Ecological drivers of a vector borne pathogen: distribution and abundance of Borrelia burgdorferi sensu lato and its vector Ixodes ricinus in Scotland

Vector-borne disease emergence in recent decades has been associated with different environmental drivers including changes in habitat, hosts and climate. Lyme borreliosis is among the most important vector-borne diseases in the Northern hemisphere and is an emerging disease in Scotland. Transmitted by Ixodid tick vectors between large numbers of wild vertebrate host species, Lyme borreliosis is caused by bacteria from the Borrelia burgdorferi sensu lato species group. Ecological studies can inform how environmental factors such as host abundance and community composition, habitat and landscape heterogeneity contribute to spatial and temporal variation in risk from B. burgdorferi s.l. In this thesis a range of approaches were used to investigate the effects of vertebrate host communities and individual host species as drivers of B. burgdorferi s.l. dynamics and its tick vector Ixodes ricinus. Host species differ in reservoir competence for B. burgdorferi s.l. and as hosts for ticks. Deer are incompetent transmission hosts for B. burgdorferi s.l. but are significant hosts of all life-stages of I. ricinus. Rodents and birds are important transmission hosts of B. burgdorferi s.l. and common hosts of immature life-stages of I. ricinus. In this thesis, surveys of woodland sites revealed variable effects of deer density on B. burgdorferi prevalence, from no effect (Chapter 2) to a possible ‘dilution’ effect resulting in lower prevalence at higher deer densities (Chapter 3). An invasive species in Scotland, the grey squirrel (Sciurus carolinensis), was found to host diverse genotypes of B. burgdorferi s.l. and may act as a spill-over host for strains maintained by native host species (Chapter 4). Habitat fragmentation may alter the dynamics of B. burgdorferi s.l. via effects on the host community and host movements. In this thesis, there was lack of persistence of the rodent associated genospecies of B. burgdorferi s.l. within a naturally fragmented landscape (Chapter 3). Rodent host biology, particularly population cycles and dispersal ability are likely to affect pathogen persistence and recolonization in fragmented habitats. Heterogeneity in disease dynamics can occur spatially and temporally due to differences in the host community, habitat and climatic factors. Higher numbers of I. ricinus nymphs, and a higher probability of detecting a nymph infected with B. burgdorferi s.l., were found in areas with warmer climates estimated by growing degree days (Chapter 2). The ground vegetation type associated with the highest number of I. ricinus nymphs varied between studies in this thesis (Chapter 2 & 3) and does not appear to be a reliable predictor across large areas. B. burgdorferi s.l. prevalence and genospecies composition was highly variable for the same sites sampled in subsequent years (Chapter 2). This suggests that dynamic variables such as reservoir host densities and deer should be measured as well as more static habitat and climatic factors to understand the drivers of B. burgdorferi s.l. infection in ticks. Heterogeneity in parasite loads amongst hosts is a common finding which has implications for disease ecology and management. Using a 17-year data set for tick infestations in a wild bird community in Scotland, different effects of age and sex on tick burdens were found among four species of passerine bird (Chapter 5). There were also different rates of decline in tick burdens among bird species in response to a long term decrease in questing tick pressure over the study. Species specific patterns may be driven by differences in behaviour and immunity and highlight the importance of comparative approaches. Combining whole genome sequencing (WGS) and population genetics approaches offers a novel approach to identify ecological drivers of pathogen populations. An initial analysis of WGS from B. burgdorferi s.s. isolates sampled 16 years apart suggests that there is a signal of measurable evolution (Chapter 6). This suggests demographic analyses may be applied to understand ecological and evolutionary processes of these bacteria. This work shows how host communities, habitat and climatic factors can affect the local transmission dynamics of B. burgdorferi s.l. and the potential risk of infection to humans. Spatial and temporal heterogeneity in pathogen dynamics poses challenges for the prediction of risk. New tools such as WGS of the pathogen (Chapter 6) and blood meal analysis techniques will add power to future studies on the ecology and evolution of B. burgdorferi s.l.

Neural representations of social and non-social uncertainty in human decision making

The social landscape is filled with an intricate web of species-specific desired objects and course of actions. Humans are highly social animals and, as they navigate this landscape, they need to produce adapted decision-making behaviour. Traditionally social and non-social neural mechanisms affecting choice have been investigated using different approaches. Recently, in an effort to unite these findings, two main theories have been proposed to explain how the brain might encode social and non-social motivational decision-making: the extended common currency and the social valuation specific schema (Ruff & Fehr 2014). One way to test these theories is to directly compare neural activity related to social and non-social decision outcomes within the same experimental setting. Here we address this issue by focusing on the neural substrates of social and non-social forms of uncertainty. Using functional magnetic resonance imaging (fMRI) we directly compared the neural representations of reward and risk prediction and errors (RePE and RiPE) in social and non- social situations using gambling games. We used a trust betting game to vary uncertainty along a social dimension (trustworthiness), and a card game (Preuschoff et al. 2006) to vary uncertainty along a non-social dimension (pure risk). The trust game was designed to maintain the same structure of the card game. In a first study, we exposed a divide between subcortical and cortical regions when comparing the way these regions process social and non-social forms of uncertainty during outcome anticipation. Activity in subcortical regions reflected social and non-social RePE, while activity in cortical regions correlated with social RePE and non-social RiPE. The second study focused on outcome delivery and integrated the concept of RiPE in non-social settings with that of fairness and monetary utility maximisation in social settings. In particular these results corroborate recent models of anterior insula function (Singer et al. 2009; Seth 2013), and expose a possible neural mechanism that weights fairness and uncertainty but not monetary utility. The third study focused on functionally defined regions of the early visual cortex (V1) showing how activity in these areas, traditionally considered only visual, might reflect motivational prediction errors in addition to known perceptual prediction mechanisms (den Ouden et al 2012). On the whole, while our results do not support unilaterally one or the other theory modeling the underlying neural dynamics of social and non-social forms of decision making, they provide a working framework where both general mechanisms might coexist.