Pons to Posterior Cingulate Functional Projections Predict Affective Processing Changes in the Elderly Following Eight Weeks of Meditation Training.
EBioMedicine. 2016 Aug;10:236-48
Authors: Shao R, Keuper K, Geng X, Lee TM
Evidence indicates meditation facilitates affective regulation and reduces negative affect. It also influences resting-state functional connectivity between affective networks and the posterior cingulate (PCC)/precuneus, regions critically implicated in self-referential processing. However, no longitudinal study employing active control group has examined the effect of meditation training on affective processing, PCC/precuneus connectivity, and their association. Here, we report that eight-week meditation, but not relaxation, training 'neutralized' affective processing of positive and negative stimuli in healthy elderly participants. Additionally, meditation versus relaxation training increased the positive connectivity between the PCC/precuneus and the pons, the direction of which was largely directed from the pons to the PCC/precuneus, as revealed by dynamic causal modeling. Further, changes in connectivity between the PCC/precuneus and pons predicted changes in affective processing after meditation training. These findings indicate meditation promotes self-referential affective regulation based on increased regulatory influence of the pons on PCC/precuneus, which new affective-processing strategy is employed across both resting state and when evaluating affective stimuli. Such insights have clinical implications on interventions on elderly individuals with affective disorders.
PMID: 27349456 [PubMed - indexed for MEDLINE]
Time-varying spectral power of resting-state fMRI networks reveal cross-frequency dependence in dynamic connectivity.
PLoS One. 2017;12(2):e0171647
Authors: Yaesoubi M, Miller RL, Calhoun VD
Brain oscillations and synchronicity among brain regions (brain connectivity) have been studied in resting-state (RS) and task-induced settings. RS-connectivity which captures brain functional integration during an unconstrained state is shown to vary with the frequency of oscillations. Indeed, high temporal resolution modalities have demonstrated both between and cross-frequency connectivity spanning across frequency bands such as theta and gamma. Despite high spatial resolution, functional magnetic resonance imaging (fMRI) suffers from low temporal resolution due to modulation with slow-varying hemodynamic response function (HRF) and also relatively low sampling rate. This limits the range of detectable frequency bands in fMRI and consequently there has been no evidence of cross-frequency dependence in fMRI data. In the present work we uncover recurring patterns of spectral power in network timecourses which provides new insight on the actual nature of frequency variation in fMRI network activations. Moreover, we introduce a new measure of dependence between pairs of rs-fMRI networks which reveals significant cross-frequency dependence between functional brain networks specifically default-mode, cerebellar and visual networks. This is the first strong evidence of cross-frequency dependence between functional networks in fMRI and our subject group analysis based on age and gender supports usefulness of this observation for future clinical applications.
PMID: 28192457 [PubMed - in process]
Adaptive testing for multiple traits in a proportional odds model with applications to detect SNP-brain network associations.
Genet Epidemiol. 2017 Feb 13;:
Authors: Kim J, Pan W, Alzheimer's Disease Neuroimaging Initiative
There has been increasing interest in developing more powerful and flexible statistical tests to detect genetic associations with multiple traits, as arising from neuroimaging genetic studies. Most of existing methods treat a single trait or multiple traits as response while treating an SNP as a predictor coded under an additive inheritance mode. In this paper, we follow an earlier approach in treating an SNP as an ordinal response while treating traits as predictors in a proportional odds model (POM). In this way, it is not only easier to handle mixed types of traits, e.g., some quantitative and some binary, but it is also potentially more robust to the commonly adopted additive inheritance mode. More importantly, we develop an adaptive test in a POM so that it can maintain high power across many possible situations. Compared to the existing methods treating multiple traits as responses, e.g., in a generalized estimating equation (GEE) approach, the proposed method can be applied to a high dimensional setting where the number of phenotypes (p) can be larger than the sample size (n), in addition to a usual small P setting. The promising performance of the proposed method was demonstrated with applications to the Alzheimer's Disease Neuroimaging Initiative (ADNI) data, in which either structural MRI driven phenotypes or resting-state functional MRI (rs-fMRI) derived brain functional connectivity measures were used as phenotypes. The applications led to the identification of several top SNPs of biological interest. Furthermore, simulation studies showed competitive performance of the new method, especially for p>n.
