Lesion Network Mapping May Untangle Neuroanatomic Areas Mediating Delusions

HILTON HEAD, SC—Delusions of a common type, whether associated with neurologic or psychiatric disease, appear likely to involve common pathways in the brain, according to new studies using lesion network mapping. This type of mapping appears to reveal the pathways that explain why single focal neurologic lesions in different brain locations cause similar delusional symptoms.

Lesion network mapping “is an approach to look at neurologic and psychiatric symptoms at the level of networks to understand brain behavior relationships,” explained Ryan Darby, MD, Assistant Professor of Neurology and Director of the Frontotemporal Dementia Clinic at Vanderbilt University Medical Center in Nashville. From the neurologic perspective, this work may provide insight into brain function, but Dr. Darby, speaking at the 41st Annual Contemporary Clinical Neurology Symposium, sees broader implications.

“This [technique] might provide insight into psychiatric symptoms that we have had trouble truly understanding in relation to neuroanatomy,” Dr. Darby said. Some of the delusions associated with focal neurologic lesions have parallels with those associated with schizoaffective disorders, and this work may explain what areas of the brain are affected, even in the absence of visible lesions on imaging.

Lesion network mapping is a technique developed to identify functionally related regions of the brain. This goal is important because focal neurologic lesions associated with specific delusions are not necessarily located in the same brain region. The concept of networks connecting brain activity and network mapping recognizes that dysfunction in one brain area can lead to dysfunction in others. Lesion network mapping provides a strategy to identify these relationships.

Capgras Syndrome

Dr. Darby provided insight into lesion network mapping based on work he performed and published on Capgras syndrome, which describes an irrational belief that a familiar person or place is an impostor or a facsimile. As examples, he described a woman who thought her home, although familiar, was a replica. In another case, a man believed that his son-in-law, whom he recognized, was an impersonator. This type of delusion is complex, because it appears to involve a disruption of processes that mediate familiarity, as well as the cognitive processes employed to recognize and reject false beliefs.

One hypothesis about Capgras syndrome is that it involves “a two-hit phenomenon” in which dysfunction occurs simultaneously in distinct areas of the brain, according to Dr. Darby. His work with network lesion mapping in Capgras syndrome supports that hypothesis.

Lesion network mapping, a technique first described in a 2015 study, has established functional connectivity between regions of the brain in normal individuals in a resting state. A 2017 study tested the potential value of lesion network mapping in 17 cases of Capgras syndrome.

Most of the cases, including the imaging data, were retrieved from previously published studies, although several contemporary cases were included. In the investigation, Dr. Darby and his coinvestigators first demonstrated the heterogeneity in lesion location. Captured on MRI scans and traced onto a brain atlas, all but one of the lesions in patients with Capgras syndrome were found in the right hemisphere, but many of the lesions had nonoverlapping areas of involvement.

Despite the heterogeneity in lesion location, lesion network mapping demonstrated that all 17 lesions were functionally connected to the retrosplenial cortex. In addition, 16 of the 17 lesions were functionally connected to the right frontal cortex.

According to Dr. Darby, both associations are potentially important. On the basis of previously published studies with functional MRI (fMRI), the left retrosplenial cortex has been implicated in mediating familiarity. The right frontal cortex has been associated with belief evaluation. Moreover, in a control evaluation of published cases in which delusions did not involve misidentification, no functional connections to either the left retrosplenial cortex or the right frontal cortex were observed, according to Dr. Darby. In contrast, patients with disorders consistent with an impaired belief evaluation, such as paranoia or pathologic jealousy, did have lesions in the right frontal cortex as predicted.

 

Insights Into Other Neuropsychiatric Disorders

Lesion network mapping is now being applied to other types of delusions. Dr. Darby described work with neurologic and psychiatric disorders associated with a perception that free will has been lost. These include neuropsychiatric conditions such as akinetic mutism, alien limb syndrome, catatonia, and psychogenic nonepileptic seizures. According to Dr. Darby, there are two potential components involved in a delusion involving an impaired sense of free will. There is a change in the volitional component that captures the motivation and desire to move, as well as an impaired sense of agency, which refers to the feeling of responsibility for movement.

Describing ongoing work with these types of delusions, Dr. Darby reported that neurologic lesion locations, like those in Capgras syndrome, were heterogeneous. Again, most of these lesions could be connected to a network functional map that was not shared by those without these symptoms.

