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How Resting-State Functional Connectivity (RSFC) is modified by learning is an important but rarely asked question. Here we used functional near-infrared spectroscopy (fNIRS) to measure changes in RSFC after learning novel subtraction and multiplication facts by forty-one young adult volunteers. We also measured changes in regional hemoglobin concentration. Fronto-parietal RSFC was modified by arithmetic learning and the fronto-parietal RSFC configuration before learning predicted the effectiveness of arithmetic learning. We also found a significant learning effect indicated by a monotonic decrease in reaction time and an increase in accuracy. Regional task-dependent oxy-hemoglobin concentration differentiated subtraction from multiplication learning supporting previous fMRI findings. These results suggest the sensitivity and importance of fronto-parietal connectivity to arithmetic learning., (Copyright © 2018. Published by Elsevier Ltd.)

Executive functions (EFs) are regulatory cognitive processes that support goal-directed thoughts and behaviors and that involve two primary networks of functional brain activity in adulthood: the fronto-parietal and cingulo-opercular networks. The current study assessed whether the same networks identified in adulthood underlie child EFs. Using task-based fMRI data from a diverse sample of N = 117 children and early adolescents (M age = 10.17 years), we assessed the extent to which neural activity was shared across switching, updating, and inhibition domains, and whether these patterns were qualitatively consistent with adult EF-related activity. Brain regions that were consistently engaged across switching, updating, and inhibition tasks closely corresponded to the cingulo-opercular and fronto-parietal networks identified in studies of adults. Isolating brain activity during more demanding task periods highlighted contributions of the dorsal anterior cingulate and anterior insular regions of the cingulo-opercular network. Results were independent of age and time-on-task effects. These results indicate that the two core brain networks that support EFs are in place by middle childhood, in agreement with resting-state findings of adultlike brain network organization. Improvement in EFs from middle childhood to adulthood, therefore, are likely due to quantitative changes in activity within these networks, rather than qualitative changes in the organization of the networks themselves. Improved knowledge of how the brain's functional organization supports EF in childhood has critical implications for understanding the maturation of cognitive abilities., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Early numeracy provides the foundation of acquiring mathematical skills that is essential for future academic success. This study examined numerical functional networks in relation to counting and number relational skills in preschoolers at 4 and 6 years of age. The counting and number relational skills were assessed using school readiness test (SRT). Resting-state fMRI (rs-fMRI) was acquired in 123 4-year-olds and 146 6-year-olds. Among them, 61 were scanned twice over the course of 2 years. Meta-analysis on existing task-based numeracy fMRI studies identified the left parietal-dominant network for both counting and number relational skills and the right parietal-dominant network only for number relational skills in adults. We showed that the fronto-parietal numerical networks, observed in adults, already exist in 4-year and 6-year-olds. The counting skills were associated with the bilateral fronto-parietal network in 4-year-olds and with the right parietal-dominant network in 6-year-olds. Moreover, the number relational skills were related to the bilateral fronto-parietal and right parietal-dominant networks in 4-year-olds and had a trend of the significant relationship with the right parietal-dominant network in 6-year-olds. Our findings suggested that neural fine-tuning of the fronto-parietal numerical networks may subserve the maturation of numeracy in early childhood.

Visuospatial processing deficits are typically associated with damage to the right hemisphere. However, deficits on spatial working memory have been reported among some individuals with focal left hemisphere damage (LHD). It has been suggested that the left hemisphere may play a role in such non-verbal working memory tasks due to the use of subvocal, verbally-mediated strategies. The current study investigated the role of the left hemisphere in spatial working memory by testing spatial span performance, both forward and backward, in a large group of individuals with a history of left hemisphere stroke. Our first aim was to establish whether individuals with LHD are indeed impaired on spatial span tasks using standardized span tasks with published normative data. Our second aim was to identify the role that language plays in supporting spatial working memory by comparing LHD individuals with and without aphasia, and by relating spatial span performance to performance on a series of language measures. Our third aim was to identify left hemisphere brain regions that contribute to spatial working memory using voxel-based lesion symptom mapping (VLSM), a whole-brain statistical approach that identifies regions critical to a particular behavior on a voxel-by-voxel basis. We found that 28% of individuals with LHD performed in the clinically-impaired range on forward spatial span and 16% performed in the clinically-impaired range on backward spatial span. There were no significant differences in performance between individuals with and without aphasia, and there were no correlations between spatial span performance and language functions such as repetition and comprehension. The VLSM analysis showed that backward spatial span was associated with a left fronto-parietal network consisting of somatosensory cortex, the supramarginal gyrus, lateral prefrontal cortex, and the frontal eye fields. Regions identified in the VLSM analysis of forward spatial span did not reach the conservative statistical threshold for significance. Overall, these results suggest that spatial working memory, as measured by spatial span, can be significantly disrupted in a subset of individuals with LHD whose lesions infringe on a network of regions in the left hemisphere that have been implicated in domain-general working memory and attentional control mechanisms.

