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Functional brain networks require dynamic reconfiguration to support flexible cognitive function. However, the developmental principles shaping brain network dynamics remain poorly understood. Here, we report the longitudinal development of large-scale brain network dynamics during childhood and adolescence, and its connection with gene expression profiles. Using a multilayer network model, we show the temporally varying modular architecture of child brain networks, with higher network switching primarily in the association cortex and lower switching in the primary regions. This topographical profile exhibits progressive maturation, which manifests as reduced modular dynamics, particularly in the transmodal (e.g., default-mode and frontoparietal) and sensorimotor regions. These developmental refinements mediate age-related enhancements of global network segregation and are linked with the expression profiles of genes associated with the enrichment of ion transport and nucleobase-containing compound transport. These results highlight a progressive stabilization of brain dynamics, which expand our understanding of the neural mechanisms that underlie cognitive development.

The human dorsolateral prefrontal cortex (DLPFC; approximately corresponding to Brodmann areas 9 and 46) has demonstrable roles in diverse executive functions such as working memory, cognitive flexibility, planning, inhibition, and abstract reasoning. However, it remains unclear whether this is the result of one functionally homogeneous region or whether there are functional subdivisions within the DLPFC. Here, we divided the DLPFC into seven areas along rostral-caudal and dorsal-ventral axes anatomically and explored their respective patterns of structural and functional connectivity. In vivo probabilistic tractography (11 females and 13 males) and resting-state functional magnetic resonance imaging (fMRI; 57 females and 21 males) were employed to map out the patterns of connectivity from each DLPFC subregion. Structural connectivity demonstrated graded intraregional connectivity within the DLPFC. The patterns of structural connectivity between the DLPFC subregions and other cortical areas revealed that the dorsal-rostral subregions connections were restricted to other frontal and limbic areas, whereas the ventral-caudal region was widely connected to frontal, parietal, and limbic cortex. Functional connectivity analyses demonstrated that subregions of DLPFC were strongly interconnected to each other. The dorsal subregions were associated with the default mode network (DMN), while middle dorsal-rostral subregions were linked with the multiple demand network (MDN). The ventral-caudal subregion showed increased functional coupling with both DMN and MDN. Our results suggest that the connectivity of the DLPFC may be subdivided along a dorsorostral-ventrocaudal axis with differing (albeit graded) patterns of connectivity reflecting the integrative executive function of the DLPFC.SIGNIFICANCE STATEMENTResearch has shown that the dorsolateral prefrontal cortex (DLPFC) plays a role in various executive functions. By dividing the DLPFC into seven areas along rostral-caudal and dorsal-ventral axes anatomically, we explored their patterns of structural and functional connectivity. The patterns of connectivity within DLPFC subregions demonstrated graded intraregional connectivity. There were distinctive patterns of connectivity with other cortical areas in dorsal-rostral and ventral-caudal DLPFC subregions. Divisions across DLPFC subregions seem to align with their structural and functional connectivity. Our results suggest that DLPFC may be subdivided by the diagonal axis of the dorsal-ventral axis and rostral-caudal axis, supporting the framework of a functional organization along the anterior-posterior axis in the lateral PFC.

Understanding the brain changes occurring during aging can provide new insights for developing treatments that alleviate or reverse cognitive decline. Neurostimulation techniques have emerged as potential treatments for brain disorders and to improve cognitive functions. Nevertheless, given the ethical restrictions of neurostimulation approaches, in silico perturbation protocols based on causal whole-brain models are fundamental to gaining a mechanistic understanding of brain dynamics. Furthermore, this strategy could serve to identify neurophysiological biomarkers differentiating between age groups through an exhaustive exploration of the global effect of all possible local perturbations. Here, we used a resting-state fMRI dataset divided into middle-aged (N =310

Background: The Cognitive Reserve (CR) theory posits that brains with higher reserve can cope with more cerebral damage to minimize clinical manifestations. The aim of this study was to examine the effect of education (CR proxy) on brain structure and function in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI) patients and in cognitively healthy elderly (HC) individuals.Methods: Fifty-seven AD patients, 57 aMCI patients and 48 HCs were included to investigate the relationships between education years and gray matter volume (GMV), regional homogeneity (ReHo) and functional connectivity (FC) in brain regions to show associations with both structure and function. Taking the severity of the disease into account, we further assessed the relationships in AD stratified analyses. We then compared more highly (higher CR) and less highly educated (lower CR) subjects at the same level of cognitive impairment. Results: In AD group, the GMV of the dorsal anterior cingulate cortex (dACC) and ReHo in the left inferior temporal cortex (ITC) were inversely associated with education years, after adjustment for age, sex, Mini-Mental State Examination (MMSE), and total intracranial volume or head motion parameters. Seed-based FC analyses revealed that education years were negatively correlated with the FC between the left anterior ITC and left mid frontal cortex as well as right superior frontal cortex and right angular gyrus. Stratified analyses results indicated that this negative relation between education and GMV, ReHo, FC was mainly present in mild AD, which was attenuated in moderate AD and aMCI groups. In mild and moderate AD groups, subjects with higher CR had smaller regional GMV of the dACC and lower ReHo in the left ITC than the subjects with lower CR. No significant differences were found in severe AD and aMCI groups.Conclusions: Our results support the CR theory, and suggest that CR may be protective against AD related brain pathology at the early stage of clinical dementia. These findings could provide the locus of CR-related functional brain mechanisms and a specific time-window for therapeutic interventions to help AD patients to cope better with the brain pathological damage by increasing CR.

