The associations of BMI with mean diffusivity of basal ganglia among young adults with mild obesity and without obesity

Obesity causes a wide range of systemic diseases and is associated with mood and anxiety disorders. It is also associated with dopaminergic reward system function. However, the relationships between microstructural properties of the dopaminergic system and body mass index (BMI) have not been investigated. In this study, we investigated the associations of BMI with mean diffusivity (MD), diffusion tensor imaging measure in areas of the dopaminergic system (MDDS) in 435 healthy young adults with mild obesity and without obesity (BMI < 40). We detected the association between greater BMI and lower MD of the right globus pallidus and the right putamen. These results suggest that the property of the dopaminergic system is associated with BMI among young adults with mild obesity and without obesity.


Supplemental Methods
Subjects. The present study, which is a part of an ongoing project to investigate the association between brain imaging, cognitive function, and aging, included BMI measures and imaging data from 435 healthy, right-handed individuals (266 males and 169 females). The mean age of the subjects was 20.8 years [standard deviation (SD), 1.6; age range, 18−27 years old]. The following descriptions were mostly reproduced from another study of ours from the same project using the exactly same methods regarding these issues (Hikaru Takeuchi et al., 2015). Some of the subjects who took part in this study also became subjects of our intervention studies (psychological data and imaging data recorded before the intervention were used in this study) (Maruyama et al., 2018). Psychological tests and MRI scans not described in this study were performed together with those described in this study. This study was approved by the Ethics Committee of Tohoku University.
Subjects were instructed to get sufficient sleep, maintain their conditions, eat sufficient breakfast, and to consume their normal amounts of caffeinated foods and drinks in the day of cognitive tests and MRI scans. In addition, subjects were instructed to avoid alcohol the night before the assessment.

Preprocessing of imaging data
Preprocessing and analysis of functional activation data were performed using SPM8 implemented in Matlab. Most of the following descriptions were reproduced 5 from our previous study using the similar methods (Hikaru Takeuchi et al., 2016). First, the skull in the mean b = 0 image of each participant was stripped as described previously (H. Takeuchi et al., 2010); using the resulting image, diffusion images were linearly aligned to the skull-stripped b = 0 image template created previously (H. Takeuchi et al., 2010) to assist with the following procedures.
Subsequently, using a previously validated, two-step, new segmentation algorithm of diffusion images and the previously validated diffeomorphic anatomical registration through exponentiated lie algebra (DARTEL)-based registration process that utilized the information of the FA signal distribution within the white matter tissue (for details, see Hikaru Takeuchi et al., 2013), all images, including gray matter segments [regional gray matter density (rGMD) map], white matter segments [regional white matter density (rWMD) map], and cerebrospinal fluid (CSF) segments [regional CSF density (rCSFD) map] of diffusion images were normalized. The voxel size of these normalized images was 1.5  1.5  1.5 mm 3 . In these processes, we used the template for the DARTEL process that we created in our previous study from subjects that participated in the same project (for details, see Hikaru Takeuchi et al., 2013).
Next, we created average images of normalized rGMD and rWMD images of all subjects whose diffusion imaging data were obtained in the pre-experiment. 6 Subsequently, for the analyses of MD images from the normalized images of the (a) MD, (b) rGMD, and (c) rWMD maps, we created images where areas that were not strongly likely to be gray or white matter in our averaged normalized rGMD and rWMD images (defined by "gray matter tissue probability + white matter tissue probability < 0.99") were removed (to exclude the strong effects of CSF on MD throughout analyses).
These images were then smoothed (8 mm full-width half-maximum) and carried through to the second-level analyses of MD.
We did not use T1 weighted structural images for normalization and calculation of GMC and WMC maps for correction. This is because T1 weighted structural images and EPI images have apparent differences due to the distortion caused by 3T MRI and, simply, it is apparently not suited for the accurate and precise segmentation and normalization images of MD maps.

Supplemental replication ROI analyses of the associations between BMI calculated from self-reported data and MD using the independent sample.
In addition, we conducted supplemental analyses to investigate whether the associations between BMI, and the MD of the right putamen and right globus pallidus were replicated in the independent sample for whom self-reported height and weight data was available,.
In this analysis, we used the sample from our previous study, which did not have measured 7 height and weight data, but had self-reported height and weight data and the same parameters for diffusion weighted imaging. There were 754 subjects (421 males, 332 females) with all the necessary data. The subjects' mean age was 20.8 years (standard deviation [SD], 2.0). The mean and SD values of BMI were 20.99 ± 2.35 in males and 20.31 ± 1.85 in females. All the preprocessing and analytic procedures were conducted using the same methods used in the preprocessing and analyses of the ROI in the main text.
Supplemental Results.

Supplemental replication ROI analyses of the associations between BMI calculated from self-reported data and MD using the independent sample
We investigated the associations between BMI, calculated from self-reported weight and height data, and the MD of the right globus pallidus and right putamen, regions that were anatomically defined after correcting for the effects of each ROI's rGMD, as well as age, sex, FD, and TIV. The results showed that BMI significantly and negatively correlated with the MD of the right globus pallidus [β= −0.177, t = −4.905, P (uncorrected) = 0.000001, P (corrected for FDR among 2 supplemental ROI analyses) = 0.000002] and the right putamen [β= −0.143, t = −3.951, P (uncorrected) = 0.000085, P (corrected for FDR among 2 supplemental ROI analyses) = 0.000085]. These results replicate the significant associations of greater BMI with lower MD in the right globus pallidus, and right putamen which were observed in the main text, using the 8 independent sample and BMI based on the self-reported weight and height data.