Rowe, James Benedict; (2002) Functional imaging of response selection. Doctoral thesis (Ph.D.), University College London (United Kingdom).

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Abstract

The functions of the prefrontal cortex remain controversial. Electrophysio- logical and lesion studies in monkeys have emphasised a role in working memory. In contrast, human functional neuroimaging studies and neuropsychology have emphasised a role in executive processes and volition. An alternative interpretation of the role of the prefrontal cortex is proposed in this thesis: that the prefrontal cortex mediates the attentional selection of sensory, mnemonic and motor representations in non-prefrontal cortex. This hypothesis is tested in a series of functional imaging experiments. In the first two experiments (chapters 4 and 5), event-related functional magnetic resonance imaging (fMRI) was used to re-examine the role of the prefrontal cortex in spatial and spatio-temporal working memory. Maintenance of information in memory was associated with activation of posterior prefrontal cortex (area 8). In contrast, the selection of an item from several remembered items was associated with activation of the middle and anterior parts of the prefrontal cortex (including area 46). To test the generalisation of 'selection' as a function of prefrontal cortex, experiment three (chapter 6) required subjects to select either a finger to move, or a colour from a multicolour display. Free selection was associated with activation of the prefrontal cortex (area 46) bilaterally, regardless of sensory or motor modality. The selection of voluntary actions has been proposed to depend on top-down modulation of motor regions by prefrontal cortex. The fourth and fifth experiments used structural equation modelling of fMRI time -series to measure the effective connectivity among prefrontal, premotor and parietal cortex. In young (chapter 7) and old (chapter 8) normal subjects, attention to action specifically enhanced coupling between prefrontal and premotor regions. This effect was not seen in patients with Parkinson's disease (chapter 8). Lastly, positron emission tomography was used to study planning in the Tower of London task, a common clinical measure of prefrontal function. Several variants of the task were developed, to distinguish the neural basis of the task's multiple cognitive components (chapter 9). The prefrontal cortex was activated in association with generation, selection or memory for moves, rather than planning towards a specified goal. The results support a generalised role in attentional selection of neuronal representations, whether stimuli, actions, or remembered items. The hypothesised attentional selection of responses is consistent with the activation of prefrontal cortex in working memory tasks and during attention to voluntary action. This role is compatible with the neurophysiological properties of individual neurons in the prefrontal cortex and the results of neuroimaging and lesion studies.

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