Diagnostic biomarker discovery from brain EEG data using LSTM, reservoir-SNN, and NeuCube methods in a pilot study comparing epilepsy and migraine.

The study introduces a new online spike encoding algorithm for spiking neural networks (SNN) and suggests new methods for learning and identifying diagnostic biomarkers using three prominent deep learning neural network models: deep BiLSTM, reservoir SNN, and NeuCube. EEG data from datasets related to epilepsy, migraine, and healthy subjects are employed. Results reveal that BiLSTM hidden neurons capture biological significance, while reservoir SNN activities and NeuCube spiking dynamics identify EEG channels as diagnostic biomarkers. BiLSTM and reservoir SNN achieve 90 and 85% classification accuracy, while NeuCube achieves 97%, all methods pinpointing potential biomarkers like T6, F7, C4, and F8. The research bears implications for refining online EEG classification, analysis, and early brain state diagnosis, enhancing AI models with interpretability and discovery. The proposed techniques hold promise for streamlined brain-computer interfaces and clinical applications, representing a significant advancement in pattern discovery across the three most popular neural network methods for addressing a crucial problem. Further research is planned to study how early can these diagnostic biomarkers predict an onset of brain states.

Aberrant cerebral blood flow and functional connectivity in patients with vestibular migraine: a resting-state ASL and fMRI study.

BACKGROUND: Prior neuroimaging studies on vestibular migraine (VM) have extensively certified the functional and structural alterations in multiple brain regions and networks. However, few studies have assessed the cerebral blood flow (CBF) in VM patients using arterial spin labeling (ASL). The present study aimed to investigate CBF and functional connectivity (FC) alterations in VM patients during interictal periods. METHODS: We evaluated 52 VM patients and 46 healthy controls (HC) who received resting-state pseudo-continuous ASL and functional magnetic resonance imaging (fMRI) scanning. Comparisons of voxel-based CBF and seed-based FC were performed between the two groups. Brain regions showed significant group differences in CBF analyses were chosen as seeds in FC analyses. Additionally, the associations between abnormal imaging results and clinical features were explored. RESULTS: Compared with HC, VM patients showed higher normalized CBF in the right precentral gyrus (PreCG), left postcentral gyrus (PostCG), left superior frontal gyrus and bilateral insular (p < 0.05, FDR corrected). Furthermore, VM patients exhibited increased FC between the right PreCG and areas of the left PostCG, left cuneus and right lingual gyrus (p < 0.05, FDR corrected). In addition, we observed decreased FC between the left insular and regions of the left thalamus and right anterior cingulate cortex, as well as increased FC between the left insular and right fusiform gyrus in VM patients (p < 0.05, FDR corrected). Moreover, these variations in brain perfusion and FC were significantly correlated with multiple clinical features including frequency of migraine symptoms, frequency of vestibular symptoms and disease duration of VM (all p < 0.05). CONCLUSIONS: Patients with VM during interictal period showed hyperperfusion and abnormal resting-state FC in brain regions potentially contributed to disrupted multi-sensory and autonomic processing, as well as impaired ocular motor control, pain modulation and emotional regulation. Our study provided novel insights into the complex neuropathology of VM from a CBF perspective.

Virtual dynamic interaction games reveal impaired multisensory integration in women with migraine.

