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Prediction of Brain Connectivity Map in Resting-State fMRI Data Using Shrinkage Estimator.

Tue, 04/30/2019 - 19:48
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Prediction of Brain Connectivity Map in Resting-State fMRI Data Using Shrinkage Estimator.

Basic Clin Neurosci. 2019 Mar-Apr;10(2):147-156

Authors: Nazari A, Alavimajd H, Shakeri N, Bakhshandeh M, Faghihzadeh E, Marzbani H

Abstract
Introduction: In recent years, brain functional connectivity studies are extended using the advanced statistical methods. Functional connectivity is identified by synchronous activation in a spatially distinct region of the brain in resting-state functional Magnetic Resonance Imaging (MRI) data. For this purpose there are several methods such as seed-based correlation analysis based on temporal correlation between different Regions of Interests (ROIs) or between brain's voxels of prior seed.
Methods: In the current study, test-retest Resting State functional MRI (rs-fMRI) data of 21 healthy subjects were analyzed to predict second replication connectivity map using first replication data. A potential estimator is "raw estimator" that uses the first replication data from each subject to predict the second replication connectivity map of the same subject. The second estimator, "mean estimator" uses the average of all sample subjects' connectivity to estimate the correlation map. Shrinkage estimator is made by shrinking raw estimator towards the average connectivity map of all subjects' first replicate. Prediction performance of the second replication correlation map is evaluated by Mean Squared Error (MSE) criteria.
Results: By the employment of seed-based correlation analysis and choosing precentral gyrus as the ROI over 21 subjects in the study, on average MSE for raw, mean and shrinkage estimator were 0.2169, 0.1118, and 0.1103, respectively. Also, percent reduction of MSE for shrinkage and mean estimator in comparison with raw estimator is 49.14 and 48.45, respectively.
Conclusion: Shrinkage approach has the positive effect on the prediction of functional connectivity. When data has a large between session variability, prediction of connectivity map can be improved by shrinking towards population mean.

PMID: 31031901 [PubMed]

The Brain in (Willed) Action: A Meta-Analytical Comparison of Imaging Studies on Motor Intentionality and Sense of Agency.

Tue, 04/30/2019 - 19:48
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The Brain in (Willed) Action: A Meta-Analytical Comparison of Imaging Studies on Motor Intentionality and Sense of Agency.

Front Psychol. 2019;10:804

Authors: Seghezzi S, Zirone E, Paulesu E, Zapparoli L

Abstract
Voluntary actions can be fractionated in different phenomena: from the emergence of intentions and the ensuing motor plans and actions, to the anticipation and monitoring of their outcomes, to the appreciation of their congruency with intentions and to the eventual emergence of a sense of agency. It follows that motor intention and the sense of agency should occur at different stages in the normal generation of willed actions. Both these processes have been associated with a fronto-parietal motor network, but no study has investigated to what extent the two experiences can be dissociated for the brain regions involved. To this end, we assessed the PET/fMRI literature on agency and intentionality using a meta-analytic technique based on a hierarchical clustering algorithm. Beside a shared brain network involving the meso-frontal and prefrontal regions, the middle insula and subcortical structures, we found that motor intention and the sense of agency are functionally underpinned by separable sets of brain regions: an "intentionality network," involving the rostral area of the mesial frontal cortex (middle cingulum and pre-supplementary motor area), the anterior insula and the parietal lobules, and a "self-agency network," which involves the posterior areas of the mesial frontal cortex (the SMA proper), the posterior insula, the occipital lobe and the cerebellum. We were then able to confirm this functional organization by a subsequent seed-based fMRI resting-state functional connectivity analysis, with seeds derived from the intentionality/sense of agency specific clusters of the medial wall of the frontal lobe. Our results suggest the existence of a rostro-caudal gradient within the mesial frontal cortex, with the more anterior regions linked to the concept of motor intentionality and the brain areas located more posteriorly associated with the direct monitoring between the action and its outcome. This suggestion is reinforced by the association between the sense of agency and the activation of the occipital lobes, to suggest a direct comparison between the movement and its external (e.g., visual) consequences. The shared network may be important for the integration of intentionality and agency in a coherent appreciation of self-generated actions.

PMID: 31031676 [PubMed]

Altered Local and Large-Scale Dynamic Functional Connectivity Variability in Posttraumatic Stress Disorder: A Resting-State fMRI Study.

Tue, 04/30/2019 - 19:48
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Altered Local and Large-Scale Dynamic Functional Connectivity Variability in Posttraumatic Stress Disorder: A Resting-State fMRI Study.

