Developmental dyslexia (DD) is one of the most common learning disorders, affecting millions of children and adults worldwide. To date, scientific research has attempted to explain DD primarily based on pathophysiological alterations in the cerebral cortex. In contrast, several decades ago, pioneering research on five post-mortem human brains suggested that a core characteristic of DD might be morphological alterations in a specific subdivision of the visual thalamus—the magnocellular lateral geniculate nucleus (M-LGN). However, due to considerable technical challenges in investigating LGN subdivisions non-invasively in humans, this finding was never confirmed in vivo, and its relevance for DD pathology remained highly controversial. Here, we leveraged recent advances in high resolution MRI at high field strength (7 T) to investigate the M-LGN in DD in vivo. Using a case-control design, we acquired data from a large sample of young adults with DD (n = 26; age 28 ± 7 years; 13 females) and matched control participants (n = 28; age 27 ± 6 years; 15 females). Each participant completed a comprehensive diagnostic behavioural test battery and participated in two MRI sessions, including three functional MRI experiments and one structural MRI acquisition. We measured blood oxygen level-dependent responses and longitudinal relaxation rates to compare both groups on LGN subdivision function and myelination. Based on previous research, we hypothesized that the M-LGN is altered in DD and that these alterations are associated with a key DD diagnostic score, i.e. rapid letter and number naming. The results showed aberrant responses of the M-LGN in DD compared to controls, which was reflected in a different functional lateralization of this subdivision between groups. These alterations were associated with rapid letter and number naming performance, specifically in male DD. We also found lateralization differences in the longitudinal relaxation rates of the M-LGN in DD relative to controls. Conversely, the other main subdivision of the LGN, the parvocellular LGN (P-LGN), showed comparable blood oxygen level-dependent responses and longitudinal relaxation rates between groups. The present study is the first to unequivocally show that M-LGN alterations are a hallmark of DD, affecting both the function and microstructure of this subdivision. It further provides a first functional interpretation of M-LGN alterations and a basis for a better understanding of sex-specific differences in DD with implications for prospective diagnostic and treatment strategies.

中文翻译：

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发育性阅读障碍中视丘脑大细胞分支功能障碍


发育性阅读障碍 （DD） 是最常见的学习障碍之一，影响着全球数百万儿童和成人。迄今为止，科学研究主要试图根据大脑皮层的病理生理学改变来解释 DD。相比之下，几十年前，对 5 个死后人脑的开创性研究表明，DD 的一个核心特征可能是视觉丘脑的一个特定分支——大细胞外侧膝状核 （M-LGN） 的形态改变。然而，由于在人类中非侵入性地研究 LGN 细分存在相当大的技术挑战，这一发现从未在体内得到证实，其与 DD 病理学的相关性仍然存在很大争议。在这里，我们利用高场强 （7 T） 高分辨率 MRI 的最新进展来研究体内 DD 中的 M-LGN。使用病例对照设计，我们从患有 DD 的年轻人 （n = 26;年龄 28 ± 7 岁;13 名女性） 和匹配的对照参与者 （n = 28;年龄 27 ± 6 岁;15 名女性） 的大量样本中获取了数据。每个参与者都完成了一个全面的诊断行为测试组合，并参加了两次 MRI 会议，包括 3 次功能性 MRI 实验和 1 次结构 MRI 采集。我们测量了血氧水平依赖性反应和纵向弛豫率，以比较两组的 LGN 细分功能和髓鞘形成。根据以前的研究，我们假设 M-LGN 在 DD 中发生改变，并且这些改变与关键的 DD 诊断评分有关，即 快速字母和数字命名。结果显示，与对照组相比，DD 中 M-LGN 的反应异常，这反映在组间这种细分的不同功能偏侧化中。 这些改变与快速的字母和数字命名性能有关，特别是在男性 DD 中。我们还发现 DD 中 M-LGN 的纵向弛豫率相对于对照组存在偏侧化差异。相反，LGN 的另一个主要分支，细小细胞 LGN （P-LGN），在组间显示出相当的血氧水平依赖性反应和纵向弛豫率。本研究首次明确表明 M-LGN 改变是 DD 的标志，影响该细分的功能和微观结构。它进一步提供了对 M-LGN 改变的初步功能解释，并为更好地了解 DD 的性别特异性差异奠定了基础，对前瞻性诊断和治疗策略具有影响。