OBJECTIVE: In this cross-sectional observational study, we aimed to investigate sensory profiles and multisensory integration processes in women with migraine using virtual dynamic interaction systems. BACKGROUND: Compared to studies on unimodal sensory processing, fewer studies show that multisensory integration differs in patients with migraine. Multisensory integration of visual, auditory, verbal, and haptic modalities has not been evaluated in migraine. METHODS: A 12-min virtual dynamic interaction game consisting of four parts was played by the participants. During the game, the participants were exposed to either visual stimuli only or multisensory stimuli in which auditory, verbal, and haptic stimuli were added to the visual stimuli. A total of 78 women participants (28 with migraine without aura and 50 healthy controls) were enrolled in this prospective exploratory study. Patients with migraine and healthy participants who met the inclusion criteria were randomized separately into visual and multisensory groups: Migraine multisensory (14 adults), migraine visual (14 adults), healthy multisensory (25 adults), and healthy visual (25 adults). The Sensory Profile Questionnaire was utilized to assess the participants' sensory profiles. The game scores and survey results were analyzed. RESULTS: In visual stimulus, the gaming performance scores of patients with migraine without aura were similar to the healthy controls, at a median (interquartile range [IQR]) of 81.8 (79.5-85.8) and 80.9 (77.1-84.2) (p = 0.149). Error rate of visual stimulus in patients with migraine without aura were comparable to healthy controls, at a median (IQR) of 0.11 (0.08-0.13) and 0.12 (0.10-0.14), respectively (p = 0,166). In multisensory stimulation, average gaming score was lower in patients with migraine without aura compared to healthy individuals (median [IQR] 82.2 [78.8-86.3] vs. 78.6 [74.0-82.4], p = 0.028). In women with migraine, exposure to new sensory modality upon visual stimuli in the fourth, seventh, and tenth rounds (median [IQR] 78.1 [74.1-82.0], 79.7 [77.2-82.5], 76.5 [70.2-82.1]) exhibited lower game scores compared to visual stimuli only (median [IQR] 82.3 [77.9-87.8], 84.2 [79.7-85.6], 80.8 [79.0-85.7], p = 0.044, p = 0.049, p = 0.016). According to the Sensory Profile Questionnaire results, sensory sensitivity, and sensory avoidance scores of patients with migraine (median [IQR] score 45.5 [41.0-54.7] and 47.0 [41.5-51.7]) were significantly higher than healthy participants (median [IQR] score 39.0 [34.0-44.2] and 40.0 [34.0-48.0], p < 0.001, p = 0.001). CONCLUSION: The virtual dynamic game approach showed for the first time that the gaming performance of patients with migraine without aura was negatively affected by the addition of auditory, verbal, and haptic stimuli onto visual stimuli. Multisensory integration of sensory modalities including haptic stimuli is disturbed even in the interictal period in women with migraine. Virtual games can be employed to assess the impact of sensory problems in the course of the disease. Also, sensory training could be a potential therapy target to improve multisensory processing in migraine.

Migraine eye: correlation between migraine and the retina.

Background: Activation of the trigeminal vascular system in migraine releases vasoactive neurotransmitters, causing abnormal vasoconstriction, which may affect the ocular system, leading to retinal damage. The purpose of our study was to determine whether there are differences in each retinal layer between migraine patients and healthy subjects. Methods: A case-control study recruited 38 migraine patients and 38 age- and sex-matched controls. Optical coherence tomography was used to measure the thickness of the peripapillary and macular retinal nerve fiber layer (pRNFL and mRNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), and inner nuclear layer (INL). Results: The mean ages of the migraine patients and controls were 36.29 ± 9.45 and 36.45 ± 9.27 years, respectively. Thirty-four patients (89.48%) in both groups were female. The mean disability score was 19.63 ± 20.44 (indicating severe disability). The superior-outer INL of migraine patients were thicker than controls. Thickness of the GCL at temporal-outer sector and mRNFL at the superior-outer sector of the headache-side eyes was reduced. However, the INL of the headache-side-eye showed negative correlation with the disability score. This is the first study having found thinning of the GCL and mRNFL of the headache-side eyes. The INL was also thickened in migraines but showed negative correlation with the disability score. Conclusions: Increased INL thickness in migraine patients may result from inflammation. The more severe cases with a high disability score might suffered progressive retinal neuronal loss, resulting in thinner INL than less severe cases.

Extrasynaptic δGABAA receptors mediate resistance to migraine-like phenotype in rats.

