Intranetwork and internetwork functional connectivity abnormalities in pediatric multiple sclerosis

Active motor functional magnetic resonance imaging (fMRI) studies have shown that pediatric multiple sclerosis (MS) patients have a strictly lateralized pattern of activations and a preserved functional connectivity (FC) within the motor system when compared to age‐matched healthy controls. However, it is still not clear whether a preserved FC in pediatric MS is present only in the motor system, or involves other relevant functional system. Resting‐state (RS) fMRI is a valuable tool for an unbiased investigation of FC abnormalities of multiple networks. This study explored abnormalities of RS FC within and between large‐scale neuronal networks from 44 pediatric MS patients and 27 controls and their correlation with clinical, neuropsychological, and conventional MRI measures. Compared to controls, pediatric MS patients had a decreased FC of several regions of the sensorimotor, secondary visual, default‐mode (DMN), executive control, and bilateral working memory (WMN) networks. They also experienced an increased FC in the right medial frontal gyrus of the attention network, which was correlated with T2 lesion volume. Cognitively impaired patients had decreased RS FC of the right precuneus of the left WMN. An increased FC between the sensorimotor network and the DMN, and between the L WMN and the attention network as well as a decreased FC between L WMN and the DMN were also found. A distributed pattern of FC abnormalities within large‐scale neuronal networks occurs in pediatric MS patients, contributes to their cognitive status, and is partially driven by focal white matter lesions. Internetwork connectivity is relatively preserved in these patients. Hum Brain Mapp 35:4180–4192, 2014. © 2014 Wiley Periodicals, Inc .     

Dynamic functional connectivity reveals altered variability in functional connectivity among patients with major depressive disorder

Resting‐state fMRI (RS‐fMRI) has become a useful tool to investigate the connectivity structure of mental health disorders. In the case of major depressive disorder (MDD), recent studies regarding the RS‐fMRI have found abnormal connectivity in several regions of the brain, particularly in the default mode network (DMN). Thus, the relevance of the DMN to self‐referential thoughts and ruminations has made the use of the resting‐state approach particularly important for MDD. The majority of such research has relied on the grand averaged functional connectivity measures based on the temporal correlations between the BOLD time series of various brain regions. We, in our study, investigated the variations in the functional connectivity over time at global and local level using RS‐fMRI BOLD time series of 27 MDD patients and 27 healthy control subjects. We found that global synchronization and temporal stability were significantly increased in the MDD patients. Furthermore, the participants with MDD showed significantly increased overall average (static) functional connectivity (sFC) but decreased variability of functional connectivity (vFC) within specific networks. Static FC increased to predominance among the regions pertaining to the default mode network (DMN), while the decreased variability of FC was observed in the connections between the DMN and the frontoparietal network. Hum Brain Mapp 37:2918–2930, 2016. © 2016 Wiley Periodicals, Inc.     

Angular default mode network connectivity across working memory load

Initially identified during no‐task, baseline conditions, it has now been suggested that the default mode network (DMN) engages during a variety of working memory paradigms through its flexible interactions with other large‐scale brain networks. Nevertheless, its contribution to whole‐brain connectivity dynamics across increasing working memory load has not been explicitly assessed. The aim of our study was to determine which DMN hubs relate to working memory task performance during an fMRI‐based n‐back paradigm with parametric increases in difficulty. Using a voxel‐wise metric, termed the intrinsic connectivity contrast (ICC), we found that the bilateral angular gyri (core DMN hubs) displayed the greatest change in global connectivity across three levels of n‐back task load. Subsequent seed‐based functional connectivity analysis revealed that the angular DMN regions robustly interact with other large‐scale brain networks, suggesting a potential involvement in the global integration of information. Further support for this hypothesis comes from the significant correlations we found between angular gyri connectivity and reaction times to correct responses. The implication from our study is that the DMN is actively involved during the n‐back task and thus plays an important role related to working memory, with its core angular regions contributing to the changes in global brain connectivity in response to increasing environmental demands. Hum Brain Mapp 38:41–52, 2017. © 2016 Wiley Periodicals, Inc.     

