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Migraine as a Dynamic Disorder: News about Mathematical Models and Connectivity Analysis

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A special issue of Brain Sciences (ISSN 2076-3425). This special issue belongs to the section "Computational Neuroscience and Neuroinformatics".

Deadline for manuscript submissions: closed (30 December 2020) | Viewed by 18692

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Special Issue Editor

Dr. Marina de Tommaso

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Guest Editor

Applied Neurophysiology and Pain Unit, Basic Medical, Neuroscience and Sensory System Department, Policlinico General Hospital, Bari Aldo Moro University, 70100 Bari, Italy
Interests: headache; migraine; clinical neurophysiology; psychophysiology; cognitive neuroscience; neurodegenerative diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

In the present Special Issue, we aim to exploit innovative results about dynamic models of functional and effective connectivity analysis applied to migraine pathophysiology. This complex disorder is hardly represented by simple neurophysiological and neuroimmaging patterns, though the FMRI and EEG/MEG methods showed differences in default and stimulus and event-related dynamic network interactions. Mathematical models could also be applied to the cohomprension of mechanisms related to cortical spreading depression generation and progression, as well as their clinical implications. The audience of such an issue is intended to include expert clinicians and theoretic researchers, with the aim to establish an ideal field of convergent interest and application.

Dr. Marina de Tommaso
Guest Editor

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Keywords

migraine
pathophysiology
connectivity analysis
mathematical models

Published Papers (6 papers)

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Research

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16 pages, 18054 KiB

Open AccessArticle

Thalamocortical Connectivity in Experimentally-Induced Migraine Attacks: A Pilot Study

by Daniele Martinelli, Gloria Castellazzi, Roberto De Icco, Ana Bacila, Marta Allena, Arianna Faggioli, Grazia Sances, Anna Pichiecchio, David Borsook, Claudia A. M. Gandini Wheeler-Kingshott and Cristina Tassorelli

Brain Sci. 2021, 11(2), 165; https://doi.org/10.3390/brainsci11020165 - 27 Jan 2021

Cited by 13 | Viewed by 2590

Abstract

In this study we used nitroglycerin (NTG)-induced migraine attacks as a translational human disease model. Static and dynamic functional connectivity (FC) analyses were applied to study the associated functional brain changes. A spontaneous migraine-like attack was induced in five episodic migraine (EM) patients using a NTG challenge. Four task-free functional magnetic resonance imaging (fMRI) scans were acquired over the study: baseline, prodromal, full-blown, and recovery. Seed-based correlation analysis (SCA) was applied to fMRI data to assess static FC changes between the thalamus and the rest of the brain. Wavelet coherence analysis (WCA) was applied to test time-varying phase-coherence changes between the thalamus and salience networks (SNs). SCA results showed significantly FC changes between the right thalamus and areas involved in the pain circuits (insula, pons, cerebellum) during the prodromal phase, reaching its maximal alteration during the full-blown phase. WCA showed instead a loss of synchronisation between thalami and SN, mainly occurring during the prodrome and full-blown phases. These findings further support the idea that a temporal change in thalamic function occurs over the experimentally induced phases of NTG-induced headache in migraine patients. Correlation of FC changes with true clinical phases in spontaneous migraine would validate the utility of this model. Full article

(This article belongs to the Special Issue Migraine as a Dynamic Disorder: News about Mathematical Models and Connectivity Analysis)

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11 pages, 1987 KiB

Open AccessArticle

Dynamic Causal Modelling of the Reduced Habituation to Painful Stimuli in Migraine: An EEG Study

by Iege Bassez, Frederik Van de Steen, Katia Ricci, Eleonora Vecchio, Eleonora Gentile, Daniele Marinazzo and Marina de Tommaso

Brain Sci. 2020, 10(10), 712; https://doi.org/10.3390/brainsci10100712 - 07 Oct 2020

