Titel Deelnemers "Korte inhoud" "Conflict detection and resolution in macaque frontal eye fields" "Tao Yao, Wim Vanduffel" "Stimulus-induced conflicts in decision-making tasks produce both behavioral and neuronal congruency effects. However, how and when conflicts are detected and resolved at the neuronal level remains largely unclear. To address these issues, we recorded from single neurons in the frontal eye fields of two macaques performing a conflict task. Although the temporal dynamics of the neuronal congruency effects are independent of the specific task rules, they are substantially different in target- and distractor-encoding neurons. Conflicts were detected ~100 ms after the conflict-inducing cue (20-30 ms after the visual response), which is much faster than predicted based on human EEG results. This suggests that conflict detection relies on a fast mechanism in frontal eye fields. Resolving the conflict at the neuronal level, however, requires between" "Spike rates of frontal eye field neurons predict reaction times in a spatial attention task" "Wim Vanduffel" "Which neuronal signal(s) predict reaction times when subjects respond to a target at covertly attended locations? Although recent studies showed that spike rates are not predictive, it remains a highly contested question. Therefore, we record single-unit activity from frontal eye field (FEF) neurons while macaques are performing a covert spatial attention task. We find that the attentional modulation of spike rates of FEF neurons is strongly correlated with behavioral reaction times. Moreover, this correlation already emerges 1 s before target dimming, which triggers the behavioral responses. This prediction of reaction times by spike rates is found in neurons showing attention-dependent enhanced and suppressed activity for targets and distractors, respectively, yet in varying degrees across subjects. Thus, spike rates of FEF neurons can predict reaction times persistently and well before the operant behavior during selective attention tasks. Such long prediction windows will be useful for developing spike-based brain-machine interfaces." "Pathway-selective Reversible Perturbations Using a Double-Infection Technique in the Macaque Brain" "Wim Vanduffel" "Utilizing PET and MALDI Imaging for Discovery of a Targeted Probe for Brain Endocannabinoid α/β-Hydrolase Domain 6 (ABHD6)" "Wim Vanduffel, Christopher Cawthorne, Sofie Celen, Guy Bormans" "Multimodal imaging provides rich biological information, which can be exploited to study drug activity, disease associated phenotypes, and pharmacological responses. Here we show discovery and validation of a new probe targeting the endocannabinoid α/β-hydrolase domain 6 (ABHD6) enzyme by utilizing positron emission tomography (PET) and matrix-assisted laser desorption/ionization (MALDI) imaging. [18F]JZP-MA-11 as the first PET ligand for in vivo imaging of the ABHD6 is reported and specific uptake in ABHD6-rich peripheral tissues and major brain regions was demonstrated using PET. A proof-of-concept study in nonhuman primate confirmed brain uptake. In vivo pharmacological response upon ABHD6 inhibition was observed by MALDI imaging. These synergistic imaging efforts used to identify biological information cannot be obtained by a single imaging modality and hold promise for improving the understanding of ABHD6-mediated endocannabinoid metabolism in peripheral and central nervous system disorders." "A framework and resource for global collaboration in non-human primate neuroscience." "Wim Vanduffel" "As science and technology evolve, there is an increasing need for promotion of international scientific exchange. Collaborations, while offering substantial opportunities for scientists and benefit to society, also present challenges for those working with animal models, such as non-human primates (NHPs). Diversity in regulation of animal research is sometimes mistaken for the absence of common international welfare standards. Here, the ethical and regulatory protocols for 13 countries that have guidelines in place for biomedical research involving NHPs were assessed with a focus on neuroscience. Review of the variability and similarity in trans-national NHP welfare regulations extended to countries in Asia, Europe and North America. A tabulated resource was established to advance solution-oriented discussions and scientific collaborations across borders. Our aim is to better inform the public and other stakeholders. Through cooperative efforts to identify and analyze information with reference to evidence-based discussion, the proposed key ingredients may help to shape and support a more informed, open framework. This framework and resource can be expanded further for biomedical research in other countries." "Additive Manufacturing of Subject-Conformal Receive Coils for Magnetic Resonance Imaging" "Hanne Vanduffel, Willy Gsell, Rodrigo de Oliveira Silva, Louca Goossens, Ronald Peeters, Uwe Himmelreich, Brecht Van Hooreweder, Dimitrios Sakellariou, Wim Vanduffel, Rob Ameloot" "Look twice: A generalist computational model predicts return fixations across tasks and species" "Marcelo Armendariz" "Primates constantly explore their surroundings via saccadic eye movements that bring different parts of an image into high resolution. In addition to exploring new regions in the visual field, primates also make frequent return fixations, revisiting previously foveated locations. We systematically studied a total of 44,328 return fixations out of 217,440 fixations. Return