PMID: 28191669 [PubMed - as supplied by publisher]
Abnormal cortical functional activity in patients with ischemic white matter lesions: A resting-state functional magnetic resonance imaging study.
Neurosci Lett. 2017 Feb 08;:
Authors: Ding X, Ding J, Hua B, Xiong X, Xiao L, Peng F, Chen L, Pan X, Wang Q
There is increasing evidence that white matter lesions (WMLs) are associated with cognitive impairments. The purpose of this study was to explore the relationship of WMLs with cognitive impairments from the aspect of cortical functional activity. Briefly, Sixteen patients with ischemic WMLs and 13 controls participated in this study. A regional homogeneity (ReHo) approach was used to investigate altered neural coherence in patients with ischemic WMLs during the resting state. A correlation analysis was further performed between regions with altered ReHo and cognitive test scores, including Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), in the patient group. Finally, we found regions with altered ReHo values in patients with ischemic WMLs to be involved in default mode network (DMN), frontal-parietal control network (FPCN), dorsal attention network (DAN), motor network and right temporal cortex. Moreover, some altered regions belonging to DMN, FPCN and motor network were significantly correlated with cognitive test scores. Our results provide neuroimaging evidence for the impairments of memory, attention, executive and motor function in patients with ischemic WMLs. It is interesting to note that the decreased ReHo was mainly in the anterior brain regions, while increased ReHo in the posterior brain regions, which may indicate a failure down regulation of spontaneous activity in posterior regions. In summary, this study indicates an important role of specific cortical dysfunction in cognitive associated with WMLs.
PMID: 28189742 [PubMed - as supplied by publisher]
Connectivity-based parcellation reveals distinct cortico-striatal connectivity fingerprints in Autism Spectrum Disorder.
Neuroimage. 2017 Feb 07;:
Authors: Balsters JH, Mantini D, Wenderoth N
Autism Spectrum Disorder (ASD) has been associated with abnormal synaptic development causing a breakdown in functional connectivity. However, when measured at the macro scale using resting state fMRI, these alterations are subtle and often difficult to detect due to the large heterogeneity of the pathology. Recently, we outlined a novel approach for generating robust biomarkers of resting state functional magnetic resonance imaging (RS-fMRI) using connectivity based parcellation of gross morphological structures to improve single-subject reproducibility and generate more robust connectivity fingerprints. Here we apply this novel approach to investigating the organization and connectivity strength of the cortico-striatal system in a large sample of ASD individuals and typically developed (TD) controls (N=130 per group). Our results showed differences in the parcellation of the striatum in ASD. Specifically, the putamen was found to be one single structure in ASD, whereas this was split into anterior and posterior segments in an age, IQ, and head movement matched TD group. An analysis of the connectivity fingerprints revealed that the group differences in clustering were driven by differential connectivity between striatum and the supplementary motor area, posterior cingulate cortex, and posterior insula. Our approach for analysing RS-fMRI in clinical populations has provided clear evidence that cortico-striatal circuits are organized differently in ASD. Based on previous task-based segmentations of the striatum, we believe that the anterior putamen cluster present in TD, but not in ASD, likely contributes to social and language processes.
PMID: 28188914 [PubMed - as supplied by publisher]
Abnormal regional activity and functional connectivity in resting-state brain networks associated with etiology confirmed unilateral pulsatile tinnitus in the early stage of disease.
Hear Res. 2017 Feb 07;:
Authors: Lv H, Zhao P, Liu Z, Li R, Zhang L, Wang P, Yan F, Liu L, Wang G, Zeng R, Li T, Dong C, Gong S, Wang Z
Abnormal neural activities can be revealed by resting-state functional magnetic resonance imaging (rs-fMRI) using analyses of the regional activity and functional connectivity (FC) of the networks in the brain. This study was designed to demonstrate the functional network alterations in the patients with pulsatile tinnitus (PT). In this study, we recruited 45 patients with unilateral PT in the early stage of disease (less than 48 months of disease duration) and 45 normal controls. We used regional homogeneity (ReHo) and seed-based FC computational methods to reveal resting-state brain activity features associated with pulsatile tinnitus. Compared with healthy controls, PT patients showed regional abnormalities mainly in the left middle occipital gyrus (MOG), posterior cingulate gyrus (PCC), precuneus and right anterior insula (AI). When these regions were defined as seeds, we demonstrated widespread modification of interaction between the auditory and non-auditory networks. The auditory network was positively connected with the cognitive control network (CCN), which may associate with tinnitus related distress. Both altered regional activity and changed FC were found in the visual network. The modification of interactions of higher order networks were mainly found in the DMN, CCN and limbic networks. Functional connectivity between the left MOG and left parahippocampal gyrus could also be an index to reflect the disease duration. This study helped us gain a better understanding of the characteristics of neural network modifications in patients with pulsatile tinnitus.