Front Psychiatry. 2019;10:234

Authors: Fu S, Ma X, Wu Y, Bai Z, Yi Y, Liu M, Lan Z, Hua K, Huang S, Li M, Jiang G

Abstract
Posttraumatic stress disorder (PTSD) is a psychiatric condition that can emerge after exposure to an exceedingly traumatic event. Previous neuroimaging studies have indicated that PTSD is characterized by aberrant resting-state functional connectivity (FC). However, few existing studies on PTSD have examined dynamic changes in resting-state FC related to network formation, interaction, and dissolution over time. In this study, we compared the dynamic resting-state local and large-scale FC between PTSD patients (n = 22) and healthy controls (HC; n = 22; conducted as standard deviation in resting-state local and large-scale FC over a series of sliding windows). Local dynamic FC was examined by calculating the dynamic regional homogeneity (dReHo), and large-scale dynamic FC (dFC) was investigated between regions with significant dReHo group differences. For the PTSD patients, we also investigated the relationship between symptom severity and dFC/dReHo. Our results showed that PTSD patients were characterized by I) increased dynamic (more variable) dReHo in left precuneus (PCu); II) increased dynamic (more variable) dFC between the left PCu and left insula; and III) decreased dFC between left PCu and left inferior parietal lobe (IPL), and decreased dFC between left PCu and right PCu. However, there is no significant correlation between the clinical indicators and dReHo/dFC after the family-wise-error (FWE) correction. These findings provided the initial evidence that PTSD is characterized by aberrant patterns of fluctuating communication within brain system such as the default mode network (DMN) and among different brain systems such as the salience network and the DMN.

PMID: 31031661 [PubMed]

Cognitive Training and Transcranial Direct Current Stimulation in Mild Cognitive Impairment: A Randomized Pilot Trial.

Tue, 04/30/2019 - 19:48
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Cognitive Training and Transcranial Direct Current Stimulation in Mild Cognitive Impairment: A Randomized Pilot Trial.

Front Neurosci. 2019;13:307

Authors: Das N, Spence JS, Aslan S, Vanneste S, Mudar R, Rackley A, Quiceno M, Chapman SB

Abstract
Background: Transcranial direct current stimulation (tDCS), a non-invasive stimulation, represents a potential intervention to enhance cognition across clinical populations including Alzheimer's disease and mild cognitive impairment (MCI). This randomized clinical trial in MCI investigated the effects of anodal tDCS (a-tDCS) delivered to left inferior frontal gyrus (IFG) combined with gist-reasoning training (SMART) versus sham tDCS (s-tDCS) plus SMART on measures of cognitive and neural changes in resting cerebral blood flow (rCBF). We were also interested in SMART effects on cognitive performance regardless of the tDCS group.
Methods: Twenty-two MCI participants, who completed the baseline cognitive assessment (T1), were randomized into one of two groups: a-tDCS + SMART and s-tDCS + SMART. Of which, 20 participants completed resting pCASL MRI scan to measure rCBF. Eight SMART sessions were administered over 4 weeks with a-tDCS or s-tDCS stimulation for 20 min before each session. Participants were assessed immediately (T2) and 3-months after training (T3).
Results: Significant group × time interactions showed cognitive gains at T2 in executive function (EF) measure of inhibition [DKEFS- Color word (p = 0.047)], innovation [TOSL (p = 0.01)] and on episodic memory [TOSL (p = 0.048)] in s-tDCS + SMART but not in a-tDCS + SMART group. Nonetheless, the gains did not persist for 3 months (T3) after the training. A voxel-based analysis showed significant increase in regional rCBF in the right middle frontal cortex (MFC) (cluster-wise p = 0.05, k = 1,168 mm3) in a-tDCS + SMART compared to s-tDCS + SMART. No significant relationship was observed between the increased CBF with cognition. Irrespective of group, the combined MCI showed gains at T2 in EF of conceptual reasoning [DKEFS card sort (p = 0.033)] and category fluency [COWAT (p = 0.055)], along with gains at T3 in EF of verbal fluency [COWAT (p = 0.009)].
Conclusion: One intriguing finding is a-tDCS to left IFG plus SMART increased blood flow to right MFC, however, the stimulation seemingly blocked cognitive benefits of SMART on EF (inhibition and innovation) and episodic memory compared to s-tDCS + SMART group. Although the sample size is small, this paper contributes to growing evidence that cognitive training provides a way to significantly enhance cognitive performance in adults showing memory loss, where the role of a-tDCS in augmenting these effects need further study.

PMID: 31031581 [PubMed]

Isoflurane-Induced Burst Suppression Increases Intrinsic Functional Connectivity of the Monkey Brain.

Tue, 04/30/2019 - 19:48
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Isoflurane-Induced Burst Suppression Increases Intrinsic Functional Connectivity of the Monkey Brain.

