Funk Adrian T, Hassan Asim A O, Brüggemann Norbert, Sharma Nutan, Breiter Hans C, Blood Anne J, Waugh Jeff L
Division of Pediatric Neurology, Department of Pediatrics, University of Texas Southwestern, Dallas, TX, United States.
Department of Natural Sciences and Mathematics, University of Texas at Dallas, Richardson, TX, United States.
Front Neurosci. 2023 Oct 25;17:1178473. doi: 10.3389/fnins.2023.1178473. eCollection 2023.
Cortico-striato-thalamo-cortical (CSTC) loops are fundamental organizing units in mammalian brains. CSTCs process limbic, associative, and sensorimotor information in largely separated but interacting networks. CTSC loops pass through paired striatal compartments, striosome (aka patch) and matrix, segregated pools of medium spiny projection neurons with distinct embryologic origins, cortical/subcortical structural connectivity, susceptibility to injury, and roles in behaviors and diseases. Similarly, striatal dopamine modulates activity in striosome and matrix in opposite directions. Routing CSTCs through one compartment may be an anatomical basis for regulating discrete functions. We used differential structural connectivity, identified through probabilistic diffusion tractography, to distinguish the striatal compartments (striosome-like and matrix-like voxels) in living humans. We then mapped compartment-specific projections and quantified structural connectivity between each striatal compartment, the globus pallidus interna (GPi), and 20 thalamic nuclei in 221 healthy adults. We found that striosome-originating and matrix-originating streamlines were segregated within the GPi: striosome-like connectivity was significantly more rostral, ventral, and medial. Striato-pallido-thalamic streamline bundles that were seeded from striosome-like and matrix-like voxels transited spatially distinct portions of the white matter. Matrix-like streamlines were 5.7-fold more likely to reach the GPi, replicating animal tract-tracing studies. Striosome-like connectivity dominated in six thalamic nuclei (anteroventral, central lateral, laterodorsal, lateral posterior, mediodorsal-medial, and medial geniculate). Matrix-like connectivity dominated in seven thalamic nuclei (centromedian, parafascicular, pulvinar-anterior, pulvinar-lateral, ventral lateral-anterior, ventral lateral-posterior, ventral posterolateral). Though we mapped all thalamic nuclei independently, functionally-related nuclei were matched for compartment-level bias. We validated these results with prior thalamostriate tract tracing studies in non-human primates and other species; where reliable data was available, all agreed with our measures of structural connectivity. Matrix-like connectivity was lateralized (left > right hemisphere) in 18 thalamic nuclei, independent of handedness, diffusion protocol, sex, or whether the nucleus was striosome-dominated or matrix-dominated. Compartment-specific biases in striato-pallido-thalamic structural connectivity suggest that routing CSTC loops through striosome-like or matrix-like voxels is a fundamental mechanism for organizing and regulating brain networks. Our MRI-based assessments of striato-thalamic connectivity in humans match and extend the results of prior tract tracing studies in animals. Compartment-level characterization may improve localization of human neuropathologies and improve neurosurgical targeting in the GPi and thalamus.
皮质-纹状体-丘脑-皮质（CSTC）环路是哺乳动物大脑中的基本组织单位。CSTC环路在很大程度上相互分离但又相互作用的网络中处理边缘系统、联想和感觉运动信息。CTSC环路穿过成对的纹状体区室，即纹状体小体（又称斑块）和基质，它们是中等棘状投射神经元的分离池，具有不同的胚胎起源、皮质/皮质下结构连接性、对损伤的易感性以及在行为和疾病中的作用。同样，纹状体多巴胺以相反的方向调节纹状体小体和基质中的活动。将CSTC环路通过一个区室进行路由可能是调节离散功能的解剖学基础。我们利用通过概率性扩散张量成像识别出的差异结构连接性，来区分活体人类中的纹状体区室（类纹状体小体和类基质体素）。然后，我们绘制了区室特异性投射图，并对221名健康成年人中每个纹状体区室、内侧苍白球（GPi）和20个丘脑核之间的结构连接性进行了量化。我们发现，源自纹状体小体和基质的纤维束在GPi内是分离的：类纹状体小体的连接性在更靠前、腹侧和内侧的位置更为显著。从类纹状体小体和类基质体素发出的纹状体-苍白球-丘脑纤维束在白质中穿过空间上不同的部分。类基质体素发出的纤维束到达GPi的可能性是类纹状体小体发出的纤维束的5.7倍，这与动物纤维束追踪研究结果一致。类纹状体小体的连接性在六个丘脑核（前腹侧、中央外侧、背外侧、外侧后、背内侧-内侧和内侧膝状体）中占主导地位。类基质体素的连接性在七个丘脑核（中央中、束旁、前丘脑、外侧丘脑、腹外侧-前、腹外侧-后、腹后外侧）中占主导地位。尽管我们独立绘制了所有丘脑核的图谱，但功能相关的核在区室水平偏差方面是匹配的。我们用先前在非人灵长类动物和其他物种中进行的丘脑纹状体纤维束追踪研究验证了这些结果；在有可靠数据的情况下，所有结果都与我们的结构连接性测量结果一致。在18个丘脑核中，类基质体素的连接性表现出偏侧化（左半球>右半球），与利手、扩散协议、性别或该核是由纹状体小体还是基质主导无关。纹状体-苍白球-丘脑结构连接性中的区室特异性偏差表明，将CSTC环路通过类纹状体小体或类基质体素进行路由是组织和调节脑网络的基本机制。我们基于MRI对人类纹状体-丘脑连接性的评估与先前动物纤维束追踪研究的结果相匹配并进行了扩展。区室水平的特征描述可能会改善人类神经病理学的定位，并改善在GPi和丘脑中的神经外科手术靶点。
