VEP indices of cortical lateral interactions in epilepsy treatment

Abstract

We extend Spekreijse's strategy for analyzing lateral interactions in visual evoked potentials (VEPs) to clinical neurophysiologic testing of patients with epilepsy. Stimuli consisted of the radial windmill/dartboard pattern [Ratliff, F., & Zemon, V. (1982). Some new methods for the analysis of lateral interactions that influence the visual evoked potential. In: Bodis-Wollner (Ed.), Evoked potentials, Vol. 388. (pp. 113-124). New York: Annals of the New York Academy of Sciences.] and conventional checkerboards. The fundamental and 2nd-harmonic components of the steady-state responses were used to calculate indices reflecting facilitatory (FI) and suppressive (SI) cortical interactions. We carried out two studies. In the first, VEPs in 38 patients receiving antiepileptic drug (AED) therapy were compared to those of age-matched controls. For three AEDs (tiagabine, topiramate, and felbamate), addition of the drug did not change the FI and SI compared to baseline values or those of normal controls. However, the addition of gabapentin was associated with an increase of the FI, and this change was reversed when the medication was withdrawn. This suggested a medication-specific change in cortical lateral interactions. The second study focused on the effects of neurostimulation therapy. Eleven epilepsy patients receiving chronic vagus nerve stimulation (VNS) treatment were tested. By comparing VEPs recorded with the stimulator on (Stim-ON) and turned off (Stim-OFF) in the same session, we determined that VNS did not have a short-acting effect on lateral interactions. However, when compared with normal controls, the VNS patients had a significantly smaller SI (p<.05), but no difference in the FI, demonstrating the presence of a chronic effect. We conclude that with the appropriate stimuli, VEPs can be used as a measure of cortical lateral interactions in normals and epileptic patients, and demonstrate specific changes in these interactions associated with certain treatment modalities.

Fig. 1

(A) Windmill–Dartboard stimuli. Left: W/D-OFF. Right: W/D-ON. The modulated regions are identical in the W/D-ON and W/D-OFF configurations, but the static component of the pattern is present only in the W/D-ON configuration. Thus, interactions between the modulated and static regions result in differences between the VEP waveforms that the two stimuli elicit. (B) Averaged steady-state responses elicited by these stimuli from one normal control. Each waveform represents the averaged response over one cycle of the stimulus. Modulation rate: 4.19 Hz, contrast: 0.3.

Fig. 2

(A) VEPs elicited by the windmill/dartboard (W/D-ON and W/D-OFF) and checkerboard stimuli from one normal control (data from Fig. 1B). Averaged waveforms are separated into even and odd harmonic components. Top row: raw signals, middle: even harmonics, bottom: odd harmonics. The light gray shading in the top row indicates the un-averaged EEG traces. (B) Fourier components (fundamental and 2nd harmonic) represented as vectors, whose magnitude indicates amplitude and whose direction indicates response phase. The positive X-axis corresponds to an in-phase response, and counterclockwise rotation corresponds to phase advance.

Fig. 3

Polar plots of fundamental (F1) and 2nd harmonic (F2) responses from controls and both patient groups (GBP and VNS). (A) Fundamental responses to the W/D-ON stimulus. (B) Second harmonic responses to the W/D-ON, (C) Second harmonic to the checkerboard stimuli, (D) Second harmonic to the W/D-OFF. Phase convention as in Fig. 2B.

Fig. 4

Plot of the log Facilitation versus log Suppression Indices calculated from responses obtained from 18 normal controls and 24 patients receiving add-on gabapentin (GBP) treatment.

Fig. 5

Decomposition of averaged responses, as in Fig. 2A, recorded from two VNS patients in the stimulator on (Stim-ON) and off (Stim-OFF) conditions. Top row: raw signals, middle: even harmonics, bottom: odd harmonics. The light gray shading indicates the un-averaged EEG traces. (A) Patient 3 (F, age: 46, seizure type: complex-partial, duration of VNS: 5 yrs), (B) Patient 5 (M, age: 27, seizure type: complex-partial with secondary generalization, duration of VNS: 6.5 yrs).

Fig. 6

Plot of the log Facilitation versus log Suppression Indices calculated from responses obtained from 24 normal controls and 11 VNS patients. For each patient, a line connects the data collected in the Stim-ON (filled circle) and Stim-OFF (open circle) conditions. For the patients, there were no differences (paired t-tests, p = .4) in the indices obtained with the Stim-ON vs. the Stim-OFF conditions, and no differences in the facilitation index compared with normal controls (p = .5). However, there is a significant (p < .05) decrease in the suppression index.