Abstract
Neuroimaging has consistently shown engagement of the prefrontal cortex during episodic memory tasks, but the functional relevance of this metabolic/hemodynamic activation in memory processing is still to be determined. We used repetitive transcranial magnetic stimulation (rTMS) to transiently interfere with either left or right prefrontal brain activity during the encoding or retrieval of pictures showing complex scenes. We found that the right dorsolateral prefrontal cortex (DLPFC) was crucial for the retrieval of the encoded pictorial information, whereas the left DLPFC was involved in encoding operations. This 'interference' approach allowed us to establish whether a cortical area activated by a memory task actually contributes to behavioral performance.
Similar content being viewed by others
References
Squire, L. R. Memory and the hippocampus: a synthesis from findings with rats, monkeys, and humans. Psychol. Rev. 99, 195–231 (1992).
Schacter, D. L. & Wagner, A. D. Medial temporal lobe activations in fMRI and PET studies of episodic encoding and retrieval. Hippocampus 9, 7–24 (1999).
Haxby, J. V., Petit, L., Ungerleider, L. G. & Courtney, S. M. Distinguishing the functional roles of multiple regions in distributed neural systems for visual working memory. Neuroimage 11, 380–391 (2000).
Cabeza, R. & Nyberg, L. Neural bases of learning and memory: functional neuroimaging evidence. Curr. Opin. Neurol. 13, 415–421 (2000).
Fletcher, P. C. & Henson, R. N. A. Frontal lobes and human memory. Insights from functional neuroimaging. Brain 124, 849–881 (2001).
Janowsky, J. S., Shimamura, A. P., Kritchevsky, M. & Squire, L.R. Cognitive impairment following frontal lobe damage and its relevance to human amnesia. Behav. Neurosci. 103, 548–560 (1989).
Milner, B., Corsi, P. & Leonard, G. Frontal-lobe contribution to recency judgements. Neuropsychologia 29, 601–618 (1991).
Wheeler, M. A., Stuss, D. T. & Tulving, E. Frontal lobe damage produces episodic memory impairment. J. Int. Neuropsychol. Soc. 1, 525–536 (1995).
Tulving, E., Kapur, S., Craik, F. I., Moscovitch, M. & Houle, S. Hemispheric encoding/retrieval asymmetry in episodic memory: positron emission tomography findings. Proc. Natl. Acad. Sci. USA 91, 2016–2020 (1994).
Milner, B. in The Frontal Agranular Cortex and Behavior (eds. Warren, J. M. & Akert, K.) (New York, McGraw-Hill, 1964).
McDermott, K. B., Buckner, R. L., Petersen, S. E., Kelley, W. M. & Sanders, A. L. Set- and code-specific activation in frontal cortex: an fMRI study of encoding and retrieval of faces and words. J. Cogn. Neurosci. 11, 631–640 (1999).
Kirchhoff, B. A., Wagner, A. D., Maril, A. & Stern, C. E. Prefrontal-temporal circuitry for episodic encoding and subsequent memory. J. Neurosci. 20, 6173–6180 (2000).
Fletcher, P. C., Frith, C. D. & Rugg, M. D. The functional neuroanatomy of episodic memory. Trends Neurosci. 20, 213–218 (1997).
Nyberg, L. et al. Functional brain maps of retrieval mode and recovery of episodic information. Neuroreport 29, 249–252 (1995).
Buckner, R. L., Koutstaal, W., Schacter, D. L., Wagner, A. D. & Rosen, B. R. Functional–anatomic study of episodic retrieval using fMRI. I. Retrieval effort versus retrieval success. Neuroimage 7, 151–162 (1998).
Schacter, D. L. et al. Neuroanatomical correlates of veridical and illusory recognition memory: evidence from positron emission tomography. Neuron 17, 267–274 (1996).
Shallice, T. et al. Brain regions associated with acquisition and retrieval of verbal episodic memory. Nature 368, 633–635 (1994).
Schacter, D. L., Buckner, R. L., Koutstaal, W., Dale, A. M. & Rosen, B. R. Late onset of anterior prefrontal activity during true and false recognition: an event-related fMRI study. Neuroimage 6, 259–269 (1997).
Rugg, M. D., Fletcher, P. C., Chua, P. M. & Dolan, R. J. The role of the prefrontal cortex in recognition memory and memory for source. Neuroimage 10, 520–529 (1999).
Rossini, P. M. & Rossi, S. Clinical application of motor evoked potentials. Electroencephalogr. Clin. Neurophysiol. 106,180–194 (1998).
Hallett, M. Trascranial magnetic stimulation and the human brain. Nature 406, 147–150 (2000).
Oliveri, M. et al. Time-dependent activation of parieto-frontal networks for directing attention to tactile space: a study with paired TMS pulses in right brain damaged patients with extinction. Brain 123, 1939–1947 (2000).
Rossi, S. et al. Effects of repetitive transcranial magnetic stimulation on movement-related cortical activity in humans. Cereb. Cortex 10, 802–808 (2000).