BACKGROUND: GABA, a key inhibitory neurotransmitter, has synaptic and extrasynaptic receptors on the postsynaptic neuron. Background GABA, which spills over from the synaptic cleft, acts on extrasynaptic delta subunit containing GABAA receptors. The role of extrasynaptic GABAergic input in migraine is unknown. We investigated the susceptibility to valid migraine-provoking substances with clinically relevant behavioral readouts in Genetic Absence Epilepsy of Rats Strasbourg (GAERS), in which the GABAergic tonus was altered. Subsequently, we screened relevant GABAergic mechanisms in Wistar rats by pharmacological means to identify the mechanisms. METHODS: Wistar and GAERS rats were administered nitroglycerin (10 mg/kg) or levcromakalim (1 mg/kg). Mechanical allodynia and photophobia were assessed using von Frey monofilaments and a dark-light box. Effects of GAT-1 blocker tiagabine (5 mg/kg), GABAB receptor agonist baclofen (2 mg/kg), synaptic GABAA receptor agonist diazepam (1 mg/kg), extrasynaptic GABAA receptor agonists gaboxadol (4 mg/kg), and muscimol (0.75 mg/kg), T-type calcium channel blocker ethosuximide (100 mg/kg) or synaptic GABAA receptor antagonist flumazenil (15 mg/kg) on levcromakalim-induced migraine phenotype were screened. RESULTS: Unlike Wistar rats, GAERS exhibited no reduction in mechanical pain thresholds or light aversion following nitroglycerin or levcromakalim injection. Ethosuximide did not reverse the resistant phenotype in GAERS, excluding the role of T-type calcium channel dysfunction in this phenomenon. Tiagabine prevented levcromakalim-induced mechanical allodynia in Wistar rats, suggesting a key role in enhanced GABA spillover. Baclofen did not alleviate mechanical allodynia. Diazepam failed to mitigate levcromakalim-induced migraine phenotype. Additionally, the resistant phenotype in GAERS was not affected by flumazenil. Extrasynaptic GABAA receptor agonists gaboxadol and muscimol inhibited periorbital allodynia in Wistar rats. CONCLUSION: Our study introduced a rat strain resistant to migraine-provoking agents and signified a critical involvement of extrasynaptic δGABAergic receptors. Extrasynaptic δ GABAA receptors, by mediating constant background inhibition on the excitability of neurons, stand as a novel drug target with a therapeutic potential in migraine.

Female-selective mechanisms promoting migraine.

Sexual dimorphism has been revealed for many neurological disorders including chronic pain. Prelicinal studies and post-mortem analyses from male and female human donors reveal sexual dimorphism of nociceptors at transcript, protein and functional levels suggesting different mechanisms that may promote pain in men and women. Migraine is a common female-prevalent neurological disorder that is characterized by painful and debilitating headache. Prolactin is a neurohormone that circulates at higher levels in females and that has been implicated clinically in migraine. Prolactin sensitizes sensory neurons from female mice, non-human primates and humans revealing a female-selective pain mechanism that is conserved evolutionarily and likely translationally relevant. Prolactin produces female-selective migraine-like pain behaviors in rodents and enhances the release of calcitonin gene-related peptide (CGRP), a neurotransmitter that is causal in promoting migraine in many patients. CGRP, like prolactin, produces female-selective migraine-like pain behaviors. Consistent with these observations, publicly available clinical data indicate that small molecule CGRP-receptor antagonists are preferentially effective in treatment of acute migraine therapy in women. Collectively, these observations support the conclusion of qualitative sex differences promoting migraine pain providing the opportunity to tailor therapies based on patient sex for improved outcomes. Additionally, patient sex should be considered in design of clinical trials for migraine as well as for pain and reassessment of past trials may be warranted.

Physical impairment during and between migraine attacks: A daily diary study of patients with chronic migraine.

