Functional recovery of the upper limb after stroke is influenced by many factors, one being amount of affected arm and hand use following stroke. In the healthy population, amount of hand use is influenced by degree of hand dominance. Depending on side of stroke and previous hand dominance, these preferences may be altered, consequently affecting the amount of upper limb use. Determining hand preference in patients after stroke, when measured, is commonly assessed with questionnaires; however, these reports are subjective and patients may have difficulty recalling from memory which hand they use for the numerous activities on the questionnaire. A preferential reaching task has been shown to correlate with the degree of hand dominance as determined by the Waterloo Handedness Questionnaire, providing an objective performance-based method to assess the continuum of hand dominance in healthy subjects. A modified version of this preferential reaching task, with varying degrees of proximal to distal control, was used to investigate the influence of impairment, pre-stroke dominance and task difficulty on affected arm reach percentage. Results of the study revealed that it is feasible to administer a modified preferential reaching task in the stroke population, as the test could be completed in less than 10 minutes with no adverse effects reported from the patients. Heterogeneity made it difficult to detect statistical effects of task difficulty and pre-stroke dominance on post-stroke preference; however, there were trends observed indicating that patients with their dominant arm affected may have greater preference for the affected arm compared to those with their non-dominant arm affected. This was despite similar impairment levels between these patient groups. Preference for the dominant arm (whether affected or unaffected) was stronger when the task was at midline or in contralateral space, and when tasks required the greatest degree of distal control. In future, the degree of hand preference measured with this tool will have important implications for identifying areas in therapy requiring greater focus as well as identifying individuals who would most benefit from therapies that promote affected arm use, such as constraint induced movement therapy

The thesis introduces a novel search paradigm, and explores a previously unreported behavioural error detectable in this paradigm. In particular, the ‘Unpacking Task’ is introduced – a search task in which participants use a computer mouse to sort through random heaps of items in order to locate a unique target. The task differs from traditional search paradigms by including an active motor component in addition to purely perceptual inspection. While completing this task, participants are often found to select and move the unique target item without recognizing it, at times continuing to make many additional moves before correcting the error. This ‘unpacking error’ is explored with perceptual, memory load, and instructional manipulations, evaluating eye-movements and motor characteristics in additional to traditional response time and error rate metrics. It is concluded that the unpacking error arises because perceptual and motor systems fail to adequately coordinate during completion of the task. In particular, the motor system is found to ‘process’ items (i.e., to select and discard them) more quickly than the perceptual system is able to reliably identify those same items. On those occasions where the motor system selects and rejects the target item before the perceptual system has had time to resolve its identity, the unpacking error results. These findings have important implications for naturalistic search, where motor interaction is common, and provide further insights into the conditions under which perceptual and motor systems will interact in a coordinated or an uncoordinated fashion.

The neural correlates that underpin fine motor control of the hand and their connections with the primary motor cortex (M1) require further investigation. Brodmann’s area 5 located in the superior parietal lobule (SPL) is suggested to be an important cortical area involved in the processing of somatosensory input important for precision movements. Area 5 is present in monkey species capable of opposable thumb movements and it is proposed that this area evolved with the ability to execute manual behaviours such as pinch grip. Further, area 5 is dominated by the representation of the hand and forelimb, and has direct connectivity with M1 implicating its role in the control of hand movements. Few studies have investigated the function of area 5 in humans and none have examined the connectivity between area 5 and ipsilateral M1. This thesis presents a novel approach to study the influence of area 5 on M1 output in healthy and awake humans during the processing of somatosensory inputs and during performance of motor tasks involving the hand. Using paired pulse transcranial magnetic stimulation over left area 5 and ipsilateral M1, the connections between the two cortical loci was probed. It was hypothesized that area 5 would facilitate M1 output at short and long latencies during the processing of tactile inputs and during the performance of motor tasks compared to rest. The current results demonstrate that changes in M1 output are task and temporally specific. Facilitation of the motor evoked potential (MEP) was present at short latency of 6 ms during the processing of somatosensory input whereas inhibition was present during conditions where the hand was performing a task with the thumb and index finger. Further, an inhibitory effect was seen at 40 ms during cutaneous stimulation. In experiments 1 and 2, there was no net influence of area 5 on M1 output observed at rest. The findings presented may have revealed a novel path with which to alter the motor output, and possibly movement of hand muscles.

