The effects of multi-echo fMRI combination and rapid T2*-mapping on offline and real-time BOLD sensitivity.

A variety of strategies are used to combine multi-echo functional magnetic resonance imaging (fMRI) data, yet recent literature lacks a systematic comparison of the available options. Here we compare six different approaches derived from multi-echo data and evaluate their influences on BOLD sensitivity for offline and in particular real-time use cases: a single-echo time series (based on Echo 2), the real-time T2*-mapped time series (T2*FIT) and four combined time series (T2*-weighted, tSNR-weighted, TE-weighted, and a new combination scheme termed T2*FIT-weighted). We compare the influences of these six multi-echo derived time series on BOLD sensitivity using a healthy participant dataset (N = 28) with four task-based fMRI runs and two resting state runs. We show that the T2*FIT-weighted combination yields the largest increase in temporal signal-to-noise ratio across task and resting state runs. We demonstrate additionally for all tasks that the T2*FIT time series consistently yields the largest offline effect size measures and real-time region-of-interest based functional contrasts and temporal contrast-to-noise ratios. These improvements show the promising utility of multi-echo fMRI for studies employing real-time paradigms, while further work is advised to mitigate the decreased tSNR of the T2*FIT time series. We recommend the use and continued exploration of T2*FIT for offline task-based and real-time region-based fMRI analysis. Supporting information includes: a data repository (https://dataverse.nl/dataverse/rt-me-fmri), an interactive web-based application to explore the data (https://rt-me-fmri.herokuapp.com/), and further materials and code for reproducibility (https://github.com/jsheunis/rt-me-fMRI).

Treatment with Diazepam in Acute Stroke Prevents Poststroke Seizures: A Substudy of the EGASIS Trial.

OBJECTIVE: The frequency of seizures after stroke is high, with a severe impact on the quality of life. However, little is known about their prevention. Therefore, we investigated whether early administration of diazepam prevents the development of seizures in acute stroke patients. METHODS: We performed a substudy of the EGASIS trial, a multicenter double-blind, randomized trial in which acute stroke patients were treated with diazepam or placebo for 3 days. Follow-up was after 2 weeks and 3 months. The occurrence of seizures was registered prospectively as one of the prespecified secondary outcomes. RESULTS: 784 EGASIS patients were eligible for this substudy (389 treated with diazepam [49.6%] and 395 treated with placebo [50.4%]). Seizures were reported in 19 patients (2.4% of the total patient group). Seizures occurred less frequently in patients treated with diazepam (1.5 vs. 3.3% in the placebo group); however, this difference was only statistically significant in patients with a cortical anterior circulation infarction (0.9% in the diazepam group vs. 4.6% in the placebo group, incidence rate ratio 0.20, 95% CI: 0.05-0.78, p = 0.02, NNT = 27). CONCLUSION: We found that a 3-day treatment with diazepam after acute cortical anterior circulation stroke prevents the occurrence of seizures in the first 3 months following stroke.

Correction to: Towards a Better Understanding of Cognitive Deficits in Absence Epilepsy: a Systematic Review and Meta-Analysis.

Due to an error during the editorial phase, a correction regarding Fig. 2 is added to the original article: "Towards a Better Understanding of Cognitive Deficits in Absence Epilepsy: a Systematic Review and Meta-Analysis". Please see below correct Fig. 2.

Indirect frontocingulate structural connectivity predicts clinical response to accelerated rTMS in major depressive disorder

Background: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment for major depressive disorder (MDD), but its clinical efficacy remains rather modest. One reason for this could be that the propagation of rTMS effects via structural connections from the stimulated area to deeper brain structures (such as the cingulate cortices) is suboptimal. Methods: We investigated whether structural connectivity ­ derived from diffusion MRI data ­ could serve as a biomarker to predict treatment response. We hypothesized that stronger structural connections between the patient-specific stimulation position in the left dorsolateral prefrontal cortex (dlPFC) and the cingulate cortices would predict better clinical outcomes. We applied accelerated intermittent theta burst stimulation (aiTBS) to the left dlPFC in 40 patients with MDD. We correlated baseline structural connectivity, quantified using various metrics (fractional anisotropy, mean diffusivity, tract density, tract volume and number of tracts), with changes in depression severity scores after aiTBS. Results: Exploratory results (p < 0.05) showed that structural connectivity between the patient-specific stimulation site and the caudal and posterior parts of the cingulate cortex had predictive potential for clinical response to aiTBS. Limitations: We used the diffusion tensor to perform tractography. A main limitation was that multiple fibre directions within voxels could not be resolved, which might have led to missing connections in some patients. Conclusion: Stronger structural frontocingular connections may be of essence to optimally benefit from left dlPFC rTMS treatment in MDD. Even though the results are promising, further investigation with larger numbers of patients, more advanced tractography algorithms and classic daily rTMS treatment paradigms is warranted. Clinical trial registration: http://clinicaltrials.gov/show/NCT01832805

Neurocognitive and behavioural profile in Panayiotopoulos syndrome.

