Lateral inhibition in visual cortex of migraine patients between attacks

Abstract

Background: The interictal deficit of habituation to repetitive visual stimuli in migraine patients could be due to deficient intracortical inhibition and/or to low cortical pre-activation levels. Which of these abnormalities contributes more to the habituation deficit cannot be determined with the common methods used to record transient visual responses.We investigated lateral inhibition in the visual cortex during the migraine cycle and in healthy subjects by using differential temporal modulations of radial windmill-dartboard (WD) or partial-windmill (PW) visual patterns.

Methods: Transient (TR-VEP) and steady-state visual-evoked potentials (SS-VEP) were recorded in 65 migraine patients (21 without and 22 with aura between attacks; 22 patients during an attack) and in 21 healthy volunteers (HV). Three stimulations were used in each subject: classic checkerboard pattern (contrast-reversion 3.1 Hz), WD and PW (contrast-reversion ~4 Hz). For each randomly presented stimulation protocol, 600 sweeps were acquired and off-line partitioned in 6 blocks of 100. Fourier analysis allowed data to extract in SS-VEP the fundamental (1H) and the second harmonic (2H) components that reflect respectively short-(WD) and long- range lateral inhibition (attenuation of 2H in WD compared to PW).

Results: Compared to HV, migraineurs recorded interictally had significantly less habituation of the N1-P1 TR-VEP component over subsequent blocks and they tended to have a smaller 1st block amplitude. 1H amplitude in the 1st block of WD SS-VEP was significantly greater than in HV and habituated in successive blocks, contrasting with an amplitude increase in HV. Both the interictal TR-VEP and SS-VEP abnormalities normalized during an attack. There was no significant between group difference in the PW 2H amplitude and its attenuation. When data of HV and migraine patients were combined, the habituation slope of WD-VEP 1H was negatively correlated with that of TR-VEP N1-P1 and with number of days since the last migraine attack.

Conclusion: These results are in favour of a migraine cycle-dependent imbalance between excitation and inhibition in the visual cortex. We hypothesize that an interictal hypoactivity of monaminergic pathways may cause a functional disconnection of the thalamus in migraine leading to an abnormal intracortical short-range lateral inhibition that could contribute to the habituation deficit observed during stimulus repetition.

Figure 1

Illustrative traces of visual evoked potentials obtained by checkerboard (left column), windmill-dartboard (middle column) and partial-windmill (right column) stimulation in a healthy volunteer (upper row) and a migraine without aura patient between attacks (lower row).

Figure 2

Steady-state waveforms are converted into the frequency domain by Discrete Fourier Transformation in order to measure the amplitude at the first harmonic (4Hz, 1H) in the windmill-dartboard (W-D) stimulation, and of the second harmonic (8Hz, 2H) in both the windmill-dartboard and partial-windmill (W-D) stimulations. To assess long-range lateral interactions, we calculated attenuation of the 2nd harmonic component in the W-D respective to the P-W pattern.

Figure 3

Left panel: transient N1-P1 [upper], steady-state windmill-dartboard 1H [middle] and partial-windmill 2H [lower] mean amplitudes in the first block of 100 averaged responses; Right panel: Visual evoked potential (VEP) amplitude block averages in each study group and for the three types of visual stimuli: transient (TR-)VEP [upper], steady state windmill-dartboard (W-D) [middle] and partial-windmill (P-R) [lower] VEPs (HV, healthy volunteers; MO, migraine without aura interictally; MA, migraine with aura interictally; Ictal, migraine without aura ictally); data expressed as mean ± SD).

Figure 4

Correlation between the number of days since the last migraine attack and the slope of 1H WD-VEP amplitude changes (negative, linear regression: uninterrupted line) or the slope of N1-P1 TR-VEP amplitude changes (positive, linear regression: dashed line) in the total cohort of migraine patients.

Figure 5

Negative correlation between the habituation slope of 1H WD-VEP amplitudes and that of N1-P1 TR-VEP amplitudes in the total cohort of recorded subjects.

Figure 6

Schematic representation of visual information processing pathway describing the neural network model that can encompass the present findings in both healthy volunteers and migraineurs. In the normal condition (left panel), in presence of a regular brainstem and thalamic activation, visual information travels normally across subcortical areas, then at the cortical level increases the firing rate of excitatory pyramidal cells at the beginning and of fast-spiking (FS) inhibitory interneurons during stimulus repetition. The latter leads to a normal inhibition in adjacent cortical columns manifesting as a decrement in short-range lateral inhibition (LI) followed by its recovery with increasing inhibition of pyramidal cell (modified from [59]). In the thalamo-cortical dysrhythmia model (right panel), used to explain our findings in migraine, the presence of an anatomical or functional disconnection of the thalamus from subcortical areas, causes a change of rhythmic thalamocortical activity that favour low frequency activity which at the cortical level will reduce firing rates of excitatory pyramidal cells at the beginning and of FS inhibitory interneurons during stimulus repetition. The latter leads to a disinhibition in adjacent cortical columns manifesting as a progressive increase in short range LI, the so-called “edge effect”, which, in our migraineurs, is followed by its recovery with increasing excitation of pyramidal cells (modified from [60]).