A remarkable feature of the human visual system is that it is possible to extrapolate a large amount of information about the three-dimensional structure of the environment simply from the pattern of light that falls on the retinae. This information is derived from a number of different cues to depth. The mechanisms by which these are encoded in the brain, combined into an overall percept, and subsequently interpreted are reasonably well understood. However, individuals who participate in studies of depth perception tend to have acute sensitivity to certain depth cues, meaning that the consequences of individual differences in depth perception have been largely ignored. In this thesis I investigate how individual differences in the ability to utilise a single cue, binocular disparity, affects overall perception of depth and then go on to explore the wider function significance of such a deficit. I also examine whether an underlying deficit in stereopsis may account for some of the perceptual differences observed in autism spectrum disorder (ASD). The first set of experiments explored the consequences of individual differences in stereopsis upon perception. The initial study of this thesis used a shape constancy paradigm to identify how individual cues to depth are utilised and combined in typical children and adults. I report that while children are more sensitive to certain depth cues compared to adults, they still show some degree of cue combination (though only for higher- level information). In addition, I observed that an inability to use binocular information appears to cause re-weighting to occur in favour of monocular cues, regardless of age. In the second study, I used the same paradigm to explore depth cue sensitivity and combination in typically-developing (TD) and ASD teenagers. The results from this experiment indicated that contextual and binocular information interact when creating an overall percept of depth. A main effect of ASD diagnosis was found, with this group reporting perception that was less biased and closer to the raw sensory input. Although participants with ASD exhibited poorer stereoacuity than their TD counterparts, this did not explain the differences between the groups. I propose this indicates that perceptual differences in autism likely stem from underlying neurological differences specific to the disorder as opposed to a more general stereopsis deficit. The third study assessed the combination of ordinal and metric depth cues in TD and ASD adults. Cue integration did not depend on sensitivity to disparity or autism diagnosis. Unlike previous research, and inconsistent with perceptual theories of autism, I found that individuals with ASD automatically integrated depth cues, even when it was not advantageous to do so. Additionally, I found that the processing of uncrossed disparities was particularly difficult for those with an ASD. The second part of the thesis aimed to characterise the functional significance of impaired stereopsis. For the fourth study, I wanted to establish whether the functional significance of stereopsis followed a developmental trajectory. I was also interested if the motor deficits observed in those with poor stereopsis were limited to hand-eye coordination tasks. Using three tasks derived from a standardised test of motor proficiency – catching a ball, balancing on one leg, and bead-threading – I measured the effect of binocular vision and stereoacuity on motor ability. Stereoacuity affected performance across a range of tasks involving the use of fine and gross motor skill, and – importantly – the effect of stereopsis did not change with age. In the final study, I enquired as to the further-reaching consequences of poor stereopsis. Using a quantitative survey I aimed to establish how stereopsis, motor skills, and social skills related to one another. While motor ability mediated the relationship between stereopsis and social skill, stereopsis also directly contributed to social skill, causing me to suggest that the functional significance of stereopsis is not limited to motor ability. It is concluded that while individual differences in stereoacuity may affect the amount of depth experienced, they do not affect the ability to combine different cues to depth. While those with ASD experience differences in perception, these cannot be attributed to the increased prevalence of stereopsis impairment. It does, however, seem that individual differences in stereoacuity impact upon the development of motor proficiency and social skill, which are typically compromised in those with ASD.