Frontoparietal networks contribute to complex cognitive functions in humans and macaques such as working memory, attention, task-switching, response suppression, grasping, reaching, and eye movement control. However, little is known about the organization of frontoparietal networks in the New World common marmoset monkey (Callithrix jacchus) which is now widely recognized as a powerful nonhuman primate experimental animal. In this study, we employed hierarchical clustering of interareal BOLD signals to investigate the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. We found that the posterior part of the lateral frontal cortex (premotor regions) was functionally connected to the anterior parietal areas while more anterior frontal regions (frontal eye field (FEF)) were connected to more posterior parietal areas (the area around lateral intraparietal area (LIP)). These overarching patterns of inter-areal organization are consistent with a recent macaque study. These findings demonstrate parallel frontoparietal processing streams in marmosets and support the functional homologies of FEF-LIP and premotor-anterior parietal pathways between marmoset and macaque.Significant StatementFrontoparietal networks contribute to many cognitive functions in humans and macaques, but little is known about the organization of frontoparietal networks in the New World common marmoset monkey. Here, we investigated the hypothesis that the organization of the frontoparietal cortex in the marmoset follows the organizational principles of the macaque frontoparietal system. These frontoparietal connection showed overarching pattern of interareal organization consistent with Old world monkeys. These findings demonstrate parallel frontoparietal processing streams in marmosets.

Aging is closely associated with cognitive decline affecting attention, memory and executive functions. The hippocampus is the core brain area for human memory, learning, and cognition processing. To delineate the individual functional patterns of hippocampus is pivotal to reveal the neural basis of aging. In this study, we developed a group‐guided individual parcellation approach based on semisupervised affinity propagation clustering using the resting‐state functional magnetic resonance imaging to identify individual functional subregions of hippocampus and to identify the functional patterns of each subregion during aging. A three‐way group parcellation was yielded and was taken as prior information to guide individual parcellation of hippocampus into head, body, and tail in each subject. The superiority of individual parcellation of hippocampus is validated by higher intraregional functional similarities by compared to group‐level parcellation results. The individual variations of hippocampus were associated with coactivation patterns of three typical functions of hippocampus. Moreover, the individual functional connectivities of hippocampus subregions with predefined target regions could better predict age than group‐level functional connectivities. Our study provides a novel framework for individual brain functional parcellations, which may facilitate the future individual researches for brain cognitions and brain disorders and directing accurate neuromodulation., A new individual parcellation approach was developed. Individual variations were associated with coactivation patterns of cognitive functions. The individual functional connections can better predict age.

The neural correlates of subjective cognitive decline (SCD; i.e., without objectifiable deficit) remain to be elucidated. Possible causes of SCD include early neurodegeneration related to Alzheimer's disease or functional and structural changes related to sub-clinical depression. We investigated the relationship between episodic memory performance or memory complaints and structural or functional magnetic resonance imaging (MRI) measures in participants with SCD ( n = 18) but without psychiatric disorders and healthy controls ( n = 31). In SCD, memory complaints were not associated with memory performance but with sub-clinical depression and executive functions. SCD-associated memory complaints correlated with higher amygdala and parahippocampal gyrus (specifically subiculum) gray matter density. In controls, but not in SCD, mesiotemporal gray matter density and superior frontal gyrus functional connectivity predicted memory performance. In contrast, in SCD, only a trend toward a correlation between memory performance and gray matter density in the parietooccipital lobes was observed. In our memory-clinic sample of SCD, we did not observe incipient neurodegeneration (limited to structural and functional MRI) but rather sub-clinical depression underlying subjective cognitive complaints. (c) 2021 Elsevier Inc. All rights reserved.

Patients with age-related sensorineural hearing loss (HL) may benefit from auditory input amplification by using hearing aids (HA). However, the impact of both HL and HA-based rehabilitation on central auditory functional connectivity (FC) is not clear.

There is a need to identify brain connectivity alterations predictive of transdiagnostic processes that may confer vulnerability for affective symptomology. Here, we tested whether amygdala resting-state functional connectivity (rsFC) mediated the relationship between catastrophizing (negative threat appraisals and predicting poorer functioning) and altered threat-safety discrimination learning (critical to flexibly adapt to new and changing environments) in adolescents with persistent pain. We examined amygdala rsFC in 46 youth with chronic pain and 29 healthy peers (age M = 15.8, SD = 2.9; 64 females) and its relationship with catastrophizing and threat-safety learning. We used a developmentally appropriate threat-safety learning paradigm and performed amygdala seed-based rsFC and whole-brain mediation analyses. Patients exhibited enhanced connectivity between the left amygdala and right supramarginal gyrus (SMG) (cluster-level P-FDR < 0.05), whereas right amygdala rsFC showed no group differences. Only in patients, elevated catastrophizing was associated with facilitated threat-safety learning (CS+>CS-; rp = 0.49, P = 0.001). Furthermore, in patients, elevated catastrophizing was associated with reduced left amygdala connectivity with SMG / parietal operculum, and increased left amygdala connectivity with hippocampus, dorsal striatum, paracingulate, and motor regions (P < 0.001). In addition, blunted left amygdala rsFC with right SMG/parietal operculum mediated the association between catastrophizing and threat-safety learning (P < 0.001). To conclude, rsFC between the left amygdala (a core emotion hub) and inferior parietal lobe (involved in appraisal and integration of bodily signals and attentional reorienting) explains associations between daily-life relevant catastrophizing and threat-safety learning. Findings provide a putative model for understanding pathophysiology involved in core psychological processes that cut across diagnoses, including disabling pain, and are relevant for their etiology.

