognitive and affective as well as gene expression profiles of the 3 subregions reflecting the core properties of the insular cortex. In summary, given the central role of the insular in the human brain, our results revealing correspondence between DTI and RSFC mappings provide a complementary approach and insight for clinical researchers to identify dysfunctional brain organization in various neurological disorders associated with insular pathology.

Corticostriatal causality analysis in children and adolescents with attention-deficit/hyperactivity disorder.

AIM: The effective connectivity between the striatum and cerebral cortex has not been fully investigated in attention-deficit/hyperactivity disorder (ADHD). Our objective was to explore the interaction effects between diagnosis and age on disrupted corticostriatal effective connectivity and to represent the modulation function of altered connectivity pathways in children and adolescents with ADHD. METHODS: We performed Granger causality analysis on 300 participants from a publicly available Attention-Deficit/Hyperactivity Disorder-200 dataset. By computing the correlation coefficients between causal connections between striatal subregions and other cortical regions, we estimated the striatal inflow and outflow connection to represent intermodulation mechanisms in corticostriatal pathways. RESULTS: Interactions between diagnosis and age were detected in the superior occipital gyrus within the visual network, medial prefrontal cortex, posterior cingulate gyrus, and inferior parietal lobule within the default mode network, which is positively correlated with hyperactivity/impulsivity severity in ADHD. Main effect of diagnosis exhibited a general higher cortico-striatal causal connectivity involving default mode network, frontoparietal network and somatomotor network in ADHD compared with comparisons. Results from high-order effective connectivity exhibited a disrupted information pathway involving the default mode-striatum-somatomotor-striatum-frontoparietal networks in ADHD. CONCLUSION: The interactions detected in the visual-striatum-default mode networks pathway appears to be related to the potential distraction caused by long-term abnormal information input from the retina in ADHD. Higher causal connectivity and weakened intermodulation may indicate the pathophysiological process that distractions lead to the impairment of motion planning function and the inhibition/control of this unplanned motion signals in ADHD.

Estimation of neuronal task information in fMRI using zero frequency resonator.

In functional magnetic resonance imaging (fMRI), temporal onsets of BOLD events contain crucial information on activity-inducing signals and make a significant impact in the analysis of functional connectivity (FC). In literature, the estimation of the onsets of the BOLD events from the acquired blood oxygen level-dependent (BOLD) signal using fMRI is mostly performed by choosing locations with a high value of the BOLD signal. This approach may give false onset points because it can incorporate redundant onsets which could be due to non-neuronal activity or can exclude true low-valued BOLD signals. In this study, we present a novel approach to estimating the temporal onsets of the BOLD events using a zero frequency resonator (ZFR) without necessitating information regarding the experimental paradigm (EP). The proposed approach exploits the impulse-like characteristic of activity-inducing signal to estimate the temporal onset points of BOLD events using ZFR which has been widely studied in the area of speech signal processing to estimate the glottal closure instances. The idea behind the approach is that an ideal neuronal impulse has, in principle, equal energy at all frequencies, including around the zero frequency, and will preserve the information of the temporal onsets of the BOLD events at its output. The ZFR-based approach estimates two important features, namely: 1) task-induced temporal onsets of the BOLD events in the fMRI time course and 2) high SNR (HSNR) regions around the estimated BOLD events. Both the estimated features are used to obtain the FC. Results are demonstrated using both the synthetic and experimental (event-related finger tapping and block design working memory) data. We show that a small number of plausible time points, estimated by ZFR, can convey sufficient information indicating the associated activation pattern. The method also illustrates its significance over the conventional correlation and threshold-based conditional rate analysis to estimate FC. The study demonstrates that ZFR-estimated BOLD events and HSNR regions can produce sufficient functionality of the brain in the task paradigm.

Enhancing the network specific individual characteristics in rs-fMRI functional connectivity by dictionary learning.

