Lesions Connected to Two Brain Areas May Cause Delusional Misidentification

Deborah Brauser

January 06, 2017

Patients with a neurologic injury who develop the belief that known people are imposters (Capgras syndrome) or that strangers are actually loved ones in disguise (Fregoli syndrome) may have a single lesion that's connected to two specific areas of the brain, a small study suggests.

Using a "lesion network mapping" technique they developed, the investigators assessed data on 17 patients with delusional misidentification syndromes (DMS).

They found that all 17 had lesion locations connected to the retrosplenial cortex, which is responsible for familiarity processing. In addition, all but 1 of the lesions were also connected to the belief evaluation region of the right ventral frontal cortex.

In further analyses, patients who had delusions not classified as DMS, such as those related to persecution, had lesions connected to belief violation areas only, "suggesting that these regions are involved in monitoring for delusional beliefs in general," lead author R. Ryan Darby, MD, Department of Neurology at Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, Massachusetts, said in a release.

Dr R. Ryan Darby

"However, only lesions causing delusional misidentifications were connected to familiarity regions [in DMS], explaining the specific bizarre content," he added. "In other words, lesions had to be connected to both regions."

Still, Dr Darby noted that follow-up research using functional MRI and a much larger patient population is needed before they can definitively say that the two regions must be dysfunctional to cause the onset of this type of delusion.

"But hopefully just showing that we're beginning to understand all of this can be comforting to families and help physicians to separate the psychiatric symptoms from changes in the brain," he said to Medscape Medical News.

The findings were published online December 3 in Brain.

Imposter Family, Homes, Cats

Although Capgras syndrome was first written about in 1923, it is extremely rare, note the researchers. Patients with the disorder recognize a loved one but also feel that something is unfamiliar, leading to their belief that an imposter is pretending to be the loved one.

A version of this syndrome is reduplicative amnesia, which involves underfamiliarity with what should be a known place, such as a home.

In Fregoli syndrome, a patient believes that a stranger is a known person in disguise. Reduplicative paramnesia is this same feeling, but about a place.

Dr Darby reported that DMS can also involve animals. In fact, he wrote earlier this year about a case of a 73-year-old man who believed that an imposter animal had replaced his cat.

"He said that the replica cat was spying on him and he really believed that," he said.

"The first time you meet someone with delusional misidentification is so striking. They can seem otherwise rational, yet maintain their delusional belief," said Dr Darby.

The neuroanatomic mechanism for the onset of DMS after a focal brain injury has not been known previously, although speculation from the field has suggested that a second lesion or comorbid dementia, delirium, or psychiatric disorder is needed.

Instead, the investigators hypothesized that these types of delusional syndromes "arise from single lesions at unique locations within the human brain connectome."

"This hypothesis is motivated by evidence that symptoms emerge from sites functionally connected to a lesion location, not just the lesion location itself," they write.

Strong Pattern of Connectivity

In the study, the researchers identified 17 cases of lesion-induced DMS. All of these patients had had an ischemic or hemorrhagic stroke. Among the population, 15 were found through a literature search and 2 were patients who presented at BIDMC.

This included an 83-year-old woman who, 4 months after having a right frontal hemorrhage, reported that her house had been replaced by an identical one in a different location — and wished to return to her real home. This delusion went away 4 months later.

The other BIDMC patient was also an older woman who said her home felt like a duplicate in a different city. Her delusion resolved itself the following day.

The investigators added MRI data for all of the lesions to one overarching brain atlas. Next, using their network mapping application, they identified brain regions connected to the lesion locations. Finally, meta-analyses of past studies that used functional MRI were examined.

"We found that all 17 lesion locations were functionally connected to the left retrosplenial cortex, the region most activated in functional [MRI] studies of familiarity," report the researchers.

Dr Darby said this finding was somewhat surprising "because this isn't one of the areas people thought of initially" regarding DMS.

Sixteen of the patients also had lesions functionally connected to the right ventral frontal cortex/anterior insula.

"I think this fits with what a lot of people thought was going on with the belief evaluation. But I think giving it a more precise definition was unique," said Dr Darby.

In addition, this pattern of connectivity to both regions was significantly stronger for lesions that caused DMS than for lesions that caused other neurologic disorders, such as auditory or visual hallucinations and subcortical aphasia (P < .0001).

When asked, Dr Darby said that they saw no differences between patients who had Capgras syndrome and those with Fregoli syndrome.

"We didn't put that information into the paper because in other work we've done, patients could have both syndromes at the same time. Because of that, we felt that the underlying reason why someone would develop this was probably similar between the two," he said.

"To really assess whether there are differences, we'd need a bigger number of subjects."

Disrupting Brain's Detector, Monitor

Overall, "we showed how complex symptoms can emerge based on brain connectivity," coinvestigator Michael D. Fox, MD, PhD, director of the Laboratory for Brain Network Imaging and Modulation at BIDMC, said in the release.

"With a lesion in exactly the right place, you can disrupt the brain's familiarity detector and reality monitor simultaneously, resulting in bizarre delusions," he said. "Understanding where these symptoms come from is an important step toward treating them."

Dr Darby noted that intimacy is often lost when a patient believes a spouse is an imposter.

"The impact on the patient's family can be heart-breaking," he said. "In these cases, even just knowing that the delusion has a name and is part of a neurological disorder can be helpful."

He added that a past review by the investigators of patients who had a stroke or traumatic brain injury causing DMS showed that the syndrome usually lasted for several months to a year, and then "in the majority of the cases" improved on its own.

"We don't really know why that's happening. It's not clear if it's due to the brain having plasticity and changing and whether that's helping to compensate for this — or if it's some other mechanism," said Dr Darby. "But it is fortunate that these syndromes can resolve with enough time."

However, he noted that there have been cases where the beliefs continue without resolving or resolve and then come back if someone gets sick later on with infection or delirium.

The study was funded by the Sidney R. Baer Jr Foundation, grants from the National Institutes of Health, the Football Players Health Study at Harvard University, Harvard Catalyst/The Harvard Clinical and Translational Science Center, and the American Brain Foundation. The study authors have disclosed no relevant financial relationships.

Brain. Published online December 3, 2016. Abstract

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