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Series of six brain scan images showing: a health human brain; claustrum and external capsule; external capsule only; and claustrum only.

A new review paper, published in the journal Brain, has shown that a poorly understood region of the brain called the claustrum may play an important role in how we experience pain. 

The little understood area of the brain called the claustrum may be the next frontier in improving outcomes for brain damage patients.

A collaboration of Oxford University research groups from the Department of Physiology, Anatomy & Genetics (DPAG), the Nuffield Department of Clinical Neurosciences (NDCN)

Representative T2-weighted image of a healthy human brain (red arrows indicate the claustrum)Representative T2-weighted image of a healthy human brain (red arrows indicate the claustrum) and Experimental Psychology (EP) has uncovered new clues regarding the function of one of most densely interconnected, yet rarely studied, areas of the brain.

The researchers reviewed studies of patients with lesions in the claustrum, which although rare show cognitive impairments and seizures. Furthermore, the lack of clinical focus on the claustrum may mean there are many more cases yet to be uncovered.

They also uncovered an under-appreciated link between the claustrum and pain. It is already known that there are links between the claustrum and perception, salience and the sleep-wake cycle, but this is the first time a research team has shown how the claustrum might be more involved in the debilitating experience of pain.

Dr Adam Packer, the lead author of the study, said: "The problem with understanding how the claustrum works is that it is deep inside the brain, and damage that is specific to it is a very rare occurrence. What makes it more difficult to work out what the claustrum actually does is that these rare occurrences are also linked to such a broad range of symptoms.

"Clearly, when the claustrum is damaged the effects are severe and better therapies are

T2-weighted image showing a lesion reported as affecting the claustrum. From Ishii et al 2011 AJNR, DOI:10.3174/ajnr.A2603T2-weighted image showing a lesion reported as affecting the claustrum. From Ishii et al 2011 AJNR, DOI:10.3174/ajnr.A2603 urgently needed. It is possible that claustrum damage is more common than we currently realise, and it may be a crucial component in many more brain damage cases. This work is important because it gives us some insight into the cognitive and neurological processes in which the claustrum may be involved, and gives us targets to pursue in basic research in the lab."

The researchers found several recorded instances of either infection, auto immune, or other process that attacked the claustrum in particular, and by analysing the results of these studies and others the most common symptoms in patients were cognitive impairment and seizures.

Associate Professor Sanjay Manohar from EP and NDCN said: "The claustrum is very often damaged in stroke, but almost never on its own. This makes it especially hard to infer its  function from lesions. We found it almost impossible to assign the claustrum any particular computational role. One thing that makes it unlike other subcortical nuclei, though, is that damage to the claustrum seems to promote seizures."

More work is required to better understand the claustrum and better understand the impact of damage to the claustrum, which could ultimately change clinical guidelines.

The multidisciplinary team included three first authors Dr Huriye Atilgan, Dr Max Doody (DPAG), Dr David Oliver (University of Toronto), Professor Vladyslav Vyazovskiy (DPAG’s sleep PI), Dr Adam Packer, Professor Irene Tracey (FMRIB and NDCN), and Associate Professor Sanjay Manohar (EP).

More information about the research, including a video interview with Dr Adam Packer, can be found here: https://www.dpag.ox.ac.uk/news/adam-packer-set-to-explore-uncharted-territory-in-the-brain.

The full paper, ‘Human lesions and animal studies link the claustrum to perception, salience, pain, and sleep’, is available to read in the journal Brain.

This story is also featured on the University of Oxford website.

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