Proefschrift_Holstein

Controlling dorsolateral striatal function via anterior frontal cortex stimulation

based on the main effect of reward anticipation (motivation), task switching (cognition) and response switching (action) in an independent dataset that used the same paradigm (Aarts et al., 2010 unpublished observations). Hence, a region in the anterior prefrontal cortex (aPFC) was selected as a target for modulating the reward circuit, a region in the dlPFC as the target for the task-switching circuit, and a region in the PMC to target the response switching circuit. These three cortical sites were stimulated on three separate days, using a counterbalanced within-subject crossover design, to directly compare effects on task-related processing between and within circuitries. Based on in vivo evidence about the topography of striatal connectivity from diffusion weighted imaging work (Draganski et al., 2008), we predicted that cTBS over the aPFC would attenuate the main effect of reward on BOLD signals in the anterior/ventral caudate nucleus, i.e. the main striatal target of the aPFC. In addition, we hypothesized that cTBS over the aPFC would influence reward-related task-switching signals in the posterior caudate nucleus, via connections between the motivational and cognitive striatum ( figure 7.1 ), and that cTBS over the aPFC would influence the integration of reward, task switching and response switching in the putamen via connections between the motivational, cognitive, and motor striatum ( figure 7.1 ). Stimulation over the dlPFC was predicted to attenuate BOLD signal in the posterior caudate nucleus during task switching. This effect should propagate to the putamen, via connections between the cognitive and motor striatum during the integration of task switching and response switching ( figure 7.1 ). Finally, cTBS over the PMC was predicted to attenuate BOLD signals in the putamen during response switching. The goal of this experiment was to provide evidence for interactions between the different corticostriatal circuits, as well as for the directionality of these interactions, as has been shown in non- human primates (Haber et al., 2000). Forty-two healthy participants were recruited to take part in the initial ‘intake’ session ( experimental design and procedures ). Eleven participants were excluded: Six participants did not tolerate the prefrontal stimulation well ( experimental design and procedures ), two did not feel comfortable during the TMS, one brain abnormality was revealed during intake, and for two participants no reliable motor evoked potential (MEP) measure could be obtained. The remaining 31 participants proceeded to the main experiment ( experimental design and procedures ). During the experimental sessions, one participant was excluded due to a contra-indication for MRI, one participants’ session was discontinued due to dizziness during MRI, and one participant was excluded due to technical TMS problems and one participant due to technical MRI problems. This resulted in 27 participants, ranging from 18 – 25 (mean 21.7, SD 1.95) years old (14 Methods Participants

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