Lingzhong Fan

The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture

The human brain atlases that allow correlating brain anatomy with psychological and cognitive functions are in transition from ex vivo histology-based printed atlases to digital brain maps providing multimodal in vivo information. Many current human brain atlases cover only specific structures, lack fine-grained parcellations, and fail to provide functionally important connectivity information. Using noninvasive multimodal neuroimaging techniques, we designed a connectivity-based parcellation framework that identifies the subdivisions of the entire human brain, revealing the in vivo connectivity architecture. The resulting human Brainnetome Atlas, with 210 cortical and 36 subcortical subregions, provides a fine-grained, cross-validated atlas and contains information on both anatomical and functional connections. Additionally, we further mapped the delineated structures to mental processes by reference to the BrainMap database. It thus provides an objective and stable starting point from which to explore the complex relationships between structure, connectivity, and function, and eventually improves understanding of how the human brain works. The human Brainnetome Atlas will be made freely available for download at http://atlas.brainnetome.org, so that whole brain parcellations, connections, and functional data will be readily available for researchers to use in their investigations into healthy and pathological states.

Subregions of the human superior frontal gyrus and their connections

The superior frontal gyrus (SFG) is located at the superior part of the prefrontal cortex and is involved in a variety of functions, suggesting the existence of functional subregions. However, parcellation schemes of the human SFG and the connection patterns of each subregion remain unclear. We firstly parcellated the human SFG into the anteromedial (SFGam), dorsolateral (SFGdl), and posterior (SFGp) subregions based on diffusion tensor tractography. The SFGam was anatomically connected with the anterior and mid-cingulate cortices, which are critical nodes of the cognitive control network and the default mode network (DMN). The SFGdl was connected with the middle and inferior frontal gyri, which are involved in the cognitive execution network. The SFGp was connected with the precentral gyrus, caudate, thalamus, and frontal operculum, which are nodes of the motor control network. Resting-state functional connectivity analysis further revealed that the SFGam was mainly correlated with the cognitive control network and the DMN; the SFGdl was correlated with the cognitive execution network and the DMN; and the SFGp was correlated with the sensorimotor-related brain regions. The SFGam and SFGdl were further parcellated into three and two subclusters that are well corresponding to Brodmann areas. These findings suggest that the human SFG consists of multiple dissociable subregions that have distinct connection patterns and that these subregions are involved in different functional networks and serve different functions. These results may improve our understanding on the functional complexity of the SFG and provide us an approach to investigate the SFG at the subregional level.

Connectivity-Based Parcellation of the Human Frontal Pole with Diffusion Tensor Imaging

The human frontal pole (FP) approximately corresponds to Brodmanns area 10 and is a highly differentiated cortical area with unique cytoarchitectonic characteristics. However, its functional diversity is highly suggestive of the existence of functional subregions. Based on anatomical connection patterns derived from diffusion tensor imaging data, we applied a spectral clustering algorithm to parcellate the human right FP into orbital (FPo), lateral (FPl), and medial (FPm) subregions. This parcellation scheme was validated by corresponding analyses of the left FP and right FP in another independent dataset. Both visual observation and quantitative comparison of the anatomical connection patterns of the three FP subregions revealed that the FPo showed greater connection probabilities to brain regions of the social emotion network (SEN), including the orbitofrontal cortex, temporal pole, and amygdala, the FPl showed stronger connections to the dorsolateral prefrontal cortex of the cognitive processing network (CPN), and the FPm showed stronger connections to brain areas of the default mode network (DMN), including the anterior cingulate cortex and medial prefrontal cortex. We further analyzed the resting-state functional connectivity patterns of the three FP subregions. Consistent with the findings of anatomical connection analyses, the FPo was functionally correlated with the SEN, the FPl was correlated with the CPN, and the FPm was correlated with the DMN. These findings suggest that the human FP includes three separable subregions with different anatomical and functional connectivity patterns and that these subregions are involved in different brain functional networks and serve different functions.

