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.
Highlights
The hypothalamus has been attributed an important role during the premonitory phase of a migraine attack
Considering that in previous studies the hypothalamus has been involved in the pre-ictal period of migraine and that the activity of cortical networks is dysfunctional even outside attacks, we hypothesized that the microstructure of the hypothalamus could be altered during the pain-free period, as a favoring anatomical substrate to the recurrence of migraine, and that would be independent from aberrant resting-state network (RSN) connectivity and migraine clinical features
No significant difference emerged between migraine without aura (MO) and healthy controls (HC) in gender (χ 12 = 0.102, p = 0.749) and age (t38 = − 1.628, p = 0.112)
Summary
The hypothalamus has been attributed an important role during the premonitory phase of a migraine attack. We measure the hypothalamic microstructure through diffusion tensor imaging (DTI), a useful sensitive method to detect white matter tracts in grey matter nuclei—as is the case for the hypothalamus[10] and the independent cortical networking by acquiring resting-state functional MRI taking the advantages of the non-linearity of the Higuchi’s fractal dimension (FD) analysis[11,12,13,14] This non-linear approach is more suitable to describe the irregular and non-periodic patterns characterizing the BOLD signature of discrete cortical areas belonging to a resting-state network (RSN) recorded by n euroimaging[15,16] as well as electrophysiological techniques[17,18]. Considering that in previous studies the hypothalamus has been involved in the pre-ictal period of migraine and that the activity of cortical networks is dysfunctional even outside attacks, we hypothesized that the microstructure of the hypothalamus could be altered during the pain-free period, as a favoring anatomical substrate to the recurrence of migraine, and that would be independent from aberrant RSN connectivity and migraine clinical features
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