Models of human anxiety an investigation into the psychophysiological, neuropharmacological and behavioural facets of anxious experience

Human anxiety consists of a complex pattern of cognitive, affective, physiological and behavioural changes in response to threat, loss, or perceived negative outcome. While anxiety reactions are frequently adaptive responses, they can cross into the spectrum of clinical disorders if they are situationally inappropriate or excessive in duration or degree. Neuro-scientific research has demonstrated that human anxiety is mediated by neural circuitry which encompasses specific brain stem, limbic and cortical structures. The development of anxiolytic drugs also added to the increased understanding of the neural bases of human anxiety. This thesis presents an electrophysiological investigation into Anticipatory Anxiety. Steady State Probe Topography (SSPT) is an electrophysiological method which investigates Steady State Visual Evoked Potentials (SSVEP’s), which are evoked by a flickering visual stimulus. SSPT allows an investigation of neural activity with a much higher temporal resolution than is typically afforded by PET or fMRI research. Further, SSPT may provide insight into the excitatory or inhibitory nature of neural activity. In this thesis we first examine the susceptibility of SSPT to artifacts associated with increased muscle tension, an issue of relevance in the imaging of anticipatory anxiety. While repetitive jaw clenching was observed to significantly alter EEG power across a range of bandwidths, SSPT measures were not significantly altered by these artifacts. We then explored SSPT profiles within 26 right handed males while relaxed and during theanticipation of an electric shock. Relative to the baseline condition, the AA condition was associated with significantly higher levels of self-reported anxiety and increased phasic skin conductance levels. AA was associated with increased SSVEP latency within medial anterior frontal, left dorsolateral prefrontal and bilateral temporal regions. In contrast, increased SSVEP amplitude and decreased SSVEP latency were observed within occipital regions. The observed SSVEP latency increases within frontal and temporal cortical regions are suggestive of increased localised inhibitory processes within regions reciprocally connected to subcortical limbic structures. Occipital SSVEP latency decreases are suggestive of increased excitatory activity. SSVEP amplitude increases within occipital regions may be associated with an attentional shift from external to internal environment. The current findings provide further support for the involvement of frontal, anterior temporal and occipital cortical regions during anticipatory anxiety, and suggest that both excitatory and inhibitory processes are associated with AA alterations. Finally we examined the acute influence of three common anxiolytics, the benzodiazepine alprazolam, the SSRI citalopram and the 5-HT1A parital agonist, buspirone. Acutely administered anxiolytics did not significantly reduce induced anxiety, but baseline anxiety was reduced following buspirone and alprazolam. During AA, increased SSVEP latency was again observed within prefrontal and temporal electrodes. Citalopram was associated with attenuated SSVEP amplitude decreases and buspirone was associated with significantly augmented occipital SSVEP latency decreases. Attenuations in SSVEP amplitude are consistent with reductions in overactive prefrontal circuitry following pharmacological or behavioural treatment. These findings contribute to our knowledge of how the cortex is involved in human anxiety, and suggest that previous findings of increased cortical rCBF of metabolism may be associated with increased localised neuronal inhibition