| The mediodorsal thalamic nucleus(MD)is closely connected to the prefrontal cortex as part of complex relay system in the brain,and primarily maintains synchronization between brain regions and directs the widespread convey of information,facilitating cognitive and emotional processing.In particular,the MD has now been shown to influence many cognitive processes,including memory,decisionmaking,and executive functions.The MD is a key brain structure associated with many neurological disorders,meanwhile,it is also a key target for deep brain stimulation.Whereas the fine anatomical organization of the MD and the function of each subregion remain elusive,further investigations are needed to better understand its structure and function.Current studies on the function of MD were largely derived from animal studies,and it remains controversial whether these findings can be directly translated to humans.The emergence of comparative neuroimaging provides methodological support for the identification of homologous regions between different species and also helps to further translate the conclusion obtained in non-human primates to humans.Cross-species comparisons based on neuroimaging with high accuracy and generalizability have thrived in recent years and becomes an important tool for brain projects.Studies on animals and humans have revealed a more complex and extensive role of MD in high-order cognitive functions.This study focuses on the construction of a cross-species brain atlas,cross-species comparisons,and the structural organization of MD from an evolutionary and developmental perspective.The main contributions of this study include the following:1.Construction of the brain atlas of MD in humans.This study used highresolution data from the Human Connectome Project to redefine the organization of the MD in humans using an anatomical connectivity-based approach.Four fine-scale subregions were identified in each hemisphere,namely the medial(MDm),central(MDc),dorsal(MDd),and lateral(MDl)parts,which match the cytoarchitectonic boundaries of previous histological studies.Divergent patterns of anatomical and functional connectivity were unraveled in each subregion,particularly in the prefrontal cortex,using.The function of the MD subregion was further explored using partial least squares correlation analysis,revealing the relationship between connectivity of each subregion and prefrontal cortices and behavioral indicators in 1012 subjects.The results suggest that MD is specifically involved in a range of cognitive functions.Specifically,the MDm was primarily related to the domain of emotional cognition,while MDl is involved in a variety of cognitive functions,particularly cognitive flexibility and inhibition.MDc and MDd are associated with fluid intelligence,processing speed,and emotional cognition.These results provide new insights into the anatomical and functional organization of the dorsomedial thalamic nucleus and highlight the various roles of prefrontal-thalamic circuits in human cognition.2.Construction of the brain atlas of MD in macaques.In this study,the MD was divided into four subregions using anatomical connectivity-based parcellation on exvivo macaque MRI data of different spatial resolutions and multi-sites.The parcellation and connectivity patterns of the subregions were consistent across datasets.The connectivity patterns of the subregions were consistent with the previous tracer projections on macaques.The atlas of the macaque MD provides a basis for crossspecies comparisons.3.Exploration of the homology of MD between macaques and humans.Based on the cross-species brain atlas of the MD constructed in this study,the relationship of subregions of the MD in evolution has been explored using anatomical connectivities.With the connections to homologous white matter tracts,it suggested that the corresponding subregions according to anatomical locations are highly homologous between macaques and humans.The MD subregions mainly connected with the anterior thalamic radiation and fornix,and the prefrontal subregions were identified as targets area for further study.After identification of the homology of prefrontal cortices between the human and macaque,the connectivities of the MD subregion were quantitatively compared across species.Although the MD subregions have strong correspondence across species,analysis based on individual connections revealed those that the connectivities between the MDm and the orbitofrontal cortex differed significantly between species.Such difference contributeutes to the human functions in cognitive decision-making.In general,the MD and its subregions are evolutionarily conserved and stable.4.Construction of a developmental atlas of human MD using adolescent MRI data.The changes in the MD during development were revealed.We found that there was a high correspondence between subregions at different ages,and the anatomically corresponding subregions at different ages had the strongest similarity in connectivity.Especially,in late adolescence at the age of 15-17 years,the connectivity between the medial frontal lobe and the medial orbitofrontal underwent more pronounced changes compared to other age groups,which may be caused by the greater fluctuations in emotional control.Overall,the MD has been relatively stable across different ages,and these findings support the alternatives in human cognitive behavior during development. |
