Salience Network Atrophy Links Neuron Type-Specific Pathobiology to Loss of Empathy in Frontotemporal Dementia

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Von Economo neurons are large, spindle-shaped neurons that are sparsely studded through just three small regions of the human brain. enter image description here Source: The Allen Institute

They were first identified approximately 140 years ago by the Russian scientist Vladimir Betz and later named after the anatomist Constantin von Economo, and have since been spotted in the brains of great apes, whales, dolphins, cows and elephants.

There’s a theory that these rare neurons evolved independently in animals with particularly large brains, or perhaps particularly social animals. They seem to be lost in people with certain brain diseases and are overabundant in "super-agers," older people who don’t suffer the standard memory loss of aging.

But scientists don’t really understand what they do, in part because they aren’t found in common lab animals like mice and rats, making them difficult to study.

Von Economo neurons and neurodegenerative diseases

Each neurodegenerative syndrome reflects a stereotyped pattern of cellular, regional, and large-scale brain network degeneration. In behavioral variant of frontotemporal dementia (bvFTD), a disorder of social-emotional function, von Economo neurons, and fork cells are among the initial neuronal targets.

These large projection neurons are concentrated in the anterior cingulate and frontoinsular cortices. Both structures are found deep within the mammalian brain. The Frontoinsular are believed to be involved in consciousness and play a role in diverse functions usually linked to emotion. the fronto-insular cortex, a region which appears to have undergone significant evolutionary adaptations in mankind – perhaps as recently as 100,000 years ago. The anterior cingulate is also involved in certain higher-level functions, such as attention allocation, reward anticipation, decision-making.

In the article discussed today, the scientists studied patients with bvFTD, amyotrophic lateral sclerosis (ALS), or both, given that these syndromes share common pathobiological and genetic factors.

Patients were selected from a previous histopathological study(Nana et al. 2018) based on availability of a complete neuroimaging and histopathological dataset. They included 16 patients in total 5 patientswith bvFTD, 9 with bvFTD-MND, and 2 with ALS.

The goal of the scientists was to determine how neuron type-specific TAR DNA-binding protein of 43 kDa (TDP-43) pathobiology relates to atrophy in specific brain structures and to loss of emotional empathy, a cardinal feature of bvFTD. The authors combined questionnaire-based empathy assessments, in vivo structural MR imaging, and quantitative histopathological data.

The authors show that TDP-43 pathobiology within right frontoinsular von Economo neurons and fork cells is associated with salience network atrophy spanning insular, medial frontal, and thalamic regions. The salience network is a large scale brain network of the human brain that is primarily composed of the anterior insula and dorsal anterior cingulate cortex. Gray matter degeneration within these structures mediated loss of emotional empathy, suggesting a chain of influence linking the cellular, regional/network, and behavioral levels in producing signature bvFTD clinical features.


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