The neurological manifestations of Zika and chikungunya viruses

During 2015-16 Brazil experienced the largest epidemic of Zika virus ever reported. This arthropod-borne virus (arbovirus) has been linked to Guillain-Barré syndrome (a disorder of the peripheral nervous system) in adults but other neurological associations are uncertain. I designed and performed a retrospective clinical study in Rio de Janeiro, Brazil, investigating patients presenting with an acute neurological disorder and suspected recent Zika virus infection. I found a wider spectrum of neurological disease associated with Zika than reported previously, including that of the central nervous system. This has implications for clinical diagnostic pathways and public health measures. The study also highlighted some of the diagnostic challenges associated with arbovirus-associated neurological disease, and showed an unexpected role of chikungunya virus, another arbovirus that has spread rapidly through the Americas since 2013 and continues to affect millions in explosive outbreaks throughout the tropics. This led me to perform a systematic review of neurological disease associated with chikungunya virus; I summarise all described neurological manifestations, highlighting the wide spectrum of disease in adults and children, its importance in vertical transmission in neonates, comparison with Zika and dengue viruses and recent insights into disease mechanisms. The review will be a useful reference tool for clinicians, researchers and public health officials involved in managing complications of this emerging pathogen. Looking forward, this thesis also discusses the important unanswered questions relating to arbovirus-associated neurological disease, including establishing causality, defining the burden of disease and considerations for vaccines, and how we might approach these challenges

An investigation of Laughter and Crying: from behavioural, physiological and neuroimaging studies

This PhD investigates the perception of laughter and crying, two non verbal expressions of emotion, and how this perception is affected by the authenticity of the expressed emotions. Three separate approaches were used to address the perception of these stimuli by healthy participants: behavioural rating tasks, physiological responses recordings, and functional magnetic resonance imaging (fMRI) techniques. A series of behavioural ratings established that naïve listeners can reliably differentiate involuntary laughter from voluntary laughter, however, their performance was poorer when discriminating between involuntary crying and voluntary crying. In a larger set of behavioural ratings collected at the Science Museum (n=1723, age range = 3-76 years old), the ratings accuracy of voluntary and involuntary emotional vocalizations were both found to improve over age, however, the developmental trajectories of the voluntary expressions were shown to have a steeper slope throughout early adulthood than involuntary expressions. This difference may reflect a developmental learning process of perceiving voluntary emotional expressions through social interactions. The results of behavioural and developmental experiments consistently show that the involuntary crying was perceived as moe similar to voluntary crying than voluntary and involuntary laughter However the physiological responses (pupil size) shows a different pattern: listeners’ pupils were significantly more dilated for involuntary vocalizations than for voluntary ones, regardless of emotions. This discrepancy between physiological responses and behavioural ratings on crying suggests that social learning processes influence the perceivers’ judgments of involuntary crying, other than pure perceptual processes. In the fMRI study, we found that perceiving laughter and crying requires activation of similar areas in an emotional motor task as well as in a theory-of-mind task, suggesting that a shared interactive neural network of perceiving and interpreting emotions is involved. However, the cortical areas involved in differentiating voluntary and involuntary vocalizations are partly distinct for laughter and for crying, implying different neural networks may be responsible for the authenticity differentiation of different emotions. In summary, this thesis demonstrates the existence of emotion-specific differences in perception of non-verbal emotional vocalizations and these differences may be due to developmental factors. Moreover, multiple neural networks were shown to play important roles in perceiving and differentiating positive and negative emotions