Abstract:
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 LGN (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 magnetic resonance imaging (MRI) at high field strength (7 Tesla) 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 behavioral 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 (RANln). 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 RANln 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.
摘要:
发展性阅读障碍(DD)是最常见的学习障碍之一,影响全世界数百万儿童和成人。迄今为止,科学研究试图主要基于大脑皮层的病理生理改变来解释DD。相比之下,几十年前,对五个死后人类大脑的开创性研究表明,DD的核心特征可能是视觉丘脑特定细分的形态改变-大细胞LGN(M-LGN)。然而,由于在人类非侵入性调查LGN细分方面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。这里,我们利用高分辨率磁共振成像(MRI)在高场强(7特斯拉)的最新进展来研究DD体内的M-LGN。使用病例控制设计,我们从患有DD的年轻成年人(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)的大样本中获得了数据.每位参与者完成了全面的诊断行为测试,并参加了两次MRI会议,包括三个功能性MRI实验和一个结构性MRI采集。我们测量了血氧水平依赖性反应和纵向松弛率,以比较两组的LGN细分功能和髓鞘形成。在前人研究的基础上,我们假设M-LGN在DD中发生改变,并且这些改变与关键DD诊断评分相关,即,快速字母和数字命名(RANLN)。结果表明,与对照组相比,DD中M-LGN的异常反应,这反映在群体之间这种细分的不同功能侧化中。这些改变与RANln表现相关,特别是男性DD。我们还发现DD中M-LGN的纵向弛豫率相对于对照的侧向差异。相反,LGN的另一个主要细分,细小细胞LGN(P-LGN),显示两组之间具有可比性的血氧水平依赖性反应和纵向松弛率。本研究首次明确表明M-LGN改变是DD的标志,影响这个细分的功能和微观结构。它进一步提供了M-LGN改变的第一个功能解释,并为更好地了解DD的性别特异性差异提供了基础,并对未来的诊断和治疗策略产生了影响。