Learning induces functional and structural plasticity. This thesis used a range of neuroimaging approaches in both humans and rodents to address three main questions: (1) Can we predict learning performance using baseline imaging measures? (2) To what extent do performance outcomes or training amount determine experience-dependent plastic changes? (3) What biological mechanisms underlie white matter plasticity detected using MRI? Effects of performance and amount of practice on brain structure were studied by varying the amount of juggling practice. Brain structure was found to predict performance on a complex juggling task before learning acquisition. Both performance and practice were found to affect brain structure after learning. Overall, participants that achieved higher performances had higher grey matter (GM) and WM matter change. Also, participants that trained juggling for longer had higher positive brain changes than participants that practiced less. The effects of juggling performance and practice in functional connectivity and GABA levels as measured by MR spectroscopy (MRS) were also investigated. High intensity training was found to decrease the motor resting-state network strength while lower intensity increased the network strength. The increase in strength was associated with a decrease in GABA concentration. A correlation was also found between motor resting-state strength change and GABA concentration change after learning. Finally, since WM plasticity has not been thoroughly investigated and to understand which cellular events underlie WM change, an animal model of motor learning was combined with diffusion tensor imaging (DTI) and immunohistochemistry. Learning a novel motor task increased WM fractional anisotropy, an indirect measure of WM microstructure, in the contralateral hemisphere to the used paw. Immunohistochemistry staining with myelin basic protein (MBP) antibody of this region revealed higher myelin stain intensity for the learning group that correlated with performance in the task.

In recent years the role of offline consolidation in supporting word learning has attracted great interest and has provided valuable insight into how novel spoken and written words are learned. Relatively little attention has focused on whether offline consolidation supports the learning and generalisation of novel orthographic knowledge. Meanwhile, laboratory-based approaches have proven valuable in overcoming the methodological challenges of studying reading acquisition, i.e. learning letter-sound knowledge. This thesis combines laboratory-based orthographic learning with an overnight consolidation framework to track the effects of sleep on learning novel letters and novel written words in six experiments. Experiment 1 validated the artificial orthography paradigm by using fMRI to show the novel orthography activated similar neural regions to pseudowords written in familiar orthography. Comparing recently learned words and objects additionally highlighted the componential and holistic processes that distinguish reading from object naming. Experiments 2, 3, and 4 investigated whether overnight consolidation had contrasting effects on learning novel letters and learning novel written words. All three studies showed overnight improvements in the ability to use and generalise knowledge of letters. Experiment 3 further assessed whether consolidation supported the formation of bigram representations. While the results did not show bigram consolidation, a recognition memory task indicated participants had consolidated the novel spoken words. Experiment 4 manipulated the internal statistical structure of the novel words finding, in contrast to Experiment 3, participants had consolidated the written forms of the novel words. Experiments 5 and 6 asked whether consolidated and unconsolidated spoken words would support orthographic learning. These studies failed to observe previous findings of spoken word consolidation and did not demonstrate clear effects of lexical knowledge on orthographic learning. The findings of the thesis demonstrate the importance of letter-level learning and consolidation during reading acquisition as well as highlighting the value of laboratory-based studies for understanding the interdependent trajectories of the skills involved in reading.