AIM: To determine neurocognitive performance and behavioural problems in children with Panayiotopoulos syndrome. METHOD: All 18 children (10 females, 8 males; mean age 4y 7mo; SD 1y 10mo) diagnosed with Panayiotopoulos syndrome at the Kempenhaeghe Epilepsy Center in the Netherlands between 2010 and 2017 were analysed retrospectively. All underwent a neuropsychological/behavioural assessment, an academic assessment, and a 24-hour electroencephalogram. RESULTS: Mean full-scale IQ (93.5; range 76-123; p=0.04) and performance IQ (93.2; range 76-126; p=0.04) were within the normal range, although significantly lower compared to the normative mean. Verbal IQ (96.3; range 76-118) and processing speed (96.1; range 74-114) were not significantly lower. Simple auditory/visual reaction times, visual attention, visual-motor integration, and verbal memory were significantly lower compared to normative values. On average, patients with Panayiotopoulos syndrome were 8 months behind in arithmetic speed and 11 months behind in reading speed for the number of months in school. Behavioural questionnaires revealed significantly higher scores on reported internalizing behavioural problems. INTERPRETATION: Children with Panayiotopoulos syndrome demonstrated diffuse cognitive dysfunction in full-scale IQ, performance IQ, visual attention, visual-motor integration, and verbal memory. A high incidence of internalizing behavioural problems was reported. This strongly suggests neuropsychological and behavioural comorbidity in children with Panayiotopoulos syndrome. WHAT THIS PAPER ADDS: Children with Panayiotopoulos syndrome are at risk for cognitive deficits in various cognitive domains. Children with Panayiotopoulos syndrome are also prone to internalizing behavioural problems. Mild-to-severe academic underachievement was present in more than half of the children with Panayiotopoulos syndrome.

Applicability and reproducibility of 2D multi-slice GRASE myelin water fraction with varying acquisition acceleration.

Non-invasive quantification of the in vivo myelin content may provide valuable information regarding healthy maturation of the brain, as well as insights into demyelination of several neurological disorders. However, these scans are often long thereby limiting acquisition of large brain parts in clinically feasible acquisition times. Therefore, fast acquisition of whole brain myelin content is important. To avoid errors related to slice-selective pulses, most of the previous whole brain studies on myelin content relied on a 3D acquisition. However, multi-slice (2D) acquisition methods are often faster, and less susceptible to motion artifacts. Therefore, multi-slice approaches can be beneficial in a clinical setting. We investigated the applicability and reproducibility of whole brain multi-slice GRASE myelin-water imaging with post-acquisition slice-profile correction in healthy volunteers (aged 25-32y). The applicability was evaluated using the agreement between the multi-slice GRASE and the reference method for myelin-water imaging, single-slice multi spin-echo (MSE) acquisition. Additionally, we assessed the effect of varying acquisition acceleration using parallel imaging on the reproducibility values. First, the multi-slice myelin-water maps showed good agreement with the single-slice reference method, with a bias of at most 1.2% in absolute MWF values. Second, we found an average within-subject coefficient of variation (CoV) of 5.9% and an average intra-class correlation coefficient (ICC) of 0.90 for myelin-water estimation using a multi-slice GRASE sequence without parallel acceleration (scan time 14:06 min), while acquisition with a parallel acceleration factor of 2 resulted in a slightly worse average within-subject CoV of 6.4% and an average ICC of 0.83 at half the scan time. Hence, a multi-slice GRASE acquisition with parallel acceleration factor 2 and a scan time of 7:30 min still provides an excellent reproducibility.

Focal application of accelerated iTBS results in global changes in graph measures.

Graph analysis was used to study the effects of accelerated intermittent theta burst stimulation (aiTBS) on the brain's network topology in medication-resistant depressed patients. Anatomical and resting-state functional MRI (rs-fMRI) was recorded at baseline and after sham and verum stimulation. Depression severity was assessed using the Hamilton Depression Rating Scale (HDRS). Using various graph measures, the different effects of sham and verum aiTBS were calculated. It was also investigated whether changes in graph measures were correlated to clinical responses. Furthermore, by correlating baseline graph measures with the changes in HDRS in terms of percentage, the potential of graph measures as biomarker was studied. Although no differences were observed between the effects of verum and sham stimulation on whole-brain graph measures and changes in graph measures did not correlate with clinical response, the baseline values of clustering coefficient and global efficiency showed to be predictive of the clinical response to verum aiTBS. Nodal effects were found throughout the whole brain. The distribution of these effects could not be linked to the strength of the functional connectivity between the stimulation site and the node. This study showed that the effects of aiTBS on graph measures distribute beyond the actual stimulation site. However, additional research into the complex interactions between different areas in the brain is necessary to understand the effects of aiTBS in more detail.

