Numerical Rule Coding in the Prefrontal, Premotor, and Posterior Parietal Cortices of Macaques

Switching flexibly between behavioral goals is a hallmark of executive control and requires integration of external and internal information. We recorded single-neuron correlates of different numerical representations (sensory-, working memory-, and rule-related activity) in the dorsal premotor area (PMd), the cingulate motor areas (CMA), and the ventral intraparietal sulcus (VIP) and compared them to previous recordings in the lateral prefrontal cortex (PFC). Two monkeys were trained to encode and memorize numerosities and flexibly switch between two abstract quantitative rules based on rule cues. Almost 20% of randomly selected PFC and PMd neurons significantly represented the numerical rule in a behaviorally relevant manner, approximately twice as many as in the CMA and VIP. Rule selectivity was significantly better for PMd neurons than for PFC cells. Seemingly at the expense of rule selectivity, however, sensory- and memory-related numerosity activity was greatly diminished compared with previous delayed match-to-numerosity studies. These findings suggest the involvement of the frontal premotor areas in strategic planning such as rule following. Moreover, the results emphasize that the coding capacities of neurons in association cortical areas are far more dynamic depending on task demands than previously thought.

[1]  P. Goldman-Rakic,et al.  Inactivation of parietal and prefrontal cortex reveals interdependence of neural activity during memory-guided saccades. , 2000, Journal of neurophysiology.

[2]  E. Miller,et al.  Analog Numerical Representations in Rhesus Monkeys: Evidence for Parallel Processing , 2004, Journal of Cognitive Neuroscience.

[3]  B. Milner.  Effects of Different Brain Lesions on Card Sorting: The Role of the Frontal Lobes , 1963 .

[4]  E. Miller,et al.  Neural Activity in the Primate Prefrontal Cortex during Associative Learning , 1998, Neuron.

[5]  A. Murata,et al.  Largely segregated parietofrontal connections linking rostral intraparietal cortex (areas AIP and VIP) and the ventral premotor cortex (areas F5 and F4) , 1999, Experimental Brain Research.

[6]  J. Fuster,et al.  Effects of cooling parietal cortex on prefrontal units in delay tasks , 1989, Brain Research.

[7]  H. Nelson.  A Modified Card Sorting Test Sensitive to Frontal Lobe Defects , 1976, Cortex.

[8]  E. Brannon,et al.  Nonverbal representation of time and number in adults. , 2007, Acta psychologica.

[9]  Jonathan D. Wallis,et al.  A Comparison of Abstract Rules in the Prefrontal Cortex, Premotor Cortex, Inferior Temporal Cortex, and Striatum , 2006, Journal of Cognitive Neuroscience.

[10]  A. Nieder,et al.  Complementary Contributions of Prefrontal Neuron Classes in Abstract Numerical Categorization , 2008, The Journal of Neuroscience.

[11]  A. Nieder.  Prefrontal cortex and the evolution of symbolic reference , 2009, Current Opinion in Neurobiology.

[12]  Paul B. Johnson,et al.  Premotor and parietal cortex: corticocortical connectivity and combinatorial computations. , 1997, Annual review of neuroscience.

[13]  E. Miller,et al.  From rule to response: neuronal processes in the premotor and prefrontal cortex. , 2003, Journal of neurophysiology.

[14]  Andreas Nieder,et al.  Behavioral and Prefrontal Representation of Spatial Proportions in the Monkey , 2008, Current Biology.

[15]  Andreas Nieder,et al.  Neuronal population coding of continuous and discrete quantity in the primate posterior parietal cortex , 2007, Proceedings of the National Academy of Sciences.

[16]  Philippe Pinel,et al.  Tuning Curves for Approximate Numerosity in the Human Intraparietal Sulcus , 2004, Neuron.

[17]  J. B. Preston,et al.  Interconnections between the prefrontal cortex and the premotor areas in the frontal lobe , 1994, The Journal of comparative neurology.

[18]  Andrew R. Mitz,et al.  Prefrontal Cortex Activity Related to Abstract Response Strategies , 2005, Neuron.

[19]  Andreas Nieder,et al.  A Labeled-Line Code for Small and Large Numerosities in the Monkey Prefrontal Cortex , 2007, The Journal of Neuroscience.

[20]  Andreas Nieder,et al.  Semantic Associations between Signs and Numerical Categories in the Prefrontal Cortex , 2007, PLoS biology.

[21]  D. Boussaoud,et al.  Parietal inputs to dorsal versus ventral premotor areas in the macaque monkey: evidence for largely segregated visuomotor pathways , 2002, Experimental Brain Research.

[22]  Keiji Tanaka,et al.  Conflict-induced behavioural adjustment: a clue to the executive functions of the prefrontal cortex , 2009, Nature Reviews Neuroscience.

[23]  D. Pandya,et al.  Comparative cytoarchitectonic analysis of the human and the macaque ventrolateral prefrontal cortex and corticocortical connection patterns in the monkey , 2002, The European journal of neuroscience.

[24]  S. Dehaene,et al.  Representation of number in the brain. , 2009, Annual review of neuroscience.

[25]  P. Strick,et al.  Motor areas in the frontal lobe of the primate , 2002, Physiology & Behavior.

