Retrospective Studies
Research Papers
Brainmarker-I Differentially Predicts Remission to Various Attention-Deficit/Hyperactivity Disorder Treatments: A Discovery, Transfer, and Blinded Validation Study
BACKGROUND: Attention-deficit/hyperactivity disorder is characterized by neurobiological heterogeneity, possibly explaining why not all patients benefit from a given treatment. As a means to select the right treatment (stratification), biomarkers may aid in personalizing treatment prescription, thereby increasing remission rates. METHODS: The biomarker in this study was developed in a heterogeneous clinical sample (N = 4249) and first applied to two large transfer datasets, a priori stratifying young males (<18 years) with a higher individual alpha peak frequency (iAPF) to methylphenidate (N = 336) and those with a lower iAPF to multimodal neurofeedback complemented with sleep coaching (N = 136). Blinded, out-of-sample validations were conducted in two independent samples. In addition, the association between iAPF and response to guanfacine and atomoxetine was explored. RESULTS: Retrospective stratification in the transfer datasets resulted in a predicted gain in normalized remission of 17% to 30%. Blinded out-of-sample validations for methylphenidate (n = 41) and multimodal neurofeedback (n = 71) corroborated these findings, yielding a predicted gain in stratified normalized remission of 36% and 29%, respectively. CONCLUSIONS: This study introduces a clinically interpretable and actionable biomarker based on the iAPF assessed during resting-state electroencephalography. Our findings suggest that acknowledging neurobiological heterogeneity can inform stratification of patients to their individual best treatment and enhance remission rates.
View Full Paper →Acute and chronic management of posttraumatic headache in children: A systematic review
OBJECTIVES: The goal of this paper is to provide a compilation of the evidence for the treatment of posttraumatic headache (PTH) in the pediatric population. Headache features and timing of therapy were considered. BACKGROUND: Headache is the most common symptom following mild traumatic brain injury (mTBI), affecting more than 80% of children and adolescents. It is unclear whether treatment for PTH should be tailored based on headache characteristics, particularly the presence of migraine features, and/or chronicity of the headache. METHODS: Systematic literature searches of PubMed, Embase, Scopus, and Cochrane databases (1985-2021, limited to English) were performed, and key characteristics of included studies were entered into RedCAP® (Prospero ID CRD42020198703). Articles and conference abstracts that described randomized controlled trials (RCTs), cohort studies, retrospective analyses, and case series were included. Participants included youth under 18 years of age with acute (<3 months) and persistent (≥3 months) PTH. Studies that commented on headache improvement in response to therapy were included. RESULTS: Twenty-seven unique studies met criteria for inclusion describing abortive pharmacologic therapies (9), preventative pharmacotherapies (5), neuromodulation (1), procedures (5), physical therapy and exercise (6), and behavioral therapy (2). Five RCTs were identified. Studies that focused on abortive pharmacotherapies were completed in the first 2 weeks post-mTBI, whereas other treatment modalities focused on outcomes 1 month to over 1-year post-injury. Few studies reported on migrainous features (7), personal history of migraine (7), or family history of migraine (3). CONCLUSIONS: There is limited evidence on the timing and types of therapies that are effective for treating PTH in the pediatric population. Prospective studies that account for headache characteristics and thoughtfully address the timing of therapies and outcome measurement are needed.
View Full Paper →The impact of real-time fMRI denoising on online evaluation of brain activity and functional connectivity
Objective. Comprehensive denoising is imperative in functional magnetic resonance imaging (fMRI) analysis to reliably evaluate neural activity from the blood oxygenation level dependent signal. In real-time fMRI, however, only a minimal denoising process has been applied and the impact of insufficient denoising on online brain activity estimation has not been assessed comprehensively. This study evaluated the noise reduction performance of online fMRI processes in a real-time estimation of regional brain activity and functional connectivity.Approach.We performed a series of real-time processing simulations of online fMRI processing, including slice-timing correction, motion correction, spatial smoothing, signal scaling, and noise regression with high-pass filtering, motion parameters, motion derivatives, global signal, white matter/ventricle average signals, and physiological noise models with image-based retrospective correction of physiological motion effects (RETROICOR) and respiration volume per time (RVT).Main results.All the processing was completed in less than 400 ms for whole-brain voxels. Most processing had a benefit for noise reduction except for RVT that did not work due to the limitation of the online peak detection. The global signal regression, white matter/ventricle signal regression, and RETROICOR had a distinctive noise reduction effect, depending on the target signal, and could not substitute for each other. Global signal regression could eliminate the noise-associated bias in the mean dynamic functional connectivity across time.Significance.The results indicate that extensive real-time denoising is possible and highly recommended for real-time fMRI applications.
