Inter-individual differences in associative memory : structural and functional brain correlates and genetic modulators

Our memory for personal experiences (e.g., the first day at school) is termed episodic memory. This form of memory involves the recollection of single information as well as the connection between these pieces of information (e.g., what happened when, and where), referred to as associative memory. Associative memory declines markedly in aging; however, some individuals have proficient associative memory even until late life. These individual differences in associative-memory performance are also observable at younger ages. The underlying sources of these individual differences remain unclear. In this thesis, we aimed to identify the neural underpinnings of individual differences in associative memory, with special regard to brain structure, function, and neurochemistry. In the first part of the thesis, we investigated structural brain correlates of and dopaminergic contributions to associative memory in healthy older adults (studies I and II). In study I, we examined the relationship between regional gray-matter volume and associative memory. Individuals with better associative memory had larger gray-matter volume in dorsolateral and ventrolateral prefrontal cortex, suggesting that organizational and strategic processes distinguish older adults with good from those with poor associative memory. In study II, we examined the influence of dopamine (DA) receptor genes on item and associative memory. Individuals with less beneficial DA genotypes performed worse in the associative-memory task compared with carriers of more beneficial genotypes. Because no such group differences were found with regard to item memory, this suggests that dopaminergic neuromodulation is particularly important for associative memory in older adults. In the second part of the thesis, we examined in a sample of younger adults how different task instructions influence associative encoding, as well as the structural-functional coupling between task-relevant brain regions during associative-memory formation (studies III and IV). In study III, we investigated the effect of encoding instruction on associative memory. Specifically, we examined functional brain correlates of intentional and incidental encoding and demonstrated differential involvement of anterior hippocampus in intentional relative to incidental associative encoding. This suggests that the intent to remember associative information triggers a binding process accomplished by this brain region. Finally, in study IV we explored how gray-matter volume is associated with brain activity during associative-memory formation. We observed a relationship between gray-matter volume in the medial-temporal lobe (MTL) and functional brain activity in the inferior frontal gyrus (IFG). Importantly, this structure-function coupling correlated with performance, such that younger individuals with a stronger MTL-IFG coupling had better associative memory. Collectively, these four studies show that the neural underpinnings of individual differences in associative memory are many-faceted, interacting with each other and vary with regard to age and specific features of the associative task