A Hypothalamic Mechanism Regulates the Duration of a Migraine Attack: Insights from Microstructural and Temporal Complexity of Cortical Functional Networks Analysis

Abstract

The role of the hypothalamus and the limbic system at the onset of a migraine attack has recently received significant interest. We analyzed diffusion tensor imaging (DTI) parameters of the entire hypothalamus and its subregions in 15 patients during a spontaneous migraine attack and in 20 control subjects. We also estimated the non-linear measure resting-state functional MRI BOLD signal's complexity using Higuchi fractal dimension (FD) and correlated DTI/fMRI findings with patients' clinical characteristics. In comparison with healthy controls, patients had significantly altered diffusivity metrics within the hypothalamus, mainly in posterior ROIs, and higher FD values in the salience network (SN). We observed a positive correlation of the hypothalamic axial diffusivity with migraine severity and FD of SN. DTI metrics of bilateral anterior hypothalamus positively correlated with the mean attack duration. Our results show plastic structural changes in the hypothalamus related to the attacks severity and the functional connectivity of the SN involved in the multidimensional neurocognitive processing of pain. Plastic changes to the hypothalamus may play a role in modulating the duration of the attack.

Keywords: diffusion tensor imaging (DTI); fractal dimension (FD); hypothalamus; migraine ictal; resting-state networks (RSN).

Figure 1

Bilateral anterior (in red) and posterior (in blue) hypothalamic regions of interest are shown on axial slice of an MRI template (T1-weighted MNI 2 mm).

Figure 2

Twenty-one spatial maps divided into nine functional networks were found: Auditory (AN—IC2); Cerebellum (Cb—IC1); Default Mode (DMN—IC15, IC20, IC21, IC25, IC27, IC28, and IC31); Dorsal Attention System (DAS: IC6—lDAS and IC17—rDAS); Fronto–Parietal (FPN: IC3—rFPN and IC23—lFPN); Language (LN—IC 26); Salience (SN—IC 10 and IC19); Sensory Motor (SMN—IC7, IC8, IC33); and Visual (VN: IC11—Primary Visual and IC24—Higher Visual) networks based on their anatomical view. Montreal Neurological Institute (MNI) coordinates are shown as well.

Figure 3

Grand average and standard error for the FD values are shown for both groups HC (blue) and MI (red). Upper panel shows the results obtained for aSN (IC 10). All were co-registered into the Montreal Neurological Institute (MNI) space.

Figure 4

Linear regression analysis between FD values (dimensionless) of IC10 (aSN) BOLD activity and the mean severity of headache (VAS) (left panel) and between axial diffusivity (AD) DTI measure and VAS (right panel).

Figure 5

Linear regression analysis between duration of migraine attacks in hours and bilateral anterior hypothalamic MD, AD, and RD values.