Fiore Giorgio, Giampiccolo Davide, Xiao Fenglai, Koepp Matthias J, Iglesias Juan E, Vos Sjoerd B, de Tisi Jane, McEvoy Andrew W, Bertani Giulio A, Locatelli Marco, Finn Roisin, Caciagli Lorenzo, Sidhu Meneka, Galovic Marian, Baxendale Sallie, Duncan John S, Miserocchi Anna
Victor Horsley Department of Neurosurgery, National Hospital for Neurology and Neurosurgery, London WC1N 3BG, UK.
Unit of Neurosurgery, IRCCS Ca' Granda Foundation Ospedale Maggiore Policlinico, Milan 20122, Italy.
Brain Commun. 2025 Feb 12;7(2):fcaf067. doi: 10.1093/braincomms/fcaf067. eCollection 2025.
Knowledge of the structural underpinnings of human verbal memory is scarce. Understanding the human verbal memory network at a finer anatomical scale will have important clinical implications for the management of patients with verbal memory impairment. In this cross-sectional study, we aimed to assess the contributions of cerebral cortex and hippocampal subfields to verbal memory encoding in temporal lobe epilepsy. We included consecutive patients ( = 84) with radiologically and pathologically defined hippocampal sclerosis (HS) (44 left-sided) and unilateral temporal lobe epilepsy, and healthy volunteers ( = 43) who were comparable regarding age and sex. The morphometric and volumetric measures of cerebral cortex and hippocampal subfields were extracted from high-resolution MRI scans. People included in this study underwent standardized neuropsychological evaluation, including measures of verbal memory assessed through the Adult Memory and Information Processing Battery. Verbal memory performances were -scores corrected by using means and standard deviations published for sample standardization. Associations between verbal learning -scores and the grey matter volume of the cerebral cortex and hippocampal subfields were investigated. Reduction of grey matter volumes in the left and right medial and dorsolateral prefrontal cortex ( < 0.0001), superior and middle temporal gyri ( < 0.0001), anterior and posterior cingulate cortex ( < 0.0001) and of the left ventrolateral prefrontal cortex ( < 0.0001) and parietal-temporal-occipital junction ( < 0.0001) were associated with worse verbal learning. These findings were consistent across both the entire cohort and in a subgroup analysis focused exclusively on HS patients. Within hippocampi, smaller volumes of the left dentate gyrus ( = 0.003), cornu ammonis 4 ( = 0.005) and cornu ammonis 3 ( = 0.03) were associated with worse verbal learning -scores. This study demonstrates that verbal learning in patients with temporal lobe epilepsy is strongly related to the volume of distinct regions of the prefrontal, temporal and cingulate cortices and left dentate gyrus, cornu ammonis 4 and cornu ammonis 3 hippocampal subfields. It provides the basis to suggest a corticohippocampal network for verbal learning in these patients, improving our understanding of human verbal memory. These biomarkers may inform attractive targets for forthcoming modulating therapies. Future work may also analyse the impact of sparing part of the left dentate gyrus, cornu ammonis 4 and cornu ammonis 3 as a protective measure against verbal memory impairment after surgery for temporal lobe epilepsy.
关于人类言语记忆的结构基础的知识十分匮乏。在更精细的解剖学尺度上理解人类言语记忆网络，对于言语记忆受损患者的管理具有重要的临床意义。在这项横断面研究中，我们旨在评估大脑皮层和海马亚区对颞叶癫痫患者言语记忆编码的贡献。我们纳入了连续的患者（n = 84），这些患者经影像学和病理学确诊为海马硬化（HS）（44例为左侧）且患有单侧颞叶癫痫，以及健康志愿者（n = 43），他们在年龄和性别方面具有可比性。从高分辨率MRI扫描中提取大脑皮层和海马亚区的形态学和体积测量数据。本研究中的受试者接受了标准化神经心理学评估，包括通过成人记忆与信息处理成套测验评估的言语记忆测量。言语记忆表现为使用为样本标准化公布的均值和标准差校正后的z分数。研究了言语学习z分数与大脑皮层和海马亚区灰质体积之间的关联。左侧和右侧内侧及背外侧前额叶皮层（p < 0.0001）、颞上回和颞中回（p < 0.0001）、前扣带回和后扣带回皮层（p < 0.0001）以及左侧腹外侧前额叶皮层（p < 0.0001）和顶颞枕交界区（p < 0.0001）的灰质体积减少与较差的言语学习相关。这些发现在整个队列以及专门针对HS患者的亚组分析中都是一致的。在海马体中，左侧齿状回（p = 0.003）、海马4区（p = 0.005）和海马3区（p = 0.03）体积较小与较差的言语学习z分数相关。这项研究表明，颞叶癫痫患者的言语学习与前额叶、颞叶和扣带回皮层以及左侧齿状回、海马4区和海马3区海马亚区的不同区域体积密切相关。它为提出这些患者言语学习的皮质 - 海马网络提供了依据，增进了我们对人类言语记忆的理解。这些生物标志物可能为即将到来的调节治疗提供有吸引力的靶点。未来的工作还可以分析保留部分左侧齿状回、海马4区和海马3区作为预防颞叶癫痫手术后言语记忆损害的保护措施的影响。