OBJECTIVE: While a substantial body of research describes the disabling impacts of migraine attacks, less research has described the impacts of migraine on physical functioning between migraine attacks. The objective of this study is to describe physical impairment during and between migraine attacks as a dimension of burden experienced by people living with chronic migraine. METHODS: The physical impairment domain of the Migraine Physical Function Impact Diary was recorded in headache diaries from the Medication Overuse Treatment Strategy trial. Days with moderate to severe headache were used to approximate migraine attacks. Factor analysis and regression analysis were used to describe associations between migraine and physical impairment. RESULTS: 77,662 headache diary entries from 720 participants were analyzed, including 25,414 days with moderate to severe headache, 19,149 days with mild headache, and 33,099 days with no headache. Mean physical impairment score was 41.5 (SD = 26.1) on days with moderate to severe headache, 12.8 (SD = 15.0) on days with mild headache, and 5.2 (SD = 13.1) on days with no headache. Physical impairment on days with mild headache and days with no headache was significantly associated with days since last moderate to severe headache, physical impairment with last moderate to severe headache, mild headache (compared to no headache), depression, hypersensitivities and cranial autonomic symptoms. CONCLUSIONS: Physical impairment occurs on migraine and non-migraine days. Study participants with frequent headaches, symptoms of depression, hypersensitivities and cranial autonomic symptoms experience physical impairment at a higher rate on days with no headache and days with mild headache.Clinical Trial Registration: ClinicalTrials.gov (NCT02764320).

Pathological claustrum activity drives aberrant cognitive network processing in human chronic pain.

Aberrant cognitive network activity and cognitive deficits are established features of chronic pain. However, the nature of cognitive network alterations associated with chronic pain and their underlying mechanisms require elucidation. Here, we report that the claustrum, a subcortical nucleus implicated in cognitive network modulation, is activated by acute painful stimulation and pain-predictive cues in healthy participants. Moreover, we discover pathological activity of the claustrum and a region near the posterior inferior frontal sulcus of the right dorsolateral prefrontal cortex (piDLPFC) in migraine patients during acute pain and cognitive task performance. Dynamic causal modeling suggests a directional influence of the claustrum on activity in this piDLPFC region, and diffusion weighted imaging verifies their structural connectivity. These findings advance understanding of claustrum function during acute pain and provide evidence of a possible circuit mechanism driving cognitive impairments in chronic pain.

Possible mechanisms of auricular acupoint stimulation in the treatment of migraine by activating auricular vagus nerve. / 从耳迷走神经探讨耳穴治疗偏头痛的可能机制.

Under the guidance of traditional Chinese medicine theory, the clinical research of auricular acupoint stimulation in the treatment of migraine has gained a lot, and the curative efficacy is definite, but its mechanism remains unclear. In the present paper, we discussed the efficacy of auricular acupoint stimulation including "transcutaneous auricular vagus nerve stimulation" (taVNS) in the treatment of migraine in recent years. Through bibliometric analysis, we screened out top 10 auricular acupoints (Shenmenï¼»TF4ï¼½, Pizhixiaï¼»AT4ï¼½, Jiaoganï¼»AH6aï¼½, Ganï¼»CO12ï¼½, Yidanï¼»CO11ï¼½, Neifenmiï¼»CO18ï¼½, Shenï¼»CO10ï¼½, Nieï¼»AT2ï¼½, Zhenï¼»AT3ï¼½ and Eï¼»AT1ï¼½) which were the most frequently used for migraine. Majority of these auricular acupoints just distributed in the region innervated by auricular vagus nerve. Thus, we thought that the analgesic effect of needling these auricular acupoints for migraine was produced by triggering the auricular vagus nerve, and concluded that the central mechanism underlying induction of analgesic effect by activating auricular vagus nerve may be achieved by activating the descending pain regulation pathway of the locus coeruleus nucleus and dorsal raphe nucleus. In addition, taVNS-induced 1) regulation of the activities of brain's default network and pain matrix, 2) activation of the cortical descending pain regulation pathway, and 3) inhibition of the neuroinflammatory response may also contribute to its ameliorating effect of migraine. This paper may provide ideas for the future research on the mechanism of auricular acupoint treatment of migraine.

Implications of high homocysteine levels in migraine pain: An experimental study of the excitability of peripheral meningeal afferents in rats with hyperhomocysteinemia.

