Working with memory: evidence for a role for the medial prefrontal cortex in performance monitoring during spatial delayed alternation.

Neuronal spike activity was recorded in the medial prefrontal cortex (mPFC) as rats performed an operant spatial delayed alternation task. The sensitivities of neurons to choice, outcome, and temporal information-related aspects of the task were examined. About one-third of neurons were sensitive to the location of delayed responding while animals were at one of two spatially distinct response ports. However, many fewer neurons (<10%) maintained choice information over the delay, each exhibiting persistent differences in firing rates for only a portion of the delay. Another third of cells encoded information about behavioral outcomes, and some of these neurons (>20% of all cells) fired at distinct rates in advance of correct and incorrect responses (i.e., prospective encoding of outcome). Other cells were sensitive to reward-related feedback stimuli (>20%), the outcome of the preceding trial (retrospective encoding, 5-10%), and/or the time since a trial was last performed (10-20%). An anatomical analysis of the recording sites found that cells that were sensitive to choice, temporal, and outcome information were commingled within the middle layers of the mPFC. Together, our results suggest that spatial processing is only part of what drives mPFC neurons to become active during spatial working memory tasks. We propose that the primary role of mPFC in these tasks is to monitor behavioral performance by encoding information about recent trial outcomes to guide expectations and responses on the current trial. By encoding these variables, the mPFC is able to exert control over action and ensure that tasks are performed effectively and efficiently.

[1]  K. Pribram,et al.  Analysis of the effects of frontal lesions in monkey. II. Variations of delayed response. , 1956, Journal of comparative and physiological psychology.

[2]  T. Preuss Do Rats Have Prefrontal Cortex? The Rose-Woolsey-Akert Program Reconsidered , 1995, Journal of Cognitive Neuroscience.

[3]  Eldon Emberly,et al.  Action and outcome activity state patterns in the anterior cingulate cortex. , 2013, Cerebral cortex.

[4]  D. B. Mitchell,et al.  The handbook of aging and cognition , 2001 .

[5]  Daniel Durstewitz,et al.  Comparing the prefrontal cortex of rats and primates: Insights from electrophysiology , 2008, Neurotoxicity Research.

[6]  L. Chen,et al.  Neuronal responses in the frontal cortico-basal ganglia system during delayed matching-to-sample task: ensemble recording in freely moving rats , 2001, Experimental Brain Research.

[7]  A. S. Batuev,et al.  Unit activity of the medial wall of the frontal cortex during delayed performance in rats , 1990, Behavioural Brain Research.

[8]  M. Laubach,et al.  Lost in Transition: Aging-Related Changes in Executive Control by the Medial Prefrontal Cortex , 2012, The Journal of Neuroscience.

[9]  H. Niki,et al.  Prefrontal cortical unit activity and delayed alternation performance in monkeys. , 1971, Journal of neurophysiology.

[10]  C. V. van Eden,et al.  Acquisition of conditional associations and operant delayed spatial response alternation: effects of lesions in the medial prefrontal cortex. , 1988, Behavioral neuroscience.

[11]  D. Stuss,et al.  Staying on the job: the frontal lobes control individual performance variability. , 2003, Brain : a journal of neurology.

[12]  F. Vanhaaren,et al.  Acquisition of conditional associations and operant delayed spatial response alternation: effects of lesions in the medial prefrontal cortex. , 1988 .

[13]  K. Pribram,et al.  Analysis of the effects of frontal lesions in monkey. I. Variations of delayed alternation. , 1955, Journal of comparative and physiological psychology.

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

[15]  R. Passingham,et al.  The functions of the medial premotor cortex , 2004, Experimental Brain Research.

[16]  Michael E. Ragozzino,et al.  "Differential involvement of the dorsal anterior cingulate and prelimbic-infralimbic areas of the rodent prefrontal cortex in spatial working memory": Correction to Ragozzino et al. (1998). , 1998 .

[17]  M. Jung,et al.  Dynamics of Population Code for Working Memory in the Prefrontal Cortex , 2003, Neuron.

[18]  J. Aggleton,et al.  Spontaneous object recognition and object location memory in rats: the effects of lesions in the cingulate cortices, the medial prefrontal cortex, the cingulum bundle and the fornix , 1997, Experimental Brain Research.

