Lesions that Cause Psychosis Map to a Common Brain Circuit Involving the Hippocampus
Poster No:
611
Submission Type:
Abstract Submission
Authors:
Andrew Pines1, Summer Frandsen1, William Drew1, Garance Meyer1, Calvin Howard1, Stephan Palm1, Frederic Schaper1, Clemens Neudorfer1, Andreas Horn1, Shan Siddiqi1
Institutions:
1Brigham & Women's Hospital, Harvard Medical School, Boston, MA
First Author:
Co-Author(s):
Introduction:
Schizophrenia is characterized by chronic symptoms of psychosis such as delusions, hallucinations, and thought disorder. Antipsychotic medications frequently cause intolerable side effects, and often do not fully resolve symptoms. To investigate alternative treatments, transcranial magnetic stimulation (TMS) has been studied to ameliorate psychotic symptoms. TMS trials for schizophrenia, however, have not consistently reduced psychotic symptoms. Defining the neuroanatomy that is causally implicated in psychotic symptoms could reveal a TMS target specific to schizophrenia.
Methods:
We identified published cases of brain lesions associated with psychosis and screened them for causality. Functional and structural connectivity of each lesion was estimated using a human connectome database (n=1000). To determine connections common to lesions causing psychosis, we performed a sensitivity analysis by examining regions covered by a one-sample T-test and the overlap of the functional correlates of each lesion. We performed a specificity analysis using a Family-Wise-Error(FWE)-corrected voxel-wise two-sample t-test between the functional maps of lesions causing psychosis and control lesions that did not cause psychosis.
Results:
155 cases from the literature were determined to be causal of psychosis. Regions that were significant in a one-sample T-test (threshold T>7), functional overlap tests (50% overlap, T>7), and a two-sample T-test (pFWE<5 x 10-4) were the the hippocampus, ventral tegmental area, retrosplenial cortex, ventromedial prefrontal cortex, cerebbelar lobule IX, and the medial dorsal nuclei of the thalamus. The most sensitive and specific anatomy was the posterior subiculum of the hippocampus. We repeated the analyses after excluding lesions intersecting the hippocampus (n=52) and found similar functional connections across the whole brain with the same peak in the posterior hippocampus. In an independent cohort, lesions associated with psychosis-like symptoms exhibited significantly similar connectivity profiles to the psychosis network.
Voxels in the ventromedial prefrontal cortex are highly correlated with the psychosis circuit and an appropriate target for TMS.
Voxels in the ventromedial prefrontal cortex are highly correlated with the psychosis circuit and an appropriate target for TMS.
·Common Functional Connectivity of Lesions that Cause Psychosis
Conclusions:
Lesions causing psychosis map to a common brain circuit. The posterior subiculum of the hippocampus is the most sensitive and specific area involved in this circuit. A region in this ventromedial prefrontal cortex is highly connected to this psychosis circuit and could serve as a TMS target for future studies.
Brain Stimulation:
TMS 2
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
Neuroanatomy Other
Keywords:
Schizophrenia
Transcranial Magnetic Stimulation (TMS)
1|2Indicates the priority used for review