Monofractal analysis of functional magnetic resonance imaging: An introductory review.

The following review will aid readers in providing an overview of scale-free dynamics and monofractal analysis, as well as its applications and potential in functional magnetic resonance imaging (fMRI) neuroscience and clinical research. Like natural phenomena such as the growth of a tree or crashing ocean waves, the brain expresses scale-invariant, or fractal, patterns in neural signals that can be measured. While neural phenomena may represent both monofractal and multifractal processes and can be quantified with many different interrelated parameters, this review will focus on monofractal analysis using the Hurst exponent (H). Monofractal analysis of fMRI data is an advanced analysis technique that measures the complexity of brain signaling by quantifying its degree of scale-invariance. As such, the H value of the blood oxygenation level-dependent (BOLD) signal specifies how the degree of correlation in the signal may mediate brain functions. This review presents a brief overview of the theory of fMRI monofractal analysis followed by notable findings in the field. Through highlighting the advantages and challenges of the technique, the article provides insight into how to best conduct fMRI fractal analysis and properly interpret the findings with physiological relevance. Furthermore, we identify the future directions necessary for its progression towards impactful functional neuroscience discoveries and widespread clinical use. Ultimately, this presenting review aims to build a foundation of knowledge among readers to facilitate greater understanding, discussion, and use of this unique yet powerful imaging analysis technique.

Myelin water imaging and R2* mapping in neonates: Investigating R2* dependence on myelin and fibre orientation in whole brain white matter.

R2* relaxation provides a semiquantitative method of detecting myelin, iron and white matter fibre orientation angles. Compared with standard histogram-based analyses, angle-resolved analysis of R2* has previously been shown to substantially improve the detection of subtle differences in the brain between healthy siblings of subjects with multiple sclerosis and unrelated healthy controls. Neonates, who are born with very little myelin and iron, and an underdeveloped connectome, provide researchers with an opportunity to investigate whether R2* is intimately linked with fibre-angle or myelin content as it is in adults, which may in future studies be explored as a potential white matter developmental biomarker. Five healthy adult volunteers (mean age [±SD] = 31.2 [±8.3] years; three males) were recruited from Vancouver, Canada. Eight term neonates (mean age = 38.6 ± 1.2 weeks; five males) were recruited from the Children's Hospital of Chongqing Medical University neonatal ward. All subjects were scanned on identical 3 T Philips Achieva scanners equipped with an eight-channel SENSE head coil and underwent a multiecho gradient echo scan, a 32-direction DTI scan and a myelin water imaging scan. For both neonates and adults, bin-averaged R2* variation across the brain's white matter was found to be best explained by fibre orientation. For adults, this represented a difference in R2* values of 3.5 Hz from parallel to perpendicular fibres with respect to the main magnetic field. In neonates, the fibre orientation dependency displayed a cosine wave shape, with a small R2* range of 0.4 Hz. This minor relationship in neonates provides further evidence for the key role myelin probably plays in creating this fibre orientation dependence later in life, but suggests limited clinical application in newborn populations. Future studies should investigate fibre-orientation dependency in infants in the first 5 years, when substantial myelin development occurs.

Changes in cortical grey matter volume with Cognitive Orientation to daily Occupational Performance intervention in children with developmental coordination disorder.