Following long‐duration spaceflight, some astronauts exhibit ophthalmic structural changes referred to as Spaceflight Associated Neuro‐ocular Syndrome (SANS). Optic disc edema is a common sign of SANS. The origin and effects of SANS are not understood as signs of SANS have not manifested in previous spaceflight analog studies. In the current spaceflight analog study, 11 subjects underwent 30 days of strict head down‐tilt bed rest in elevated ambient carbon dioxide (HDBR+CO2). Using functional magnetic resonance imaging (fMRI), we acquired resting‐state fMRI data at 6 time points: before (2), during (2), and after (2) the HDBR+CO2 intervention. Five participants developed optic disc edema during the intervention (SANS subgroup) and 6 did not (NoSANS group). This occurrence allowed us to explore whether development of signs of SANS during the spaceflight analog impacted resting‐state functional connectivity during HDBR+CO2. In light of previous work identifying genetic and biochemical predictors of SANS, we further assessed whether the SANS and NoSANS subgroups exhibited differential patterns of resting‐state functional connectivity prior to the HDBR+CO2 intervention. We found that the SANS and NoSANS subgroups exhibited distinct patterns of resting‐state functional connectivity changes during HDBR+CO2 within visual and vestibular‐related brain networks. The SANS and NoSANS subgroups also exhibited different resting‐state functional connectivity prior to HDBR+CO2 within a visual cortical network and within a large‐scale network of brain areas involved in multisensory integration. We further present associations between functional connectivity within the identified networks and previously identified genetic and biochemical predictors of SANS. Subgroup differences in resting‐state functional connectivity changes may reflect differential patterns of visual and vestibular reweighting as optic disc edema develops during the spaceflight analog. This finding suggests that SANS impacts not only neuro‐ocular structures, but also functional brain organization. Future prospective investigations incorporating sensory assessments are required to determine the functional significance of the observed connectivity differences., We investigated resting‐state functional connectivity (FC) during a spaceflight analog with elevated carbon dioxide. A subset of participants developed optic disc edema, a sign of spaceflight‐associated neuro‐ocular syndrome (SANS) during the spaceflight analog. Subjects who developed optic disc edema exhibited a distinct pattern of FC changes within visual and vestibular‐related networks during the intervention.

Prediction of the initial compatibility of heterosexual individuals based on self-reported traits and preferences has not been successful, even with significantly developed information technology. To overcome the limitations of self-reported measures and predict compatibility, we used functional connectivity profiles from resting-state functional magnetic resonance imaging (fMRI) data that carry rich individual-specific information sufficient to predict psychological constructs and activation patterns during social cognitive tasks. Several days after collecting data from resting-state fMRIs, participants undertook a speed-dating experiment in which they had a 3-min speed date with every other opposite-sex participant. Our machine learning algorithm successfully predicted whether pairs in the experiment were compatible or not using (dis)similarity of functional connectivity profiles obtained before the experiment. The similarity and dissimilarity of functional connectivity between individuals and these multivariate relationships contributed to the prediction, hence suggesting the importance of complementarity (observed as dissimilarity) as well as the similarity between an individual and a potential partner during the initial attraction phase. The result indicates that the salience network, limbic areas, and cerebellum are especially important for the feeling of compatibility. This research emphasizes the utility of neural information to predict complex phenomena in a social environment that behavioral measures alone cannot predict.

Bipolar disorder (BD) is a major mental illness characterized by periods of (hypo) mania and depression with inter-episode remission periods. Functional studies in BD have consistently implicated a set of linked cortical and subcortical limbic regions in the pathophysiology of the disorder, also including the cerebellum. However, the cerebellar role in the neurobiology of BD still needs to be clarified. Seventeen euthymic patients with BD type1 (BD1) (mean age/SD, 38.64/13.48; M/F, 9/8) and 13 euthymic patients with BD type 2 (BD2) (mean age/SD, 41.42/14.38; M/F, 6/7) were compared with 37 sex- and age-matched healthy subjects (HS) (mean age/SD, 45.65/14.15; M/F, 15/22). T1 weighted and resting-state functional connectivity (FC) scans were acquired. The left and right dentate nucleus were used as seed regions for the seed based analysis. FC between each seed and the rest of the brain was compared between patients and HS. Correlations between altered cerebello-cerebral connectivity and clinical scores were then investigated. Different patterns of altered dentate-cerebral connectivity were found in BD1 and BD2. Overall, impaired dentate-cerebral connectivity involved regions of the anterior limbic network specifically related to the (hypo)manic states of BD. Cerebello-cerebral connectivity is altered in BD1 and BD2. Interestingly, the fact that these altered FC patterns persist during euthymia, supports the hypothesis that cerebello-cerebral FC changes reflect the neural correlate of subthreshold symptoms, as trait-based pathophysiology and/or compensatory mechanism to maintain a state of euthymia.

