The optimal performance of an action depends to a great extend on the ability of a person to prepare in advance the appropriate kinetic and kinematic parameters at a specific point in time in order to meet the demands of a given situation and to foresee its consequences to the surrounding environment. In the research presented in this thesis, I employed high-density electroencephalography in order to study the neural processes underlying preparation for action. A typical way for studying preparation for action in neuroscience is to divide it in temporal preparation (when to respond) and event preparation (what response to make). In Chapter 2, we identified electrophysiological signs of implicit temporal preparation in a task where such preparation was not essential for the performance of the task. Electrophysiological traces of implicit timing were found in lateral premotor, parietal as well as occipital cortices. In Chapter 3, explicit temporal preparation was assessed by comparing anticipatory and reactive responses to periodically or randomly applied external loads, respectively. Higher (pre)motor preparatory activity was recorded in the former case, which resulted in lower post-load motor cortex activation and consequently to lower long-latency reflex amplitude. Event preparation was the theme of Chapter 4, where we introduced a new method for studying (at the source level) the generator mechanisms of lateralized potentials related to response selection, through the interaction with steady-state somatosensory responses. Finally, in Chapter 5 we provided evidence for the existence of concurrent and mutually inhibiting representations of multiple movement options in premotor and primary motor areas.

Aims: To investigate the motivation for concealment and disclosure of issues related to acquired and traumatic brain injury, and the association of these motivations with a range of possible predictors and outcomes (specifically, self-esteem, social support, social avoidance, loneliness, life satisfaction and community integration). Method: Three studies were carried out. The first (N=18) was a qualitative exploration of the reasons why people with acquired brain injury and their family carers chose to disclose or conceal information about the brain injury. In the second (N=55) two questionnaires were developed from the first study (the Non-Disclosure and Self-Disclosure questionnaires). These focused on the motivations of the person with the brain injury, one addressing motivations to conceal and the other motivations to disclose. Assessments of the reliability and validity of these measures were carried out. The third study (N=65) investigated the relationships between these motivations to conceal/disclose and some possible predictors and outcomes of these motivations. Findings: In the first study, a range of motivations for disclosure (e.g. seeking social support) and for concealment (e.g. avoiding the negative reactions of others) emerged from the data. In the second study, the derived questionnaires showed good internal consistency (the Cronbach’s alpha levels are N-DQ = .92 and S-DQ = .92) and the test-retest reliability (ICC= ranged from .38 to .805). Predicted significant correlations with Brief Fear of Negative Evaluation and N-DQ1 (r=.418, n=55, p=.002) and with the Distress Disclosure Index and S-DQ2 (r=.595, n=54, p=.001) provided evidence of their concurrent validity. In the third study, as hypothesized, higher motivations to conceal (i.e. high N-DQ scores) were significantly correlated with lower self esteem (r = -.357, n = 65, p = .003 with the Rosenberg Self-Esteem Inventory); higher social avoidance (r = .345, n = 64, p = .005 with the SAD); and greater loneliness (r = .380, n = 65, p = .002 with the University of California Los Angeles loneliness scale). The results of a mediation analysis were consistent with the hypothesis that higher motivations to conceal had an impact on general life satisfaction (as measured by the LiSat-11) via the mediation of social avoidance (SAD) and loneliness scale (UCLA). However, the hypothesis related to social support was not supported. Conclusions and implications: Many people affected by a brain injury and their families are concerned about the negative and positive impact that disclosure of information about the brain injury may have. Concern about the negative impact may be associated with negative views of the self, and have a range of negative social consequences. However, disclosure in some circumstances does, in reality, have a negative impact. People with an acquired brain injury and their families may need support in learning to conceal and disclose information about their injury in a more effective way.

Injection of tetanus toxin (TeNT), systemically or directly into the brain, has long been known to cause spastic paralysis or seizures respectively: thought to be due to disruption of inhibitory neurons and cleavage of vesicle associated membrane protein 2 (VAMP2). Here we investigate mechanisms involved in TeNT-induced chronic epilepsy in the first 16 days following injections in vivo and focally onto organotypic hippocampal slice cultures. Immunohistochemical analysis identified a spatial and temporal cleavage of both VAMP1 and VAMP2 progressing from day 2 post injection through to days 8 and 16. This was concentration dependent in slice cultures. VAMP1 has been shown to co-localise predominantly with inhibitory and VAMP2 with excitatory neurons. Contradicting previous results we have shown cleavage of both VAMP1 and VAMP2, disruption of both inhibition and excitation and direct effects of the toxin in the contralateral hippocampus. This indicates that inhibitory neurons and VAMP2 are not specifically targeted by TeNT. This project benefits from the combination of electrophysiological and immunohistochemical techniques to uncover functional changes induced by TeNT. It is also the first study of focally injected TeNT onto slice cultures and offers benefits for future long term studies of the effects of the toxin and drug screening.

