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The thalamic pulvinar and the lateral intraparietal area (LIP) share reciprocal anatomical connections and are part of an extensive cortical and subcortical network involved in spatial attention and oculomotor processing. The goal of this study was to compare the effective connectivity of dorsal pulvinar (dPul) and LIP and to probe the dependency of microstimulation effects on task demands and spatial tuning properties of a given brain region. To this end, we applied unilateral electrical microstimulation in the dPul (mainly medial pulvinar) and LIP in combination with event-related BOLD fMRI in monkeys performing fixation and memory-guided saccade tasks. Microstimulation in both dPul and LIP enhanced task-related activity in monosynaptically-connected fronto-parietal cortex and along the superior temporal sulcus (STS) including putative face patch locations, as well as in extrastriate cortex. LIP microstimulation elicited strong activity in the opposite homotopic LIP while no homotopic activation was found with dPul stimulation. Both dPul and LIP stimulation also elicited activity in several heterotopic cortical areas in the opposite hemisphere, implying polysynaptic propagation of excitation. Despite extensive activation along the intraparietal sulcus evoked by LIP stimulation, there was a difference in frontal and occipital connectivity elicited by posterior and anterior LIP stimulation sites. Comparison of dPul stimulation with the adjacent but functionally dissimilar ventral pulvinar also showed distinct connectivity. On the level of single trial timecourses within each region of interest (ROI), most ROIs did not show task-dependence of stimulation-elicited response modulation. Across ROIs, however, there was an interaction between task and stimulation, and task-specific correlations between the initial spatial selectivity and the magnitude of stimulation effect were observed. Consequently, stimulation-elicited modulation of task-related activity was best fitted by an additive model scaled down by the initial response amplitude. In summary, we identified overlapping and distinct patterns of thalamocortical and corticocortical connectivity of pulvinar and LIP, highlighting the dorsal bank and fundus of STS as a prominent node of shared circuitry. Spatial task-specific and partly polysynaptic modulations of cue and saccade planning delay period activity in both hemispheres exerted by unilateral pulvinar and parietal stimulation provide insight into the distributed interhemispheric processing underlying spatial behavior.

Brain perturbation studies allow detailed causal inferences of behavioral and neural processes. Because the combination of brain perturbation methods and neural measurement techniques is inherently challenging, research in humans has predominantly focused on non-invasive, indirect brain perturbations, or neurological lesion studies. Non-human primates have been indispensable as a neurobiological system that is highly similar to humans while simultaneously being more experimentally tractable, allowing visualization of the functional and structural impact of systematic brain perturbation. This review considers the state of the art in non-human primate brain perturbation with a focus on approaches that can be combined with neuroimaging. We consider both non-reversible (lesions) and reversible or temporary perturbations such as electrical, pharmacological, optical, optogenetic, chemogenetic, pathway-selective, and ultrasound based interference methods. Method-specific considerations from the research and development community are offered to facilitate research in this field and support further innovations. We conclude by identifying novel avenues for further research and innovation and by highlighting the clinical translational potential of the methods.

Patients with Parkinson's disease (PD) frequently suffer from visual misperceptions and hallucinations, which are difficult to objectify and quantify. We aimed to develop an image recognition task to objectify misperceptions and to assess performance fluctuations in PD patients with and without self-reported hallucinations. Thirty-two non-demented patients with Parkinson's disease (16 with and 16 without self-reported visual hallucinations) and 25 age-matched healthy controls (HC) were tested. Participants performed a dynamic image recognition task with real and scrambled images. We assessed misperception scores and intra-individual variability in recognition times. To gain insight into possible neural mechanisms related to misperceptions and performance fluctuations we correlated resting state network connectivity to the behavioral outcomes in a subsample of Parkinson's disease patients (N = 16). We found that PD patients with self-reported hallucinations (PD-VH) exhibited higher perceptual error rates, due to decreased perceptual sensitivity and not due to changed decision criteria. In addition, PD-VH patients exhibited higher intra-individual variability in recognition times than HC or PD-nonVH patients. Both, misperceptions and intra-individual variability were negatively correlated with resting state functional connectivity involving frontal and parietal brain regions, albeit in partly different subregions. Consistent with previous research suggesting that hallucinations arise from dysfunction in attentional networks, misperception scores correlated with reduced functional connectivity between the dorsal attention and salience network. Intra-individual variability correlated with decreased connectivity between somatomotor and right fronto-parietal networks. We conclude that our task can detect visual misperceptions that are more prevalent in PD-VH patients. In addition, fluctuating visual performance appear to be a signature of PD-VH patients, which might assist further studies of the underlying pathophysiological mechanisms and cognitive processes. Keywords: Parkinson's disease, Visual hallucinations, Misperceptions, Trial-by-trial variability, Continuous flash suppression