PMID: 28188881 [PubMed - as supplied by publisher]
How people with multiple sclerosis cope with a sustained finger motor task: a behavioural and fMRI study.
Behav Brain Res. 2017 Feb 07;:
Authors: Bonzano L, Pardini M, Roccatagliata L, Mancardi GL, Bove M
Motor and non-motor basal ganglia (BG) circuits can help healthy subjects cope with task-induced central fatigue and re-establish motor performance after deterioration. This work aimed to assess whether patients with multiple sclerosis (MS) were able to recover motor performance after deterioration due to a demanding task and whether BG activity played a role in performance recovery in this population. Fourteen patients with MS performed a finger-tapping sequence with their right hand during three fMRI sessions: at baseline, after a demanding finger motor task (5-min sequence repetition) and after a short rest period. We observed deterioration of spatial and temporal accuracy with task repetition, as expected; after rest, temporal but not spatial accuracy recovered. Further, higher subjective fatigue was associated with increased motor performance deterioration and reduced temporal accuracy recovery. The amplitude of the BOLD signal change in the left caudate, putamen, globus pallidus, thalamus and amygdala was high at baseline and significantly reduced after the demanding task. Following rest, activity achieved values similar to the baseline in all these regions except for the amygdala. These findings suggest that patients were in a fatigue-like state since task beginning, as they showed enhanced BOLD signal change in the subcortical structures known to be recruited in healthy subjects only when coping with fatigue to recover motor performance. Abnormalities in motor and non-motor BG functions can contribute to fatigue in MS.
PMID: 28188814 [PubMed - as supplied by publisher]
Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease.
Neurology. 2017 Feb 10;:
Authors: Franzmeier N, Duering M, Weiner M, Dichgans M, Ewers M, Alzheimer's Disease Neuroimaging Initiative (ADNI)
OBJECTIVE: To test whether higher global functional connectivity of the left frontal cortex (LFC) in Alzheimer disease (AD) is associated with more years of education (a proxy of cognitive reserve [CR]) and mitigates the association between AD-related fluorodeoxyglucose (FDG)-PET hypometabolism and episodic memory.
METHODS: Forty-four amyloid-PET-positive patients with amnestic mild cognitive impairment (MCI-Aβ+) and 24 amyloid-PET-negative healthy controls (HC) were included. Voxel-based linear regression analyses were used to test the association between years of education and FDG-PET in MCI-Aβ+, controlled for episodic memory performance. Global LFC (gLFC) connectivity was computed through seed-based resting-state fMRI correlations between the LFC (seed) and each voxel in the gray matter. In linear regression analyses, education as a predictor of gLFC connectivity and the interaction of gLFC connectivity × FDG-PET hypometabolism on episodic memory were tested.
RESULTS: FDG-PET metabolism in the precuneus was reduced in MCI-Aβ+ compared to HC (p = 0.028), with stronger reductions observed in MCI-Aβ+ with more years of education (p = 0.006). In MCI-Aβ+, higher gLFC connectivity was associated with more years of education (p = 0.021). At higher levels of gLFC connectivity, the association between precuneus FDG-PET hypometabolism and lower memory performance was attenuated (p = 0.027).
CONCLUSIONS: Higher gLFC connectivity is a functional substrate of CR that helps to maintain episodic memory relatively well in the face of emerging FDG-PET hypometabolism in early-stage AD.
PMID: 28188306 [PubMed - as supplied by publisher]
Thalamocortical Dysconnectivity in Paroxysmal Kinesigenic Dyskinesia: Combining Functional Magnetic Resonance Imaging and Diffusion Tensor Imaging.
