Hypothalamic structural integrity and temporal complexity of cortical information processing at rest in migraine without aura patients between attacks

Abstract

The hypothalamus has been attributed an important role during the premonitory phase of a migraine attack. Less is known about the role played by the hypothalamus in the interictal period and its relationship with the putative neurocognitive networks previously identified in the pathophysiology of migraine. Our aim was to test whether the hypothalamic microstructure would be altered during the interictal period and whether this co-existed with aberrant connectivity at cortical level. We collected multimodal MRI data from 20 untreated patients with migraine without aura between attacks (MO) and 20 healthy controls (HC) and studied fractional anisotropy, mean (MD), radial (RD), and axial diffusivity of the hypothalamus ROI as a whole from diffusion tensor imaging (DTI). Moreover, we performed an exploratory analysis of the same DTI metrics separately for the anterior and posterior hypothalamic ROIs bilaterally. From resting-state functional MRI, we estimated the Higuchi’s fractal dimension (FD), an index of temporal complexity sensible to describe non-periodic patterns characterizing BOLD signature. Finally, we correlated neuroimaging findings with migraine clinical features. In comparison to HC, MO had significantly higher MD, AD, and RD values within the hypothalamus. These findings were confirmed also in the exploratory analysis on the sub-regions of the hypothalamus bilaterally, with the addition of lower FA values on the posterior ROIs. Patients showed higher FD values within the salience network (SN) and the cerebellum, and lower FD values within the primary visual (PV) network compared to HC. We found a positive correlation between cerebellar and SN FD values and severity of migraine. Our findings of hypothalamic abnormalities between migraine attacks may form part of the neuroanatomical substrate that predisposes the onset of the prodromal phase and, therefore, the initiation of an attack. The peculiar fractal dimensionality we found in PV, SN, and cerebellum may be interpreted as an expression of abnormal efficiency demand of brain networks devoted to the integration of sensory, emotional, and cognitive information related to the severity of migraine.

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

“…However, diffusivity metrics reflect not only myelin content, but also rapid changes in membrane volume, glial cell morphology, and the number of local neuronal circuits [ 26 ]. In a previous study using the same methodology in the interictal phase, we detected significantly higher MD, AD, and RD values within the hypothalamus as a whole and in the anterior and posterior ROIs bilaterally as well, with the addition of lower FA values on the posterior ROIs [ 18 ].…”

“…Diffusion tensor imaging (DTI) was acquired by using single shot echo-planar imaging (TR 12,200 ms, TE 94 ms, 72 axial slices, 2 mm thickness, isotropic voxels) [ 18 ] and using SPAIR (Spectral Attenuated Inversion Recovery) as a fat suppression technique. Images from the same participants and during the same session were obtained with diffusion gradients applied along 30 non-collinear directions, effective b values of 0 and 1000 s/mm 2 were used.…”

“…Using diffusion tensor imaging (DTI) data recorded in patients with migraine without aura between attacks, we have recently described abnormal proton diffusivity in the anterior and posterior hypothalamus. In the same study, we found abnormal fractal dimensionality of BOLD signals in cortical networks that support the integration of sensory, emotional, and cognitive information [ 18 ] and that correlated with the clinical presentation of migraine pain. In the present study, we investigated the microstructural integrity of the hypothalamus through DTI and the non-linear functional connectivity of the resting state network (RSN) computed from fMRI measures in a group of patients with migraine without aura in whom imaging data acquisition occurred in close temporal proximity with a spontaneous attack.…”

The Patent Foramen Ovale and Migraine: Associated Mechanisms and Perspectives from MRI Evidence

“…In addition to the structural changes in migraine, we need to pay attention to the functional changes detected by fMRI. On the one hand, the activation of the thalamus, brainstem, and related functional areas such as the cingulate gyrus, insular lobe, and temporal lobe can be observed under task stimulation, indicating that these areas are involved in the pathophysiological process of inducing migraine [ 57 , 58 , 59 ]. On the other hand, abnormal brain networks and functional connections can also be observed in the resting state, including the occipital lobe, the sensorimotor network, bilateral lateral and inferior cerebellum, the cingulo–opercular network, the default mode network, and the frontal–parietal network [ 62 , 63 ].…”

Cerebro-Cerebellar Networks in Migraine Symptoms and Headache

“…In another recent study, interictal assessment of episodic migraineurs has found alterations in dynamic functional coupling between the hypothalamus and brain regions, processing pain and vision, as well as high-order sensations, representing clinical features, such as disease duration and disability in the orbitofrontal gyrus of the prefrontal cortex ( 37 ). In a resting-state analysis, decreased functional connectivity between the hypothalamus and medial prefrontal cortex was also observed, suggesting hypothalamic network involvement for pain perception and severity during attacks in chronic migraine ( 38 , 39 ). These aversive sensations (i.e., pain, photophobia, nausea, etc.)…”