In the last decade, the advent of neuroimaging techniques has considerably increased our understanding of disease progression in various neurodegenerative conditions, such as Alzheimer’s disease (AD). For example, characteristic patterns of brain atrophy (i.e. shrinkage of brain regions due to diseases) as well as disconnections between brain regions have been widely described in AD. More recently, the field is undergoing a paradigm shift with increasing attention to the integrative nature of the functional organisation in the brain, and how this network-level integration might be compromised in disease.
While this macro-level framework has exciting potential to uncover novel insights beyond conventional analyses (i.e brain volumes and function), previous studies have restricted their analyses by considering only the strongest connections in the brain.This simplification overlooks the role of weaker connections in maintaining an optimal mechanism of information exchange of the brain. This is largely because they can form part of indirect paths which could, in turn, be shorter than the direct paths. Shorter paths facilitate greater efficiency of information transfer between brain regions.
To overcome this simplification, a group of researchers from the Department of Psychiatry including Professor John Suckling and Professor John O’Brien, has recently conducted a novel study in which all possible brain connections – irrespective of strength – were investigated in a group of AD patients and healthy individuals. Firstly, the wiring map of connections in the brain (i.e. brain network) were constructed from resting-state functional imaging data from all participants. Structural differences in gray matter volumes were also compared between AD and controls. The functional networks were then analysed to determine the distribution of all direct and indirect connections in both AD and control groups – one of the first attempts in the prevailing literature.
Interestingly, although Suckling and colleagues found very minimal atrophy in the brain structures, a significantly greater proportion of indirect connections was observed in the AD group. This suggests that the flow of information was traversing in a long-winded or circuitous fashion compared to healthy controls of the same age. Analogous to the scenario where drivers are forced to take a different, indirect route because the main road has been damaged by an earthquake, the loss of direct connections due to neurodegeneration could trigger a compensatory reorganisation of the brain where indirect pathways emerge as the main routes of information transfer. This notion also receives credence from the fact that these AD patients were still in the early stages of their illness, with very little in the way of the characteristic changes in brain atrophy, and had limited cognitive decline.
Commenting on the significance of these findings, lead author Prof John Suckling said:
“In our everyday lives we recognise that weak links can also have a powerful influence; for example, although we may not personally know a potential employer, most job opportunities arise from friend-of-a-friend, professional relationships. This is potentially also how the brain communicates with “indirect” pathways forming a large proportion of the possible routes for information flow. The compensatory increase in indirect paths to preserve cognition is potentially an important period in the early stages of Alzheimer’s disease when therapies that maintain function might be, and are, most effective. Understanding these changes to brain organisation, along with the progression of brain atrophy and deposition amyloid plaques is a central challenge to brain imaging research in Alzheimer’s disease.”
Professor John O’Brien from the Old Age Psychiatry Group added:
“This study showed that different methods of analysing connectivity in different brain disorders provided new insights into the study of neural networks. The significant changes seen occurred in the absence of marked atrophy in Alzheimer’s disease, showing this method of looking at all brain connections may be a sensitive marker of abnormalities in brain connectivity in dementia.”
Written by Elijah Mak.