Migraine Cycle Research Articles

Preserved working memory performance along with subcortical modulation during peri-ictal phases in spontaneous migraine attacks.

To analyze cognitive performance and brain activation during a working memory task in patients with migraine during various phases of the migraine cycle and compare to healthy participants. Cognitive difficulties reported during migraine attacks remain poorly understood, despite evidence that the lateral frontoparietal network undergoes reversible disturbances and decreased activation during attacks. Recent findings in resting state functional magnetic resonance imaging suggest that brain areas involved in this network interact with subcortical regions during spontaneous migraine attacks. In this prospective, within-subject study, 10 patients with diagnosed menstrual-related episodic migraine without aura underwent 3T functional magnetic resonance imaging assessments while performing a working memory task across four phases of the natural migraine cycle: peri-ictal (preictal, ictal, postictal) phases and interictally (between attacks). Migraine prophylaxis was an exclusion criterion. Fourteen healthy controls were assessed during the corresponding phases of their menstrual cycles. The protocol was completed by 24 female participants aged 21 to 47 years: 10 with migraine (four sessions each) and 14 healthy controls (two sessions each) yielding a total of 68 analyzed datasets. Patients and controls showed similar performance on the working memory task and displayed increased brain activity in regions linked to this function, namely the middle frontal gyrus, inferior parietal lobe, and anterior cingulate cortex, during all phases of the migraine/menstrual cycle. Patients with migraine (N = 10) exhibited a significant decrease in hypothalamic activity (p = 0.007) as measured by the percent signal change (PSC) during the postictal phase compared to perimenstrual controls (N = 14), with -2 (16) and 31 (35) PSC, respectively. Comparing across the migraine cycle, the change in hypothalamic activity relative to controls in the postictal phase -0.33 (0.2) ΔPSC was significantly different from the ones in the interictal (0.006 [0.5] ΔPSC; p = 0.002) and preictal (-0.08 [0.4] ΔPSC; p = 0.034) phases. During a working memory task, cognition-related brain activation was present across all phases of the migraine cycle similarly to healthy control participants. Patients with migraine, however, displayed lower neural activity at the subcortical level in the postictal phase. Nonetheless, the sample size is a limitation for the generalization of our results. More research is needed to fully understand how the brain copes with cognitive demands during spontaneous migraine attacks.

Symptoms across the phases of the migraine cycle from the patient's perspective: Results of the MiCOAS qualitative study.

To better understand the breadth and frequency of symptoms across the phases of the migraine cycle using data captured from qualitative patient interviews conducted through the Migraine Clinical Outcome Assessment System (MiCOAS) project. People living with migraine experience a range of symptoms across the pre-headache, headache, post-headache, and interictal phases of the migraine cycle. Although clinical diagnostic criteria and clinical trial endpoints focus largely on cardinal symptoms or monthly migraine days, migraine symptom profiles are far more complex. As a part of the MiCOAS project, semi-structured qualitative interviews were undertaken to better understand the migraine-related symptomology from the patient's viewpoint. This concept elicitation study used iterative purposeful sampling to select 40 people with self-reported medical diagnosis of migraine for interviews that were conducted via audio-only web conferencing. Key topics related to migraine symptoms, including mood/emotion symptoms, were identified using content analysis. Interview transcripts were also coded to reflect the phase of migraine under discussion, so that patient experiences could be compared by phase. Forty participants (50%, n = 20 episodic migraine; 50%, n = 20 chronic migraine), aged from 21 to 70 years old reported a total of 60 unique symptoms, which were categorized into 30 broader symptom categories. Participants reported between 7 and 22 unique symptom categories across all phases. During pre-headache and headache, participants reported a median of 7.5 (interquartile range [IQR] = 5.5) and 8 (IQR = 4.0) different symptom categories compared to 4 (IQR = 3.0) and 1.5 (IQR = 2.5) for the post-headache and interictal periods, respectively. Head pain during the headache phase was the only universally reported symptom (100%, n = 40). Pooling across all phases, the next most reported symptoms were light sensitivity (93%, n = 37), nausea (88%, n = 35), irritability/impatience (83%, n = 24), sound sensitivity (80%, n = 32), and fatigue/exhaustion (80%, n = 32). One or more interictal symptoms were reported by 73% (n = 29) of participants and included mood/emotion symptoms, such as anxiety (30%, n = 12), depression (18%, n = 7), and anger (15%, n = 6), as well as cardinal symptoms, such as light sensitivity (13%, n = 5) and nausea (13%, n = 5). Patients experience a range of symptoms across the phases of the migraine cycle. Results often aligned with clinical expectations, but non-cardinal migraine-related symptoms were reported both inside and outside the headache phase, including between attacks. These discoveries highlight the importance of assessing a range of symptoms and timing when developing patient-reported outcome measures for migraine clinical trials.