Synaesthesia is a fascinating condition whereby individuals report extraordinary experiences when presented with ordinary stimuli. In this thesis, we examine an individual (L) who experiences time units (i.e., months and hours) and numbers as occupying specific spatial locations (e.g., January is 30º to the left). This type of spatial-form synaesthesia has been recently investigated by Smilek et al. (2007), demonstrating that synaesthetic time-space associations are highly consistent, occur regardless of intention, and can direct spatial attention. We extended this work in Chapter 2 by showing that for L, her time-space vantage point changed depending on whether the time units were seen or heard. For example, when L saw the word JANUARY, she reported experiencing January on her left side, however when she heard the word "January" she experienced the month on her right side. In this thesis, we validated L’s subjective reports using a spatial cueing task. The names of months were centrally presented followed by targets on the left or right. L was faster at detecting targets in validly cued locations relative to invalidly cued locations both for visually presented cues (January orients attention to the left) and for aurally presented cues (January orients attention to the right). We replicated these vantage-point dependent cueing effects also using hours of day. In Chapter 3, we further explored whether synaesthetic number forms could bias spatial attention using a spatial cueing and SNARC-type task. Two synaesthetes (L and B) both described experiencing the numbers 1 through 10 running vertically from bottom to top. Both experiments confirmed their synaesthetic number forms, such that when making odd-even judgments for the numbers 1, 2, 8, and 9, they showed SNARC-compatibility effects for up-down movements (aligned with their number form), but not left-right (misaligned) movements. Likewise in the spatial cueing task, both synaesthetes showed significantly faster response times to detect targets on the bottom of the display if preceded by a low number (1,2) and the top of the display if preceded by a high number (8,9), whereas they showed no cueing effects when targets appeared on the left or right (misaligned with their number forms). Both synaesthetes were, however, reliably faster to detect left targets following the presentation of numbers 10, and 11, and right targets following numbers 19 and 20 (running from left to right). Hence, we demonstrated that cueing and SNARC tasks could be used to empirically verify synaesthetic number forms. Moreover, we showed that numbers could direct spatial attention to idiosyncratic locations similar to time-units, replicating and extending our findings from Chapter 2. Lastly, Chapter 4 was aimed to explore the automaticity and involuntary nature of L’s number-forms. We continued to use the spatial cueing task and sought to eliminate any influence of strategy on L’s performance by: (1) shortening the interval between the cue and target onset to only 150 ms and (2) having the targets only fall in synaesthetically cued locations on 14.2% of trials. As a result, these manipulations should eliminate any cuing effects if L’s performance was attributable to intentionally using the cue to predict target location. However, our findings still showed an attentional bias consistent with L’s synaesthesia. We attributed L’s resilient cueing effects to the automaticity of her number-forms, thus demonstrating one of the hallmark attributes of synaesthesia. Overall, this series of studies convincingly demonstrated the reality of time-space and number-form synaesthesia and Chapter 5 concludes by discussing how this work has significantly contributed to the synaesthesia literature and to the study of perception overall.

Functional recovery of the upper limb after stroke is influenced by many factors, one being amount of affected arm and hand use following stroke. In the healthy population, amount of hand use is influenced by degree of hand dominance. Depending on side of stroke and previous hand dominance, these preferences may be altered, consequently affecting the amount of upper limb use. Determining hand preference in patients after stroke, when measured, is commonly assessed with questionnaires; however, these reports are subjective and patients may have difficulty recalling from memory which hand they use for the numerous activities on the questionnaire. A preferential reaching task has been shown to correlate with the degree of hand dominance as determined by the Waterloo Handedness Questionnaire, providing an objective performance-based method to assess the continuum of hand dominance in healthy subjects. A modified version of this preferential reaching task, with varying degrees of proximal to distal control, was used to investigate the influence of impairment, pre-stroke dominance and task difficulty on affected arm reach percentage. Results of the study revealed that it is feasible to administer a modified preferential reaching task in the stroke population, as the test could be completed in less than 10 minutes with no adverse effects reported from the patients. Heterogeneity made it difficult to detect statistical effects of task difficulty and pre-stroke dominance on post-stroke preference; however, there were trends observed indicating that patients with their dominant arm affected may have greater preference for the affected arm compared to those with their non-dominant arm affected. This was despite similar impairment levels between these patient groups. Preference for the dominant arm (whether affected or unaffected) was stronger when the task was at midline or in contralateral space, and when tasks required the greatest degree of distal control. In future, the degree of hand preference measured with this tool will have important implications for identifying areas in therapy requiring greater focus as well as identifying individuals who would most benefit from therapies that promote affected arm use, such as constraint induced movement therapy

