Jiaojian Wang

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.

Low operating voltage bright organic light-emitting diode using iridium complex doped in 4,4′-bis[N-1-napthyl-N-phenyl-amino]biphenyl

A low driving voltage organic light-emitting diode using a yellow phosphor bis[2-(4-tert-butylphenyl)benzothiazolato-N,C2′] iridium (acetylacetonate) as a dopant and 4,4′-bis[N-1-napthyl-N-phenyl-amino]biphenyl as a host was fabricated. The device without p- or n-doped transporting layer shows a turn-on voltage as low as 2.45V, and a luminance of 1000cd∕m2 at 4.3V. A maximum luminance of 23230cd∕m2 at 10V was achieved. The decrease of the device turn-on voltage may result from direct charge carrier trapping in the dopant and hole only transporting characteristic of the host material. Both charge carrier trapping and energy transfer mechanisms were found in the electroluminescence process.

Determination of the posterior boundary of Wernicke's area based on multimodal connectivity profiles

Wernickes area is one of the most important language regions and has been widely studied in both basic research and clinical neurology. However, its exact anatomy has been controversial. In this study, we proposed to address the anatomy of Wernickes area by investigating different connectivity profiles. First, the posterior superior temporal gyrus (STG), traditionally called “Wernickes area”, was parcellated into three component subregions with diffusion MRI. Then, whole‐brain anatomical connectivity, resting‐state functional connectivity (RSFC) and meta‐analytic connectivity modeling (MACM) analyses were used to establish the anatomical, resting‐state and task‐related coactivation network of each subregion to identify which subregions participated in the language network. In addition, behavioral domain analysis, meta‐analyses of semantics, execution speech, and phonology and intraoperative electrical stimulation were used to determine which subregions were involved in language processing. Anatomical connectivity, RSFC and MACM analyses consistently identified that the two anterior subregions in the posterior STG primarily participated in the language network, whereas the most posterior subregion in the temporoparietal junction area primarily participated in the default mode network. Moreover, the behavioral domain analyses, meta‐analyses of semantics, execution speech and phonology and intraoperative electrical stimulation mapping also confirmed that only the two anterior subregions were involved in language processing, whereas the most posterior subregion primarily participated in social cognition. Our findings revealed a convergent posterior anatomical border for Wernickes area and indicated that the brains functional subregions can be identified on the basis of its specific structural and functional connectivity patterns. Hum Brain Mapp 36:1908–1924, 2015.

Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys

Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT. Moreover, blood transcriptome profiling revealed that mutant monkeys resembled RTT patients in immune gene dysregulation. Taken together, the stark similarity in phenotype and/or endophenotype between monkeys and patients suggested that gene-edited RTT founder monkeys would be of value for disease mechanistic studies as well as development of potential therapeutic interventions for RTT.