•Harmonization with rotation invariant spherical harmonic (RISH) features and network thresholding improve cross-site consistency of dMRI-based brain networks.•RISH harmonization enables multicentre ...data pooling to increase sample size and infer patterns of network injury with improved sensitivity.•When network thresholding is applied in combination with harmonization, false positive connections are removed from the network, thus improving the precision of the detected patterns of injury.
To investigate if network thresholding and raw data harmonization improve consistency of diffusion MRI (dMRI)-based brain networks while also increasing precision and sensitivity to detect disease effects in multicentre datasets.
Brain networks were reconstructed from dMRI of five samples with cerebral small vessel disease (SVD; 629 patients, 166 controls), as a clinically relevant exemplar condition for studies on network integrity. We evaluated consistency of network architecture in age-matched controls, by calculating cross-site differences in connection probability and fractional anisotropy (FA). Subsequently we evaluated precision and sensitivity to disease effects by identifying connections with low FA in sporadic SVD patients relative to controls, using more severely affected patients with a pure form of genetically defined SVD as reference.
In controls, thresholding and harmonization improved consistency of network architecture, minimizing cross-site differences in connection probability and FA. In patients relative to controls, thresholding improved precision to detect disrupted connections by removing false positive connections (precision, before: 0.09–0.19; after: 0.38–0.70). Before harmonization, sensitivity was low within individual sites, with few connections surviving multiple testing correction (k = 0–25 connections). Harmonization and pooling improved sensitivity (k = 38), while also achieving higher precision when combined with thresholding (0.97).
We demonstrated that network consistency, precision and sensitivity to detect disease effects in SVD are improved by thresholding and harmonization. We recommend introducing these techniques to leverage large existing multicentre datasets to better understand the impact of disease on brain networks.
We describe the results of a functional and structural brain connectivity analysis comparing a homogeneous group of 10 young adults with Williams Syndrome (WS; 3 females, age 20. 7 ± 3.7 years, age ...range 17.4-28.7 years) to a group of 18 controls of similar age (3 females, age 23.9 ± 4.4 years, age range 16.8-30.2), with the aim to increase knowledge of the structure - function relationship in WS. Subjects underwent a 3T brain MRI exam including anatomical, functional (resting state) and structural (diffusion MRI) sequences. We found convergent anomalies in structural and functional connectivity in the WS group. Altered Fractional Anisotropy (FA) values in parieto-occipital regions were associated with increased connectivity in the antero-posterior pathways linking parieto-occipital with frontal regions. The analysis of resting state data showed altered functional connectivity in the WS group in main brain networks (default mode, executive control and dorsal attention, sensori-motor, fronto-parietal, ventral stream). The combined analysis of functional and structural connectivity displayed a different pattern in the two groups: in controls the highest agreement was found in frontal and visual areas, whereas in WS patients in posterior regions (parieto-occipital and temporal areas). These preliminary findings may reflect an altered "wiring" of the brain in WS, which can be driven by hyper-connectivity of the posterior regions as opposed to disrupted connectivity in the anterior areas, supporting the hypothesis that a different brain (organization) could be associated with a different (organization of) behavior in Williams Syndrome.
•RISH harmonization is applicable to multicentre dMRI of elderly subjects with SVD.•Harmonization removes site-differences in dMRI metrics in matched controls.•Associations between dMRI metrics and ...SVD markers in patients are preserved.•Harmonized scans can be pooled to into a single large dataset to increased power.
Acquisition-related differences in diffusion magnetic resonance imaging (dMRI) hamper pooling of multicentre data to achieve large sample sizes. A promising solution is to harmonize the raw diffusion signal using rotation invariant spherical harmonic (RISH) features, but this has not been tested in elderly subjects. Here we aimed to establish if RISH harmonization effectively removes acquisition-related differences in multicentre dMRI of elderly subjects with cerebral small vessel disease (SVD), while preserving sensitivity to disease effects.