Cited by 10 | Viewed by 2798

Abstract

A consistent finding in migraine is reduced cortical habituation to repetitive sensory stimuli. This study investigated brain dynamics underlying the atypical habituation to painful stimuli in interictal migraine. We investigated modulations in effective connectivity between the sources of laser evoked potentials (LEPs) from a first to final block of trigeminal LEPs using dynamic causal modelling (DCM) in a group of 23 migraine patients and 20 controls. Additionally, we looked whether the strength of dynamical connections in the migrainous brain is initially different. The examined network consisted of the secondary somatosensory areas (lS2, rS2), insulae (lIns, rIns), anterior cingulate cortex (ACC), contralateral primary somatosensory cortex (lS1), and a hidden source assumed to represent the thalamus. Results suggest that migraine patients show initially heightened communication between lS1 and the thalamus, in both directions. After repetitive stimulations, connection strengths from the thalamus to all somatosensory areas habituated in controls whereas this was not apparent in migraine. Together with further abnormalities in initial connectivity strengths and modulations between the thalamus and the insulae, these results are in line with altered thalamo-cortical network dynamics in migraine. Group differences in connectivity from and to the insulae including interhemispheric connections, suggests an important role of the insulae. Full article

(This article belongs to the Special Issue Migraine as a Dynamic Disorder: News about Mathematical Models and Connectivity Analysis)

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33 pages, 14578 KiB

Open AccessArticle

Alternative Microstructural Measures to Complement Diffusion Tensor Imaging in Migraine Studies with Standard MRI Acquisition

by Álvaro Planchuelo-Gómez, David García-Azorín, Ángel L. Guerrero, Rodrigo de Luis-García, Margarita Rodríguez and Santiago Aja-Fernández

Brain Sci. 2020, 10(10), 711; https://doi.org/10.3390/brainsci10100711 - 06 Oct 2020

Cited by 11 | Viewed by 3324

Abstract

The white matter state in migraine has been investigated using diffusion tensor imaging (DTI) measures, but results using this technique are conflicting. To overcome DTI measures, we employed ensemble average diffusion propagator measures obtained with apparent measures using reduced acquisitions (AMURA). The AMURA measures were return-to-axis (RTAP), return-to-origin (RTOP) and return-to-plane probabilities (RTPP). Tract-based spatial statistics was used to compare fractional anisotropy, mean diffusivity, axial diffusivity and radial diffusivity from DTI, and RTAP, RTOP and RTPP, between healthy controls, episodic migraine and chronic migraine patients. Fifty healthy controls, 54 patients with episodic migraine and 56 with chronic migraine were assessed. Significant differences were found between both types of migraine, with lower axial diffusivity values in 38 white matter regions and higher RTOP values in the middle cerebellar peduncle in patients with a chronic migraine (p < 0.05 family-wise error corrected). Significantly lower RTPP values were found in episodic migraine patients compared to healthy controls in 24 white matter regions (p < 0.05 family-wise error corrected), finding no significant differences using DTI measures. The white matter microstructure is altered in a migraine, and in chronic compared to episodic migraine. AMURA can provide additional results with respect to DTI to uncover white matter alterations in migraine. Full article

(This article belongs to the Special Issue Migraine as a Dynamic Disorder: News about Mathematical Models and Connectivity Analysis)

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Graphical abstract

14 pages, 2981 KiB

Open AccessArticle

by Arne May, Laura Helene Schulte, Guido Nolte and Jan Mehnert

Brain Sci. 2020, 10(9), 603; https://doi.org/10.3390/brainsci10090603 - 02 Sep 2020

Cited by 1 | Viewed by 2218

Abstract

Imaging studies help us understand the important role of brainstem and midbrain regions in human trigeminal pain processing without solving the question of how these regions actually interact. In the current study, we describe this connectivity and its dynamics during nociception with a novel analytical approach called Partial Similarity (PS). We developed PS specifically to estimate the communication between individual hubs of the network in contrast to the overall communication within that network. Partial Similarity works on trial-to-trial variance of neuronal activity acquired with functional magnetic resonance imaging. It discovers direct communication between two hubs considering the remainder of the network as confounds. A similar method to PS is Representational Similarity, which works with ordinary correlations and does not consider any external influence on the communication between two hubs. Particularly the combination of Representational Similarity and Partial Similarity analysis unravels brainstem dynamics involved in trigeminal pain using the spinal trigeminal nucleus (STN)—the first relay station of peripheral trigeminal input—as a seed region. The combination of both methods can be valuable tools in discovering the network dynamics in fMRI and an important instrument for future insight into the nature of various neurological diseases like primary headaches. Full article