Most fMRI inferences are based on analyzing the scans of a cohort. Thus, the individual variability of a subject is often overlooked in these studies. Recently, there has been a growing interest in individual differences in brain connectivity also known as individual connectome. Various studies have demonstrated the individual specific component of functional connectivity (FC), which has enormous potential to identify participants across consecutive testing sessions. Many machine learning and dictionary learning-based approaches have been used to extract these subject-specific components either from the blood oxygen level dependent (BOLD) signal or from the FC. In addition, several studies have reported that some resting-state networks have more individual-specific information than others. This study compares four different dictionary-learning algorithms that compute the individual variability from the network-specific FC computed from resting-state functional Magnetic Resonance Imaging (rs-fMRI) data having 10 scans per subject. The study also compares the effect of two FC normalization techniques, namely, Fisher Z normalization and degree normalization on the extracted subject-specific components. To quantitatively evaluate the extracted subject-specific component, a metric named Overlap is proposed, and it is used in combination with the existing differential identifiability I diff metric. It is based on the hypothesis that the subject-specific FC vectors should be similar within the same subject and different across different subjects. Results indicate that Fisher Z transformed subject-specific fronto-parietal and default mode network extracted using Common Orthogonal Basis Extraction (COBE) dictionary learning have the best features to identify a participant.

The complexity of spontaneous brain activity changes in schizophrenia, bipolar disorder, and ADHD was examined using different variations of entropy.

Adult attention deficit/hyperactivity disorder (ADHD), schizophrenia (SCHZ), and bipolar disorder (BP) have common symptoms and differences, and the underlying neural mechanisms are still unclear. This article will thoroughly discuss the differences between ADHD, BP, and SCHZ (31 healthy control and 31 ADHD; 34 healthy control and 34 BP; 42 healthy control and 42 SCHZ) relative to healthy subjects in combination with three atlases (et al., the Brainnetome atlas, the Dosenbach atlas, the Power atlas) and seven entropies (et al., approximate entropy (ApEn), sample entropy (SaEn), permutation entropy (PeEn), fuzzy entropy (FuEn), differential entropy (DiffEn), range entropy (RaEn), and dispersion entropy (DispEn)), as well as the prominent significant brain regions, in the hope of giving information that is more suitable for analyzing different diseases' entropy. First, the reliability (et al., intraclass correlation coefficient [ICC]) of seven kinds of entropy is calculated and analyzed by using the MSC dataset (10 subjects and 100 sessions in total) and simulation data; then, seven types of entropy and multiscale entropy expanded based on seven kinds of entropy are used to explore the differences and brain regions of ADHD, BP, and SCHZ relative to healthy subjects; and finally, by verifying the classification performance of the seven information entropies on ADHD, BP, and SCHZ, the effectiveness of the seven entropy methods is evaluated through these three methods. The core brain regions that affect the classification are given, and DiffEn performed best on ADHD, SaEn for BP, and RaEn for SCHZ.

Cerebello-cerebral resting-state functional connectivity in spinocerebellar ataxia type 3.

Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder characterized by progressive motor and nonmotor deficits concomitant with degenerative pathophysiological changes within the cerebellum. The cerebellum is topographically organized into cerebello-cerebral circuits that create distinct functional networks regulating movement, cognition, and affect. SCA3-associated motor and nonmotor symptoms are possibly related not only to intracerebellar changes but also to disruption of the connectivity within these cerebello-cerebral circuits. However, to date, no comprehensive investigation of cerebello-cerebral connectivity in SCA3 has been conducted. The present study aimed to identify cerebello-cerebral functional connectivity alterations and associations with downstream clinical phenotypes and upstream topographic markers of cerebellar neurodegeneration in patients with SCA3. This study included 45 patients with SCA3 and 49 healthy controls. Voxel-based morphometry and resting-state functional magnetic resonance imaging (MRI) were performed to characterize the cerebellar atrophy and to examine the cerebello-cerebral functional connectivity patterns. Structural MRI confirmed widespread gray matter atrophy in the motor and cognitive cerebellum of patients with SCA3. We found reduced functional connectivity between the cerebellum and the cerebral cortical networks, including the somatomotor, frontoparietal, and default networks; however, increased connectivity was observed between the cerebellum and the dorsal attention network. These abnormal patterns correlated with the CAG repeat expansion and deficits in global cognition. Our results indicate the contribution of cerebello-cerebral networks to the motor and cognitive impairments in patients with SCA3 and reveal that such alterations occur in association with cerebellar atrophy. These findings add important insights into our understanding of the role of the cerebellum in SCA3.