“For many of these complex disorders, what we are seeing is that pathology in different areas causes the same behavior syndrome by affecting different parts of the same network,” Dr. Darby said. He believes neurologic and psychiatric diseases producing the same delusions are likely to be mediated by dysfunction in the same areas of the brain.

In patients with psychiatric diseases who have delusions associated with loss of a sense of free will, lesions are not readily observed, but Dr. Darby reported that there is evidence of modest changes, such as atrophy or diminished metabolism, that can be “linked up to those areas of the brain involved in agency and volition, and not to areas that are associated with other comorbid symptoms.”

Broader Implications

The fact that the same or similar delusions are shared by neurologic and psychiatric disorders provides the basis for speculating that this work may lead to a more detailed understanding of brain function. According to Dr. Darby, the work with lesion network mapping in neurologic disorders “may tell us where to look for the pathology in psychiatric diseases.”

The lesion network testing may be an important tool for understanding the relationship of brain pathology to behavior, according to Dr. Darby. Prior to lesion network mapping, the heterogeneity of lesion location for patients with shared types of delusion has been difficult to understand, but Dr. Darby indicated that lesion network mapping shows potential for placing specific symptom expression into a context of neuroanatomy.

—Theodore Bosworth

Suggested Reading

Boes AD, Prasad S, Liu Q, et al. Network localization of neurological symptoms from focal brain lesions. Brain. 2015;138(Pt 10):3061-3075.

Darby RR, Laganiere S, Pascual-Leone A, et al. Finding the imposter: brain connectivity of lesions causing delusional misidentifications. Brain. 2017;140(2):497-507.

HILTON HEAD, SC—Delusions of a common type, whether associated with neurologic or psychiatric disease, appear likely to involve common pathways in the brain, according to new studies using lesion network mapping. This type of mapping appears to reveal the pathways that explain why single focal neurologic lesions in different brain locations cause similar delusional symptoms.

Lesion network mapping “is an approach to look at neurologic and psychiatric symptoms at the level of networks to understand brain behavior relationships,” explained Ryan Darby, MD, Assistant Professor of Neurology and Director of the Frontotemporal Dementia Clinic at Vanderbilt University Medical Center in Nashville. From the neurologic perspective, this work may provide insight into brain function, but Dr. Darby, speaking at the 41st Annual Contemporary Clinical Neurology Symposium, sees broader implications.

“This [technique] might provide insight into psychiatric symptoms that we have had trouble truly understanding in relation to neuroanatomy,” Dr. Darby said. Some of the delusions associated with focal neurologic lesions have parallels with those associated with schizoaffective disorders, and this work may explain what areas of the brain are affected, even in the absence of visible lesions on imaging.

Lesion network mapping is a technique developed to identify functionally related regions of the brain. This goal is important because focal neurologic lesions associated with specific delusions are not necessarily located in the same brain region. The concept of networks connecting brain activity and network mapping recognizes that dysfunction in one brain area can lead to dysfunction in others. Lesion network mapping provides a strategy to identify these relationships.

Capgras Syndrome

Dr. Darby provided insight into lesion network mapping based on work he performed and published on Capgras syndrome, which describes an irrational belief that a familiar person or place is an impostor or a facsimile. As examples, he described a woman who thought her home, although familiar, was a replica. In another case, a man believed that his son-in-law, whom he recognized, was an impersonator. This type of delusion is complex, because it appears to involve a disruption of processes that mediate familiarity, as well as the cognitive processes employed to recognize and reject false beliefs.

One hypothesis about Capgras syndrome is that it involves “a two-hit phenomenon” in which dysfunction occurs simultaneously in distinct areas of the brain, according to Dr. Darby. His work with network lesion mapping in Capgras syndrome supports that hypothesis.

Lesion network mapping, a technique first described in a 2015 study, has established functional connectivity between regions of the brain in normal individuals in a resting state. A 2017 study tested the potential value of lesion network mapping in 17 cases of Capgras syndrome.

Most of the cases, including the imaging data, were retrieved from previously published studies, although several contemporary cases were included. In the investigation, Dr. Darby and his coinvestigators first demonstrated the heterogeneity in lesion location. Captured on MRI scans and traced onto a brain atlas, all but one of the lesions in patients with Capgras syndrome were found in the right hemisphere, but many of the lesions had nonoverlapping areas of involvement.

Despite the heterogeneity in lesion location, lesion network mapping demonstrated that all 17 lesions were functionally connected to the retrosplenial cortex. In addition, 16 of the 17 lesions were functionally connected to the right frontal cortex.