Temporal lobe epilepsy (TLE) patients are at risk of memory deficits, which have been linked to functional network disturbances, particularly of integration of the default mode network (DMN). However, the cellular substrates of functional network integration are unknown. We leverage a unique cross-scale dataset of drug-resistant TLE patients (n = 31), who underwent pseudo resting-state functional magnetic resonance imaging (fMRI), resting-state magnetoencephalography (MEG) and/or neuropsychological testing before neurosurgery. fMRI and MEG underwent atlas-based connectivity analyses. Functional network centrality of the lateral middle temporal gyrus, part of the DMN, was used as a measure of local network integration. Subsequently, non-pathological cortical tissue from this region was used for single cell morphological and electrophysiological patch-clamp analysis, assessing integration in terms of total dendritic length and action potential rise speed. As could be hypothesized, greater network centrality related to better memory performance. Moreover, greater network centrality correlated with more integrative properties at the cellular level across patients. We conclude that individual differences in cognitively relevant functional network integration of a DMN region are mirrored by differences in cellular integrative properties of this region in TLE patients. These findings connect previously separate scales of investigation, increasing translational insight into focal pathology and large-scale network disturbances in TLE.

Purpose Parkinson’s disease (PD) is primarily defined by motor symptoms and is associated with alterations of sensorimotor areas. Evidence for network changes of the sensorimotor network (SMN) in PD is inconsistent and a systematic evaluation of SMN in PD yet missing. We investigate functional connectivity changes of the SMN in PD, both, within the network, and to other large-scale connectivity networks. Methods Resting-state fMRI was assessed in 38 PD patients under long-term dopaminergic treatment and 43 matched healthy controls (HC). Independent component analysis (ICA) into 20 components was conducted and the SMN was identified within the resulting networks. Functional connectivity within the SMN was analyzed using a dual regression approach. Connectivity between the SMN and the other networks from group ICA was investigated with FSLNets. We investigated for functional connectivity changes between patients and controls as well as between medication states (OFF vs. ON) in PD and for correlations with clinical parameters. Results There was decreased functional connectivity within the SMN in left inferior parietal and primary somatosensory cortex in PD OFF. Across networks, connectivity between SMN and two motor networks as well as two visual networks was diminished in PD OFF. All connectivity decreases partially normalized in PD ON. Conclusion PD is accompanied by functional connectivity losses of the SMN, both, within the network and in interaction to other networks. The connectivity changes in short- and long-range connections are probably related to impaired sensory integration for motor function in PD. SMN decoupling can be partially compensated by dopaminergic therapy.

Functional brain networks have been shown to undergo fundamental changes associated with aging or schizophrenia. However, the mechanism of how these factors exert influences jointly or interactively on brain networks remains elusive. A unified recognition of connectomic alteration patterns was also hampered by heterogeneities in network construction and thresholding methods. Recently, an unbiased network representation method regardless of network thresholding, so called minimal spanning tree algorithm, has been applied to study the critical skeleton of the brain network. In this study, we aimed to use minimum spanning tree (MST) as an unbiased network reconstruction and employed structural equation modeling (SEM) to unravel intertwined relationships among multiple phenotypic and connectomic variables in schizophrenia. First, we examined global and local brain network properties in 40 healthy subjects and 40 schizophrenic patients aged 21–55 using resting‐state functional magnetic resonance imaging (rs‐fMRI). Global network alterations are measured by graph theoretical metrics of MSTs and a connectivity‐transitivity two‐dimensional approach was proposed to characterize nodal roles. We found that networks of schizophrenic patients exhibited a more star‐like global structure compared to controls, indicating excessive integration, and a loss of regional transitivity in the dorsal frontal cortex (corrected p, Different minimum spanning tree global organizations. On the top is the hypothesized normal structure, which should be expected to be seen in healthy adults. The state is an intermediate configuration between two extremes. When nodes become increasingly segregated, the tree would transform into the line‐like structure in the lower‐left corner; on the other hand, the star‐like structure represent highly centralized network arrangement.

Funder: GE Healthcare; doi: http://dx.doi.org/10.13039/100006775, Previous resting-state fMRI studies in dementia with Lewy bodies have described changes in functional connectivity in networks related to cognition, motor function, and attention as well as alterations in connectivity dynamics. However, whether these changes occur early in the course of the disease and are already evident at the stage of mild cognitive impairment is not clear. We studied resting-state fMRI data from 31 patients with mild cognitive impairment with Lewy bodies compared to 28 patients with mild cognitive impairment due to Alzheimer's disease and 24 age-matched controls. We compared the groups with respect to within- and between-network functional connectivity. Additionally, we applied two different approaches to study dynamic functional connectivity (sliding-window analysis and leading eigenvector dynamic analysis). We did not find any significant changes in the mild cognitive impairment groups compared to controls and no differences between the two mild cognitive impairment groups, using static as well as dynamic connectivity measures. While patients with mild cognitive impairment with Lewy bodies already show clear functional abnormalities on EEG measures, the fMRI analyses presented here do not appear to be sensitive enough to detect such early and subtle changes in brain function in these patients.

