Functional and neural mechanisms of human fear conditioning: studies in healthy and brain-damaged individuals

Fear conditioning represents the learning process by which a stimulus, after repeated pairing with an aversive event, comes to evoke fear and becomes intrinsically aversive. This learning is essential to organisms throughout the animal kingdom and represents one the most successful laboratory paradigm to reveal the psychological processes that govern the expression of emotional memory and explore its neurobiological underpinnings. Although a large amount of research has been conducted on the behavioural or neural correlates of fear conditioning, some key questions remain unanswered. Accordingly, this thesis aims to respond to some unsolved theoretic and methodological issues, thus furthering our understanding of the neurofunctional basis of human fear conditioning both in healthy and brain-damaged individuals. Specifically, in this thesis, behavioural, psychophysiological, lesion and non-invasive brain stimulation studies were reported. Study 1 examined the influence of normal aging on context-dependent recall of extinction of fear conditioned stimulus. Study 2 aimed to determine the causal role of the ventromedial PFC (vmPFC) in the acquisition of fear conditioning by systematically test the effect of bilateral vmPFC brain-lesion. Study 3 aimed to interfere with the reconsolidation process of fear memory by the means of non-invasive brain stimulation (i.e. TMS) disrupting PFC neural activity. Finally, Study 4 aimed to investigate whether the parasympathetic – vagal – modulation of heart rate might reflect the anticipation of fearful, as compared to neutral, events during classical fear conditioning paradigm. Evidence reported in this PhD thesis might therefore provide key insights and deeper understanding of critical issues concerning the neurofunctional mechanisms underlying the acquisition, the extinction and the reconsolidation of fear memories in humans

Development of A Versatile Multichannel CWNIRS Instrument for Optical Brain-Computer Interface Applications

This thesis describes the design, development, and implementation of a versatile multichannel continuous-wave near-infrared spectroscopy (CWNIRS) instrument for brain-computer interface (BCI) applications. Specifically, it was of interest to assess what gains could be achieved by using a multichannel device compared to the single channel device implemented by Coyle in 2004. Moreover, the multichannel approach allows for the assessment of localisation of functional tasks in the cerebral cortex, and can identify lateralisation of haemodynamic responses to motor events. The approach taken to extend single channel to multichannel was based on a software-controlled interface. This interface allowed flexibility in the control of individual optodes including their synchronisation and modulation (AM, TDM, CDMA). Furthermore, an LED driver was developed for custom-made triple-wavelength LEDs. The system was commissioned using a series of experiments to verify the performance of individual components in the system. The system was then used to carry out a set of functional studies including motor imagery and cognitive tasks. The experimental protocols based on motor imagery and overt motor tasks were verified by comparison with fMRI. The multichannel approach identified stroke rehabilitation as a new application area for optical BCI. In addition, concentration changes in deoxyhaemoglobin were identified as being a more localised indicator of functional activity, which is important for effective BCI design. An assessment was made on the effect of the duration of the stimulus period on the haemodynamic signals. This demonstrated the possible benefits of using a shorter stimulus period to reduce the adverse affects of low blood pressure oscillations. i