OBJECTIVES: Investigation of chronic homocysteine action on the excitability and N-methyl-D-aspartate (NMDA) sensitivity of the peripheral trigeminovascular system of rats. BACKGROUND: Migraine is a neurological disease that affects 15%-20% of the general population. Epidemiological observations show that an increase of the sulfur-containing amino acid homocysteine in plasma-called hyperhomocysteinemia-is associated with a high risk of migraine, especially migraine with aura. In animal studies, rats with hyperhomocysteinemia demonstrated mechanical allodynia, photophobia, and anxiety, and higher sensitivity to cortical spreading depression. In addition, rats with hyperhomocysteinemia were more sensitive in a model of chronic migraine induced by nitroglycerin which indicated the involvement of peripheral nociceptive mechanisms. The present work aimed to analyze the excitability of meningeal afferents and neurons isolated from the trigeminal ganglion of rats with prenatal hyperhomocysteinemia. METHODS: Experiments were performed on male rats born from females fed with a methionine-rich diet before and during pregnancy. The activity of meningeal afferents was recorded extracellularly in hemiskull preparations ex vivo and action potentials were characterized using cluster analysis. The excitability of trigeminal ganglion neurons was assessed using whole-cell patch clamp recording techniques and calcium imaging studies. Meningeal mast cells were stained using toluidine blue. RESULTS: The baseline extracellular recorded electrical activity of the trigeminal nerve was higher in the hyperhomocysteinemia group with larger amplitude action potentials. Lower concentrations of KCl caused an increase in the frequency of action potentials of trigeminal afferents recorded in rat hemiskull ex vivo preparations. In trigeminal ganglion neurons of rats with hyperhomocysteinemia, the current required to elicit at least one action potential (rheobase) was lower, and more action potentials were induced in response to stimulus of 2 × rheobase. In controls, short-term application of homocysteine and its derivatives increased the frequency of action potentials of the trigeminal nerve and induced Ca2+ transients in neurons, which are associated with the activation of NMDA receptors. At the same time, in rats with hyperhomocysteinemia, we did not observe an increased response of the trigeminal nerve to NMDA. Similarly, the parameters of Ca2+ transients induced by NMDA, homocysteine, and its derivatives were not changed in rats with hyperhomocysteinemia. Acute incubation of the meninges in homocysteine and homocysteinic acid did not change the state of the mast cells, whereas in the model of hyperhomocysteinemia, an increased degranulation of mast cells in the meninges was observed. CONCLUSIONS: Our results demonstrated higher excitability of the trigeminal system of rats with hyperhomocysteinemia. Together with our previous finding about the lower threshold of generation of cortical spreading depression in rats with hyperhomocysteinemia, the present data provide evidence of homocysteine as a factor that increases the sensitivity of the peripheral migraine mechanisms, and the control of homocysteine level may be an important strategy for reducing the risk and/or severity of migraine headache attacks.

Decreased Cerebral Perfusion in Chronic Migraine: A Voxel-based Cerebral Blood Flow Analysis Using 3D Pseudo-continuous Arterial Spin Labeling.

BACKGROUND: A contrast agent-free approach would be preferable to the frequently used invasive approaches for evaluating cerebral perfusion in chronic migraineurs (CM). In this work, non-invasive quantitative volumetric perfusion imaging was used to evaluate alterations in cerebral perfusion in CM. METHODS: We used conventional brain structural imaging sequences and 3D pseudo-continuous arterial spin labeling (3D PCASL) to examine thirteen CM patients and fifteen normal controls (NCs). The entire brain gray matter underwent voxel-based analysis, and the cerebral blood flow (CBF) values of the altered positive areas were retrieved to look into the clinical variables' significant correlation. RESULTS: Brain regions with the decreased perfusion were located in the left postcentral gyrus, bilateral middle frontal gyrus, left middle occipital gyrus, left superior parietal lobule, left medial segment of superior frontal gyrus, and right orbital part of the inferior frontal gyrus. White matter fibers with decreased perfusion were located in bilateral superior longitudinal tracts, superior corona radiata, external capsules, anterior and posterior limbs of the internal capsule, anterior corona radiata, inferior longitudinal fasciculus, and right corticospinal tract. However, the correlation analysis showed no significant correlation between the CBF value of the above positive brain regions with clinical variables (p > 0.05). CONCLUSION: The current study provided more useful information to comprehend the pathophysiology of CM and revealed a new insight into the neural mechanism of CM from the pattern of cerebral hypoperfusion.

