The Insular Cortex and Frontotemporal Dementia

Figure showing the insular cortex (circled) in a coronal section indicated by the blue line in the inset*

Neurologist Dr William Seeley has a review article on the relationship between the anterior insula and frontotemporal dementia which is freely available here and which is written under a creative commons license**. I found this really interesting as it ties together a diverse amount of material on both frontotemporal dementia and the insular cortex at the same time as generating a number of profound hypotheses. Damasio and later Craig have generated a lot of interest in the insular cortex and its possible relation to how we feel. Seeley makes a lot of links in this review and this perspective opens up a number of avenues for further research into frontotemporal dementia. The main focus in his review however is on behavioural variant frontotemporal dementia (bvFTD) (although he also examines semantic dementia and progressive non-fluent aphasia) and in the first few sections he sets the scene for more detailed hypotheses about the relationship between the insular cortex and bvFTD.

bvFTD is associated with dramatic changes in social–emotional processing which result from targeted medial frontal and frontoinsular degeneration

Furthermore in frontotemporal dementia, Seeley cites seminal research showing that in the early stages of the disease process at post-mortem that

Stage 1 showed atrophy limited to dorsomedial frontal cortex (including ACC) and posterior orbitofrontal cortex where it meets the frontoinsula

He then introduces the reader to the ‘salience network’ – a functional network in the brain and cites research showing that bvFTD involves this network initially before affecting other networks as the disease progresses. He makes interesting points about Von Economo neurons and points to interesting research suggesting involvement of these specialised neurons in FTD rather than Alzheimer’s Disease. He suggests the extremely interesting hypothesis that the Von Economo neurons might in some way be related to the disease process itself. I think the Von Economo neurons have been considered to be a rather mysterious class of neurons given that they have massively widespread connections. Indeed authors such as Craig have suggested that they together with the insular cortex might represent the anatomical correlate of ‘self-awareness’. Certainly if researchers such as Sebastian Seung are interested in clarifying the role of networks, or connectomes – those featuring the Von Economo neurons might present a fascinating starting point.

Seeley cites other research providing even more specific hypotheses

Strikingly, bvFTD clinical severity correlated with connectivity disruption in only one Salience Network region: the right frontoinsula

For those interested in Frontotemporal Dementia research, such very specific hypotheses give very useful insights and one has only to think of the Amyloid hypothesis to think of how useful this can be in offering a framework for developing further insights through hypothesis-driven research initiatives (e.g the Alzheimer’s Disease Neuroimaging Initiative).


*Modified from Original Image by John Beal PhD, Dep’t. of Cellular Biology & Anatomy, Louisiana State University Health Sciences Center Shreveport

** Creative Commons Non-Commercial Attribution License

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