Project in DFG Priority Program SPP2411
We present a novel hypothesis of the functions of the pulvinar in the primate and make proposals for specific tests to probe predictions of this hypothesis. The pulvinar nuclei are greatly enlarged in primates compared with other mammals. We advance the view that the pulvinar may function as a computational system that is specifically suited to adaptive computation. As a specific case of this general hypothesis, we will examine how the pulvinar and its connected neocortical areas may support the structuring of 3-D spatial relationships in the visual world. Information about the 3-D structure of the immediately visible world is important for both sensory, perceptual judgments about the size, shape and position or objects, but also for motor activity, particular the control of eye movements. In humans, such movements are inherently binocular in nature and therefore embedded in 3-D spatial processing. Few, if any, studies of the pulvinar nuclei have examined binocular 3-D properties of pulvinar neurons. By contrast, there has been extensive study of the binocular function of sensory cortical areas. We seek to build upon the current canonical view that the pulvinar nuclei provide a relay or ‘efference copy’ of cognitive signals such as spatial attention. This project will test the hypothesis that the pulvinar relay applies a transform to neuronal signals about 3-D spatial relationships as they pass from one visual cortical area to another. We will make dual electrophysiological recordings from the pulvinar nuclei and anatomically connected visual cortical areas The project will test the adaptive, regulatory role of the pulvinar by employing standard visuomotor adaptation paradigms, in combination with interventions that aim to temporarily and reversibly disrupt pulvinar function.

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HORIZON TMA MSCA Postdoctoral Fellowship - European Fellowship for Dr. Corentin Gaillard:
Computational models of vision often address problems that have a single and definite end-point, such as visual recognition: an example of this might be to find a ripe banana in a complex scene. However, not all computation is of this form. Visual information is processed continuously in sensory areas and the nervous system has the capacity to alter or halt an ongoing behavioural response to changes in incoming information. We can therefore react flexibly to updated sensory input or changed requirements for motor output. On the other hand, these same neuronal mechanisms must also support perceptual stability, so that noisy signals do not cause loss of a crucial goal. In project COGSTIM, I will investigate the functional neuronal networks that support the balance between perceptual flexibility and stability, within primate visual areas. I will use a highly innovative approach, combining dense electrophysiological recording with online (real-time) decoding of neuronal correlates of the subject’s perceptual choice, based on adaptive machine-learning algorithms. In order to control visual perception effectively and predictably, closed-loop electrical stimulation will be applied under dynamically adjusted feedback to identified neuronal circuits that causally modulate associated percepts. Crucially, this novel approach using joint decoding and stimulation in real time will allow me to target dynamically visual percepts, representing a significant advance in our understanding of on-going, continuous computations of the primate brain. Such developments offer promising bases for the future development of rehabilitative therapeutical protocols, as well as innovative brain machine interfaces suitable for real-world use.

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Der SFB 1436 hat das Ziel, neuronale Ressourcen auf allen Größenskalen zu untersuchen durch einen interdisziplinären Ansatz, welcher funktionelle und strukturelle Eigenschaften von kortikalen und subkortikalen Schaltkreisen mit Verhalten und Leistungsfähigkeit in Zusammenhang bringt und Interventionen untersucht. Technologische Fortschritte im Bereich der in vivo Gehirnbildgebung des menschlichen Gehirns sowie der multimodalen Modellierung sollen eine Brücke zwischen Molekularen Studien an Tiermodellen und Verhaltensstudien an Versuchspersonen und Patienten bauen.

Projekt C05 des SFB 1436 - in Kollaboration mit Prof. Dr. Petra Ritter (Charite, Berlin) - verfolgt einen kombinierten theoretischen und empirischen Ansatz, um kausal - von den Neuronen bis zum Verhalten - zu untersuchen, wie die Ressourcenzuteilung in visuellen und parietalen Hirnregionen durch die Veränderung der funktionalen Verbindungen in dem der menschlichen Kognition am nächsten kommenden Tiermodell, dem Rhesusaffen, gesteuert werden kann.

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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.

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When we walk along a busy street against the flow of people, looking for someone we hope to meet, we face a flood of visual inputs. In this situation, the brain mechanisms underlying visual processing are engaged continuously and for an unpredictable length of time. They must analyse incoming sensory information continuously to evaluate, initiate and guide motor actions at all times (walking, avoiding obstacles, scanning faces, etc). In contrast, most of our knowledge of the neuronal basis of visual processing is based on simple ‘laboratory’ situations: discrete trials with predictable start (cue), a fixed stimulus, end (another cue) and motor action (one of a few known alternative responses). One of the next major challenges for systems neuroscience will be to incorporate in our experimental paradigms some aspects of ‘normal vision’ such as the continuous integration of information over time and the ongoing evaluation for motor actions. My current proposal builds onto the well-defined experimental framework of perceptual decision-making, but rather than treating perception and behaviour as a sequence of discrete, finite episodes, each culminating in a decision, new experimental paradigms will probe how the brain engages in active, continuous monitoring of the dynamically changing flow of information. Previous work by myself and others has shown that neurons in extrastriate visual area V5/MT of primates can control 3D and motion components of a complex perceptual experience. Undertaking high-dimensional recordings from many neurons simultaneously in this well-described area of the visual system of awake behaving primates, I propose to investigate the broader questions of how neurons interact dynamically in space and time in order to shape visual perception and decision-making. This project has four parts. Firstly, in order to probe the role of cooperativity in neuronal circuits for visual perception, I will introduce unpredictable dynamic changes in visual stimuli and investigate the temporal relationship between these stimulus changes and percept-related neuronal activity and interactions. Do dynamical responses provide evidence for hysteresis in state-dependent neuronal interactions? Secondly, as a visual 3D-motion percept emerges, we will track the interactions between task-relevant neurons across functional subdomains like columns in real time. As a bistable stimulus is viewed over time (seconds), we will investigate the relationship between changes in neuronal interactions and the reported percept. Thirdly, we will test whether neuronal response patterns obtained with simple motion and 3D stimuli predict responses to more complex visual stimuli (such as biological motion and 3D motion patterns embedded in movie sequences). Lastly, we will employ the empirical data obtained from these high-dimensional recordings to challenge neuro-computational models of network dynamics for perceptual decisions and collaborate on their construction.