Vestibular migraine: an update.

PURPOSE OF REVIEW: We performed a narrative review of the recent findings in epidemiology, clinical presentation, mechanisms and treatment of vestibular migraine. RECENT FINDINGS: Vestibular migraine is an underdiagnosed condition that has a high prevalence among general, headache and neuro-otology clinics. Vestibular migraine has a bimodal presentation probably associated with a hormonal component in women. These patients could have a complex clinical phenotype including concomitant autonomic, inflammatory or connective tissue conditions that have a higher prevalence of psychological symptoms, which may mistakenly lead to a diagnosis of a functional neurological disorder. A high proportion of patients with postural perceptual persistent dizziness have a migraine phenotype. Independently of the clinical presentation and past medical history, patients with the vestibular migraine phenotype can respond to regular migraine preventive treatments, including those targeting the calcitonin gene-related peptide pathways. SUMMARY: Vestibular migraine is an underdiagnosed migraine phenotype that shares the pathophysiological mechanisms of migraine, with growing interest in recent years. A thorough anamnesis is essential to increase sensitivity in patients with unknown cause of dizziness and migraine treatment should be considered (see supplemental video-abstract).

Evaluation of Masseteric Vestibular Evoked Myogenic Potentials in Patients With Migraine.

PURPOSE: Masseter vestibular evoked myogenic potentials (mVEMP) involve the connection between the vestibular complex and trigeminal nerve nuclei. Given the theory that migraine is caused by increased activation of the trigeminal nerve, it is believed that mVEMP responses may have influenced in migraine patients. METHOD: The study included 20 individuals with migraine and 20 healthy controls. Latency, amplitude, and interaural amplitude asymmetry ratio of mVEMP responses recorded in migraine patients were compared with control group. RESULTS: Considering the mVEMP normalization study conducted by Basöz et al. (2021) in a similar age group and in the same clinic, latency prolongation and amplitude decrease were observed in subjects with migraines. Migraine is considered a central pathology, as shown in the cervical and ocular VEMP (cVEMP/oVEMP) literature. No difference was observed in the interaural amplitude asymmetry ratio, which is important in peripheral pathologies. Additionally, when the number of pathological ears was examined in order to understand the total exposure, it was observed that the number of pathological ears was significantly higher in the migraine group. CONCLUSION: In future studies, using mVEMP together with cVEMP and oVEMP tests, which allow evaluation of otolith organs and vestibular nuclei, will be valuable in determining the lesion location. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25607901.

Evaluation of Tpeak-end interval, Tpeak-end/QT, and Tpeak-end/Qtc ratio during acute migraine attack in the emergency department.

INTRODUCTION: During an acute migraine attack, changes in ventricular repolarisation parameters may occur due to an imbalance in the autonomic nervous system. Tpeak-tend (Tp-e) interval, Tp-e/QT ratio, and Tp-e/corrected QT (QTc) ratio are novel parameters of arrhythmogenesis and can be easily calculated in electrocardiography (ECG). The objective of this study is to demonstrate that novel ventricular repolarisation parameters can anticipate the risk of ventricular dysrhythmia in the migraine attack period. METHODS: This research was a prospective case-control study, which recruited a total of 144 participants, including 74 migraine patients and 70 healthy volunteers in the control group (CG) who met the criteria for migraine with or without aura. All participants underwent 12-lead ECG recordings, and the study compared the Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio with those of the CG. RESULTS: The average age of patients experiencing migraine attacks was 38.14 ± 10.82, with 58 (76%) of these patients being female. The Tp-e interval mean was higher in the migraine attack group than the CG, with a statistically significant difference discovered (74.22 ± 20.20 ms [ms] compared to 65.39 ± 11.33 ms, p = 0.001). However, there were higher mean Tp-e/QT and Tp-e/QTc ratios in the migraine attack group compared to the CG, and this difference was found to be statistically significant (0.20 ± 0.05 vs. 0.17 ± 0.03, p = 0.001, 0.18 ± 0.52 vs 0.16 ± 0.29, p = 0.003, respectively). CONCLUSION: Prolonged Tp-e interval and elevated Tp-e/QT and Tp-e/QTc ratios were observed in migraine patients who presented to the emergency department, indicating a potential risk of ventricular dysrhythmia.

