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Functional but not structural changes associated with learning: an exploration of longitudinal voxel-based morphometry (VBM).

ABSTRACT: Voxel-Based Morphometry (VBM) has been used for several years to study differences in brain structure between populations. Recently, a longitudinal version of VBM has been used to show changes in gray matter associated with relatively short periods of training. In the present study we use fMRI and three different standard implementations of longitudinal VBM: SPM2, FSL, and SPM5 to assess functional and structural changes associated with a simple learning task. Behavioral and fMRI data clearly showed a significant learning effect. However, initially positive VBM results were found to be inconsistent across minor perturbations of the analysis technique and ultimately proved to be artifactual. When alignment biases were controlled for and recommended statistical procedures were used, no significant changes in grey matter density were found. This work, initially intended to show structural and functional changes with learning, rather demonstrates some of the potential pitfalls of existing longitudinal VBM methods and prescribes that these tools be applied and interpreted with extreme caution.

SUBMITTER: Thomas AG

PROVIDER: S-EPMC2981435 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

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Functional but not structural changes associated with learning: an exploration of longitudinal voxel-based morphometry (VBM).

Thomas Adam G AG Marrett Sean S Saad Ziad S ZS Ruff Douglas A DA Martin Alex A Bandettini Peter A PA

NeuroImage 20090609 1

Voxel-Based Morphometry (VBM) has been used for several years to study differences in brain structure between populations. Recently, a longitudinal version of VBM has been used to show changes in gray matter associated with relatively short periods of training. In the present study we use fMRI and three different standard implementations of longitudinal VBM: SPM2, FSL, and SPM5 to assess functional and structural changes associated with a simple learning task. Behavioral and fMRI data clearly sh ...[more]

PMID: 19520171

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Project description:PurposeMRI has become an essential tool for prion disease diagnosis. However there exist only a few serial MRI studies of prion patients, and these mostly used whole brain summary measures or region of interest based approaches. We present here the first longitudinal voxel-based morphometry (VBM) study in prion disease. The aim of this study was to systematically characterise progressive atrophy in patients with prion disease and identify whether atrophy in specific brain structures correlates with clinical assessment.MethodsTwenty-four prion disease patients with early stage disease (3 sporadic, 2 iatrogenic, 1 variant and 18 inherited CJD) and 25 controls were examined at 3T with a T1-weighted 3D MPRAGE sequence at multiple time-points (2-6 examinations per subject, interval range 0.1-3.2 years). Longitudinal VBM provided intra-subject and inter-subject image alignment, allowing voxel-wise comparison of progressive structural change. Clinical disease progression was assessed using the MRC Prion Disease Rating Scale. Firstly, in patients, we determined the brain regions where grey and white matter volume change between baseline and final examination correlated with the corresponding change in MRC Scale score. Secondly, in the 21/24 patients with interscan interval longer than 3 months, we identified regions where annualised rates of regional volume change in patients were different from rates in age-matched controls. Given the heterogeneity of the cohort, the regions identified reflect the common features of the different prion sub-types studied.ResultsIn the patients there were multiple regions where volume loss significantly correlated with decreased MRC scale, partially overlapping with anatomical regions where yearly rates of volume loss were significantly greater than controls. The key anatomical areas involved included: the basal ganglia and thalamus, pons and medulla, the hippocampal formation and the superior parietal lobules. There were no areas demonstrating volume loss significantly higher in controls than patients or negative correlation between volume and MRC Scale score.ConclusionsUsing 3T MRI and longitudinal VBM we have identified key anatomical regions of progressive volume loss which correlate with an established clinical disease severity index and are relevant to clinical deterioration. Localisation of the regions of progressive brain atrophy correlating most strongly with clinical decline may help to provide more targeted imaging endpoints for future clinical trials.

Dataset Information

Functional but not structural changes associated with learning: an exploration of longitudinal voxel-based morphometry (VBM).

Publications

Functional but not structural changes associated with learning: an exploration of longitudinal voxel-based morphometry (VBM).

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