Objective: Pediatric bipolar disorder (PBD) has extremely high morbidity and mortality. Understanding the abnormalities in brain function is the first critical step in identifying the biomarkers of pathophysiology and treatment predictors. Together, functional magnetic neuroimaging (fMRI) and diffusion tensor imaging (DTI) act as complementary methods in pinpointing the abnormalities in gray matter regions and white matter tracts in PBD patients.
1.To characterize interfacing cognitive and affective circuitries in PBD using fMRI technology.
2. To assess axonal organization and/or integrity, myelinization and fiber tract coherence of white matter fiber tracts that link the areas connecting fronto-limbic circuitry identified on fMRI using DTI.
Methods: Subjects include 30 manic, never-treated bipolar disorder type I PBD patients age 10-20 years and 30 healthy adolescents matched for age, gender, educational level, IQ, socioeconomic status, and ethnic background. Data will be collected using 3T scanner. Tasks for the fMRI study include an N-Back task with emotional faces to emotionally challenge subjects while performing a working memory task with facial stimuli; a Stop signal task to probe response inhibition; and an Affective Stroop task to probe the impact of negative emotions on attention. The fMRI data processing involves FIASCO software (http://www.stat.cmu.edu/~fiasco/) for motion correction and preprocessing which will yield t-maps.
We will use AFNI software to superimpose activation maps on anatomic images, to create group statistical maps and perform group statistical comparisons in Talairach space. A set of DTI images will be acquired along with the fMRI data acquisition and analyzed using customized software. For each subject, fractional anisotropy (FA), increased apparent diffusion coefficient (ADC), and decreased fiber coherence index (FCI) maps will be computed, and region of interest (ROI) analyses will be performed on the five white-matter fiber tracts bilaterally with the seed voxel being in the ROI that defines the gray matter ROI.
Using these methods, we will test the hypothesis that activation of higher cortical areas of cognitive and affective processing, namely the dorsolateral prefrontal cortex (DLPFC) and ventro lateral prefrontal cortex (VLPFC) will be reduced, and activation of subcortical regions of affective processing, such as amygdala, will be increased in individuals with pediatric bipolar disorder (PBD). This dysfunctional top-down regulation will impair the cognitive and affective circuitry interface. We hypothesized that the white matter fiber tracts connecting these fronto-limbic areas such as anterior corona radiate (ACR), inferior longitudinal fasciculus (ILF) and superior longitudinal fasciculus (SLF) will demonstrate decreased FA, increased ADC, and decreased FCI.