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Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials.

ABSTRACT: To examine the feasibility and test-retest reliability of encoding-task functional magnetic resonance imaging (fMRI) in mild Alzheimer disease (AD).Randomized, double-blind, placebo-controlled study.Memory clinical trials unit.We studied 12 patients with mild AD (mean [SEM] Mini-Mental State Examination score, 24.0 [0.7]; mean Clinical Dementia Rating score, 1.0) who had been taking donepezil hydrochloride for more than 6 months from the placebo arm of a larger 24-week study (n = 24, 4 scans on weeks 0, 6, 12, and 24, respectively).Placebo and 3 face-name, paired-associate encoding, block-design blood oxygenation level-dependent fMRI scans in 12 weeks.We performed whole-brain t maps (P < .001, 5 contiguous voxels) and hippocampal regions-of-interest analyses of extent (percentage of active voxels) and magnitude (percentage of signal change) for novel-greater-than-repeated face-name contrasts. We also calculated intraclass correlation coefficients and power estimates for hippocampal regions of interest.Task tolerability and data yield were high (95 of 96 scans yielded favorable-quality data). Whole-brain maps were stable. Right and left hippocampal regions-of-interest intraclass correlation coefficients were 0.59 to 0.87 and 0.67 to 0.74, respectively. To detect 25.0% to 50.0% changes in week-0 to week-12 hippocampal activity using left-right extent or right magnitude with 80.0% power (2-sided ? = .05) requires 14 to 51 patients. Using left magnitude requires 125 patients because of relatively small signal to variance ratios.Encoding-task fMRI was successfully implemented in a single-site, 24-week, AD randomized controlled trial. Week 0 to 12 whole-brain t maps were stable, and test-retest reliability of hippocampal fMRI measures ranged from moderate to substantial. Right hippocampal magnitude may be the most promising of these candidate measures in a leveraged context. These initial estimates of test-retest reliability and power justify evaluation of encoding-task fMRI as a potential biomarker for signal of effect in exploratory and proof-of-concept trials in mild AD. Validation of these results with larger sample sizes and assessment in multisite studies is warranted.

SUBMITTER: Atri A

PROVIDER: S-EPMC3291175 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials.

Atri Alireza A O'Brien Jacqueline L JL Sreenivasan Aishwarya A Rastegar Sarah S Salisbury Sibyl S DeLuca Amy N AN O'Keefe Kelly M KM LaViolette Peter S PS Rentz Dorene M DM Locascio Joseph J JJ Sperling Reisa A RA

Archives of neurology 20110501 5

<h4>Objective</h4>To examine the feasibility and test-retest reliability of encoding-task functional magnetic resonance imaging (fMRI) in mild Alzheimer disease (AD).<h4>Design</h4>Randomized, double-blind, placebo-controlled study.<h4>Setting</h4>Memory clinical trials unit.<h4>Participants</h4>We studied 12 patients with mild AD (mean [SEM] Mini-Mental State Examination score, 24.0 [0.7]; mean Clinical Dementia Rating score, 1.0) who had been taking donepezil hydrochloride for more than 6 mont ...[more]

PMID: 21555634

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Project description:Neural and behavioral mechanisms during approach-avoidance conflict decision-making are relevant across various psychiatric disorders, particularly anxiety disorders. Studies using approach-avoidance conflict paradigms in healthy adults have identified preliminary neural mechanisms, but findings must be replicated and demonstrated as reliable before further application. This study sought to replicate previous findings and examine test-retest reliability of behavioral (approach behavior, reaction time) and neural (regions of interest [ROIs]) responses during an approach-avoidance conflict task conducted during functional magnetic resonance imaging (fMRI). Thirty healthy adults completed an approach-avoidance conflict task during fMRI on two occasions (mean interval: 17 days; range: 11-32). Effects of task condition during three task phases (decision-making, affective outcome and monetary reward) and intraclass correlation coefficients (ICCs) were calculated across time points. Results replicated that approach behavior was modulated by conflict during decision-making. ROI activations were replicated such that dorsal anterior cingulate cortex (dACC) was modulated by conflict during decision-making, and dACC, striatum, and anterior insula were modulated by valence during affective outcomes (p's <.0083). Approach behavior during conflict demonstrated excellent reliability (ICCs ≥.77). Activation of dACC during conflict decision-making and anterior insula during negative outcomes demonstrated fair reliability (ICCs = .51 and .54), and dACC and striatum activation demonstrated good reliability during negative outcomes (ICCs = .63 and .69). Two additional ROIs (amygdala, left dorsolateral prefrontal cortex) showed good reliability during negative outcomes (ICCs ≥.60). These results characterize several specific behavioral and neuroimaging responses that are replicable and sufficiently reliable during approach-avoidance conflict decision-making to support future utility.

Project description:Empirical studies reporting low test-retest reliability of individual blood oxygen-level dependent (BOLD) signal estimates in functional magnetic resonance imaging (fMRI) data have resurrected interest among cognitive neuroscientists in methods that may improve reliability in fMRI. Over the last decade, several individual studies have reported that modeling decisions, such as smoothing, motion correction and contrast selection, may improve estimates of test-retest reliability of BOLD signal estimates. However, it remains an empirical question whether certain analytic decisions consistently improve individual and group level reliability estimates in an fMRI task across multiple large, independent samples. This study used three independent samples (Ns: 60, 81, 120) that collected the same task (Monetary Incentive Delay task) across two runs and two sessions to evaluate the effects of analytic decisions on the individual (intraclass correlation coefficient [ICC(3,1)]) and group (Jaccard/Spearman rho) reliability estimates of BOLD activity of task fMRI data. The analytic decisions in this study vary across four categories: smoothing kernel (five options), motion correction (four options), task parameterizing (three options) and task contrasts (four options), totaling 240 different pipeline permutations. Across all 240 pipelines, the median ICC estimates are consistently low, with a maximum median ICC estimate of .44 - .55 across the three samples. The analytic decisions with the greatest impact on the median ICC and group similarity estimates are the Implicit Baseline contrast, Cue Model parameterization and a larger smoothing kernel. Using an Implicit Baseline in a contrast condition meaningfully increased group similarity and ICC estimates as compared to using the Neutral cue. This effect was largest for the Cue Model parameterization, however, improvements in reliability came at the cost of interpretability. This study illustrates that estimates of reliability in the MID task are consistently low and variable at small samples, and a higher test-retest reliability may not always improve interpretability of the estimated BOLD signal.

Dataset Information

Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials.

Publications

Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials.

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