Skip to main content
SpringerLink
Log in

Microstimulation of monkey dorsolateral prefrontal cortex impairs antisaccade performance

  • Research Article
  • Published:
Experimental Brain Research Aims and scope Submit manuscript

Abstract

The dorsolateral prefrontal cortex (DLPFC) has been implicated in various cognitive functions, including response suppression. This function is frequently probed with the antisaccade task, which requires suppression of the automatic tendency to look toward a flashed peripheral stimulus (prosaccade), and instead generate a voluntary saccade to the mirror location. To test whether activity in the DLPFC is causally linked to antisaccade performance, we applied electrical microstimulation to sites in the DLPFC of two monkeys, while they performed randomly interleaved pro- and antisaccade trials. Microstimulation resulted in significantly longer saccadic reaction times for ipsilaterally directed prosaccades and antisaccades, and increased the error rate on ipsilateral antisaccade trials. These findings provide causal evidence that activity in the DLPFC influences saccadic eye movements.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Abe M, Hanakawa T, Takayama Y, Kuroki C, Ogawa S, Fukuyama H (2007) Functional coupling of human prefrontal and premotor areas during cognitive manipulation. J Neurosci 27:3429–3438

    Article  PubMed  CAS  Google Scholar 

  • Bell AH, Everling S, Munoz DP (2000) Influence of stimulus eccentricity and direction on characteristics of pro- and antisaccades in non-human primates. J Neurophysiol 84:2595–2604

    PubMed  CAS  Google Scholar 

  • Brown MR, Vilis T, Everling S (2007) Frontoparietal activation with preparation for antisaccades. J Neurophysiol 98:1751–1762

    Article  PubMed  Google Scholar 

  • Bruce CJ, Friedman HR, Kraus MS, Stanton GB (2004) The primate frontal eye field. In: Chalupa LM, Werner JS (eds) The visual neurosciences, vol 2. The MIT Press, Cambridge, pp 1428–1448

    Google Scholar 

  • Butovas S, Schwarz C (2003) Spatiotemporal effects of microstimulation in rat neocortex: a parametric study using multielectrode recordings. J Neurophysiol 90:3024–3039

    Article  PubMed  Google Scholar 

  • Butovas S, Hormuzdi SG, Monyer H, Schwarz C (2006) Effects of electrically coupled inhibitory networks on local neuronal responses to intracortical microstimulation. J Neurophysiol 96:1227–1236

    Article  PubMed  CAS  Google Scholar 

  • Churchland MM, Shenoy KV (2007) Delay of movement caused by disruption of cortical preparatory activity. J Neurophysiol 97:348–359

    Article  PubMed  Google Scholar 

  • Condy C, Wattiez N, Rivaud-Pechoux S, Tremblay L, Gaymard B (2007) Antisaccade deficit after inactivation of the principal sulcus in monkeys. Cereb Cortex 17:221–229

    Article  PubMed  Google Scholar 

  • Corbetta M, Miezin FM, Shulman GL, Petersen SE (1993) A PET study of visuospatial attention. J Neurosci 13:1202

    PubMed  CAS  Google Scholar 

  • Corbetta M, Akbudak E, Conturo TE, Snyder AZ, Ollinger JM, Drury HA, Linenweber MR, Petersen SE, Raichle ME, Van Essen DC, Shulman GL (1998) A common network of functional areas for attention and eye movements. Neuron 21:761–773

    Article  PubMed  CAS  Google Scholar 

  • Curtis CE, D’Esposito M (2003) Success and failure suppressing reflexive behavior. J Cogn Neurosci 15:409–418

    Article  PubMed  Google Scholar 

  • Desouza JF, Everling S (2004) Focused attention modulates visual responses in the primate prefrontal cortex. J Neurophysiol 91:855

    Article  PubMed  Google Scholar 

  • Desouza JF, Menon RS, Everling S (2003) Preparatory set associated with pro-saccades and anti-saccades in humans investigated with event-related FMRI. J Neurophysiol 89:1016–1023