Alzheimer’s disease (AD) is a progressive neurodegenerative disease defined by severe memory loss and the accumulation of amyloid plaques and neurofibrillary tangles in the brain. The experiments presented in this thesis examined cognitive performance in a well-­‐characterised mouse model of AD, the APPswe/PS1dE9 (TG) mouse, at 4-­‐5 months old prior to extensive amyloid plaque deposition. The experiments employed were associative learning tasks, which are not often used to measure cognitive performance in classical neuroscience research into neurodegenerative disease. Chapter 1 looked at appetitive Pavlovian cue and context conditioning and extinction, and found some evidence of impaired contextual discrimination during conditioning. Cue conditioning and extinction was found to be intact in the TG mouse model. Chapter 2 looked at appetitive Pavlovian delay and trace conditioning before examining the ability to time the arrival of the unconditioned stimulus (US). No genotype differences were found during delay or trace conditioning; however, TG mice were impaired (lost precision) in their ability to time the arrival of the US during test trials. Chapter 3 examined recognition memory performance, via the spontaneous novel object recognition (sNOR), relative recency (RR) and context priming (CP) tasks, interpreting the results in terms of Wagner’s SOP model of memory. No genotype differences were found in the sNOR or RR tasks, supporting intact stimulus-­‐generated priming; however, evidence from Bonardi et al. (2016) and non-­‐significant trends in the CP task supported impaired retrieval-generated priming. Chapter 4 looked at the levels of neuro-­‐inflammation (microglia) in the cortex, hippocampus and striatum to assess the possible early contribution of inflammation on the development of AD. This chapter reported greater levels of microglia in the hippocampus and striatum of TG mice compared to wild types. Greater microglia clusters were also seen in the cortex and hippocampus of TG mice compared to wild types. The results from this thesis show evidence of impaired cognitive performance, prior to extensive plaque deposition, in associative learning tasks that are not routinely employed in neuroscience research. Further work is required in these learning tasks to establish whether they could be effectively used to diagnose AD at an early stage.

The British population are increasingly using mobile devices (e.g. smartphones, tablets) to gamble. The empirical work in this thesis looks at how the interaction of gambling’s schedule of reinforcement and mobile device behaviours accelerate the acquisition of learned maladaptive behaviours. The first four chapters report psychometric modelling of gambling prevalence data to understand problem gambling further and identify key indicators relevant to associative processes in gambling behaviour. Chapter 2 reports a taxometric analysis of problem gambling assessment data to test whether these screens measure a dimensional or latent class model, finding stronger support for the latter. However, this only identified a small taxon consisting of around 5% of gamblers endorsing more than one problem gambling symptom. Chapter 3 reports the use of latent class analysis to examine distinct subtypes of responding to different screens, findings a common three-class model that showed signs of a mixed latent structure: the same taxon as Chapter 2 was observed, but the three classes showed little overlap in symptom count. Chapter 4 reports further work modelling the sociodemographic characteristics of these different subgroups. Together the data from these chapters were used help to identify indicators of those most likely to a) be most susceptible to gambling harm and b) common to all problem gamblers. In Chapter 5 a Monte Carlo analysis was conducted to understand the efficacy of taxometric procedures on binary variables, before replicating the taxometric analysis reported in Chapter 2 using dichotomous variables and extending the work to the South Oaks Gambling Screen. The indicators derived from these chapters were then used in laboratory and field studies to study mobile gambling behaviour. The laboratory study in Chapter 6 manipulated two behavioural processes, trial spacing and partial reinforcement, that are relevant to mobile gambling behaviour, showing how a mobile-like schedule is related to increased perseverance and loss-chasing. The same paradigm was used to deliver an experiment on participants’ mobile phones in a field environment in Chapter 7. They further demonstrate that a mobile style schedule of reinforcement is associated with considerable persistence in the face of mounting losses, as participants continued to persevere in the face of losses despite a free choice to cease playing. Finally in the discussion I apply the key themes of the thesis to in-play betting, a form of play that has been heavily promoted alongside mobile gambling, and to an understanding of behavioural addictions.

Behaviour is considered to be compulsive when it is performed automatically regardless of whether it results in deleterious consequences. Although most prominently associated with obsessive-compulsive disorder, compulsivity is also present in a host of other psychiatric disorders and likely represents a trans-diagnostic trait with shared dysfunctional circuitry (Gillan et al., 2016a). Despite this, no single treatment shows anticompulsive efficacy across disorders, and disorder-specific treatments are not particularly efficacious either (Grant et al., 2016). This may be because different circuitry parameters are disrupted in different disorders, but result in similar behavioural outcomes, therefore a treatment targeting one parameter will not alleviate dysfunction caused by alterations in a different parameter. This thesis investigates the circuitry of compulsivity by administering drugs that differentially target these parameters to rats undergoing associative learning tasks shown to be dependent on this neural circuitry. We found that the acute administration of phencyclidine – a drug which models the psychotic state (by blocking NMDA receptors; Rafter et al., 2016) – promoted compulsive approach towards a formerly rewarded stimulus but not compulsive avoidance to a formerly unrewarded stimulus. We also found that administration of this drug to neonatal pups in combination with adolescent social isolation led to the opposite effect, that is, reduced compulsive approach towards a formerly rewarded stimulus once it became unrewarded. Administration of a serotonin 5-HT2C receptor antagonist (a putative anti-compulsive agent) had no effect on choices but accelerated the speed of responding. Meanwhile intra-orbitofrontal cortex infusion of the dopamine neurotoxin 6-hydroxydopamine or the serotonin neurotoxin 5,7-dihydroxytryptamine failed to reliably induce neurotransmitter depletion, and subsequently had no effect on any behavioural measure. These findings suggest that targeting glutamate systems upstream of dopamine and serotonin systems may result in better treatment outcomes for compulsivity driven by formerly reinforced associations, e.g. in delusions, behavioural addictions, and drug addiction.