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Mit diesem Projekt planen wir in Magdeburg eine neue Technologieplattform einrichten, um die MR-Spektroskopie (MRS) im visuellen Kortex des Rhesusaffen zu ermöglichen, die MRS-Messungen mit der Aufzeichnung und Manipulation physiologischer Signale im MR-Scanner kombinieren soll. Magdeburg verfügt für Europa fast einzigartig über einen 7-Tesla-Hochfeld-MRT-Scanner, in dem auch die Rhesusaffen gebracht und gemessen werden können. Die Hochfeldstärke des Magdeburger Scanners ist ein wesentlicher Bestandteil bei der Einrichtung der vorgeschlagenen spektroskopischen Messungen.

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DFG Programme Heisenberg Professorship

My Heisenberg project addresses the questions of how neurons interact dynamically in space
and time in order to shape visual perception and decision-making. I propose a new programme
of research that combines (i) high dimensional neurophysiological recordings, (ii) causal
interventions directly applied to the relevant neuronal circuits in a time or state-dependent manner
and (iii) a detailed analysis of the underlying neuronal circuitry. The only available experimental
model system to support this currently is the non-human primate, specifically the macaque
monkey. These animals have a visual system closely similar to humans, so that we can
experimentally adopt sophisticated behavioural paradigms. To investigate the underlying brain
connectivity and translate results to the human brain, cutting-edge recording and imaging
technologies for human and non-human primates will be essential for the future, as they are in
my present research.
The long-term scientific aim of my research is to understand and control the neuronal signals that
generate our rich visual experience. In recent years, the closest experimental links between brain
signals and perception have been established in awake primates between the activity of single
neurons and perceptual decisions. I have significant experience and contributions in this area and
now wish to extend this powerful research platform to more naturalistic settings of perception and
action. Specifically, the new work will focus on the continuity of perceptual activities. Rather than
treating perception and behaviour as a sequence of discrete, finite episodes, each culminating in
a decision, the new experimental paradigms will study of how the brain engages in active,
continuous monitoring of the dynamically changing incoming flow of information.

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Die direkte elektrische Stimulation im Gehirn von Menschen ist ein wichtiges therapeutisches Mittel, z.B. kann die Tiefenhirnstimulation für Parkinson oder Depressionen Symptome lindern und Gehör-Prothesen können Schallwellen in elektrische Ströme übersetzen. Allerdings werden in vieler Hinsicht solche klinischen Anwendungen der direkten elektrischen Stimulation im Gehirn wie in einer "Blackbox" angewandt, also ohne genau in mechanistischer Weise zu verstehen, wie ein bestimmtes Stimulationsprogramm, seine spezifische Wirkung entfaltet und in wieweit dies von der stimulierten Hirnstruktur abhängt. Um die funktionalen Effekte direkt induzierter elektrischer Signale, wie sie in der Tiefenhirnstimulation im Menschen bereits in einigen wenigen Hirnstrukturen und Erkrankungen, z.B. Parkinson, verwendet werden, besser zu verstehen und gezielter auch für andere Krankheiten einsetzen zu können, planen wir Experimente mit elektrischer Gehirn-Stimulation im hochauflösenden 7T Siemens MRT am Leibniz-Institut in Magdeburg. Ein mechanistisches Verständnis soll zu einer patientengerechteren Anwendung führen.
Wir werden am 7T MRT des Leibniz-Institutes arbeiten und profitieren von der dortigen hohen Expertise und den Sequenzen, die für die Erforschung des menschlichen Gehirns in Gesundheit und Krankheit, eingerichtet wurde. Während die Sequenzen zur Messung nur eine geringe Anpassung zwischen Affe und Mensch benötigen, können die Kopfspulen, die zur Signalmessung benötigt werden, nicht einfach übernommen werden. Die Kopfspule muss für das bestmöglichste Signal so geformt sein, dass sie nahe am Kopf des wesentlich kleineren Affen sitzt und dass sie spezifische Zugänge für das Ableiten von implantierten Elektroden hat.

Projekt im Forschungsportal ansehen

Der SFB 1436 hat das Ziel, neuronale Ressourcen auf allen Größenskalen zu untersuchen durch einen interdisziplinären Ansatz, welcher funktionelle und strukturelle Eigenschaften von kortikalen und subkortikalen Schaltkreisen mit Verhalten und Leistungsfähigkeit in Zusammenhang bringt und Interventionen untersucht. Technologische Fortschritte im Bereich der in vivo Gehirnbildgebung des menschlichen Gehirns sowie der multimodalen Modellierung sollen eine Brücke zwischen Molekularen Studien an Tiermodellen und Verhaltensstudien an Versuchspersonen und Patienten bauen.
Projekt C05 des SFB 1436 - in Kollaboration mit Prof. Dr. Petra Ritter (Charite, Berlin) - verfolgt einen kombinierten theoretischen und empirischen Ansatz, um kausal - von den Neuronen bis zum Verhalten - zu untersuchen, wie die Ressourcenzuteilung in visuellen und parietalen Hirnregionen durch die Veränderung der funktionalen Verbindungen in dem der menschlichen Kognition am nächsten kommenden Tiermodell, dem Rhesusaffen, gesteuert werden kann.

Projekt im Forschungsportal ansehen