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Early and Late Age of Seizure Onset have a Differential Impact on Brain Resting-State Organization in Temporal Lobe Epilepsy.

Tue, 06/03/2014 - 16:00

Early and Late Age of Seizure Onset have a Differential Impact on Brain Resting-State Organization in Temporal Lobe Epilepsy.

Brain Topogr. 2014 Jun 1;

Authors: Doucet GE, Sharan A, Pustina D, Skidmore C, Sperling MR, Tracy JI

Abstract
Temporal lobe epilepsy (TLE) is associated with abnormalities which extend into the entire brain. While the age of seizure onset (SO) has a large impact on brain plasticity, its effect on brain connectivity at rest remains unclear, especially, in interaction with factors such as the presence of mesial temporal sclerosis (MTS). In this context, we investigated whole-brain and regional functional connectivity (FC) organization in 50 TLE patients who underwent a resting-state fMRI scan, in comparison to healthy controls, using graph-theory measures. We first classified TLE patients according to the presence of MTS or not. Then, we categorized the patients based on their age of SO into two subgroups (early or late age of SO). Results revealed whole-brain differences with both reduced functional segregation and increased integration in the patients, regardless of the age of SO and MTS, relative to the controls. At a local level, we revealed that the connectivity of the ictal hippocampus remains the most impaired for an early SO, even in the absence of MTS. Importantly, we showed that the impact of age of SO on whole-brain and regional resting-state FC depends on the presence of MTS. Overall, our results highlight the importance of investigating the effect of age of SO when examining resting-state activity in TLE, as this factor leads different perturbations of network modularity and connectivity at the global and local level, with different implications for regional plasticity and adaptive organization.

PMID: 24881003 [PubMed - as supplied by publisher]

Shrinkage prediction of seed-voxel brain connectivity using resting state fMRI.

Mon, 06/02/2014 - 14:00

Shrinkage prediction of seed-voxel brain connectivity using resting state fMRI.

Neuroimage. 2014 May 28;

Authors: Shou H, Eloyan A, Nebel MB, Mejia A, Pekar JJ, Mostofsky S, Caffo B, Lindquist MA, Crainiceanu CM

Abstract
Resting-state functional magnetic resonance imaging (rs-fMRI) is used to investigate synchronous activations in spatially distinct regions of the brain, which are thought to reflect functional systems supporting cognitive processes. Analyses are often performed using seed-based correlation analysis, allowing researchers to explore functional connectivity between data in a seed region and the rest of the brain. Using scan-rescan rs-fMRI data, we investigate how well the subject-specific seed-based correlation map from the second replication of the study can be predicted using data from the first replication. We show that one can dramatically improve prediction of subject-specific connectivity by borrowing strength from the group correlation map computed using all other subjects in the study. Even more surprisingly, we found that the group correlation map provided a better prediction of a subject's connectivity than the individual's own data. While further discussion and experimentation is required to understand how this can be used in practice, results indicate that shrinkage-based methods that borrow strength from the population mean should play a role in rs-fMRI data analysis.

PMID: 24879924 [PubMed - as supplied by publisher]

Test-Retest Reliabilities of Resting-state FMRI Measurements in Human Brain Functional Connectomics: A Systems Neuroscience Perspective.

Sun, 06/01/2014 - 13:00

Test-Retest Reliabilities of Resting-state FMRI Measurements in Human Brain Functional Connectomics: A Systems Neuroscience Perspective.

Neurosci Biobehav Rev. 2014 May 26;

Authors: Zuo XN, Xing XX

Abstract
Resting-state functional magnetic resonance imaging (RFMRI) enables researchers to monitor fluctuations in the spontaneous brain activities of thousands of regions in the human brain simultaneously, representing a popular tool for macro-scale functional connectomics to characterize normal brain function, mind-brain associations, and the various disorders. However, the test-retest reliability of RFMRI remains largely unknown. We review previously published papers on the test-retest reliability of voxel-wise metrics and conduct a meta-summary reliability analysis of seven common brain networks. This analysis revealed that the heteromodal associative (default, control, and attention) networks were mostly reliable across the seven networks. Regarding examined metrics, independent component analysis with dual regression, local functional homogeneity and functional homotopic connectivity were the three mostly reliable RFMRI metrics. These observations can guide the use of reliable metrics and further improvement of test-retest reliability for other metics in functional connectomics. We discuss the main issues with low reliability related to sub-optimal design and the choice of data processing options. Future research should use large-sample test-retest data to rectify both the within-subject and between-subject variability of RFMRI measurements and accelerate the application of functional connectomics.

