The role of the medial part of the thalamus, and in particular the mediodorsal nucleus (MD) and the mammillothalamic tract (MTT), in memory has long been studied, but their contribution remains unclear. While the main functional hypothesis regarding the MTT focuses on memory, some authors postulate that the MD plays a supervisory executive role (indirectly affecting memory retrieval) due to its dense structural connectivity with the prefrontal cortex (PFC). Recently, it has been proposed that the MD, MTT and PFC form part of the DMN the default mode network (DMN). Due to the theoretical presence of MD and MTT in the DMN, we aimed to show the effect of thalamic lesions on functional connectivity (FC) and its putative role in cognitive impairment. We recruited 12 patients with left thalamic infarction and 12 matched healthy controls. They underwent neuropsychological assessment including memory tasks, morphological 3D MRI and resting state fMRI. A ROI-to-ROI method was used for group-level FC analyses. Patients had lesions in the MD and ventrolateral nuclei, with a damaged mammillothalamic tract (MTT) in seven of them. They showed lower performance than controls on verbal memory, executive function and language tests, with more impairment in memory, working memory, semantic verbal fluency and attention in the MTT-damaged patients. Contrast analyses between patients and matched controls showed lower FC in the ventral and dorsal DMN. Correlation analyses (patients and controls pooled) showed i/a positive correlation between memory and DMN, and ii/that MTT volume correlated with decreased functional connectivity in the dorsal DMN, whereas there was no correlation with MD lesion volume. These results suggest that both the memory impairment and the DMN functional change we observed may reflect an effect of the MTT lesion rather than MD damage.
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