Mov Disord. 2017 Feb 10;:
Authors: Long Z, Xu Q, Miao HH, Yu Y, Ding MP, Chen H, Liu ZR, Liao W
BACKGROUND: Paroxysmal kinesigenic dyskinesia is associated with macrostructural and microstructural abnormalities in the thalamus.
OBJECTIVES: To examine functional and structural connectivity of thalamocortical networks in paroxysmal kinesigenic dyskinesia and to further investigate the effect of mutation of the proline-rich transmembrane protein 2 on thalamocortical networks.
METHODS: Patients with paroxysmal kinesigenic dyskinesia (n = 20), subdivided into proline-rich transmembrane protein 2-mutated (n = 8) and nonmutated patients (n = 12) and healthy controls (n = 20) underwent resting-state functional MRI and diffusion imaging scan. The functional properties of correlations in neural activity (functional connectivity) and the structural properties of white matter probabilistic tractography (structural connectivity) were analyzed to characterize thalamocortical networks. Furthermore, the effect of proline-rich transmembrane protein 2 mutation on functional and structural connectivity of thalamocortical networks were examined using one-way analysis of variance among three groups.
RESULTS: Patients had increased functional and structural connectivity between ventral lateral/anterior thalamic nuclei and a lateral motor area, as compared to controls. This functional connectivity positively correlated with disease duration. Interestingly, proline-rich transmembrane protein 2-mutated patients showed decreased functional connectivity and preserved structural connectivity, between mediodorsal nucleus and prefrontal cortex, compared to nonmutated patients and controls.
CONCLUSIONS: Thalamomotor/premotor hyperconnectivity suggests abnormal communication between thalamus and motor cortex in patients. Furthermore, thalamoprefrontal hypoconnectivity in proline-rich transmembrane protein 2-mutated patients might indicate that proline-rich transmembrane protein 2 mutations result in inefficient thalamoprefrontal integration. Our findings facilitate a deeper understanding of the crucial role of thalamocortical dysconnectivity in the pathophysiological mechanisms of paroxysmal kinesigenic dyskinesia. © 2017 International Parkinson and Movement Disorder Society.
PMID: 28186667 [PubMed - as supplied by publisher]
Increased network centrality as markers of relapse risk in nicotine-dependent individuals treated with varenicline.
Prog Neuropsychopharmacol Biol Psychiatry. 2017 Feb 06;75:142-147
Authors: Shen Z, Huang P, Wang C, Qian W, Yang Y, Zhang M
Identifying smokers at high risk of relapse could improve the effectiveness of cessation therapies. Although altered regional brain function in smokers has been reported, whether the whole-brain functional organization differs smokers with relapse vulnerability from others remains unclear. Thus, the goal of this study is to investigate the baseline functional connectivity differences between relapsers and quitters. Using resting-state fMRI, we acquired images from 57 smokers prior to quitting attempts. After 12-week treatment with varenicline, smokers were divided into relapsers (n=36) and quitters (n=21) (quitter: continuously abstinent for weeks 9-12). The smoking cessation outcomes were cross-validated by self-reports and expired carbon monoxide. We then used eigenvector centrality (EC) mapping to identify the functional connectivity differences between relapsers and quitters. When compared to quitters, increased EC in the right dorsolateral prefrontal cortex (DLPFC), left middle temporal gyrus (MTG) and cerebellum anterior lobe was observed in relapsers. In addition, a logistic regression analysis of EC data (with DLPFC, MTG and cerebellum included) predicted relapse with 80.7% accuracy. These findings suggest that the DLPFC, MTG and cerebellum may be important substrates of smoking relapse vulnerability. The data also suggest that relapse-vulnerable smokers can be identified before quit attempts, which could enable personalized treatment and improve smoking cessation outcomes.
PMID: 28185963 [PubMed - as supplied by publisher]
Mu Opioid Receptors in Gamma-Aminobutyric Acidergic Forebrain Neurons Moderate Motivation for Heroin and Palatable Food.