PMID: 24875392 [PubMed - as supplied by publisher]

Time of Acquisition and Network Stability in Pediatric Resting-State Functional MRI.

Sun, 06/01/2014 - 13:00

Time of Acquisition and Network Stability in Pediatric Resting-State Functional MRI.

Brain Connect. 2014 May 29;

Authors: White T, Muetzel R, Schmidt M, Langeslag SJ, Jaddoe V, Hofman A, Calhoun VD, Verhulst FC, Tiemeier H

Abstract
Resting-state functional magnetic resonance imaging (rs-fMRI) has been shown to elucidate reliable patterns of brain networks in both children and adults. Studies in adults have shown that rs-fMRI acquisition times of approximately five to six minutes provide adequate sampling to produce stable spatial maps of a number of different brain networks. However, it is unclear if the acquisition time translates directly to studies of children. While there are many similarities between the brains of children and adults, many differences are also evident. Children have increased metabolism, differences in brain morphology and connectivity strengths, greater brain plasticity, and increased brain noise. Furthermore, there are differences in physiologic parameters, such as heart and respiratory rates, and compliance of the blood vessels. These developmental differences could translate into different acquisition times for rs-fMRI studies in pediatric populations. Longer scan times, however, increase the subject burden and the risk for greater movement, especially in children. Thus, the goal of this study was to assess the optimum acquisition time of rs-fMRI to extract stable brain networks in school-age children. We utilized fuzzy set theory in 84 six-to-eight year-old children and found that eight networks, including the default mode, salience, frontal, left frontoparietal, right frontoparietal, sensorimotor, auditory, and visual networks, all stabilized after approximately 5½ minutes. The sensorimotor network showed the least stability whereas the salience and auditory networks showed the greatest stability. A secondary analysis using dual regression confirmed these results. In conclusion, in young children with little head motion, rs-fMRI acquisition times of approximately 5½ minutes can extract the full complement of brain networks.

PMID: 24874884 [PubMed - as supplied by publisher]

Abnormal baseline brain activity in patients with pulsatile tinnitus: a resting-state FMRI study.

Sat, 05/31/2014 - 17:30

Abnormal baseline brain activity in patients with pulsatile tinnitus: a resting-state FMRI study.

Neural Plast. 2014;2014:549162

Authors: Han L, Zhaohui L, Fei Y, Ting L, Pengfei Z, Wang D, Cheng D, Pengde G, Xiaoyi H, Xiao W, Rui L, Zhenchang W

Abstract
Numerous investigations studying the brain functional activity of the tinnitus patients have indicated that neurological changes are important findings of this kind of disease. However, the pulsatile tinnitus (PT) patients were excluded in previous studies because of the totally different mechanisms of the two subtype tinnitus. The aim of this study is to investigate whether altered baseline brain activity presents in patients with PT using resting-state functional magnetic resonance imaging (rs-fMRI) technique. The present study used unilateral PT patients (n = 42) and age-, sex-, and education-matched normal control subjects (n = 42) to investigate the changes in structural and amplitude of low-frequency (ALFF) of the brain. Also, we analyzed the relationships between these changes with clinical data of the PT patients. Compared with normal controls, PT patients did not show any structural changes. PT patients showed significant increased ALFF in the bilateral precuneus, and bilateral inferior frontal gyrus (IFG) and decreased ALFF in multiple occipital areas. Moreover, the increased THI score and PT duration was correlated with increased ALFF in precuneus and bilateral IFG. The abnormalities of spontaneous brain activity reflected by ALFF measurements in the absence of structural changes may provide insights into the neural reorganization in PT patients.

PMID: 24872895 [PubMed - in process]

In Alzheimer's disease, hypometabolism in low-amyloid brain regions may be a functional consequence of pathologies in connected brain regions.

Sat, 05/31/2014 - 17:30

In Alzheimer's disease, hypometabolism in low-amyloid brain regions may be a functional consequence of pathologies in connected brain regions.