Connectivity-Based Parcellation of the Human Temporal Pole Using Diffusion Tensor Imaging

The temporal pole (TP) is an association cortex capable of multisensory integration and participates in various high-order cognitive functions. However, an accepted parcellation of the human TP and its connectivity patterns have not yet been well established. Here, we sought to present a scheme for the parcellation of human TP based on anatomical connectivity and to reveal its subregional connectivity patterns. Three distinct subregions with characteristic fiber pathways were identified, including the dorsal (TAr), the medial (TGm), and lateral (TGl) subregions, which are located ventrally. According to the connectivity patterns, a dorsal/ventral sensory segregation of auditory and visual processing and the medial TGm involved in the olfactory processing were observed. Combined with the complementary resting-state functional connectivity analysis, the connections of the TGm with the orbitofrontal cortex and other emotion-related areas, the TGl connections with the MPFC and major default mode network regions, and the TAr connections with the perisylvian language areas were observed. To the best of our knowledge, the present study represents the first attempt to parcel the human TP based on its anatomical connectivity features, which may help to improve our understanding of its connectional anatomy and to extend the available knowledge in TP-related clinical research.

Tractography-based parcellation of the human left inferior parietal lobule.

The inferior parietal lobule (IPL) is a functionally and anatomically heterogeneous region. Much of the information about the anatomical connectivity and parcellation of this region was obtained from histological studies on non-human primates. However, whether these findings from non-human primates can be applied to the human inferior parietal lobule, especially the left inferior parietal lobule, which shows evidence of considerable evolution from primates to humans, remains unclear. In this study, diffusion MRI was employed to investigate the anatomical connectivities of the human left inferior parietal lobule. Using a new algorithm, spectral clustering with edge-weighted centroidal voronoi tessellations, to search for regional variations in the probabilistic connectivity profiles of all left inferior parietal lobule voxels with all the rest of the brain identified six subregions with distinctive connectivity properties in the left inferior parietal lobule. Consistent with cytoarchitectonic findings, four subregions were found in the left supramarginal gyrus and two subregions in the left angular gyrus. The specific connectivity patterns of each subregion of the left inferior parietal lobule were supported by both the anatomical and functional connectivity properties for each subregion, as calculated by a meta-analysis-based target method and by voxel-based whole brain anatomical and functional connectivity analyses. The proposed parcellation scheme for the human left inferior parietal lobule and the maximum probability map for each subregion may facilitate more detailed future studies of this brain area.

Connectivity-Based Parcellation of the Human Posteromedial Cortex

Regional structural and functional variations in the posteromedial cortex (PMC) have been found in both animals and humans, strongly suggesting the presence of subdivisions. However, there is no consensus on how to subdivide the human PMC. Here, we investigated the anatomical parcellation scheme and the connectivity pattern of each subdivision of the human PMC using diffusion tensor imaging data from 2 independent groups of volunteers. The parcellation analyses of the 2 datasets consistently demonstrated that the human PMC can be parcellated into 5 subregions. The dorsal portion of the PMC was subdivided into anterior, central, and posterior subregions, which participate in sensorimotor, associative, and visual functions. The ventral PMC contained a transitional region in the dorsal portion and a ventral subregion that is the core of the default mode network. The parcellation results for the human PMC and its anatomical connectivity patterns were further supported by evidence from the macaque PMC. Furthermore, functional connectivity analysis revealed that each subregion exhibited a specific pattern similar to that of its anatomical connectivity. The proposed parcellation scheme may facilitate the study of the human PMC at a subtler level and improve our understanding of its functions.

Convergent functional architecture of the superior parietal lobule unraveled with multimodal neuroimaging approaches

The superior parietal lobule (SPL) plays a pivotal role in many cognitive, perceptive, and motor‐related processes. This implies that a mosaic of distinct functional and structural subregions may exist in this area. Recent studies have demonstrated that the ongoing spontaneous fluctuations in the brain at rest are highly structured and, like coactivation patterns, reflect the integration of cortical locations into long‐distance networks. This suggests that the internal differentiation of a complex brain region may be revealed by interaction patterns that are reflected in different neuroimaging modalities. On the basis of this perspective, we aimed to identify a convergent functional organization of the SPL using multimodal neuroimaging approaches. The SPL was first parcellated based on its structural connections as well as on its resting‐state connectivity and coactivation patterns. Then, post hoc functional characterizations and connectivity analyses were performed for each subregion. The three types of connectivity‐based parcellations consistently identified five subregions in the SPL of each hemisphere. The two anterior subregions were found to be primarily involved in action processes and in visually guided visuomotor functions, whereas the three posterior subregions were primarily associated with visual perception, spatial cognition, reasoning, working memory, and attention. This parcellation scheme for the SPL was further supported by revealing distinct connectivity patterns for each subregion in all the used modalities. These results thus indicate a convergent functional architecture of the SPL that can be revealed based on different types of connectivity and is reflected by different functions and interactions. Hum Brain Mapp, 36:238–257, 2015.