Complex discharge‐affecting networks in juvenile myoclonic epilepsy: A simultaneous EEG‐fMRI study

Juvenile myoclonic epilepsy (JME) is a common subtype of idiopathic generalized epilepsies (IGEs) and is characterized by myoclonic jerks, tonic‐clonic seizures and infrequent absence seizures. The network notion has been proposed to better characterize epilepsy. However, many issues remain not fully understood in JME, such as the associations between discharge‐affecting networks and the relationships among resting‐state networks. In this project, eigenspace maximal information canonical correlation analysis (emiCCA) and functional network connectivity (FNC) analysis were applied to simultaneous EEG‐fMRI data from JME patients. The main findings of our study are as follows: discharge‐affecting networks comprising the default model (DMN), self‐reference (SRN), basal ganglia (BGN) and frontal networks have linear and nonlinear relationships with epileptic discharge information in JME patients; the DMN, SRN and BGN have dense/specific associations with discharge‐affecting networks as well as resting‐state networks; and compared with controls, significantly increased FNCs between the salience network (SN) and resting‐state networks are found in JME patients. These findings suggest that the BGN, DMN and SRN may play intermediary roles in the modulation and propagation of epileptic discharges. These roles further tend to disturb the switching function of the SN in JME patients. We also postulate that emiCCA and FNC analysis may provide a potential analysis platform to provide insights into our understanding of the pathophysiological mechanism of epilepsy subtypes such as JME. Hum Brain Mapp 37:3515–3529, 2016. © 2016 Wiley Periodicals, Inc.     

Connectivity patterns during music listening: Evidence for action‐based processing in musicians

Musical expertise is visible both in the morphology and functionality of the brain. Recent research indicates that functional integration between multi‐sensory, somato‐motor, default‐mode (DMN), and salience (SN) networks of the brain differentiates musicians from non‐musicians during resting state. Here, we aimed at determining whether brain networks differentially exchange information in musicians as opposed to non‐musicians during naturalistic music listening. Whole‐brain graph‐theory analyses were performed on participants' fMRI responses. Group‐level differences revealed that musicians' primary hubs comprised cerebral and cerebellar sensorimotor regions whereas non‐musicians' dominant hubs encompassed DMN‐related regions. Community structure analyses of the key hubs revealed greater integration of motor and somatosensory homunculi representing the upper limbs and torso in musicians. Furthermore, musicians who started training at an earlier age exhibited greater centrality in the auditory cortex, and areas related to top‐down processes, attention, emotion, somatosensory processing, and non‐verbal processing of speech. We here reveal how brain networks organize themselves in a naturalistic music listening situation wherein musicians automatically engage neural networks that are action‐based while non‐musicians use those that are perception‐based to process an incoming auditory stream. Hum Brain Mapp 38:2955–2970, 2017. © 2017 Wiley Periodicals, Inc.     

Altered resting‐state connectivity during interictal generalized spike‐wave discharges in drug‐naïve childhood absence epilepsy

Purpose: To investigate the intrinsic brain connections at the time of interictal generalized spike‐wave discharges (GSWDs) to understand their mechanism of effect on brain function in untreated childhood absence epilepsy (CAE). Methods: The EEG‐functional MRI (fMRI) was used to measure the resting state functional connectivity during interictal GSWDs in drug‐naïve CAE, and three different brain networks—the default mode network (DMN), cognitive control network (CCN), and affective network (AN)—were investigated. Results: Cross‐correlation functional connectivity analysis with priori seed revealed decreased functional connectivity within each of these three networks in the CAE patients during interictal GSWDS. It included precuneus‐dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and inferior parietal lobule in the DMN; DLPFC‐inferior frontal junction (IFJ), and pre‐supplementary motor area (pre‐SMA) subregions connectivity disruption in CCN; ACC‐ventrolateral prefrontal cortex (VLPFC) and DMPFC in AN; There were also some regions, primarily the parahippcampus, paracentral in AN, and the left frontal mid orb in the CCN, which showed increased connectivity. Conclusions: The current findings demonstrate significant alterations of resting‐state networks in drug naïve CAE subjects during interictal GSWDs and interictal GSWDs can cause dysfunction in specific networks important for psychosocial function. Impairment of these networks may cause deficits both during and between seizures. Our study may contribute to the understanding of neuro‐pathophysiological mechanism of psychosocial function impairments in patients with CAE. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Neuronal oscillations and functional interactions between resting state networks