Brain Connect. 2014 May 28;

Authors: Klupp E, Förster S, Grimmer T, Tahmasian M, Yakushev I, Sorg C, Yousefi B, Drzezga A

Abstract
In patients with Alzheimer's disease (AD) prominent hypometabolism has been observed in brain-regions with minor amyloid load. These hypometabolism only (HO)-areas cannot be explained merely as consequence of local amyloid-toxicity. Aim of this multimodal imaging study was to explore if such HO-phenomenon may be related to pathologies in functionally connected, remote brain-regions. 19 AD-patients and 15 matched controls underwent examinations with [11C]PiB-PET and [18F]FDG-PET. Voxel-based statistical group comparisons were performed to obtain maps of significantly elevated amyloid-burden and reduced cerebral glucose metabolism respectively in patients. An HO-area was identified by subtraction of equally thresholded result-maps (hypometabolism minus amyloid-burden). To identify the network typically functionally connected to this HO-area, it was used as seed-region for a functional connectivity analysis in resting state fMRI data of 17 elderly healthy controls, The resulting intrinsic connectivity network (HO-ICN) was retransferred into the brains of AD-patients to be able to analyze pathologies within this network in the PET-datasets. Most prominent HO-area was detected in the left middle frontal gyrus of AD-patients. The HO-ICN in healthy controls showed major overlap with brain areas significantly affected by both, amyloid-deposition and hypometabolism in patients. This association was substantiated by the results of ROI-based and voxel-wise correlation-analyses, which revealed strong correlations between the degree of hypometabolism within the HO-region and within the HO-ICN. These results support the notion that hypometabolism in brain regions not strongly affected by locoregional amyloid-pathology may be related to on-going pathologies in remote but functionally connected regions, i.e. by reduced neuronal input from these regions.

PMID: 24870443 [PubMed - as supplied by publisher]

Two distinct neural mechanisms underlying indirect reciprocity.

Sat, 05/31/2014 - 17:30
Related Articles

Two distinct neural mechanisms underlying indirect reciprocity.

Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):3990-5

Authors: Watanabe T, Takezawa M, Nakawake Y, Kunimatsu A, Yamasue H, Nakamura M, Miyashita Y, Masuda N

Abstract
Cooperation is a hallmark of human society. Humans often cooperate with strangers even if they will not meet each other again. This so-called indirect reciprocity enables large-scale cooperation among nonkin and can occur based on a reputation mechanism or as a succession of pay-it-forward behavior. Here, we provide the functional and anatomical neural evidence for two distinct mechanisms governing the two types of indirect reciprocity. Cooperation occurring as reputation-based reciprocity specifically recruited the precuneus, a region associated with self-centered cognition. During such cooperative behavior, the precuneus was functionally connected with the caudate, a region linking rewards to behavior. Furthermore, the precuneus of a cooperative subject had a strong resting-state functional connectivity (rsFC) with the caudate and a large gray matter volume. In contrast, pay-it-forward reciprocity recruited the anterior insula (AI), a brain region associated with affective empathy. The AI was functionally connected with the caudate during cooperation occurring as pay-it-forward reciprocity, and its gray matter volume and rsFC with the caudate predicted the tendency of such cooperation. The revealed difference is consistent with the existing results of evolutionary game theory: although reputation-based indirect reciprocity robustly evolves as a self-interested behavior in theory, pay-it-forward indirect reciprocity does not on its own. The present study provides neural mechanisms underlying indirect reciprocity and suggests that pay-it-forward reciprocity may not occur as myopic profit maximization but elicit emotional rewards.

PMID: 24591599 [PubMed - indexed for MEDLINE]

Altered temporal variance and neural synchronization of spontaneous brain activity in anesthesia.

Fri, 05/30/2014 - 16:30

Altered temporal variance and neural synchronization of spontaneous brain activity in anesthesia.

Hum Brain Mapp. 2014 May 28;

Authors: Huang Z, Wang Z, Zhang J, Dai R, Wu J, Li Y, Liang W, Mao Y, Yang Z, Holland G, Zhang J, Northoff G

