Movement-related activity dominates cortex during sensory-guided decision making

An animal’s movements and internal state generate an “internal backdrop” of activity that is dynamically modulated. During behavior, this internal backdrop interacts with signals arising from incoming sensory stimuli and may have a substantial impact on task-related computations, like those underlying decision-making. To understand the joint effects of internal backdrop and task-imposed variables, we measured neural activity across the entire dorsal cortex of task-performing mice. We characterized internal backdrop using multiple measures of self-generated parameters including pupil diameter, whisking and body motion. Surprisingly, internal backdrop dominated neural activity across the entire cortex, dwarfing task-related variables and even sensory stimuli. Single neurons in frontal cortex were likewise dominated by internal backdrop. A linear model allowed us to account for multiple dimensions of internal backdrop and uncover hidden signatures of task-related activity. We show that complex, ongoing behavior fundamentally shapes neural activity throughout cortex and must be accounted for when studying decision-making. Highlights We imaged cortex-wide neural activity during auditory and visual decisions in mice. Cortical activity was surprisingly similar during sensory-guided versus random decisions. Movement and state variables vastly outperformed task variables in predicting neural activity. A linear model revealed hidden task-related activity in brain areas and single neurons.

[1]  Nicholas A. Steinmetz,et al.  Spontaneous behaviors drive multidimensional, brainwide activity , 2019, Science.

[2]  Georg B. Keller,et al.  Predictive Processing: A Canonical Cortical Computation , 2018, Neuron.

[3]  Ashley L. Juavinett,et al.  Chronically implanted Neuropixels probes enable high-yield recordings in freely moving mice , 2018, bioRxiv.

[4]  Kevin M. Cury,et al.  DeepLabCut: markerless pose estimation of user-defined body parts with deep learning , 2018, Nature Neuroscience.

[5]  F. Helmchen,et al.  Behavioral Strategy Determines Frontal or Posterior Location of Short-Term Memory in Neocortex , 2018, Neuron.

[6]  George Karabatsos,et al.  Marginal maximum likelihood estimation methods for the tuning parameters of ridge, power ridge, and generalized ridge regression , 2018, Commun. Stat. Simul. Comput..

[7]  Mikhail Kislin,et al.  Fast animal pose estimation using deep neural networks , 2018, Nature Methods.

[8]  Itai Cohen,et al.  Motor cortical inactivation reduces the gain of kinematic primitives in mice performing a hold-still center-out reach task , 2018, bioRxiv.

[9]  Joel Z. Leibo,et al.  Prefrontal cortex as a meta-reinforcement learning system , 2018, bioRxiv.

[10]  Matthias Bethge,et al.  DeepLabCut: markerless pose estimation of user-defined body parts with deep learning , 2018, Nature Neuroscience.

[11]  C. Gerfen,et al.  Activation of Striatal Neurons Causes a Perceptual Decision Bias during Visual Change Detection in Mice , 2018, Neuron.

[12]  Kenneth D. Harris,et al.  Effects of Arousal on Mouse Sensory Cortex Depend on Modality , 2018, Cell reports.

[13]  A. Ayaz,et al.  Layer-specific integration of locomotion and concurrent wall touching in mouse barrel cortex , 2018, bioRxiv.

[14]  Amy M. Ni,et al.  Learning and attention reveal a general relationship between population activity and behavior , 2018, Science.

[15]  C. Petersen,et al.  Reward-Based Learning Drives Rapid Sensory Signals in Medial Prefrontal Cortex and Dorsal Hippocampus Necessary for Goal-Directed Behavior , 2018, Neuron.

[16]  Ben Deverett,et al.  An Accumulation-of-Evidence Task Using Visual Pulses for Mice Navigating in Virtual Reality , 2017, bioRxiv.

[17]  Sergey L. Gratiy,et al.  Fully integrated silicon probes for high-density recording of neural activity , 2017, Nature.

[18]  Georg B. Keller,et al.  A Sensorimotor Circuit in Mouse Cortex for Visual Flow Predictions , 2017, Neuron.

[19]  Carlos D. Brody,et al.  Fronto-parietal Cortical Circuits Encode Accumulated Evidence with a Diversity of Timescales , 2017, Neuron.

[20]  Stefano Panzeri,et al.  Distinct timescales of population coding across cortex , 2017, Nature.

[21]  V. Gradinaru,et al.  Engineered AAVs for efficient noninvasive gene delivery to the central and peripheral nervous systems , 2017, Nature Neuroscience.

[22]  William E. Allen,et al.  Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex , 2017, Neuron.

[23]  Tsai-Wen Chen,et al.  A Map of Anticipatory Activity in Mouse Motor Cortex , 2017, Neuron.

[24]  Elina A K Jacobs,et al.  Aberrant Cortical Activity in Multiple GCaMP6-Expressing Transgenic Mouse Lines , 2017, eNeuro.

[25]  Zengcai V. Guo,et al.  Maintenance of persistent activity in a frontal thalamocortical loop , 2017, Nature.

[26]  Ralf D. Wimmer,et al.  Thalamic amplification of cortical connectivity sustains attentional control , 2017, Nature.

