Intervening in circuits for cognitive resource allocation in primates

C05

Complex cognitive functions like decision-making rely on the coordinated activity across several brain regions. While the role of local brain circuits has been intensively studied, the influence of long-range functional connectivity on local activity is less well understood. We investigate how changes in functional interactions between local and long-range circuits generate neural activations and shape behaviour. Combing empirical and computational approaches, we causally modulate functional connectivity to understand its impact on cognitive resource allocation for decision-making in primates.

Principal Investigators

CRC 1436 member Kristine Krug

Prof. Dr. Kristine Krug

CRC 1436 member Petra Ritter

Prof. Dr. med. Petra Ritter

Prof. Dr. Kristine Krug

Kristine Krug moved in 2019 as a Heisenberg Professor [DFG] and the Chair in Sensory Physiology to the Otto-von-Guericke Universität Magdeburg. Her programme of research investigates the neural circuits and mechanisms of perceptual decision-making. Her long-term scientific aim is to understand and control the neuronal signals that shape perception and decision-making from the level of single brain cells through to mental states. She currently serves on the Editorial Board of eLife, as the Chair of the Scientific Advisory Board of the German Primate Centre (DPZ) and is a Visiting Professor at the University of Oxford.

Institut:Otto von Guericke University Magdeburg, Faculty of Natural Sciences

Project Title:C05 Intervening in circuits for cognitive resource allocation in primates

Prof. Dr. med. Petra Ritter

Petra Ritter is full Professor and director of the Brain Simulation Section at the Berlin Institute of Health, Charité University Medicine Berlin. Her research focus is the integration of neuroimaging and computational neuroscience for eHealth applications. She serves as lead of several large scale consortia and projects such as the Charité & BIH Virtual Research Environment, the National Research Data Infrastructure Initiative in Neuroscience and the European Open Science Cloud project VirtualBrainCloud. She additionally served as lead of the Co-design Project The Virtual Brain in the EU Flagship Human Brain Project.

Institut:Charité – Universitätsmedizin Berlin

Project Title:C05 Intervening in circuits for cognitive resource allocation in primates

Co-Workers

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Dr. Carine De Sousa

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Lion David Deger 

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Amrit Kashyap 

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Mark Revan Rangotis

Dr. Carine De Sousa

Carine De Sousa is a postdoctoral researcher since August 2021 in the team of Prof. Dr. Kristine Krug at OVGU. She obtained her PhD in neuroscience at the University of Lyon in France. Her thesis topic was the local neural encoding of higher cognitive functions using electrophysiological recordings. Her current research focuses on larger-scale neural networks to understand the neural mechanisms of decision-making using neuroimaging and brain stimulation.

Lion David Deger 

coming soon

Amrit Kashyap 

coming soon

Brain networks for perceptual decision-making

Perceptual decision-making is the process by which sensory information is integrated and evaluated to generate a behavioural choice. Local activity of neurons in the extrastriate visual, parietal cortex and prefrontal cortex contribute to perceptual decisions in primates (Gold, Shadlen 2007; Krug et al. 2013). Cognitive processes such as attention, working memory or reward can also modulate decision-making performance; it is affected by ageing or psychological disorders (Takagaki, Krug 2020). As neural mechanism, altered modulation of local activity in visual circuits by prefrontal and posterior parietal cortex has been implicated. To test this hypothesis, we will directly study the interactions between the visual cortex and more distal areas and their impact on local resource allocation in perceptual decision-making.

Functional connectivity

Coordinated activity in neural networks is essential for optimal cognitive processing. Decision-making is an example of high cognitive function that depends on local circuits distributed over a large network (Krug 2020). Importantly, neural network dynamics are reflected in functional connectivity, which represents the correlation of neural activity between different brain regions over time. To understand how the decision-making network dynamics shape the efficiency of this function, we will alter the functional connectivity between local neural circuits, including the visual, parietal and prefrontal cortex in macaque monkeys.

Transcranial focused
ultrasound stimulation

We use transcranial focused ultrasound stimulation (FUS) to causally modulate network activity. FUS is a new non-invasive neurostimulation technique that can be used to reach deep brain structures with high spatial resolution. Depending on the stimulation protocol, FUS can be used to up- and down-regulate functional connectivity specific to the stimulated brain area with an effect lasting at least two hours (Verhagen et al. 2019). We combine FUS with structural and functional magnetic resonance imaging (7T MRI) as well as neurophysiological and behavioural measures.

Large scale brain network modeling

Using neuroimaging coupled with FUS allows us to modulate and measure the functional connectivity between brain regions. On its own, this is not sufficient to address the complexity of brain circuits. Factors such as the functional and structural specificity of brain circuits generate multiple computing possibilities. Recent studies use mathematical tools such as the virtual brain (VBT) to build biologically plausible computational models of brain network dynamics in humans (Ritter et al. 2013) and macaques (Shen et al. 2019). The models provide a mechanistic understanding of how distributed brain regions interact to process neural information. Using our own connectivity data, we build VBT models by reproducing observed data, test our hypotheses and generate new predictions. The predictions will in turn be tested through neurophysiological and behavioural data and thus provide a quantitative understanding of decision-making network dynamics and the consequences of their disruption.

Gold JI, Shadlen MN. 2007. The neural basis of decision making. Annu Rev Neurosci 30:535-74.

Krug K, Cicmil N, Parker AJ, Cumming BG. 2013. Causal interference with neuronal signals in V5/MT influences perceptual judgments about a stereo-motion task. Current Biology 23:1454-9.

K Krug (2020) Coding perceptual decisions: from single units to emergent signaling properties in cortical circuits. Annual Review of Vision Science 6:387-409.

Ritter P, Schirner M, McIntosh AR, Jirsa VK. 2013. The virtual brain integrates computational modeling and multimodal neuroimaging. Brain Connect 3:121-45. 

Shen K, Bezgin G, Schirner M, Ritter P, Everling S, McIntosh AR. 2019. A macaque connectome for large-scale network simulations in TheVirtualBrain. Scientific Data 6:123.

Takagaki K, Krug K. 2020. The effects of reward and social context on visual processing for perceptual decision-making. Current Opinion in Physiology 16, 109-117.

Verhagen L, Gallea C, Folloni D, Constans C, Jensen D, Ahnine H, Roumazeilles L, Santin M, Ahmed B, Lehericy S, Klein-Flügge M, Krug K, Mars RB, Rushworth MF, Pouget P, Aubry JF, Sallet J. 2019. Offline impact of transcranial focused ultrasound on cortical activation in primates. eLIFE 8:e40541.

Goals and prospects

A biologically plausible, quantitative model of cognitive brain mechanisms in non-human primates is essential for understanding the basic neural mechanisms of our own cognitive functions. The homology between macaque and human allows a direct transposition of neural architecture and computational models. The combination of approaches including high resolution neuroimaging, brain stimulation, neurophysiology and behaviour will provide a detailed, multi-level understanding of the neural mechanisms that shape decision-making. Specifically, integrative models of brain function should provide a comprehensive understanding of the structural and functional organisation of local and long-range brain networks and their interactions. Psychological disorders such as autism or schizophrenia have been associated with altered functional connectivity of specific neuronal networks. Therefore, the neurophysiological validation of FUS stimulation protocol represents a promising prospect toward the development of non-invasive therapeutic interventions and treatments in human to improve and restore human cognitive performances.

Publications of the project C05