Biol Psychiatry. 2016 Dec 26;:
Authors: Charbogne P, Gardon O, Martín-García E, Keyworth HL, Matsui A, Mechling AE, Bienert T, Nasseef T, Robé A, Moquin L, Darcq E, Ben Hamida S, Robledo P, Matifas A, Befort K, Gavériaux-Ruff C, Harsan LA, von Elverfeldt D, Hennig J, Gratton A, Kitchen I, Bailey A, Alvarez VA, Maldonado R, Kieffer BL
BACKGROUND: Mu opioid receptors (MORs) are central to pain control, drug reward, and addictive behaviors, but underlying circuit mechanisms have been poorly explored by genetic approaches. Here we investigate the contribution of MORs expressed in gamma-aminobutyric acidergic forebrain neurons to major biological effects of opiates, and also challenge the canonical disinhibition model of opiate reward.
METHODS: We used Dlx5/6-mediated recombination to create conditional Oprm1 mice in gamma-aminobutyric acidergic forebrain neurons. We characterized the genetic deletion by histology, electrophysiology, and microdialysis; probed neuronal activation by c-Fos immunohistochemistry and resting-state functional magnetic resonance imaging; and investigated main behavioral responses to opiates, including motivation to obtain heroin and palatable food.
RESULTS: Mutant mice showed MOR transcript deletion mainly in the striatum. In the ventral tegmental area, local MOR activity was intact, and reduced activity was only observed at the level of striatonigral afferents. Heroin-induced neuronal activation was modified at both sites, and whole-brain functional networks were altered in live animals. Morphine analgesia was not altered, and neither was physical dependence to chronic morphine. In contrast, locomotor effects of heroin were abolished, and heroin-induced catalepsy was increased. Place preference to heroin was not modified, but remarkably, motivation to obtain heroin and palatable food was enhanced in operant self-administration procedures.
CONCLUSIONS: Our study reveals dissociable MOR functions across mesocorticolimbic networks. Thus, beyond a well-established role in reward processing, operating at the level of local ventral tegmental area neurons, MORs also moderate motivation for appetitive stimuli within forebrain circuits that drive motivated behaviors.
PMID: 28185645 [PubMed - as supplied by publisher]
Abnormal functional connectivity strength in patients with adolescent-onset schizophrenia: a resting-state fMRI study.
Eur Child Adolesc Psychiatry. 2017 Feb 09;:
Authors: Wang S, Zhan Y, Zhang Y, Lv L, Wu R, Zhao J, Guo W
Structural and functional abnormalities were reported in the brain of patients with adolescent-onset schizophrenia (AOS). However, evidence of abnormal functional connectivity of the brain in AOS patients is limited. Thus, we analyzed the resting-state functional magnetic resonance scans of 48 drug-naive AOS patients and 31 healthy controls to determine their functional connectivity strength (FCS) and examined if FCS abnormalities were correlated with clinical characteristics. Compared with healthy controls, AOS patients showed significantly increased FCS in the left cerebellum VI and right inferior frontal gyrus/insula. A positive correlation was observed between FCS values in the right inferior frontal gyrus/insula and general psychopathology scores of positive and negative syndrome scale. Results suggest that functional connectivity pattern is disrupted in drug-naive AOS patients. The FCS values in this abnormal region have potential for evaluating the disease severity.
PMID: 28185094 [PubMed - as supplied by publisher]
Altered spontaneous brain activity in adolescent boys with pure conduct disorder revealed by regional homogeneity analysis.
Eur Child Adolesc Psychiatry. 2017 Feb 09;:
Authors: Wu Q, Zhang X, Dong D, Wang X, Yao S
Functional magnetic resonance imaging (fMRI) studies have revealed abnormal neural activity in several brain regions of adolescents with conduct disorder (CD) performing various tasks. However, little is known about the spontaneous neural activity in people with CD in a resting state. The aims of this study were to investigate CD-associated regional activity abnormalities and to explore the relationship between behavioral impulsivity and regional activity abnormalities. Resting-state fMRI (rs-fMRI) scans were administered to 28 adolescents with CD and 28 age-, gender-, and IQ-matched healthy controls (HCs). The rs-fMRI data were subjected to regional homogeneity (ReHo) analysis. ReHo can demonstrate the temporal synchrony of regional blood oxygen level-dependent signals and reflect the coordination of local neuronal activity facilitating similar goals or representations. Compared to HCs, the CD group showed increased ReHo bilaterally in the insula as well as decreased ReHo in the right inferior parietal lobule, right middle temporal gyrus and right fusiform gyrus, left anterior cerebellum anterior, and right posterior cerebellum. In the CD group, mean ReHo values in the left and the right insula correlated positively with Barratt Impulsivity Scale (BIS) total scores. The results suggest that CD is associated with abnormal intrinsic brain activity, mainly in the cerebellum and temporal-parietal-limbic cortices, regions that are related to emotional and cognitive processing. BIS scores in adolescents with CD may reflect severity of abnormal neuronal synchronization in the insula.