A fronto-parietal network, comprised of the posterior parietal cortex (PPC) and the dorsal premotor cortex (PMd) has been proposed to be involved in planning and guiding movement. However, the issue of how the network is expressed across the bilateral cortical area according to the effector's side remains unclear. In this study, we tested these questions using electrocorticographic (ECoG) recordings in non-human primates and using a simple visual guided reaching task that induced a left or right hand response based on relevant cues provided for the task. The findings indicate that right hemisphere lateralized network patterns in which the right PMd was strongly coordinated with bilateral PPC immediately after presentation of the movement cue occurred, while the coherence with the left PMd was not enhanced. No difference was found in the coherence pattern between the effector's side (left hand or right hand), but the strength of coherence was different, in that animals showed a higher coherence in the right hand response compared to the left. Our data support that right lateralization in long-range phase synchrony in the 10-20 Hz low beta band is involved in motor preparation stage, irrespective of the upcoming effector's side.

Introduction: Attentional bias modification (ABM) alleviates anxiety by moderating biased attentional processing toward threat; however, its neural mechanisms remain unclear. We examined how ABM changes functional connectivity (FC) and functional network measures, leading to anxiety reduction., Methods: Fifty-four healthy anxious individuals received either ABM or sham training for 1 month in a double-blind randomized controlled trial. Anxious traits, attentional control, and attentional bias were assessed. Thirty-five participants completed resting-state functional magnetic resonance imaging (MRI) scans before and after training., Results: ABM significantly mitigated an anxious traits regarding physical stress vulnerability (η 2  = 0.12, p = 0.009). As compared to sham training, ABM significantly strengthened FC between the pulvinar and transverse temporal gyrus along the temporoparietal junction (T = 3.90, FDR-corrected p = 0.010), whereas it decreased FC between the postCG and ventral fronto-parietal network (vFPN) regions such as the anterior insula and ventrolateral prefrontal cortex (all T ≤ - 3.19, FDR-corrected p ≤ 0.034). Although ABM diminished network measures of the postcentral gyrus (postCG) (all T ≤ - 4.30, FDR-corrected p ≤ 0.006), only the pulvinar-related FC increase was specifically correlated with anxiety reduction (r = - 0.46, p = 0.007)., Limitations: Per-protocol analysis and reduced sample size in MRI analysis., Conclusions: ABM might augment the pulvinar's control over vFPN to maintain endogenous attention to a behavioral goal, while diminishing the information exchanges of the postCG with vFPN to inhibit the capture of exogenous attention by potential threats. The pulvinar might play a critical role in ABM anxiolytic efficacy., (Copyright © 2018 Elsevier B.V. All rights reserved.)

We all vary in our mental health, even among people not meeting diagnostic criteria for mental illness. Understanding this individual variability may reveal factors driving the risk for mental illness, as well as factors driving subclinical problems that still adversely affect quality of life. To better understand the large-scale brain network mechanisms underlying this variability, we examined the relationship between mental health symptoms and resting-state functional connectivity patterns in cognitive control systems. One such system is the fronto-parietal cognitive control network (FPN). Changes in FPN connectivity may impact mental health by disrupting the ability to regulate symptoms in a goal-directed manner. Here we test the hypothesis that FPN dysconnectivity relates to mental health symptoms even among individuals who do not meet formal diagnostic criteria but may exhibit meaningful symptom variation. We found that depression symptoms severity negatively correlated with between-network global connectivity (BGC) of the FPN. This suggests that decreased connectivity between the FPN and the rest of the brain is related to increased depression symptoms in the general population. These findings complement previous clinical studies to support the hypothesis that global FPN connectivity contributes to the regulation of mental health symptoms across both health and disease., Competing Interests: Competing Interests: The authors have declared that no competing interests exist.