Introduction: Cognitive Orientation to daily Occupational Performance (CO-OP) is a cognitive-based, task-specific intervention recommended for children with developmental coordination disorder (DCD). We recently showed structural and functional brain changes after CO-OP, including increased cerebellar grey matter. This study aimed to determine whether CO-OP intervention induced changes in cortical grey matter volume in children with DCD, and if these changes were associated with improvements in motor performance and movement quality. Methods: This study is part of a randomized waitlist-control trial (ClinicalTrials.gov ID: NCT02597751). Children with DCD (N = 78) were randomized to either a treatment or waitlist group and underwent three MRIs over 6 months. The treatment group received intervention (once weekly for 10 weeks) between the first and second scan; the waitlist group received intervention between the second and third scan. Cortical grey matter volume was measured using voxel-based morphometry (VBM). Behavioral outcome measures included the Performance Quality Rating Scale (PQRS) and Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2). Of the 78 children, 58 were excluded (mostly due to insufficient data quality), leaving a final N = 20 for analyses. Due to the small sample size, we combined both groups to examine treatment effects. Cortical grey matter volume differences were assessed using a repeated measures ANOVA, controlling for total intracranial volume. Regression analyses examined the relationship of grey matter volume changes to BOT-2 (motor performance) and PQRS (movement quality). Results: After CO-OP, children had significantly decreased grey matter in the right superior frontal gyrus and middle/posterior cingulate gyri. We found no significant associations of grey matter volume changes with PQRS or BOT-2 scores. Conclusion: Decreased cortical grey matter volume generally reflects greater brain maturity. Decreases in grey matter volume after CO-OP intervention were in regions associated with self-regulation and motor control, consistent with our other studies. Decreased grey matter volume may be due to focal increases in synaptic pruning, perhaps as a result of strengthening networks in the brain via the repeated learning and actions in therapy. Findings from this study add to the growing body of literature demonstrating positive neuroplastic changes in the brain after CO-OP intervention.

Cerebrovascular Reactivity Following Spinal Cord Injury.

Background: Spinal cord injuries (SCI) often result in cardiovascular issues, increasing the risk of stroke and cognitive deficits. Objectives: This study assessed cerebrovascular reactivity (CVR) using functional magnetic resonance imaging (fMRI) during a hypercapnic challenge in SCI participants compared to noninjured controls. Methods: Fourteen participants were analyzed (n = 8 with SCI [unless otherwise noted], median age = 44 years; n = 6 controls, median age = 33 years). CVR was calculated through fMRI signal changes. Results: The results showed a longer CVR component (tau) in the grey matter of SCI participants (n = 7) compared to controls (median difference = 3.0 s; p < .05). Time since injury (TSI) correlated negatively with steady-state CVR in the grey matter and brainstem of SCI participants (RS = -0.81, p = .014; RS = -0.84, p = .009, respectively). Lower steady-state CVR in the brainstem of the SCI group (n = 7) correlated with lower diastolic blood pressure (RS = 0.76, p = .046). Higher frequency of hypotensive episodes (n = 7) was linked to lower CVR outcomes in the grey matter (RS = -0.86, p = .014) and brainstem (RS = -0.89, p = .007). Conclusion: Preliminary findings suggest a difference in the dynamic CVR component, tau, between the SCI and noninjured control groups, potentially explaining the higher cerebrovascular health burden in SCI individuals. Exploratory associations indicate that longer TSI, lower diastolic blood pressure, and more hypotensive episodes may lead to poorer CVR outcomes. However, further research is necessary to establish causality and support these observations.

Fractal-Based Analysis of fMRI BOLD Signal During Naturalistic Viewing Conditions.

Background: Temporal fractals are characterized by prominent scale-invariance and self-similarity across time scales. Monofractal analysis quantifies this scaling behavior in a single parameter, the Hurst exponent (H). Higher H reflects greater correlation in the signal structure, which is taken as being more fractal. Previous fMRI studies have observed lower H during conventional tasks relative to resting state conditions, and shown that H is negatively correlated with task difficulty and novelty. To date, no study has investigated the fractal dynamics of BOLD signal during naturalistic conditions. Methods: We performed fractal analysis on Human Connectome Project 7T fMRI data (n = 72, 41 females, mean age 29.46 ± 3.76 years) to compare H across movie-watching and rest. Results: In contrast to previous work using conventional tasks, we found higher H values for movie relative to rest (mean difference = 0.014; p = 5.279 × 10-7; 95% CI [0.009, 0.019]). H was significantly higher in movie than rest in the visual, somatomotor and dorsal attention networks, but was significantly lower during movie in the frontoparietal and default networks. We found no cross-condition differences in test-retest reliability of H. Finally, we found that H of movie-derived stimulus properties (e.g., luminance changes) were fractal whereas H of head motion estimates were non-fractal. Conclusions: Overall, our findings suggest that movie-watching induces fractal signal dynamics. In line with recent work characterizing connectivity-based brain state dynamics during movie-watching, we speculate that these fractal dynamics reflect the configuring and reconfiguring of brain states that occurs during naturalistic processing, and are markedly different than dynamics observed during conventional tasks.