Pascual-Leone, A., Walsh, V. & Rothwell, J. Transcranial magnetic stimulation in cognitive neuroscience—virtual lesion, chronometry, and functional connectivity. Curr. Opin. Neurobiol. 10, 232–237 (2000).
Walsh, V. & Cowey, A. Transcranial magnetic stimulation and cognitive neuroscience. Nat. Rev. Neurosci. 1, 73–79 (2000).
Lepage, M., Ghaffar, O., Nyberg, L. & Tulving, E. Prefrontal cortex and episodic memory retrieval mode. Proc. Natl. Acad. Sci. USA 97, 506–511 (2000).
Curran, T., Schacter, D. L., Norman, K. A. & Galluccio, L. False recognition after a right frontal lobe infarction: memory for general and specific information. Neuropsychologia 35, 1035–1049 (1997).
Swick, D. & Knight, R. T. Contributions of prefrontal cortex to recognition memory: electrophysiological and behavioral evidence. Neuropsychology 13, 155–170 (1999).
Desgranges, B., Baron, J. C. & Eustache, F. The functional neuroanatomy of episodic memory: the role of the frontal lobes, the hippocampal formation, and other areas. Neuroimage 8, 198–213 (1998).
Wagner, A. D. Working memory contributions to human learning and remembering. Neuron 22, 19–22 (1999).
Callicott, J. H. et al. Physiological characteristics of capacity constraints in working memory as revealed by functional MRI. Cereb. Cortex 9, 20–26 (1999).
Rowe, J. B., Toni, I., Josephs, O., Frackowiak, R. S. & Passingham, R. E. The prefrontal cortex: response selection or maintenance within working memory? Science 288, 1656–1660 (2000).
Brandt, S. A., Ploner, C. J., Meyer, B. U., Leistner, S. & Villringer, A. Effects of repetitive transcranial magnetic stimulation over dorsolateral prefrontal and posterior parietal cortex on memory-guided saccades. Exp. Brain Res. 118, 197–204 (1998).
Nickerson, R. S. Intersensory facilitation of reaction time: energy summation or preparation enhancement? Psychol. Rev. 80, 489–509 (1973).
Amassian, V. E., Qirck, G. J. & Stewart, M. A comparison of corticospinal activation by magnetic coil and electrical stimulation of monkey motor cortex. Electroencephalogr. Clin. Neurophysiol. 77, 390–401 (1990).
Illmoniemi, R. J. et al. Neuronal responses to magnetic stimulation reveal cortical reactivity and connectivity. Neuroreport 8, 3537–3540 (1997).
Paus, T. et al. Transcranial magnetic stimulation during Positron Emission Tomography: a new method for studying connectivity of the human cerebral cortex. J. Neurosci. 17, 3178–3184 (1997).
Mottaghy, F. M. et al. Modulation of the neural circuitry subserving working memory in healthy human subjects by repetitive transcranial magnetic stimulation. Neurosci. Lett. 280, 167–170 (2000).
Jahanshahi, M. et al. The effects of transcranial magnetic stimulation over the dorsolateral prefrontal cortex on suppression of habitual counting during random number generation. Brain 121, 1533–1544 (1998).
Pascual-Leone, A., Wassermann, E. M., Grafman, J. & Hallett, M. The role of the prefrontal cortex in implicit procedural learning. Exp. Brain Res. 107, 479–485 (1966).
Flitman, S. S. et al. Linguistic processing during repetitive transcranial magnetic stimulation. Neurology 50, 175–181 (1998).
Oldfield, R. C. The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9, 97–113 (1971).
Rossini, P. M. et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Electroencephalogr. Clin. Neurophysiol. 91, 79–92 (1994).
Kamman, R. in Workbook for General Psychology 228–236 (Prentice–Hall, 1970).
Acknowledgements
We thank A. Polese, K. Sosta and I. Benaglio for help with experiments. The work was partly supported by Ministero della Sanità (Progetto Finalizzato 1999) and by Fondazione Telethon Onlus (E.C0985).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Rossi, S., Cappa, S., Babiloni, C. et al. Prefontal cortex in long-term memory: an “interference” approach using magnetic stimulation. Nat Neurosci 4, 948–952 (2001). https://doi.org/10.1038/nn0901-948
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nn0901-948
- Springer Nature America, Inc.
This article is cited by
-
BDNF Val66Met gene polymorphism modulates brain activity following rTMS-induced memory impairment
Scientific Reports (2022)
-
Effects of Transcranial Direct Current Stimulation on effort during a working-memory task
Scientific Reports (2021)
-
Modulating Long Term Memory at Late-Encoding Phase: An rTMS Study
Brain Topography (2021)
-
Evidence against benefits from cognitive training and transcranial direct current stimulation in healthy older adults
Nature Human Behaviour (2020)
-
Neurostimulation for Memory Enhancement in Epilepsy
Current Neurology and Neuroscience Reports (2018)