Abstract
Recent studies at the cellular and regional levels have pointed out the multifaceted importance of neural synchronization and temporal variance of neural activity. For example, neural synchronization and temporal variance has been shown by us to be altered in patients in the vegetative state (VS). This finding nonetheless leaves open the question of whether these abnormalities are specific to VS or rather more generally related to the absence of consciousness. The aim of our study was to investigate the changes of inter- and intra-regional neural synchronization and temporal variance of resting state activity in anesthetic-induced unconsciousness state. Applying an intra-subject design, we compared resting state activity in functional magnetic resonance imaging (fMRI) between awake versus anesthetized states in the same subjects. Replicating previous studies, we observed reduced functional connectivity within the default mode network (DMN) and thalamocortical network in the anesthetized state. Importantly, intra-regional synchronization as measured by regional homogeneity (ReHo) and temporal variance as measured by standard deviation (SD) of the BOLD signal were significantly reduced in especially the cortical midline regions, while increased in the lateral cortical areas in the anesthetized state. We further found significant frequency-dependent effects of SD in the thalamus, which showed abnormally high SD in Slow-5 (0.01-0.027 Hz) in the anesthetized state. Our results show for the first time of altered temporal variance of resting state activity in anesthesia. Combined with our findings in the vegetative state, these findings suggest a close relationship between temporal variance, neural synchronization and consciousness. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.

PMID: 24867379 [PubMed - as supplied by publisher]

Independent component analysis of resting state activity in pediatric obsessive-compulsive disorder.

Fri, 05/30/2014 - 16:30

Independent component analysis of resting state activity in pediatric obsessive-compulsive disorder.

Hum Brain Mapp. 2014 May 28;

Authors: Gruner P, Vo A, Argyelan M, Ikuta T, Degnan AJ, John M, Peters BD, Malhotra AK, Uluğ AM, Szeszko PR

Abstract
Obsessive-compulsive disorder (OCD) is an often severely disabling illness with onset generally in childhood or adolescence. Little is known, however, regarding the pattern of brain resting state activity in OCD early in the course of illness. We therefore examined differences in brain resting state activity in patients with pediatric OCD compared with healthy volunteers and their clinical correlates. Twenty-three pediatric OCD patients and 23 healthy volunteers (age range 9-17), matched for sex, age, handedness, and IQ completed a resting state functional magnetic resonance imaging exam at 3T. Patients completed the Children's Yale Brown Obsessive Scale. Data were decomposed into 36 functional networks using spatial group independent component analysis (ICA) and logistic regression was used to identify the components that yielded maximum group separation. Using ICA we identified three components that maximally separated the groups: a middle frontal/dorsal anterior cingulate network, an anterior/posterior cingulate network, and a visual network yielding an overall group classification of 76.1% (sensitivity = 78.3% and specificity = 73.9%). Independent component expression scores were significantly higher in patients compared with healthy volunteers in the middle frontal/dorsal anterior cingulate and the anterior/posterior cingulate networks, but lower in patients within the visual network. Higher expression scores in the anterior/posterior cingulate network correlated with greater severity of compulsions among patients. These findings implicate resting state fMRI abnormalities within the cingulate cortex and related control regions in the pathogenesis and phenomenology of OCD early in the course of the disorder and prior to extensive pharmacologic intervention. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.

PMID: 24867148 [PubMed - as supplied by publisher]

Resting-state functional connectivity abnormalities in patients with obsessive-compulsive disorder and their healthy first-degree relatives.

Fri, 05/30/2014 - 16:30

Resting-state functional connectivity abnormalities in patients with obsessive-compulsive disorder and their healthy first-degree relatives.

J Psychiatry Neurosci. 2014 Jul 1;39(4):130220

Authors: Hou JM, Zhao M, Zhang W, Song LH, Wu WJ, Wang J, Zhou DQ, Xie B, He M, Guo JW, Qu W, Li HT

Abstract
BACKGROUND: Obsessive-compulsive disorder (OCD) is a common, heritable neuropsychiatric disorder, hypothetically underpinned by dysfunction of brain cortical-striatal-thalamic-cortical (CSTC) circuits; however, the extent of brain functional abnormalities in individuals with OCD is unclear, and the genetic basis of this disorder is poorly understood. We determined the whole brain functional connectivity patterns in patients with OCD and their healthy first-degree relatives.
METHODS: We used resting-state fMRI to measure functional connectivity strength in patients with OCD, their healthy first-degree relatives and healthy controls. Whole brain functional networks were constructed by measuring the temporal correlations of all brain voxel pairs and further analyzed using a graph theory approach.
RESULTS: We enrolled 39 patients with OCD, 20 healthy first-degree relatives and 39 healthy controls in our study. Compared with healthy controls, patients with OCD showed increased functional connectivity primarily within the CSTC circuits and decreased functional connectivity in the occipital cortex, temporal cortex and cerebellum. Moreover, patients with OCD and their first-degree relatives exhibited overlapping increased functional connectivity strength in the bilateral caudate nucleus, left orbitofrontal cortex (OFC) and left middle temporal gyrus.
LIMITATIONS: Potential confounding factors, such as medication use, heterogeneity in symptom clusters and comorbid disorders, may have impacted our findings.
CONCLUSION: Our preliminary results suggest that patients with OCD have abnormal resting-state functional connectivity that is not limited to CSTC circuits and involves abnormalities in additional large-scale brain systems, especially the limbic system. Moreover, resting-state functional connectivity strength abnormalities in the left OFC, bilateral caudate nucleus and left middle temporal gyrus may be neuroimaging endophenotypes for OCD.