Quantifying sensory thresholds along the migraine cycle: An exploratory longitudinal study.

To date, a number of studies on migraine have cross-sectionally evaluated sensory sensitivity with aversion thresholds/scores along the migraine cycle, reporting a decreased tolerance to sensory stimuli in different sensory modalities. Our hypothesis was that patients with migraine would exhibit heightened sensitivity to sound, light, touch and smell on days where they reported greater headache intensity. This is an exploratory, longitudinal study, carried out over the course of 27 days. Aversion thresholds or scores to sound, light, touch and smell were quantified in six patients with migraine (11.33 ± 6.53 headache days/month). Patients reported an increased sensitivity to light (padj = 0.0297), touch (padj = 0.0077), and smell (padj = 0.0201) on days with higher headache intensity. However, a greater sensitivity to sound on days with higher headache intensity was only reported when anxiety levels were high (padj = 1.4e-06). Interestingly, variable levels of tolerance to bothersome light over time can also influence the correlation between light sensitivity and headache intensity (padj = 1.4e-06). Based on the present findings, future longitudinal studies evaluating sensory threshold changes along the migraine cycle in patients with migraine should account for the increased tolerance to bothersome light over time as well as the effect of anxiety on auditory sensitivity.

Electrophysiological findings in migraine may reflect abnormal synaptic plasticity mechanisms: A narrative review.

The cyclical brain disorder of sensory processing accompanying migraine phases lacks an explanatory unified theory. We searched Pubmed for non-invasive neurophysiological studies on migraine and related conditions using transcranial magnetic stimulation, electroencephalography, visual and somatosensory evoked potentials. We summarized the literature, reviewed methods, and proposed a unified theory for the pathophysiology of electrophysiological abnormalities underlying migraine recurrence. All electrophysiological modalities have determined specific changes in brain dynamics across the different phases of the migraine cycle. Transcranial magnetic stimulation studies show unbalanced recruitment of inhibitory and excitatory circuits, more consistently in aura, which ultimately results in a substantially distorted response to neuromodulation protocols. Electroencephalography investigations highlight a steady pattern of reduced alpha and increased slow rhythms, largely located in posterior brain regions, which tends to normalize closer to the attacks. Finally, non-painful evoked potentials suggest dysfunctions in habituation mechanisms of sensory cortices that revert during ictal phases. Electrophysiology shows dynamic and recurrent functional alterations within the brainstem-thalamus-cortex loop varies continuously and recurrently in migraineurs. Given the central role of these structures in the selection, elaboration, and learning of sensory information, these functional alterations suggest chronic, probably genetically determined dysfunctions of the synaptic short- and long-term learning mechanisms.

Altered functional connectivity in a sensorimotor-insular network during spontaneous migraine attacks: A resting-state FMRI study

BackgroundPrevious functional magnetic resonance imaging studies have identified brain-connectivity alterations across multiple regions in people with migraine when compared to healthy controls. Few studies have focused on such changes throughout the different phases of the migraine cycle. We aimed to investigate functional connectivity during spontaneous occurring episodic migraine attacks, in comparison to interictal periods. MethodsEleven women with episodic migraine without aura underwent two sessions of resting-state fMRI, during and outside of a spontaneous migraine attack. Functional connectivity changes were assessed across canonical resting-state networks, identified by independent component analysis. Significantly altered connectivity was correlated with migraine attack symptoms. ResultsDecreased functional connectivity between subregions of the sensorimotor network (specifically, the primary somatosensory and motor cortices) and the posterior insula, bilaterally, was found during attacks. In both sessions, the functional connectivity between these regions was lower in patients who usually suffered longer attacks. DiscussionThe sensorimotor and insular regions are involved in nociceptive, autonomic, and somatosensory processing so the finding of reduced connectivity between these structures within a migraine attack is likely associated to the perception of pain and the heighten sensitivity to stimuli experienced in this disorder.