OBJECTIVEEpilepsy affects neural processing and often causes intra- or interhemispheric language reorganization, rendering localization solely based on anatomical landmarks (e.g., Broca’s area) unreliable. Preoperative brain mapping is necessary to weigh the risk of resection with the risk of postoperative deficit. However, the use of conventional mapping methods (e.g., somatosensory stimulation, task-based functional MRI [fMRI]) in pediatric patients is technically difficult due to low compliance and their unique neurophysiology. Resting-state fMRI (rs-fMRI), a “task-free” technique based on the neural activity of the brain at rest, has the potential to overcome these limitations. The authors hypothesized that language networks can be identified from rs-fMRI by applying functional connectivity analyses.METHODSCases in which both task-based fMRI and rs-fMRI were acquired as part of the preoperative clinical protocol for epilepsy surgery were reviewed. Task-based fMRI consisted of 2 language tasks and 1 motor task. Resting-state fMRI data were acquired while the patients watched an animated movie and were analyzed using independent component analysis (i.e., data-driven method). The authors extracted language networks from rs-fMRI data by performing a similarity analysis with functionally defined language network templates via a template-matching procedure. The Dice coefficient was used to quantify the overlap.RESULTSThirteen children underwent conventional task-based fMRI (e.g., verb generation, object naming), rs-fMRI, and structural imaging at 1.5T. The language components with the highest overlap with the language templates were identified for each patient. Language lateralization results from task-based fMRI and rs-fMRI mapping were comparable, with good concordance in most cases. Resting-state fMRI–derived language maps indicated that language was on the left in 4 patients (31%), on the right in 5 patients (38%), and bilateral in 4 patients (31%). In some cases, rs-fMRI indicated a more extensive language representation.CONCLUSIONSResting-state fMRI–derived language network data were identified at the patient level using a template-matching method. More than half of the patients in this study presented with atypical language lateralization, emphasizing the need for mapping. Overall, these data suggest that this technique may be used to preoperatively identify language networks in pediatric patients. It may also optimize presurgical planning of electrode placement and thereby guide the surgeon’s approach to the epileptogenic zone.

Resting‐state functional connectivity in the human brain is heritable, and previous studies have investigated the genetic basis underlying functional connectivity. However, at present, the molecular mechanisms associated with functional network centrality are still largely unknown. In this study, functional networks were constructed, and the graph‐theory method was employed to calculate network centrality in 100 healthy young adults from the Human Connectome Project. Specifically, functional connectivity strength (FCS), also known as the “degree centrality” of weighted networks, is calculated to measure functional network centrality. A multivariate technique of partial least squares regression (PLSR) was then conducted to identify genes whose spatial expression profiles best predicted the FCS distribution. We found that FCS spatial distribution was significantly positively correlated with the expression of genes defined by the first PLSR component. The FCS‐related genes we identified were significantly enriched for ion channels, axon guidance, and synaptic transmission. Moreover, FCS‐related genes were preferentially expressed in cortical neurons and young adulthood and were enriched in numerous neurodegenerative and neuropsychiatric disorders. Furthermore, a series of validation and robustness analyses demonstrated the reliability of the results. Overall, our results suggest that the spatial distribution of FCS is modulated by the expression of a set of genes associated with ion channels, axon guidance, and synaptic transmission., This transcription‐neuroimaging association study identified that the expression profiles of a set of genes, especially those involved in processes related to ion channels, the axon guidance pathway and synaptic transmission, are related to FCS. These findings provide new insight into the biological substrates underlying intrinsic functional network centrality.

BackgroundA subset of patients with chronic pain who receive exposure in vivo (EXP) treatment experience clinically relevant relief of pain intensity. Although pain relief is not an explicit therapeutic target, it is important to understand how and why this concomitant effect occurs in some patients but not others. This longitudinal study therefore aimed to characterize brain plasticity as well as to explore pretreatment factors related to pain relief.MethodsResting-state functional magnetic resonance imaging data were acquired in 30 patients with chronic pain. Twenty-three patients completed EXP, and 6-month follow-up data were available in 20 patients (magnetic resonance imaging data in 17 patients). Pain-free control data were acquired at two time points (n = 29, n = 21). Seed-based resting-state functional connectivity (rsFC) analyses were performed, with seeds in the amygdala, hippocampus, and nucleus accumbens.ResultsPain relief after EXP was highly variable, with 60% of patients reporting a clinically relevant improvement. Amygdala rsFC with the middle frontal gyrus decreased significantly over time in patients but was not associated with pain relief. In contrast, greater pain relief was associated with greater decreases over time in hippocampus rsFC with the precuneus, which was related to reductions in catastrophizing (EXP therapeutic target) as well. Greater pain relief was also associated with lower pretreatment rsFC between nucleus accumbens and postcentral gyrus.ConclusionsWhile changes in hippocampus rsFC were associated with pain relief after EXP, pretreatment nucleus accumbens rsFC showed potential prognostic value. Our findings further support the importance of corticolimbic circuitry in chronic pain, emphasizing its relation to pain relief and identifying potential underlying mechanisms and prognostic factors, warranting further testing in independent samples.

Until now, dynamic functional connectivity (dFC) based on functional magnetic resonance imaging is typically estimated on a set of predefined regions of interest (ROIs) derived from an anatomical or static functional atlas which follows an implicit assumption of functional homogeneity within ROIs underlying temporal fluctuation of functional coupling, potentially leading to biases or underestimation of brain network dynamics. Here, we presented a novel computational method based on dynamic functional connectivity degree (dFCD) to derive meaningful brain parcellations that can capture functional homogeneous regions in temporal variance of functional connectivity. Several spatially distributed but functionally meaningful areas that are well consistent with known intrinsic connectivity networks were identified through independent component analysis (ICA) of time‐varying dFCD maps. Furthermore, a systematical comparison with commonly used brain atlases, including the Anatomical Automatic Labeling template, static ICA‐driven parcellation and random parcellation, demonstrated that the ROI‐definition strategy based on the proposed dFC‐driven parcellation could better capture the interindividual variability in dFC and predict observed individual cognitive performance (e.g., fluid intelligence, cognitive flexibility, and sustained attention) based on chronnectome. Together, our findings shed new light on the functional organization of resting brains at the timescale of seconds and emphasized the significance of a dFC‐driven and voxel‐wise functional homogeneous parcellation for network dynamics analyses in neuroscience., We presented a novel computational method based on dynamic functional connectivity degree (dFCD) to derive meaningful brain parcellations for capturing functional homogeneous regions in temporal variance of functional connectivity.

