Common hippocampal structural and functional changes in migraine

Abstract

The hippocampus is classically involved in memory consolidation, spatial navigation and is involved in the stress response. Migraine is an episodic disorder characterized by intermittent attacks with a number of physiological and emotional stressors associated with or provoking each attack. Given that migraine attacks can be viewed as repeated stressors, alterations in hippocampal function and structure may play an important role in migraine pathophysiology. Using high-resolution magnetic resonance imaging, hippocampal morphometric and functional differences (in response to noxious heat stimulation) were compared in age and gender-matched acute episodic migraineurs with high (HF) versus low (LF) frequency of migraine attacks. Morphometric results were compared with age and gender-matched healthy control (HC) cohort. Significant larger bilateral hippocampal volume was found in LF group relative to the HF and HC groups suggestive of an initial adaptive plasticity that may then become dysfunctional with increased frequency. Functional correlates of greater deactivation (LF > HF) in the same hippocampal regions in response to noxious stimulation was also accompanied by overall reduction in functional connectivity of the hippocampus with other brain regions involved in pain processing in the HF group. The results implicate involvement of hippocampus in the pathophysiology of the migraine.

Fig. 1

Differences in hippocampal volume. The bar plots show the hippocampus volume comparisons for low frequency (LF), high frequency (HF) and healthy controls (HC). LF migraineurs had a significantly larger hippocampal volume. (i) Raw volume comparisons—for the statistical analysis the left and right hippocampal volumes of the cohorts were compared while using the total intracranial volume and age as covariates. (ii) The same comparison for normalized volumes (normalized to the total intracranial volume) volumes. Bar heights represent the mean value for each volumetric measurement. Error bars represent the 95 % confidence interval of the mean. Asterisk denotes a significance level of the corresponding P value reported (see text)

Fig. 2

Migraine attacks and hippocampal volumetric differences. The plots represent the correlation between the left and right hippocampal volumes and estimate of the total number of migraine attacks in low frequency (LF left panel) and high frequency (HF right panel) migraine patients. Average hippocampal volume in healthy control (HC) subjects are also shown in gray scale colors in each panel for comparison

Fig. 3

Response to pain. Contrast analysis of the HF versus LF migraine group in response to the “pain threshold +1 °C” stimuli revealed significantly higher deactivation in bilateral hippocampus in the LF patients

Fig. 4

Functional connectivity contrast maps. Functional connectivity contrast map of the hippocampus during intermittent heat stimuli (pain threshold +1 °C on hand) in high versus low frequency migraine patients. PCC posterior cingulate cortex, PCin paracingulate, SM supramarginal, SF superior frontal, Ins (ant) anterior insula, TP temporal pole, NAc nucleus accumbens, FO frontal orbital, MF middle frontal, PAG periaqeductal gray