Trigeminocervical pain sensitivity during the migraine cycle depends on headache frequency

ObjectiveThis experimental study aimed to assess pain sensitivity in low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM), and chronic migraine (CM) patients across the different phases of the migraine cycle.MethodIn this observational, experimental study, clinical characteristics (diary and time from the last/next headache attack), and quantitative sensory testing (QST) (wind-up pain ratio (WUR) and pressure pain threshold (PPT) from the trigeminal area and PPT from the cervical spine) was performed. LFEM, HFEM, and CM were assessed in each of the 4 migraine phases (HFEM and LFEM: interictal, preictal, ictal, and postictal; CM: interictal and ictal) and compared vs. each other’s (matched for the phase) and controls.ResultsA total of 56 controls, 105 LFEM, 74 HFEM, and 32 CM were included. No differences in QST parameters were observed between LFEM, HFEM, and CM in any of the phases.During the interictal phase and when comparing with controls the following were found: 1) LFEM had lower trigeminal PPT (p = 0.001) and 2) lower cervical PPT (p = 0.001). No differences were observed between HFEM or CM and healthy controls. During the ictal phase and when comparing with controls the following were found: HFEM and CM had 1) lower trigeminal PPTs (HFEM p = 0.001; CM = p < 0.001), 2) lower cervical PPT s (HFEM p = 0.007; CM p < 0.001), and 3) higher trigeminal WUR (HFEM p = 0.001, CM p = 0.006). No differences were observed between LFEM and healthy controls. During the preictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.007), 2) HFEM had lower trigeminal (p = 0.013) and 3) HFEM had lower cervical (p = .006) PPTs. During the postictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.003), 2) HFEM had lower trigeminal PPT (p = 0.005), and 3) and HFEM had lower cervical (p = 0.007) PPTs.ConclusionThis study suggested that HFEM patients have a sensory profile matching CM better than LFEM. When assessing pain sensitivity in migraine populations, the phase with respects to headache attacks is of utmost importance and can explain the inconsistency in pain sensitivity data reported in the literature.

Characterizing inter- and intra-individual differences in migraine-related cognitive symptoms and impairment across the migraine cycle: An analysis of the MiCOAS qualitative project (P7-12.007)

Characterizing inter- and intra-individual differences in migraine-related cognitive symptoms and impairment across the migraine cycle: An analysis of the MiCOAS qualitative project (P7-12.007)

Exploring within-person differences in migraine-associated symptoms across phases of the migraine cycle: Results of the MiCOAS Qualitative Study (P7-12.006)

Exploring within-person differences in migraine-associated symptoms across phases of the migraine cycle: Results of the MiCOAS Qualitative Study (P7-12.006)

Increase pain sensitivity during the four phases of the migraine cycle in patients with episodic migraine.

Understanding the importance of immigrant entrepreneurship in today's globalized world is crucial for economic, political, and social development. This study is one of the first in the field to explore one immigrant community's entrepreneurship experiences across three different countries. A typology of three different types of immigrant entrepreneurs is identified based on time and space, namely, the displaced, the transnational, and the frustrated. The results show that the UK presents more adverse and racialized experiences for immigrant business start-up in comparison to Denmark and especially Norway. This paper contributes to discourse of intra-ethnic variation, transnationalism, and mixed embeddedness.

Investigating the Migraine Cycle over 21 Consecutive Days Using Proton Magnetic Resonance Spectroscopy and Resting-State fMRI: A Pilot Study.