Spatial working memory (SWM) relies on the interplay of anatomically separated and interconnected large-scale brain networks. EEG studies often observe load-associated sustained negative activity during SWM retention. Yet, whether and how such sustained negative activity in retention relates to network-specific functional activation/deactivation and relates to individual differences in SWM capacity remain to be elucidated. To cover these gaps, we recorded concurrent EEG-fMRI data in 70 healthy young adults during the Sternberg delayed-match-to-sample SWM task with three memory load levels. To a subset of participants (N = 28) that performed the task properly and had artefact-free fMRI and EEG data, we employed a novel temporo-spatial principal component analysis to derive load-dependent negative slow wave (NSW) from retention-related event-related potentials. The associations between NSW responses with SWM capacity were divergent in the higher (N = 14) and lower (N = 14) SWM capacity groups. Specifically, larger load-related increase in NSW amplitude was associated with greater SWM capacity for the higher capacity group but lower SWM capacity for the lower capacity group. Furthermore, for the higher capacity group, larger NSW amplitude was related to greater activation in bilateral parietal areas of the fronto-parietal network (FPN) and greater deactivation in medial frontal gyrus and posterior mid-cingulate cortex of the default mode network (DMN) during retention. In contrast, the lower capacity group did not show similar pattern. Instead, greater NSW was linked to higher deactivation in right posterior middle temporal gyrus. Our findings shed light on the possible differential EEG-informed neural network mechanism during memory maintenance underlying individual differences in SWM capacity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background : Previous evidence suggests that postural control processing may be more related to spatial working memory (SWM) than to nonspatial working memory (NWM). Methodological discrepancies between spatial and nonspatial cognitive tasks have made direct comparisons between the two systems difficult. Methods : To explore the neural mechanisms of SWM and NWM relative to that of postural control, participants were subjected a cognitive-posture dual-task paradigm, consisting of a 3-back letter working memory (WM) task, using physically identical stimuli with spatial and nonspatial components memorized in different sessions, and a standing balance task with a tandem stance. Additionally, there were two control sessions: a single-postural control session wherein participants pressed mouse buttons at random while standing; and a single-cognitive task control session wherein subjects completed a WM task while seated. The subjects underwent functional near-infrared spectral imaging (fNIRS) during task performance, wherein oxygenated hemoglobin concentration ([HbO]) was measured in frontal and parietal regions. Results : Postural control reduced discernment in the SWM task significantly, but did not affect NWM task performance. fNIRS showed that postural control had a significant tendency to decrease the [HbO] in the frontal-parietal network of the left hemisphere when participants completed the SWM task. No posture-associated differences in [HbO] were observed in NWM-related areas during NWM task performance. Behavioral and fNIRS data demonstrated that postural control had a selective interaction with SWM. Specifically, postural control reduced SWM discrimination and SWM-related brain activity (frontal-parietal network), but not NWM discrimination or NWM-related brain activity. Furthermore, the multiple linear regression analysis showed that SWM, but not NWM, was an important predictor of postural control. These results suggest that postural control may share more cognitive resources with SWM than with NWM.

According to the triple network hypothesis the brain is equipped with three core neurocognitive networks: the default mode (DMN), the salience (SN), and the central executive (CEN) network. Moreover, the so called dorsal nexus, has met growing interest as it is a hub region connecting these three networks. Assessment of resting-state functional connectivity (rsFC) of these networks enables the elucidation of drug-induced brain alterations. Gamma-hydroxybutyrate (GHB) is a GHB/GABA-B receptor agonist that induces a paradoxical state of mixed stimulation and sedation at moderate doses, which makes it a valuable tool to investigate neural signatures of subjective drug effects. Employing a placebo-controlled, double-blind, randomized, cross-over design, we assessed the effects of GHB (35 mg/kg p. o.) in 19 healthy male subjects on DMN-, SN-, CEN-, and dorsal nexus-rsFC measured by functional magnet resonance imaging and applying independent component as well as seed-based analyses, while subjective drug effects were investigated using visual analog scales (VAS). Subjectively, GHB increased VAS ratings of a general drug effect, stimulation, and sedation. Intrinsic DMN-, and CEN-rsFC remained largely unchanged under GHB, but the drug increased SN-DMN-rsFC and SN-dorsal nexus-rsFC, while dorsal nexus-rsFC was reciprocally increased to both the SN (right anterior insula) and to the CEN (right middle frontal gyrus). Increased sedation significantly predicted the observed SN-dorsal nexus-rsFC. In conclusion, GHB generates a unique stimulant/sedative subjective state that is paralleled by a complex pattern of increased functional connectivity encompassing all three core neurocognitive networks of the brain, while increased SN-dorsal nexus-rsFC was demonstrated to be a potential signature of the sedative component of the drug effect., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Past attempts to characterize the neural mechanisms of affective priming have conceptualized it in terms of classic cognitive conflict, but have not examined the neural oscillatory mechanisms of subliminal affective priming. Using behavioral and electroencephalogram (EEG) time frequency (TF) analysis, the current study examines the oscillatory dynamics of unconsciously triggered conflict in an emotional facial expressions version of the masked affective priming task. The results demonstrate that the power dynamics of conflict are characterized by increased midfrontal theta activity and suppressed parieto-occipital alpha activity. Across-subject and within-trial correlation analyses further confirmed this pattern. Phase synchrony and Granger causality analyses (GCAs) revealed that the fronto-parietal network was involved in unconscious conflict detection and resolution. Our findings support a response conflict account of affective priming, and reveal the role of the fronto-parietal network in unconscious conflict control.