PMID: 28185093 [PubMed - as supplied by publisher]
Decoupling between the hand territory and the default mode network after bilateral arm transplantation: four-year follow-up case study.
Brain Imaging Behav. 2017 Feb 09;:
Authors: Hernandez-Castillo CR, Diedrichsen J, Aguilar-Castañeda E, Iglesias M
Several studies have suggested both a local and network reorganization of the sensorimotor system following amputation. Transplantation of a new limb results in a new shifting of cortical activity in the local territory of the transplanted limb. However, there is a lack of information about the reversibility of the abnormalities at the network level. The objective of this study was to characterize the functional connectivity changes between the cortical territory of the new hand and two intrinsic network of interest: the sensorimotor network (SMN) and the default mode network (DMN) of one patient whom received bilateral forearm transplants. Using resting-state fMRI these two networks were identified across four different time points, starting four months after the transplantation surgery and during three consecutive years while the patient underwent physical rehabilitation. The topology of the SMN was disrupted at the first acquisition and over the years returned to its canonical pattern. Analysis of the DMN showed the normal topology with no significant changes across acquisitions. Functional connectivity between the missing hand's cortical territory and the SMN increased over time. Accordingly, functional connectivity between the missing hand's cortical territory and the DMN became anticorrelated over time. Our results suggest that after transplantation a new reorganization occurs at the network level, supporting the idea that extreme behavioral changes can affect not only the local rewiring but also the intrinsic network organization in neurologically healthy subjects. Overall this study provides new insight on the complex dynamics of brain organization.
PMID: 28185062 [PubMed - as supplied by publisher]
Selective functional disconnection of the orbitofrontal subregions in schizophrenia.
Psychol Med. 2017 Feb 10;:1-10
Authors: Xu Y, Qin W, Zhuo C, Xu L, Zhu J, Liu X, Yu C
BACKGROUND: As a disconnection syndrome, schizophrenia has shown impaired resting-state functional connectivity (rsFC) in the orbitofrontal cortex (OFC); however, the OFC is a rather heterogeneous region and the rsFC changes in the OFC subregions remain unknown.
METHOD: A total of 98 schizophrenia patients and 102 healthy controls underwent resting-state functional MRI using a sensitivity-encoded spiral-in imaging sequence (SENSE-SPIRAL) to reduce susceptibility-induced signal loss and distortion. The OFC subregions were defined according to a previous parcellation study that divided the OFC into the anterior (OFCa), medial (OFCm), posterior (OFCp), intermediate (OFCi), and lateral (OFCl) subregions. The rsFC was compared using two-way repeated-measures ANOVA.
RESULTS: Whether or not global signal regression, compared with healthy controls, schizophrenia patients consistently exhibited decreased rsFC between the left OFCi and the left middle temporal gyrus and the right middle frontal gyrus (MFG), between the right OFCi and the right MFG and the left inferior frontal gyrus, between the right OFCm and the middle cingulate cortex and the left Rolandic operculum. These rsFC changes still remained significant even after cortical atrophy correction.
CONCLUSIONS: These findings suggest a selective functional disconnection of the OFC subregions in schizophrenia, and provide more precise information about the functional disconnections of the OFC in this disorder.
PMID: 28183367 [PubMed - as supplied by publisher]
Multicenter stability of resting state fMRI in the detection of Alzheimer's disease and amnestic MCI.