    Article  PubMed  Google Scholar 

  • Doricchi F, Perani D, Incoccia C, Grassi F, Cappa SF, Bettinardi V, Galati G, Pizzamiglio L, Fazio F (1997) Neural control of fast-regular saccades and antisaccades: an investigation using positron emission tomography. Exp Brain Res 116:50

    Article  PubMed  CAS  Google Scholar 

  • Dorris MC, Pare M, Munoz DP (1997) Neuronal activity in monkey superior colliculus related to the initiation of saccadic eye movements. J Neurosci 17:8566

    PubMed  CAS  Google Scholar 

  • Everling S, Desouza JF (2005) Rule-dependent activity for prosaccades and antisaccades in the primate prefrontal cortex. J Cogn Neurosci 17:1483–1496

    Article  PubMed  Google Scholar 

  • Everling S, Fischer B (1998) The antisaccade: a review of basic research and clinical studies. Neuropsychologia 36:885–899

    Article  PubMed  CAS  Google Scholar 

  • Everling S, Dorris MC, Klein RM, Munoz DP (1999) Role of primate superior colliculus in preparation and execution of anti-saccades and pro-saccades. J Neurosci 19:2740–2754

    PubMed  CAS  Google Scholar 

  • Everling S, Tinsley CJ, Gaffan D, Duncan J (2002) Filtering of neural signals by focused attention in the monkey prefrontal cortex. Nat Neurosci 5:671

    Article  PubMed  CAS  Google Scholar 

  • Everling S, Tinsley CJ, Gaffan D, Duncan J (2006) Selective representation of task-relevant objects and locations in the monkey prefrontal cortex. Eur J Neurosci 23:2197–2214

    Article  PubMed  Google Scholar 

  • Fischer B, Weber H (1992) Characteristics of “anti” saccades in man. Exp Brain Res 89:415

    Article  PubMed  CAS  Google Scholar 

  • Forbes K, Klein RM (1996) The magnitude of the fixation offset effect with endogenously and exogenously controlled saccades. J Cogn Neurosci 8:344–352

    Article  Google Scholar 

  • Ford KA, Goltz HC, Brown MR, Everling S (2005) Neural processes associated with antisaccade task performance investigated with event-related FMRI. J Neurophysiol 94:429–440

    Article  PubMed  Google Scholar 

  • Funahashi S, Chafee MV, Goldman-Rakic PS (1993) Prefrontal neuronal activity in rhesus monkeys performing a delayed anti-saccade task. Nature 365:753

    Article  PubMed  CAS  Google Scholar 

  • Gaymard B, Ploner CJ, Rivaud-Pechoux S, Pierrot-Deseilligny C (1999) The frontal eye field is involved in spatial short-term memory but not in reflexive saccade inhibition. Exp Brain Res 129:288

    Article  PubMed  CAS  Google Scholar 

  • Gaymard B, Francois C, Ploner CJ, Condy C, Rivaud-Pechoux S (2003) A direct prefrontotectal tract against distractibility in the human brain. Ann Neurol 53:542–545

    Article  PubMed  Google Scholar 

  • Goldman PS, Nauta WJ (1976) Autoradiographic demonstration of a projection from prefrontal association cortex to the superior colliculus in the rhesus monkey. Brain Res 116:145

    Article  PubMed  CAS  Google Scholar 

  • Goldman-Rakic PS (1988) Topography of cognition: parallel distributed networks in primate association cortex. Annu Rev Neurosci 11:137

    Article  PubMed  CAS  Google Scholar 

  • Guitton D, Buchtel HA, Douglas RM (1985) Frontal lobe lesions in man cause difficulties in suppressing reflexive glances and in generating goal-directed saccades. Exp Brain Res 58:455

    Article  PubMed  CAS  Google Scholar 

  • Gustafsson B, Jankowska E (1976) Direct and indirect activation of nerve cells by electrical pulses applied extracellularly. J Physiol 258:33–61

    PubMed  CAS  Google Scholar 

  • Hallett PE (1978) Primary and secondary saccades to goals defined by instructions. Vision Res 18:1279–1296