PMID: 24866415 [PubMed - as supplied by publisher]

Functional network connectivity during rest and task conditions: a comparative study.

Fri, 05/30/2014 - 16:30
Related Articles

Functional network connectivity during rest and task conditions: a comparative study.

Hum Brain Mapp. 2013 Nov;34(11):2959-71

Authors: Arbabshirani MR, Havlicek M, Kiehl KA, Pearlson GD, Calhoun VD

Abstract
Functional connectivity (FC) examines temporal statistical dependencies among distant brain regions by means of seed-based analysis or independent component analysis (ICA). Spatial ICA also makes it possible to investigate FC at the network level, termed functional network connectivity (FNC). The dynamics of each network (ICA component), which may consist of several remote regions is described by the ICA time-course of that network; hence, FNC studies statistical dependencies among ICA time-courses. In this article, we compare comprehensively FNC in the resting state and during performance of an auditory oddball (AOD) task in 28 healthy subjects on relevant (nonartifactual) brain networks. The results show global FNC decrease during the performance of the task. In addition, we show that specific networks enlarge and/or demonstrate higher activity during the performance of the task. The results suggest that performing an active task like AOD may be facilitated by recruiting more neurons and higher activation of related networks rather than collaboration among different brain networks. We also evaluated the impact of temporal filtering on FNC analyses. Results showed that the results are not significantly affected by filtering.

PMID: 22736522 [PubMed - indexed for MEDLINE]

Baseline activity predicts working memory load of preceding task condition.

Fri, 05/30/2014 - 16:30
Related Articles

Baseline activity predicts working memory load of preceding task condition.

Hum Brain Mapp. 2013 Nov;34(11):3010-22

Authors: Pyka M, Hahn T, Heider D, Krug A, Sommer J, Kircher T, Jansen A

Abstract
The conceptual notion of the so-called resting state of the brain has been recently challenged by studies indicating a continuing effect of cognitive processes on subsequent rest. In particular, activity in posterior parietal and medial prefrontal areas has been found to be modulated by preceding experimental conditions. In this study, we investigated which brain areas show working memory dependent patterns in subsequent baseline periods and how specific they are for the preceding experimental condition. During functional magnetic resonance imaging, 94 subjects performed a letter-version of the n-back task with the conditions 0-back and 2-back followed by a low-level baseline in which subjects had to passively observe the letters appearing. In a univariate analysis, 2-back served as control condition while 0-back, baseline after 0-back and baseline after 2-back were modeled as regressors to test for activity changes between both baseline conditions. Additionally, we tested, using Gaussian process classifiers, the recognition of task condition from functional images acquired during baseline. Besides the expected activity changes in the precuneus and medial prefrontal cortex, we found differential activity in the thalamus, putamen, and postcentral gyrus that were affected by the preceding task. The multivariate analysis revealed that images of the subsequent baseline block contain task related patterns that yield a recognition rate of 70%. The results suggest that the influence of a cognitive task on subsequent baseline is strong and specific for some areas but not restricted to areas of the so-called default mode network.

PMID: 22696432 [PubMed - indexed for MEDLINE]

Advantages and Challenges of Small Animal Magnetic Resonance Imaging as a Translational Tool.

Thu, 05/29/2014 - 14:00

Advantages and Challenges of Small Animal Magnetic Resonance Imaging as a Translational Tool.

