Research reportInduction of orientation-specific LTP-like changes in human visual evoked potentials by rapid sensory stimulation
Introduction
Long-term potentiation (LTP) refers to an enduring increase in synaptic efficacy, and is the principal candidate synaptic mechanism underlying learning, memory and other forms of experience-dependent plasticity [2], [3], [8]. Over the past 30 years considerable progress has been made in elucidating the cellular and molecular bases of LTP [14]. However, it has been only relatively recently that researchers have begun to investigate the link between LTP and naturally occurring plasticity in the intact brain [8]. Some of the most promising research investigating this link has come from studies of plasticity in the visual system. In particular, it has recently been reported that N-methyl-d-aspartate (NMDA)-dependent LTP can be induced in the visual cortex of anesthetized adult rats after high-frequency trains of invasive electrical stimulation [9], and externally presented, non-invasive visual stimulation [5].
The study of LTP has been hampered by the absence of a human model. However, in a recent electroencephalography (EEG) study, Teyler et al. [16] reported the first demonstration of an LTP-like effect induced non-invasively by sensory stimulation in humans. A ‘photic tetanus’ (a 2-min block of checkerboards presented at 9 Hz) induced a long-term (measured up to 55 min after tetanization) enhancement of a specific component of the visual-evoked potential (VEP) recorded over the occipital lobe. The potentiated component of the VEP was a late phase of the N1 complex (the N1b), with bilateral striate and extrastriate areas implicated as apparent sites of generation [16]. This result has subsequently been supported by studies that use almost identical experimental procedures and show complementary enhancements lasting for at least 1 h in cortical haemodynamic responses [7] and event-related desynchronization of the alpha rhythm [6]. Furthermore, an animal study using identical stimulation protocols to those employed by Teyler et al. [16] has demonstrated NMDA-dependent LTP in the visual cortex of anesthetized rats lasting well over 1 h [5].
A fundamental property of cellular LTP as studied in animal preparations is input-specificity—when a single pathway is potentiated, adjacent pathways that have not been activated by the induction protocol do not show potentiation [1], [8]. Recently, McNair et al. [15] refined the EEG paradigm employed by Teyler et al. [16] to explore whether or not LTP-like effects induced by photic tetanization can be shown to be input-specific to the spatial frequency of the visual stimuli. One group of participants was tetanized using a low spatial frequency (one cycle per degree) sine grating and another group was tetanized using a high spatial frequency (five cycles per degree) sine grating. Both groups, however, received presentations of both types of stimuli during the pre-tetanus and post-tetanus recordings. The results obtained showed a significant potentiation of the N1b during subsequent presentations of sine gratings of the same spatial frequency as the tetanizing stimulus, but not to sine gratings of the non-tetanized spatial frequency. McNair et al. [15] suggested that this spatial frequency-specific enhancement of the N1b is a cortical analogue of the input-specificity property of cellular LTP.
Although McNair et al. [15] provided evidence for spatial frequency-specific potentiation, they did not investigate other features of visual stimuli that could plausibly show input-specificity. A well-characterised feature of the visual system is orientation-specific processing—that is, differently oriented visual stimuli excite discrete and functionally distinct populations of neurons. There is considerable neurophysiological evidence that orientation-tuning is an important characteristic of cortical columns and single neurons in cat [10] and monkey [9] visual cortices, and that orientation-tuning does not occur further upstream in the lateral geniculate nuclei. It is widely believed that orientation-tuning first emerges in an analogous manner and location in human visual cortex. This assumption has been supported by various forms of indirect evidence, including studies utilizing transcranial magnetic stimulation [12] and functional magnetic resonance imaging [13], [17].
In the present study we aim to expand the evidence for input-specificity by exploring whether orientation-specific LTP-like enhancements of the VEP can be induced using sine wave gratings of two different orientations (horizontal and vertical). We hypothesize that LTP-like effects should be specific to gratings of the same orientation as the photic tetanus, as indexed by changes in the amplitude of the N1b. Furthermore, McNair et al. [15] only tested for a period of 10 min after the photic tetanus which leaves unexplored the longevity of the potentiation. So in addition to testing for an orientation-specific enhancement of the N1b immediately after tetanization, we also investigate whether any LTP-like enhancement can be shown to last for at least 1 h.
Section snippets
Materials and methods
Eighteen healthy right-handed participants, with normal or corrected-to-normal vision, took part in this experiment. Nine participants (six female) were in the horizontal orientation tetanus condition, and nine participants (three female) were in the vertical orientation tetanus condition. The mean age was 25.9 years (range 20–44; standard deviation 6.2). The experimental procedures were approved by the University of Auckland Human Participants Ethics Committee, and all participants gave
Results
The analysis of variance of the within-subjects effects indicated a significant interaction between block and grating [F(2,33.9) = 9.8, p = 0.001]. There was no significant interaction between hemisphere, grating and block [F(1.9,32.8) = 1.2, p = 0.317]; grating, block and time [F(1.8,30.4) = 2.9, p = 0.074]; or hemisphere, grating, block and time [F(1.4,23.7) = 0.2, p = 0.942].
The simple effects for the significant block-by-grating interaction were examined further. For the tetanized grating there was a
Discussion
The present study demonstrates that LTP-like increases in amplitude of the VEP induced by rapid visual stimulation can show orientation-specificity. Significant increases in the N1b component were observed over both hemispheres for 10 min after tetanization for sine gratings of the same orientation as the tetanizing stimulus, but not for sine gratings of the alternative orientation to the tetanizing stimulus (see Fig. 1, Fig. 2, Fig. 3).
These results support the claim made by McNair et al. [15]
Conclusion
Previous research had demonstrated that tetanic visual stimulation can induce LTP-like changes non-invasively in human visual cortex, and that this potentiation exhibits a cortical analogue of input-specificity, a fundamental property of cellular LTP. Here we extend the evidence for input-specificity by demonstrating that the orientation of the tetanic visual stimuli can be manipulated to selectively potentiate the N1b component of the VEP. In addition, because orientation-specificity is
Conflict of interest
None.
Acknowledgements
Supported by grants from NIH (Grant no. R01 MH064508) and the NZ Neurological Foundation (Grant no. 0311-SPG). We thank Ben Knight for helpful comments.
References (17)
- et al.
Long-term enhanced desynchronization of the alpha rhythm following tetanic stimulation of human visual cortex
Neurosci. Lett.
(2006) - et al.
The assessment of two methods for removing eye movement artefact from the EEG
Electroencephalogr. Clin. Neurophysiol.
(1985) - et al.
Possible mechanisms for long-lasting potentiation of synaptic transmission in hippocampal slices from guinea-pigs
J. Physiol.
(1980) - et al.
A synaptic model of memory: long-term potentiation in the hippocampus
Nature
(1993) - et al.
Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the preforant path
J. Physiol.
(1973) - et al.
Long-term modifications of synaptic efficacy in the human inferior and middle temporal cortex
Proc. Natl. Acad. Sci. U.S.A.
(1996) - et al.
Rapid visual stimulation induces N-methyl-d-aspartate receptor-dependent sensory long-term potentiation in the rat cortex
Neuroreport
(2006) - et al.
Effects of long-term potentiation in the human visual cortex: a functional magnetic resonance imaging study
Neuroreport
(2005)
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