Functional magnetic imaging (fMRI) studies showed that resting state activity in the healthy brain is organized into multiple large‐scale networks encompassing distant regions. A key finding of resting state fMRI studies is the anti‐correlation typically observed between the dorsal attention network (DAN) and the default mode network (DMN), which—during task performance—are activated and deactivated, respectively. Previous studies have suggested that alcohol administration modulates the balance of activation/deactivation in brain networks, as well as it induces significant changes in oscillatory activity measured by electroencephalography (EEG). However, our knowledge of alcohol‐induced changes in band‐limited EEG power and their potential link with the functional interactions between DAN and DMN is still very limited. Here we address this issue, examining the neuronal effects of alcohol administration during resting state by using simultaneous EEG‐fMRI. Our findings show increased EEG power in the theta frequency band (4–8 Hz) after administration of alcohol compared to placebo, which was prominent over the frontal cortex. More interestingly, increased frontal tonic EEG activity in this band was associated with greater anti‐correlation between the DAN and the frontal component of the DMN. Furthermore, EEG theta power and DAN‐DMN anti‐correlation were relatively greater in subjects who reported a feeling of euphoria after alcohol administration, which may result from a diminished inhibition exerted by the prefrontal cortex. Overall, our findings suggest that slow brain rhythms are responsible for dynamic functional interactions between brain networks. They also confirm the applicability and potential usefulness of EEG‐fMRI for central nervous system drug research. Hum Brain Mapp 35:3517–3528, 2014. © 2013 Wiley Periodicals, Inc .     

Large‐scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy

Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large‐scale RSNs is differently affected in patients with right‐ and left‐MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting‐state functional‐MRIs of 99 subjects (52 controls, 26 right‐ and 21 left‐MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF²C‐toolbox, which provided ROI‐wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right‐MTLE. Both groups showed abnormal correlation between the dorsal‐DMN and the posterior salience, as well as between the dorsal‐DMN and the executive‐control network. Patients with left‐MTLE also showed reduced correlation between the dorsal‐DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left‐MTLE expressed a low cluster coefficient, whereas the altered connections on right‐MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right‐ and left‐MTLE patients with HS have widespread abnormal interactions of large‐scale brain networks; however, all parameters evaluated indicate that left‐MTLE has a more intricate bihemispheric dysfunction compared to right‐MTLE. Hum Brain Mapp 37:3137–3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc .     

Disrupted functional connectivity of cerebellar default network areas in attention‐deficit/hyperactivity disorder

Attention‐deficit/hyperactivity disorder (ADHD) is increasingly understood as a disorder of spontaneous brain‐network interactions. The default mode network (DMN), implicated in ADHD‐linked behaviors including mind‐wandering and attentional fluctuations, has been shown to exhibit abnormal spontaneous functional connectivity (FC) within‐network and with other networks (salience, dorsal attention and frontoparietal) in ADHD. Although the cerebellum has been implicated in the pathophysiology of ADHD, it remains unknown whether cerebellar areas of the DMN (CerDMN) exhibit altered FC with cortical networks in ADHD. Here, 23 adults with ADHD and 23 age‐, IQ‐, and sex‐matched controls underwent resting state fMRI. The mean time series of CerDMN areas was extracted, and FC with the whole brain was calculated. Whole‐brain between‐group differences in FC were assessed. Additionally, relationships between inattention and individual differences in FC were assessed for between‐group interactions. In ADHD, CerDMN areas showed positive FC (in contrast to average FC in the negative direction in controls) with widespread regions of salience, dorsal attention and sensorimotor networks. ADHD individuals also exhibited higher FC (more positive correlation) of CerDMN areas with frontoparietal and visual network regions. Within the control group, but not in ADHD, participants with higher inattention had higher FC between CerDMN and regions in the visual and dorsal attention networks. This work provides novel evidence of impaired CerDMN coupling with cortical networks in ADHD and highlights a role of cerebro‐cerebellar interactions in cognitive function. These data provide support for the potential targeting of CerDMN areas for therapeutic interventions in ADHD. Hum Brain Mapp 36:3373–3386, 2015. © 2015 Wiley Periodicals, Inc.     

