The neural correlates of personal semantic memory across the lifecourse

点击翻译按钮获取中文摘要

Even though progressive memory loss is a defining feature of Alzheimer's disease (AD), there is currently no universally recognised diagnostic test. One major challenge for research and clinical practice is that it is difficult to differentiate healthy ageing from AD, both being associated with decline in memory function. It is thus critical to develop more specific tests of memory functions to differentiate memory profiles associated with healthy ageing and those associated with risk for AD. Our long-term memories are generally divided into two categories. On the one hand, semantic memory is our general knowledge of the world (for instance: "1984" is the title of a book written by George Orwell). This knowledge is considered to be detached from its context of acquisition (i.e., we would not remember when or where we have learned it) and to be culturally shared. On the other hand, episodic memory concerns our memories of context-specific personal events (I remember reading "1984" at Hyde Park yesterday). The distinction between these 2 types of long-term memory, semantic and episodic, is now well-established. We know that these memory systems are associated with different brain regions and are impaired differently in healthy ageing and AD: semantic memory tends to be well-preserved in ageing and in early AD, while episodic memory performance tends to decrease with advancing age and to be impaired in AD.However, recent data suggest that there may be additional forms of memory between the categories of semantic and episodic. These additional types, collectively referred to as personal semantics concerns knowledge of one's past (for instance: "I was born on the 25th of June like Orwell"; " I used to study Orwell's work at secondary school", or "'I am a fast reader"). Personal semantics share features with both semantic and episodic memory but appear to be distinguishable from them. Personal semantic memories are personal (like episodic memory), yet detached from a specific context of acquisition (like semantic memory). However, these forms of memories have not been comprehensively studied and we do not know how they are represented in the brain. What is crucially needed to better understand memory are experiments that compare different types of personal semantics against semantic and episodic memory processes. Moreover, since these distinct types of memory are known to evolve differently through ageing and AD, it is therefore important to study personal semantics in young and older adults and to identify the specific memory profiles of individuals at risk for AD. This is what we are proposing to do in the present research project. We will study the distinct types of personal semantics that have been described so far and compare their neural bases in groups of young and older adults, taking into account genetic risk for AD. For this, we will recruit 60 young (18-30) and 100 older (65-80) participants, half of which are at genetic risk for AD. Using electroencephalography (EEG) and magnetic resonance imaging (MRI), we will be able to: 1) Uncover how personal semantics, as a new component of declarative memory, is represented in the brain; 2) Identify how personal semantics evolve with age and in those associated with risk for AD; and 3) Propose new tools for the clinical diagnosis of AD by monitoring early departure from memory profiles observed in healthy older adults. Crucially, as no psychological test currently available allows the evaluation of the 3 types of memory together (i.e., semantic, episodic and personal semantics), our results will directly contribute to the development of new memory tests.Taken together, the present project will provide unique opportunities to better understand understudied forms of memory in younger and older adults, but also to improve the evaluation of memory functions in healthy ageing and in those at risk for AD.