Five cohorts of patients with SVD (N = 397) and elderly controls (N = 175) with 3 Tesla MRI on different systems were included. First, to establish effectiveness of harmonization, the RISH method was trained with data of 13 to 15 age and sex-matched controls from each site. Fractional anisotropy (FA) and mean diffusivity (MD) were compared in matched controls between sites using tract-based spatial statistics (TBSS) and voxel-wise analysis, before and after harmonization. Second, to assess sensitivity to disease effects, we examined whether the contrast (effect sizes of FA, MD and peak width of skeletonized MD - PSMD) between patients and controls within each site remained unaffected by harmonization. Finally, we evaluated the association between white matter hyperintensity (WMH) burden, FA, MD and PSMD using linear regression analyses both within individual cohorts as well as with pooled scans from multiple sites, before and after harmonization.
Before harmonization, significant differences in FA and MD were observed between matched controls of different sites (p < 0.05). After harmonization these site-differences were removed. Within each site, RISH harmonization did not alter the effect sizes of FA, MD and PSMD between patients and controls (relative change in Cohen’s d = 4 %) nor the strength of association with WMH volume (relative change in R2 = 2.8 %). After harmonization, patient data of all sites could be aggregated in a single analysis to infer the association between WMH volume and FA (R2 = 0.62), MD (R2 = 0.64), and PSMD (R2 = 0.60).
We showed that RISH harmonization effectively removes acquisition-related differences in dMRI of elderly subjects while preserving sensitivity to SVD-related effects. This study provides proof of concept for future multicentre SVD studies with pooled datasets.
Mood has been argued to impact the breadth of human attention, but the empirical evidence supporting this claim remains shaky. Gable and Harmon-Jones (2008) have attributed previous empirical ...inconsistencies regarding the effect of mood on attentional breath to a critical role of approach/avoidance motivation. They demonstrated that the combination of positive affect with high, but not with low, motivational intensity improves performance during processing local information and impairs performance during processing global information. The latter, but not the former, was replicated by Domachowska et al. (2016). Since we were interested in the modulation of attention by valence and motivation, and considering the inconsistencies in the findings, we replicated the critical experiments of both studies in four online experiments but found no significant effect of either valence or motivational intensity on attention. Taken together, our evidence casts doubt on a systematic relationship between mood or motivation on the one hand and global/local processing on the other.
Mood has been argued to impact the breadth of human attention, but the empirical evidence supporting this claim remains shaky. Gable and Harmon-Jones (2008) have attributed previous empirical ...inconsistencies regarding the effect of mood on attentional breath to a critical role of approach/avoidance motivation. They demonstrated that the combination of positive affect with high, but not with low, motivational intensity improves performance during processing local information and impairs performance during processing global information. The latter, but not the former, was replicated by Domachowska et al. (2016). Since we were interested in the modulation of attention by valence and motivation, and considering the inconsistencies in the findings, we replicated the critical experiments of both studies in four online experiments but found no significant effect of either valence or motivational intensity on attention. Taken together, our evidence casts doubt on a systematic relationship between mood or motivation on the one hand and global/local processing on the other.
During long-duration spaceflight, astronauts experience headward fluid shifts and expansion of the cerebral perivascular spaces (PVS). A major limitation to our understanding of the changes in brain ...structure and physiology induced by spaceflight stems from the logistical difficulties of studying astronauts. The current study aimed to determine whether PVS changes also occur on Earth with the spaceflight analog head-down tilt bed rest (HDBR). We examined how the number and morphology of magnetic resonance imaging-visible PVS (MV-PVS) are affected by HDBR with and without elevated carbon dioxide (CO
). These environments mimic the headward fluid shifts, body unloading, and elevated CO
observed aboard the International Space Station. Additionally, we sought to understand how changes in MV-PVS are associated with signs of Spaceflight Associated Neuro-ocular Syndrome (SANS), ocular structural alterations that can occur with spaceflight. Participants were separated into two bed rest campaigns: HDBR (60 days) and HDBR + CO
(30 days with elevated ambient CO
). Both groups completed multiple magnetic resonance image acquisitions before, during, and post-bed rest. We found that at the group level, neither spaceflight analog affected MV-PVS quantity or morphology. However, when taking into account SANS status, persons exhibiting signs of SANS showed little or no MV-PVS changes, whereas their No-SANS counterparts showed MV-PVS morphological changes during the HDBR + CO
campaign. These findings highlight spaceflight analogs as models for inducing changes in MV-PVS and implicate MV-PVS dynamic compliance as a mechanism underlying SANS. These findings may lead to countermeasures to mitigate health risks associated with human spaceflight.
