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1.  Function in the Human Connectome: Task-fMRI and Individual Differences in Behavior 
NeuroImage  2013;80:169-189.
The primary goal of the Human Connectome Project (HCP) is to delineate the typical patterns of structural and functional connectivity in the healthy adult human brain. However, we know that there are important individual differences in such patterns of connectivity, with evidence that this variability is associated with alterations in important cognitive and behavioral variables that affect real world function. The HCP data will be a critical stepping-off point for future studies that will examine how variation in human structural and functional connectivity play a role in adult and pediatric neurological and psychiatric disorders that account for a huge amount of public health resources. Thus, the HCP is collecting behavioral measures of a range of motor, sensory, cognitive and emotional processes that will delineate a core set of functions relevant to understanding the relationship between brain connectivity and human behavior. In addition, the HCP is using task-fMRI (tfMRI) to help delineate the relationships between individual differences in the neurobiological substrates of mental processing and both functional and structural connectivity, as well as to help characterize and validate the connectivity analyses to be conducted on the structural and functional connectivity data. This paper describes the logic and rationale behind the development of the behavioral, individual difference, and tfMRI batteries and provides preliminary data on the patterns of activation associated with each of the fMRI tasks, at both a group and individual level.
PMCID: PMC4011498  PMID: 23684877
Cognitive; Emotion; Sensory and Motor Function; Individual Differences; Task-fMRI; Personality; Connectivity
2.  Diffusion MRI at 25: Exploring brain tissue structure and function 
NeuroImage  2011;61(2):324-341.
Diffusion MRI (or dMRI) came into existence in the mid-1980s. During the last 25 years, diffusion MRI has been extraordinarily successful (with more than 300,000 entries on Google Scholar for diffusion MRI). Its main clinical domain of application has been neurological disorders, especially for the management of patients with acute stroke. It is also rapidly becoming a standard for white matter disorders, as diffusion tensor imaging (DTI) can reveal abnormalities in white matter fiber structure and provide outstanding maps of brain connectivity. The ability to visualize anatomical connections between different parts of the brain, non-invasively and on an individual basis, has emerged as a major breakthrough for neurosciences. The driving force of dMRI is to monitor microscopic, natural displacements of water molecules that occur in brain tissues as part of the physical diffusion process. Water molecules are thus used as a probe that can reveal microscopic details about tissue architecture, either normal or in a diseased state.
PMCID: PMC3683822  PMID: 22120012
Diffusion MRI; fMRI; Tractography; Connectivity; Human brain connectome; White matter; Stroke
3.  The future of functionally-related structural change assessment 
NeuroImage  2011;62(2):1293-1298.
The brain is continually changing its function and structure in response to changing environmental demands. Magnetic resonance imaging (MRI) methods can be used to repeatedly scan the same individuals over time and in this way have provided powerful tools for assessing such brain change. Functional MRI has provided important insights into changes that occur with learning or recovery but this review will focus on the complementary information that can be provided by structural MRI methods. Structural methods have been powerful in indicating when and where changes occur in both gray and white matter with learning and recovery. However, the measures that we derive from structural MRI are typically ambiguous in biological terms. An important future challenge is to develop methods that will allow us to determine precisely what has changed.
PMCID: PMC3677804  PMID: 22056531
Plasticity; learning; recovery; MRI; fMRI; diffusion MRI
4.  Myelin Water Imaging Reflects Clinical Variability in Multiple Sclerosis 
NeuroImage  2011;60(1):263-270.
Whilst MRI is routinely used for the assessment and diagnosis of multiple sclerosis, there is poor correspondence between clinical disability in primary progressive multiple sclerosis (PPMS) patients and conventional MRI markers of disease activity (e.g., number of enhancing lesions). As PPMS patients show diffuse and global myelin loss, the aim of this study was to evaluate the efficacy of whole-brain myelin water fraction (MWF) imaging in PPMS. Specifically, we sought to use full-brain analysis techniques to: 1) determine the reproducibility of MWF estimates in PPMS brain; 2) compare MWF values in PPMS brain to healthy controls; and 3) establish the relationship between MWF and clinical disability, regionally and globally throughout the brain. Seventeen PPMS patients and seventeen age-matched controls were imaged using a whole-brain multi-component relaxation imaging technique to measure MWF. Analysis of MWF reduction was performed on three spatial levels: 1) histogram; 2) white matter skeleton; and 3) voxel-wise at the single-subject level. From histogram analysis, PPMS patients had significantly reduced global normal appearing white matter MWF (6%, p=0.04) compared to controls. Focal lesions showed lower MWF values than white matter in controls (61%, p<0.001) and patients (59%, p<0.001). Along the white matter skeleton, MWF was diffusely reduced throughout the PPMS brain, with significant correlations between reduced MWF and increased clinical disability (more severe symptoms), as measured by the Expanded Disability Status Scale, within the corpus callosum and frontal, temporal, parietal and occipital white matter. Correlations with the more specific mental and sensory functional system scores were localized to clinically eloquent locations: reduced MWF was significantly associated with increased mental scores in anterior regions (i.e., frontal lobes and genu of the corpus callosum), and increased sensory scores in more posterior regions closer to the sensory cortex. Individual patient MWF maps were also compared to a normative population atlas, which highlighted areas of statistical difference between the individual patient and the population mean. A significant correlation was found between the volume of significantly reduced MWF and clinical disability (p=0.008, R = 0.58). Our results show that clinical disability is reflected in particular regions of cerebral white matter that are consistent between subjects, and illustrates a method to examine tissue alteration throughout the brain of individual patients. These results strongly support the use of MWF imaging to evaluate disease activity in PPMS.
PMCID: PMC3671155  PMID: 22155325
multiple sclerosis (MS); magnetic resonance imaging (MRI); brain; myelin water imaging; multi-component relaxation
5.  Integrity of white matter in the corpus callosum correlates with bimanual co-ordination skills 
NeuroImage  2007;36(Suppl 2):T16-T21.
Variation in brain structure may reflect variation in functional properties of specific brain systems. Structural variation may therefore reflect variation in behavioural performance. Here, we use diffusion-weighted magnetic resonance imaging to show that variation in white matter integrity in a specific region in the body of the corpus callosum is associated with variation in performance of a bimanual co-ordination task. When the callosal region showing this association is used as a seed for probabilistic tractography, inter-hemispheric pathways are generated to the supplementary motor area and caudal cingulate motor area. This provides further evidence for the role of medial wall motor areas in bimanual co-ordination and supports the idea that variation in brain structure reflects inter-individual differences in skilled performance.
PMCID: PMC3119816  PMID: 17499163

Results 1-5 (5)