Cacciatore Martina, Magnani Francesca Giulia, Barbadoro Filippo, Ippoliti Camilla, Stanziano Mario, Clementi Letizia, Nigri Anna, Nanetti Lorenzo, Marino Silvia, La Porta Fabio, Lucca Lucia Francesca, Prada Francesco, Leonardi Matilde
SC Neurologia, Salute Pubblica, Disabilità, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy.
Neuroradiology Unit, Fondazione IRCCS Istituto Neurologico "Carlo Besta", Milan, Italy.
Front Neurol. 2025 Jun 18;16:1509668. doi: 10.3389/fneur.2025.1509668. eCollection 2025.
Consciousness relies on both cortical and subcortical structures and their feedforward and feedback pathways. Within this framework, the thalamus represents a relay station enabling the transmission, reception, and integration of information. However, it is divided into several nuclear groups each composed of functionally heterogeneous nuclei, and, to date, an agreement on which nuclei are most involved in the generation, maintenance, and modulation of consciousness is still lacking.
To fill this gap, we performed a systematic review by querying 5 electronic databases (MEDLINE/Pubmed, Scopus, EMBASE, Web of Science, and Cinahl Complete) about studies published in the last 20 years exploring the relationship between specific thalamic nuclei/nuclear groups and consciousness. For each included study, we extracted data supporting (i.e., positive evidence) or not (i.e., negative evidence) the relationship between a specific nucleus/nuclear group and the consciousness.
167 articles were included leading to 346 pieces of evidence of which 284 were positive. Most of the retrieved positive evidence pertained to the intralaminar nuclear group, followed by the mediodorsal and ventral nuclear groups. Furthermore, when considering the specific nuclei within the intralaminar nuclear group, results highlighted the centromedian-parafascicular complex (CM-Pf) as the nucleus most related to consciousness. Despite the high heterogeneity characterizing the adopted methodologies (e.g., brain stimulation, anesthesia, brain damage), as well as the study population (e.g., either healthy and pathological humans or animals) across studies, the greatest amount of evidence supported a key role of CM-Pf for the generation, modulation, and maintenance of the level of consciousness.
Though there is more research on the role of intralaminar nuclei, there is proportionally more positive evidence supporting these nuclei (particularly the CM-Pf) as key nodes in the network underlying consciousness compared to other thalamic nuclei. These results support ongoing therapeutic approaches to disorders of consciousness by reinforcing the rationale behind brain stimulation targeting CM-Pf and paving the way for other potential candidates for targeted interventions.
意识依赖于皮质和皮质下结构及其前馈和反馈通路。在此框架内，丘脑是一个中继站，能够实现信息的传递、接收和整合。然而，丘脑被分为几个核团，每个核团都由功能异质性的核组成，迄今为止，对于哪些核在意识的产生、维持和调节中最为重要仍未达成共识。
为填补这一空白，我们通过查询5个电子数据库（MEDLINE/ PubMed、Scopus、EMBASE、Web of Science和Cinahl Complete），对过去20年发表的探索特定丘脑核/核团与意识之间关系的研究进行了系统综述。对于每项纳入研究，我们提取了支持（即阳性证据）或不支持（即阴性证据）特定核/核团与意识之间关系的数据。
纳入167篇文章，得到346条证据，其中284条为阳性。检索到的大多数阳性证据与板内核团有关，其次是背内侧核团和腹侧核团。此外，在考虑板内核团内的特定核时，结果突出显示中央中-束旁复合体（CM-Pf）是与意识最相关的核。尽管各研究所采用的方法（如脑刺激、麻醉、脑损伤）以及研究人群（如健康和患病的人类或动物）具有高度异质性，但大量证据支持CM-Pf在意识水平的产生、调节和维持中起关键作用。
尽管关于板内核作用的研究较多，但与其他丘脑核相比，有比例更高的阳性证据支持这些核（特别是CM-Pf）作为意识基础网络中的关键节点。这些结果通过强化针对CM-Pf的脑刺激背后的理论依据，为意识障碍的现有治疗方法提供了支持，并为其他潜在的靶向干预候选方法铺平了道路。