View Full Paper →Unified Retrospective EEG Motion Educated Artefact Suppression for EEG-fMRI to Suppress Magnetic Field Gradient Artefacts During Motion
The data quality of simultaneously acquired electroencephalography and functional magnetic resonance imaging (EEG-fMRI) can be strongly affected by motion. Recent work has shown that the quality of fMRI data can be improved by using a Moiré-Phase-Tracker (MPT)-camera system for prospective motion correction. The use of the head position acquired by the MPT-camera-system has also been shown to correct motion-induced voltages, ballistocardiogram (BCG) and gradient artefact residuals separately. In this work we show the concept of an integrated framework based on the general linear model to provide a unified motion informed model of in-MRI artefacts. This model (retrospective EEG motion educated gradient artefact suppression, REEG-MEGAS) is capable of correcting voltage-induced, BCG and gradient artefact residuals of EEG data acquired simultaneously with prospective motion corrected fMRI. In our results, we have verified that applying REEG-MEGAS correction to EEG data acquired during subject motion improves the data quality in terms of motion induced voltages and also GA residuals in comparison to standard Artefact Averaging Subtraction and Retrospective EEG Motion Artefact Suppression. Besides that, we provide preliminary evidence that although adding more regressors to a model may slightly affect the power of physiological signals such as the alpha-rhythm, its application may increase the overall quality of a dataset, particularly when strongly affected by motion. This was verified by analysing the EEG traces, power spectra density and the topographic distribution from two healthy subjects. We also have verified that the correction by REEG-MEGAS improves higher frequency artefact correction by decreasing the power of Gradient Artefact harmonics. Our method showed promising results for decreasing the power of artefacts for frequencies up to 250 Hz. Additionally, REEG-MEGAS is a hybrid framework that can be implemented for real time prospective motion correction of EEG and fMRI data. Among other EEG-fMRI applications, the approach described here may benefit applications such as EEG-fMRI neurofeedback and brain computer interface, which strongly rely on the prospective acquisition and application of motion artefact removal.
View Full Paper →Spatially aggregated multiclass pattern classification in functional MRI using optimally selected functional brain areas
In previous works, boosting aggregation of classifier outputs from discrete brain areas has been demonstrated to reduce dimensionality and improve the robustness and accuracy of functional magnetic resonance imaging (fMRI) classification. However, dimensionality reduction and classification of mixed activation patterns of multiple classes remain challenging. In the present study, the goals were (a) to reduce dimensionality by combining feature reduction at the voxel level and backward elimination of optimally aggregated classifiers at the region level, (b) to compare region selection for spatially aggregated classification using boosting and partial least squares regression methods and (c) to resolve mixed activation patterns using probabilistic prediction of individual tasks. Brain activation maps from interleaved visual, motor, auditory and cognitive tasks were segmented into 144 functional regions. Feature selection reduced the number of feature voxels by more than 50%, leaving 95 regions. The two aggregation approaches further reduced the number of regions to 30, resulting in more than 75% reduction of classification time and misclassification rates of less than 3%. Boosting and partial least squares (PLS) were compared to select the most discriminative and the most task correlated regions, respectively. Successful task prediction in mixed activation patterns was feasible within the first block of task activation in real-time fMRI experiments. This methodology is suitable for sparsifying activation patterns in real-time fMRI and for neurofeedback from distributed networks of brain activation.
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