Ineffective reduction of functional connectivity between the default mode network (DMN) and frontoparietal network (FPN) during cognitive control can interfere with performance in healthy individuals-a phenomenon present in psychiatric disorders, such as depression. Here, this mechanism is studied in healthy adolescents by examining gender differences in task-regressed functional connectivity using functional magnetic resonance imaging (MRI) and a novel task designed to place the DMN-supporting self-referential processing (SRP)-and FPN-supporting cognitive control-into conflict. Compared to boys, girls showed stronger functional connectivity between DMN and FPN during cognitive control in an SRP context ( n = 40; boys = 20), a context that also elicited more errors of omission in girls. The gender difference in errors of omission was mediated by higher self-reported co-rumination-the extensive and repetitive discussion of problems and focus on negative feelings with a same-gender peer-by girls, compared to boys. These findings indicate that placing internal and external attentional demands in conflict lead to persistent functional connectivity between FPN and DMN in girls, but not boys; however, deficits in performance during this context were explained by co-rumination, such that youth with higher co-rumination displayed the largest performance deficits. Previous research shows that co-rumination predicts depressive symptoms during adolescence; thus, gender differences in the mechanisms involved with transitioning from internal to external processing may be relevant for understanding heightened vulnerability for depression in adolescent girls.

Previous neuroimaging studies have revealed cognitive dysfunction in patients with systemic lupus erythematosus (SLE) and suggested that it may be related to disrupted brain white matter (WM) connectivity. However, no study has examined the topological properties of brain WM structural networks in SLE patients, especially in patients with non-neuropsychiatric SLE (non-NPSLE). In this study, we acquired DTI datasets from 28 non-NPSLE patients and 24 healthy controls, constructed their brain WM structural networks by using a deterministic fiber tracking approach, estimated the topological parameters of their structural networks, and compared their group differences. We reached the following results: 1) At the global level, the non-NPSLE patients showed significantly increased characteristic path length, normalized clustering coefficient and small-worldness, but significantly decreased global efficiency and local efficiency compared to the controls; 2) At the nodal level, the non-NPSLE patients had significantly decreased nodal efficiency in regions related to movement control, executive control, and working memory (bilateral precentral gyri, bilateral middle frontal gyri, bilateral inferior parietal lobes, left median cingulate gyrus and paracingulate gyrus, and right middle temporal gyrus). In addition, to pinpointing the injured WM fiber tracts in the non-NPSLE patients, we reconstructed the major brain WM pathways connecting the abnormal regions at the nodal level with the corticospinal tract (CST), superior longitudinal fasciculus-parietal terminations (SLFP), and superior longitudinal fasciculus-temporal terminations (SLFT). By analyzing the diffusion parameters along these WM fiber pathways, we detected abnormal diffusion parameters in the bilateral CST and right SLFT in the non-NPSLE patients. These results seem to indicate that injured brain WM connectivity exists in SLE patients even in the absence of neuropsychiatric symptoms.

Cognitive flexibility is essential to cope with changing task demands and often it is necessary to adapt to combined changes in a coordinated manner. The present fMRI study examined how the brain implements such multi-level adaptation processes. Specifically, on a "local," hierarchically lower level, switching between two tasks was required across trials while the rules of each task remained unchanged for blocks of trials. On a "global" level regarding blocks of twelve trials, the task rules could reverse or remain the same. The current task was cued at the start of each trial while the current task rules were instructed before the start of a new block. We found that partly overlapping and partly segregated neural networks play different roles when coping with the combination of global rule reversal and local task switching. The fronto-parietal control network (FPN) supported the encoding of reversed rules at the time of explicit rule instruction. The same regions subsequently supported local task switching processes during actual implementation trials, irrespective of rule reversal condition. By contrast, a cortico-striatal network (CSN) including supplementary motor area and putamen was increasingly engaged across implementation trials and more so for rule reversal than for nonreversal blocks, irrespective of task switching condition. Together, these findings suggest that the brain accomplishes the coordinated adaptation to multi-level demand changes by distributing processing resources either across time (FPN for reversed rule encoding and later for task switching) or across regions (CSN for reversed rule implementation and FPN for concurrent task switching)., (© 2017 Wiley Periodicals, Inc.)