The work presented in this thesis aims to increase clinical capacity for magnetoencephalography (MEG) by developing an understanding of how, in healthy participants, individual differences in brain structure, personality, and demographics influence measurements of neural oscillatory responses and functional connectivity. To this end, a large cohort of normative data was acquired using MEG with additional data acquisition using high-field MRI and supplementary individual difference data collected via a psychometric battery and screening questionnaire. MEG data were analysed to elucidate both primary sensory responses to stimulation and functional connectivity within task and task-free acquisitions. Chapters two and three introduce the physiological origins of the MEG signal and the instrumentation required to record it. Chapter four describes data acquisition and preprocessing, from the methods used in the recruitment of participants to the scanning parameters employed for our MEG and MRI acquisitions. Chapters five to seven present three empirical studies. The first investigates the relationship between MEG derived measurements of functional connectivity and cortical myeloarchitecture. We demonstrate that covariation of cortical myelin is significantly predicted by MEG-derived measurements of functional connectivity both within individual frequency bands and by their linear and non-linear combination. Chapter six presents an exploratory analysis into the impact of aging and sex-differences on MEG derived measurements of sensorimotor responses and whole-brain functional connectivity. We find trends indicating increased oscillatory responses with age. Further, we find female volunteers to exhibit greater induced responses than males. Analysis of whole-brain functional connectivity revealed a near-global increase in connectivity in female participants as compared to males. The final empirical chapter assesses the shared neuronal representations between patients diagnosed with schizophrenia and healthy individuals scoring highly on a personality questionnaire measuring schizotypy. We found highly schizotypal individuals to exhibit attenuated sensorimotor responses akin to those previously observed in schizophrenia. Patients displayed reduced functional connectivity within an occipital network, identified in task and task free data. We found this aberrant network connectivity to also be present in healthy subjects scoring highly on a questionnaire assessing schizotypy. The thesis, in sum, presents work demonstrating the significant modulatory effects of individual differences ranging from sex differences to schizotypy. This work highlights the need for consideration of participant demographics and individual differences in both clinical and basic science studies. Further, the thesis presents a newly identified relationship between MEG-derived measurements of functional connectivity and cortical myeloarchitecture. Future work assessing the role of other sources of individual difference in modulating MEG measurements is required. Moreover, the framework for assessing the relationship between functional connectivity and cortical myeloarchitecture is well suited to application in clinical populations where this relationship is hypothesised to break down.

Mirror Neuron Theory’ is a brain process model which is based on a direct-matching model, that encodes the motor features, mental states, and the goal of observed actions onto the observer’s own motor system. MNs abnormalities and Autism Spectrum Disorder (ASD) have been empirically associated as they are alleged to represent the neural basis of deficits in social competence and imitative learning in ASD. Neurophysiological evidences nonetheless appear to validate the enhanced activity of MNs when utilizing a familiar agent (person) with ASD. Similar evidence suggests influence of the individual’s own culture, compared to others, on modulating the mirror neuron; however, this hypothesis has never been tested on an ASD group. Other behavioural data show that the use of typically developing peers as models in a social intervention setting with ASD was advocated for its significant outcomes, but the impact of age similarity on modulating MNs in ASD children was not directly investigated. In these four EEG experiments, we investigate the effect of observing a familiar person, a person from a similar age group and someone from a similar ethnic group, performing actions, on the capacity of understanding and imitation of others’ actions. Additionally, we consider if observing a prime, familiar person, similar ethnic-person, or similarly-aged person would facilitate action understanding and imitation if this action were then seen performed later by an unfamiliar person, dissimilar-ethnic person, or dissimilarly-aged person, in young children with ASD, compared to a control group. Participants watched people performing gestures, crossing familiarity of the person (parent/stranger), similarity of the person’s age (child/adult), or of the person’s ethnicity (Saudi/European), with familiarity of the action (meaningful/meaningless). MNs activity was indexed by alpha (8-12 Hz), low beta (13-20 Hz), and theta (5.5-7.5Hz) desynchronization over the sensorimotor cortex. Behavioural performance was recorded through the imitation stage.

