Elsevier

Neuroscience

Volume 146, Issue 3, 25 May 2007, Pages 1082-1108
Neuroscience

Cognitive neuroscience
Variability in neuronal activity in primate cortex during working memory tasks

https://doi.org/10.1016/j.neuroscience.2006.12.072Get rights and content

Abstract

Persistent elevated neuronal activity has been identified as the neuronal correlate of working memory. It is generally assumed in the literature and in computational and theoretical models of working memory that memory-cell activity is stable and replicable; however, this assumption may be an artifact of the averaging of data collected across trials, and needs experimental verification. In this study, we introduce a classification scheme to characterize the firing frequency trends of cells recorded from the cortex of monkeys during performance of working memory tasks. We examine the frequency statistics and variability of firing during baseline and memory periods. We also study the behavior of cells on individual trials and across trials, and explore the stability of cellular firing during the memory period. We find that cells from different firing-trend classes possess markedly different statistics. We also find that individual cells show substantial variability in their firing behavior across trials, and that firing frequency also varies markedly over the course of a single trial. Finally, the average frequency distribution is wider, the magnitude of the frequency increases from baseline to memory smaller, and the magnitude of frequency decreases larger than is generally assumed. These results may serve as a guide in the evaluation of current theories of the cortical mechanisms of working memory.

Section snippets

Single unit recording

The database for this study consists of 961 cells. In that sample, there are 521 parietal cells recorded from areas 2, 3, 5, and 7 of one monkey during performance of a haptic delayed-matching task (Zhou and Fuster, 1996); 291 prefrontal cells recorded from areas 6, 8, 9 and 46 of another monkey during performance of a CM audiovisual task (Bodner et al 1996, Fuster et al 2000); and 149 prefrontal cells recorded primarily from area 9 and the dorsal portion of area 46 of a third monkey during

Statistics by memoranda

Unless otherwise noted, the analyses presented in the Results section were conducted in a memorandum-specific manner (see Experimental Procedures). The cell-specific responses to each memorandum were pooled together (see Experimental Procedures). The results of the analysis on the pooled data are presented below. A summary of the major statistical results for the various analysis described in detail below is shown in Table 2. Detailed statistical summaries are presented in the appendix.

Parietal

In

Systematic fluctuations over trials

To address the question of whether there are systematic fluctuations over trial number, two additional analyses were performed. First, we assessed the correlation of the delay period AF on consecutive trials in cells showing significant delay-activated memorandum-specific responses (see Experimental Procedures). The distribution of consecutive-trial correlation coefficients for all three datasets is presented in Fig. 9a. In parietal cortex, substantial numbers of cells showed high

Inter-trial variability and population averaging

To address the question of how the variability in the response across trials is related to the size of the population, we generated population firing rate data for populations ranging in size from 1 cell to 109 cells, 10,000 times for each population size (see Experimental Procedures). The mean population firing rate for all population sizes was between 21.7 and 21.8 Hz. The results for the SD of the population firing rate are presented in Fig. 10. The CV (SD/mean) of the population firing rate

Discussion

In the present study we have shown that the cellular average frequency distributions are broad during both the baseline and delay periods of a working memory task. During the delay period of working memory tasks, cells with significant inhibitory or excitatory changes in average frequency (relative to baseline) are common, at least in parietal cortex. Although these delay-period changes can be large (>10 Hz), most are generally small (<5 Hz), especially in prefrontal cortex. Typically, large

Conclusions

In this study, we have characterized the frequency behavior of cortical cells in working memory tasks. The statistics and variability of cortical firing suggest that the mnemonic retention of stimuli is achieved by widely distributed, multifunctional cortical networks that vary substantially in both their composition and behavior across multiple trials; no reliable, distinct, memory-related bistable states could be clearly identified. These conclusions are based on the identification of cells

Acknowledgments

We thank William Bergerson and Bradford Lubell for technical support. We also acknowledge David Rex for his help in the use of the LONI Pipeline Processing Environment (NIH/NCRR 2 P41 RR13642) used in carrying out the frequency analysis. This work was supported by NIMH grants MH-25082 and MH-51697, a grant from the Whitehall Foundation, and by the MIND Institute. C. Chow was supported by NIMH grant MH-01508, and a grant from the Sloan Foundation.

References (100)

  • J. Quintana et al.

    Prefrontal representation of stimulus attributes during delay tasksI. Unit activity in cross-temporal integration of sensory and sensory-motor information

    Brain Res

    (1988)
  • A. Renart et al.

    Robust spatial working memory through homeostatic synaptic scaling in heterogeneous cortical networks

    Neuron

    (2003)
  • D.E. Rex et al.

    The LONI pipeline processing environment

    Neuroimage

    (2003)
  • S. Tanaka

    Dopamine controls fundamental cognitive operations of multi-target spatial working memory

    Neural Netw

    (2002)
  • M. Abeles et al.

