Material specific lateralisation of medial temporal lobe function: an fMRI investigation

The theory of material specific lateralization of memory function posits that left and right MTL regions are asymmetrically involved in mnemonic processing of verbal and nonverbal material respectively. Lesion and functional imaging (fMRI) studies provide robust evidence for a left MTL asymmetry in the verbal memory domain. Evidence for a right MTL/nonverbal asymmetry is not as robust. A handful of fMRI studies have investigated this issue but have generally utilised nonverbal stimuli which are amenable to semantic elaboration. This fMRI study aimed to investigate the neural correlates of recognition memory processing in 20 healthy young adults (mean age = 26 years) for verbal stimuli and nonverbal stimuli that were specifically designed to minimize verbalisation. Analyses revealed that the neural correlates of recognition memory processing for verbal and nonverbal stimuli were differentiable and asymmetrically recruited the left and right MTL respectively. The right perirhinal cortex and hippocampus were preferentially involved in successful recognition memory of items devoid of semantic information. In contrast, the left anterior hippocampus was preferentially involved in successful recognition memory of stimuli which contained semantic meaning. These results suggest that the left MTL is preferentially involved in mnemonic processing of verbal/semantic information. In contrast, the right MTL is preferentially involved in visual/non-semantic mnemonic processing. We propose that during development, the left MTL becomes specialised for verbal mnemonic processing due to its proximity with left lateralised cortical language processing areas while visual/non-semantic mnemonic processing gets ‘crowded out’ to become predominantly, but not completely, the domain of the right MTL. Hum Brain Mapp 37:933–941, 2016. © 2015 Wiley Periodicals, Inc

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

Neural correlates of associative memory processing in the human brain

Episodic memory refers to memory for specific events from our own experienced past and is referred to as the ability to engage in mental time travel. Episodic memory, however, is not a unitary process. Our ability to create and retrieve episodic memories is dependent upon the ability to link or bind different elements of an episode into a single unit and retrieve this information. Associative memory processes crucially underlie our ability to do this and different types of associative memory are responsible for processing separate elements of an episodic memory. Substructures within the medial temporal lobes subserve associative memory processing but the extent to which different subregions contribute to processing different elements of an episodic memory remains unclear. This thesis investigates which medial temporal lobe substructures contribute to associative memory processing for verbal and non-verbal stimuli in the human brain using a combination of neuropsychological and neuroimaging approaches in healthy young (Chapters 3 and 4) and older adults (Chapter 5) and in patients with Alzheimer’s disease and frontotemporal dementia (Chapters 6 and 7). The results of the experiments conducted in this thesis provide complementary evidence using different methodologies and subject groups that medial temporal lobe substructures differentially contribute to different associative memory processes. In addition, the results of this thesis provide evidence that the left and right medial temporal lobe are asymmetrically recruited during associative memory processing of verbal and non-verbal stimuli respectively regardless of task demands. In older adults, however, medial temporal lobe structures are recruited in a more bilateral manner than was observed in their younger counterparts. Taken together, results from this collection of experiments provide new insights which may be used to extend current theoretical models of medial temporal lobe contributions to associative memory processing in the human brain. Importantly, the results of these studies reveal that the neural correlates of verbal and non-verbal associative memory processing differ and that updated models of associative memory processing must make separate predictions regarding medial temporal lobe contributions to verbal and non-verbal associative memory processing

Associative memory in ageing: Changes in anticipatory brain activity

Older adults are impaired in the ability to remember, especially for the associations across different elements of an event. It has been shown that during both memory encoding and retrieval, brain activities in anticipation to an upcoming event can influence memory for that event. To explore the role of the anticipatory brain activity in associative memory processing and how it may be affected by ageing, three electroencephalography (EEG) experiments were performed with both younger and older participants. Analyses were conducted in both ERP and time-frequency domains. Experiment 1 demonstrated that unlike older adults, younger adults were able to engage encoding-related anticipatory neural mechanisms before encountering any to-be-remembered information. During retrieval, however, older adults showed a pronounced ERP anticipatory effect for associative retrieval that was not seen in younger adults. Experiment 2 provided evidence suggesting that age-related differences in anticipatory associative memory effects were due, at least partly, to inefficient encoding as a consequence of diminished processing resources in older adults. Experiment 3 further revealed that when participants switched between words and pictures in an associative recognition task, only younger adults engaged anticipatory encoding-related activity, and they were more likely to recruit material-selective anticipatory mechanisms. Older adults were able to recruit anticipatory mechanisms during retrieval but not during encoding. In conclusion, older adults are impaired in anticipatory activity for associative encoding, but they are able to recruit anticipatory neural mechanisms at retrieval possibly to compensate for poor associative encoding. Compared to younger adults, however, they are less able to recruit these mechanisms flexibly in a goal-directed manner. The present findings advance the understanding of neural mechanisms of associative memory deficits in ageing, which may open new doors for cognitive training in ageing by targeting these mechanisms