Neuropsychobiology. 2014 May 23;69(4):187-201

Authors: Hoyer C, Gass N, Weber-Fahr W, Sartorius A

Abstract
The utilization of magnetic resonance imaging (MRI) methods in rodent models of psychiatric disorders provides considerable benefits for the identification of disease-associated brain circuits and metabolic changes. In this review, we discuss advantages and challenges of animal MRI and provide an overview of the major structural (voxel-based morphometry and diffusion tensor imaging) and functional approaches [resting-state functional MRI (rs-fMRI), MR spectroscopy (MRS), regional cerebral blood volume measurement and arterial spin labelling] that are applied in animal MRI research. The review mainly focuses on rs-fMRI and MRS. Finally, we take a look at some recent developments and refinements in the field. © 2014 S. Karger AG, Basel.

PMID: 24863537 [PubMed - as supplied by publisher]

Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety.

Thu, 05/29/2014 - 14:00

Evolutionarily conserved prefrontal-amygdalar dysfunction in early-life anxiety.

Mol Psychiatry. 2014 May 27;

Authors: Birn RM, Shackman AJ, Oler JA, Williams LE, McFarlin DR, Rogers GM, Shelton SE, Alexander AL, Pine DS, Slattery MJ, Davidson RJ, Fox AS, Kalin NH

Abstract
Some individuals are endowed with a biology that renders them more reactive to novelty and potential threat. When extreme, this anxious temperament (AT) confers elevated risk for the development of anxiety, depression and substance abuse. These disorders are highly prevalent, debilitating and can be challenging to treat. The high-risk AT phenotype is expressed similarly in children and young monkeys and mechanistic work demonstrates that the central (Ce) nucleus of the amygdala is an important substrate. Although it is widely believed that the flow of information across the structural network connecting the Ce nucleus to other brain regions underlies primates' capacity for flexibly regulating anxiety, the functional architecture of this network has remained poorly understood. Here we used functional magnetic resonance imaging (fMRI) in anesthetized young monkeys and quietly resting children with anxiety disorders to identify an evolutionarily conserved pattern of functional connectivity relevant to early-life anxiety. Across primate species and levels of awareness, reduced functional connectivity between the dorsolateral prefrontal cortex, a region thought to play a central role in the control of cognition and emotion, and the Ce nucleus was associated with increased anxiety assessed outside the scanner. Importantly, high-resolution 18-fluorodeoxyglucose positron emission tomography imaging provided evidence that elevated Ce nucleus metabolism statistically mediates the association between prefrontal-amygdalar connectivity and elevated anxiety. These results provide new clues about the brain network underlying extreme early-life anxiety and set the stage for mechanistic work aimed at developing improved interventions for pediatric anxiety.Molecular Psychiatry advance online publication, 27 May 2014; doi:10.1038/mp.2014.46.

PMID: 24863147 [PubMed - as supplied by publisher]

Additional resources and the default mode network: Evidence of increased connectivity and decreased white matter integrity in amyotrophic lateral sclerosis.

Thu, 05/29/2014 - 14:00

Additional resources and the default mode network: Evidence of increased connectivity and decreased white matter integrity in amyotrophic lateral sclerosis.

Amyotroph Lateral Scler Frontotemporal Degener. 2014 May 27;:1-9

Authors: Heimrath J, Gorges M, Kassubek J, Müller HP, Birbaumer N, Ludolph AC, Lulé D

Abstract
In amyotrophic lateral sclerosis (ALS), cognition is affected. Cortical atrophy in frontal and temporal areas has been associated with the cognitive profile of patients. Additionally, reduced metabolic turnover and regional cerebral blood flow in frontal areas indicative of reduced neural activity have been reported for ALS. We hypothesize that functional connectivity in non-task associated functional default mode network (DMN) is associated with cognitive profile and white matter integrity. This study focused on specific cognitive tasks known to be impaired in ALS such as verbal fluency and attention, and the relationship with functional connectivity in the DMN and white matter integrity. Nine patients and 11 controls were measured with an extensive neuropsychological battery. Resting-state functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) data were acquired. Results showed that ALS patients performed significantly worse in attention and verbal fluency task. Patients showed increased functional connectivity in parahippocampal and parietal areas of the non-task associated DMN compared to controls. The more pronounced the cognitive deficits, the stronger the increase in functional connectivity in those areas. White matter integrity was reduced in frontal areas in the patients. In conclusion, increased connectivity in the DMN in parahippocampal and parietal areas might represent recruitment of accessory brain regions to compensate for dysfunctional frontal networks.

PMID: 24862983 [PubMed - as supplied by publisher]

The effects of methylphenidate on whole brain intrinsic functional connectivity.