Front Neurosci. 2019;13:296

Authors: Zhang Z, Cai DC, Wang Z, Zeljic K, Wang Z, Wang Y

Abstract
Animal functional magnetic resonance imaging (fMRI) has provided key insights into the physiological mechanisms underlying healthy and diseased brain states. In non-human primates, resting-state fMRI studies are commonly conducted under isoflurane anesthesia, where anesthetic concentration is used to roughly infer anesthesia depth. However, within the recommended isoflurane concentration range (1.00-1.50%), the brain state can switch from moderate anesthesia characterized by stable slow wave (SW) electroencephalogram (EEG) signals to deep anesthesia characterized by burst suppression (BS), which is electrophysiologically distinct from the resting state. To confirm the occurrence rate of BS activity in common setting of animal fMRI study, we conducted simultaneous resting-state EEG and fMRI experiments on 16 monkeys anesthetized using 0.80-1.30% isoflurane, and detected BS activity in two of them. Datasets either featured with BS or SW activity from these two monkeys were analyzed to investigate the intrinsic functional connectivity (FC) patterns during BS. In datasets with BS activity, we observed robust coupling between the BS pattern (the binary alternation between burst and suppression activity in EEG signal) and filtered BOLD signals in most brain areas, which was associated with a non-specific enhancement in whole brain connectivity. After eliminating the BS coupling effect by regressing out the BS pattern, we detected an overall increase in FC with a few decreased connectivity compared to datasets with SW activity. These affected connections were preferentially distributed within orbitofrontal cortex, between orbitofrontal and prefrontal/cingulate/occipital cortex, and between temporal and parietal cortex. Persistence of the default mode network and recovery of thalamocortical connections were also detected under deep anesthesia with BS activity. Taken together, the observed spatially specific alterations in BS activity induced by isoflurane not only highlight the necessity of EEG monitoring and careful data preprocessing in fMRI studies on anesthetized animals, but also advance our understanding of the underlying multi-phased mechanisms of anesthesia.

PMID: 31031580 [PubMed]

Bottom-up sensory processing can induce negative BOLD responses and reduce functional connectivity in nodes of the default mode-like network in rats.

Mon, 04/29/2019 - 22:47
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Bottom-up sensory processing can induce negative BOLD responses and reduce functional connectivity in nodes of the default mode-like network in rats.

Neuroimage. 2019 Apr 25;:

Authors: Hinz R, Peeters LM, Shah D, Missault S, Belloy M, Vanreusel V, Malekzadeh M, Verhoye M, Van der Linden A, Keliris GA

Abstract
The default mode network is a large-scale brain network that is active during rest and internally focused states and deactivates as well as desynchronizes during externally oriented (top-down) attention demanding cognitive tasks. However, it is not sufficiently understood if salient stimuli, able to trigger bottom-up attentional processes, could also result in similar reduction of activity and functional connectivity in the DMN. In this study, we investigated whether bottom-up sensory processing could influence the default mode-like network (DMLN) in rats. DMLN activity was examined using block-design visual functional magnetic resonance imaging (fMRI) while its synchronization was investigated by comparing functional connectivity during a resting versus a continuously stimulated brain state by unpredicted light flashes. We demonstrated that the BOLD response in DMLN regions was decreased during visual stimulus blocks and increased during blanks. Furthermore, decreased inter-network functional connectivity between the DMLN and visual networks as well as decreased intra-network functional connectivity within the DMLN was observed during the continuous visual stimulation. These results suggest that triggering of bottom-up attention mechanisms in sedated rats can lead to a cascade similar to top-down orienting of attention in humans and is able to deactivate and desynchronize the DMLN.

PMID: 31029872 [PubMed - as supplied by publisher]

Thalamo-cortical coupling during encoding and consolidation is linked to durable memory formation.

Sun, 04/28/2019 - 19:45
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Thalamo-cortical coupling during encoding and consolidation is linked to durable memory formation.

Neuroimage. 2019 Apr 24;:

Authors: Wagner IC, van Buuren M, Fernández G

Abstract
Memory formation transforms experiences into durable engrams. The stabilization critically depends on processes during and after learning, and involves hippocampal-medial prefrontal interactions that appear to be mediated by the nucleus reuniens of the thalamus in rodents, which corresponds to the human medioventral thalamus. How this region contributes to durable memory formation in humans is, however, unclear. Furthermore, the anterior-, lateral dorsal-, and mediodorsal nuclei appear to promote mnemonic function as well. We hypothesized that durable memory formation is associated with increases in thalamo-cortical interactions during encoding and consolidation. Thirty-three human subjects underwent fMRI while studying picture-location associations. To assess consolidation, resting-state brain activity was measured after study and compared to a pre-study baseline. Memory was tested on the same day and 48 h later. While "weak" memories could only be remembered at the immediate test, "durable" memories persisted also after the delay. We found increased coupling of the medioventral-, adjacent anterior-, lateral dorsal-, and mediodorsal thalamus with the hippocampus and surrounding medial temporal lobe, as well as with anterior and posterior midline regions related to durable memory encoding. The medioventral and lateral dorsal thalamus showed increased connectivity with posterior medial and parietal cortex from baseline to post-encoding rest, positively scaling with the proportion of durable memories formed across subjects. Additionally, the lateral dorsal thalamus revealed consolidation-related coupling with the inferior temporal, retrosplenial, and medial prefrontal cortex. We suggest that thalamo-cortical cross-talk strengthens mnemonic representations at initial encoding, and that cortical coupling of specific thalamic subregions supports consolidation thereafter.

PMID: 31028921 [PubMed - as supplied by publisher]

Levodopa imparts a normalizing effect on default-mode network connectivity in non-demented Parkinson's disease.

Sat, 04/27/2019 - 19:44
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Levodopa imparts a normalizing effect on default-mode network connectivity in non-demented Parkinson's disease.

