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The aim of this research was to use novel functional imaging approaches to investigate connectivity between key brain regions affected in late-life depression (LLD), Alzheimer‟s disease (AD) and dementia with Lewy bodies (DLB). Using functional magnetic resonance imaging (fMRI), spontaneous low-frequency fluctuations (SLFs) in the blood oxygenation level dependent (BOLD) signal were measured at rest. SLFs represent synchronisation of neuronal activity; therefore differences between subjects reflect differences in underlying networks. Methods The first resting-state study investigated connectivity in LLD and involved 33 subjects aged 65 years and over; 17 control and 16 LLD subjects. It was planned to apply this methodology in the dementia study also. However, a global synchronicity pattern was evident in some subjects, which had not previously been seen in the LLD study. Methods were investigated to correct for these spurious fluctuations, thought to be unrelated to neuronal activity (e.g. physiological artefacts), meaning connectivity of neuronal origin only was investigated. The second study investigated connectivity in 47 subjects aged 60 years and over; 16 control, 16 AD and 15 DLB subjects. Additional pre-processing steps were used to remove non-neuronal fluctuations, informed by the previous study. All subjects were scanned using a 3 Tesla MRI System. Functional connectivity was measured by extracting the mean BOLD signal time-series from seed regions in the brain and cross-correlating with all other brain voxels using the FMRIB Software Library (FSL) tools. Results In the LLD study, control subjects showed frontal connectivity with the head of caudate nucleus, whereas the LLD group showed a more widespread pattern of connectivity. LLD subjects showed significantly greater connectivity than controls between the bilateral caudate and a number of brain regions, whereas controls showed no brain regions of greater connectivity than LLD subjects. Pre-processing methods, to correct for non-neuronal fluctuations, were found to remove global synchronicity and improve data accuracy. In the second study, AD and DLB subjects showed significantly greater functional connectivity with a number of seed regions compared to the control group. No brain regions showed significantly greater connectivity in control compared to AD or DLB subjects. Additionally, specific seed regions showed greater connectivity in AD compared to DLB, and vice versa. Conclusions This study reported abnormalities in connectivity in LLD, AD and DLB. The potential outcome of these findings is that they will inform greater understanding of the neurobiology of these disorders and in turn aid in early diagnosis and in the development of specific treatments to target the abnormally functioning brain regions.

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