State-dependent decoding and control of neuronal circuits and signals for perceptual decisions

Summary for the extension of the Heisenberg-Professorship.
Everyday life presents perceptual tasks every moment of the waking day. Walking up and down in a built environment, we may have to find the building we have an appointment in, while we navigate static objects and moving people in our path, meanwhile our gaze might be drawn to faces we recognize. In the past decades, we have made significant strides in understanding the neural substrates that support perceptual judgements about three-dimensional figures and objects and their movement trajectories (Gold & Shadlen 2007; Krug 2020). Most of the underlying evidence has been generated using judgments that take place over clearly-defined finite time periods requiring a response to one perceptual dimension of a simple object or stimulus. The level of inquiry focussed on the single neuron (neurophysiology) and single brain area (functional MRI) (Krug, 2020; Parker & Newsome, 1998).
Building on my previous work, I have developed a new set of 3D-motion stimuli, that allows us to probe how neural signals contribute to perceptual decisions as the incoming stimulus is changing dynamically and unpredictably. In Project 1, we are using these stimuli to probe in real-time the interactions between multiple groups of neurons recorded simultaneously. This project uses high-dimensional recordings with linear electrode arrays as trained Rhesus macaques make perceptual decisions about them. To decode the current state of perceptual circuits from ongoing recorded neuronal activity (SUA, MUA, LFP), I have implemented, together with my postdoc Dr. Corentin Gaillard, modern machine-learning approaches for analysing perceptual decision signals for 3D-motion. We will also use the linear decoder to target causal interventions in ongoing decision-making in a state-dependent manner (Project 2).
The correlative study of real-time signals in Projects 1 informs Project 2. Across Projects 1 & 2, using our detailed knowledge of single neurons and the dynamics of local circuits in area V5/MT for decisions about 3D-motion stimuli (DeAngelis et al.,1998; Dodd et al. 2001 Krug et al., 2004; Krug et al. 2013; Wasmuht et al 2019; Krug 2020), we aim to achieve detailed knowledge of the relevant circuits in extrastriate area V5/MT across columns and their interactions with cortical areas directly connected (V4/V4t, MST, LIP). Project 3 addresses functional decision-making in primates across brain-wide circuits. This is the same overarching question as Projects 1 & 2, but from the starting point of combining high resolution MRI and causal stimulation methods to pinpoint the neuroanatomical localisation of decision-making circuits. One particular focus is here how changes in functional connectivity between key brain areas (V5/MT, LIP, FEF) affect local activation, perceptual state, and decisions. For this, I use focussed ultrasound stimulation (FUS) to manipulate functional connectivity, a new method I was involved in establishing (Verhagen et al. 2019). Ultimately, these changes in functional connectivity will be linked to the real-time neural activity changes we characterize in Projects 1 and 2.