Neurosci Lett. 2019 Apr 23;:

Authors: Zhong J, Guan X, Zhong X, Cao F, Gu Q, Guo T, Zhou C, Zeng Q, Wang J, Gao T, Zhang M

Abstract
INTRODUCTION: Parkinson's disease (PD) is characterized with reduced dopamine level in the brain, resulting from the nigral degeneration. It is commonly accepted that the function of default mode network (DMN) is disturbed in PD, even in those who have no significant cognitive impairment. However, the relationship between the depletion of dopamine and DMN dysconnectivity is not fully clear. The aim of this study was to investigate the seed-based DMN connectivity and the influence of dopaminergic therapy on the DMN integrity in non-demented PD by using resting-state fMRI.
MATERIAL AND METHODS: Resting-state fMRI data was collected from 24 non-demented PD patients before and after taking levodopa and 36 healthy controls (HCs). Functional connectivity (FC) was examined by a seed-based correlation approach.
RESULTS: Compared with HCs, decreased DMN connectivity in PD patients was observed, a number of which were significantly improved after taking levodopa therapy. Moreover, by directly comparing the DMN connectivity between ON- and OFF-medication conditions, we found significantly enhanced FC in a set of regions of DMN in the ON- medication condition. Conversely, we also found that the PCC revealed decreased FC with left inferior temporal.
CONCLUSION: DMN connectivity was found to be impaired in no-demented PD patients, and levodopa has the ability to impart a normalizing effect on DMN connectivity.

PMID: 31026534 [PubMed - as supplied by publisher]

Abnormalities of interhemispheric functional connectivity in individuals with acute eye pain: a resting-state fMRI study.

Sat, 04/27/2019 - 19:44
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Abnormalities of interhemispheric functional connectivity in individuals with acute eye pain: a resting-state fMRI study.

Int J Ophthalmol. 2019;12(4):634-639

Authors: Dong ZZ, Zhu FY, Shi WQ, Shu YQ, Chen LL, Yuan Q, Lin Q, Zhu PW, Liu KC, Min YL, Ye L, Shao Y

Abstract
AIM: To study the changes of the resting state functional connectivity (rsFC) between acute eye pain (EP) subjects and healthy controls (HCs) in the two hemispheres by using voxel-mirrored homotopic connectivity (VMHC) method.
METHODS: Totally 20 patients with EP and 20 HCs were enrolled, sex, age, and education were matched, and all subjects were examined by functional magnetic resonance imaging (fMRI) scans at resting-state. The changes of rsFC between the hemispheres were evaluated by the VMHC method according to Gaussian random field (GRF) theory. In order to identify the VMHC, as biomarkers for distinguishing EP and from HC, the receiver operating characteristic curves (ROC) had been analyzed. The relationships were evaluated with Pearson correlation analysis between the mean VMHC signal values and clinical features in these patients.
RESULTS: By comparing with health subjects, the significant decreased VMHC values was observed in lingual/calcarine (Brodmann area, BA 30), precentral/postcentral gyrus (PreCG/PosCG; BA 4) and medial frontal gyrus (MFG; BA 8) (false discovery rate corrected <0.01) in the acute EP individuals. The accuracy of area under curve was excellent indicated by the ROC curve analysis of each brain regions.
CONCLUSION: Our study demonstrates preliminary evidence of disrupted interhemispheric rsFC in acute EP in sensorimotor and limbic system and somatosensory cortex, which might give some useful information for understanding the neurological mechanisms in acute EP individuals.

PMID: 31024819 [PubMed]

Persistent Quantitative Vitality of Stem Cell Graft Is Necessary for Stabilization of Functional Brain Networks After Stroke.

Sat, 04/27/2019 - 19:44
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Persistent Quantitative Vitality of Stem Cell Graft Is Necessary for Stabilization of Functional Brain Networks After Stroke.

Front Neurol. 2019;10:335

Authors: Green C, Minassian A, Vogel S, Diedenhofen M, Wiedermann D, Hoehn M

Abstract
Stem cell treatment after stroke has demonstrated substantial outcome improvement. However, monitoring of stem cell fate in vivo is still challenging and not routinely performed, yet important to quantify the role of the implanted stem cells on lesion improvement; in several studies even mortality of the graft has been reported. Resting state functional magnetic resonance imaging (rs-fMRI) is a highly sensitive imaging modality to monitor the brain-wide functional network alterations of many brain diseases in vivo. We monitor for 3 months the functional connectivity changes after intracortical stem cell engraftment in large, cortico-striatal (n = 9), and in small, striatal (n = 6) ischemic lesions in the mouse brain with non-invasive rs-fMRI on a 9.4T preclinical MRi scanner with GE-EPI sequence. Graft vitality is continuously recorded by bioluminescence imaging (BLI) roughly every 2 weeks after implantation of 300 k neural stem cells. In cortico-striatal lesions, the lesion extension induces graft vitality loss, in consequence leading to a parallel decrease of functional connectivity strength after a few weeks. In small, striatal lesions, the graft vitality is preserved for the whole observation period and the functional connectivity is stabilized at values as in the pre-stroke situation. But even here, at the end of the observation period of 3 months, the functional connectivity strength is found to decrease despite preserved graft vitality. We conclude that quantitative graft viability is a necessary but not sufficient criterion for functional neuronal network stabilization after stroke. Future studies with even longer time periods after stroke induction will need to identify additional players which have negative influence on the functional brain networks.

