Proefschrift_Holstein

Controlling dorsolateral striatal function via anterior frontal cortex stimulation

Results Neural effects Main task effects irrespective of site and TMS revealed an anterior/ventrodorsal to posterior/ dorsolateral activity gradient in the striatum Comparing the neural signal during high versus low Reward cues revealed a large bilateral network of regions, including the striatum, lingual gyrus, thalamus, cingulate cortex and the aPFC, overlapping with the stimulation site (SVC aPFC stimulation site: (PSVC_FWE < 0.001) ( table 7.1, figure 7.4 ). During trials on which the task switched, compared with trials on which the task was repeated, a network including the inferior frontal gyrus, cingulate gyrus, superior parietal lobe, and inferior temporal gyrus was activated ( table 7.2 ), overlapping with the stimulation site (dlPFC stimulation site: (PSVC_FWE < 0.001) ( table 7.2, figure 7.4a ). Analysis of signal in the striatum did not reveal any significant effects of Task switching (but see below-threshold signal in figure 7.4b ). One large cluster was more active during response switching compared with response repetition trials. This left lateralized cluster included the primary motor cortex (B4), premotor cortex (B6), primary somatosensory cortex, precentral gyrus (premotor cortex, B6 and primary motor cortex, B4) and the primary somatosensory cortex (B3) and extended posterior into the parietal lobe, i.e. the postcentral gyrus (peak PFWE < 0.001, t = 6.61, z = 6.19, cluster size = 3250, peak x, y, z = -40, -36, 54). However, this cluster did not show any overlap with the stimulation site ( figure 7.4a ). Exploring effects (at p < 0.005) in the striatum revealed no FWE corrected effects in the putamen (but see below-threshold effects in figure 7.4b ). We did not observe significant neural interaction effects between Reward, Task switching and/or Response switching (across site and TMS). Functionally specific effects in the striatum after stimulation of the aPFC During high versus low Reward, neural signaling in the right caudate nucleus was significantly decreased after aPFC stimulation compared with baseline (aPFCSTIM-BASE x Reward, PSVC_FWE = 0.040, k = 17, T = 3.78, z = 3.69, peak x, y, z = 6, 16, 2; figure 7.5 – red coloring ). There were no reward-related effects of dlPFC or PMC stimulation. The effect of aPFC stimulation was located in the anterior portion of the caudate nucleus ( figure 7.5 ) and was regionally specific within the striatum: there was no such effect of aPFC stimulation on reward-related signal in the putamen. Analysis of the two-way interactionbetweenReward andTask switching revealed that signaling in a different, more posterior region of the caudate nucleus ( figure 7.5 – green coloring ) was decreased by aPFC stimulation (but not by dlPFC or PMC stimulation), although this effect did not reach significance according to our statistical threshold (aPFCSTIM-BASE x reward x task switch: PSVC_UNC = 0.003, t = 2.78, z = 2.74, peak x, y, z = -6, 6, -6).

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