According to Dr. Darby, both associations are potentially important. On the basis of previously published studies with functional MRI (fMRI), the left retrosplenial cortex has been implicated in mediating familiarity. The right frontal cortex has been associated with belief evaluation. Moreover, in a control evaluation of published cases in which delusions did not involve misidentification, no functional connections to either the left retrosplenial cortex or the right frontal cortex were observed, according to Dr. Darby. In contrast, patients with disorders consistent with an impaired belief evaluation, such as paranoia or pathologic jealousy, did have lesions in the right frontal cortex as predicted.

 

Insights Into Other Neuropsychiatric Disorders

Lesion network mapping is now being applied to other types of delusions. Dr. Darby described work with neurologic and psychiatric disorders associated with a perception that free will has been lost. These include neuropsychiatric conditions such as akinetic mutism, alien limb syndrome, catatonia, and psychogenic nonepileptic seizures. According to Dr. Darby, there are two potential components involved in a delusion involving an impaired sense of free will. There is a change in the volitional component that captures the motivation and desire to move, as well as an impaired sense of agency, which refers to the feeling of responsibility for movement.

Describing ongoing work with these types of delusions, Dr. Darby reported that neurologic lesion locations, like those in Capgras syndrome, were heterogeneous. Again, most of these lesions could be connected to a network functional map that was not shared by those without these symptoms.

“For many of these complex disorders, what we are seeing is that pathology in different areas causes the same behavior syndrome by affecting different parts of the same network,” Dr. Darby said. He believes neurologic and psychiatric diseases producing the same delusions are likely to be mediated by dysfunction in the same areas of the brain.

In patients with psychiatric diseases who have delusions associated with loss of a sense of free will, lesions are not readily observed, but Dr. Darby reported that there is evidence of modest changes, such as atrophy or diminished metabolism, that can be “linked up to those areas of the brain involved in agency and volition, and not to areas that are associated with other comorbid symptoms.”

Broader Implications

The fact that the same or similar delusions are shared by neurologic and psychiatric disorders provides the basis for speculating that this work may lead to a more detailed understanding of brain function. According to Dr. Darby, the work with lesion network mapping in neurologic disorders “may tell us where to look for the pathology in psychiatric diseases.”

The lesion network testing may be an important tool for understanding the relationship of brain pathology to behavior, according to Dr. Darby. Prior to lesion network mapping, the heterogeneity of lesion location for patients with shared types of delusion has been difficult to understand, but Dr. Darby indicated that lesion network mapping shows potential for placing specific symptom expression into a context of neuroanatomy.

—Theodore Bosworth

Suggested Reading

Boes AD, Prasad S, Liu Q, et al. Network localization of neurological symptoms from focal brain lesions. Brain. 2015;138(Pt 10):3061-3075.

Darby RR, Laganiere S, Pascual-Leone A, et al. Finding the imposter: brain connectivity of lesions causing delusional misidentifications. Brain. 2017;140(2):497-507.

HILTON HEAD, SC—Delusions of a common type, whether associated with neurologic or psychiatric disease, appear likely to involve common pathways in the brain, according to new studies using lesion network mapping. This type of mapping appears to reveal the pathways that explain why single focal neurologic lesions in different brain locations cause similar delusional symptoms.

Lesion network mapping “is an approach to look at neurologic and psychiatric symptoms at the level of networks to understand brain behavior relationships,” explained Ryan Darby, MD, Assistant Professor of Neurology and Director of the Frontotemporal Dementia Clinic at Vanderbilt University Medical Center in Nashville. From the neurologic perspective, this work may provide insight into brain function, but Dr. Darby, speaking at the 41st Annual Contemporary Clinical Neurology Symposium, sees broader implications.

“This [technique] might provide insight into psychiatric symptoms that we have had trouble truly understanding in relation to neuroanatomy,” Dr. Darby said. Some of the delusions associated with focal neurologic lesions have parallels with those associated with schizoaffective disorders, and this work may explain what areas of the brain are affected, even in the absence of visible lesions on imaging.

Lesion network mapping is a technique developed to identify functionally related regions of the brain. This goal is important because focal neurologic lesions associated with specific delusions are not necessarily located in the same brain region. The concept of networks connecting brain activity and network mapping recognizes that dysfunction in one brain area can lead to dysfunction in others. Lesion network mapping provides a strategy to identify these relationships.