In a previous study, we investigated the resting‐state fMRI effective connectivity (EC) between the bed nucleus of the stria terminalis (BNST) and the laterobasal (LB), centromedial (CM), and superficial (SF) amygdala. We found strong negative EC from all amygdala nuclei to the BNST, while the BNST showed positive EC to the amygdala. However, the validity of these findings remains unclear, since a reproduction in different samples has not been done. Moreover, the association of EC with measures of anxiety offers deeper insight, due to the known role of the BNST and amygdala in fear and anxiety. Here, we aimed to reproduce our previous results in three additional samples. We used spectral Dynamic Causal Modeling to estimate the EC between the BNST, the LB, CM, and SF, and its association with two measures of self‐reported anxiety. Our results revealed consistency over samples with regard to the negative EC from the amygdala nuclei to the BNST, while the positive EC from BNST to the amygdala was also found, but weaker and more heterogenic. Moreover, we found the BNST‐BNST EC showing a positive and the CM‐BNST EC, showing a negative association with anxiety. Our study suggests a reproducible pattern of negative EC from the amygdala to the BNST along with weaker positive EC from the BNST to the amygdala. Moreover, less BNST self‐inhibition and more inhibitory influence from the CM to the BNST seems to be a pattern of EC that is related to higher anxiety., We investigated the reproducibility of resting‐state fMRI effective connectivity (EC) between the bed nucleus of the stria terminalis (BNST) and amygdala nuclei and its relation to anxiety. We found a reproducible pattern of negative EC from the amygdala to the BNST and a positive EC from the BNST to the amygdala. Less BNST self‐inhibition and higher inhibitory influence from the CM to the BNST was associated with higher anxiety.

Epilepsy is a common brain network disorder associated with disrupted large‐scale excitatory and inhibitory neural interactions. Recent resting‐state fMRI evidence indicates that global signal (GS) fluctuations that have commonly been ignored are linked to neural activity. However, the mechanisms underlying the altered global pattern of fMRI spontaneous fluctuations in epilepsy remain unclear. Here, we quantified GS topography using beta weights obtained from a multiple regression model in a large group of epilepsy with different subtypes (98 focal temporal epilepsy; 116 generalized epilepsy) and healthy population (n = 151). We revealed that the nonuniformly distributed GS topography across association and sensory areas in healthy controls was significantly shifted in patients. Particularly, such shifts of GS topography disturbances were more widespread and bilaterally distributed in the midbrain, cerebellum, visual cortex, and medial and orbital cortex in generalized epilepsy, whereas in focal temporal epilepsy, these networks spread beyond the temporal areas but mainly remain lateralized. Moreover, we found that these abnormal GS topography patterns were likely to evolve over the course of a longer epilepsy disease. Our study demonstrates that epileptic processes can potentially affect global excitation/inhibition balance and shift the normal GS topological distribution. These progressive topographical GS disturbances in subcortical–cortical networks may underlie pathophysiological mechanisms of global fluctuations in human epilepsy., This study demonstrated spatial shifts of non‐uniform GS topography across higher‐order prefrontal cortex and sensory areas in generalized and focal epilepsy. We found that these abnormal GS topography patterns were likely to evolve over the course of a longer disease. Our findings have potential implications for understanding the neuronal mechanisms of disrupted global excitation/inhibition balance in epilepsy.

Background/Objective: This study aims to characterize the differences on the short-term temporal network dynamics of the undirected and weighted whole-brain functional connectivity between healthy aging individuals and people with mild cognitive impairment (MCI). The Network Change Point Detection algorithm was applied to identify the significant change points in the resting-state fMRI register, and we analyzed the fluctuations in the topological properties of the sub-networks between significant change points. Method: Ten MCI patients matched by gender and age in 1:1 ratio to healthy controls screened during patient recruitment. A neuropsychological evaluation was done to both groups as well as functional magnetic images were obtained with a Philips 3.0T. All the images were preprocessed and statistically analyzed through dynamic point estimation tools. Results: No statistically significant differences were found between groups in the number of significant change points in the functional connectivity networks. However, an interaction effect of age and state was detected on the intra-participant variability of the network strength. Conclusions: The progression of states was associated to higher variability in the patient's group. Additionally, higher performance in the prospective and retrospective memory scale was associated with higher median network strength.

Purpose: High-grade glioma surgery has evolved around the principal belief that a safe maximal tumor resection improves symptoms, quality of life, and survival. Mapping brain function has been recently improved by resting-state functional magnetic resonance imaging (rest-fMRI), a novel imaging technique that explores networks connectivity at “rest.” Methods: This prospective study analyzed 10 patients with high-grade glioma in whom rest-fMRI connectivity was assessed both in single-subject and in group analysis before and after surgery. Seed-based functional connectivity analysis was performed with CONN toolbox. Network identification focused on 8 major functional connectivity networks. A voxel-wise region of interest (ROI) to ROI correlation map to assess functional connectivity throughout the whole brain was computed from a priori seeds ROI in specific resting-state networks before and after surgical resection in each patient. Results: Reliable topography of all 8 resting-state networks was successfully identified in each participant before surgical resection. Single-subject functional connectivity analysis showed functional disconnection for dorsal attention and salience networks, whereas the language network demonstrated functional connection either in the case of left temporal glioblastoma. Functional connectivity in group analysis showed wide variations of functional connectivity in the default mode, salience, and sensorimotor networks. However, salience and language networks, salience and default mode networks, and salience and sensorimotor networks showed a significant correlation (P uncorrected

