Thalamic amnesia after infarct: The role of the mammillothalamic tract and mediodorsal nucleus

Abstract

Objective: To improve current understanding of the mechanisms behind thalamic amnesia, as it is unclear whether it is directly related to damage to specific nuclei, in particular to the anterior or mediodorsal nuclei, or indirectly related to lesions of the mammillothalamic tract (MTT).

Methods: We recruited 12 patients with a left thalamic infarction and 25 healthy matched controls. All underwent a comprehensive neuropsychological assessment of verbal and visual memory, executive functions, language, and affect, and a high-resolution structural volumetric MRI scan. Thalamic lesions were manually segmented and automatically localized with a computerized thalamic atlas. As well as comparing patients with controls, we divided patients into subgroups with intact or damaged MTT.

Results: Only one patient had a small lesion of the anterior nucleus. Most of the lesions included the mediodorsal (n = 11) and intralaminar nuclei (n = 12). Patients performed worse than controls on the verbal memory tasks, but the 5 patients with intact MTT who showed isolated lesions of the mediodorsal nucleus (MD) only displayed moderate memory impairment. The 7 patients with a damaged MTT performed worse on the verbal memory tasks than those whose MTT was intact.

Conclusions: Lesions in the MTT and in the MD result in memory impairment, severely in the case of MTT and to a lesser extent in the case of MD, thus highlighting the roles played by these 2 structures in memory circuits.

© 2015 American Academy of Neurology.

Figures

Figure 1. Lesions

(A) T1 axial sections of the patients' native MRI. The red circles show infarcts. P5's lesion is scarcely visible on the image (lesion volume = 5 mm3). We therefore provide a zoom on the lesion on the fluid-attenuated inversion recovery sequence. (B) Overlap of the lesions across patients (% of patients, n = 12) in an axial view (top; A = anterior, P = posterior), sagittal view (bottom left; A = anterior, P = posterior), and coronal view (bottom right). A mask of the right thalamus (in green) obtained using the FIRST tool in FSL is provided for information. A slice of the Morel atlas featuring structures of interest is overlaid on the axial view. CeM = central medial; CL = central lateral; CM = centromedian; GPe = external globus pallidus; Hb = habenula; ic = internal capsule; MDpc = parvocellular part of the mediodorsal nucleus; mtt = mammillothalamic tract; PuT = putamen; R = reticular nucleus; VA = ventral-anterior.

Figure 2. MTTs in patients and controls, volumes of the MTTs, memory and language performance in groups (patients vs controls) and subgroups (dMTT vs iMTT), and MTT volume and memory performance

(A) Illustration of mammillothalamic tracts (MTTs) in patients and controls. Segmentation of left and right MTTs in native brains of a patient (top, in red) and a control (bottom, in blue). (B) Volumes of the patients' MTTs. Left and right volumetric distribution in patients (z scores). (C) Memory and language performance in groups (patients vs controls) and subgroups (damaged MTT subgroup [dMTT] vs intact MTT subgroup [iMTT]). Intergroup comparisons of patients and controls. **p < 0.01. ***p < 0.001. Blue circles represent controls, empty orange circles represent iMTT patients, filled orange circles represent dMTT patients. (D) MTT volume and memory performance. Correlation between verbal memory performance (assessed here using the Logical Memory Test and Free and Cued Selective Reminding Test [FCSRT]) and MTT. *p < 0.05, 2-tailed.