Poster No:
578
Submission Type:
Late-Breaking Abstract Submission
Authors:
Jie Lisa Ji1, Christopher Whelan1, Srinivasan Vairavan1, Lining Pan2, Markus Helmer1, John Murray3, William Martin1, Gayle Wittenberg1, Alan Anticevic1
Institutions:
1Janssen R&D, Titusville, NJ, 2Yale University, New Haven, CT, 3Dartmouth College, Hanover, NH
First Author:
Co-Author(s):
Introduction:
Variation in behavioral symptoms must be reflected as variation in the neural circuits giving rise to them. Prior work suggested that lower-dimensional quantifications of psychosis-spectrum disorder symptom variance can produce robust brain-behavioral associations. Here we evaluate a non-negative matrix factorization (NMF) of behavioral symptoms for replicability and ability to yield a clinically-interpretable, robust brain-behavioral solution.
Methods:
Results were computed in discovery (BSNIP-1, n=393), replication (BSNIP-2, n=298), and combined datasets (n=691). Behavioral decomposition by NMF was performed on combined BACS (cognition) and PANSS symptoms with rank=5. For each NMF, group-level brain-behavior maps were constructed using mass univariate regression to map NMF scores to global brain connectivity (GBC) from resting-state fMRI. Split-half replication (100 runs) was performed for each NMF component both for the full brain map and for the top 25% of symptom-relevant neural parcels.
Results:
Behavioral decomposition by NMF yields an interpretable and replicable solution (cosine similarity 0.75-0.995). Brain-behavioral associations with GBC vary in strength and replicability across the 5 behavioral components. R-values for split-half replicability for each NMF are as follows (whole brain|top 25%): NMF1 (0.24|0.59), NMF2 (0.08|0.15), NMF3 (0.40|0.81), NMF4(0.53|0.92), NMF5 (0.11|0.29). Restricting brain-behavior mapping to the most significant symptom-relevant circuits may improve replicability of results. Some behavioral components may associate more strongly with neural metrics beyond GBC; exploration is underway.
Conclusions:
This work opens the possibility of developing new clinical scales optimized to represent variation in key neural circuits that can be targeted therapeutically, helping to advance the development of accessible precision medicines.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Higher Cognitive Functions:
Executive Function, Cognitive Control and Decision Making
Modeling and Analysis Methods:
fMRI Connectivity and Network Modeling 2
Novel Imaging Acquisition Methods:
BOLD fMRI
Keywords:
MRI
Psychiatric
Psychiatric Disorders
1|2Indicates the priority used for review
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Please indicate below if your study was a "resting state" or "task-activation” study.
Resting state
Healthy subjects only or patients (note that patient studies may also involve healthy subjects):
Patients
Was this research conducted in the United States?
Yes
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
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Not applicable
Please indicate which methods were used in your research:
Functional MRI
Structural MRI
Behavior
Neuropsychological testing
For human MRI, what field strength scanner do you use?
3.0T
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FSL
Free Surfer
Other, Please list
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HCP, QuNex
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