Paired-pulse flash-visual evoked potentials: New methods revive an old test
Highlights
► Modern methods revive the paired flash-visual evoked potential (F-VEP) technique. ► Paired (and single) F-VEPs change according to the eye state (closed/open). ► Paired F-VEPs explore neural inhibition in the visual system. ► They are a promising tool for research on photosensitivity.
Introduction
Clinical neurophysiology is witnessing research on cortical excitability to become a core subject in human disease, including the field of epilepsy and migraine. Probably, this is largely due to the advent of paired-pulse transcranial magnetic stimulation (TMS), whose main target however remains the primary motor cortex (Rossi et al., 2009). This is a serious limitation, since non-motor systems are more directly involved in the physiology of most forms of epilepsy (and migraine). An important example is the visual system, as far as photosensitive epilepsies (or migraine) are considered. In these disorders, a direct physiological exploration through the specific modality (i.e. visual stimulation) appears – in principle – the most eligible. Availability of a physiologic tool analogous to paired-pulse TMS, but for the visual modality, would thus be welcome. Indeed, there are recent studies of migraine with paired-pulse pattern-visual evoked potentials (VEPs) (Höffken et al., 2009). In this context, it may seem surprising that protocols based on paired-flash stimulation are no longer studied. Indeed it is the flash stimulus, in the context of intermittent light stimulation (ILS), the most usual and widespread means of revealing epileptiform paroxysms in photosensitive patients. Paired-pulse flash-VEPs (F-VEPs) or the “recovery cycle” of the visual system were explored in the pioneering VEP era (Ciganek, 1964, Schwartz and Shagass, 1964, Bergamasco, 1966). However they were somewhat abandoned, possibly for the technical limitations typical of that time, when for instance electronic subtraction methods were available to a minority of laboratories (Schwartz and Shagass, 1964). Moreover, the original measurements were extremely complex, since they considered separately the many components that characterize the F-VEP (Ciganek, 1964). Finally, there was little or no statistical approach to paired F-VEPs and their disease-related changes (Bergamasco, 1966). At the same time, approaching paired-pulse F-VEPs made us realize that a precise description of the single F-VEP in the same subjects was the precondition. Of course, a wide, historical literature exists about F-VEPs (review in Bergamini and Bergamasco, 1967). However, statistical evaluation of the influence of the eye state (closed or open) onto F-VEPs was very limited (single response) (Tartaglione et al., 1995) or absent (paired response). Yet, the eye state is of paramount importance for ILS.
Thus, it was our goal to exploit simple and reliable measurements of the F-VEP, both single and paired, using modern equipment, and exploring the influence of the eye state (closed or open). For reasons that will be discussed, we chose an elementary recording model: EEG activity was derived from over the midline occipital cortex and from over the central areas. Stimulation was binocular, since it was our exclusive goal to reproduce the physiologic conditions that underlie the routine ILS.
Overall, we aimed at showing that previous difficulties with the paired-pulse F-VEP technique can be overcome. This way, a powerful tool becomes available, providing specific information on the excitability properties of the visual system.
Section snippets
Subjects and methods
All procedures received approval from the Human Research Ethics Committee of the University of Piedmont East“A. Avogadro” in Novara. All participants gave written, informed consent and the studies were conducted in accordance with the Declaration of Helsinki.
Single F-VEP
Table 1 shows numerical data on the variables analyzed, which will be described according to the ISCEV nomenclature (Odom et al., 2010). In the EC condition (Fig. 1a), the grand-average tracings showed, over the posterior midline, the classical waveform recently re-assessed by Tartaglione et al. (1995) and by Coburn et al. (2005), with a main positive peak (P2) at an average latency of 124.5 ms. P2 showed a negative indenture with a latency of 103 ms. A negative peak (N2) preceded P2, and before
Discussion
The main purpose of the study was to revive the paired-flash technique as a practical tool for studying the visual system excitability, with a special reference to epileptology. We exploited simple but renewed methods, to overcome the problems that previously hindered this test.
Conclusion
Modern equipment and simple methodology can revive the paired F-VEP technique effectively. This method depicts features of the overall visual system excitability, in the form of time-dependent inhibitory curves having statistical significance in a group analysis. As to interindividual variability of the most significant data points, we found Coefficients of Variation (CVs) of about 25–30%. This CV magnitude is for instance lower than that affecting short-latency cortical inhibition (SICI),
Acknowledgement
This work was funded by a Grant from Regione Piemonte, Italy: “Ricerca Sanitaria Finalizzata 2009”.
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