Recent neuroimaging studies have revealed important aspects of the underlying pathophysiological mechanisms of migraine suggesting abnormal brain energy metabolism and altered functional connectivity. Proton magnetic resonance spectroscopy (1H-MRS) studies investigated migraine patients in the interictal or ictal state. This first-of-its-kind study aimed to investigate the whole migraine cycle using 1H-MRS and resting-state functional magnetic resonance imaging (fMRI). A migraine patient underwent 1H-MRS and resting-state fMRI for 21 consecutive days, regardless of whether he was in an interictal or ictal state. Metabolite ratios were assessed and compared to the intrinsic connectivity of subcortical brain areas. Probable migraine phase-dependent changes in N-acetyl aspartate (NAA)/total creatine (tCr) and choline (Cho)/tCr levels are found in the left occipital lobe and left basal ganglia. NAA reflects neuronal integrity and Cho cellular membrane turnover. Such abnormalities may increase the susceptibility to excitatory migraine triggers. Functional connectivity between the right hippocampus and right or left pallidum was strongly correlated to the NAA/Cho ratio in the right thalamus, suggesting neurochemical modulation of these brain areas through thalamic connections. To draw statistically significant conclusions a larger cohort is needed.

Cyclic changes of sensory parameters in migraine patients.

Migraine shows a cyclic pattern with an inter-ictal-, a pre-ictal, an ictal- and a post-ictal phase. We aimed to examine changes in psychophysical parameters during the migraine cycle. The perception of nociceptive and non-nociceptive stimuli and an electrically induced axon-reflex-erythema were assessed in 20 healthy controls and 14 migraine patients on five consecutive days according to different phases of the migraine cycle. Pain was rated three times during a 10-second electrical stimulus. The size of the axon-reflex-erythema was determined using laser-Doppler-imaging. Intensity and hedonic estimates of odours presented by Sniffin' Sticks were rated. In healthy controls, no significant changes over the test days were observed. In migraine patients pain thresholds at the head decreased with an ictal minimum. Less habituation after five seconds of stimulation at the head was found pre-ictally, whereas reduced habituation to 10-second electrical stimulation was present in all phases. The axon-reflex-erythema size showed an inter-ictal-specific minimum at the head. odours were perceived ictally as more unpleasant and intense. Somatosensory functions, pain thresholds and habituation as predominantly central parameters, axon-reflex-erythema as a peripheral function of trigeminal neurons and odour perception as a predominantly extra-thalamic sensation change specifically over the migraine cycle indicating complex variations of neuronal signal processing.

Cervical musculoskeletal impairments in the 4 phases of the migraine cycle in episodic migraine patients.

To assess cervical musculoskeletal impairments during the 4 phases of a migraine cycle in episodic migraine patients, controlling for the presence of concomitant neck pain. Differences in cervical musculoskeletal impairments were assessed during the 4 migraine phases in episodic migraine patients and compared with healthy controls controlling for concomitant neck pain. Cervical musculoskeletal impairments were assessed as follow: cervical active range of motion; flexion rotation test; craniocervical flexion test and calculation of activation pressure score; the total number of myofascial trigger points in head/neck muscles; the number of positivevertebral segments (headache's reproduction) during passive accessory intervertebral movement; pressure pain thresholds over C1, C2, C4, C6 vertebral segments bilaterally, trigeminal area, hand, and leg. Signs of pain sensitization were assessed by evaluating mechanical pain threshold over trigeminal area and hand, pressure pain thresholds, and the wind-up ratio. The Bonferroni-corrected p-value (05/4 = 0.013) was adopted to assess the difference between groups, while a p-value of 0.05 was considered significant for the correlation analysis. A total of 159 patients and 52 controls were included. Flexion rotation test and craniocervical flexion test were reduced in all 4 phases of the migraine cycle versus healthy controls (p < 0.001). The number of myofascial trigger points and positive vertebral segments was increased in all 4 phases of the migraine cycle versus healthy controls (p < 0.001). Flexion, extension, and total cervical active range of motion and cervical pressure pain thresholds were reduced in episodic migraine in the ictal phase versus controls (p < 0.007) with no other significant differences. Outside the ictal phase, the total cervical active range of motion was positively correlated with trigeminal and leg pressure pain threshold (p < 0.026), the number of active myofascial trigger points and positive positive vertebral segments were positively correlated with higher headache frequency (p=0.045), longer headache duration (p < 0.008), and with headache-related disability (p = 0.031). Cervical pressure pain thresholds were positively correlated with trigeminal, hand, and leg pressure pain threshold (p < 0.001), and trigeminal and leg mechanical pain thresholds (p < 0.005), and negatively correlated with the wind-up ratio (p < 0.004). In all phases of the migraine cycle, independent of the presence of concomitant neck pain, episodic migraine patients showed reduced flexion rotation test and craniocervical flexion test and an increased number of myofascial trigger points and passive accessory vertebral segments. These impairments are correlated with enhanced headache duration, headache-related disability, and signs of widespread pain sensitization. Reduction in active cervical movement and increased mechanical hyperalgesia of the cervical was consistent in ictal episodic migraine patients and the subgroups of episodic migraine patients with more pronounced widespread sensitization.