[27]  Hye-Won Jeong,et al.  A Neural Circuit for Auditory Dominance over Visual Perception , 2017, Neuron.

[28]  Dmitriy Aronov,et al.  Mapping of a non-spatial dimension by the hippocampal/entorhinal circuit , 2017, Nature.

[29]  Yang Li,et al.  An extended retinotopic map of mouse cortex , 2017, eLife.

[30]  César Caballero-Gaudes,et al.  Methods for cleaning the BOLD fMRI signal , 2016, NeuroImage.

[31]  Jessica A. Cardin,et al.  Developmental Dysfunction of VIP Interneurons Impairs Cortical Circuits , 2016, Neuron.

[32]  A. Zador,et al.  A self-initiated two-alternative forced choice paradigm for head-fixed mice , 2016, bioRxiv.

[33]  Matthew T. Kaufman,et al.  Posterior Parietal Cortex Guides Visual Decisions in Rats , 2016, The Journal of Neuroscience.

[34]  Mario Dipoppa,et al.  Suite2p: beyond 10,000 neurons with standard two-photon microscopy , 2016, bioRxiv.

[35]  Tatiana A. Engel,et al.  Selective modulation of cortical state during spatial attention , 2016, Science.

[36]  Ari S. Morcos,et al.  History-dependent variability in population dynamics during evidence accumulation in cortex , 2016, Nature Neuroscience.

[37]  Matteo Carandini,et al.  Kilosort: realtime spike-sorting for extracellular electrophysiology with hundreds of channels , 2016, bioRxiv.

[38]  Dario L Ringach,et al.  Enhanced Spatial Resolution During Locomotion and Heightened Attention in Mouse Primary Visual Cortex , 2016, The Journal of Neuroscience.

[39]  Jonathan W. Pillow,et al.  Dissociated functional significance of decision-related activity in the primate dorsal stream , 2016, Nature.

[40]  Justin L. Gardner,et al.  Adaptable history biases in human perceptual decisions , 2016, Proceedings of the National Academy of Sciences.

[41]  Denise M. Piscopo,et al.  Large-scale imaging of cortical dynamics during sensory perception and behavior. , 2016, Journal of neurophysiology.

[42]  Masato Inoue,et al.  Error Signals in Motor Cortices Drive Adaptation in Reaching , 2016, Neuron.

[43]  Mriganka Sur,et al.  Distinct roles of visual, parietal, and frontal motor cortices in memory-guided sensorimotor decisions , 2016, eLife.

[44]  Ryan P. Adams,et al.  Mapping Sub-Second Structure in Mouse Behavior , 2015, Neuron.

[45]  Talia N. Lerner,et al.  Intact-Brain Analyses Reveal Distinct Information Carried by SNc Dopamine Subcircuits , 2015, Cell.

[46]  M. Häusser,et al.  Synaptic representation of locomotion in single cerebellar granule cells , 2015, eLife.

[47]  Ashesh K Dhawale,et al.  Motor Cortex Is Required for Learning but Not for Executing a Motor Skill , 2015, Neuron.

[48]  Russell A. Poldrack,et al.  Orthogonalization of Regressors in fMRI Models , 2015, PloS one.

[49]  David J. Freedman,et al.  Choice-correlated activity fluctuations underlie learning of neuronal category representation , 2015, Nature Communications.

[50]  Zengcai V. Guo,et al.  A motor cortex circuit for motor planning and movement , 2015, Nature.

[51]  Bingni W. Brunton,et al.  Distinct effects of prefrontal and parietal cortex inactivations on an accumulation of evidence task in the rat , 2015, bioRxiv.

[52]  M. Sahani,et al.  State-Dependent Population Coding in Primary Auditory Cortex , 2015, The Journal of Neuroscience.

[53]  Nicholas A. Steinmetz,et al.  Diverse coupling of neurons to populations in sensory cortex , 2015, Nature.

[54]  Bingni W. Brunton,et al.  Distinct relationships of parietal and prefrontal cortices to evidence accumulation , 2014, Nature.

[55]  Martin Vinck,et al.  Arousal and Locomotion Make Distinct Contributions to Cortical Activity Patterns and Visual Encoding , 2014, Neuron.

[56]  M. Goldberg,et al.  Memory-Guided Saccade to a Distractor Flashed During the Delay Period of a Response of Neurons in the Lateral Intraparietal Area , 2015 .

[57]  Matthew T. Kaufman,et al.  A category-free neural population supports evolving demands during decision-making , 2014, Nature Neuroscience.

[58]  George H. Denfield,et al.  Pupil Fluctuations Track Fast Switching of Cortical States during Quiet Wakefulness , 2014, Neuron.

[59]  Ian Nauhaus,et al.  Topography and Areal Organization of Mouse Visual Cortex , 2014, The Journal of Neuroscience.

[60]  R. Mooney,et al.  A synaptic and circuit basis for corollary discharge in the auditory cortex , 2014, Nature.

[61]  Il Memming Park,et al.  Encoding and decoding in parietal cortex during sensorimotor decision-making , 2014, Nature Neuroscience.

