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Previous research on the neural basis of cognitive control processes has mainly focused on cortical areas, while the role of subcortical structures in cognitive control is less clear. Models of basal ganglia function as well as clinical studies in neurodegenerative diseases suggest that the striatum (putamen and caudate nucleus) modulates the inhibition of interfering responses and thereby contributes to an important aspect of cognitive control, namely response interference control. To further investigate the putative role of the striatum in the control of response interference, 23 patients with stroke-induced lesions of the striatum and 32 age-matched neurologically healthy controls performed a unimanual version of the Simon task. In the Simon task, the correspondence between stimulus location and response location is manipulated so that control over response interference can be inferred from the reaction time costs in incongruent trials. Results showed that stroke patients responded overall slower and more erroneous than controls. The difference in response times (RTs) between incongruent and congruent trials (known as the Simon effect) was smaller in the ipsilesional/-lateral hemifield, but did not differ significantly between groups. However, in contrast to controls, stroke patients exhibited an abnormally stable Simon effect across the reaction time distribution indicating a reduced efficiency of the inhibition process. Thus, in stroke patients unilateral lesions of the striatum did not significantly impair the general ability to control response interference, but led to less efficient selective inhibition of interfering responses.

The deployment of spatial attention is highly sensitive to stimulus predictability. Despite evidence for strong crossmodal links in spatial attentional systems, it remains to be elucidated how concurrent but divergent predictions for targets in different sensory modalities are integrated. In a series of behavioral studies, we investigated the processing of modality-specific expectancies using a multimodal cueing paradigm in which auditory cues predicted the location of visual or tactile targets with modality-specific cue predictability. The cue predictability for visual and tactile targets was manipulated independently. A Bayesian ideal observer model with a weighting factor was applied to trial-wise individual response speed to investigate how the two probabilistic contexts are integrated. Results showed that the degree of integration depended on the level of predictability and on the divergence of the modality-specific probabilistic contexts (Experiments 1–2). However, when the two probabilistic contexts were matched in their level of predictability and were highly divergent (Experiment 3), higher separate processing was favored, especially when visual targets were processed. These findings suggest that modality-specific predictions are flexibly integrated according to their reliability, supporting the hypothesis of separate modality-specific attentional systems that are however linked to guarantee an efficient deployment of spatial attention across the senses.

The exact mechanisms whereby the cholinergic neurotransmitter system contributes to attentional processing remain poorly understood. Here, we applied computational modeling to psychophysical data (obtained from a spatial attention task) under a psychopharmacological challenge with the cholinesterase inhibitor galantamine (Reminyl). This allowed us to characterize the cholinergic modulation of selective attention formally, in terms of hierarchical Bayesian inference. In a placebo-controlled, within-subject, crossover design, 16 healthy human subjects performed a modified version of Posner's location-cueing task in which the proportion of validly and invalidly cued targets (percentage of cue validity, % CV) changed over time. Saccadic response speeds were used to estimate the parameters of a hierarchical Bayesian model to test whether cholinergic stimulation affected the trial-wise updating of probabilistic beliefs that underlie the allocation of attention or whether galantamine changed the mapping from those beliefs to subsequent eye movements. Behaviorally, galantamine led to a greater influence of probabilistic context (% CV) on response speed than placebo. Crucially, computational modeling suggested this effect was due to an increase in the rate of belief updating about cue validity (as opposed to the increased sensitivity of behavioral responses to those beliefs). We discuss these findings with respect to cholinergic effects on hierarchical cortical processing and in relation to the encoding of expected uncertainty or precision., The Journal of Neuroscience, 34 (47), ISSN:0270-6474, ISSN:1529-2401

The detection of relevant stimuli occurring outside of the current focus of attention is an essential cognitive ability of both animals and humans. The present thesis concentrates on the neural and neurochemical mechanisms in the human brain that underlie the processing of unattended stimuli requiring reorienting of visuospatial attention. To study these processes, Posner’s location-cueing paradigm (Posner, 1980) was employed. Here, spatial cues predict the location of a behaviourally relevant target stimulus with a certain probability and the difference in reaction times between invalidly and validly cued targets (termed the ‘validity effect’) is taken as an indicator for the speed of reorienting of attention. Functional magnetic resonance imaging (fMRI) in combination with psychopharmacology was used to investigate the reorienting-related neural systems in the brain. This thesis is concerned with the question how the neural processes of attentional reorienting are modulated by cognitive as well as by pharmacological factors. Prior studies have shown that attentional reorienting is one cognitive function that can be modulated pharmacologically by cholinergic agents. In the location-cueing paradigm the administration of the cholinergic agonist nicotine leads to faster reaction times to invalidly cued targets and consequently to a decreased validity effect (e.g., Witte, Davidson & Marrocco, 1997). This behavioural effect is accompanied by a reduction of reorienting-related neural activity in the parietal cortex (Thiel, Zilles & Fink, 2005). Drug-induced changes in the processing of the probabilistic top-down information of the spatial cues about the target location have been proposed to underlie this pharmacological effect (Yu & Dayan, 2005). Thus, a first aim of the present thesis was to study how reorienting towards unattended events can be manipulated by the top-down information about their location (i.e., by cue validity) and how the effects of this cognitive modulation are represented in the brain in a placebo condition. It was observed that the effects of a cue validity manipulation resembled the effect of nicotine in the location-cueing paradigm, since low cue validity (60%) decreased the validity effect as well as reorienting-related neural activity in right frontal and parietal cortex when compared to a high cue validity condition (90%). A further aim of the thesis was to examine the interaction effects between the cognitive and the pharmacological modulation of attentional reorienting at the behavioural as well as the neural level. Given that nicotine is supposed to reduce the [...]