PMID: 31024429 [PubMed]

Sex Differences in Resting-State Functional Connectivity of the Cerebellum in Autism Spectrum Disorder.

Sat, 04/27/2019 - 19:44
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Sex Differences in Resting-State Functional Connectivity of the Cerebellum in Autism Spectrum Disorder.

Front Hum Neurosci. 2019;13:104

Authors: Smith REW, Avery JA, Wallace GL, Kenworthy L, Gotts SJ, Martin A

Abstract
Autism spectrum disorder (ASD) is more prevalent in males than females, but the underlying neurobiology of this sex bias remains unclear. Given its involvement in ASD, its role in sensorimotor, cognitive, and socio-affective processes, and its developmental sensitivity to sex hormones, the cerebellum is a candidate for understanding this sex difference. The current study used resting-state functional magnetic resonance imaging (fMRI) to investigate sex-dependent differences in cortico-cerebellar organization in ASD. We collected resting-state fMRI scans from 47 females (23 ASD, 24 controls) and 120 males (56 ASD, 65 controls). Using a measure of global functional connectivity (FC), we ran a linear mixed effects analysis to determine whether there was a sex-by-diagnosis interaction in resting-state FC. Subsequent seed-based analyses from the resulting clusters were run to clarify the global connectivity effects. Two clusters in the bilateral cerebellum exhibited a diagnosis-by-sex interaction in global connectivity. These cerebellar clusters further showed a pattern of interaction with regions in the cortex, including bilateral fusiform, middle occipital, middle frontal, and precentral gyri, cingulate cortex, and precuneus. Post hoc tests revealed a pattern of cortico-cerebellar hyperconnectivity in ASD females and a pattern of hypoconnectivity in ASD males. Furthermore, cortico-cerebellar FC in females more closely resembled that of control males than that of control females. These results shed light on the sex-specific pathophysiology of ASD and are indicative of potentially divergent neurodevelopmental trajectories for each sex. This sex-dependent, aberrant cerebellar connectivity in ASD might also underlie some of the motor and/or socio-affective difficulties experienced by members of this population, but the symptomatic correlate(s) of these brain findings remain unknown. Clinical Trial Registration: www.ClinicalTrials.gov, NIH Clinical Study Protocol 10-M-0027 (ZIA MH002920-09) identifier #NCT01031407.

PMID: 31024276 [PubMed]

Multilevel Mapping of Sexual Dimorphism in Intrinsic Functional Brain Networks.

Sat, 04/27/2019 - 19:44
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Multilevel Mapping of Sexual Dimorphism in Intrinsic Functional Brain Networks.

Front Neurosci. 2019;13:332

Authors: de Lacy N, McCauley E, Kutz JN, Calhoun VD

Abstract
Differences in cognitive performance between males and females are well-described, most commonly in certain spatial and language tasks. Sex-related differences in cognition are relevant to the study of the neurotypical brain and to neuropsychiatric disorders, which exhibit prominent disparities in the incidence, prevalence and severity of symptoms between men and women. While structural dimorphism in the human brain is well-described, controversy exists regarding the existence and degree of sex-related differences in brain function. We analyzed resting-state functional MRI from 650 neurotypical young adults matched for age and sex to determine the degree of sexual dimorphism present in intrinsic functional networks. Multilevel modeling was pursued to create 8-, 24-, and 51-network models of whole-brain data to quantify sex-related effects in network activity with increasing resolution. We determined that sexual dimorphism is present in the majority of intrinsic brain networks and affects ∼0.5-2% of brain locations surveyed in the three whole-brain network models. It is particularly common in task-positive control networks and is pervasive among default mode networks. The size of sex-related effects varied by network but can be moderate or even large in size. Female > male effects were on average larger, but male > female effects spread across greater network territory. Using a novel methodology, we mapped dimorphic locations to meta-analytic association test maps derived from task fMRI, demonstrating that the neurocognitive footprint of intrinsic neural correlates is much larger in males. All results were replicated in a motion-matched sub-sample. Our findings argue that sex is an important biological variable in human brain function and suggest that observed differences in neurocognitive performance have identifiable intrinsic neural correlates.

PMID: 31024243 [PubMed]

Altered structural and causal connectivity in frontal lobe epilepsy.

Sat, 04/27/2019 - 19:44
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Altered structural and causal connectivity in frontal lobe epilepsy.