Prenatal drug exposure (PDE) is known to affect fetal brain development with documented long‐term consequences. Most studies of PDE effects on the brain are based on animal models. In this study, based on a large sample of 133 human neonates and leveraging a novel linear mixed‐effect model designed for intersubject variability analyses, we studied the effects of six prenatally exposed drugs (i.e., nicotine, alcohol, selective serotonin reuptake inhibitor, marijuana, cocaine, and opioids) on neonatal whole‐brain functional organization and compared them with five other critical nondrug variables (i.e., gestational age at birth/scan, sex, birth weight, and maternal depression). The behavioral implications were also examined. Magnitude‐wise, through summing across individual drug effects, our results highlighted ~5% of whole‐brain functional connections (FCs) affected by PDE, which was highly comparable with the combined effects of the five nond rug variables. Spatially, the detected PDE effects featured drug‐specific patterns with a common bias in higher‐order brain regions/networks. Regarding brain–behavioral relationships, the detected connections showing significant drug effects also demonstrated significant correlations with 3‐month behavioral outcomes. Further mediation analyses supported a mediation role of the detected brain FCs between PDE status and cognitive/language outcomes. Our findings of widespread, and spatially biased PDE effect patterns coupled with significant behavioral implications may hopefully stimulate more human‐based studies into effects of PDE on long‐term developmental outcomes., In this study, based on a large sample of 133 human neonates and leveraging a novel linear mixed‐effect model designed for intersubject variability analyses, we studied the effects of six prenatally exposed drugs (i.e., nicotine, alcohol, selective serotonin reuptake inhibitor, marijuana, cocaine, and opioids) on neonatal whole‐brain functional organization and compared them with five other critical nondrug variables (i.e., gestational age at birth/scan, sex, birth weight, and maternal depression).Our findings of widespread, and spatially biased drug effects coupled with significant behavioral implications may hopefully stimulate more human‐based studies into effects of Prenatal drug exposure on long‐term developmental outcomes.

Preferences can change as a consequence of making hard decisions whereby the value of chosen options increases and the value of rejected options decreases. Such choice‐induced preference changes have been associated with brain areas detecting choice conflict (anterior cingulate cortex, ACC), updating stimulus value (dorsolateral prefrontal cortex, dlPFC) and supporting memory of stimulus value (hippocampus and ventromedial prefrontal cortex, vmPFC). Here we investigated whether resting‐state neuronal activity within these regions is associated with the magnitude of individuals' preference updates. We fitted a dynamic causal model (DCM) to resting‐state neuronal activity in the spectral domain (spDCM) and estimated the causal connectivity among core regions involved in preference formation following hard choices. The extent of individuals' choice‐induced preference changes were found to be associated with a diminished resting‐state excitation between the left dlPFC and the vmPFC, whereas preference consistency was related to a higher resting‐state excitation from the ACC to the left hippocampus and vmPFC. Our results point to a model of preference formation during which the dynamic network configurations between left dlPFC, ACC, vmPFC and left hippocampus at rest are linked to preference change or stability.

Previous studies have suggested that resting-state functional connectivity plays a central role in the physiopathology of major depressive disorder (MDD). However, the individualized diagnosis of MDD based on resting-state functional connectivity is still unclear, especially in first episode drug-naive patients with MDD. Resting state functional magnetic resonance imaging was enrolled from 30 first episode drug-naive patients with MDD and age- and gender-matched 31 healthy controls. Whole brain functional connectivity was computed and viewed as classification features. Multivariate pattern analysis (MVPA) was performed to discriminate patients with MDD from controls. The experimental results exhibited a correct classification rate of 82.25% (p

In vivo functional and structural brain imaging of synucleinopathies in humans have provided a rich new understanding of the affected networks across the cortex and subcortex. Despite this progress, the temporal relationship between α-synuclein (α-syn) pathology and the functional and structural changes occurring in the brain is not well understood., In vivo functional and structural brain imaging of synucleinopathies in humans have provided a rich new understanding of the affected networks across the cortex and subcortex. Despite this progress, the temporal relationship between α-synuclein (α-syn) pathology and the functional and structural changes occurring in the brain is not well understood. Here, we examine the temporal relationship between locomotor ability, brain microstructure, functional brain activity, and α-syn pathology by longitudinally conducting rotarod, diffusion magnetic resonance imaging (MRI), resting-state functional MRI (fMRI), and sensory-evoked fMRI on 20 mice injected with α-syn fibrils and 20 PBS-injected mice at three timepoints (10 males and 10 females per group). Intramuscular injection of α-syn fibrils in the hindlimb of M83+/− mice leads to progressive α-syn pathology along the spinal cord, brainstem, and midbrain by 16 weeks post-injection. Our results suggest that peripheral injection of α-syn has acute systemic effects on the central nervous system such that structural and resting-state functional activity changes occur in the brain by four weeks post-injection, well before α-syn pathology reaches the brain. At 12 weeks post-injection, a separate and distinct pattern of structural and sensory-evoked functional brain activity changes was observed that are co-localized with previously reported regions of α-syn pathology and immune activation. Microstructural changes in the pons at 12 weeks post-injection were found to predict survival time and preceded measurable locomotor deficits. This study provides preliminary evidence for diffusion and fMRI markers linked to the progression of synuclein pathology and has translational importance for understanding synucleinopathies in humans. SIGNIFICANCE STATEMENT α-Synuclein (α-syn) pathology plays a critical role in neurodegenerative diseases such as Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. The longitudinal effects of α-syn pathology on locomotion, brain microstructure, and functional brain activity are not well understood. Using high field imaging, we show preliminary evidence that peripheral injection of α-syn fibrils induces unique patterns of functional and structural changes that occur at different temporal stages of α-syn pathology progression. Our results challenge existing assumptions that α-syn pathology must precede changes in brain structure and function. Additionally, we show preliminary evidence that diffusion and functional magnetic resonance imaging (fMRI) are capable of resolving such changes and thus should be explored further as markers of disease progression.

