Although blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) is a widely available, non-invasive technique that offers excellent spatial resolution, it remains limited by practical constraints imposed by the scanner environment. More recently, functional near infrared spectroscopy (fNIRS) has emerged as an alternative hemodynamic-based approach that possesses a number of strengths where fMRI is limited, most notably in portability and higher tolerance for motion. To date, fNIRS has shown promise in its ability to shed light on the functioning of the human brain in populations and contexts previously inaccessible to fMRI. Notable contributions include infant neuroimaging studies and studies examining full-body behaviors, such as exercise. However, much like fMRI, fNIRS has technical constraints that have limited its application to clinical settings, including a lower spatial resolution and limited depth of recording. Thus, by combining fMRI and fNIRS in such a way that the two methods complement each other, a multimodal imaging approach may allow for more complex research paradigms than is feasible with either technique alone. In light of these issues, the purpose of the current review is to: (1) provide an overview of fMRI and fNIRS and their associated strengths and limitations; (2) review existing combined fMRI-fNIRS recording studies; and (3) discuss how their combined use in future research practices may aid in advancing modern investigations of human brain function.

BackgroundAlzheimer's disease (AD) is a progressive neurodegenerative disorder. Current avenues of AD research focus on pre-symptomatic biomarkers that will assist with early diagnosis of AD. The majority of magnetic resonance imaging (MRI) based biomarker research to date has focused on neuronal loss in grey matter and there is a paucity of research on white matter.MethodsLongitudinal DTI data from the Alzheimer's Disease Neuroimaging Initiative 2 database were used to examine 1) the within-group microstructural white matter changes in individuals with AD and healthy controls at baseline and year one; and 2) the between-group microstructural differences in individuals with AD and healthy controls at both time points.Results1) Within-group: longitudinal Tract-Based Spatial Statistics revealed that individuals with AD and healthy controls both had widespread reduced fractional anisotropy (FA) and increased mean diffusivity (MD) with changes in the hippocampal cingulum exclusive to the AD group. 2) Between-group: relative to healthy controls, individuals with AD had lower FA and higher MD in the hippocampal cingulum, as well as the corpus callosum, internal and external capsule; corona radiata; posterior thalamic radiation; superior and inferior longitudinal fasciculus; fronto-occipital fasciculus; cingulate gyri; fornix; uncinate fasciculus; and tapetum.ConclusionThe current results indicate that sensitivity to white matter microstructure is a promising avenue for AD biomarker research. Additional longitudinal studies on both white and grey matter are warranted to further evaluate potential clinical utility.

Introduction: Alzheimer’s disease (AD) is a neurodegenerative disorder with a clinical presentation characterized by memory impairment and executive dysfunction. Our group previously demonstrated significant alterations in white matter microstructural metrics in AD compared to healthy older adults. We aimed to further investigate the relationship between white matter microstructure in AD and cognitive function, including memory and executive function.Methods: Diffusion tensor imaging (DTI) and neuropsychological data were downloaded from the AD Neuroimaging Initiative database for 49 individuals with AD and 48 matched healthy older adults. The relationship between whole-brain fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AxD), radial diffusivity (RD), and composite scores of memory and executive function was examined. We also considered voxel-wise relationships using Tract-Based Spatial Statistics.Results: As expected, individuals with AD had lower composite scores on tests of memory and executive function, as well as disrupted white matter integrity (low FA, high MD, AxD, and RD) relative to healthy older adults in widespread regions, including the hippocampus. When the AD and healthy older adult groups were combined, we found significant relationships between DTI metrics (FA/MD/AxD/RD) and memory scores across widespread regions of the brain, including the medial temporal regions. We also found significant relationships between DTI metrics (FA/MD/AxD/RD) and executive function in widespread regions, including the frontal areas in the combined group. However, when the groups were examined separately, no significant relationships were found between DTI metrics (FA/MD/AxD/RD) and memory performance for either group. Further, we did not find any significant relationships between DTI metrics (FA/MD/AxD/RD) and executive function in the AD group, but we did observe significant relationships between FA/RD, and executive function in healthy older adults.Conclusion: White matter integrity is disrupted in AD. In a mixed sample of AD and healthy elderly persons, associations between measures of white matter microstructure and memory and executive cognitive test performance were evident. However, no significant linear relationship between the degree of white matter disruption and level of cognitive functioning (memory and executive abilities) was found in those with AD. Future longitudinal studies of the relations between DTI metrics and cognitive function in AD are required to determine whether DTI has potential to measure progression of AD and/or treatment efficacy.

Motor function recovery can occur beyond 6 years after severe traumatic brain injury, both in neural plasticity and clinical outcome. This demonstrates that continued benefits in physical function due to rehabilitative efforts can be achieved for many years following injury. The finding challenges current practices and assumptions in rehabilitation following traumatic brain injury.

Multiple Sclerosis (MS) is a chronic neurological condition typically diagnosed in early adulthood that often requires lifelong treatment for symptom management.Despite pharmacological treatment, many individuals with MS continue to experience symptoms. Exercise may hold promise for MS treatment, but changes in brain structure following exercise have not been thoroughly investigated, and important cognitive and psychosocial symptoms are less frequently included as primary outcome measures. This dissertation is comprised of three manuscripts that investigate the relationships between exercise, white matter microstructure, and cognitive and psychosocial symptoms in MS. Study One: The first study used a mail-out questionnaire to investigate the relationship between physical activity and common MS symptoms, including fatigue, depressed mood, and perceived cognitive impairment. Results indicated that individuals with MS who reported more strenuous and/or frequent physical activity reported less fatigue, less depression, and fewer perceived memory problems. Study Two: The second study used a type of magnetic resonance imaging known as diffusion tensor imaging (DTI), along with neuropsychological measures and questionnaires to investigate whether reported physical activity, neuropsychological performance, and common self-reported MS symptoms of fatigue and depressed mood were related to brain structure in relapsing-remitting MS (RRMS). There was no evidence of a relationship between white matter microstructure and level of physical activity for individuals with RRMS, nor was there evidence for a relationship between white matter iv microstructure and MS symptoms related to cognition, fatigue, and mood. Study Three: The third study used pre-and post-intervention DTI, neuropsychological testing and self-report questionnaires to investigate whether a 12-week exercise intervention improved white matter microstructure, cognition, or symptoms of fatigue and depressed mood in RRMS. Results indicated that following a 12-week exercise intervention, individuals with RRMS performed better on measures of information processing speed, reported fewer prospective memory problems, and reported fewer problems with fatigue. There were no increases or decreases in white matter microstructure. Together, these studies suggest that exercise may be helpful in the management of some cognitive and psychosocial MS symptoms.v Table of ContentsSupervisory Committee .