Functional segregation loss over time is moderated by APOE genotype in healthy elderly

We investigated the influence of the apolipoprotein E‐?4 allele (APOE‐?4) on longitudinal age‐related changes in brain functional connectivity (FC) and cognition, in view of mixed cross‐sectional findings. One hundred and twenty‐two healthy older adults (aged 58–79; 25 APOE‐?4 carriers) underwent task‐free fMRI scans at baseline. Seventy‐eight (16 carriers) had at least one follow‐up (every 2 years). Changes in intra‐ and internetwork FCs among the default mode (DMN), executive control (ECN), and salience (SN) networks, as well as cognition, were quantified using linear mixed models. Cross‐sectionally, APOE‐?4 carriers had lower functional connectivity between the ECN and SN than noncarriers. Carriers also showed a stronger age‐dependent decrease in visuospatial memory performance. Longitudinally, carriers had steeper increase in inter‐ECN‐DMN FC, indicating loss of functional segregation. The longitudinal change in processing speed performance was not moderated by APOE‐?4 genotype, but the brain–cognition association was. In younger elderly, faster loss of segregation was correlated with greater decline in processing speed regardless of genotype. In older elderly, such relation remained for noncarriers but reversed for carriers. APOE‐?4 may alter aging by accelerating the change in segregation between high‐level cognitive systems. Its modulation on the longitudinal brain–cognition relationship was age‐dependent.     

Multimodal description of whole brain connectivity: A comparison of resting state MEG,fMRI, and DWI

Structural and functional connectivity (SC and FC) have received much attention over the last decade, as they offer unique insight into the coordination of brain functioning. They are often assessed independently with three imaging modalities: SC using diffusion‐weighted imaging (DWI), FC using functional magnetic resonance imaging (fMRI), and magnetoencephalography/electroencephalography (MEG/EEG). DWI provides information about white matter organization, allowing the reconstruction of fiber bundles. fMRI uses blood‐oxygenation level‐dependent (BOLD) contrast to indirectly map neuronal activation. MEG and EEG are direct measures of neuronal activity, as they are sensitive to the synchronous inputs in pyramidal neurons. Seminal studies have targeted either the electrophysiological substrate of BOLD or the anatomical basis of FC. However, multimodal comparisons have been scarcely performed, and the relation between SC, fMRI‐FC, and MEG‐FC is still unclear. Here we present a systematic comparison of SC, resting state fMRI‐FC, and MEG‐FC between cortical regions, by evaluating their similarities at three different scales: global network, node, and hub distribution. We obtained strong similarities between the three modalities, especially for the following pairwise combinations: SC and fMRI‐FC; SC and MEG‐FC at theta, alpha, beta and gamma bands; and fMRI‐FC and MEG‐FC in alpha and beta. Furthermore, highest node similarity was found for regions of the default mode network and primary motor cortex, which also presented the highest hubness score. Distance was partially responsible for these similarities since it biased all three connectivity estimates, but not the unique contributor, since similarities remained after controlling for distance. Hum Brain Mapp 37:20–34, 2016. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.     

Reconfiguration of dynamic large‐scale brain network functional connectivity in generalized tonic–clonic seizures

An increasing number of studies in patients with generalized tonic–clonic seizures (GTCS) have reported the alteration of functional connectivity (FC) in many brain networks. However, little is known about the underlying temporal variability of FC in large‐scale brain functional networks in patients. Recently, dynamic FC could provide novel insight into the physiological mechanisms in the brain. Here, we recruited 63 GTCS and 65 age‐ and sex‐matched healthy controls. Dynamic FC approaches were used to evaluate alterations in the temporal variability of FC in patients at the region‐ and network‐levels. In addition, two kinds of brain templates (>10² and > 10³ regions) and two kinds of temporal variability FC approaches were adopted to verify the stability of the results. Patients showed increased FC variability in regions of the default mode network (DMN), ventral attention network (VAN) and motor‐related areas. The DAN, VAN, and DMN illustrated enhanced FC variability at the within‐network level. In addition, increased FC variabilities between networks were found between the DMN and cognition‐related networks, including the VAN, dorsal attention network and frontal–parietal network in GTCS. Meanwhile, the alterations in FC variability were relatively consistent across different methods and templates. Therefore, the consistent alteration of FC variability would reflect a dynamic restructuring of the large‐scale brain networks in patients with GTCS. Overly frequent information communication among cognition‐related networks, especially in the DMN, might play a role in the epileptic activity and/or cognitive dysfunction in patients.     