Dynamic brainstem and somatosensory cortical excitability during migraine cycles

BackgroundMigraine has complex pathophysiological characteristics and episodic attacks. To decipher the cyclic neurophysiological features of migraine attacks, in this study, we compared neuronal excitability in the brainstem and primary somatosensory (S1) region between migraine phases for 30 consecutive days in two patients with episodic migraine.MethodsBoth patients underwent EEG recording of event-related potentials with the somatosensory and paired-pulse paradigms for 30 consecutive days. The migraine cycle was divided into the following phases: 24–48 h before headache onset (Pre2), within 24 h before headache onset (Pre1), during the migraine attack (Ictal), within 24 h after headache offset (Post1), and the interval of ˃48 h between the last and next headache phase (Interictal). The normalised current intensity in the brainstem and S1 and gating ratio in the S1 were recorded and examined.ResultsSix migraine cycles (three for each patient) were analysed. In both patients, the somatosensory excitability in the brainstem (peaking at 12–14 ms after stimulation) and S1 (peaking at 18–19 ms after stimulation) peaked in the Pre1 phase. The S1 inhibitory capability was higher in the Ictal phase than in the Pre1 phase.ConclusionThis study demonstrates that migraine is a cyclic excitatory disorder and that the neural substrates involved include the somatosensory system, starting in the brainstem and spanning subsequently to the S1 before the migraine occurs. Further investigations with larger sample sizes are warranted.

Trigeminal and cervical sensitization during the four phases of the migraine cycle in patients with episodic migraine.

Assessing mechanical pain thresholds from trigeminal, cervical, and distal pain-free areas during the four phases of a migraine cycle in patients with episodic migraine (EM). This multicenter, cross-sectional, observational study conducted in Parma and Genoa's Headache Centers assessed quantitative sensory tests during the fourmigraine phases in patients with EM compared to controls. Temporal summation of pain (TSP), static pressure pain threshold (sPPT), and mechanical pinprick pain threshold (MPT) were assessed from the trigeminal area, sPPT and dynamic PPT (dPPT) from the cervical area, sPPT and MPT over the hand, and sPPT from the tibialis anterior. A total of 135 patients and 46 controls were included. TSP was facilitated in ictal EM (EM vs. controls: mean [standard deviation] 2.7 [2.0] vs. 1.4 [1.8]; p=0.004); trigeminal sPPT and MPT were reduced in interictal (sPPT: 198.5 [79.3] kPa; p=0.021; MPT: 12.6 [15.7] g; p=0.001), preictal (sPPT: 200.6 [71.6] kPa; p=0.033; MPT: 10.7 [12.4] g; p<0.001), ictal (sPPT: 171.4 [95.9] kPa; p<0.001; MPT: 7.3 [12.0] g; p<0.001), and postictal EM (sPPT: 182.2 [76.3] kPa; p=0.006; MPT: 10.1 [14.9] g; p=0.001), compared to controls (sPPT: 238.3 [73.8] kPa; MPT: 21.9 [17.3] g). Cervical sPPTs and dPPT were reduced in interictal (sPPT upper cervical spine: 420.5 [176.7] kPa; p=0.031; sPPT lower cervical spine: 458.6 [207.3] kPa; p=0.002; dPPT: 4826.5 [2698.0] g; p<0.001), preictal (sPPT upper cervical spine: 389.3 [133.4] kPa; p=0.006; sPPT lower cervical spine: 450.8 [174.3] kPa; p=0.005; dPPT: 4184.2 [2628.3] g; p<0.001), ictal (sPPT upper cervical spine: 379.9 [205.6] kPa p=0.003; sPPT lower cervical spine: 436.3 [271.1] kPa; p=0.001; dPPT: 3838.3 [2638.7] g; p<0.001), and postictal EM (sPPT upper cervical spine: 385.5 [131.6] kPa; p=0.020; sPPT lower cervical spine: 413.0 [150.3] kPa; p=0.002; dPPT: 4679.6 [2894.9] g; p=0.001), compared to controls (sPPT upper cervical spine: 494.9 [171.5] kPa; sPPT lower cervical spine: 586.9 [210.8] kPa; dPPT: 7693.9 [2896.8] g). Preictal EM had reduced hand sPPT and MPT (sPPT: 248.8 [96.6] kPa vs. 319.8 [112.3] kPa; p=0.006; MPT: 23.6 [12.2] g vs. 32.5 [14.4] g; p=0.035), while EM in the other phases showed reduction in hand MPT (interictal: 22.3 [15.6] g vs. 32.5 [14.4] g; p=0.002; ictal: 22.4 [17.0] g vs. 32.5 [14.4] g; p=0.004; postictal: 24.2 [18.8] g vs. 32.5 [14.4] g; p=0.003) without significant reduction in hand sPPT. No difference in sPPT over the tibialis anterior was found. Hand MPT was negatively correlated with longer disease duration (r=-0.25; p=0.011) and hand sPPT was negatively correlated with higher drug usage (r=-0.31; p=0.002). TSP during the ictal phase was positively correlated with the physical (r=0.38; p=0.040) and emotional headache-related disability (r=0.53; p=0.003). In all phases of the migraine cycle, patients with EM show signs of sensitization in the trigeminocervical area, with patients with the most prominent sensitization in the ictal phase. Signs of widespread sensitization were consistent in the preictal phase in patients with EM and in the subgroups of patients with EM with the longest disease duration and more usage of symptomatic drugs.