Heterogeneous nuclear ribonucleoprotein-U like 1 (hnRNP-UL1) is a protein with numerous roles within the cell, including RNA processing and responses to DNA damage. Within this study two novel aspects of the protein are explored: the role of a putative nucleotide-binding domain and the protein's possible involvement in amyotrophic lateral sclerosis (ALS). hnRNP-UL1 is known to have a putative nucleotide-binding domain within its central region containing both a Walker A and Walker B motif. This region had not been investigated previously and was therefore of great interest in this study. The Walker A motif was shown to bind adenosine triphosphate (ATP) and the region appears to possess protein kinase activity. A biological substrate and function for these activities were not established, but these observations suggest that there are still layers of complexity to hnRNP-UL1's cellular roles to be elucidated. ALS is a late-onset neurodegenerative disease with limited treatment strategies and poor patient outcomes. Many of the proteins involved in its pathogenesis have two properties in common: they have roles in RNA-processing and possess prion-like domains (PrLDs). The properties of hnRNP-UL1 appertain to both of these and therefore it was of great interest when ALS patients were discovered with heterozygous hnRNP-UL1 mutations. Results showed that cells possessing the ALS patient mutations (R639C and R468C) had no DNA damage response (DDR) defects or mislocalisation of the protein, but their ssDNA/RNA-binding capability was markedly reduced. Whilst no direct causative links to ALS pathogenesis were shown with the hnRNP-UL1 patient mutations in this study, growing evidence implies good reason for the protein to have involvement in the disease.

The current thesis investigates the link between gestures and metaphor. In Chapter 3, we investigated whether left-hand gestures improve metaphor explanation compared to right-hand gestures or not gesturing at all. Additionally, we collected individual measurements for hemispheric involvement during speech production using the mouth asymmetry technique. We found a left-over-right hand gesturing advantage, which was higher for those with stronger right hemispheric involvement during speech production. This finding suggested that gestures’ self-oriented functions are hemisphere specific. In Chapter 4, we investigated whether left-hand gestures rather than taps trigger metaphorical language use. We found no such evidence, but we found that gestures compared to taps increased the number of words uttered, which in turn led to the use of more metaphors. This points towards gestures’ facilitative effect on speech production, but further research is needed to pin-point exactly what process is facilitated. In Chapter 5, we investigated whether gestures with a particular hand, when produced without speech, prime semantic categorisation of sentences (metaphorical and literal). We found no evidence for priming effects, and further research is needed to examine the effects that gestures, when produced alone might have on semantic processing. Finally, in Chapter 6 we found that producing content compared to function words, makes metaphor processing right hemisphere specific. This indicated that semantic processing is the key to the lateralisation of metaphor processing. The results validated the use of the mouth asymmetry technique as an indirect measurement of hemispheric involvement during speech production tasks.

The work presented in this thesis explored the effectiveness and reflexiveness of attentional reorienting in response to different types of socially salient gestures. A traditional target detection paradigm was employed across experiments, allowing for the direct comparison of validity effects in response to eye gaze shifts, human pointing gestures, and symbolic arrows. Previous research has tended to compare the effects of eye gaze shifts and symbolic arrows, so this thesis attempted to ‘bridge the gap’ in the social orienting literature. The effects of these different types of socially relevant stimuli were investigated in three distinct populations. Firstly, we examined whether pointing gestures were as effective as eye gaze shifts in reorienting attention to the impaired hemifield of patients with parietal lobe damage. We then carried out the same set of experiments with a patient displaying an acquired ‘theory of mind’ deficit, to establish the relative social nature of pointing gestures in comparison to gaze. Finally, we assessed the effects in typically developing adults who display a high proportion of autistic traits, to draw inferences about how these cues are attended to in autistic spectrum disorders. We found that pointing gestures hold a similar social relevance as gaze shifts, and produce largely the same attentional reorienting effects in normal observers. Effects are discussed in terms of reflexive visual attention, neuropsychological disorders, and social cognition, with inferences regarding social networks in the brain.