fixations were ubiquitous across different behavioral tasks, in monkeys and humans, both when subjects viewed static images and when subjects performed natural behaviors. Return fixations locations were consistent across subjects, tended to occur within short temporal offsets, and typically followed a 180-degree turn in saccadic direction. To understand the origin of return fixations, we propose a proof-of-principle, biologically-inspired and image-computable neural network model. The model combines five key modules: an image feature extractor, bottom-up saliency cues, task-relevant visual features, finite inhibition-of-return, and saccade size constraints. Even though there are no free parameters that are fine-tuned for each specific task, species, or condition, the model produces fixation sequences resembling the universal properties of return fixations. These results provide initial steps towards a mechanistic understanding of the trade-off between rapid foveal recognition and the need to scrutinize previous fixation locations." "Neuronal congruency effects in macaque prefrontal cortex" "Tao Yao, Wim Vanduffel" "The interplay between task-relevant and task-irrelevant information may induce conflicts that impair behavioral performance, a.k.a. behavioral congruency effects. The neuronal mechanisms underlying behavioral congruency effects, however, are poorly understood. We recorded single unit activity in monkey prefrontal cortex using a task-switching paradigm and discovered a neuronal congruency effect (NCE) that is carried by target and distractor neurons which process target and distractor-related information, respectively. The former neurons provide more signal, the latter less noise in congruent compared to incongruent conditions, resulting in a better target representation. Such NCE is dominated by the level of congruency, and is not determined by the task rules the subjects used, their reaction times (RT), the length of the delay period, nor the response levels of the neurons. We propose that this NCE can explain behavioral congruency effects in general, as well as previous fMRI and EEG results in various conflict paradigms." "Limited Pairings of Electrical Micro-stimulation of the Ventral Tegmental Area and a Visual Stimulus Enhance Visual Cortical Responses." "Jerome Herpers, Wim Vanduffel, Rufin Vogels" "Previous studies demonstrated that pairing a visual stimulus and electrical micro-stimulation of the ventral tegmental area (VTA-EM) for multiple days is sufficient to induce visual cortical plasticity and changes perception. However, a brief epoch of VTA-EM-stimulus pairing within a single day has been shown to result in a behavioral preference for the paired stimulus. Here, we investigated whether a brief single-day session of VTA-EM-stimulus pairings is sufficient to induce changes in visual cortical responses. We examined macaque posterior inferior temporal (PIT) cortex because previous studies demonstrated response changes after VTA-EM stimulus pairing in that area. Multi-unit recordings in PIT were interleaved with VTA-EM-stimulus pairing epochs. During the short VTA-EM-stimulus pairing epochs (60 pairings), one image (fractal) was paired with VTA-EM (STIM) whereas another, unpaired fractal was presented as control. Two other fractals (dummies) were presented only during the recordings. The difference in response between the STIM and control fractals already increased after the first VTA-EM-stimulus pairing epoch, reflecting a relative increase of the response to the STIM fractal. However, the response to the STIM fractal did not increase further with more VTA-EM-stimulus pairing epochs. The relative increase in firing rate for the paired fractal was present early in the response, in line with a local/ bottom-up origin. These effects were absent when comparing the responses to the dummies pre- and post-VTA-EM. This study shows that pairing a visual image and VTA-EM in a brief single-day session is sufficient to increase the response for the paired image in macaque PIT." "A reference tissue forward model for improved PET accuracy using within-scan displacement studies" "Wim Vanduffel" "We report a novel forward-model implementation of the full reference tissue model (fFTRM) that addresses the fast-exchange approximation employed by the simplified reference tissue model (SRTM) by incorporating a non-zero dissociation time constant from the specifically bound compartment. The forward computational approach avoided errors associated with noisy and nonorthogonal basis functions using an inverse linear model. Compared to analysis by a multilinear single-compartment reference tissue model (MRTM), fFTRM provided improved accuracy for estimation of binding potentials at early times in the scan, with no worse reproducibility across sessions. To test the model's ability to identify small focal changes in binding potential using a within-scan challenge, we employed a nonhuman primate model of focal dopamine release elicited by deep brain microstimulation remote to ventral striatum (VST) during imaging by simultaneous PET and fMRI. The new model reported an unambiguously lateralized response in VST consistent with fMRI, whereas the MRTM-derived response was not lateralized and was consistent with simulations of model bias. The proposed model enabled better accuracy in PET [11C]raclopride displacement studies and may also facilitate challenges sooner after injection, thereby recovering some sensitivity lost to radioactive decay of the PET tracer."