[26]  J. Tanji,et al.  Neuronal activity in the primate prefrontal cortex in the process of motor selection based on two behavioral rules. , 2000, Journal of neurophysiology.

[27]  Timothy E. J. Behrens,et al.  Optimal decision making and the anterior cingulate cortex , 2006, Nature Neuroscience.

[28]  G. F. Tremblay,et al.  The Prefrontal Cortex , 1989, Neurology.

[29]  E. Miller,et al.  An integrative theory of prefrontal cortex function. , 2001, Annual review of neuroscience.

[30]  D. Stuss,et al.  Wisconsin Card Sorting Test performance in patients with focal frontal and posterior brain damage: effects of lesion location and test structure on separable cognitive processes , 2000, Neuropsychologia.

[31]  S. Dehaene,et al.  A Magnitude Code Common to Numerosities and Number Symbols in Human Intraparietal Cortex , 2007, Neuron.

[32]  K. Johnston,et al.  Top-Down Control-Signal Dynamics in Anterior Cingulate and Prefrontal Cortex Neurons following Task Switching , 2007, Neuron.

[33]  L. Snyder,et al.  Neural correlates of executive control functions in the monkey , 2009, Trends in Cognitive Sciences.

[34]  D. Pandya,et al.  Prefrontal cortex in relation to other cortical areas in rhesus monkey: architecture and connections. , 1990, Progress in brain research.

[35]  Jeffrey W. Cooney,et al.  Hierarchical cognitive control deficits following damage to the human frontal lobe , 2009, Nature Neuroscience.

[36]  G. Luppino,et al.  ß Federation of European Neuroscience Societies Prefrontal and agranular cingulate projections to the dorsal premotor areas F2 and F7 in the macaque monkey , 2022 .

[37]  D. Pandya,et al.  Architecture and intrinsic connections of the prefrontal cortex in the rhesus monkey , 1989, The Journal of comparative neurology.

[38]  R. Romo,et al.  Neuronal correlates of parametric working memory in the prefrontal cortex , 1999, Nature.

[39]  S. Wise,et al.  Rule-dependent neuronal activity in the prefrontal cortex , 1999, Experimental Brain Research.

[40]  David J. Freedman,et al.  Representation of the Quantity of Visual Items in the Primate Prefrontal Cortex , 2002, Science.

[41]  D. M. Green,et al.  Signal detection theory and psychophysics , 1966 .

[42]  David J Freedman.  Posterior Parietal Cortex Space…and Beyond , 2004, Neuron.

[43]  Philip G. F. Browning,et al.  Dissociable Components of Rule-Guided Behavior Depend on Distinct Medial and Prefrontal Regions , 2009, Science.

[44]  K. C. Anderson,et al.  Single neurons in prefrontal cortex encode abstract rules , 2001, Nature.

[45]  J. Tanji,et al.  Numerical representation for action in the parietal cortex of the monkey , 2002, Nature.

[46]  Keiji Tanaka,et al.  Effects of novelty on activity of lateral and medial prefrontal neurons , 2007, Neuroscience Research.

[47]  Stefan Everling,et al.  Theta-activity in anterior cingulate cortex predicts task rules and their adjustments following errors , 2010, Proceedings of the National Academy of Sciences.

[48]  D. Pandya,et al.  Architecture and frontal cortical connections of the premotor cortex (area 6) in the rhesus monkey , 1987, The Journal of comparative neurology.

[49]  Andreas Nieder,et al.  Contributions of primate prefrontal and posterior parietal cortices to length and numerosity representation. , 2009, Journal of neurophysiology.

[50]  R. Andersen,et al.  Multimodal representation of space in the posterior parietal cortex and its use in planning movements. , 1997, Annual review of neuroscience.

[51]  Lawrence H Snyder,et al.  Single Neurons in Posterior Parietal Cortex of Monkeys Encode Cognitive Set , 2004, Neuron.

[52]  Andreas Nieder,et al.  Basic mathematical rules are encoded by primate prefrontal cortex neurons , 2010, Proceedings of the National Academy of Sciences.

[53]  T. Paus.  Primate anterior cingulate cortex: Where motor control, drive and cognition interface , 2001, Nature Reviews Neuroscience.

[54]  Andreas Nieder,et al.  Representations of visual proportions in the primate posterior parietal and prefrontal cortices , 2010, The European journal of neuroscience.

[55]  Andreas Nieder,et al.  Temporal and Spatial Enumeration Processes in the Primate Parietal Cortex , 2006, Science.

[56]  David J. Freedman,et al.  Distinct Encoding of Spatial and Nonspatial Visual Information in Parietal Cortex , 2009, The Journal of Neuroscience.

[57]  N. R. Franks,et al.  Chimpanzees and the mathematics of battle , 2002, Proceedings of the Royal Society of London. Series B: Biological Sciences.

[58]  Keiji Tanaka,et al.  Mnemonic Function of the Dorsolateral Prefrontal Cortex in Conflict-Induced Behavioral Adjustment , 2007, Science.

[59]  J. Tanji,et al.  Distinctions between dorsal and ventral premotor areas: anatomical connectivity and functional properties , 2007, Current Opinion in Neurobiology.