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Table 3 Overview of included studies. For each recording modality, more recent articles appear first in the table

From: Headache-related circuits and high frequencies evaluated by EEG, MRI, PET as potential biomarkers to differentiate chronic and episodic migraine: Evidence from a systematic review

Source (DOI)

Recording modality

Population

Study design

Potential biomarker

Major findings

Pan L et al. (2022) [14]

EEG and MEG

NA

Non-systematic review article

Beta connectivity (node degree) in anterior cingulate cortex

The resting state electrophysiology (power and connectivity) can be used to detect pathological alterations in patients with migraine

Ong J et al. (2012) [15]

EEG (from PSG)

NA

Non-systematic review article

Slow-wave sleep activity

Biobehavioral model to describe the interaction between headache, its impact on insomnia and sleep physiology, and the downstream propensity for future headache attacks

Gomez-Pilar J et al. (2020) [16]

EEG

HC: 39

CM: 42

EM: 45 (interictal)

Spectral and nonlinear analysis during resting state recordings (eyes closed)

Relative power in high beta frequency band

Significant differences in relative power between CM and EM around high beta frequency band. Significant differences in alpha between HC and migraine patients

Lisicki M et al. (2020) [17]

EEG

HC: 20

CM: 20

EM: 50 (30 interictal and 20 ictal)

Spectral analysis of Visual Evoked Potentials (VEPs)

Spectral power in gamma band in occipital areas during VEPs recordings

Gamma/alpha activity ratio can distinguish between CM and EM in the interictal stage. Non-significant differences were found between CM and EM during migraine attack

Fogang Y et al. (2015) [18]

EEG

HC: 24

CM: 48

EM: 232 (61 with aura and 171 without aura)

Spectral analysis of Steady-State Visual Evoked Potentials (SSVEPs)

Photic driving power at 20 Hz during SSVEPs in occipital areas

Increased photic driving power is related to attack duration and identifies subgroups of migraine patients with different habituation of cortical visual responses

Hsiao F et al. (2021a) [19]

MEG

HC: 65

CM: 80

EM: 70

Connectivity analysis of resting state activity (eyes closed)

Node strength in the beta band based on imaginary coherence in the ACC

Reduced beta connectivity in the anterior cingulate cortex linked to migraine chronification

Hsiao F et al. (2021b) [20]

MEG

CM: 37

EM: 30

Temporal analysis of SEF recordings during interictal stage

Amplitude of SEF after treatment

Somatosensory gating responses are similarly associated with treatment outcomes in patients with CM and EM

Wu T et al. (2018) [21]

MEG

HC: 35

CM: 15

EM: 20 (interictal)

Time–frequency analysis of emotional stimulation responses focused on M100 and M170 components

NA (authors did not find significant differences between EM and CM groups)

CM and EM have abnormal brain activity in the gamma band in response to negative emotional stimuli during interictal stage

Chen W et al. (2012) [22]

MEG

CM: 15

EM: 10 (remitted CM)

Temporal analysis of visual evoked fields (VEF)

P100m amplitude

Visual cortex excitability is dynamically modulated (reduced) in remission from CM to EM

Chen W et al. (2011a) [23]

MEG

HC: 24

CM: 18

EM: 39

Persistent visual aura patients: 6

Temporal analysis of visual evoked fields (VEF)

NA (authors did not find significant differences between EM and CM groups)

Patients with persistent visual aura maintains a steady-state hyperexcitability without significant dynamic modulation

Chen W et al. (2011b) 24[]

MEG

HC: 32

CM: 25

EM: 38 (29 interictal and 9 ictal)

Temporal analysis of visual evoked fields (VEF)

P100m amplitude

Different underlying mechanisms for interictal excitability of CM (hyperexcitability with habituation) and EM (hypo-excitability with potentiation)

Dai W et al. (2021) [25]

fMRI

HC: 30

CM: 17 (with medication-overuse)

EM: 18

Connectivity analysis during resting state

Functional connectivity between bilateral habenula and salience network

Increased functional connectivity between bilateral habenula and salience network (correlated with medication overuse duration) in patients with CM compared with patients with EM and HC, respectively

Chen C et al. (2019) [26]

fMRI

HC: 32

CM: 17

EM: 39 (19 infrequent EM and 20 frequent EM)

ReHo applied to resting state fMRI recordings

ReHo in resting state at bilateral precentral gyri

The regions affected by migraine change with the chronification of the disease

Chen Z et al. (2019) [27]

fMRI

HC: 21

CM: 16

EM: 18

Anatomical and functional connectivity analysis during fMRI resting state recordings

Functional connectivity in anterior hypothalamus

Volume of hypothalamus (HTH) was significantly decreased on CM and EM vs HC. Decreased volume of anterior HTH in CM vs HC and CM vs EM. Increased functional connectivity between anterior HTH and MOrG in CM vs EM