Background: The study aimed to isolate and localize mutually independent cognitive processes evoked during a word recognition task involving food-related and food-neutral words using independent component analysis (ICA) for continuously recorded EEG data. Recognition memory (old/new effect) involves cognitive subcomponents-familiarity and recollection-which may be temporally and spatially dissociated in the brain. Food words may evoke additional attentional salience which may interact with the old/new effect., Methods: Sixteen satiated female participants undertook a word recognition task consisting of an encoding phase (learning of presented words, 40 food-related and 40 food neutral) and a test phase (recognition of previously learned words and new words). Simultaneously recorded 64-channel EEG data were decomposed into mutually independent components using the Infomax algorithm in EEGLAB. The components were localized using single dipole fitting using a four-shell BESA head model. The resulting (nonartefactual) components with <15% residual variance were clustered across subjects using the kmeans algorithm resulting in five meaningful clusters localized to fronto-parietal regions. Repeated-measures anova was employed to test main effects (old/new and food relevance) and their interaction on cluster time courses., Results: Early task-relevant old/new effects were localized to the medial frontal gyrus (MFG) and later old/new effects to the right parietal regions (precuneus). Food-related (nontask-relevant) salience effects were localized to bilateral parietal regions (left precuneus and right postcentral gyrus). Food-related salience interacted with task relevance, the old/new effect in MFG being significant only for food-neutral words highlighting central the role of MFG as the converging site of endogenous and exogenous salience inputs., Conclusion: Our results indicate ICA to be a valid technique to decompose complex neurophysiological signals involving multiple cognitive processes and implicate the fronto-parietal network as an important attentional network for processing salience and task demands.

Individuals prenatally exposed to alcohol often have impaired spatial working memory (SWM). This study examines functional connections of frontal and parietal regions that support SWM in children with and without prenatal alcohol exposure. Children ages 10 to 16 with histories of heavy prenatal alcohol exposure (AE group; n = 18) and controls (CON group; n = 19) underwent functional magnetic resonance imaging (fMRI) while performing a SWM task. Whole brain task-related functional connectivity of bilateral dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) seed regions were estimated for each participant using a psychophysiological interaction approach. Children in the AE group were less accurate than children in the CON group when performing the SWM task (p = 0.008). Positive coupling between bilateral DLPFC seeds and regions within the fronto-parietal network was observed in the CON group, whereas the AE group showed negative connectivity. In contrast to the CON group, the AE group showed positive connectivity between PPC seeds and frontal lobe regions. Across seeds, decreased negative coupling with regions outside the fronto-parietal network (e.g., left middle occipital gyrus) were observed in the AE group relative to the CON group. Functional data clusters were considered significant at p < 0.05. Overall findings suggest that localized alterations in neural activity, aberrant fronto-parietal network synchrony, and poor coordination of neural responses with regions outside of this network may help explain SWM deficits in individuals with a history of heavy prenatal alcohol exposure., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: The aim of this paper is to investigate cortical electric neuronal activity as an indicator of brain function, in a mental arithmetic task that requires sustained attention, as compared to the resting state condition. The two questions of interest are the cortical localization of different oscillatory activities, and the directional effective flow of oscillatory activity between regions of interest, in the task condition compared to resting state. In particular, theta and alpha activity are of interest here, due to their important role in attention processing., Methods: We adapted mental arithmetic as an attention ask in this study. Eyes closed 61-channel EEG was recorded in 14 participants during resting and in a mental arithmetic task ("serial sevens subtraction"). Functional localization and connectivity analyses were based on cortical signals of electric neuronal activity estimated with sLORETA (standardized low resolution electromagnetic tomography). Functional localization was based on the comparison of the cortical distributions of the generators of oscillatory activity between task and resting conditions. Assessment of effective connectivity was based on the iCoh (isolated effective coherence) method, which provides an appropriate frequency decomposition of the directional flow of oscillatory activity between brain regions. Nine regions of interest comprising nodes from the dorsal and ventral attention networks were selected for the connectivity analysis., Results: Cortical spectral density distribution comparing task minus rest showed significant activity increase in medial prefrontal areas and decreased activity in left parietal lobe for the theta band, and decreased activity in parietal-occipital regions for the alpha1 band. At a global level, connections among right hemispheric nodes were predominantly decreased during the task condition, while connections among left hemispheric nodes were predominantly increased. At more detailed level, decreased flow from right inferior frontal gyrus to anterior cingulate cortex for theta, and low and high alpha oscillations, and increased feedback (bidirectional flow) between left superior temporal gyrus and left inferior frontal gyrus, were observed during the arithmetic task., Conclusions: Task related medial prefrontal increase in theta oscillations possibly corresponds to frontal midline theta, while parietal decreased alpha1 activity indicates the active role of this region in the numerical task. Task related decrease of intracortical right hemispheric connectivity support the notion that these nodes need to disengage from one another in order to not interfere with the ongoing numerical processing. The bidirectional feedback between left frontal-temporal-parietal regions in the arithmetic task is very likely to be related to attention network working memory function., Significance: The methods of analysis and the results presented here will hopefully contribute to clarify the roles of the different EEG oscillations during sustained attention, both in terms of their functional localization and in terms of how they integrate brain function by supporting information flow between different cortical regions. The methodology presented here might be clinically relevant in evaluating abnormal attention function.

