BRAIN-WIDE COMPUTATIONS DURING DECISION-MAKING

Mrsic-Flogel Lab

Research Area

Decisions are an integral part of our lives and we make thousands of them every day, often under conditions of uncertainty. We want to explain how the brain makes decisions by combining sensory information with previously learned knowledge.

Research Topics

The way we think of the decision process is that the brain dynamically updates an inferred state of the outside world by sensory evidence and prior knowledge. This inferred neural representation feeds into a decision processes that selects potential actions that will maximise favourable outcomes, which have been previously evaluated by learning. We know very little about how this inferred state of the world is represented in the brain, and how is it updated by sensory evidence and expectations before committing to a decision. 


Decision processes are likely managed by a network of interconnected brain areas. Previous work, including our own, has given ideas how different brain structures map onto these decision processes, and how they might interact with each other. For example, the frontal-premotor cortex is a key node for decision making because its activity reflects the evolving decision variable, it is the first area active prior to choice and its inactivation results in failures to commit to choices. Although historically, decision making has been studied almost exclusively in the neocortex, we have good reasons to believe that subcortical structures play a key role is decision-relevant computations. These include a set of inhibitory nuclei in the basal ganglia which may contribute to evaluation of sensory information and learning of goal directed actions, and expectation, as well as the cerebellum which - as we have recently discovered - plays an unexpected role influencing the timing of activity in premotor cortex during movement planning (Chabrol et al 2019). 
 

Interconnected brain areas used in visual processing

We now aim to determine how distributed regions of the brain work together to combine ambiguous sensory evidence with prior knowledge, and how they transform it into action plans, with a particular focus on local circuits and long-range mechanisms. With this in mind, have developed a new perceptual decision-making task in mice designed to probe brain-wide mechanisms of decision making under conditions of uncertainty. This task allows us to uncover the computations leading up to a decision devoid of motor confounds, and to reveal how behaviourally-relevant sensory information is transformed across the brain to drive choice. We study these processes in mice because we can make use advanced techniques to record and manipulate identified circuits in the brain during behaviour (2-photon and 3-photon imaging, Neuropixels multi-channel recordings, widefield calcium imaging, regional and cell-type specific activity manipulations with optogenetics, circuit mapping). The aim is to integrate neural and behavioural data into a mechanistic model that explains decision-related neural dynamics leading to choice commitment (collaboration with P. Latham and M. Sahani, GCNU).

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Tom Mrsic-Flogel
Professor of Neuroscience & Director
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Jai Bhagat
PhD Student
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Tadej Bozic
Senior Research Technician
Ryan Cini
Research Technician
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Hannah Davies
Research Technician
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Shohei Furutachi
Senior Research Fellow
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Naureen Ghani
PhD Student
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Ben Jerry Gonzales
Research Fellow
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Diksha Gupta
Senior Research Fellow
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Morio Hamada
PhD Student
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Takahiro Kanamori
Senior Research Fellow
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Andrei Khilkevich
Research Fellow
Jesse Krichefski
Research Assistant
Sumiya Kuroda
PhD Student, Optical Biology
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Michelle Li
Laboratory Manager
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Michael Lohse
Sir Henry Wellcome Postdoctoral Fellow
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Marta Maciel
PhD Student
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Nate Miska
Senior Research Fellow
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Svenja Nierwetberg
Research Fellow
Sandra Reinert
Senior Research Fellow
Selected publications

Brain-wide dynamics linking sensation to action during decision-making

Khilkevich A, Lohse M, Low R, Orsolic I, Bozic T, Windmill P & Mrsic-Flogel TD
Published by:
Nature (doi: https://doi.org/10.1038/s41586-024-07908-w)
11 September 2024

Cortical feedback loops bind distributed representations of working memory

Voitov I, Mrsic-Flogel TD
Published by:
Nature (doi: 10.1038/s41586-022-05014-3)
27 July 2022

The sensory representation of causally controlled objects

Clancy KB, Mrsic-Flogel TD
Published by:
Neuron (109: 677-689) (doi: 10.1016/j.neuron.2020.12.001)
22 December 2020

Cerebellar Contribution to Preparatory Activity in Motor Neocortex

Chabrol F, Blot A, Mrsic-Flogel TD
Published by:
Neuron (103: 506-519) (doi: 10.1016/j.neuron.2019.05.022)
11 March 2019

Locomotion-dependent remapping of distributed cortical networks

Clancy KB, Orsolic I, Mrsic-Flogel TD
Published by:
Nature Neuroscience (22: 778-786) (doi: 10.1038/s41593-019-0357-8)
11 March 2019

Mesoscale cortical dynamics reflect the interaction of sensory evidence and temporal expectation during perceptual decision-making

Orsolic I, Rio M, Mrsic-Flogel TD, Znamenskiy P
Published by:
Neuron (109: 1861-1875) (doi: 10.1016/j.neuron.2021.03.031)
15 February 2019

Segregated Subnetworks of Intracortical Projection Neurons in Primary Visual Cortex

Kim M, Znamenskiy P, Iacaruso MF, Mrsic-Flogel TD
Published by:
Neuron (100: 1313-1321) (doi: 10.1016/j.neuron.2018.10.023)
08 November 2018

The logic of single-cell projections from visual cortex

Han Y, Kebschull JM, Campbell RAA, Cowan D, Imhof F, Zador AM, Mrsic-Flogel TD
Published by:
Nature (556: 51-56) (doi: 10.1038/nature26159)
05 April 2018

Functional organization of excitatory synaptic strength in primary visual cortex

Cossell L, Iacaruso MF, Muir DR, Houlton R, Sader EN, Ko H, Hofer S, Mrsic-Flogel TD
Published by:
Nature (518: 399–403) (doi: 10.1038/nature14182)
19 February 2015