| The insular cortex,located in the depth of the lateral fissure,is a structurally and functionally heterogeneous brain region.The insula presents an overall microscopic organization with gradual change and can be subdivided into three architectonic areas with distinct granularities,and is responsible for integrating various sensory information such as taste,smell,interoception,hearing,somatesthesia,motion,and so on,and moreover,is involved in high-order cognitive functions such as social behavior,emotion regulation,reward,and so on.Von Economo neurons（VENs）exist in the human anterior insula,and abnormalities of the VENs are involved in a wide variety of psychiatric disorders,and are also thought to be associated with primate evolution.Early studies found that VENs existed in the anterior insula of higher primates,such as Homo sapiens and apes,but not in the macaque insula.Recently,as VENs have also been found in the macaque anterior insula,the homology of the primate insula required further investigation.In addition,the human insular cortex showed significant expansion during primate evolution.Therefore,research on regional homologies and connectivity differences between the human and macaque insular cortex from an evolutionary perspective could provide a better understanding of the human brain’s functional specificity.Using multimodal magnetic resonance imaging data,this dissertation investigates the global connectivity gradients and subdivision of the insular cortex in humans and macaques,and explores the homologies and connectivity-specific differences between the human and macaque insular subregions from the perspective of connectivity patterns.The main achievements of the present dissertation are as follows:1.A macaque subcortical brain atlas was constructed using a connectivity-based parcellation method.Using high-quality diffusion-weighted image（DWI）data from eight macaque brain specimens,a connectivity-based parcellation method was used to subdivide eight macaque subcortical regions,including the accumbens nucleus,amygdaloid nucleus,caudate nucleus,hippocampus formation,hypothalamus,globus pallidus,putamen,and thalamus,which were subdivided into up to 56 subregions within the bilateral hemisphere.Moreover,using the publicly available DWI data of macaque brain specimens,the overall subcortical parcellation patterns were confirmed and showed consistency in the two datasets.Furthermore,structural connectivity pattern of each subregion was constructed by probabilistic fiber tracking,and the subregion connectivity fingerprint was also mapped by the defined 48 cortical and subcortical regions in the other macaque whole brain atlas.Taken together,such a connectivity-based brain atlas of the macaque subcortex contributes to a better understanding of subcortical anatomy and function,and could help us understand the complex connectivity and diverse functions of the insula.2.A finer-grained atlas of the macaque insular cortex was obtained using a gradient combining parcellation method.Using high-quality DWI data from eight macaque brain specimens,a diffusion map embedding method was used to examine global gradients of macaque insula based on structural connectivity,and the dominant gradient presented a gradually rostrocaudal increase across insula territory.Meanwhile,by extracting the top and bottom 25% components from the dominant and second gradient respectively,which explained variance over 55% in total within ten gradients,a 4-subregion subdivision pattern was constructed and showed an anteroposterior pattern.Then,a connectivitybased parcellation method was performed to subdivide each component into two subregions showing the mediolateral or ventrodorsal pattern,which were confirmed by the cross-validation analysis.Furthermore,permutation tests identified that two subregions from each one of these components showed significant differences between their connectivity fingerprints.Finally,the dominant and second gradients were both significantly correlated with the T1w/T2 w and cortical thickness maps,suggesting that the macroscopic structural connectivity gradient may capture the underlying morphological and microscopic features of macaque insula.3.A 4-subregion human insula atlas was obtained by integrating the first two gradients and the finer-grained parcellation of the human insular cortex.Similarly,using in vivo DWI data from 40 humans,the diffusion map embedding method was performed to reveal global gradients of the human insula based on structural connectivity,and the first two gradients presented the gradually rostrocaudal and ventrodorsal increase separately.Confirmed by the cross-validation analysis,a connectivity-based parcellation method was used to subdivide the whole human insula into seven subregions.By integrating the first two gradients and seven subregions of the human insula,the four subregions of the human insula,similar to the macaque 4-subregion pattern,exhibited significant differences both in the structural and functional connectivity patterns.In addition,the dominant gradient of the human insula was significantly correlated with the thickness and T1w/T2 w maps,suggesting that the macroscopic structural connectivity gradient could capture the underlying morphological and microscopic features of the human insula.Moreover,using in vivo DWI data from 90 humans,the microstructural insula granularity was mapped from macroscopic neuroimaging,and the four subregions of the human insula showed significant differences in granularity and also exhibited regionally gradual changes.Based on structural and functional neuroimaging data,this dissertation investigates the global structural connectivity variation and subdivision of the human insula in detail,which may provide a better understanding of the insula anatomy and contribute to the subsequent studies of insula-related psychiatric disorders.4.Subregion homologies of the insular cortex in humans and rhesus monkeys were revealed,and structural connectivity differences were found in the insular subregions with VENs across species.Based on the established 4-subregion pattern of the human and macaque insula,this dissertation explored the subregion homologies and connectivity differences of the insular cortex between the human and macaque from structural connectivity.By comparing the ratio of the gray matter volume of the primate insula to the gray matter volume of the whole brain,the gray matter volume of the human insula exhibited significant expansion among three primate species,including humans,chimpanzees and rhesus monkeys.Based on structural connectivity patterns of insular subregions with the defined 46 homologous brain regions in the human and macaque,the four subregions of the human and macaque insula presented one-to-one homology by calculating the KL divergence across species,and moreover,the KL divergence of the most anterior insular subregion was higher than the relative posterior subregion,indicating that the evolution of the most anterior insular subregion was predominant over the posterior insular subregions.More interestingly,the insular subregions with the VENs,located in the human anteroventral insula and the posterior surface of the macaque orbitofrontal cortex,showed the highest evolutional change within all four homologous subregions across species.Based on the subregion connectivity fingerprints within 46 homologous brain regions across species,this anteroventral subregion of the human insula had stronger structural connectivity with the amygdala than the connectivity between the homologous region and the amygdala in macaques,indicating that humans were predominant over macaques in the emotion regulation.In addition,this anteroventral subregion of the human insula had stronger structural connectivity with the gustatory cortex than the connectivity between the homologous region and the amygdala in macaques,indicating that humans were predominant over macaques in the integration and feedback of taste information.Overall,such a cross-species comparison of the insular cortex in humans and macaques contributes to a better understanding of the evolution of brain structure and function.Overall,by exploring the anatomical structure of the macaque subcortex,insular cortex,and human insular cortex,this dissertation mainly revealed the topographic organization and connectivity of the insular cortex,in which the subregions showed the homologous organization from the structural connectivity across species.Combining prior research on the anatomical location of the primate VENs,this dissertation revealed the subregion homologies of the insular cortex in humans and rhesus monkeys,and yet the insular subregions with the VENs presented structural connectivity differences between humans and macaques,indicating that humans were predominant over macaques in the emotion regulation and taste function. |
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