Capgras Syndrome

Dr. Darby provided insight into lesion network mapping based on work he performed and published on Capgras syndrome, which describes an irrational belief that a familiar person or place is an impostor or a facsimile. As examples, he described a woman who thought her home, although familiar, was a replica. In another case, a man believed that his son-in-law, whom he recognized, was an impersonator. This type of delusion is complex, because it appears to involve a disruption of processes that mediate familiarity, as well as the cognitive processes employed to recognize and reject false beliefs.

One hypothesis about Capgras syndrome is that it involves “a two-hit phenomenon” in which dysfunction occurs simultaneously in distinct areas of the brain, according to Dr. Darby. His work with network lesion mapping in Capgras syndrome supports that hypothesis.

Lesion network mapping, a technique first described in a 2015 study, has established functional connectivity between regions of the brain in normal individuals in a resting state. A 2017 study tested the potential value of lesion network mapping in 17 cases of Capgras syndrome.

Most of the cases, including the imaging data, were retrieved from previously published studies, although several contemporary cases were included. In the investigation, Dr. Darby and his coinvestigators first demonstrated the heterogeneity in lesion location. Captured on MRI scans and traced onto a brain atlas, all but one of the lesions in patients with Capgras syndrome were found in the right hemisphere, but many of the lesions had nonoverlapping areas of involvement.

Despite the heterogeneity in lesion location, lesion network mapping demonstrated that all 17 lesions were functionally connected to the retrosplenial cortex. In addition, 16 of the 17 lesions were functionally connected to the right frontal cortex.

According to Dr. Darby, both associations are potentially important. On the basis of previously published studies with functional MRI (fMRI), the left retrosplenial cortex has been implicated in mediating familiarity. The right frontal cortex has been associated with belief evaluation. Moreover, in a control evaluation of published cases in which delusions did not involve misidentification, no functional connections to either the left retrosplenial cortex or the right frontal cortex were observed, according to Dr. Darby. In contrast, patients with disorders consistent with an impaired belief evaluation, such as paranoia or pathologic jealousy, did have lesions in the right frontal cortex as predicted.

 

Insights Into Other Neuropsychiatric Disorders

Lesion network mapping is now being applied to other types of delusions. Dr. Darby described work with neurologic and psychiatric disorders associated with a perception that free will has been lost. These include neuropsychiatric conditions such as akinetic mutism, alien limb syndrome, catatonia, and psychogenic nonepileptic seizures. According to Dr. Darby, there are two potential components involved in a delusion involving an impaired sense of free will. There is a change in the volitional component that captures the motivation and desire to move, as well as an impaired sense of agency, which refers to the feeling of responsibility for movement.

Describing ongoing work with these types of delusions, Dr. Darby reported that neurologic lesion locations, like those in Capgras syndrome, were heterogeneous. Again, most of these lesions could be connected to a network functional map that was not shared by those without these symptoms.

“For many of these complex disorders, what we are seeing is that pathology in different areas causes the same behavior syndrome by affecting different parts of the same network,” Dr. Darby said. He believes neurologic and psychiatric diseases producing the same delusions are likely to be mediated by dysfunction in the same areas of the brain.

In patients with psychiatric diseases who have delusions associated with loss of a sense of free will, lesions are not readily observed, but Dr. Darby reported that there is evidence of modest changes, such as atrophy or diminished metabolism, that can be “linked up to those areas of the brain involved in agency and volition, and not to areas that are associated with other comorbid symptoms.”

Broader Implications

The fact that the same or similar delusions are shared by neurologic and psychiatric disorders provides the basis for speculating that this work may lead to a more detailed understanding of brain function. According to Dr. Darby, the work with lesion network mapping in neurologic disorders “may tell us where to look for the pathology in psychiatric diseases.”

The lesion network testing may be an important tool for understanding the relationship of brain pathology to behavior, according to Dr. Darby. Prior to lesion network mapping, the heterogeneity of lesion location for patients with shared types of delusion has been difficult to understand, but Dr. Darby indicated that lesion network mapping shows potential for placing specific symptom expression into a context of neuroanatomy.

—Theodore Bosworth

Suggested Reading

Boes AD, Prasad S, Liu Q, et al. Network localization of neurological symptoms from focal brain lesions. Brain. 2015;138(Pt 10):3061-3075.

Darby RR, Laganiere S, Pascual-Leone A, et al. Finding the imposter: brain connectivity of lesions causing delusional misidentifications. Brain. 2017;140(2):497-507.