Thu, 05/29/2014 - 14:00

The effects of methylphenidate on whole brain intrinsic functional connectivity.

Hum Brain Mapp. 2014 May 23;

Authors: Mueller S, Costa A, Keeser D, Pogarell O, Berman A, Coates U, Reiser MF, Riedel M, Möller HJ, Ettinger U, Meindl T

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

PMID: 24862742 [PubMed - as supplied by publisher]

Early life stress modulates amygdala-prefrontal functional connectivity: Implications for oxytocin effects.

Thu, 05/29/2014 - 14:00

Early life stress modulates amygdala-prefrontal functional connectivity: Implications for oxytocin effects.

Hum Brain Mapp. 2014 May 26;

Authors: Fan Y, Herrera-Melendez AL, Pestke K, Feeser M, Aust S, Otte C, Pruessner JC, Böker H, Bajbouj M, Grimm S

Abstract
Recent evidence suggests that early life stress (ELS) changes stress reactivity via reduced resting state functional connectivity (rs-FC) between amygdala and the prefrontal cortex. Oxytocin (OXT) modulates amygdala connectivity and attenuates responses to psychosocial stress, but its effect appears to be moderated by ELS. Here we first investigate the effect of ELS on amygdala-prefrontal rs-FC, and examine whether ELS-associated changes of rs-FC in this neural circuit predict its response to psychosocial stress. Secondly, we explore the joint effect of OXT and ELS on the amygdala-prefrontal circuit. Eighteen healthy young males participated in a resting-state fMRI study of OXT effects using a double-blind, randomized, placebo-controlled, within-subject crossover design. We measured the rs-FC to bilateral amygdalae and subsequently assessed changes of state anxiety and prefrontal responses to psychosocial stress. Multiple linear regressions showed that ELS, specifically emotional abuse, predicted reduced rs-FC between the right amygdala and pregenual anterior cingulate cortex (pgACC), which in turn predicted elevated state anxiety after psychosocial stress. In subjects with lower ELS scores, stronger pgACC-amygdala rs-FC predicted stronger pgACC deactivation during the psychosocial stress task, and this rest-task interaction was attenuated by OXT. In subjects with higher ELS scores however, the rest-task interaction was altered and OXT showed no significant effect. These findings highlight that ELS reduces pgACC-amygdala rs-FC and alters how rs-FC of this circuit predicts its stress responsiveness. Such changes in pgACC-amygdala functional dynamics may underlie the altered sensitivity to the effects of OXT after ELS. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.

PMID: 24862297 [PubMed - as supplied by publisher]

On nodes and modes in resting state fMRI.

Thu, 05/29/2014 - 14:00

On nodes and modes in resting state fMRI.

Neuroimage. 2014 May 23;

Authors: Friston KJ, Kahan J, Razi A, Stephan KE, Sporns O

Abstract
This paper examines intrinsic brain networks in light of recent developments in the characterisation of resting state fMRI timeseries - and simulations of neuronal fluctuations based upon the connectome. Its particular focus is on patterns or modes of distributed activity that underlie functional connectivity. We first demonstrate that the eigenmodes of functional connectivity - or covariance among regions or nodes - are the same as the eigenmodes of the underlying effective connectivity, provided we limit ourselves to symmetrical connections. This symmetry constraint is motivated by appealing to proximity graphs based upon multidimensional scaling. Crucially, the principal modes of functional connectivity correspond to the dynamically unstable modes of effective connectivity that decay slowly and show long term memory. Technically, these modes have small negative Lyapunov exponents that approach zero from below. Interestingly, the superposition of modes - whose exponents are sampled from a power law distribution - produces classical 1/f (scale free) spectra. We conjecture that the emergence of dynamical instability - that underlies intrinsic brain networks - is inevitable in any system that is separated from external states by a Markov blanket. This conjecture appeals to a free energy formulation of nonequilibrium steady-state dynamics. The common theme that emerges from these theoretical considerations is that endogenous fluctuations are dominated by a small number of dynamically unstable modes. We use this as the basis of a dynamic causal model (DCM) of resting state fluctuations - as measured in terms of their complex cross spectra. In this model, effective connectivity is parameterised in terms of eigenmodes and their Lyapunov exponents - that can also be interpreted as locations in a multidimensional scaling space. Model inversion provides not only estimates of edges or connectivity but also the topography and dimensionality of the underlying scaling space. Here, we focus on conceptual issues with simulated fMRI data and provide an illustrative application using an empirical multi-region timeseries.