Hallucination‐ and speech‐specific hypercoupling in frontotemporal auditory and language networks in schizophrenia using combined task‐based fMRI data: An fBIRN study

Hypercoupling of activity in speech‐perception‐specific brain networks has been proposed to play a role in the generation of auditory‐verbal hallucinations (AVHs) in schizophrenia; however, it is unclear whether this hypercoupling extends to nonverbal auditory perception. We investigated this by comparing schizophrenia patients with and without AVHs, and healthy controls, on task‐based functional magnetic resonance imaging (fMRI) data combining verbal speech perception (SP), inner verbal thought generation (VTG), and nonverbal auditory oddball detection (AO). Data from two previously published fMRI studies were simultaneously analyzed using group constrained principal component analysis for fMRI (group fMRI‐CPCA), which allowed for comparison of task‐related functional brain networks across groups and tasks while holding the brain networks under study constant, leading to determination of the degree to which networks are common to verbal and nonverbal perception conditions, and which show coordinated hyperactivity in hallucinations. Three functional brain networks emerged: (a) auditory‐motor, (b) language processing, and (c) default‐mode (DMN) networks. Combining the AO and sentence tasks allowed the auditory‐motor and language networks to separately emerge, whereas they were aggregated when individual tasks were analyzed. AVH patients showed greater coordinated activity (deactivity for DMN regions) than non‐AVH patients during SP in all networks, but this did not extend to VTG or AO. This suggests that the hypercoupling in AVH patients in speech‐perception‐related brain networks is specific to perceived speech, and does not extend to perceived nonspeech or inner verbal thought generation.     

Relationship between structural and functional connectivity change across the adult lifespan: A longitudinal investigation

Extensive efforts are devoted to understand the functional (FC) and structural connections (SC) of the brain. FC is usually measured by functional magnetic resonance imaging (fMRI), and conceptualized as degree of synchronicity in brain activity between different regions. SC is typically indexed by measures of white matter (WM) properties, for example, by diffusion weighted imaging (DWI). FC and SC are intrinsically related, in that coordination of activity across regions ultimately depends on fast and efficient transfer of information made possible by structural connections. Convergence between FC and SC has been shown for specific networks, especially the default mode network (DMN). However, it is not known to what degree FC is constrained by major WM tracts and whether FC and SC change together over time. Here, 120 participants (20–85 years) were tested at two time points, separated by 3.3 years. Resting‐state fMRI was used to measure FC, and DWI to measure WM microstructure as an index of SC. TRACULA, part of FreeSurfer, was used for automated tractography of 18 major WM tracts. Cortical regions with tight structural couplings defined by tractography were only weakly related at the functional level. Certain regions of the DMN showed a modest relationship between change in FC and SC, but for the most part, the two measures changed independently. The main conclusions are that anatomical alignment of SC and FC seems restricted to specific networks and tracts, and that changes in SC and FC are not necessarily strongly correlated. Hum Brain Mapp 38:561–573, 2017. © 2016 Wiley Periodicals, Inc.     

Self‐regulation of ventromedial prefrontal cortex activation using real‐time fMRI neurofeedback—Influence of default mode network

