Ten simple rules for reporting voxel-based morphometry studies

Voxel-based morphometry [Ashburner, J. and Friston, K.J., 2000. Voxel-based morphometry—the methods. NeuroImage 11(6 Pt 1), 805–821] is a commonly used tool for studying patterns of brain change in development or disease and neuroanatomical correlates of subject characteristics. In performing a VBM study, many methodological options are available; if the study is to be easily interpretable and repeatable, the processing steps and decisions must be clearly described. Similarly, unusual methods and parameter choices should be justified in order to aid readers in judging the importance of such options or in comparing the work with other studies. This editorial suggests core principles that should be followed and information that should be included when reporting a VBM study in order to make it transparent, replicable and useful

A Longitudinal Study of Closed Head Injury: Neuropsychological Outcome and Structural Analysis using Region of Interest Measurements and Voxel-Based Morphometry

Background: The hippocampus and corpus callosum have been shown to be vulnerable in head injury. Various neuroimaging modalities and quantitative measurement techniques have been employed to investigate pathological changes in these structures. Cognitive and behavioural deficiencies have also been well documented in head injury. Aims: The aim of this research project was to investigate structural changes in the hippocampus and corpus callosum. Two different quantitative methods were used to measure physical changes and neuropsychological assessment was performed to determine cognitive and behavioural deficit. It was also intended to investigate the relationship between structural change and neuropsychology at 1 and 6 months post injury. Method: Forty-seven patients with head injury (ranging from mild to severe) had undergone a battery of neuropsychological tests and an MRI scan at 1 and 6 months post injury. T1-weighted MRI scans were obtained and analysis of hippocampus and corpus callosum was performed using region-of-interest techniques and voxel-based morphometry which also included comparison to 18 healthy volunteers. The patients completed neuropsychological assessment at 1 and 6 months post injury and data obtained was analysed with respect to each assessment and with structural data to determine cognitive decline and correlation with neuroanatomy. Results: Voxel-based morphometry illustrated reduced whole scan signal differences between patients and controls and changes in patients between 1 and 6 months post injury. Reduced grey matter concentration was also found using voxel-based morphometry and segmented images between patients and controls. A number of neuropsychological aspects were related to injury severity and correlations with neuroanatomy were present. Voxel-based morphometry provided a greater number of associations than region-of-interest analysis. No longitudinal changes were found in the hippocampus or corpus callosum using region-of-interest methodology or voxel-based morphometry. Conclusions: Decreased grey matter concentration identified with voxel-based morphometry illustrated that structural deficit was present in the head injured patients and does not change between 1 and 6 months. Voxel-based morphometry appears more sensitive for detecting structural changes after head injury than region- of-interest methods. Although the majority of patients had suffered mild head injury, cognitive and neurobehavioural deficits were evidenced by a substantial number of patients reporting increased anxiety and depression levels. Also, the findings of relationships between reduced grey matter concentration and cognitive test scores are indicative of the effects of diffuse brain damage in the patient group

A comparison of Voxel compression mapping & longitudinal Voxel-Based morphometry

Clinical motivation: Serial brain imaging can reveal patterns of change over time with important clinical implications for neurodegenerative disease [1]. We investigate the performance of four analysis methods, in terms of a comparison of 20 patients with probable AD to 20 age- and sex-matched controls, characterising differences in change from baseline to later scans

Cortical neuronal loss and hippocampal sclerosis are not detected by voxel-based morphometry in individual epilepsy surgery patients

Voxel-based morphometry (VBM) has detected differences between brains of groups of patients with epilepsy and controls, but the sensitivity for detecting subtle pathological changes in single subjects has not been established. The aim of the study was to test the sensitivity of VBM using statistical parametric mapping (SPM5) to detect hippocampal sclerosis (HS) and cortical neuronal loss in individual patients. T1-weighted volumetric 1.5 T MR images from 13 patients with HS and laminar cortical neuronal loss were segmented, normalised and smoothed using SPM5. Both modulated and non-modulated analyses were performed. Comparisons of one control subject against the rest (n ¼ 23) were first performed to ascertain the smoothing level with the lowest number of SPM changes in controls. Each patient was then compared against the whole control group. The lowest number of SPM changes in control subjects was found at a smoothing level of 10 mm full width half maximum for modulated and non-modulated data. In the patient group, no SPM abnormalities were found in the affected temporal lobe or hippocampus at this smoothing level. At lower smoothing levels there were numerous SPM findings in controls and patients. VBM did not detect any abnormalities associated with either laminar cortical neuronal loss or HS. This may be due to normalisation and smoothing of images and low statistical power in areas with larger interindividual differences. This suggests that the methodology may currently not be suitable to detect particular occult abnormalities possibly associated with seizure onset zone in individual epilepsy patients with unremarkable standard structural MRI

Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

Gray matter structural correlates of fatigue in multiple sclerosis

We aimed to assess whether frontal cortex-striatum-thalamus (FCST) pathway or other grey matter (GM) structures are associated with longitudinal patterns of fatigue, namely reversible (RF) versus sustained fatigue (SF). MS patients enrolled in our prospective cohort were grouped based on their longitudinal Modified Fatigue Impact Scale (MFIS) scores: 1. SF: MFIS≥38 at the two most recent yearly assessments; 2. RF: MFIS<38 at last assessment, but presence of at least one previous MFIS≥38; 3. Never Fatigued (NF): at least five MFIS<38. Accordingly, we selected 98 patients (30 SF, 31 RF, 37 NF; age-range:29-66, female/male:76/22, Extended Disability Status Scale (EDSS)6; 13 patients with secondary progressive (SP) MS and 85 with relapsing remitting (RR) MS in remission). Disability and depression were assessed using the EDSS and CES-D, respectively. 3T T1-weighted MRI was used for voxel based morphometry (VBM) to survey for GM atrophy associated with fatigue, controlling for age, sex and EDSS. Group-wise volumetric comparison was performed on deep GM structures identified by VBM, controlling for age, sex, EDSS and CES-D score. VBM showed significant inverse relation between the MFIS cognitive subscale score and areas within the bilateral fronto-medial and fronto-orbital cortices, anterior striata, thalami, temporal poles, insulae and left lateral occipital cortex (peak FWE-p value of 0.021), and between the MFIS physical subscale and areas within the bilateral frontal poles, and frontal medial cortices (peak FWE-p value of 0.043). Volumetric analysis showed significant atrophy in the putamen (RF<NF p<0.0004; SF<NF p<0.0085) and thalamus (RF<NF p<0.00048)

Prospective memory impairments in Alzheimer's Disease and behavioral variant frontotemporal dementia: Clinical and neural correlates

BACKGROUND: Prospective memory (PM) refers to a future-oriented form of memory in which the individual must remember to execute an intended action either at a future point in time (Time-based) or in response to a specific event (Event-based). Lapses in PM are commonly exhibited in neurodegenerative disorders including Alzheimer's disease (AD) and frontotemporal dementia (FTD), however, the neurocognitive mechanisms driving these deficits remain unknown. OBJECTIVE: To investigate the clinical and neural correlates of Time- and Event-based PM disruption in AD and the behavioral-variant FTD (bvFTD). METHODS: Twelve AD, 12 bvFTD, and 12 healthy older Control participants completed a modified version of the Cambridge Prospective Memory test, which examines Time- and Event-based aspects of PM. All participants completed a standard neuropsychological assessment and underwent whole-brain structural MRI. RESULTS: AD and bvFTD patients displayed striking impairments across Time- and Event-based PM relative to Controls, however, Time-based PM was disproportionately affected in the AD group. Episodic memory dysfunction and hippocampal atrophy was found to correlate strongly with PM integrity in both patient groups, however, dissociable neural substrates were also evident for PM performance across dementia syndromes. CONCLUSION: Our study reveals the multifaceted nature of PM dysfunction in neurodegenerative disorders, and suggests common and dissociable neurocognitive mechanisms, which subtend these deficits in each patient group. Future studies of PM disturbance in dementia syndromes will be crucial for the development of successful interventions to improve functional independence in the patient's daily life

Grey-matter texture abnormalities and reduced hippocampal volume are distinguishing features of schizophrenia

Neurodevelopmental processes are widely believed to underlie schizophrenia. Analysis of brain texture from conventional magnetic resonance imaging (MRI) can detect disturbance in brain cytoarchitecture. We tested the hypothesis that patients with schizophrenia manifest quantitative differences in brain texture that, alongside discrete volumetric changes, may serve as an endophenotypic biomarker. Texture analysis (TA) of grey matter distribution and voxel-based morphometry (VBM) of regional brain volumes were applied to MRI scans of 27 patients with schizophrenia and 24 controls. Texture parameters (uniformity and entropy) were also used as covariates in VBM analyses to test for correspondence with regional brain volume. Linear discriminant analysis tested if texture and volumetric data predicted diagnostic group membership (schizophrenia or control). We found that uniformity and entropy of grey matter differed significantly between individuals with schizophrenia and controls at the fine spatial scale (filter width below 2 mm). Within the schizophrenia group, these texture parameters correlated with volumes of the left hippocampus, right amygdala and cerebellum. The best predictor of diagnostic group membership was the combination of fine texture heterogeneity and left hippocampal size. This study highlights the presence of distributed grey-matter abnormalities in schizophrenia, and their relation to focal structural abnormality of the hippocampus. The conjunction of these features has potential as a neuroimaging endophenotype of schizophrenia

Longitudinal Voxel-based morphometry with unified segmentation: evaluation on simulated Alzheimer’s disease

The goal of this work is to evaluate Voxel-Based Morphometry and three longitudinally-tailored methods of VBM.We use a cohort of simulated images produced by deforming original scans using a Finite Element Method, guided to emulate Alzheimer-like changes. The simulated images provide quite realistic data with a known pattern of spatial atrophy, with which VBM’s findings can be meaningfully compared. We believe this is the first evaluation of VBM for which anatomically-plausible ‘gold-standard’ results are available. The three longitudinal VBM methods have been implemented within the unified segmentation framework of SPM5; one of the techniques is a newly developed procedure, which shows promising potential