    Cortical activity flips among quasi-stationary states

    Proc Natl Acad Sci U S A

    (1995)
  • D.J. Amit

    Modeling brain function: The world of attractor neural networks

    (1989)
  • D.J. Amit

    The Hebbian paradigm reintegrated: local reverberations as internal representation

    Behav Brain Sci

    (1995)
  • D.J. Amit et al.

    Model of global spontaneous activity and local structured activity during delay periods in the cerebral cortex

    Cereb Cortex

    (1997)
  • D.J. Amit et al.

    Dynamics of a recurrent network of spiking neurons before and following learning

    Network

    (1997)
  • D.J. Amit et al.

    Multiple-object working memory: A model for behavioral performance

    Cereb Cortex

    (2003)
  • R.A. Andersen et al.

    Eye position effects on visual, memory, and saccade-related activity in areas LIP and 7a of macaque

    J Neurosci

    (1990)
  • S. Barash et al.

    Saccade-related activity in the lateral intraparietal areaI. Temporal properties; comparison with area 7a

    J Neurophysiol

    (1991)
  • M. Bodner et al.

    Auditory memory cells in dorsolateral prefrontal cortex

    Neuroreport

    (1996)
  • M. Bodner et al.

    Symmetric temporal patterns in cortical spike trains during performance of a short-term memory task

    Neurol Res

    (1997)
  • C.D. Brody et al.

    Timing and neural encoding of somatosensory parametric working memory in macaque prefrontal cortex

    Cereb Cortex

    (2003)
  • N. Brunel

    Persistent activity and the single-cell frequency-current curve in a cortical network model

    Network

    (2000)
  • N. Brunel

    Dynamics of sparsely connected networks of excitatory and inhibitory spiking neurons

    J Comput Neurosci

    (2000)
  • N. Brunel

    Dynamics and plasticity of stimulus-selective persistent activity in cortical network models

    Cereb Cortex

    (2003)
  • N. Brunel et al.

    Effects of neuromodulation in a cortical network model of object working memory dominated by recurrent inhibition

    J Comput Neurosci

    (2001)
  • M. Camperi et al.

    A model of visuospatial working memory in prefrontal cortex: recurrent network and cellular bistability

    J Comput Neurosci

    (1998)
  • G.L. Chadderdon et al.

    A large scale neurocomputational model of task-oriented behavior selection and working memory in prefrontal cortex

    J Cogn Neurosci

    (2006)
  • M.V. Chafee et al.

    Matching patterns of activity in primate prefrontal area 8a and parietal area 7ip neurons during a spatial working memory task

    J Neurophysiol

    (1998)
  • L. Chelazzi et al.

    A neural basis for visual search in inferior temporal cortex

    Nature

    (1993)
  • L. Chelazzi et al.

    Responses of neurons in inferior temporal cortex during memory-guided visual search

    J Neurophysiol

    (1998)
  • M. Colombo et al.

    Responses of inferior temporal cortex and hippocampal neurons during delayed matching to sample in monkeys (Macaca fascicularis)

    Behav Neurosci

    (1994)
  • A. Compte et al.

    Synaptic mechanisms and network dynamics underlying spatial working memory in a cortical network model

    Cereb Cortex

    (2000)
  • A. Compte et al.

    Temporally irregular mnemonic persistent activity in prefrontal neurons of monkeys during a delayed-response task

    J Neurophysiol

    (2003)
  • C. Constantinidis et al.

    Neuronal activity in posterior parietal area 7a during the delay periods of a spatial memory task

    J Neurophysiol

    (1996)
  • B. Delord et al.

    Bistable behaviour in a neocortical neurone model

    Neuroreport

    (1997)
  • B. Delord et al.

    A model study of cellular short-term memory produced by slowly inactivating potassium conductances

    J Comput Neurosci

    (2000)
  • D. Durstewitz et al.

    Dopamine-mediated stabilization of delay-period activity in a network model of prefrontal cortex

    J Neurophysiol

    (2000)
  • D. Durstewitz

    Self-organizing neural integrator predicts interval times through climbing activity

    J Neurosci

    (2003)
  • A.V. Egorov et al.

    Graded persistent activity in entorhinal cortex neurons

    Nature

    (2002)
  • C.A. Erickson et al.

    Responses of the macaque perirhinal neurons during and after visual stimulus association learning

    J Neurosci

    (1999)
  • E. Fransen et al.

    Simulations of the role of the muscarinic-activated calcium-sensitive nonspecific cation current I-NCM in entorhinal neuronal activity during delayed matching tasks

    J Neurosci

    (2002)
  • S. Funahashi et al.

    Mnemonic coding of visual space in the monkey’s dorsolateral prefrontal cortex

    J Neurophysiol

    (1989)
  • J.M. Fuster

    Unit activity in prefrontal cortex during delayed-response performance: neuronal correlates of transient memory

    J Neurophysiol

    (1973)
  • J.M. Fuster

    Inferotemporal units in selective visual attention and short-term memory

    J Neurophysiol

    (1990)
  • J.M. Fuster

    Memory in the cerebral cortex

    (1995)
  • J.M. Fuster

    The prefrontal cortex

    (1997)
  • Cited by (153)

    View all citing articles on Scopus
    View full text