The ventromedial prefrontal cortex (vmPFC) is involved in regulation of negative emotion and decision‐making, emotional and behavioral control, and active resilient coping. This pilot study examined the feasibility of training healthy subjects (n = 27) to self‐regulate the vmPFC activity using a real‐time functional magnetic resonance imaging neurofeedback (rtfMRI‐nf). Participants in the experimental group (EG, n = 18) were provided with an ongoing vmPFC hemodynamic activity (rtfMRI‐nf signal represented as variable‐height bar). Individuals were instructed to raise the bar by self‐relevant value‐based thinking. Participants in the control group (CG, n = 9) performed the same task; however, they were provided with computer‐generated sham neurofeedback signal. Results demonstrate that (a) both the CG and the EG show a higher vmPFC fMRI signal at the baseline than during neurofeedback training; (b) no significant positive training effect was seen in the vmPFC across neurofeedback runs; however, the medial prefrontal cortex, middle temporal gyri, inferior frontal gyri, and precuneus showed significant decreasing trends across the training runs only for the EG; (c) the vmPFC rtfMRI‐nf signal associated with the fMRI signal across the default mode network (DMN). These findings suggest that it may be difficult to modulate a single DMN region without affecting other DMN regions. Observed decreased vmPFC activity during the neurofeedback task could be due to interference from the fMRI signal within other DMN network regions, as well as interaction with task‐positive networks. Even though participants in the EG did not show significant positive increase in the vmPFC activity among neurofeedback runs, they were able to learn to accommodate the demand of self‐regulation task to maintain the vmPFC activity with the help of a neurofeedback signal.     

The organization of intrinsic brain activity differs between genders: A resting‐state fMRI study in a large cohort of young healthy subjects

Objectives: To investigate, using resting state (RS) functional MRI (fMRI), gender‐related differences of functional connectivity (FC) and functional network connectivity (FNC) of the human brain. Experimental design: One‐hundred and four young healthy subjects (48/56 men/women), aged between 20 and 29 years, underwent a 10‐min RS fMRI acquisition. Independent component analysis (ICA) and statistical parametric mapping were used to assess gender‐related differences in RSNs, with and without correction for regional gray matter (GM) volume. The relationships among all RSNs was also assessed using a FNC method. Principal observations: For all networks, significant between‐group differences of RS activity were found. Between‐group comparisons of RSNs changed when adjusting for GM volume, as follows: (1) there was only marginal effect on the analysis of sensory (i.e., sensorimotor, visual, and auditory) networks; and (2) there was a significantly increased difference when cognitive networks (apart from one related to attention) were considered. Compared with women, men experienced increased FC in parietal and occipital regions in most RSNs, whereas women experienced a higher RS FC in frontal and temporal regions, and in the cerebellum. When compared to women, increased FNC was found in men between several cognitive and sensory networks, whereas women showed an increased FNC only between attention and right working‐memory networks. Conclusions: The organization of intrinsic FC and FNC differ between genders. The detected differences could contribute to the understanding of the known between‐gender variation in task‐related recruitments, and the patterns of abnormalities detected in neurologic and psychiatric diseases with a gender prevalence. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Common and distinct brain networks underlying verbal and visual creativity

Creativity is imperative to the progression of human civilization, prosperity, and well‐being. Past creative researches tends to emphasize the default mode network (DMN) or the frontoparietal network (FPN) somewhat exclusively. However, little is known about how these networks interact to contribute to creativity and whether common or distinct brain networks are responsible for visual and verbal creativity. Here, we use functional connectivity analysis of resting‐state functional magnetic resonance imaging data to investigate visual and verbal creativity‐related regions and networks in 282 healthy subjects. We found that functional connectivity within the bilateral superior parietal cortex of the FPN was negatively associated with visual and verbal creativity. The strength of connectivity between the DMN and FPN was positively related to both creative domains. Visual creativity was negatively correlated with functional connectivity within the precuneus of the pDMN and right middle frontal gyrus of the FPN, and verbal creativity was negatively correlated with functional connectivity within the medial prefrontal cortex of the aDMN. Critically, the FPN mediated the relationship between the aDMN and verbal creativity, and it also mediated the relationship between the pDMN and visual creativity. Taken together, decreased within‐network connectivity of the FPN and DMN may allow for flexible between‐network coupling in the highly creative brain. These findings provide indirect evidence for the cooperative role of the default and executive control networks in creativity, extending past research by revealing common and distinct brain systems underlying verbal and visual creative cognition. Hum Brain Mapp 38:2094–2111, 2017. © 2017 Wiley Periodicals, Inc.     