Establishing continuum in Transcranial Doppler characteristics of IIH, migraine and healthy controls- An exploratory study.

BACKGROUND: IIH is a severe form of headache that often has superimposed migraine and often it is very difficult to distinguish the two forms of headache. Intracranial hemodynamics is a relatively unexplored means of distinguishing between the two forms of headache. OBJECTIVES: We aimed to study intracranial flow dynamics using Transcranial Doppler in patients with IIH, migraine, and normal controls. MATERIALS AND METHODS: It was a hospital-based observational study that included 51 people with IIH, 87 people with migraine, and 101 healthy controls and all were subjected to TCD study after detailed clinical examination. RESULTS: Mean age of patients in three groups were similar with the mean age in IIH being 33.41 ± 10.75 (age in years ± SD). Vision loss was present in 66.67% of patients with IIH, and most common field defect was generalized constriction (27.5%). Neuroimaging was abnormal in 94.11% of patients of IIH with mean CSF pressure was 31.27±5.32 cm of water. Of all the TCD-measured velocities, mean flow velocity (MFV) showed a significant difference in all three groups with (p-value <0.001). The pulsatility index, both for middle cerebral arteries as well as ophthalmic arteries showed a significant difference in the three groups with the highest values in IIH patients (p-value<.001). The mean VMR in IIH (1.11±0.32) was lower than the mean VMR in migraine (1.34±0.43) as well as controls (1.49±0.46). CONCLUSION: TCD parameters like MFV and PI are useful parameters that show considerable variation and can be used to differentiate between IIH and migraine.

Machine learning models help differentiate between causes of recurrent spontaneous vertigo.

BACKGROUND: Vestibular migraine (VM) and Menière's disease (MD) are two common causes of recurrent spontaneous vertigo. Using history, video-nystagmography and audiovestibular tests, we developed machine learning models to separate these two disorders. METHODS: We recruited patients with VM or MD from a neurology outpatient facility. One hundred features from six "feature subsets": history, acute video-nystagmography and four laboratory tests (video head impulse test, vestibular-evoked myogenic potentials, caloric testing and audiogram) were used. We applied ten machine learning algorithms to develop classification models. Modelling was performed using three "tiers" of data availability to simulate three clinical settings. "Tier 1" used all available data to simulate the neuro-otology clinic, "Tier 2" used only history, audiogram and caloric test data, representing the general neurology clinic, and "Tier 3" used history alone as occurs in primary care. Model performance was evaluated using tenfold cross-validation. RESULTS: Data from 160 patients with VM and 114 with MD were used for model development. All models effectively separated the two disorders for all three tiers, with accuracies of 85.77-97.81%. The best performing algorithms (AdaBoost and Random Forest) yielded accuracies of 97.81% (95% CI 95.24-99.60), 94.53% (91.09-99.52%) and 92.34% (92.28-96.76%) for tiers 1, 2 and 3. The best feature subset combination was history, acute video-nystagmography, video head impulse test and caloric testing, and the best single feature subset was history. CONCLUSIONS: Machine learning models can accurately differentiate between VM and MD and are promising tools to assist diagnosis by medical practitioners with diverse levels of expertise and resources.

High-definition tDCS over primary motor cortex modulates brain signal variability and functional connectivity in episodic migraine.

