Structural Co‐Variance Patterns in Migraine: A Cross‐Sectional Study Exploring the Role of the Hippocampus

Abstract

Objective To interrogate hippocampal morphology and structural co-variance patterns in migraine patients and to investigate whether structural co-variance patterns relate to migraine disease characteristics. Background Migraine is associated with structural alterations in widespread cortical and subcortical regions associated with the sensory, cognitive, and affective components of pain processing. Recent studies have shown that migraine patients have differences in hippocampal structure and function relative to healthy control subjects, but whether hippocampal structure relates to disease characteristics including frequency of attacks, years lived with migraine and symptoms of allodynia remains unknown. Furthermore, this study investigated hippocampal volume co-variance patterns in migraineurs, an indirect measure of brain network connectivity. Here, we explore differences in hippocampal volume and structural co-variance patterns in migraine patients relative to healthy controls and examine whether these hippocampal measures relate to migraine disease burden. Methods This study included 61 migraine patients and 57 healthy control subjects (healthy controls: median age=34.0, IQR=19.0; migraine patients: median age=35.0, IQR=17.5; p=0.65). Regional brain volumes were automatically calculated using FreeSurfer version 5.3. Symptoms of allodynia were determined using the Allodynia Symptom Checklist 12 (ASC-12). Structural covariance patterns were interrogated using pairwise correlations and group differences in correlation strength were estimated using Euclidian distance. A stepwise regression was used to investigate the relationship between structural co-variance patterns with migraine burden. Results Migraine patients had less left hippocampal volume (healthy controls: left hippocampal volume = 4276.8mm3, SD= 425.3mm3, migraine patients: left hippocampal volume= 4089.5mm3, SD= 453.9mm3, p= 0.02) and less total (right plus left) hippocampal volume (healthy controls: total hippocampal volume= 8690.8mm3, SD= 855.1mm3; migraine patients: total hippocampal volume= 8341.8mm3, SD=917.9mm3; p= 0.03) compared to healthy controls. Migraineurs had stronger structural covariance between the hippocampi and cortico-limbic regions in the frontal lobe (inferior opercular gyrus), temporal lobe (planum temporale, amygdala), parietal lobe (angular gyrus, precuneus,) and the cerebellar white matter. Results of a stepwise regression showed that hippocampal volumes and the interactions between hippocampal volumes with the volumes of other cortico-limbic regions associate with migraine-related allodynia but not with headache frequency or years lived with migraine. Conclusion Migraineurs have less hippocampal volume and stronger hippocampal-cortico-limbic connectivity compared to healthy controls. Hippocampal volumes and measures of hippocampal volume connectivity with other cortico-limbic network regions associate with symptoms of allodynia.

Impact of Decorin on the Physical Function and Prognosis of Patients with Hepatocellular Carcinoma

“…The differences between the High and Low decorin groups were analyzed using Wilcoxon rank sum tests. Factors correlated with serum decorin levels were evaluated by pairwise correlations [31]. In addition, independent factors associated with survival were analyzed using Cox regression analysis, as previously described [27].…”

Clinical utility of the Liver Frailty Index for predicting muscle atrophy in chronic liver disease patients with hepatocellular carcinoma

“…Factors correlated with SMI were evaluated by pairwise correlations. 26 In addition, independent factors associated with muscle atrophy were analyzed using a logistic regression analysis, as previously described. 21 Briefly, in this study, we did not conduct the univariate analysis for selection of candidates for logistic regression analysis.…”

“…Differences between the two groups were analyzed using the Wilcoxon rank‐sum test. Factors correlated with SMI were evaluated by pairwise correlations . In addition, independent factors associated with muscle atrophy were analyzed using a logistic regression analysis, as previously described .…”

A Regions of Interest Voxel‐Based Morphometry Study of the Human Brain During High‐Frequency Spinal Cord Stimulation in Patients With Failed Back Surgery Syndrome

“…This idea was supported by several studies in which important similarities between pain chronification and the learning mechanism, coordinated by the hippocampus, were mentioned. [48][49][50][51][52][53][54][55][56][57][58] The hippocampus is involved in learning processes whereby it is considered the primary brain structure for storage and retrieval of long-term explicit memories. 59 In 2012, Mutso et al redefined chronic pain in terms of context conditioning and extinction.…”