Emotion regulation by means of cognitive reappraisal has been widely studied with functional magnetic resonance imaging (fMRI). To date, several meta-analyses of studies using cognitive reappraisal tasks in healthy volunteers have been carried out, but no meta-analyses have yet been performed on the fMRI data of clinical populations with identified alterations in emotion regulation capacity. We provide a comprehensive meta-analysis of cognitive reappraisal fMRI studies in populations of patients with mood or anxiety disorders, yielding a pooled sample of 247 patients and 262 controls from thirteen independent studies. As a distinguishing feature of this meta-analysis, original statistical brain maps were obtained from six of these studies. Our primary results demonstrated that patients with mood and anxiety disorders recruited the regulatory fronto-parietal network involved in cognitive reappraisal to a lesser extent in comparison to healthy controls. Conversely, they presented increased activation in regions that may be associated with the emotional experience (i.e., insula, cerebellum, precentral and inferior occipital gyri) and in regions whose activation may be the consequence of compensatory mechanisms (i.e., supramarginal gyri and superior parietal lobule). Moreover, activations in the left ventrolateral prefrontal cortex and the left superior temporal gyrus were associated with reinterpretation emotion regulation strategies, whereas medial frontal and parietal activations were associated with the deployment of distancing strategies. The regions revealed by this meta-analysis conform to a pattern of dysfunctional brain activation during cognitive reappraisal common to mood and anxiety disorders. As such, this neural pattern may reflect a transdiagnostic feature of these disorders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The locus coeruleus-norepinephrine (LC-NE) system is thought to act as a reset signal allowing brain network reorganization in response to salient information in the environment. However, no direct evidence of NE-dependent whole-brain reorganization has ever been described. We used resting-state functional magnetic resonance imaging in monkeys to investigate the impact of NE-reuptake inhibition on whole-brain connectivity patterns. We found that boosting NE transmission changes functional connectivity between and within resting-state networks. It modulated the functional connectivity pattern of a brainstem network including the LC region and interactions between associative and sensory-motor networks as well as within sensory-motor networks. Among the observed changes, those involving the fronto-parietal attention network exhibited a unique pattern of uncoupling with other sensory-motor networks and correlation switching from negative to positive with the brainstem network that included the LC nucleus. These findings provide the first empirical evidence of NE-dependent large-scale brain network reorganization and further demonstrate that the fronto-parietal attention network represents a central feature within this reorganization., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Consciousness loss in patients with severe brain injuries is associated with reduced functional connectivity of the default mode network (DMN), fronto-parietal network, and thalamo-cortical network. However, it is still unclear if the brain white matter connectivity between the above mentioned networks is changed in patients with disorders of consciousness (DOC). In this study, we collected diffusion tensor imaging (DTI) data from 13 patients and 17 healthy controls, constructed whole-brain white matter (WM) structural networks with probabilistic tractography. Afterward, we estimated and compared topological properties, and revealed an altered structural organization in the patients. We found a disturbance in the normal balance between segregation and integration in brain structural networks and detected significantly decreased nodal centralities primarily in the basal ganglia and thalamus in the patients. A network-based statistical analysis detected a subnetwork with uniformly significantly decreased structural connections between the basal ganglia, thalamus, and frontal cortex in the patients. Further analysis indicated that along the WM fiber tracts linking the basal ganglia, thalamus, and frontal cortex, the fractional anisotropy was decreased and the radial diffusivity was increased in the patients compared to the controls. Finally, using the receiver operating characteristic method, we found that the structural connections within the NBS-derived component that showed differences between the groups demonstrated high sensitivity and specificity (>90%). Our results suggested that major consciousness deficits in DOC patients may be related to the altered WM connections between the basal ganglia, thalamus, and frontal cortex., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: Both major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) are characterized by alterations in intrinsic functional connectivity. Here we investigated changes in intrinsic functional connectivity across these disorders as a function of cognitive behavioral therapy (CBT), an effective treatment in both disorders., Methods: 53 unmedicated right-handed participants were included in a longitudinal study. Patients were diagnosed with PTSD ( n  = 18) and MDD ( n  = 17) with a structured diagnostic interview and treated with 12 sessions of manualized CBT over a 12-week period. Patients received an MRI scan (Siemens 3 T Trio) before and after treatment. Longitudinal functional principal components analysis (LFPCA) was performed on functional connectivity of the bilateral amygdala with the fronto-parietal network. A matched healthy control group ( n  = 18) was also scanned twice for comparison., Results: LFPCA identified four eigenimages or principal components (PCs) that contributed significantly to the longitudinal change in connectivity. The second PC differentiated CBT-treated patients from controls in having significantly increased connectivity of the amygdala with the fronto-parietal network following CBT., Limitations: Analysis of CBT-induced amygdala connectivity changes was restricted to the a priori determined fronto-parietal network. Future studies are needed to determine the generalizability of these findings, given the small and predominantly female sample., Conclusion: We found evidence for the hypothesis that CBT treatment is associated with changes in connectivity between the amygdala and the fronto-parietal network. CBT may work by strengthening connections between the amygdala and brain regions that are involved in cognitive control, potentially providing enhanced top-down control of affective processes that are dysregulated in both MDD and PTSD.

