Diffusion time-related structure-function coupling reveals differential association with inter-individual variations in body mass index.

Body mass index (BMI) is an indicator of obesity, and recent neuroimaging studies have demonstrated that inter-individual variations in BMI are associated with altered brain structure and function. However, the mechanism underlying the alteration of structure-function correspondence according to BMI is under-investigated. In this study, we studied structural and functional connectivity derived from diffusion MRI tractography and inter-regional correlations of functional MRI time series, respectively. We combined the structural and functional connectivity information using the Riemannian optimization approach. First, the low-dimensional principal eigenvectors (i.e., gradients) of the structural connectivity were generated by applying diffusion map embedding with varying diffusion times. A transformation was identified so that the structural and functional embeddings share the same coordinate system, and subsequently, the functional connectivity matrix was simulated. Then, we generated gradients from the simulated functional connectivity matrix. We found the most apparent cortical hierarchical organization differentiating between low-level sensory and higher-order transmodal regions in the middle of the diffusion time, indicating that the hierarchical organization of the brain may reflect the intermediate mechanisms of mono- and polysynaptic communications. Associations between the functional gradients and BMI were strongest when the hierarchical structure was the most evident. Moreover, the gradient-BMI association map was related to the microstructural features, and the findings indicated that the BMI-related structure-function coupling was significantly associated with brain microstructure, particularly in higher-order transmodal areas. Finally, transcriptomic association analysis revealed the potential biological underpinnings specifying gene enrichment in the striatum, hypothalamus, and cortical cells. Our findings provide evidence that structure-function correspondence is strongly coupled with BMI when hierarchical organization is the most apparent and that the associations are related to the multiscale properties of the brain, leading to an advanced understanding of the neural mechanisms related to BMI.

GAN-MAT: Generative adversarial network-based microstructural profile covariance analysis toolbox.

Multimodal magnetic resonance imaging (MRI) provides complementary information for investigating brain structure and function; for example, an in vivo microstructure-sensitive proxy can be estimated using the ratio between T1- and T2-weighted structural MRI. However, acquiring multiple imaging modalities is challenging in patients with inattentive disorders. In this study, we proposed a comprehensive framework to provide multiple imaging features related to the brain microstructure using only T1-weighted MRI. Our toolbox consists of (i) synthesizing T2-weighted MRI from T1-weighted MRI using a conditional generative adversarial network; (ii) estimating microstructural features, including intracortical covariance and moment features of cortical layer-wise microstructural profiles; and (iii) generating a microstructural gradient, which is a low-dimensional representation of the intracortical microstructure profile. We trained and tested our toolbox using T1- and T2-weighted MRI scans of 1,104 healthy young adults obtained from the Human Connectome Project database. We found that the synthesized T2-weighted MRI was very similar to the actual image and that the synthesized data successfully reproduced the microstructural features. The toolbox was validated using an independent dataset containing healthy controls and patients with episodic migraine as well as the atypical developmental condition of autism spectrum disorder. Our toolbox may provide a new paradigm for analyzing multimodal structural MRI in the neuroscience community and is openly accessible at https://github.com/CAMIN-neuro/GAN-MAT.

The macroscale routing mechanism of structural brain connectivity related to body mass index.

Understanding the brain's mechanisms in individuals with obesity is important for managing body weight. Prior neuroimaging studies extensively investigated alterations in brain structure and function related to body mass index (BMI). However, how the network communication among the large-scale brain networks differs across BMI is underinvestigated. This study used diffusion magnetic resonance imaging of 290 young adults to identify links between BMI and brain network mechanisms. Navigation efficiency, a measure of network routing, was calculated from the structural connectivity computed using diffusion tractography. The sensory and frontoparietal networks indicated positive associations between navigation efficiency and BMI. The neurotransmitter association analysis identified that serotonergic and dopaminergic receptors, as well as opioid and norepinephrine systems, were related to BMI-related alterations in navigation efficiency. The transcriptomic analysis found that genes associated with network routing across BMI overlapped with genes enriched in excitatory and inhibitory neurons, specifically, gene enrichments related to synaptic transmission and neuron projection. Our findings suggest a valuable insight into understanding BMI-related alterations in brain network routing mechanisms and the potential underlying cellular biology, which might be used as a foundation for BMI-based weight management.

Shifts in structural connectome organization in the limbic and sensory systems of patients with episodic migraine.

Migraine is a complex neurological condition characterized by recurrent headaches, which is often accompanied by various neurological symptoms. Magnetic resonance imaging (MRI) is a powerful tool for investigating whole-brain connectivity patterns; however, systematic assessment of structural connectome organization has rarely been performed. In the present study, we aimed to examine the changes in structural connectivity in patients with episodic migraines using diffusion MRI. First, we computed structural connectivity using diffusion MRI tractography, after which we applied dimensionality reduction techniques to the structural connectivity and generated three low-dimensional eigenvectors. We subsequently calculated the manifold eccentricity, defined as the Euclidean distance between each data point and the center of the data in the manifold space. We then compared the manifold eccentricity between patients with migraines and healthy controls, revealing significant between-group differences in the orbitofrontal cortex, temporal pole, and sensory/motor regions. Between-group differences in subcortico-cortical connectivity further revealed significant changes in the amygdala, accumbens, and caudate nuclei. Finally, supervised machine learning effectively classified patients with migraines and healthy controls using cortical and subcortical structural connectivity features, highlighting the importance of the orbitofrontal and sensory cortices, in addition to the caudate, in distinguishing between the groups. Our findings confirmed that episodic migraine is related to the structural connectome changes in the limbic and sensory systems, suggesting its potential utility as a diagnostic marker for migraine.

Differences in cortical microstructure according to body mass index in neurologically healthy populations using structural magnetic resonance imaging.

Associations between brain structure and body mass index (BMI) are increasingly gaining attention. Although BMI-related regional alterations in brain morphology have been previously reported, the effect of BMI on the microstructural profiles, which provide information on the proxy of neuronal density within the cortex, is unexplored. In this study, we investigated the links between cortical layer-specific microstructural profiles and BMI in 302 neurologically healthy young adults. Using the microstructure-sensitive proxy based on the T1-and T2-weighted ratio, we estimated microstructural profile covariance (MPC) by calculating linear correlations of cortical depth-wise intensity profiles between different brain regions. Then, low-dimensional gradients of the MPC matrix were estimated using dimensionality reduction techniques, and the gradients were associated with BMI. Significant effects in the heteromodal association areas were observed. The BMI-gradient association map was related to the geodesic distance along the cortical surface, curvature, and sulcal depth, suggesting that the microstructural alterations occurred along the cortical topology. The BMI-gradient association map was further linked to cognitive states related to negative emotions. Our findings may provide insights into understanding the atypical cortical microstructure associated with BMI.