Neuroimage Clin. 2017;14:183-194
Authors: Teipel SJ, Wohlert A, Metzger C, Grimmer T, Sorg C, Ewers M, Meisenzahl E, Klöppel S, Borchardt V, Grothe MJ, Walter M, Dyrba M
BACKGROUND: In monocentric studies, patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) dementia exhibited alterations of functional cortical connectivity in resting-state functional MRI (rs-fMRI) analyses. Multicenter studies provide access to large sample sizes, but rs-fMRI may be particularly sensitive to multiscanner effects.
METHODS: We used data from five centers of the "German resting-state initiative for diagnostic biomarkers" (psymri.org), comprising 367 cases, including AD patients, MCI patients and healthy older controls, to assess the influence of the distributed acquisition on the group effects. We calculated accuracy of group discrimination based on whole brain functional connectivity of the posterior cingulate cortex (PCC) using pooled samples as well as second-level analyses across site-specific group contrast maps.
RESULTS: We found decreased functional connectivity in AD patients vs. controls, including clusters in the precuneus, inferior parietal cortex, lateral temporal cortex and medial prefrontal cortex. MCI subjects showed spatially similar, but less pronounced, differences in PCC connectivity when compared to controls. Group discrimination accuracy for AD vs. controls (MCI vs. controls) in the test data was below 76% (72%) based on the pooled analysis, and even lower based on the second level analysis stratified according to scanner. Only a subset of quality measures was useful to detect relevant scanner effects.
CONCLUSIONS: Multicenter rs-fMRI analysis needs to employ strict quality measures, including visual inspection of all the data, to avoid seriously confounded group effects. While pending further confirmation in biomarker stratified samples, these findings suggest that multicenter acquisition limits the use of rs-fMRI in AD and MCI diagnosis.
PMID: 28180077 [PubMed - in process]
Increased default-mode network centrality in cognitively impaired multiple sclerosis patients.
Neurology. 2017 Feb 08;:
Authors: Eijlers AJ, Meijer KA, Wassenaar TM, Steenwijk MD, Uitdehaag BM, Barkhof F, Wink AM, Geurts JJ, Schoonheim MM
OBJECTIVE: To investigate how changes in functional network hierarchy determine cognitive impairment in multiple sclerosis (MS).
METHODS: A cohort consisting of 332 patients with MS (age 48.1 ± 11.0 years, symptom duration 14.6 ± 8.4 years) and 96 healthy controls (HCs; age 45.9 ± 10.4 years) underwent structural MRI, fMRI, and extensive neuropsychological testing. Patients were divided into 3 groups: cognitively impaired (CI; n = 87), mildly cognitively impaired (MCI; n = 65), and cognitively preserved (CP; n = 180). The functional importance of brain regions was quantified with degree centrality, the average strength of the functional connections of a brain region with the rest of the brain, and eigenvector centrality, which adds to this concept by adding additional weight to connections with brain hubs because these are known to be especially important. Centrality values were calculated for each gray matter voxel based on resting-state fMRI data, registered to standard space. Group differences were assessed with a cluster-wise permutation-based method corrected for age, sex, and education.
RESULTS: CI patients demonstrated widespread centrality increases compared to both HCs and CP patients, mainly in regions making up the default-mode network. Centrality decreases were similar in all patient groups compared to HCs, mainly in occipital and sensorimotor areas. Results were robust across centrality measures.
CONCLUSIONS: Patients with MS with cognitive impairment show hallmark alterations in functional network hierarchy with increased relative importance (centrality) of the default-mode network.
PMID: 28179464 [PubMed - as supplied by publisher]
Selective TMS-induced modulation of functional connectivity correlates with changes in behavior.