Traditionally, early visual cortex (V1-3) was thought of as merely a relay centre for feedforward retinal input, providing entry to the cortical visual processing steam. However, in addition to feedforward retinal input, V1 receives a large amount of intracortical information through feedback and lateral connections. Human visual perception is constructed from combining feedforward inputs with these feedback and lateral contributions. Feedback connections allow the visual cortical response to feedforward information to be affected by expectation, knowledge, and context; even at the level of early visual cortex. In Chapter 1 we discuss the feedforward and feedback visual processing streams. We consider historical philosophical and scientific propositions about constructive vision. We introduce modern theories of constructive vision, which suggest that vision is an active process that aims to infer or predict the cause of sensory inputs. We discuss how V1 therefore represents not only retinal input but also high-level effects related to constructive predictive perception. Visual illusions are a ‘side effect’ of constructive and inferential visual perception. For the vast majority of stimulus inputs, integration with context and knowledge facilitates clearer, more veridical perception. In illusion these constructive mechanisms produce incorrect percepts. Illusory effects can be observed in early visual cortex, even when there is no change in the feedforward visual input. We suggest that illusions therefore provide us with a tool to probe feedforward and feedback integration, as they exploit the difference between retinal stimulation and resulting perception. Thus, illusions allow us to see the changes in activation and perception induced only by feedback without changes in feedforward input. We discuss a few specific examples of illusion generation through feedback and the accompanying effects on V1 processing. In Schizophrenia, the integration of feedback and feedforward information is thought to be dysfunctional, with unbalanced contributions of the two sources. This is evidenced by disrupted contextual binding in visual perception and corresponding deficits in contextual illusion perception. We propose that illusions can provide a window into constructive and inferential visual perception in Schizophrenia. Use of illusion paradigms could help elucidate the deficits existing within feedback and feedforward integration. If we can establish clear effects of illusory feedback to V1 in a typical population, we can apply this knowledge to clinical subjects to observe the differences in feedback and feedforward information. Chapter 2 describes a behavioural study of the rubber hand illusion. We probe how multimodal illusory experience arises under varying reliabilities of visuotactile feedforward input. We recorded Likert ratings of illusion experience from subjects, after their hidden hand was stimulated either synchronously or asynchronously with a visible rubber hand (200, 300, 400, or 600ms visuotactile asynchronicity). We used two groups, assessed by a questionnaire measuring a subject’s risk of developing Schizophrenia - moderate/high scorers and a control group of zero-scorers. We therefore consider how schizotypal symptoms contribute to rubber hand illusory experience and interact with visuotactile reliability. Our results reveal that the impact of feedforward information on higher level illusory body schema is modulated by its reliability. Less reliable feedforward inputs (increasing asynchronicity) reduce illusion perception. Our data suggests that some illusions may not be affected on a spectrum of schizotypal traits but only in the full schizophrenic disorder, as we found no effect of group on illusion perception. In Chapter 3 we present an fMRI investigation of the rubber hand illusion in typical participants. Cortical feedback allows information about other modalities and about cognitive states to be represented at the level of V1. Using a multimodal illusion, we investigated whether crossmodal and illusory states could be represented in early visual cortex in the absence of differential visual input. We found increased BOLD activity in motion area V5 and global V1 when the feedforward tactile information and the illusory outcome were incoherent (for example when the subject was experiencing the illusion during asynchronous stimulation). This is suggestive of increased predictive error, supporting predictive coding models of cognitive function. Additionally, we reveal that early visual cortex contains pattern representations specific to the illusory state, irrespective of tactile stimulation and under identical feedforward visual input. In Chapter 4 we use the motion-induced blindness illusion to demonstrate that feedback modulates stimulus representations in V1 during illusory disappearance. We recorded fMRI data from subjects viewing a 2D cross array rotating around a central axis, passing over an oriented Gabor patch target (45°/ 135°). We attempted to decode the target orientation from V1 when the target was either visible or invisible to subjects. Target information could be decoded