BMC Neurol. 2019 Apr 25;19(1):70

Authors: Klugah-Brown B, Luo C, Peng R, He H, Li J, Dong L, Yao D

Abstract
BACKGROUND: Albeit the few resting-state fMRI neuroimaging studies in frontal lobe epilepsy (FLE) patients, these studies focused on functional connectivity. The aim of this current study was to examine the effective connectivity based on voxel-based morphometry in FLE patients.
METHODS: Resting-state structural and functional magnetic resonance imaging (fMRI) data were acquired from 19 FLE patients and 19 age and gender-matched healthy controls using the 3.0 Tesla magnetic resonance imaging (3.0 T MRI). The investigations were done by acquiring the structural information through voxel-based morphometry, then based on the seed obtained, Granger causality analysis was used to evaluate the causal flow of the designated seed to and from other significant voxels.
RESULTS: Our results showed altered structural and effective connectivity. Compared with healthy controls, FLE patients showed reduced grey matter volume in bilateral putamen and right caudate as well as altered causality with increased, and decreased causal outflow from the right caudate (seed region) to inferior frontal gyrus-triangular, from bilateral putamen (seed regions) to right middle frontal gyrus and frontal gyrus medial-orbital representing the frontal executive areas, respectively. Also, significantly increased and decreased inflow from left calcarine to right caudate and from cerebellum_6 and vermis_6 to bilateral putamen, respectively. Moreover, we found that the causal alterations to and from the seed regions (from vermis_6 to right putamen and from left putamen to right middle frontal gyrus) negatively correlated with clinical scores (duration of epilepsy).
CONCLUSIONS: The findings point to the impairment within the executive and motor-controlled system including the cerebellum, frontal, caudate and putamen regions in FLE patients. These results would therefore enhance our understanding of structural and effective mechanisms in FLE.

PMID: 31023252 [PubMed - in process]

Altered spontaneous brain activity in retinal vein occlusion as determined by regional homogeneity: a resting-state fMRI study.

Sat, 04/27/2019 - 19:44
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Altered spontaneous brain activity in retinal vein occlusion as determined by regional homogeneity: a resting-state fMRI study.

Acta Radiol. 2019 Apr 25;:284185119845089

Authors: Wen SM, Min YL, Yuan Q, Li B, Lin Q, Zhu PW, Shi WQ, Shu YQ, Shao Y, Zhou Q

Abstract
BACKGROUND: Retinal vein occlusion (RVO) is among the commonest retinal vascular conditions that can cause severe visual loss. However, the relationship between RVO and altered spontaneous brain activity is still unknown.
PURPOSE: To apply regional homogeneity (ReHo) for the evaluation of abnormal brain activity in patients with RVO and explore the relationship between anomalous cerebral activity and behavioral manifestations.
MATERIAL AND METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) was performed in 26 patients with RVO (12 men, 14 women) and 24 healthy controls (12 men, 12 women) matched by age, sex, and education. ReHo was used to evaluate the local characteristics of spontaneous brain activity. The receiver operating characteristic (ROC) curve was applied to classify RVO and healthy control characteristics. Pearson correlation analysis was used to assess the relationship between the ReHo value of specific brain regions and clinical manifestations in RVO patients.
RESULTS: ReHo values of the right posterior lobe of the cerebellum, fusiform gyrus, and right inferior temporal gyrus of patients with RVO were remarkably higher than those of controls (P < 0.05). ReHo values of the right cuneus in patients with RVO were significantly lower than those of controls (P < 0.05). ROC curve analysis of each brain region revealed a perfect accuracy of the areas under the curve (AUC). There was a negative correlation between the ReHo values of some regions and clinical manifestations.
CONCLUSION: RVO may cause dysfunction in many brain regions, which may help reveal the neural mechanisms underlying RVO.

PMID: 31023069 [PubMed - as supplied by publisher]

Investigating the impact of autocorrelation on time-varying connectivity.

Fri, 04/26/2019 - 19:41
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Investigating the impact of autocorrelation on time-varying connectivity.

Neuroimage. 2019 Apr 22;:

Authors: Honari H, Choe AS, Pekar JJ, Lindquist MA

Abstract
In recent years, a number of studies have reported on the existence of time-varying functional connectivity (TVC) in resting-state functional magnetic resonance imaging (rs-fMRI) data. The sliding-window technique is currently one of the most commonly used methods to estimate TVC. Although previous studies have shown that autocorrelation can negatively impact estimates of static functional connectivity, its impact on TVC estimates is not well known at this time. In this paper, we show both theoretically and empirically that the existence of autocorrelation within a time series can inflate the sampling variability of TVC estimated using the sliding-window technique. This can in turn increase the risk of misinterpreting noise as true TVC and negatively impact subsequent estimation of whole-brain time-varying FC profiles, or "brain states". The latter holds as more variable input measures lead to more variable output measures in the state estimation procedure. Finally, we demonstrate that prewhitening the data prior to analysis can lower the variance of the estimated TVC and improve brain state estimation. These results suggest that careful consideration is required when making inferences on TVC.

PMID: 31022568 [PubMed - as supplied by publisher]

Replicability of Neural and Behavioral Measures of Tinnitus Handicap in Civilian and Military Populations: Preliminary Results.

Fri, 04/26/2019 - 19:41
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Replicability of Neural and Behavioral Measures of Tinnitus Handicap in Civilian and Military Populations: Preliminary Results.