The thesis introduces a novel search paradigm, and explores a previously unreported behavioural error detectable in this paradigm. In particular, the ‘Unpacking Task’ is introduced – a search task in which participants use a computer mouse to sort through random heaps of items in order to locate a unique target. The task differs from traditional search paradigms by including an active motor component in addition to purely perceptual inspection. While completing this task, participants are often found to select and move the unique target item without recognizing it, at times continuing to make many additional moves before correcting the error. This ‘unpacking error’ is explored with perceptual, memory load, and instructional manipulations, evaluating eye-movements and motor characteristics in additional to traditional response time and error rate metrics. It is concluded that the unpacking error arises because perceptual and motor systems fail to adequately coordinate during completion of the task. In particular, the motor system is found to ‘process’ items (i.e., to select and discard them) more quickly than the perceptual system is able to reliably identify those same items. On those occasions where the motor system selects and rejects the target item before the perceptual system has had time to resolve its identity, the unpacking error results. These findings have important implications for naturalistic search, where motor interaction is common, and provide further insights into the conditions under which perceptual and motor systems will interact in a coordinated or an uncoordinated fashion.

Perinatal stroke, which occurs before or shortly after birth, may result in both beneficial and maladaptive plasticity in surviving tissue. However, current preclinical and clinical work have an unclear understanding on the relationship between functional outcome and neurophysiology. This thesis aims to dually characterize and correlate behaviour with cortical motor representations in a mouse model of perinatal stroke. On postnatal day 7, a unilateral photothrombotic stroke was produced in the primary motor cortex of Thy1-ChR2 mice. Sensorimotor function was evaluated in adulthood with a battery of behavioural tests. Subsequently, a transcranial window was implanted, and motor maps were created through optogenetic point stimulation. To evaluate the impact of skilled motor training on cortical reorganization, mapping was conducted before and after training on the single pellet reaching task. P7 stroke caused functional impairments across a battery of motor tasks, while both motor map size and movement latency were bilaterally impacted. Spontaneous limb use was positively correlated with map size of both hemispheres, but single pellet performance was only positively correlated with map size in the injured hemisphere. Following skilled motor training, both map size reductions and delayed latency was partially restored. Additionally, significant correlations between map size expansion and movement latency reduction following skilled motor training not only demonstrate that training-induced plasticity was beneficial, but also primarily mediated by the uninjured hemisphere. As the first study to conduct within-animal optogenetic motor mapping following perinatal stroke, we show that 1) perinatal stroke bilaterally impacts both cortical and descending aspects of the motor system, 2) the remaining movement sites in both the uninjured and injured hemispheres have a positive impact on functional outcome, and 3) skilled forelimb training can partially restore cortical and descending motor neurophysiology.