Mood has been argued to impact the breadth of human
attention, but the empirical evidence supporting this claim remains shaky. Gable
and Harmon-Jones (2008) have attributed previous empirical ...inconsistencies
regarding the effect of mood on attentional breath to a critical role of
approach/avoidance motivation. They demonstrated that the combination of
positive affect with high, but not with low, motivational intensity improves
performance during processing local information and impairs performance during
processing global information. The latter, but not the former, was replicated by
Domachowska et al. (2016). Since we were interested in the modulation of
attention by valence and motivation, and considering the inconsistencies in the
findings, we replicated the critical experiments of both studies in four online
experiments but found no significant effect of either valence or motivational
intensity on attention. Taken together, our evidence casts doubt on a systematic
relationship between mood or motivation on the one hand and global/local
processing on the other.
Complementary aspects of tissue microstructure can be studied with diffusion‐weighted imaging (DWI). However, there is no consensus on how to design a diffusion acquisition protocol for multiple ...models within a clinically feasible time. The purpose of this study is to provide a flexible framework that is able to optimize the shell acquisition protocol given a set of DWI models. Eleven healthy subjects underwent an extensive DWI acquisition protocol, including 15 candidate shells, ranging from 10 to 3500 s/mm2. The proposed framework aims to determine the optimized acquisition scheme (OAS) with a data‐driven procedure minimizing the squared error of model‐estimated parameters. We tested the proposed method over five heterogeneous DWI models exploiting both low and high b‐values (i.e., diffusion tensor imaging DTI, free water, intra‐voxel incoherent motion IVIM, diffusion kurtosis imaging DKI, and neurite orientation dispersion and density imaging NODDI). A voxel‐level and region of interest (ROI)‐level analysis was conducted over the white matter and in 48 fiber bundles, respectively. Results showed that acquiring data for the five abovementioned models via OAS requires 14 min, compared with 35 min for the joint recommended acquisition protocol. The parameters derived from the reference acquisition scheme and the OAS are comparable in terms of estimated values, noise, and tissue contrast. Furthermore, the power analysis showed that the OAS retains the potential sensitivity to group‐level differences in the parameters of interest, with the exception of the free water model. Overall, there is a linear correspondence (R2 = 0.91) between OAS and reference‐derived parameters. In conclusion, the proposed framework optimizes the shell acquisition scheme for a given set of DWI models (i.e., DTI, free water, IVIM, DKI, and NODDI), combining low and high b‐values while saving acquisition time.
The proposed framework optimizes the DWI shells acquisition strategy, enabling the quantification of multiple models within a clinically feasible acquisition time. We tested five popular models, including low b‐values models (free water and IVIM), high b‐values models (DKI and NODDI), and the diffusion tensor model (DTI).
Cerebral small vessel diseases (SVDs) are a major cause of stroke and dementia. Yet, specific treatment strategies are lacking in part because of a limited understanding of the underlying disease ...processes. There is therefore an urgent need to study SVDs at their core, the small vessels themselves.
This paper presents the rationale and design of the ZOOM@SVDs study, which aims to establish measures of cerebral small vessel dysfunction on 7T MRI as novel disease markers of SVDs.
ZOOM@SVDs is a prospective observational cohort study with two years follow-up. ZOOM@SVDs recruits participants with Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL, N = 20), sporadic SVDs (N = 60), and healthy controls (N = 40). Participants undergo 7T brain MRI to assess different aspects of small vessel function including small vessel reactivity, cerebral perforating artery flow, and pulsatility. Extensive work-up at baseline and follow-up further includes clinical and neuropsychological assessment as well as 3T brain MRI to assess conventional SVD imaging markers. Measures of small vessel dysfunction are compared between patients and controls, and related to the severity of clinical and conventional MRI manifestations of SVDs.
ZOOM@SVDs will deliver novel markers of cerebral small vessel function in patients with monogenic and sporadic forms of SVDs, and establish their relation with disease burden and progression. These small vessel markers can support etiological studies in SVDs and may serve as surrogate outcome measures in future clinical trials to show target engagement of drugs directed at the small vessels.
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