Am J Audiol. 2019 Apr 22;28(1S):191-208

Authors: Husain FT, Schmidt SA, Tai Y, Granato EC, Ramos P, Sherman P, Esquivel C

Abstract
Purpose In the past decade, resting-state functional connectivity, acquired using functional magnetic resonance imaging (fMRI), has emerged as a popular measure of tinnitus, especially as related to self-reported handicap or psychological reaction. The goal of this study was to assess replicability of neural correlates of tinnitus, namely, resting-state functional connectivity, in the same individuals acquired over 2 sessions. Method Data were collected at 2 different sites (University of Illinois at Urbana-Champaign and Joint Base San Antonio Wilford Hall Ambulatory Surgical Center) using similar 3T magnets and similar data acquisition paradigms. Thirty-six patients (all civilians) were scanned using resting-state fMRI at the University of Illinois at Urbana-Champaign. Ten patients, active-duty Service members and Veterans, were scanned at the Wilford Hall Ambulatory Surgical Center and the Department of Defense Hearing Center of Excellence. Each participant was scanned twice, a week apart, using identical protocols of 10 min resting-state fMRI. Results Tinnitus handicap scores using the Tinnitus Functional Index and the Tinnitus Primary Function Questionnaire ranged between no or mild handicap to moderately severe handicap but did not significantly differ between visits. We examined the default mode, dorsal attention, and auditory resting-state networks and found that the strength of the within-network functional connections across visit was similar for the attention and default mode networks but not for the auditory network. In addition, the functional connection between the attention network and precuneus, a region of the default mode network, was also replicable across visits. Conclusions Our results show that resting-state fMRI measures are replicable and reliable in patients with a subjective condition, although some networks and functional connections may be more stable than others. This paves the way for using resting-state fMRI to measure the efficacy of tinnitus interventions and as a tool to help propose better management options.

PMID: 31022364 [PubMed - in process]

An Investigation of Brain Functional Connectivity by Form of Craniosynostosis.

Fri, 04/26/2019 - 19:41
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An Investigation of Brain Functional Connectivity by Form of Craniosynostosis.

J Craniofac Surg. 2019 Apr 18;:

Authors: Sun AH, Eilbott J, Chuang C, Yang JF, Brooks ED, Beckett J, Steinbacher DM, Pelphrey K, Persing JA

Abstract
PURPOSE: Long-term neurocognitive sequelae of nonsyndromic craniosynostosis (NSC) patients are just beginning to be clarified. This study uses functional MRI (fMRI) to determine if there is evidence of altered brain functional connectivity in NSC, and whether these aberrations vary by form of synostosis.
METHODS: Twenty adolescent participants with surgically treated NSC (10 sagittal synostosis, 5 right unilateral coronal synostosis [UCS], 5 metopic synostosis [MSO]) were individually matched to controls by age, gender, and handedness. A subgroup of MSO was classified as severe metopic synostosis (SMS) based on the endocranial bifrontal angle. Resting state fMRI was acquired in a 3T Siemens TIM Trio scanner (Erlangen, Germany), and data were motion corrected and then analyzed with BioImage Suite (Yale School of Medicine). Resulting group-level t-maps were cluster corrected with nonparametric permutation tests. A region of interest analysis was performed based on the left Brodmann's Areas 7, 39, and 40.
RESULTS: Sagittal synostosis had decreased whole-brain intrinsic connectivity compared to controls in the superior parietal lobules and the angular gyrus (P = 0.071). Unilateral coronal synostosis had decreased intrinsic connectivity throughout the prefrontal cortex (P = 0.031). The MSO cohort did not have significant findings on intrinsic connectivity, but the SMS subgroup had significantly decreased connectivity among multiple subcortical structures.
CONCLUSION: Sagittal synostosis had decreased connectivity in regions associated with visuomotor integration and attention, while UCS had decreased connectivity in circuits crucial in executive function and cognition. Finally, severity of metopic synostosis may influence the degree of neurocognitive aberration. This study provides data suggestive of long-term sequelae of NSC that varies by suture type, which may underlie different phenotypes of neurocognitive impairment.

PMID: 31022138 [PubMed - as supplied by publisher]

Restricted, Repetitive, and Stereotypical Patterns of Behavior in Autism - an fMRI Perspective.

Fri, 04/26/2019 - 19:41
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Restricted, Repetitive, and Stereotypical Patterns of Behavior in Autism - an fMRI Perspective.

IEEE Trans Neural Syst Rehabil Eng. 2019 Apr 22;:

Authors: Noriega G

Abstract
The main objective of this work is to determine whether resting-state fMRI can identify functional connectivity differences between individuals with autism who experience severe issues with restricted, repetitive and stereotypical behaviors, those who experience only mild issues, and controls. We use resting-state fMRI data from the ABIDE-I preprocessed repository, with participants grouped according to their ADI-R Restricted, Repetitive, and Stereotyped Patterns of Behavior Subscore. Three processing methods are used for analysis. A time-correlation approach establishes a basic baseline, and we introduce a method based on sliding time windows, with means across time adjusted to consider the fraction of time the correlation measure is above/below average. We complement these with a band-limited coherence approach. For completeness, preprocessing schemes with and without global signal regression are considered. Our results are in line with recent ones which find both over-and under-connectivities in the autistic brain. We find there are indeed significant differences in connectivity between various regions that differentiate between ASD subjects with severe stereotypical/restrictive behavior issues, those with only mild issues, and controls. Interestingly, for some regions the "signature" of subjects in the milder of the ASD groups appears to be distinct (i.e., over-or under-connected) relative to both the more severe ASD group and the controls.