[19]  Bruce L McNaughton,et al.  Selective delay activity in the medial prefrontal cortex of the rat: contribution of sensorimotor information and contingency. , 2007, Journal of neurophysiology.

[20]  Mark Laubach A Comparative Perspective on Executive and Motivational Control by the Medial Prefrontal Cortex , 2011 .

[21]  K. Pribram,et al.  An experimental critique of the effects of anterior cingulate ablations in monkey. , 1954, Brain : a journal of neurology.

[22]  Morris Moscovitch,et al.  The neuropsychology of memory and aging. , 1992 .

[23]  D. S. Olton,et al.  Effects of fornix transection and cingulate cortical ablation on spatial memory in rhesus monkeys , 2004, Experimental Brain Research.

[24]  J. Muir,et al.  A behavioural analysis of the delayed non-matching to position task: the effects of scopolamine, lesions of the fornix and of the prelimbic region on mediating behaviours by rats , 1997, Psychopharmacology.

[25]  G. N. Brito,et al.  Prelimbic cortex, mediodorsal thalamus, septum, and delayed alternation in rats , 2004, Experimental Brain Research.

[26]  Mark Laubach,et al.  Neuronal correlates of post-error slowing in the rat dorsomedial prefrontal cortex. , 2008, Journal of neurophysiology.

[27]  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.

[28]  P. Gisquet-Verrier,et al.  The role of the rat prelimbic/infralimbic cortex in working memory: Not involved in the short-term maintenance but in monitoring and processing functions , 2006, Neuroscience.

[29]  Timothy E. J. Behrens,et al.  Review Frontal Cortex and Reward-guided Learning and Decision-making Figure 1. Frontal Brain Regions in the Macaque Involved in Reward-guided Learning and Decision-making Finer Grained Anatomical Divisions with Frontal Cortical Systems for Reward-guided Behavior , 2022 .

[30]  Bruce L McNaughton,et al.  Apparent Encoding of Sequential Context in Rat Medial Prefrontal Cortex Is Accounted for by Behavioral Variability , 2006, The Journal of Neuroscience.

[31]  H. Eichenbaum,et al.  Hippocampal “Time Cells” Bridge the Gap in Memory for Discontiguous Events , 2011, Neuron.

[32]  K. A. Hadland,et al.  The Effect of Cingulate Cortex Lesions on Task Switching and Working Memory , 2003, Journal of Cognitive Neuroscience.

[33]  K. Pribram,et al.  Effects of lesions of the medial forebrain on alternation behavior of rhesus monkeys. , 1962, Experimental neurology.

[34]  Asohan Amarasingham,et al.  Internally Generated Cell Assembly Sequences in the Rat Hippocampus , 2008, Science.

[35]  P. Gisquet-Verrier,et al.  Prelimbic cortex specific lesions disrupt delayed-variable response tasks in the rat. , 1996, Behavioral neuroscience.

[36]  R P Kesner,et al.  Differential involvement of the dorsal anterior cingulate and prelimbic-infralimbic areas of the rodent prefrontal cortex in spatial working memory. , 1998, Behavioral neuroscience.

[37]  H. E. Rosvold,et al.  Analysis of the delayed-alternation deficit produced by dorsolateral prefrontal lesions in the rhesus monkey. , 1971, Journal of comparative and physiological psychology.

[38]  B. McNaughton,et al.  Firing characteristics of deep layer neurons in prefrontal cortex in rats performing spatial working memory tasks. , 1998, Cerebral cortex.

[39]  M. Laubach,et al.  The role of rat dorsomedial prefrontal cortex in spatial working memory , 2009, Neuroscience.

[40]  G. E. Alexander,et al.  Neuron Activity Related to Short-Term Memory , 1971, Science.

[41]  P. J. Brasted,et al.  Medial prefrontal and neostriatal lesions disrupt performance in an operant delayed alternation task in rats , 1999, Behavioural Brain Research.

[42]  P. Gisquet-Verrier,et al.  Involvement of the dorsal anterior cingulate cortex in temporal behavioral sequencing: subregional analysis of the medial prefrontal cortex in rat , 2001, Behavioural Brain Research.