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Fischer, David

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Fischer

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Fischer, David

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2015 - 20162

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Author's Publications: search.filters.isAuthorOfPublication.1241c686-4fc1-4f2b-91e1-08af5446f18d

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    Altered threat and safety neural processing linked to persecutory delusions in schizophrenia: a two-task fMRI study
    (Elsevier BV, 2015) Perez, David; Pan, Hong; Weisholtz, Daniel; Root, James C.; Tuescher, Oliver; Fischer, David; Butler, Tracy; Vago, David R.; Isenberg, Nancy; Epstein, Jane; Landa, Yulia; Smith, Thomas; Savitz, Adam J.; Silbersweig, David; Stern, Emily
    Persecutory delusions are a clinically important symptom in schizophrenia associated with social avoidance and increased violence. Few studies have investigated the neurobiology of persecutory delusions, which is a prerequisite for developing novel treatments. The aim of this two-paradigm functional magnetic resonance imaging (fMRI) study is to characterize social “real world” and linguistic threat brain activations linked to persecutory delusions in schizophrenia (n=26) using instructed-fear/safety and emotional word paradigms. Instructed-fear/safety activations correlated to persecutory delusion severity demonstrated significant increased lateral orbitofrontal cortex and visual association cortex activations for the instructed-fear vs. safety and instructed-fear vs. baseline contrasts; decreased lateral orbitofrontal cortex and ventral occipital-temporal cortex activations were observed for the instructed-safety stimuli vs. baseline contrast. The salience network also showed divergent fear and safety cued activations correlated to persecutory delusions. Emotional word paradigm analyses showed positive correlations between persecutory delusion severity and left-lateralized linguistic and hippocampal–parahippocampal activations for the threat vs. neutral word contrast. Visual word form area activations correlated positively with persecutory delusions for both threat and neutral word vs. baseline contrasts. This study links persecutory delusions to enhanced neural processing of threatening stimuli and decreased processing of safety cues, and helps elucidate systems-level activations associated with persecutory delusions in schizophrenia.
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    Localization and Network of Coma-Causing Brainstem Lesions: Evidence for a Human Consciousness Network
    (2016-05-17) Fischer, David
    Focal brainstem lesions can disrupt arousal and cause coma, yet the exact location of the brainstem region critical to arousal and its associated network are unknown. First, we compare brainstem lesions between 12 patients with coma and 24 patients without coma to identify a region specific to coma-causing lesions. Second, we determine the network connectivity of this brainstem region and each individual coma-causing lesion using resting state functional connectivity MRI data acquired from 98 healthy subjects. Third, we evaluate the functional connectivity of this network in patients with disorders of consciousness (51 patients versus 21 controls). These analyses reveal a small, coma-specific region in the left pontine tegmentum, near the medial parabrachial nucleus. This brainstem region, and each individual coma-causing lesion, is functionally connected to the left agranular, anterior insula (AI), and pregenual anterior cingulate cortex (pACC). These cortical sites align poorly with previously defined functional networks but match the distribution of von Economo neurons (VENs). Finally, functional connectivity between AI and pACC is disrupted in patients with impaired awareness. These results show that coma-causing lesions overlap a specific brainstem location that is functionally connected to specific cortical areas, defining a unique human brain network. The brainstem node, if lesioned, disrupts arousal while the VEN-containing cortical nodes exhibit abnormalities in patients with disrupted awareness. We propose that this network may represent a neuroanatomical substrate linking arousal and awareness, the two principal components of human consciousness.