The fornical tract, a major input-output pathway of the hippocampus, of the primate brain makes crucial contributions to visual memory, as effects after surgical or aetiological lesions of this tract are widely documented in the monkey and human literature. Here, a series of experiments sought to further elucidate the functions of this structure with a battery of novel tasks in macaque monkeys, conducted either on a touchscreen or in an ambulatory chamber, so as to offer a more global view of the mnemonic role accomplished by it. After receiving bilateral transection of the fornix, monkeys are impeded in the 'fast learning' phase of a large number of new visuospatial conditional problems, with major impairments seen in eliminating non-perseverative errors. These fornix transected monkeys are however facilitated in the initial acquisition of a visuovisual conditional task, with facilitation seen in their improved ability in eliminating perseverative errors. It is also demonstrated in an ambulatory apparatus, in comparison to control monkeys, these monkeys are impaired in the new learning of visuospatial context of environments, albeit still displaying intact locomotor and exploratory behaviour patterns. Contrary to the relatively clear role in new learning, the involvement of the fornix in memory retention over the very long-term is unknown. It is shown here that once some visuospatial information is learnt; the fornix is no longer implicated in the retention of the material. The effects of fornix transection are also found to be detrimental on a spatial recognition task, with impairments observed in acquisition of the more demanding stages of the task. The overall results covered in this thesis support previous work suggesting that the fornix mediates the new learning of visual information, and I further propose that this fornical involvement lies primarily in the learning of spatio-temporal contexts, particularly during 'fast learning', as well as in task-sets acquisition. I also argue for dissociation in the contributions of the fornix and hippocampus to some memory processes in the macaque.

Missing pages were blank, therefore omitted. / Practice improves sensory perception, a phenomenon known as perceptual learning. Perceptual learning is interesting because it reflects plasticity in the brain where none was imagined, and because of its enormous applied potential. In vision, learning of simple discriminations is well-described. Here, I study the learning of two complex visual tasks, texture-and face identification, using a ten-alternative forced-choice procedure. The data are clear: learning of complex patterns is much like learning of simple patterns in its specificity, stability and time-course. Therefore, learning obeys similar rules at several levels in visual processing. The characteristics of learning, in particular the specificity and stability of learning, affect inherent aspects of object recognition. / Thesis / Doctor of Philosophy (PhD)

Overexpression of the NR2B subunit of the NMDA receptor in the forebrain has been shown to improve learning and memory in mice (Tang et al 1999), which provides exciting implications for the enhancement of human cognition. However, it was first essential to establish replicability, and since the Tang et al (1999) study used only male mice we wished to investigate possible sex differences. On the hidden platform watermaze, we found a trend for male NR2BOE mice to learn the task more quickly than male wildtype mice (as observed by Tang et al. 1999), but the opposite trend in female mice; female NR2BOE mice were slower to reach the hidden platform than female wildtype mice. This pattern of results was also observed on the spatial reference Y memory task and open field task (for anxiety), although not on the spatial working memory T maze task (despite a sex difference). However, wildtype and NR2BOE mice performed at similar levels on the novel object recognition task, the spatial novelty preference task, visible platform watermaze and visual discrimination task. A battery of tests considering some species typical behaviours of mice demonstrated that wildtype and NR2BOE mice were comparable on tests of motor ability, strength, co-ordination, anxiety, burrowing and nesting. This suggests that our behavioural results are not due to a general impairment or enhancement of species typical behaviours. We considered the possibility that the difference between the results of Tang et al (1999) and those we observed may be caused by age differences; hence we attempted to replicate our results on the hidden platform watermaze, spatial reference Y maze and open field test in age matched mice. However, the second cohort of NR2BOE mice performed at similar levels to wildtype mice, and at significantly improved levels compared to the mice of the first cohort. We also considered the effects of knocking out the NR2B subunit on learning and memory, and NR1 subunit deletion within the hippocampus. On the spatial working memory T maze, these mouse strains performed similarly to their respective wildtype strains. Similarly, on a two beacon watermaze (with one indicating the platform position), mice lacking the NR2B subunit were able to locate the platform in a similar length of time. To ensure that the null results we had observed in the second cohort were not due to loss of the NR2B protein overexpression in the forebrain, we performed polymerase chain reactions (PCR), quantitative real-time PCR, and Western blots. We ascertained that the transgene was indeed present and that NR2B mRNA and protein levels were elevated in the hippocampi of the NR2BOE mice. In conclusion, it is unclear why the behaviours we observed in the NR2BOE mice are different to those published in the literature. It is possible that they may be due to differences in environmental enrichment, but the cause of the genotype by sex differences observed in the mice of cohort 1 is unclear. Nonetheless, we have advanced our knowledge of the effects of modifications in the levels of the NR2B subunit of the NMDA receptor on learning and behaviour.

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