during target visibility but not during motion-induced blindness. This demonstrates that the target representation in V1 is distorted or destroyed when the target is perceptually invisible. This illusion therefore has effects not only at higher cortical levels, as previously shown, but also in early sensory areas. The representation of the stimulus in V1 is related to perceptual awareness. Importantly, Chapter 4 demonstrated that intracortical processing can disturb constant feedforward information and overwrite feedforward representations. We suggest that the distortion observed occurs through feedback from V5 about the cross array in motion, overwriting feedforward orientation information. The flashed face distortion illusion is a relatively newly discovered illusion in which quickly presented faces become monstrously distorted. The neural underpinnings of the illusion remain unclear; however it has been hypothesised to be a face-specific effect. In Chapter 5 we challenged this account by exploiting two hallmarks of face-specific processing - the other-race effect and left visual field superiority. In two experiments, two ethnic groups of subjects viewed faces presented bilaterally in the visual periphery. We varied the race of the faces presented (same or different than subject), the visual field that the faces were presented in, and the duration of successive presentations (250, 500, 750 or 1000ms per face before replacement). We found that perceived distortion was not affected by stimulus race, visual field, or duration of successive presentations (measured by forced choice in experiment 1 and Likert scale in experiment 2). We therefore provide convincing evidence that FFD is not face-specific and instead suggest that it is an object-general effect created by comparisons between successive stimuli. These comparisons are underlined by a fed back higher level model which dictates that objects cannot immediately replace one another in the same retinotopic space without movement. In Chapter 6 we unify these findings. We discuss how our data show fed back effects on perception to produce visual illusion; effects which cannot be explained through purely feedforward activity processing. We deliberate how lateral connections and attention effects may contribute to our results. We describe known neural mechanisms which allow for the integration of feedback and feedforward information. We discuss how this integration allows V1 to represent the content of visual awareness, including during some of the illusions presented in this thesis. We suggest that a unifying theory of brain computation, Predictive Coding, may explain why feedback exerts top-down effects on feedforward processing. / Lastly we discuss how our findings, and others that demonstrate feedback and prediction effects, could help develop the study and understanding of schizophrenia, including our understanding of the underlying neurological pathologies.

Depression is a heterogeneous condition characterised by low mood and a lack of motivation and enjoyment of regular activities. The response rate to current treatments coupled with adverse side effect profiles requires new avenues of investigation into the development of novel therapeutics to treat the condition. Rearing rats in isolation from weaning causes behavioural, cognitive and neurochemical changes which persist into adulthood; some of the symptoms produced have relevance to depression. In the current thesis, rats raised in social isolation from weaning consistently developed a hyperactive phenotype compared to group-housed littermates when placed into a novel environment. They also developed deficits in associative learning assessed by the conditioned fear response task. They displayed some anxiety-like behaviours in the open field and novelty-suppressed feeding task and deficits in visual memory in the novel object discrimination task, although these were not reliable across cohorts. There was a reduction in levels of hippocampal neurogenesis in a number of cohorts and for the first time it was demonstrated that rats reared in isolation exhibited changes in gut bacteria, opening up a potential new avenue of investigation into potential treatments. The efficacy of novel versus established antidepressant treatments was evaluated in isolated rats. Chronic fluoxetine had some anxiolytic effects in the open field, attenuated isolation induced changes in associative memory and increased neurogenesis but also had inconsistent effects on activity. Treatment with acute ketamine increased freezing time in the conditioned freezing response task, indicating an improvement in associative memory. The final study examined, for the first time, the effect of treatment with the JNK-1 inhibitor DJNKI in isolation reared rats. DJNKI had some positive cognitive effects in both the novel object discrimination task and the conditioned freezing response task. In conclusion, the isolation rearing model induced varying levels of depression-like deficits, which were responsive to some treatments. The model is a useful tool for investigating the symptoms of depression and evaluating novel treatment options.

