Biology subjects

Schuffelgen, U.

Publications and source records attributed to Schuffelgen, U..

5 recordsLinked to original sources

bioRxiv2026

Ultrasound-mediated focal serotonin delivery causally modulates motivation in primates

Causal manipulation of neuromodulatory systems has been constrained by a trade-off between spatial precision and translational relevance: circuit-specific techniques are invasive, whereas systemic pharmacology lacks anatomical specificity. Here, we establish ultrasound-mediated neuromodulator delivery as a non-invasive, spatially precise approach for causal neuropharmacology in awake, behaving primates. By transiently opening the blood-brain barrier, we delivered systemically administered serotonin to the perigenual anterior cingulate cortex (pgACC) during a decision-making task. Combining computational modelling with multimodal imaging, pupillometry and histology, we show that elevating pgACC serotonin altered local neural activity and weakened the influence of reward environment on motivational state while leaving sensitivity to immediate reward opportunities intact. This was accompanied by reduced functional coupling, decreased local glutamatergic metabolite signal and increased serotonergic signal at the target, with repeated delivery well tolerated. Together, these findings establish a translatable platform for focal neuropharmacology and identify pgACC serotonin as a regulator of context-dependent motivation.

neuroscience↗

bioRxiv2026

Cognitive control networks in human and macaque

A much-replicated finding in human brain imaging is a distributed 'multiple-demand' or MD system, increasing in activity for many kinds of cognitive demand, and centrally involved in cognitive control. MD regions are proposed to encode a distributed mental model of critical task events, bound together in the roles and relationships needed to direct action selection. Though previous data hint at a corresponding network in the macaque, there has been no direct comparison to human data. Here we used functional magnetic resonance imaging to measure whole brain activation in a multi-step saccadic maze task, compared to a control requiring similar moves but without goal-based decisions. Human data were a close match to the canonical MD network, extended to include adjacent regions and in particular much of the canonical dorsal attention network. Data from two monkeys suggested correspondences in dorsomedial frontal, insula/orbitofrontal and posterior temporal cortex. In lateral frontal cortex there was just a single, largely dorsal activation patch, in contrast to multiple distinct human patches. In one animal, as in human, there was accompanying activation of dorsal and medial parietal cortex. In macaque as in human, together with previous data, our findings suggest an extended and strongly interconnected brain network recruited by increased cognitive challenge.

neuroscience↗

bioRxiv2024

General mechanisms of task engagement in the primate frontal cortex

Staying engaged with a task is necessary to maintain goal-directed behaviors. Although engagement varies with the specific task at hand it also exhibits continuous, intrinsic fluctuations widely. This intrinsic component of engagement is difficult to isolate behaviorally or neurally in controlled experiments with humans. By contrast, animals spontaneously move between periods of complete task engagement and disengagement, even in experimental settings. We, therefore, looked at behavior in macaques in a series of four tasks while recording fMRI signals. We identified consistent autocorrelation in task disengagement. This made it possible to build models capturing task-independent engagement and to link it to neural activity. Across all tasks, we identified common patterns of neural activity linked to impending task disengagement in mid-cingulate gyrus. By contrast, activity centered in perigenual anterior cingulate cortex (pgACC) was associated with maintenance of task performance. Importantly, we were able to carefully control for task-specific factors such as the reward history, choice value, and other motivational effects, such as response vigor, as indexed by response time, when identifying neural activity associated with task engagement. Moreover, we showed pgACC activity had a causal link to task engagement; in one of our tasks, transcranial ultrasound stimulation of pgACC, but not of control regions, changed task engagement/disengagement patterns.

neuroscience↗

bioRxiv2021

Model-based dynamic off-resonance correction for improved accelerated fMRI in awake behaving non-human primates

PurposeTo estimate dynamic off-resonance due to vigorous body motion in accelerated fMRI of awake behaving non-human primates (NHPs) using the standard EPI 3-line navigator, in order to attenuate the effects of time-varying off-resonance on the reconstruction. MethodsIn NHP fMRI the animals head is usually head-posted, and the dynamic off-resonance is mainly caused by motion in body parts that are distant from the brain and have low spatial frequency. Hence, off-resonance at each frame can be approximated as a spatially linear perturbation of the off-resonance at a reference frame, and is manifested as a relative linear shift in k-space. Using GRAPPA operators, we estimated these shifts by comparing the 3-line navigator at each time frame with that at the reference frame. Estimated shifts were then used to correct the data at each frame. The proposed method was evaluated in phantom scans, simulations, and in vivo data. ResultsThe proposed method is shown to successfully estimate low-spatial order dynamic off-resonance perturbations, including induced linear off-resonance perturbations in phantoms, and is able to correct retrospectively corrupted data in simulations. Finally, it is shown to reduce ghosting artifacts and geometric distortions by up to 20% in simultaneous multi-slice in vivo acquisitions in awake-behaving NHPs. ConclusionA method is proposed that does not need any sequence modification or extra acquisitions and makes accelerated awake behaving NHP imaging more robust and reliable, reducing the gap between what is possible with NHP protocols and state-of-the-art human imaging.

neuroscience↗

bioRxiv2021

Social prediction modulates activity of macaque superior temporal cortex

The ability to attribute thoughts to others, also called theory of mind (TOM), has been extensively studied. Computationally, the basis of TOM in humans has been interpreted within the predictive coding framework and associated with activity in the temporo-parietal junction (TPJ). However, the evolutionary origins of these human mindreading abilities have been challenged since the concept was coined. Here we identify a brain region in the Rhesus macaque that shares computational properties with the human TPJ. We revealed, using a non-linguistic task and functional magnetic resonance imaging, that activity in a region of the macaque middle superior temporal cortex was specifically modulated by the predictability of social interactions. As in human TPJ, this region could be distinguished from other temporal regions involved in face processing. Our result suggests the existence of a precursor for the theory of mind ability in the last common ancestor of human and old-world monkeys.

neuroscience↗