Dysmaturation of the default mode network in autism

Two hypotheses of autism spectrum disorder (ASD) propose that this condition is characterized by deficits in Theory of Mind and by hypoconnectivity between remote cortical regions with hyperconnectivity locally. The default mode network (DMN) is a set of remote, functionally connected cortical nodes less active during executive tasks than at rest and is implicated in Theory of Mind, episodic memory, and other self‐reflective processes. We show that children with ASD have reduced connectivity between DMN nodes and increased local connectivity within DMN nodes and the visual and motor resting‐state networks. We show that, like the trajectory of synaptogenesis, internodal DMN functional connectivity increased as a quadratic function of age in typically developing children, peaking between, 11 and 13 years. In children with ASD, these long‐distance connections fail to develop during adolescence. These findings support the “developmental disconnection model” of ASD, provide a possible mechanistic explanation for the Theory‐of‐Mind hypothesis of ASD, and show that the window for effectively treating ASD could be wider than previously thought. Hum Brain Mapp 35:1284–1296, 2014. © 2013 Wiley Periodicals, Inc.     

Abnormal functional connectivity and cortical integrity influence dominant hand motor disability in multiple sclerosis: a multimodal analysis

Functional reorganization and structural damage occur in the brains of people with multiple sclerosis (MS) throughout the disease course. However, the relationship between resting‐state functional connectivity (FC) reorganization in the sensorimotor network and motor disability in MS is not well understood. This study used resting‐state fMRI, T1‐weighted and T2‐weighted, and magnetization transfer (MT) imaging to investigate the relationship between abnormal FC in the sensorimotor network and upper limb motor disability in people with MS, as well as the impact of disease‐related structural abnormalities within this network. Specifically, the differences in FC of the left hemisphere hand motor region between MS participants with preserved (n = 17) and impaired (n = 26) right hand function, compared with healthy controls (n = 20) was investigated. Differences in brain atrophy and MT ratio measured at the global and regional levels were also investigated between the three groups. Motor preserved MS participants had stronger FC in structurally intact visual information processing regions relative to motor impaired MS participants. Motor impaired MS participants showed weaker FC in the sensorimotor and somatosensory association cortices and more severe structural damage throughout the brain compared with the other groups. Logistic regression analysis showed that regional MTR predicted motor disability beyond the impact of global atrophy whereas regional grey matter volume did not. More importantly, as the first multimodal analysis combining resting‐state fMRI, T1‐weighted, T2‐weighted and MTR images in MS, we demonstrate how a combination of structural and functional changes may contribute to motor impairment or preservation in MS. Hum Brain Mapp 37:4262–4275, 2016. © 2016 Wiley Periodicals, Inc.     

The effects of methylphenidate on whole brain intrinsic functional connectivity

Methylphenidate (MPH) is an indirect dopaminergic and noradrenergic agonist that is used to treat attention deficit hyperactivity disorder and that has shown therapeutic potential in neuropsychiatric diseases such as depression, dementia, and Parkinson's disease. While effects of MPH on task‐induced brain activation have been investigated, little is known about how MPH influences the resting brain. To investigate the effects of 40 mg of oral MPH on intrinsic functional connectivity, we used resting state fMRI in 54 healthy male subjects in a double‐blind, randomized, placebo‐controlled study. Functional connectivity analysis employing ICA revealed seven resting state networks (RSN) of interest. Connectivity strength between the dorsal attention network and the thalamus was increased after MPH intake. Other RSN located in association cortex areas, such as the left and right frontoparietal networks and the executive control network, showed MPH‐induced connectivity increase to sensory‐motor and visual cortex regions and connectivity decrease to cortical and subcortical components of cortico‐striato‐thalamo‐cortical circuits (CST). RSN located in sensory‐motor cortex areas showed the opposite pattern with MPH‐induced connectivity increase to CST components and connectivity decrease to sensory‐motor and visual cortex regions. Our results provide evidence that MPH does not only alter intrinsic connectivity between brain areas involved in sustained attention, but that it also induces significant changes in the cortico‐cortical and cortico‐subcortical connectivity of many other cognitive and sensory‐motor RSN. Hum Brain Mapp 35:5379–5388, 2014. © 2014 Wiley Periodicals, Inc.