Lerebours F et al. (2019) [28]

fMRI

CM: 25 (with medication-overuse)

EM: 22 (interictal)

Connectivity analysis during fMRI resting state recordings

Functional connectivity in hypothalamus

Significant connectivity between anterior hypothalamus and trigeminal nucleus for CM vs. EM, no correlated with pain intensity. This connectivity is similar to that seen in the preictal phase of EM, suggesting that CM are locked in the preictal phase

Bogdanov V et al. (2019) [29]

fMRI

HC: 24

CM: 7 (with medication-overuse)

EM: 19 (14 interictal and 5 ictal)

fMRI during transitions between continuous noxious cold and innocuous warm thermal stimulations

BOLD response to cold/warm transitions of thermal stimuli over motor cortex and superior temporal sulcus

Migraine patients showed hyperactivation on “salience-matrix” areas compared to HC. CM and EM (ictal) showed increased unspecific transitional BOLD responses in motor cortex and superior temporal sulcus versus EM (interictal) and HC. CM overactivated also other “salience” matrix areas compared to EM-b

Imai N (2018) [30]

fMRI

CM: 31

EM: 31

Functional connectivity analysis during resting state

Functional connectivity in ACC and ROcG

Increased FC in ACC and ROcG for CM vs EM, suggesting that occipital pole plays a key role in migraine chronification

Schulte L et al. (2017) [31]

fMRI

HC:19

CM: 17

EM: 18

Analysis of fMRI during painful ammonia stimulation

Functional activation of the hypothalamus during ammonia stimulation

Hypothalamus plays a crucial role in the pathophysiology of migraine chronification and acute pain stage of migraine patients

Chen Z et al. (2017) [32]

fMRI

HC: 18

CM: 16

EM: 18

Anatomical and connectivity analysis during resting state (interictal)

Functional connectivity (FC) in bilateral amygdala

Amygdala volume showed no differences between groups. Increased FC between amygdala and inferior temporal gyrus and

orbitofrontal gyrus for CM vs EM. Enhanced FC in left amygdala for EM vs. HC. Decreased FC in right amygdala for CM vs HC

Hubbard C et al. (2016) [33]

fMRI

CM: 11 (responders to BoNT-A)

CM: 12 (non-responders to BoNT-A)

Longitudinal anatomical and functional connectivity analyses during resting state (before and after treatment)

Functional connectivity between SI-DMPFC and SI-LOC

Responders showed significant cortical thickening (SI, aINS, STG, ParsOp) and functional connectivity differences (SI-LOC, SI-DMPFC) in CM that reverted to EM compared to CM that did not respond to the treatment

Chen Z et al. (2016) [34]

fMRI

HC: 32

CM: 60 (44 with medication-overuse)

EM: 18

Connectivity analysis during resting state

Functional connectivity between marginal division of neostriatum (MrD) and pain network

MrD demonstrated different pain modulation patterns in different subtypes of headache. Functional connectivity between MrD and other regions yielded significant differences between all groups. Compared with EM, both CM and HC showed decreased functional connectivity of MrD

Torres-Ferrus M et al. (2021) [35]

PET

HC: 11

CM: 7

EM: 8 (interictal)

Resting F-FDG-PET in interictal stages

Not available (no changes CM vs EM)

CM patients showed frontotemporal hypometabolism and increased frontal cortical thickness (CTh) when compared to HC. EM presented intermediated values but not significant

Jassar H et al. (2019) [36]

PET

HC: 7

CM: 7

EM: 8 (ictal)

Measure μ-opioid in resting PET after injection of μOR radiotracer with and without thermal pain threshold challenge

μOR availability measured with [11C]carfentanil nondisplaceable binding potential (BPND)

CM had decreased μOR BPND relative to HC in thalamus and left caudate. Lower μOR BPND in right parahippocampal region and right amygdala compared to EM. Increased endogenous μOR receptor is seen in the limbic system of CM patients

Deen M et al., (2019) [37]

PET

HC: 16

CM: 16

EM: 15

Measure of serotonin 5-HT in resting PET scans after injection of 5-HT4 receptor radioligand

Not available (no changes CM vs EM)

CM had 9.1% lower binding than HC. Thus, cerebral levels of 5-HT are elevated in CM. No significant differences between CM and EM. No association between binding and no migraine days. Elevated 5-HT may not be a risk factor for conversion from EM to CM

  1. NA Not applicable
  2. HC Healthy control; EM Episodic migraine; CM Chronic migraine; PSG Polysomnography; BoNT-A onabotulinumtoxinA
  3. SEF Somatosensory Evoked Field; ReHo: Regional Homology Analysis Method