Background Task-based functional MRI (tb-fMRI) is a well-established technique used to identify eloquent cortex, but has limitations, particularly in cognitively impaired patients who cannot perform language paradigms. Resting-state functional MRI (rs-fMRI) is a potential alternative modality for presurgical mapping of language networks that does not require task performance. The purpose of our study is to determine the utility of rs-fMRI for clinical preoperative language mapping when tb-fMRI is limited. Methods We retrospectively reviewed 134 brain tumor patients who underwent preoperative fMRI language mapping. rs-fMRI was post-processed with seed-based correlation (SBC) analysis, when language tb-fMRI was limited. Two neuroradiologists reviewed both the tb-fMRI and rs-fMRI results. Six neurosurgeons retrospectively rated the usefulness of rs-fMRI for language mapping in their patients. Results Of the 134 patients, 49 cases had limited tb-fMRI and rs-fMRI was post-processed. Two neuroradiologists found rs-fMRI beneficial for functional language mapping in 41(84%) and 43 (88%) cases respectively; Cohen’s kappa is 0.83, with a 95% confidence interval (0.61, 1.00). The neurosurgeons found rs-fMRI “definitely” useful in 26 cases (60%) and “somewhat” useful in 13 cases (30%) in locating potential eloquent language centers of clinical interest. Six unsuccessful rs-fMRI cases were due to: head motion (2 cases), nonspecific functionality connectivity outside the posterior language network (1 case), and an unknown system instability (3 cases). Conclusions This study is a proof of concept that shows SBC rs-fMRI may be a viable alternative for clinical language mapping when tb-fMRI is limited.

Calibrated functional magnetic resonance imaging can remove unwanted sources of signal variability in the blood oxygenation level‐dependent (BOLD) response. This is achieved by scaling, using information from a perfusion‐sensitive scan during a purely vascular challenge, typically induced by a gas manipulation or a breath‐hold task. In this work, we seek for a validation of the use of the resting‐state fluctuation amplitude (RSFA) as a scaling factor to remove vascular contributions from the BOLD response. Given the peculiarity of depth‐dependent vascularization in gray matter, BOLD and vascular space occupancy (VASO) data were acquired at submillimeter resolution and averaged across cortical laminae. RSFA from the primary motor cortex was, thus, compared to the amplitude of hypercapnia‐induced signal changes (tSDhc) and with the M factor of the Davis model on a laminar level. High linear correlations were observed for RSFA and tSDhc (R2 = 0.92 ± 0.06) and somewhat reduced for RSFA and M (R2 = 0.62 ± 0.19). Laminar profiles of RSFA‐normalized BOLD signal changes yielded good agreement with corresponding VASO profiles. Overall, this suggests that RSFA contains strong vascular components and is also modulated by baseline quantities contained in the M factor. We conclude that RSFA may replace the scaling factor tSDhc for normalizing the laminar BOLD response.

Alzheimer's disease (AD) is associated with disruptions in brain activity and networks. However, there is substantial inconsistency among studies that have investigated functional brain alterations in AD; such contradictions have hindered efforts to elucidate the core disease mechanisms. In this study, we aim to comprehensively characterize AD‐associated functional brain alterations using one of the world's largest resting‐state functional MRI (fMRI) biobank for the disorder. The biobank includes fMRI data from six neuroimaging centers, with a total of 252 AD patients, 221 mild cognitive impairment (MCI) patients and 215 healthy comparison individuals. Meta‐analytic techniques were used to unveil reliable differences in brain function among the three groups. Relative to the healthy comparison group, AD was associated with significantly reduced functional connectivity and local activity in the default‐mode network, basal ganglia and cingulate gyrus, along with increased connectivity or local activity in the prefrontal lobe and hippocampus (p

Alzheimer's disease (AD) is a chronic neurodegenerative disorder characterized by specific patterns of gray and white matter damage and cognitive/behavioral manifestations. The cerebellum has also been implicated in the pathophysiology of AD. Because the cerebellum is known to have strong functional connectivity (FC) with associative cerebral cortex regions, it is possible to hypothesize that it is incorporated into intrinsic FC networks relevant to cognitive manifestation of AD. In the present study, the cerebellar dentate nucleus, the largest cerebellar nucleus and the major output channel to the cerebral cortex, was chosen as the region of interest to test potential cerebellocerebral FC alterations and correlations with patients' memory impairment in a group of patients with AD. Compared to controls, patients with AD showed an increase in FC between the dentate nucleus and regions of the lateral temporal lobe. This study demonstrates that lower memory performances in AD may be related to altered FC within specific cerebellocortical functional modules, thus suggesting the cerebellar contribution to AD pathophysiology and typical memory dysfunctions.