Editorial: Neuroimaging: How Can Clues from the Brain Help Pain Management?

Editorial: Neuroimaging: How Can Clues from the Brain Help Pain Management?

Intrinsic network connectivity reflects the cyclic trajectory of migraine attacks

BackgroundEpisodic migraine is considered to be cyclic in nature, triggered by the hypothalamus. To assess the natural trajectory of intrinsic networks over an entire migraine cycle, we designed a longitudinal intra-individual study using functional magnetic resonance imaging (fMRI). MethodsIntrinsic network connectivity was assessed for 12 migraineurs in 82 sessions including spontaneous, untriggered headache attacks and follow-up recordings towards the next attack. ResultsWe found cyclic changes in the visual, auditory, and somatosensory networks, in limbic networks (e.g. thalamo-insular, parahippocampal), and in the salience network (anterior insula and dorsal anterior cingulate cortex). Connectivity changes also extended to further cortical networks, such as the central executive network, the default mode network, as well as subcortical networks. Almost all of these network connectivity changes followed the trajectory of a linear increase over the pain-free interval that peaked immediately prior to the headache, and “dropped” to the baseline level during the headache. These network alterations are associated with a number of cortical functions that may explain the variety of ictal and pre-ictal physiological and psychological migraine symptoms. ConclusionOur results suggest that migraine disease is associated with widespread cyclic alterations of intrinsic networks that develop before the headache is initiated, i.e. during the interictal and premonitory phase. The increasing magnitude of connectivity within these networks towards the next attack may reflect an increasing effort to maintain network integrity.

Cyclic changes of visual cortical excitability across migraine phases: A study with sound induced flash illusions

Abnormal cortical excitability has a role in migraine but the link with beginning and stop of migraine attacks remains unclear. Critical insight could come by excitability changes across the migraine cycle. Here we explore it through sound induced flash illusions (SIFI). SIFI are cross-modal illusory percepts critically dependent on visual cortical excitability (less illusions = increased excitability) that have been found to be altered in episodic and chronic migraine(1–2).

Visual snow syndrome, the spectrum of perceptual disorders, and migraine as a common risk factor: A narrative review.

