The functional role of thalamic-mediated brain networks in memory

The thalamus, a brain structure deep inside the brain, includes multiple nuclei called anterior, mediodorsal, ventral (further separated into anterior, lateral and posterior) and pulvinar thalamic nuclei. The specific contribution of these structures in memory retrieval and the way they communicate with other critical structures of the memory network remain understudied especially in humans. Damage to some of these structures is linked to memory disorders, which means they should support functions related to memory. However, whether this damage disrupts processes directly related to memory retrieval or can be explained by other cognitive dysfunction is disputed. It is also disputed whether damage in these nuclei prevents patients recollecting their memory or, in addition, it affects their feeling of familiarity for previously experienced things. The main reasons these questions are still outstanding in the memory literature, relate to key methodological considerations, including small number of participants - especially patients with damage in the thalamus - and insufficient measures of cognition and memory in previous studies. In the proposed project, we will select 40 patients with memory problems as a result of thalamic stroke resulting in reduced volumes in these structures. State-of-the-art brain imaging will be used to measure these structural volumes, as well as the size of fibre tracts and spontaneous connectivity mediated by the thalamic nuclei. Tests of cognitive function and memory, including tests of familiarity and recollection for different types of stimuli, such as scenes, objects and words, will be given to patients and healthy participants. Functional brain imaging in healthy participants, while undergoing task-based fMRI (2 experiments) will also be used to explore whether these structures contribute to memory retrieval in communication with other structures of the memory network. These functional brain measures will be also complemented by synchronised recording of eye movements to explore the way the various thalamic structures (and especially the ventrolateral and pulvinar areas) integrate visual information in the service of memory. By relating memory and cognitive tests with brain imaging data, we will determine how the various thalamic structures function in the different types of memory, whether the role of the thalamus in memory can be explained by other higher cognitive functions and whether specific thalamic nuclei are responsible for integrating and communicating memory signals. The findings will fundamentally change the way the role of the thalamus is described within the brain's memory networks.

The different thalamic nuclei of the brain - including anterior, mediodorsal, ventral anterior, ventral lateral, ventral posterior-lateral and pulvinar nuclei - play a critical role in memory functions, in concert with the regions of the Medial Temporal Lobe. However, their specific roles within the memory network remain understudied, especially in humans. We will combine advanced neuroimaging - including structural and diffusion MRI and connectivity fMRI - with neuropsychological investigation of a relatively large patient cohort with thalamic damage. Specifically, we plan to recruit 60 patients, from whom 40 participants will be selected on the basis of memory impairment and damage confined to the thalamus. MRI measures of brain volumes, fibre tract integrity (DTI) and resting-state connectivity will be obtained. Measures of general cognitive function alongside measures of memory retrieval for different types of stimuli will be obtained from patients and a group of 40 age-matched healthy controls. Finally, two task-based fMRI experiments will be performed with healthy volunteers to explore memory retrieval processes mediated by thalamic networks (fMRI Exp. 1) and the contribution of the anterior thalamus in the detection of expectation violation (fMRI Exp. 2). Using these data and appropriate analytical methods (graph-theoretic connectivity, dynamic causal modelling and multivariate pattern analysis), we will explore: i) the degree to which mediodorsal and anterior thalamus are functionally specialised for different memory types, ii) whether the role of the thalamus in memory is mediated by executive functions, iii) the role of the mediodorsal thalamus as a functional hub specialised in integrating memory signals, iv) the role of ventrolateral thalamus and pulvinar in integrating visual information in the service of visual memory and v) the role of the anterior thalamus in supporting novelty detection and expectation violation together with the hippocampus.