PMID: 31021772 [PubMed - as supplied by publisher]

Differential sensitivity of structural, diffusion, and resting-state functional MRI for detecting brain alterations and verbal memory impairment in temporal lobe epilepsy.

Fri, 04/26/2019 - 19:41
Related Articles

Differential sensitivity of structural, diffusion, and resting-state functional MRI for detecting brain alterations and verbal memory impairment in temporal lobe epilepsy.

Epilepsia. 2019 Apr 25;:

Authors: Chang YA, Marshall A, Bahrami N, Mathur K, Javadi SS, Reyes A, Hegde M, Shih JJ, Paul BM, Hagler DJ, McDonald CR

Abstract
OBJECTIVES: Temporal lobe epilepsy (TLE) is known to affect large-scale gray and white matter networks, and these network changes likely contribute to the verbal memory impairments observed in many patients. In this study, we investigate multimodal imaging patterns of brain alterations in TLE and evaluate the sensitivity of different imaging measures to verbal memory impairment.
METHODS: Diffusion tensor imaging (DTI), volumetric magnetic resonance imaging (vMRI), and resting-state functional MRI (rs-fMRI) were evaluated in 46 patients with TLE and 33 healthy controls to measure patterns of microstructural, structural, and functional alterations, respectively. These measurements were obtained within the white matter directly beneath neocortex (ie, superficial white matter [SWM]) for DTI and across neocortex for vMRI and rs-fMRI. The degree to which imaging alterations within left medial temporal lobe/posterior cingulate (LMT/PC) and left lateral temporal regions were associated with verbal memory performance was evaluated.
RESULTS: Patients with left TLE and right TLE both demonstrated pronounced microstructural alterations (ie, decreased fractional anisotropy [FA] and increased mean diffusivity [MD]) spanning the entire frontal and temporolimbic SWM, which were highly lateralized to the ipsilateral hemisphere. Conversely, reductions in cortical thickness in vMRI and alterations in the magnitude of the rs-fMRI response were less pronounced and less lateralized than the microstructural changes. Both stepwise regression and mediation analyses further revealed that FA and MD within SWM in LMT/PC regions were the most robust predictors of verbal memory, and that these associations were independent of left hippocampal volume.
SIGNIFICANCE: These findings suggest that microstructural loss within the SWM is pronounced in patients with TLE, and injury to the SWM within the LMT/PC region plays a critical role in verbal memory impairment.

PMID: 31020649 [PubMed - as supplied by publisher]

Resting fMRI as an alternative for task-based fMRI for language lateralization in temporal lobe epilepsy patients: a study using independent component analysis.

Fri, 04/26/2019 - 19:41
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Resting fMRI as an alternative for task-based fMRI for language lateralization in temporal lobe epilepsy patients: a study using independent component analysis.

Neuroradiology. 2019 Apr 25;:

Authors: Smitha KA, Arun KM, Rajesh PG, Thomas B, Radhakrishnan A, Sarma PS, Kesavadas C

Abstract
PURPOSE: Our aim is to investigate whether rs-fMRI can be used as an effective technique to study language lateralization. We aim to find out the most appropriate language network among different networks identified using ICA.
METHODS: Fifteen healthy right-handed subjects, sixteen left, and sixteen right temporal lobe epilepsy patients prospectively underwent MR scanning in 3T MRI (GE Discovery™ MR750w), using optimized imaging protocol. We obtained task-fMRI data using a visual-verb generation paradigm. Rs-fMRI and language-fMRI analysis were conducted using FSL software. Independent component analysis (ICA) was used to estimate rs-fMRI networks. Dice coefficient was calculated to examine the similarity in activated voxels of a common language template and the rs-fMRI language networks. Laterality index (LI) was calculated from the task-based language activation and rs-fMRI language network, for a range of LI thresholds at different z scores.
RESULTS: Measurement of hemispheric language dominance with rs-fMRI was highly concordant with task-fMRI results. Among the evaluated z scores for a range of LI thresholds, rs-fMRI yielded a maximum accuracy of 95%, a sensitivity of 83%, and specificity of 92.8% for z = 2 at 0.05 LI threshold.
CONCLUSION: The present study suggests that rs-fMRI networks obtained using ICA technique can be used as an alternative for task-fMRI language laterality. The novel aspect of the work is suggestive of optimal thresholds while applying rs-fMRI, is an important endeavor given that many patients with epilepsy have co-morbid cognitive deficits. Thus, an accurate method to determine language laterality without requiring a patient to complete the language task would be advantageous.

PMID: 31020344 [PubMed - as supplied by publisher]