Schizophrenia (scz) is a major public health problem affecting ~1% of the American population with devastating consequences. Structural and functional deficits in the thalamus, a critical point of convergence for multiple cortical and subcortical circuits, have been consistently implicated in scz. The thalamus is composed of multiple nuclei, each with a different pattern of anatomical and functional connectivity. These nuclei have now been redefined based on anatomical connections to other brain regions. These regions are too small to be resolved by conventional (3T) fMRI, but can be resolved by ultra-high field (7T) fMRI. We therefore propose, In aim 1, to use resting BOLD signal at 7T to test the hypothesis that functional connectivity of thalamocortical circuitry in individuals with recent onst scz is disrupted compared to matched healthy controls (N =25 per group). Based on our preliminary data in individuals with chronic schizophrenia, we hypothesize that specific thalamic regions will show enhanced functional connectivity in recent onset scz. We predict that abnormal connectivity will be most evident in the thalamic subregions anatomically connected to prefrontal cortex, with parallel but less robust connectivity to other cortical regions. Secondaril, we predict that symptom severity and cognitive deficits will be correlated with the extent of abnormal connectivity. BOLD signal, however, is strongly modulated by neurovascular function. Therefore, in Aim 2 we will use 7T fMRI to determine regional whole brain and blood flow (CBF) using arterial spin labelling (ASL), and arteriolar cerebral blood volume (CBVa) using a new method developed by our group called inflow vascular space occupancy (iVASO) MRI. These measures will enable us to better interpret BOLD signals, and may also reveal abnormalities in blood flow or blood volume in schizophrenia. We predict that robust evidence of functional connectivity detected by BOLD will remain independently significant, but that marginal findings may be accounted for by blood flow and volume changes. Secondarily, we will test the hypotheses that CBF and CBVa are intrinsically abnormal in scz, both across the brain and specifically in the thalamus. If successful, our results will support larger, longitudinal studies f these parameters in scz and other psychiatric disorders.
fMRI measures of connectivity and blood flow and volume could reveal underlying biological processes in scz and serve as powerful biomarkers that will aid in the diagnosis, prognosis, and classification of scz, and aid in monitoring the effectiveness of current and experimental therapeutic modalities. PUBLIC HEALTH RELEVANCE: Schizophrenia is a major public health problem, affecting ~1% of the American population with devastating personal, social, and economic consequences. The proposed study aims to better understand schizophrenia by using advanced technology to determine if individuals with schizophrenia have abnormal connections between the thalamus, a critical relay station in the brain, and other brain regions. Results from this study may lead to a better understanding of the biology of schizophrenia, and may be useful in predicting disease course and response to medicines.
| Hua, Jun; Blair, Nicholas I S; Paez, Adrian et al. (2018) Altered functional connectivity between sub-regions in the thalamus and cortex in schizophrenia patients measured by resting state BOLD fMRI at 7T. Schizophr Res : |
| Hua, Jun; Liu, Peiying; Kim, Tae et al. (2018) MRI techniques to measure arterial and venous cerebral blood volume. Neuroimage : |
| Hua, Jun; Brandt, Allison S; Lee, SeungWook et al. (2016) Abnormal Grey Matter Arteriolar Cerebral Blood Volume in Schizophrenia Measured With 3D Inflow-Based Vascular-Space-Occupancy MRI at 7T. Schizophr Bull : |
| Brandt, Allison S; Unschuld, Paul G; Pradhan, Subechhya et al. (2016) Age-related changes in anterior cingulate cortex glutamate in schizophrenia: A (1)H MRS Study at 7 Tesla. Schizophr Res 172:101-5 |
| Wu, Yuankui; Agarwal, Shruti; Jones, Craig K et al. (2016) Measurement of arteriolar blood volume in brain tumors using MRI without exogenous contrast agent administration at 7T. J Magn Reson Imaging 44:1244-1255 |