Previous investigations showed that the impact of negative distraction on cognitive processing is linked to increased activation in a ventral affective system (VAS) and simultaneous deactivation in a dorsal executive system (DES). However, less is known about the influences of positive valence and different arousal levels on these effects. FMRI data were recorded while participants performed a working memory (WM) task, with positive and negative pictures presented as distracters during the delay between the memoranda and probes. First, positive distraction had reduced impact on WM performance, compared with negative distraction. Second, fMRI results identified valence-specific effects in DES regions and overlapping arousal and valence effects in VAS regions, suggesting increased impact of negative distraction and enhanced engagement of coping mechanisms for positive distraction. Third, a valence-related rostro-caudal dissociation was identified in medial frontal regions associated with the default-mode network (DMN). Finally, these DMN regions showed increased functional connectivity with DES regions for negative compared with positive distraction. Overall, these findings suggest that, while both positive and negative distraction engage partly similar arousal-dependent mechanisms, their differential impact on WM performance is linked to dissociations in the engagement of, and coupling between, regions associated with emotion processing and higher lever cognitive control., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Many patients with attention-deficit/hyperactivity disorder (ADHD) display aberrant reward-related behavior. Task-based fMRI studies have related atypical reward processing in ADHD to altered BOLD activity in regions underlying reward processing such as ventral striatum and orbitofrontal cortex. However, it remains unclear whether the observed effects are region-specific or related to changes in functional connectivity of networks supporting reward processing. Here we use resting-state fMRI to comprehensively delineate the functional connectivity architecture underlying aberrant reward processing in ADHD., Methods: We assessed resting-state functional connectivity of four networks that support reward processing. These networks showed high spatial overlap with the default mode, fronto-parietal, lateral visual, and salience networks, yet only activity within the salience network was effectively sensitive to reward value. We parcelled these networks into their functional cortical and subcortical subregions and obtained functional connectivity matrices by computing Pearson correlations between the regional time series. We compared functional connectivity within each of the four networks between participants with ADHD and controls, and related functional connectivity to dimensional ADHD symptom scores across all participants ( N  = 444; age range: 8.5-30.5; mean age: 17.7)., Results: We did not observe significant ADHD-related alterations in functional connectivity of the salience network, which included key reward regions. Instead, levels of inattention symptoms modulated functional connectivity of the default-mode and fronto-parietal networks, which supported general task processing., Conclusions: The present study does not corroborate previous childhood evidence for functional connectivity alterations between key reward processing regions in adolescents and young adults with ADHD. Our findings could point to developmental normalization or indicate that reward-processing deficits result from functional connectivity alterations in general task-related networks.