OBJECTIVE: This study investigated how high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) affects brain signal variability and functional connectivity in the trigeminal pain pathway, and their association with changes in migraine attacks. METHODS: Twenty-five episodic migraine patients were randomized for ten daily sessions of active or sham M1 HD-tDCS. Resting-state blood-oxygenation-level-dependent (BOLD) signal variability and seed-based functional connectivity were assessed pre- and post-treatment. A mediation analysis was performed to test whether BOLD signal variability mediates the relationship between treatment group and moderate-to-severe headache days. RESULTS: The active M1 HD-tDCS group showed reduced BOLD variability in the spinal trigeminal nucleus (SpV) and thalamus, but increased variability in the rostral anterior cingulate cortex (rACC) compared to the sham group. Connectivity decreased between medial pulvinar-temporal pole, medial dorsal-precuneus, and the ventral posterior medial nucleus-SpV, but increased between the rACC-amygdala, and the periaqueductal gray-parahippocampal gyrus. Changes in medial pulvinar variability mediated the reduction in moderate-to-severe headache days at one-month post-treatment. CONCLUSIONS: M1 HD-tDCS alters BOLD signal variability and connectivity in the trigeminal somatosensory and modulatory pain system, potentially alleviating migraine headache attacks. SIGNIFICANCE: M1 HD-tDCS realigns brain signal variability and connectivity in migraineurs closer to healthy control levels.

Sense of direction in vestibular disorders.

BACKGROUND: Our sense of direction (SOD) ability relies on the sensory integration of both visual information and self-motion cues from the proprioceptive and vestibular systems. Here, we assess how dysfunction of the vestibular system impacts perceived SOD in varying vestibular disorders, and secondly, we explore the effects of dizziness, migraine and psychological symptoms on SOD ability in patient and control groups. METHODS: 87 patients with vestibular disorder and 69 control subjects were assessed with validated symptom and SOD questionnaires (Santa Barbara Sense of Direction scale and the Object Perspective test). RESULTS: While patients with vestibular disorders performed significantly worse than controls at the group level, only central and functional disorders (vestibular migraine and persistent postural perceptual dizziness), not peripheral disorders (benign-paroxysmal positional vertigo, bilateral vestibular failure and Meniere's disease) showed significant differences compared to controls on the level of individual vestibular groups. Additionally, orientational abilities associated strongly with spatial anxiety and showed clear separation from general dizziness and psychological factors in both patient and control groups. CONCLUSIONS: SOD appears to be less affected by peripheral vestibular dysfunction than by functional and/or central diagnoses, indicating that higher level disruptions to central vestibular processing networks may impact SOD more than reductions in sensory peripheral inputs. Additionally, spatial anxiety is highly associated with orientational abilities in both patients and control subjects.

Migraine chronification as an allostatic disorder: a proof-of-concept study.

OBJECTIVE: The underpinning biologics of migraine chronification are not well understood. We aim to investigate the role of the cumulative burden of stress, namely the allostatic load, in migraine chronification. METHODS: This was a cross-sectional study. The allostatic load was measured with a composite multi-system score (BALI: Bologna Allostatic Load Index), evaluating 20 biomarkers representing four physiological systems: immune, metabolic, cardiovascular, and neuroendocrinological systems. BALI score was subdivided into high score and low score based on the distribution in controls. Migraine patients were included and subclassified into low-frequency episodic migraine group (low-EM group), high-frequency episodic migraine group (high-EM group), and chronic migraine group (CM group). RESULTS: The distribution of BALI high-score increased in parallel with headache attacks monthly frequency: 16% in low-EM group (n = 10), 24% in high-EM group (n = 12), and 40% in CM group (n = 21) (p = 0.017). In a multivariable analysis, the odds ratio of having a high-score BALI in CM patients (vs. low-EM patients) was 2.78 (95% CI 1.07-7.22; p = 0.036). Individual BALI biomarkers values which were significantly different among migraine subgroups included systolic blood pressure (p = 0.018), diastolic blood pressure (p < 0.001), and heart rate (p = 0.019). CONCLUSION: Our study substantiates this emerging concept of migraine chronification as an allostatic disorder.