This thesis uses fMRI and DTI neuroimaging modalities to investigate relationships between chronic habitual sleep status in waking control subjects and functional and structural changes in higher order intrinsically connected brain networks (ICN). Study one investigates methodologies; compares the use of deterministic and probabilistic tractography in combination with functional imaging to charaterise structural connectivity with respect to functional connectivity in a single ICN. The following chapter examines whether inter-individual differences in habitual sleep patterns are reflected in waking measurements of network functional connectivity (FC) between three ICNs. Subsequent work investigates group differences in structural connectivity with respect to habitual sleep duration and whole brain changes in white matter in relation to subjective habitual sleep quality using tract based spatial statistics (TBSS). The final chapter builds on the work from previous chapters examining a wider range of sleep features and overall network FC. Results presented in this thesis provide evidence of functional and structural brain connectivity changes, which are modulated by chronic habitual sleep status. This may help to elucidate the link between sleep, waking sleep status, cognition and explain individual differences in susceptibility to sleep deprivation, as well as potentially the networks and systems responsible for variations in sleep patterns themselves.

Volume I of this thesis addresses the adjustment of individuals who have sustained acquired brain injuries. To date there has been a only a thin evidence base for the aetiological factors involved in people's emotional reactivity following what is a profound and potentially devastating life changing event. The first paper critically reviews the concept of 'coping' following an acquired brain injury. This draws on two main bodies of literature. First, Kurt Goldstein's 'organismic theory' and, in particular, the catastrophic reaction model is examined from its phenomenological and existential perspective on adjustment to acquired brain injury. Contemporary developments of the catastrophic reaction model have also been considered. Second, applications of Lazarus and Folkman's stress-appraisal and coping theory to adjustment following injury is reviewed for its more empirically based propositions. A comparison and contrast between the two theories is made. The second paper is a full length research report exploring the subjective nature and frequencies of threat appraisals, and related avoidance coping, reported by people with traumatic brain injury. This goes on to explore the relation of these threat-appraisals, and avoidance coping, to adjustment factors of anxiety, depression and quality of life.

This thesis had three main aims, firstly to explore the experience of auditory social and non-social stimuli upon infants brain functioning. Secondly to explore the role of the prefrontal cortex (PFC) in social and non-social visual processing and anxiety. Lastly, to investigate the effect of a mother's depression upon infant behaviour. Chapter 1 explored the literature surrounding social and non-social processing in infancy, the role of the prefrontal cortex (PFC) and the effect of depression upon mother-infant interactions and brain functioning. Chapter 2 described the methods used within this thesis. Chapter 3 investigated the impact of speech and non-speech processing upon infant brain functioning. Social and non-social processing in the PFC in infancy was explored in chapter 4. Chapter 5 looked at the impact of a mothers anxiety upon infant frontal asymmetries. Meta-analyses were conducted in Chapter 6 to investigate differences in behaviour in the still-face paradigm between infants of depressed and infants of non-depressed mothers. Chapter 7 summarised the results of the thesis in terms of findings, implications of the results, directions for future work and limitations of the current thesis.

The work presented in the present thesis investigated the neural, behavioural and genetic markers that may be associated with the manifestation of behavioural problems during the early years of life. Across four different empirical studies, and by incorporating, behavioural, neurophysiological and genetic investigations, it was demonstrated that: (1) there are neurophysiological signatures that may be associated with the manifestation of behavioural problems early in life; (2) common genetic variations that determine serotonin variability are strongly associated with affectivity-related patterns of frontal brain activation; and that (3) normal genetic variations that modulate serotonin availability and neuroplasticity are each associated with affectivity-related patterns of visual scanning behaviours in response to faces and aversive scenes. Taken together, the results illustrate the existence of robust neural, genetic and behavioural markers that may be associated with the manifestation of behavioural problems in early childhood and prompt further investigation of the area by generating novel hypotheses. Together, the empirical findings of the thesis provide a first stage contribution to the complex mechanisms that may yield risk and resilience for behavioural problems during the early years of life by generating a more comprehensive insight on the field of affectivity.