Imaging the Role of Myelin in Concussion.

Myelin water imaging (MWI) provides mild traumatic brain injury (mTBI) researchers with a specific myelin biomarker and helps to further elucidate microstructural and microarchitectural changes of white matter after mTBI. Improvement of scanner hardware and software with the implementation of MWI across scanner platforms will likely result in increased research regarding the role of myelin in traumatic brain injury (TBI). Future research should include detailed investigation of myelin between 2 weeks and 2 months after injury, the use of MWI in moderate and severe TBI, and investigation of the role of myelin in chronic TBI.

A preliminary study of functional connectivity of medication naïve children with obsessive-compulsive disorder.

BACKGROUND: Evidence suggests that obsessive-compulsive disorder (OCD) is associated with a dysfunction in the cortico-striatal-thalamic-cortical (CSTC) circuitry. Resting state functional connectivity magnetic resonance imaging (rs-fcMRI) allows measurements of resting state networks (RSNs), brain networks that are present at 'rest'. However, although OCD has a typical onset during childhood or adolescence, only two other studies have performed rs-fcMRI comparisons of RSNs in children and adolescents with OCD against healthy controls. METHODS: In the present study, we performed resting state functional magnetic resonance imaging using a 3 Tesla MRI, in 11 medication-naïve children and adolescents with OCD and 9 healthy controls. In contrast to previous studies that relied on a priori determination of RSNs, we determined resting state functional connectivity with a data-driven independent component analysis (ICA). RESULTS: Consistent with previous reports in healthy adults, we identified 13 RSNs. Case-control un-adjusted statistical significance (p<0.05) was found for two networks. Firstly, increased connectivity (OCD>control) in the right section of Brodmann area 43 of the auditory network; Secondly, decreased connectivity in the right section of Brodmann area 8 and Brodmann area 40 in the cingulate network. CONCLUSIONS: Our preliminary findings of case-control differences in RSNs lend further support to the CSTC hypothesis of OCD, as well as implicating other regions of the brain outside of the CSTC.

Proton magnetic resonance spectroscopy of prefrontal white matter in psychotropic naïve children and adolescents with obsessive-compulsive disorder.

Obsessive-compulsive disorder (OCD) has a typical onset during childhood or adolescence. Although recent in-vivo proton magnetic resonance spectroscopy ((1)H-MRS) studies report gray matter metabolite abnormalities in children and adolescents with OCD, there are no existing (1)H-MRS studies that measure white matter (WM) metabolite levels in this population. In the present study, we measured metabolite levels in the left and right prefrontal WM (LPFWM and RPFWM, respectively) of psychotropic-naïve children and adolescents with OCD (LPFWM: N=15, mean age 13.3±2.4 years; right RPFWM: N=14, mean age 13.0±2.3 years) and healthy controls (LPFWM: N=17, mean age 11.8±2.7 years; RPFWM: N=18, mean age 12.2±2.8 years). Spectra were acquired using a 3T single voxel PRESS sequence (1.5×2.0×2.0cm(3)). When age and sex effects were controlled, OCD patients had higher levels of RPFWM choline and N-acetyl-aspartate (NAA). In addition, RPFWM levels of NAA, creatine and myo-inositol were positively and significantly correlated with severity of OCD symptoms. In summary, this is the first published study of WM metabolite levels in children and adolescents with OCD. Our preliminary findings lend further support to the previous findings of WM abnormalities in OCD.