Towards Patient-Specific Brain Networks Using Functional Magnetic Resonance Imaging

fMRI applications are rare in translational medicine and clinical practice. What can be inferred from a single fMRI scan is often unreliable due to the relative low signal-to-noise ratio compared to other neuroimaging modalities. However, the potential of fMRI is promising. It is one of the few neuroimaging modalities to obtain functional brain organisation of an individual during task engagement and rest. This work extends on current fMRI image processing approaches to obtain robust estimates of functional brain organisation in two resting-state fMRI cohorts. The first cohort comprises of young adults who were born at extremely low gestations and age-matched healthy controls. Group analysis between term- and preterm-born adults revealed differences in functional organisation, which were discovered to be predominantly caused by underlying structural and physiological differences. The second cohort comprises of elderly adults with young onset Alzheimer’s disease and age-matched controls. Their corresponding resting-state fMRI scans are short in scanning time resulting in unreliable spatial estimates with conventional dual regression analysis. This problem was addressed by the development of an ensemble averaging of matrix factorisations approach to compute single subject spatial maps characterised by improved spatial reproducibility compared to maps obtained by dual regression. The approach was extended with a haemodynamic forward model to obtain surrogate neural activations to examine the subject’s task behaviour. This approach applied to two task-fMRI cohorts showed that these surrogate neural activations matched with original task timings in most of the examined fMRI scans but also revealed subjects with task behaviour different than intended by the researcher. It is hoped that both the findings in this work and the novel matrix factorisation approach itself will benefit the fMRI community. To this end, the derived tools are made available online to aid development and validation of methods for resting-state and task fMRI experiments

Physiological and motion signatures in static and time-varying functional connectivity and their subject identifiability

Human brain connectivity yields significant potential as a noninvasive biomarker. Several studies have used fMRI-based connectivity fingerprinting to characterize individual patterns of brain activity. However, it is not clear whether these patterns mainly reflect neural activity or the effect of physiological and motion processes. To answer this question, we capitalize on a large data sample from the Human Connectome Project and rigorously investigate the contribution of the aforementioned processes on functional connectivity (FC) and time-varying FC, as well as their contribution to subject identifiability. We find that head motion, as well as heart rate and breathing fluctuations, induce artifactual connectivity within distinct resting-state networks and that they correlate with recurrent patterns in time-varying FC. Even though the spatiotemporal signatures of these processes yield above-chance levels in subject identifiability, removing their effects at the preprocessing stage improves identifiability, suggesting a neural component underpinning the inter-individual differences in connectivity

Building a Science of Individual Differences from fMRI

To date, fMRI research has been concerned primarily with evincing generic principles of brain function through averaging data from multiple subjects. Given rapid developments in both hardware and analysis tools, the field is now poised to study fMRI-derived measures in individual subjects, and to relate these to psychological traits or genetic variations. We discuss issues of validity, reliability and statistical assessment that arise when the focus shifts to individual subjects and that are applicable also to other imaging modalities. We emphasize that individual assessment of neural function with fMRI presents specific challenges and necessitates careful consideration of anatomical and vascular between-subject variability as well as sources of within-subject variability

Building a Science of Individual Differences from fMRI

To date, fMRI research has been concerned primarily with evincing generic principles of brain function through averaging data from multiple subjects. Given rapid developments in both hardware and analysis tools, the field is now poised to study fMRI-derived measures in individual subjects, and to relate these to psychological traits or genetic variations. We discuss issues of validity, reliability and statistical assessment that arise when the focus shifts to individual subjects and that are applicable also to other imaging modalities. We emphasize that individual assessment of neural function with fMRI presents specific challenges and necessitates careful consideration of anatomical and vascular between-subject variability as well as sources of within-subject variability