A new analysis approach for T2 relaxometry myelin water quantification: Orthogonal Matching Pursuit.

PURPOSE: In vivo myelin quantification can provide valuable noninvasive information on neuronal maturation and development, as well as insights into neurological disorders. Multiexponential analysis of multiecho T2 relaxation is a powerful and widely applied method for the quantification of the myelin water fraction (MWF). In recent literature, the MWF is most commonly estimated using a regularized nonnegative least squares algorithm. METHODS: The orthogonal matching pursuit algorithm is proposed as an alternative method for the estimation of the MWF. The orthogonal matching pursuit is a greedy sparse reconstruction algorithm with a low computation complexity. For validation, both methods are compared to a ground truth using numerical simulations and a phantom model using comparable computation times. The numerical simulations were used to measure the theoretical errors, as well as the effects of varying the SNR, strength of the regularization, and resolution of the basis set. Additionally, a phantom model was used to estimate the performance of the 2 methods while including errors occurring due to the MR measurement. Lastly, 4 healthy subjects were scanned to evaluate the in vivo performance. RESULTS: The results in simulations and phantoms demonstrate that the MWFs determined with the orthogonal matching pursuit are 1.7 times more accurate as compared to the nonnegative least squares, with a comparable precision. The remaining bias of the MWF is shown to be related to the regularization of the nonnegative least squares algorithm and the Rician noise present in magnitude MR images. CONCLUSION: The orthogonal matching pursuit algorithm provides a more accurate alternative for T2 relaxometry myelin water quantification.

Towards a Better Understanding of Cognitive Deficits in Absence Epilepsy: a Systematic Review and Meta-Analysis.

Cognition in absence epilepsy (AE) is generally considered undisturbed. However, reports on cognitive deficits in AE in recent years have suggested otherwise. This review systematically assesses current literature on cognitive performance in children with AE. A systematic literature search was performed in Pubmed, Embase, Cochrane and Web of Science. All studies reporting on cognitive performance in children with AE were considered. In total 33 studies were eligible for inclusion. Neuropsychological tests were classified into the following domains: intelligence; executive function; attention; language; motor & sensory-perceptual examinations; visuoperceptual/visuospatial/visuoconstructional function; memory and learning; achievement. Random-effect meta-analyses were conducted by estimating the pooled mean and/or pooling the mean difference in case-control studies. Full-scale IQ in children with AE was estimated at 96.78 (95%CI:94.46-99.10) across all available studies and in case-control studies IQ was on average 8.03 (95%CI:-10.45- -5.61) lower. Verbal IQ was estimated at 97.98 (95%CI:95.80-100.16) for all studies and 9.01 (95%CI:12.11- -5.90) points lower in case-control studies. Performance IQ was estimated at 97.23 (93.24-101.22) for all available studies and 5.32 (95%CI:-8.27-2.36) points lower in case-control studies. Lower performance was most often reported in executive function (cognitive flexibility, planning, and verbal fluency) and attention (sustained, selective and divided attention). Reports on school difficulties, neurodevelopmental problems, and attentional problems were high. In conclusion, in contrast to common beliefs, lower than average neurocognitive performance was noted in multiple cognitive domains, which may influence academic and psychosocial development.

Lower myelin-water content of the frontal lobe in childhood absence epilepsy.

OBJECTIVE: The frontal lobe in childhood absence epilepsy (CAE) might be affected due to the suggested involvement of the frontal lobe during absence seizures and reports on attentional deficits. Previously, subtle white matter abnormalities have been reported in CAE. However, the impact of one of the most characteristic components of the white matter, the myelin content, remains underdetermined. Therefore, this study investigated whether the myelin content in frontal areas is adversely affected in CAE compared to controls. METHODS: Seventeen children with childhood absence epilepsy (mean age ± standard deviation [SD], 9.2 ± 2.1 years) and 15 age- and sex-matched controls (mean age ± SD, 9.8 ± 1.8 years) underwent neuropsychological assessment and a magnetic resonance imaging (MRI) examination. T2 relaxometry scans were used to distinguish myelin-water from tissue water and to determine the myelin-water fraction (MWF) in the frontal, temporal, parietal, occipital, and insular lobes. A linear regression model including age and sex as covariates was used to investigate group differences. Furthermore, the relationship of MWF with cognitive performance and epilepsy characteristics was determined. RESULTS: The frontal lobe revealed a significantly lower myelin-water content in children with CAE compared to controls over the developmental age range of 6-12 years (5.7 ± 1.0% vs 6.6 ± 1.1%, P = 0.02). This association was not found for any of the other four lobes (P > 0.10). No significant relation was found between myelin-water content and cognitive performance or epilepsy characteristics. SIGNIFICANCE: The lower frontal myelin-water content of children with CAE in comparison with healthy controls probably reflects an altered neurodevelopmental aspect in CAE, of which the underlying mechanisms still need to be unraveled.