[62]  Zengcai V. Guo,et al.  Flow of Cortical Activity Underlying a Tactile Decision in Mice , 2014, Neuron.

[63]  M. Carandini,et al.  Integration of visual motion and locomotion in mouse visual cortex , 2013, Nature Neuroscience.

[64]  P. Golshani,et al.  Cellular mechanisms of brain-state-dependent gain modulation in visual cortex , 2013, Nature Neuroscience.

[65]  F. Helmchen,et al.  Behaviour-dependent recruitment of long-range projection neurons in somatosensory cortex , 2013, Nature.

[66]  Zengcai V. Guo,et al.  Neural coding during active somatosensation revealed using illusory touch , 2013, Nature Neuroscience.

[67]  M. Carandini,et al.  Locomotion Controls Spatial Integration in Mouse Visual Cortex , 2013, Current Biology.

[68]  David J. Freedman,et al.  Independent Category and Spatial Encoding in Parietal Cortex , 2013, Neuron.

[69]  Jay A. Hennig,et al.  Signal Multiplexing and Single-Neuron Computations in Lateral Intraparietal Area During Decision-Making , 2013, The Journal of Neuroscience.

[70]  Georg B. Keller,et al.  Sensorimotor Mismatch Signals in Primary Visual Cortex of the Behaving Mouse , 2012, Neuron.

[71]  Robert L. Heath Learning and Attention , 2012 .

[72]  Christopher D. Harvey,et al.  Choice-specific sequences in parietal cortex during a virtual-navigation decision task , 2012, Nature.

[73]  James H. Marshel,et al.  Functional Specialization of Seven Mouse Visual Cortical Areas , 2011, Neuron.

[74]  Jeffrey C. Erlich,et al.  A Cortical Substrate for Memory-Guided Orienting in the Rat , 2011, Neuron.

[75]  K. Harris,et al.  Cortical state and attention , 2011, Nature Reviews Neuroscience.

[76]  Hongbo Jia,et al.  In vivo two-photon imaging of sensory-evoked dendritic calcium signals in cortical neurons , 2011, Nature Protocols.

[77]  M. Stryker,et al.  Modulation of Visual Responses by Behavioral State in Mouse Visual Cortex , 2010, Neuron.

[78]  Hatim A. Zariwala,et al.  Neural correlates, computation and behavioural impact of decision confidence , 2008, Nature.

[79]  R. Wurtz,et al.  Brain circuits for the internal monitoring of movements. , 2008, Annual review of neuroscience.

[80]  M. Shadlen,et al.  Decision-making with multiple alternatives , 2008, Nature Neuroscience.

[81]  F. Haiss,et al.  Spatiotemporal Dynamics of Cortical Sensorimotor Integration in Behaving Mice , 2007, Neuron.

[82]  Matthew S. Cain,et al.  Neural Activity Is Modulated by Trial History: A Functional Magnetic Resonance Imaging Study of the Effects of a Previous Antisaccade , 2007, The Journal of Neuroscience.

[83]  David J. Freedman,et al.  Experience-dependent representation of visual categories in parietal cortex , 2006, Nature.

[84]  J. Assad,et al.  A cognitive signal for the proactive timing of action in macaque LIP , 2006, Nature Neuroscience.

[85]  C. Petersen,et al.  Correlating whisker behavior with membrane potential in barrel cortex of awake mice , 2006, Nature Neuroscience.

[86]  S. Sara,et al.  Reward expectation, orientation of attention and locus coeruleus‐medial frontal cortex interplay during learning , 2004, The European journal of neuroscience.

[87]  W. Newsome,et al.  Representation of an abstract perceptual decision in macaque superior colliculus. , 2004, Journal of neurophysiology.

[88]  James W Bisley,et al.  Activity of neurons in cortical area MT during a memory for motion task. , 2004, Journal of neurophysiology.

[89]  J. Gold,et al.  The Influence of Behavioral Context on the Representation of a Perceptual Decision in Developing Oculomotor Commands , 2003, The Journal of Neuroscience.

[90]  M. Shadlen,et al.  Response of Neurons in the Lateral Intraparietal Area during a Combined Visual Discrimination Reaction Time Task , 2002, The Journal of Neuroscience.

[91]  S. Mizumori,et al.  Neurons in rat medial prefrontal cortex show anticipatory rate changes to predictable differential rewards in a spatial memory task , 2001, Behavioural Brain Research.

[92]  N. P. Bichot,et al.  Effects of similarity and history on neural mechanisms of visual selection , 1999, Nature Neuroscience.

[93]  D. Wolpert,et al.  Internal models in the cerebellum , 1998, Trends in Cognitive Sciences.

[94]  W. Schultz Dopamine neurons and their role in reward mechanisms , 1997, Current Opinion in Neurobiology.

[95]  M N Shadlen,et al.  Motion perception: seeing and deciding. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[96]  A. Grinvald,et al.  A tandem-lens epifluorescence macroscope: Hundred-fold brightness advantage for wide-field imaging , 1991, Journal of Neuroscience Methods.