    Article  PubMed  CAS  Google Scholar 

  • Hasegawa RP, Matsumoto M, Mikami A (2000) Search target selection in monkey prefrontal cortex. J Neurophysiol 84:1692

    PubMed  CAS  Google Scholar 

  • Histed MH, Miller EK (2006) Microstimulation of frontal cortex can reorder a remembered spatial sequence. PLoS Biol 4:e134

    Article  PubMed  Google Scholar 

  • Isoda M, Hikosaka O (2007) Switching from automatic to controlled action by monkey medial frontal cortex. Nat Neurosci 10:240–248

    Article  PubMed  CAS  Google Scholar 

  • Jahanshahi M, Dirnberger G (1999) The left dorsolateral prefrontal cortex and random generation of responses: studies with transcranial magnetic stimulation. Neuropsychologia 37:181–190

    Article  PubMed  CAS  Google Scholar 

  • Johnston K, Everling S (2006a) Monkey dorsolateral prefrontal cortex sends task-selective signals directly to the superior colliculus. J Neurosci 26:12471–12478

    Article  PubMed  CAS  Google Scholar 

  • Johnston K, Everling S (2006b) Neural activity in monkey prefrontal cortex is modulated by task context and behavioral instruction during delayed-match-to-sample and conditional prosaccade-antisaccade tasks. J Cogn Neurosci 18:749–765

    Article  PubMed  Google Scholar 

  • Judge SJ, Richmond BJ, Chu FC (1980) Implantation of magnetic search coils for measurement of eye position: an improved method. Vision Res 20:535

    Article  PubMed  CAS  Google Scholar 

  • Kuwajima M, Sawaguchi T (2007) Involvement of the lateral prefrontal cortex in conditional suppression of gaze shift. Neurosci Res 59:431–445

    Article  PubMed  Google Scholar 

  • Lebedev MA, Messinger A, Kralik JD, Wise SP (2004) Representation of attended versus remembered locations in prefrontal cortex. PLoS Biol 2:e365

    Article  PubMed  Google Scholar 

  • Leichnetz GR, Spencer RF, Hardy SG, Astruc J (1981) The prefrontal corticotectal projection in the monkey; an anterograde and retrograde horseradish peroxidase study. Neuroscience 6:1023

    Article  PubMed  CAS  Google Scholar 

  • Luks TL, Simpson GV, Dale CL, Hough MG (2007) Preparatory allocation of attention and adjustments in conflict processing. Neuroimage 35:949–958

    Article  PubMed  Google Scholar 

  • McDowell JE, Brown GG, Paulus M, Martinez A, Stewart SE, Dubowitz DJ, Braff DL (2002) Neural correlates of refixation saccades and antisaccades in normal and schizophrenia subjects. Biol Psychiatry 51:216–223

    Article  PubMed  Google Scholar 

  • McIntyre CC, Grill WM (2000) Selective microstimulation of central nervous system neurons. Ann Biomed Eng 28:219–233

    Article  PubMed  CAS  Google Scholar 

  • Moore T, Armstrong KM (2003) Selective gating of visual signals by microstimulation of frontal cortex. Nature 421:370–373

    Article  PubMed  CAS  Google Scholar 

  • Mull BR, Seyal M (2001) Transcranial magnetic stimulation of left prefrontal cortex impairs working memory. Clin Neurophysiol 112:1672–1675

    Article  PubMed  CAS  Google Scholar 

  • Munoz DP, Everling S (2004) Look away: the anti-saccade task and the voluntary control of eye movement. Nat Rev Neurosci 5:218–228

    Article  PubMed  CAS  Google Scholar 

  • Muri RM, Vermersch AI, Rivaud S, Gaymard B, Pierrot-Deseilligny C (1996) Effects of single-pulse transcranial magnetic stimulation over the prefrontal and posterior parietal cortices during memory-guided saccades in humans. J Neurophysiol 76:2102