Many cognitive theories point to key factors underlying the development and maintenance of eating disorders, such as: unhealthy food-related cognitive biases, negative body attitude, and perfectionism. The present research utilised eye-tracking during reading as a novel implicit measure of how these factors may relate to eating disorder tendencies in females and males, followed by the development of two new male body dissatisfaction scales. In four experiments female and male (N = 360) participants’ eye movements were monitored while they read third- and second-person perspective texts in which the characters’ emotional responses to food-, body image-, and perfectionism-related scenarios were described. Overall, results from these studies suggest that on-line processing of characters’ emotional responses to perfectionism-, and to a lesser extent, body image-related information is predictive of participants’ disordered eating tendencies, thus supporting theories in which these two underlying factors are key to developing and maintaining eating disorders. Interestingly, the on-line processing of characters’ emotional responses to food-related scenarios did not predict eating disorder tendencies, as participants read food-related scenarios similarly, regardless of having a higher eating disorder level. In Chapter V, two new male body dissatisfaction scales: The Male Body Scale (MBS; consisting of emaciated to obese figures) and the Male Fit Body Scale (MFBS; consisting of emaciated to muscular figures) were developed, tested, and re-tested. Male participants (N = 103) rated which of nine body figures on each scale most represented their current- and ideal- body figure, followed by the Drive for Muscularity Scale (DMS), the Eating Disorder Examination Questionnaire (EDE-Q 6.0), and the calculation of their actual body mass index (BMI), fat-, and muscularity-percentage. This was followed by a re-test and manipulation check two to six weeks later. Results found both new scales were consistently valid and reliable between test and re-test, and importantly, each scale was sensitive to different types of body dissatisfaction within males. Specifically, the MBS revealed that males’ desire for the thin-ideal significantly corresponded to higher eating disorder tendencies as shown by EDE-Q 6.0 scores, whilst the MFBS revealed much higher body dissatisfaction toward the larger, muscularity-ideal, predicting higher drive for muscularity as shown by DMS scores. Altogether, the present research findings provide novel insights into cognitive processes underlying disordered eating behaviour, demonstrate the utility of eye-tracking as a more natural implicit measure, provide tools to assess and predict eating disorder tendencies in females and males, and inform eating disorder related research.

Schizophrenia is a complex mental disorder characterised by various symptoms which fall into three categories of positive, negative and cognitive. In particular, negative symptoms are poorly treated by current medications although several adjunctive therapies are under investigation including Glycine Transporter (GlyT1) inhibitors and neuropeptides such as oxytocin. Despite accumulating preclinical and clinical evidence that such compounds can influence social behaviour and improve negative symptoms in patients, there is little information as to the precise mechanisms by which they work. Therefore, the aims of this thesis were to ultimately determine some of the key regions and potential signalling pathways activated following administration of these compounds in Lister-hooded rats. Firstly, a functional map of GlyT1 inhibitor RO4993850, an analogue to Bitopertin, identified the selective activation of neurons within the rostral and caudal prefrontal cortex (PFC), suggesting potential NMDA receptor activation in brain areas involved in motivation and goal-directed behaviour. This was further assessed in a novel ‘dual-hit’ neonatal-PCP isolation-rearing rodent model for schizophrenia which was shown herein to induce locomotor hyperactivity and social deficits including reduced social interaction (an index for negative symptoms) and increased communication (as assessed by ultrasonic vocalisations (USVs)). Interestingly neonatal-PCP isolation-reared rats emitted more pro-social 50 kHz USVs which were also longer in duration and had a greater change in call bandwidth compared to controls. Neonatal-PCP isolation-rearing was also shown to selectively decrease parvalbumin expression (a calcium binding protein present in GABAergic interneurons) in the hippocampus but not in the rostral PFC sub-regions assessed, producing similar changes to other rodent models. Microdialysis studies however revealed no change to basal PFC and striatal dopamine levels in these rats. Chronic treatment with the GlyT1 inhibitor RO4993850 improved social deficits in the social interaction test and altered both USV emissions and call characteristics but showed no effect on locomotor hyperactivity, parvalbumin expression in either the PFC or hippocampus, nor dopamine overflow in the PFC or striatum. Finally, an established dose of the neuropeptide oxytocin which did not influence core body temperature, was shown to attenuate PCP-induced hyperactivity, increase pro-social behaviour and selectively enhance dopamine release in the nucleus accumbens (NAc) in group-housed Lister-hooded rats. Thereby providing supporting evidence for regionally-specific oxytocin-dopaminergic interactions within the mesocorticolimbic circuits responsible for regulating associative and rewarding behaviour. There are therefore several potential mechanisms by which both GlyT1 inhibitors and oxytocin can influence social behaviour, most likely via activation of key brain loci involved in motivation. Although further work is required, results herein indicate the potential of GlyT1 inhibitors and oxytocin as adjunctive therapies to treat predominant negative symptoms in schizophrenia.