Response inhibition alterations in migraine: evidence from event-related potentials and evoked oscillations

Abstract

Background: Migraine is characterized by a hypersensitivity to environmental stimulation which climaxes during headache attacks but persists during attack-free period. Despite ongoing debates about the nature of the mechanisms giving rise to this abnormality, the presence of deficient inhibitory cortical processes has been proposed to be one possible mechanism underlying its pathogenesis. Empirical evidence supporting this claim is mainly based on previous accounts showing functional cortical disexcitability in the sensory domain. Considering that a general inhibitory control process can play an important role across early to later stage of information processing, this may indicate the important role other dimensions of inhibitory control can play in migraine disability. The present study examined the pathophysiological features of inhibitory control that takes place during suppression of prepotent responses in migraineurs.

Methods: Twenty-two patients with migraine without aura (mean age = 30.86 ± 5.69 years; 19 females) during the interictal period and 25 healthy controls (mean age = 30.24 ± 3.52 years; 18 females) were recruited. We used a stop signal task in combination with event-related potentials (ERPs) to examine participants' neural activity supporting response inhibition.

Results: Behaviorally, migraineurs exhibited prolonged stop signal reaction times relative to healthy controls. At the neural level, the amplitude of the stop-N2 over fronto-central, central and centro-parietal scalp regions, a component of the ERPs related to conflict monitoring during early, non-motoric stages of inhibition, was significantly increased in migraineurs. Meanwhile, the amplitude of the stop-P3 over central and centro-parietal scalp regions, a component of the ERPs reflecting late-stage inhibition of the motor system and cognitive evaluation of motor inhibition, was also significantly increased in migraineurs. Ultimately, our time-frequency analysis further revealed increased delta activity in migraineurs.

Conclusions: Consistent with the theory that alterations in cognitive cortical processes are a key signature of migraine, our findings revealed an abnormal state of suppressing prepotent responses in migraineurs, which can be attributed to cortical disexcitability of the pre-frontal executive network and centro-parietal sensorimotor network. These novel findings extend to show the existence of dysfunctional inhibition control that occurs during suppression of prepotent responses in migraneurs.

Keywords: Cortical disexcitability; Delta oscillation; ERPs; Migraine; N2; P3; Response inhibition; Theta oscillation.

Fig. 1

Stop signal paradigm. This task included 80% Go trials and 20% Stop trials. On Go trials, participants were presented with a fixation cross on a black computer screen lasting for 600–800 ms, which is immediately followed by a Go stimulus (the letter ‘X’ or ‘O’) (a Go signal) lasting for 1000 ms. Participants were instructed to judge the shape of the Go stimulus as accurately and quickly as possible via a button press with the index fingers of the left and right hands. On the remaining Stop trials (20%), the stop stimulus (a red square appearing above the location of the go stimulus) appeared after the Go stimulus after a variable delay of 0–250 ms in a step of 50 ms (the stop signal delay; SSD), cuing participants to withhold their responses to the Go stimulus. A variable intertrial interval was 1500–2000 ms.

Fig. 2

Time-domain ERPs results. a Grand average ERP waveforms recorded at Cz evoked by Go signals (dashed lines) and successful Stop signals (solid lines), and the topography of the N2 (200–250 ms) and P3 (350–500 ms) in patients with MwoA and healthy controls. b Means and standard errors (SEs) of the amplitudes of the N2 and P3 in the two groups. *denotes p < 0.05 and **denotes p < 0.01

Fig. 3

Time-frequency results. a Time-frequency plots showing delta changes in normalized power in go and stop trials (left) for patients with MwoA and healthy controls for the selected electrode (Cz). Black dotted squares indicate the time-frequency region in which theta power in stop trials was significantly higher in patients with MwoA than in healthy controls. Scalp topography maps show the spatial distribution of theta power (4–8 Hz) in go and stop trials between 350 and 500 ms. The color scale indicates spectral power in SD. b Means and standard errors (SEs) of the delta power (4–8 Hz) between 350 and 500 ms at Cz in the two groups. **, p < 0.01