Neuroimage. 2017 Feb 04;:
Authors: Balan PF, Gerits A, Mantini D, Vanduffel W
Despite the increasing use of functional connectivity (FC) studies in fundamental and clinical research, the link between FC and behavior is still poorly understood. To test the hypothesis that artificial modulation of FC correlates with changes in behavior in a quantitative manner, we performed behavioral and resting state fMRI experiments in monkeys while perturbing, offline, the frontal eye fields (FEF) using unilateral continuous theta burst transcranial magnetic stimulation (FEF-cTBS). Stimulation of left and right FEF caused remarkably specific decreases in FC, which were symmetric for intra-hemispheric and asymmetric for inter-hemispheric FC. Surprisingly, FEF-cTBS improved the performance and compensated intrinsic choice biases in saccadic behavior of four monkeys, independent of the initial bias direction. Moreover, the direction of the stimulation-induced effects on both behavior (i.e. bias compensation) and FC (i.e. decrease) were independent of the stimulated hemisphere, while their magnitude depended on the side of stimulation, choice bias and monkey. Overall, the naturally-occurring saccade biases determined the FC changes following FEF-cTBS. Finally, we showed that the average decreases in FC in the FEF network induced by cTBS can be used to predict, with high specificity, both the direction (opposite to the saccadic biases) and the magnitude of the shift in saccadic choice preference relative to the unperturbed state. To reconcile the apparent contradiction between improved performance and bias compensation vs. decrease in functional connectivity, we propose that the main functional consequences of FEF-cTBS relate to adjusting inter-hemispheric imbalances.
PMID: 28179165 [PubMed - as supplied by publisher]
Structural white matter and functional connectivity alterations in patients with shoulder apprehension.
Sci Rep. 2017 Feb 08;7:42327
Authors: Zanchi D, Cunningham G, Lädermann A, Ozturk M, Hoffmeyer P, Haller S
Previous functional magnetic resonance imaging (fMRI) findings indicate that shoulder apprehension is more complex than a pure mechanical problem of the shoulder, showing a direct modification in functional brain networks associated with motor inhibition and emotional regulation. The current study extends these findings by investigating further structural alterations in patients with shoulder apprehension compared to controls. 14 aged patients with shoulder apprehension (27.3 ± 2.0 years) and 10 matched healthy controls (29.6 ± 1.3 years) underwent clinical and fMRI examination including fMRI and diffusion tensor imaging (DTI). Tract-based spatial statistics procedure was used to analyze white matter (WM) alterations. Functional images were analyzed investigating resting state network connectivity. DTI results were correlated with different shoulder clinical scores and functional connectivity networks. Fractional anisotropy (FA), representing white matter integrity, is increased in the left internal capsule and partially in the thalamus in patients compared to controls. Moreover, FA correlates negatively with simple shoulder test (SST) scores (p < .05) and positively with a functional connectivity network qualitatively replicating previous results (p < .01). This study extends previous findings, showing that in addition to functional changes, structural white matter changes are also present in patients with shoulder apprehension.
PMID: 28176877 [PubMed - in process]
Network-level assessment of reward-related activation in patients with ADHD and healthy individuals.
Hum Brain Mapp. 2017 Feb 08;:
Authors: von Rhein D, Beckmann CF, Franke B, Oosterlaan J, Heslenfeld DJ, Hoekstra PJ, Hartman CA, Luman M, Faraone SV, Cools R, Buitelaar JK, Mennes M
INTRODUCTION: Reward processing is a key aspect of cognitive control processes, putatively instantiated by mesolimbic and mesocortical brain circuits. Deficient signaling within these circuits has been associated with psychopathology. We applied a network discovery approach to assess specific functional networks associated with reward processing in participants with attention-deficit/hyperactivity disorder (ADHD).
METHODS: To describe task-related processes in terms of integrated functional networks, we applied independent component analysis (ICA) to task response maps of 60 healthy participants who performed a monetary incentive delay (MID) task. The resulting components were interpreted on the basis of their similarity with group-level task responses as well as their similarity with brain networks derived from resting state fMRI analyses. ADHD-related effects on network characteristics including functional connectivity and communication between networks were examined in an independent sample comprising 150 participants with ADHD and 48 healthy controls.
RESULTS: We identified 23 components to be associated with 4 large-scale functional networks: the default-mode, visual, executive control, and salience networks. The salience network showed a specific association with reward processing as well as the highest degree of within-network integration. ADHD was associated with decreased functional connectivity between the salience and executive control networks as well as with peripheral brain regions.
CONCLUSIONS: Reward processing as measured with the MID task involves one reward-specific and three general functional networks. Participants with ADHD exhibited alterations in connectivity of both the salience and executive control networks and associated brain regions during task performance. Hum Brain Mapp, 2017. © 2017 Wiley Periodicals, Inc.
PMID: 28176434 [PubMed - as supplied by publisher]