(This article belongs to the Special Issue Migraine as a Dynamic Disorder: News about Mathematical Models and Connectivity Analysis)

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Review

Jump to: Research

21 pages, 326 KiB

Open AccessFeature PaperReview

by Marina de Tommaso, Eleonora Vecchio, Silvia Giovanna Quitadamo, Gianluca Coppola, Antonio Di Renzo, Vincenzo Parisi, Marcello Silvestro, Antonio Russo and Gioacchino Tedeschi

Brain Sci. 2021, 11(2), 234; https://doi.org/10.3390/brainsci11020234 - 13 Feb 2021

Cited by 17 | Viewed by 3735

Abstract

A neuronal dysfunction based on the imbalance between excitatory and inhibitory cortical-subcortical neurotransmission seems at the basis of migraine. Intercritical neuronal abnormal excitability can culminate in the bioelectrical phenomenon of Cortical Spreading Depression (CSD) with secondary involvement of the vascular system and release of inflammatory mediators, modulating in turn neuronal activity. Neuronal dysfunction encompasses the altered connectivity between the brain areas implicated in the genesis, maintenance and chronic evolution of migraine. Advanced neuroimaging techniques allow to identify changes in functional connectivity (FC) between brain areas involved in pain processes. Through a narrative review, we re-searched case-control studies on FC in migraine, between 2015 and 2020, by inserting the words migraine, fMRI, EEG, MEG, connectivity, pain in Pubmed. Studies on FC have shown that cortical processes, in the neurolimbic pain network, are likely to be prevalent for triggering attacks, in response to predisposing factors, and that these lead to a demodulation of the subcortical areas, at the basis of migraine maintenance. The link between brain dysfunction and peripheral interactions through the inhibition of CGRP, the main mediator of sterile migraine inflammation needs to be further investigated. Preliminary evidence could suggest that peripheral nerves inference at somatic and trigeminal levels, appears to change brain FC. Full article

(This article belongs to the Special Issue Migraine as a Dynamic Disorder: News about Mathematical Models and Connectivity Analysis)

17 pages, 2422 KiB

Open AccessReview

Misperception of Visual Verticality in Patients with Primary Headache Disorders: A Systematic Review with Meta-Analysis

by Esteban Obrero-Gaitán, María Manrique-Navarro, Miguel Ángel Lérida-Ortega, Daniel Rodríguez-Almagro, María Catalina Osuna-Pérez and Rafael Lomas-Vega

Brain Sci. 2020, 10(10), 664; https://doi.org/10.3390/brainsci10100664 - 24 Sep 2020

Cited by 5 | Viewed by 3389

Abstract

Migraine and tension-type headache (TTH) are the two most prevalent primary headache disorders (PHDs) that may involve visual and vestibular impairments, neck pain, and postural unsteadiness. The perception of visual verticality (VV) has been studied in patients diagnosed with PHD to assess balance disorders showing varying findings. Our study aimed to assess the VV perception in patients diagnosed with PHD in comparison to healthy controls. A systematic review with meta-analysis was carried out in PubMed MEDLINE, Scopus, WOS, CINAHL, and SciELO. The Cohen standardized mean difference (SMD) was used to estimate the differences between exposed and healthy controls. Seven studies with 816 participants were included. The quality of included studies, according to the Newcastle–Ottawa Scale (NOS), was moderate (mean score of 5.2). Patients diagnosed with PHD showed a moderate misperception of VV as assessed with the subjective visual vertical (SVV) test (SMD = 0.530; 95% CI = 0.225, 0.836; p < 0.001). Specifically, a misperception of the SVV was found in patients with migraine (SMD = 0.369; 95% CI = 0.1, 0.638; p = 0.007) and with TTH (SMD = 1.122; 95% CI = 0.540, 1.704; p < 0.001). This review shows a misperception of VV in patients with migraine and TTH when assessed with the SVV test, being higher in patients with TTH, although the THH sample size was low. Full article

(This article belongs to the Special Issue Migraine as a Dynamic Disorder: News about Mathematical Models and Connectivity Analysis)

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