Task-enhanced arterial spin labeled perfusion MRI predicts longitudinal neurodegeneration in mild cognitive impairment.

Mild cognitive impairment (MCI) is considered a prodromal stage of Alzheimer's disease (AD), but is also recognized to be a heterogeneous condition. Biomarkers that predict AD progression in MCI are of clinical significance because they can be used to better identify appropriate candidates for therapeutic intervention studies. It has been hypothesized that comparing to structural measurements, functional ones may be more sensitive to early disease abnormalities and the sensitivity could be further enhanced when combined with cognitive task, a "brain stress test." In this study, we investigated the value of regional cerebral blood flow (CBF), measured by arterial spin labeled perfusion MRI (ASL MRI) during a memory-encoding task, in predicting the estimated rate of hippocampal atrophy, an established marker of AD progression. Thirty-one amnestic MCI patients (20 male and 11 female; age: 70.9 ± 6.5 years, range from 56 to 83 years; mini mental status examination: 27.8 ± 1.8) and 42 normal control subjects (13 male and 29 female; age: 70.6 ± 8.8 years, range from 55 to 88 years; mini mental status examination: 29.1 ± 1.2) were included in this study. We compared the predictive value of CBF during task to CBF during rest and structural volumetry. Both region-of-interest and voxelwise analyses showed that baseline CBF measurements during task (strongest effect in fusiform gyrus, region-of-interest analysis statistics: r = 0.56, p = .003), but not resting ASL MRI or structural volumetry, were correlated with the estimated rate of hippocampal atrophy in amnestic MCI patients. Further, stepwise linear regression demonstrated that resting ASL MRI and volumetry did not provide complementary information in prediction. These results support the notion that physiologic measures during a cognitive challenge may increase the ability to detect subtle functional changes that predict progression. As such, ASL MRI could have important utility in stratifying candidates for AD treatment trials.

Mapping the structural and functional network architecture of the medial temporal lobe using 7T MRI.

Medial temporal lobe (MTL) subregions play integral roles in memory function and are differentially affected in various neurological and psychiatric disorders. The ability to structurally and functionally characterize these subregions may be important to understanding MTL physiology and diagnosing diseases involving the MTL. In this study, we characterized network architecture of the MTL in healthy subjects (n = 31) using both resting state functional MRI and MTL-focused T2-weighted structural MRI at 7 tesla. Ten MTL subregions per hemisphere, including hippocampal subfields and cortical regions of the parahippocampal gyrus, were segmented for each subject using a multi-atlas algorithm. Both structural covariance matrices from correlations of subregion volumes across subjects, and functional connectivity matrices from correlations between subregion BOLD time series were generated. We found a moderate structural and strong functional inter-hemispheric symmetry. Several bilateral hippocampal subregions (CA1, dentate gyrus, and subiculum) emerged as functional network hubs. We also observed that the structural and functional networks naturally separated into two modules closely corresponding to (a) bilateral hippocampal formations, and (b) bilateral extra-hippocampal structures. Finally, we found a significant correlation in structural and functional connectivity (r = 0.25). Our findings represent a comprehensive analysis of network topology of the MTL at the subregion level. We share our data, methods, and findings as a reference for imaging methods and disease-based research.

Face-to-Face Versus Online Behavioral Parent Training for Young Children at Risk for ADHD: Treatment Engagement and Outcomes.

Attention deficit/hyperactivity disorder (ADHD) is associated with significant challenges in child functioning. Although behavioral parent training (BPT) can reduce ADHD symptoms, factors associated with traditional face-to-face (F2F) delivery results in only about half of families receiving BPT. The purpose of this pilot randomized controlled trial was to examine parent engagement and program acceptability of F2F and online BPT, as well as the efficacy of both formats relative to a waitlist control (WLC) group. Participants were 47 families with preschool children (30 boys, 17 girls) who were between the ages of 3 years 0 months (3;0) and 5 years 11 months (5;11) old who were identified at risk for ADHD. Children were randomly assigned to F2F or online BPT or to WLC; parents in the two treatment conditions received 10 sessions of BPT. Assessment data for all groups were collected at pre-, mid-, and posttreatment. Both intervention formats resulted in high attendance (M = 80%) and significantly improved parent knowledge of interventions, treatment implementation fidelity, and child behavior (reduced restlessness and impulsivity, improved self-control, affect, and mood) compared with WLC. However, parents in the F2F group reported significantly higher acceptability ratings than parents in the online group. Findings indicate a streamlined BPT delivered online or F2F results in high levels of engagement, acceptability, as well as parent treatment knowledge and fidelity. Online BPT is associated with similar efficacious outcomes with F2F BPT, suggesting the need for further research to determine variables that predict greater acceptability for and adoption of this format.

Enhancing Social Skills of Young Children With ADHD: Effects of a Sibling-Mediated Intervention.

Children with attention deficit/hyperactivity disorder (ADHD) are at risk for experiencing problems with social functioning that are associated with adverse outcomes in adolescence and adulthood. To date, the most common ADHD treatments for children, psychostimulants and adult-mediated interventions, have had limited success reducing social impairments associated with ADHD. Using a non-concurrent multiple baseline across participants design, we examined the efficacy of a sibling-mediated social intervention for reducing negative and increasing positive social behaviors of three children with ADHD. We also assessed implementation integrity by the siblings, and acceptability from the perspective of the participant with ADHD, the siblings, and the parents. Results indicated that siblings learned and used specific social skills strategies with their siblings with ADHD that lead to increases in sharing, helping, and compromising behaviors for children with ADHD compared with baseline (Tau-U = 0.9531, p < .001). Summary of findings, study limitations, implications for research, and practice are discussed.

A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment.

Arterial spin labeled perfusion magnetic resonance imaging (ASL MRI) provides non-invasive quantification of cerebral blood flow, which can be used as a biomarker of brain function due to the tight coupling between cerebral blood flow (CBF) and brain metabolism. A growing body of literature suggests that regional CBF is altered in neurodegenerative diseases. Here we examined ASL MRI CBF in subjects with amnestic mild cognitive impairment (n = 65) and cognitively normal healthy controls (n = 62), both at rest and during performance of a memory-encoding task. As compared to rest, task-enhanced ASL MRI improved group discrimination, which supports the notion that physiologic measures during a cognitive challenge, or "stress test", may increase the ability to detect subtle functional changes in early disease stages. Further, logistic regression analysis demonstrated that ASL MRI and concomitantly acquired structural MRI provide complementary information of disease status. The current findings support the potential utility of task-enhanced ASL MRI as a biomarker in early Alzheimer's disease.