Poster No:
476
Submission Type:
Abstract Submission
Authors:
Jasmin Bettina1, Daniel Eisenberg2, Michael Gregory3, Philip Kohn2, Bobby Das2, Cosette Rhoads2, Nathan Mann2, Karen Berman2
Institutions:
1NIMH, North Bethesda, MD, 2NIMH, Bethesta, MD, 3NIMH, Bethesda, MD
First Author:
Co-Author(s):
Introduction:
Fractional amplitude of low-frequency fluctuation (fALFF), an important measure of spontaneous brain activity, has been investigated as a possible biomarker in schizophrenia spectrum illness (Küblböck et al., 2014) and may be modified by antipsychotic medication (Hu et al., 2016). Because atypical antipsychotic medications cause changes in striatal resting-state regional cerebral blood flow measured with oxygen-15 PET that are related to both dopaminergic tone and therapeutic response in schizophrenia (Eisenberg, et al. 2017), we hypothesized that striatal fALFF would also show important antipsychotic medication effects that may help clarify this measure's clinical relevance. Prior studies of fALFF and medication response in schizophrenia have yielded mixed results and have not specifically focused on the striatum. To address this knowledge gap, we measured fALFF both on and off medications in a cohort of inpatient research participants with schizophrenia spectrum illness.
Methods:
Inpatients with schizophrenia spectrum illness (n=27, age=29±8SD, males=21) were scanned in a resting, eyes-open state over 12 minutes with 3T rs-fMRI (TR/TE=2000/24ms, 184 images) at two time points during a blinded, cross-over design, medication-withdrawal protocol: during at least three weeks of treatment with a single antipsychotic agent and also after at least three weeks of placebo treatment. Data preprocessing included motion correction, normalization to MNI space, and scrubbing using AFNI tools (afni_proc.py; Cox, 1996). FALFF values were calculated for every voxel of the pre-processed EPI images within the low-frequency range of 0.01 to 0.1, normalized by total power, and finally converted to fALFF values as reported in Zou et al. (2008). 3dttest++ and 3dLME where appropriate were used for linear modeling voxelwise statistical comparisons in the striatum both between conditions (on versus off medication) and with symptom scores (total PANSS ratings). ETAC (Equitable Thresholding And Clustering) was used for multiple thresholding and cluster-level statistical correction (Cox, 2019) with a corrected threshold of p<0.05.
Results:
Striatal fALFF differed between medicated and unmedicated conditions, particularly in the ventral striatum, where fALFF was greater on medication than on placebo. Additionally, in the on medication condition, ventral striatal values correlated with greater symptom severity.
Conclusions:
Striatal fALFF shows susceptibility to antipsychotic medication treatment in schizophrenia spectrum illness and may be related to variability in symptoms across individuals, particularly in the ventral striatum, in accord with mesolimbic hypotheses of antipsychotic action. Further work is needed to understand the relevance of these findings for broader network activity and to determine whether antipsychotic pharmacotherapeutics with unique mechanisms share this striatal fALFF signature.
Disorders of the Nervous System:
Psychiatric (eg. Depression, Anxiety, Schizophrenia) 1
Modeling and Analysis Methods:
Activation (eg. BOLD task-fMRI) 2
Keywords:
ADULTS
Dopamine
FUNCTIONAL MRI
Schizophrenia
Sub-Cortical
Treatment
Other - fALFF Striatum
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
Are you Internal Review Board (IRB) certified?
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Were any human subjects research approved by the relevant Institutional Review Board or ethics panel?
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Yes
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Please indicate which methods were used in your research:
Functional MRI
Neuropsychological testing
For human MRI, what field strength scanner do you use?
3.0T
Which processing packages did you use for your study?
AFNI
Provide references using APA citation style.
Cox R.W., 1996. Comput Biomed Res. Jun;23(3);162-73
Cox, R.W. 2019. Brain Connect Sep;9(7):529-538
Eisenberg, D.P. et al., 2017. Neuropsychopharmacol 42, 2232–2241
Hu, M.L. et al., 2016. Sci Rep. Oct 4;6:34287
Küblböck M., 2014. Vol 103;249-257
Zou, Q.H. et al., 2008. J. Neurosci. Methods, 172 (1),137-141
No