This study examined the sociality of two phylogenetically closely related otomyine, murid rodent species that display differences in social behaviour in the wild. A fundamental characteristic of sociality in mammals is the ability to recognise conspecifics and discriminate between familiar and unfamiliar animals. In rodents, olfactory cues serve as the main source of such recognition and has been linked to dopaminergic reward centres in the brain, structures and regions responsible for short and long term memory, as well as neural processes involved in reducing stress. The neuropeptide, oxytocin, is produced by hypothalamic cells and can act as a neurotransmitter. Recent work has linked these neural, telencephalic structures (the nucleus accumbens, amygdala and hippocampus) to social recognition and oxytocin. Oxytocinergic receptor density is greater in such regions in social, monogamous or gregarious rodents, whereas it is much less in solitary species. Experimental studies have found mechanistic links between oxytocin function and social recognition and discrimination in laboratory mice and rats. However, no known study has tested social recognition and discrimination in wild-caught, non-typical model species in conjunction with a description of their oxytocinergic neuroanatomy. This justified my study to investigate whether the social-living, gregarious, colonial ice rat, Otomys sloggetti robertsi, show similar oxytocin receptor binding to other social species, and whether it has the ability to recognise conspecifics and discriminate between familiar and unfamiliar animals. Similarly, I investigated and compared these traits in a solitary, phylogenetically closely related species, the vlei rat, Otomys auratus. Neither sexes of both species showed social recognition abilities based on olfactory cues. This was surprising, as social-living ice rats were predicted to display recognition abilities. Interestingly, female vlei rats showed the ability to discriminate between a familiar and novel conspecific. The results suggest that vlei and ice rats exhibit social recognition flexibility, while social discrimination demonstrated by solitary female vlei rats may provide adaptive advantages in the wild. The impaired social recognition and discrimination observed by ice rats may be explained by their temporal flexibility in social behaviour in the wild. Colonial living and social tolerance by ice rats may indicate phenotypical plasticity, or ‘social flexibility’, to harsh ecological constraints. In contrast, the neuroanatomy of vlei and ice rats reflects their wild behaviour. Neural oxytocin receptor binding sites, identified using ligand-binding receptor autoradiography, were more intense in the nucleus accumbens, islands of Calleja, claustrum, indusium griseum, prefrontal cortex, insular cortices, extended amygdala, bed nuclei of the stria terminalis and hypothalamic nuclei of the ice rats, compared to that of the vlei rats. The overall patterns of neural oxytocin receptor (OTR) binding in ice rats are similar to that found in social voles, while that of vlei rats and solitary voles are comparable, particularly the binding intensities observed in the lateral septum. The brains of the vlei rat had OTR binding in the medial habenula and dentate gyrus, which was absent in the ice rat brains. Similarly, OTR binding was only detected in the subfields of hippocampus, intermediodorsal and rhomboid thalamic nuclei in the brain of the ice rats. As predicted from their social behaviour in the wild, the telencephalic OTR binding of the two species reflected their socially disparate behaviour, similar to other studies. Based on the lack of extreme differences in behavioural data, and various similarities in oxytocinergic receptor binding sites in the telencephalic structures, I suggest that a continuum of oxytocinergic effects on social, group-living behaviour of these related species may exist in this otomyine group. The differences in neuropeptidergic circuitry in these two species contributes further to our understanding of evolutionary neuroendocrinology of sociality. / Dissertation (MSc)--University of Pretoria, 2016. / National Research Foundation (NRF) / SARChI Behavioural Ecology / Zoology and Entomology / MSc / Unrestricted

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.

It is still unresolved whether individuals with dyslexia suffer non-verbal auditory processing deficits that may explain their phonological problems. Many studies have shown that dyslexic individuals are poor at discriminating pure tones, and this deficit has been attributed to impaired rapid auditory processing. In order to investigate the temporal properties of auditory processing in dyslexia, I have therefore studied the pure tone discrimination abilities of dyslexics, and then analysed the effects of varying interstimulus interval, the amount of frequency difference, and the effect of adding distractor tones during the interstimulus interval. In an investigation of dyslexic individuals’ ability to remember sequences of tones or digits (tonal and digit recognition memory), Rose and Rosner (2005) found that their results were affected by the education their subjects had received. The university educated dyslexics showed little tone discrimination deficit, whereas the dyslexic participants who never attended university showed greater deficits. Therefore, another aim of this thesis was to further study these findings and to identify any auditory processing compensatory mechanisms used by dyslexics who have received higher education. In eight different auditory tasks, the majority of which I programmed, I found strong evidence of non-verbal auditory processing deficits in dyslexic individuals. The comparison of university and non-university groups showed that educational differences had clear effects on many of their abilities, and should not be underestimated. The results showed that: • In general, dyslexics had poorer auditory frequency discrimination than controls. • Dyslexics who did not attend university had lower performance on almost all the auditory tests than the university dyslexic or control groups. • Unexpectedly, university educated dyslexics were less distracted by interrupting tones during frequency discrimination than university educated controls. • In a tone sequence memory task, the university educated dyslexics compensated in their performance to a level not much below that of the university educated controls, and above the controls who did not go to university. • The frequency recognition tasks positively correlated with literacy abilities, and were independent of general intelligence. The strongest correlations were in the non-university dyslexic group. The implications of these results are that not only do dyslexic individuals suffer from a low level, non-linguistic, auditory processing deficit, but those who do not get to university are less able to compensate for these difficulties. It is impossible to say if the higher performance in university educated dyslexics was due to compensation, or if their presence at university was due to a lack of these deficits in the first place. Nevertheless, since university educated dyslexics were better at resisting distractions this may underlie their ability to compensate. These findings could facilitate the creation of new teaching methods to support the development of dyslexics’ compensatory skills and new non-linguistic diagnostic aids. These would help with identifying dyslexia in second languages and enable earlier testing and identification, before reading failure exerts its inevitable negative effects on children’s self-confidence, happiness and future academic potential.