    PubMed  CAS  Google Scholar 

  • Owen AM, Evans AC, Petrides M (1996) Evidence for a two-stage model of spatial working memory processing within the lateral frontal cortex: a positron emission tomography study. Cereb Cortex 6:31

    Article  PubMed  CAS  Google Scholar 

  • Pandya DN, Kuypers HG (1969) Cortico-cortical connections in the rhesus monkey. Brain Res 13:13

    Article  PubMed  CAS  Google Scholar 

  • Peers PV, Ludwig CJ, Rorden C, Cusack R, Bonfiglioli C, Bundesen C, Driver J, Antoun N, Duncan J (2005) Attentional functions of parietal and frontal cortex. Cereb Cortex 15:1469–1484

    Article  PubMed  Google Scholar 

  • Pierrot-Deseilligny C, Rivaud S, Gaymard B, Agid Y (1991) Cortical control of reflexive visually-guided saccades. Brain 114:1473

    Article  PubMed  Google Scholar 

  • Ploner CJ, Gaymard BM, Rivaud-Pechoux S, Pierrot-Deseilligny C (2005) The prefrontal substrate of reflexive saccade inhibition in humans. Biol Psychiatry 57:1159–1165

    Article  PubMed  Google Scholar 

  • Rainer G, Asaad WF, Miller EK (1998) Selective representation of relevant information by neurons in the primate prefrontal cortex. Nature 393:577

    Article  PubMed  CAS  Google Scholar 

  • Ranck JB Jr (1975) Which elements are excited in electrical stimulation of mammalian central nervous system: a review. Brain Res 98:417–440

    Article  PubMed  Google Scholar 

  • Rivaud S, Muri RM, Gaymard B, Vermersch AI, Pierrot-Deseilligny C (1994) Eye movement disorders after frontal eye field lesions in humans. Exp Brain Res 102:110

    Article  PubMed  CAS  Google Scholar 

  • Rowe JB, Passingham RE (2001) Working memory for location and time: activity in prefrontal area 46 relates to selection rather than maintenance in memory. Neuroimage 14:77

    Article  PubMed  CAS  Google Scholar 

  • Sawaguchi T, Iba M (2001) Prefrontal cortical representation of visuospatial working memory in monkeys examined by local inactivation with muscimol. J Neurophysiol 86:2041–2053

    PubMed  CAS  Google Scholar 

  • Sweeney JA, Mintun MA, Kwee S, Wiseman MB, Brown DL, Rosenberg DR, Carl JR (1996) Positron emission tomography study of voluntary saccadic eye movements and spatial working memory. J Neurophysiol 75:454

    PubMed  CAS  Google Scholar 

  • Vandenberghe R, Duncan J, Dupont P, Ward R, Poline JB, Bormans G, Michiels J, Mortelmans L, Orban GA (1997) Attention to one or two features in left or right visual field: a positron emission tomography study. J Neurosci 17:3739–3750

    PubMed  CAS  Google Scholar 

  • Walker R, Husain M, Hodgson TL, Harrison J, Kennard C (1998) Saccadic eye movement and working memory deficits following damage to human prefrontal cortex. Neuropsychologia 36:1141–1159

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported by grants from the Canadian Institutes of Health Research (CIHR) and the Natural Sciences and Engineering Research Council of Canada (NSERC).

Author information

Authors and Affiliations

  1. Department of Physiology and Pharmacology, University of Western Ontario, London, ON, Canada

    Stephen P. Wegener, Kevin Johnston & Stefan Everling

  2. The Centre for Brain and Mind, Robarts Research Institute, 100 Perth Drive, London, ON, N6A 5K8, Canada

    Stefan Everling

Authors
  1. Stephen P. Wegener
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kevin Johnston
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Stefan Everling
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Stefan Everling.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wegener, S.P., Johnston, K. & Everling, S. Microstimulation of monkey dorsolateral prefrontal cortex impairs antisaccade performance. Exp Brain Res 190, 463–473 (2008). https://doi.org/10.1007/s00221-008-1488-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00221-008-1488-4

Keywords

Search

Navigation