Sexual dimorphism and asymmetry in human cerebellum: An MRI-based morphometric study

Structural sexual dimorphism and asymmetry in human cerebellum have been described in previous research, but results remain inconclusive or even conflicting. In this study, gender differences and hemispheric asymmetries in global and regional human cerebellum gray matter (GM) were estimated in an age-matched sample (n=112) of young Chinese adults. An optimized voxel-based morphometry (VBM) in spatial unbiased infratentorial template (SUIT) space together with an automated atlas-based volumetric approach were performed for mapping regional gray matter (GM) gender-related differences across the entire cerebellum. The two methods provided consistent findings on gender differences. The cerebellar GM volume was significantly larger in the anterior and middle posterior lobes of male group. In addition, a trend of greater GM volume in lateral posterior lobe of female group was observed. With the created symmetric cerebellar template, the asymmetric properties of cerebellar hemisphere were also assessed by VBM analysis, showing rightward asymmetry distributed in most cerebellar lobules and leftwards asymmetry distributed in the lobules around the medial posterior lobe. Gender differences in males showed higher leftward asymmetry sparsely within a few lobules and lower rightward asymmetry mainly within lobule Crus II, as compared with females. The acquired detailed morphologic knowledge of normal human cerebellum could establish a baseline for comparison with pathologic changes in the cerebellum. Moreover, our results might help to address controversies in thestudy of sexual dimorphisms and asymmetric patterns in human cerebellum.

Inferior Frontal White Matter Asymmetry Correlates with Executive Control of Attention

White matter (WM) asymmetries of the human brain have been well documented using diffusion tensor imaging (DTI). However, the relationship between WM asymmetry pattern and cognitive performance is poorly understood. By means of tract‐based spatial statistics (TBSS) and voxel‐based analyses of whole brain, this study examined the WM asymmetries and the correlations between WM integrity/asymmetries and three distinct components of attention, namely alerting, orienting, and executive control (EC), which were assessed by attention network test (ANT). We revealed a number of WM anisotropy asymmetries, including leftward asymmetry of cingulum, corticospinal tract and cerebral peduncle, rightward asymmetry of internal capsule, superior longitudinal fasciculus and posterior corona radiata, as well as heterogeneous asymmetries in anterior corpus callosum and anterior corona radiata (ACR). Moreover, specific correlation was found between asymmetric pattern of inferior frontal ACR and EC performance. Additionally, this study also proposed that there were no significant relationships of WM anisotropy asymmetries to alerting and orienting functions. Further clusters of interest analyses and probabilistic fiber tracking validated our findings. In conclusion, there are a number of differences in WM integrity between human brain hemispheres. Specially, the anisotropy asymmetry in inferior frontal ACR plays a crucial role in EC function. Our finding is supportive of the functional studies of inferior frontal regions and in keeping with the theory of the brain lateralization on human ventral attention system. Hum Brain Mapp, 2013.

Scalable and DiI-compatible optical clearance of the mammalian brain

Efficient optical clearance is fundamental for whole brain imaging. In particular, clearance of the brain without membrane damage is required for the imaging of lipophilic tracer-labeled neural tracts. Relying on an ascending gradient of fructose solutions, SeeDB can achieve sufficient transparency of the mouse brain while ensuring that the plasma membrane remains intact. However, it is challenging to extend this method to larger mammalian brains due to the extremely high viscosity of the saturated fructose solution. Here we report a SeeDB-derived optical clearing method, termed FRUIT, which utilizes a cocktail of fructose and urea. As demonstrated in the adult mouse brain, combination of these two highly water-soluble clearing agents exerts a synergistic effect on clearance. More importantly, the final FRUIT solution has low viscosity so as to produce transparency of the whole adult rabbit brain via arterial perfusion, which is impossible to achieve with a saturated fructose solution. In addition to good compatibility with enhanced yellow fluorescent protein, the cocktail also preserves the fluorescence of the lipophilic tracer DiI. This work provides a volume-independent optical clearing method which retains the advantages of SeeDB, particularly compatibility with lipophilic tracers.