Spatial working memory is a central cognitive process that matures through adolescence in conjunction with major changes in brain function and anatomy. Here we focused on late childhood and early adolescence to more closely examine the neural correlates of performance variability during this important transition period. Using a modified spatial 1-back task with two memory load conditions in an fMRI study, we examined the relationship between load-dependent neural responses and task performance in a sample of 39 youth aged 9-12 years. Our data revealed that between-subject differences in task performance was predicted by load-dependent deactivation in default network regions, including the ventral anterior cingulate cortex (vACC) and posterior cingulate cortex (PCC). Although load-dependent increases in activation in prefrontal and posterior parietal regions were only weakly correlated with performance, increased prefrontal-parietal coupling was associated with better performance. Furthermore, behavioral measures of executive function from as early as age 3 predicted current load-dependent deactivation in vACC and PCC. These findings suggest that both task positive and task negative brain activation during spatial working memory contributed to successful task performance in late childhood/early adolescence. This may serve as a good model for studying executive control deficits in developmental disorders., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Working memory (WM) is often compromised after traumatic brain injury (TBI). A number of functional and effective connectivity studies investigated the interaction between brain regions during WM task performance. However, previously used WM tasks did not allow differentiation of WM subprocesses such as capacity and manipulation. We used a novel WM paradigm, CapMan, to investigate effective connectivity associated with the capacity and manipulation subprocesses of WM in individuals with TBI relative to healthy controls (HCs). CapMan allows independent investigation of brain regions associated with capacity and manipulation, while minimizing the influence of other WM-related subprocesses. Areas of the fronto-parietal WM network, previously identified in healthy individuals as engaged in capacity and manipulation during CapMan, were analyzed with the Independent Multiple-sample Greedy Equivalence Search (IMaGES) method to investigate the differences in information flow between healthy individuals and individuals with TBI. We predicted that diffuse axonal injury that often occurs after TBI might lead to changes in task-based effective connectivity and result in hyperconnectivity between the regions engaged in task performance. In accordance with this hypothesis, TBI participants showed greater inter-hemispheric connectivity and less coherent information flow from posterior to anterior brain regions compared with HC participants. Thus, this study provides much needed evidence about the potential mechanism of neurocognitive impairments in individuals affected by TBI.

Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks., Design: Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation., Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis., Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness., Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity., (© 2015 Associated Professional Sleep Societies, LLC.)

Abstract: In this study we test the hypothesis that the functional connectivity of the frontal and parietal regions that children recruit during a basic numerical task (matching Arabic numerals to arrays of dots) is predictive of their math test scores (TEMA-3; ). Specifically, we tested 4–11-year-old children on a matching task during fMRI to localize a fronto-parietal network that responds more strongly during numerical matching than matching faces, words, or shapes. We then tested the functional connectivity between those regions during an independent task: natural viewing of an educational video that included math topics. Using this novel natural viewing method, we found that the connectivity between frontal and parietal regions during task-independent free-viewing of educational material is correlated with children''s basic number matching ability, as well as their scores on the standardized test of mathematical ability (the TEMA). The correlation between children''s mathematics scores and fronto-parietal connectivity is math-specific in the sense that it is independent of children''s verbal IQ scores. Moreover, a control network, selective for faces, showed no correlation with mathematics performance. Finally, brain regions that correlate with subjects’ overall response times in the matching task do not account for our number- and math-related effects. We suggest that the functional intersection of number-related frontal and parietal regions is math-specific. [Copyright &y& Elsevier]

Cranial electrotherapy stimulation (CES) is a U.S. Food and Drug Administration (FDA)-approved treatment for insomnia, depression, and anxiety consisting of pulsed, low-intensity current applied to the earlobes or scalp. Despite empirical evidence of clinical efficacy, its mechanism of action is largely unknown. The goal was to characterize the acute effects of CES on resting state brain activity. Our primary hypothesis was that CES would result in deactivation in cortical and subcortical regions. Eleven healthy controls were administered CES applied to the earlobes at subsensory thresholds while being scanned with functional magnetic resonance imaging in the resting state. We tested 0.5- and 100-Hz stimulation, using blocks of 22 sec "on" alternating with 22 sec of baseline (device was "off"). The primary outcome measure was differences in blood oxygen level dependent data associated with the device being on versus baseline. The secondary outcome measures were the effects of stimulation on connectivity within the default mode, sensorimotor, and fronto-parietal networks. Both 0.5- and 100-Hz stimulation resulted in significant deactivation in midline frontal and parietal regions. 100-Hz stimulation was associated with both increases and decreases in connectivity within the default mode network (DMN). Results suggest that CES causes cortical brain deactivation, with a similar pattern for high- and low-frequency stimulation, and alters connectivity in the DMN. These effects may result from interference from high- or low-frequency noise. Small perturbations of brain oscillations may therefore have significant effects on normal resting state brain activity. These results provide insight into the mechanism of action of CES, and may assist in the future development of optimal parameters for effective treatment.