The role of the thalamus in amnesia: a tractography, high-resolution MRI and neuropsychological study.

Although it is well established that thalamic lesions may lead to profound amnesia, the precise contribution of thalamic sub-regions to memory remains unclear. In an influential article Aggleton and Brown proposed that recognition memory depends on two processes supported by distinct thalamic and cortical structures. Familiarity is mediated by the mediodorsal (MD) thalamic nucleus and the entorhinal/perirhinal cortex. Recollection is mediated by the anterior thalamic nucleus (AN), the mamillothalamic tract (MTT) and the hippocampus. The authors also suggested that the lateral dorsal nucleus (LD) may contribute to the thalamic/hippocampus system, thereby implying that the LD may play a role in recollection. Given the finding that material specific amnesia can occur following thalamic lesions, we tested an extension of the Aggleton and Brown model. We predicted that patients with bilateral lesions with a bias to the left or right MD or AN/MTT/LD may exhibit impaired familiarity or recollection on verbal or non-verbal memoranda. We report two patients with highly focal thalamic lesions and profound memory impairments affecting verbal and non-verbal memoranda. For the first time, diffusion-weighted imaging was employed to perform tractography of the MTT along with high-resolution anatomical MRI and detailed assessments of verbal and non-verbal memory. Our data support only some aspects of the Aggleton and Brown model. Both patients had left MD nucleus and AN/MTT lesions and performed poorly on familiarity and recall for verbal memoranda, just as predicted by the model. However, both patients' performance for non-verbal memoranda (human faces and topography) is more difficult to reconcile with the model. Patient 1 had damage to the right AN/MTT/LD with sparing of the MD: familiarity should therefore have been preserved but was not. Patient 2 had damage to the right MD with sparing of AN/MTT: recollection should have been preserved but was not. This finding raises the possibility that fractionation of familiarity and recollection to separate thalamic nuclei may not fully capture the role of thalamic sub-regions in memory function.