PMID: 24862075 [PubMed - as supplied by publisher]

Optical imaging of disrupted functional connectivity following ischemic stroke in mice.

Thu, 05/29/2014 - 14:00

Optical imaging of disrupted functional connectivity following ischemic stroke in mice.

Neuroimage. 2014 May 23;

Authors: Bauer AQ, Kraft AW, Wright PW, Snyder AZ, Lee JM, Culver JP

Abstract
Recent human neuroimaging studies indicate that spontaneous fluctuations in neural activity, as measured by functional connectivity magnetic resonance imaging (fcMRI), are significantly affected following stroke. Disrupted functional connectivity is associated with behavioral deficits and has been linked to long-term recovery potential. FcMRI studies of stroke in rats have generally produced similar findings, although subacute cortical reorganization following focal ischemia appears to be more rapid than in humans. Similar studies in mice have not been published, most likely because fMRI in the small mouse brain is technically challenging. Extending functional connectivity methods to mouse models of stroke could provide a valuable tool for understanding the link between molecular mechanisms of stroke repair and human fcMRI findings at the systems level. We applied functional connectivity optical intrinsic signal imaging (fcOIS) to mice before and 72hours after transient middle cerebral artery occlusion (tMCAO) to examine how graded ischemic injury affects the relationship between functional connectivity and infarct volume, stimulus-induced response, and behavior. Regional changes in functional connectivity within the MCA territory were largely proportional to infarct volume. However, subcortical damage affected functional connectivity in somatosensory cortex as much as larger infarcts of cortex and subcortex. The extent of injury correlated with cortical activations following electrical stimulation of the affected forelimb and with functional connectivity in somatosensory cortex. Regional homotopic functional connectivity in motor cortex correlated with behavioral deficits measured using an adhesive patch removal test. Spontaneous hemodynamic activity within the infarct exhibited altered temporal and spectral features in comparison to intact tissue; failing to account for these regional differences significantly affected apparent post-stroke functional connectivity measures. Thus, several results were strongly dependent on how the resting-state data were processed. Specifically, global signal regression alone resulted in apparently distorted functional connectivity measures in the intact hemisphere. These distortions were corrected by regressing out multiple sources of variance, as performed in human fcMRI. We conclude that fcOIS provides a sensitive imaging modality in the murine stroke model; however, it is necessary to properly account for altered hemodynamics in injured brain to obtain accurate measures of functional connectivity.

PMID: 24862071 [PubMed - as supplied by publisher]

Atomic dynamic functional interaction patterns for characterization of ADHD.

Thu, 05/29/2014 - 14:00

Atomic dynamic functional interaction patterns for characterization of ADHD.

Hum Brain Mapp. 2014 May 23;

Authors: Ou J, Lian Z, Xie L, Li X, Wang P, Hao Y, Zhu D, Jiang R, Wang Y, Chen Y, Zhang J, Liu T

Abstract
Modeling abnormal temporal dynamics of functional interactions in psychiatric disorders has been of great interest in the neuroimaging field, and thus a variety of methods have been proposed so far. However, the temporal dynamics and disease-related abnormalities of functional interactions within specific data-driven discovered subnetworks have been rarely explored yet. In this work, we propose a novel computational framework composed of an effective Bayesian connectivity change point model for modeling functional brain interactions and their dynamics simultaneously and an effective variant of nonnegative matrix factorization for assessing the functional interaction abnormalities within subnetworks. This framework has been applied on the resting state fmagnetic resonance imaging (fMRI) datasets of 23 children with attention-deficit/hyperactivity disorder (ADHD) and 45 normal control (NC) children, and has revealed two atomic functional interaction patterns (AFIPs) discovered for ADHD and another two AFIPs derived for NC. Together, these four AFIPs could be grouped into two pairs, one common pair representing the common AFIPs in ADHD and NC, and the other abnormal pair representing the abnormal AFIPs in ADHD. Interestingly, by comparing the abnormal AFIP pair, two data-driven abnormal functional subnetworks are derived. Strikingly, by evaluating the approximation based on the four AFIPs, all of the ADHD children were successfully differentiated from NCs without any false positive. Hum Brain Mapp, 2014. © 2014 Wiley Periodicals, Inc.

PMID: 24861961 [PubMed - as supplied by publisher]