ObjectiveThe aim of this narrative review is to explore the relationship between visual snow syndrome (VSS), migraine, and a group of other perceptual disorders.BackgroundVSS is characterized by visual snow and additional visual and nonvisual disturbances. The clinical picture suggests a hypersensitivity to internal and external stimuli. Imaging and electrophysiological findings indicate a hyperexcitability of the primary and secondary visual areas of the brain possibly due to an impairment of inhibitory feedback mechanisms. Migraine is the most frequent comorbidity. Epidemiological and clinical studies indicate that other perceptual disorders, such as tinnitus, fibromyalgia, and dizziness, are associated with VSS. Clinical overlaps and parallels in pathophysiology might exist in relation to migraine.MethodsWe performed a PubMed and Google Scholar search with the following terms: visual snow syndrome, entoptic phenomenon, fibromyalgia, tinnitus, migraine, dizziness, persistent postural‐perceptual dizziness (PPPD), comorbidities, symptoms, pathophysiology, thalamus, thalamocortical dysrhythmia, and salience network.ResultsVSS, fibromyalgia, tinnitus, and PPPD share evidence of a central disturbance in the processing of different stimuli (visual, somatosensory/pain, acoustic, and vestibular) that might lead to hypersensitivity. Imaging and electrophysiological findings hint toward network disorders involving the sensory networks and other large‐scale networks involved in the management of attention and emotional processing. There are clinical and epidemiological overlaps between these disorders. Similarly, migraine exhibits a multisensory hypersensitivity even in the interictal state with fluctuation during the migraine cycle. All the described perceptual disorders are associated with migraine suggesting that having migraine, that is, a disorder of sensory processing, is a common link.ConclusionVSS, PPPD, fibromyalgia, and chronic tinnitus might lie on a spectrum of perceptual disorders with similar pathophysiological mechanisms and the common risk factor migraine. Understanding the underlying network disturbances might give insights into how to improve these currently very difficult to treat conditions.

Age-related differences in resting state functional connectivity in pediatric migraine

BackgroundMigraine affects roughly 10% of youth aged 5–15 years, however the underlying mechanisms of migraine in youth are poorly understood. Multiple structural and functional alterations have been shown in the brains of adult migraine sufferers. This study aims to investigate the effects of migraine on resting-state functional connectivity during the period of transition from childhood to adolescence, a critical period of brain development and the time when rates of pediatric chronic pain spikes.MethodsUsing independent component analysis, we compared resting state network spatial maps and power spectra between youth with migraine aged 7–15 and age-matched controls. Statistical comparisons were conducted using a MANCOVA analysis.ResultsWe show (1) group by age interaction effects on connectivity in the visual and salience networks, group by sex interaction effects on connectivity in the default mode network and group by pubertal status interaction effects on connectivity in visual and frontal parietal networks, and (2) relationships between connectivity in the visual networks and the migraine cycle, and age by cycle interaction effects on connectivity in the visual, default mode and sensorimotor networks.ConclusionsWe demonstrate that brain alterations begin early in youth with migraine and are modulated by development. This highlights the need for further study into the neural mechanisms of migraine in youth specifically, to aid in the development of more effective treatments.

Migraine Visual Aura and Cortical Spreading Depression-Linking Mathematical Models to Empirical Evidence.

This review describes the subjective experience of visual aura in migraine, outlines theoretical models of this phenomenon, and explores how these may be linked to neurochemical, electrophysiological, and psychophysical differences in sensory processing that have been reported in migraine with aura. Reaction–diffusion models have been used to model the hallucinations thought to arise from cortical spreading depolarisation and depression in migraine aura. One aim of this review is to make the underlying principles of these models accessible to a general readership. Cortical spreading depolarisation and depression in these models depends on the balance of the diffusion rate between excitation and inhibition and the occurrence of a large spike in activity to initiate spontaneous pattern formation. We review experimental evidence, including recordings of brain activity made during the aura and attack phase, self-reported triggers of migraine, and psychophysical studies of visual processing in migraine with aura, and how these might relate to mechanisms of excitability that make some people susceptible to aura. Increased cortical excitability, increased neural noise, and fluctuations in oscillatory activity across the migraine cycle are all factors that are likely to contribute to the occurrence of migraine aura. There remain many outstanding questions relating to the current limitations of both models and experimental evidence. Nevertheless, reaction–diffusion models, by providing an integrative theoretical framework, support the generation of testable experimental hypotheses to guide future research.