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Finding the imposter: understanding a rare delusional disorder using brain connectivity

In residency, I met a patient who told me a peculiar story about an encounter with his pet cat. He began to feel that his world was strange and unfamiliar. He became scared, paranoid, convinced that he was being tracked by federal agents. But the most distressing and bizarre change occurred in his pet cat. He told me he recognized his cat, that the cat had the same color and type of fur, ate the same food from the same bowl, walked and jumped and played with the same idiosyncrasies as his cat. But it wasn’t his cat. It was an imposter.

His syndrome was a variant of Capgras syndrome, where a patient develops the delusion that a family member has been replaced by an identical imposter. Knowing what to look for, I began finding more and more cases: a man with Alzheimer’s who believed his daughter was an imposter, a woman with a right frontal lobe stroke who believed her house was a replica of her real house. Some patients had the opposite feeling, believing that strangers were actually familiar persons in disguise (Fregoli Delusion).

While these delusions, collectively referred to as delusional misidentifications, were initially described in psychiatric patients, several of the patients I saw had focal brain lesions. So, my colleagues and I asked whether studying these patients might help us to understand how the brain produces such bizarre yet specific delusions. In the tradition of classical neurology, we attempted to “localize” the part of the brain that was responsible for these delusions. However, while we found that most injuries occurred on the right side of the brain, there was no single location where the brain lesions always occurred.

We therefore tried to test an alternative idea: that lesions in one brain region disrupt brain activity in other parts of the brain as well. This approach is not new; Constantin Von Monakow first proposed this idea, called diaschesis, over 100 years ago. However, we used a relatively new technique called lesion network mapping, which uses the human connectome to determine areas that are functionally connected to the location of a focal brain injury. Using this technique, we found that lesions causing delusional misidentifications in different locations had the same pattern of brain connectivity.

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Network mapping of delusional misidentification lesions overlaps with regions involved in familiarity detection. Image provided by the authors and used with permission.

Importantly, this connectivity was to brain regions that could help to explain why these patients developed these specific types of delusions. All the lesions causing delusional misidentifications were connected to regions involved in familiarity, explaining why patients with the imposter syndrome may lose this feeling of familiarity. Additionally, 16 of the 17 patients had lesions connected to regions involved in evaluating beliefs, potentially explaining why these patients accept their delusional beliefs as true. Brain lesions that didn’t cause delusions were not connected to these brain regions, explaining why these other patients did not develop delusions. Finally, we looked at lesions causing different types of delusions, like paranoia and jealousy. These delusions do not involve any abnormal feelings of familiarity, so shouldn’t be connected to familiarity regions. However, because they have delusions, these patients should have lesions connected to belief evaluation regions. That was exactly what we found: lesions were connected to belief evaluation, but not familiarity, regions.

We used lesion network mapping to “find the imposter” hiding in the brain, showing how a single brain injury might alter the relationship between two interacting sets of brain regions. Our findings don’t give the entire story for why delusional misidentifications occur, but they do provide an important step towards answering this question. Moreover, using functional connectivity to test for diaschesis could lend insight into other complex, bizarre neuropsychiatric symptoms that remain difficult to understand.

Featured image credit: Brain by Pete Linforth. CC0 Public Domain via Pixabay.

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