Chong, Catherine D

Abstract Background/Objective: Changes in speech can be detected objectively before and during migraine attacks. The goal of this study was to interrogate whether speech changes can be detected in subjects with post-traumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) and whether there are within-subject changes in speech during headaches compared to the headache-free state. Methods: Using a series of speech elicitation tasks uploaded via a mobile application, PTH subjects and healthy controls (HC) provided speech samples once every three days, over a period of 12 weeks. The following speech parameters were assessed: vowel space area, vowel articulation precision, consonant articulation precision, average pitch, pitch variance, speaking rate and pause rate. Speech samples of subjects with PTH were compared to HC. To assess speech changes associated with PTH, speech samples of subjects during headache were compared to speech samples when subjects were headache-free. All analyses were conducted using a mixed-effect model design.Results: Longitudinal speech samples were collected from nineteen subjects with PTH (mean age=42.5, SD=13.7) who were an average of 14 days (SD=32.2) from their mTBI at the time of enrollment and thirty-one HC (mean age=38.7, SD=12.5). Regardless of headache presence or absence, PTH subjects had longer pause rates and reductions in vowel and consonant articulation precision relative to HC. On days when speech was collected during a headache, there were longer pause rates, slower sentence speaking rates and less precise consonant articulation compared to the speech production of HC. During headache, PTH subjects had slower speaking rates and altered vowel articulation compared to when they were headache-free. Conclusions: Compared to HC, subjects with acute PTH demonstrate altered speech as measured by objective features of speech production. For individuals with PTH, speech was altered during headache vs. when they were headache-free, suggesting that speech alterations were related to PTH and not solely due to the underlying mTBI.

Abstract Background and Objectives Prior studies have established an association between a history of abuse and the development of migraine. This cross‐sectional observational study explored the relationship between self‐reported abuse history with migraine‐related sensory hypersensitivity symptoms. Methods In total, 588 adult patients with migraine from the American Registry for Migraine Research completed questionnaires: Generalized Anxiety Disorder‐7, Patient Health Questionnaire‐2 for depression, Photosensitivity Assessment Questionnaire, Hyperacusis Questionnaire, and Allodynia Symptom Checklist. Using four binary screening questions, patients were asked to self‐report if they believed they had suffered emotional, physical, or sexual abuse in their lifetime. Differences in questionnaire scores between groups with and without a history of abuse were determined. Regression models adjusted for age, sex, and basic headache features analyzed the relationship between abuse history and sensory hypersensitivity symptoms. Moderation analysis explored the role of headache frequency in this relationship. Mediation analysis assessed the indirect (Mediated) effect (IE) of abuse on sensory hypersensitivity through depression or anxiety. Additional models analyzed relationships between sensory hypersensitivity symptoms and abuse subtypes or the number of abuse subtypes. Results Of 588 participants, 222 (38%) reported a history of abuse. Patients with a history of abuse reported statistically significantly greater average headache frequency (7.6 vs. 4.7 days, p = 0.030). Patients with a history of abuse also reported higher average or median questionnaire scores: anxiety (7.6 vs. 4.7, p < 0.001, d = 0.56), depression (1.7 vs. 1.3, p = 0.009, d = 0.24), photophobia (0.54 vs. 0.44, p < 0.001, d = 0.32), hyperacusis (19.6 vs. 14.9, p < 0.001, d = 0.49), ictal allodynia (6.0 vs. 3.0, p < 0.001, d = 0.46), and interictal allodynia (1.0 vs. 0.0, p < 0.001, d = 0.30). After controlling for patient age, sex and years lived with headache, abuse maintained a significant association with every sensory hypersensitivity measure. Headache frequency significantly moderated the relationship between a history of abuse with increased ictal allodynia ( p = 0.036). Anxiety significantly mediated the relationships between abuse with photophobia (IE = 0.03, 95% CI = 0.01–0.04), hyperacusis (IE = 1.51, 95% CI = 0.91–2.24), ictal allodynia (IE = 0.02, 95% CI = 0.01–0.04), and interictal allodynia (IE = 0.02, 95% CI = 0.01–0.06). Depression significantly mediated the relationship between abuse with photophobia (IE = 0.02, 95% CI = 0.01–0.03) and with hyperacusis (IE = 0.45, 95% CI = 0.11–0.88). The association between the individual subtypes of abuse and the number of subtypes of abuse with sensory hypersensitivity symptoms varied. Conclusion A history of abuse is associated with greater migraine‐related sensory hypersensitivity symptoms. To reduce the impact of abuse on migraine symptoms, future studies should explore mechanistic connections between abuse and migraine‐associated symptoms.

Background and Objective: Symptoms of persistent post-traumatic headache (PPTH) most often resemble those of migraine, including the presence of photo-, phono-, and cutaneous hypersensitivities. The severity of these hypersensitivity symptoms in those with PPTH compared to those with migraine has yet to be fully elucidated. The objective of this study was to compare symptoms of sensory hypersensitivities between PPTH, migraine, and healthy controls (HCs). Further defining characteristics of PPTH and its similarities to migraine might assist with developing future diagnostic criteria for PPTH and provide insights into PPTH mechanisms. Methods: This analysis included 56 individuals with PPTH attributed to mild traumatic brain injury, 30 with migraine, and 36 HCs. To assess sensory hypersensitivities, all subjects completed the Allodynia Symptom Checklist-12, the Photosensitivity Assessment Questionnaire, and the Hyperacusis Questionnaire. Differences among groups were assessed using Fisher’s exact test, Kruskal–Wallis, or Mann–Whitney U test. Results: PPTH and migraine groups had greater severity of cutaneous, photo-, and phono-hypersensitivity symptoms compared to HCs. There were no statistically significant differences between the PPTH and migraine groups for cutaneous allodynia (median [first quartile, third quartile]; PPTH: 4.0 [2.0, 7.0]; migraine: 5.0 [3.0, 8.0]; p = 0.54) or photosensitivity severity (PPTH: 5.0 [2.0, 7.0]; migraine: 5.0 [2.0, 6.0]; p = 0.53). Those with PPTH had higher hyperacusis scores compared to those with migraine (PPTH: 23.0 [17.0, 31.0]; migraine: 13.5 [9.0, 24.0]; p = 0.001). Conclusion: Sensory hypersensitivity symptoms among individuals with PPTH are at least as severe as those experienced by people with migraine. Results further confirm symptom similarities between PPTH and migraine and could suggest that PPTH and migraine have a partially shared underlying pathophysiology.

Abstract Background Close associations between insomnia with other clinical factors have been identified in migraine, but there have been few studies investigating associations between insomnia and clinical factors in patients with persistent post-traumatic headache (PPTH). The study objective was to contrast the severity of insomnia symptoms in PPTH, migraine, and healthy controls, and to identify factors associated with insomnia in patients with PPTH vs. migraine. Methods In this cross-sectional cohort study, 57 individuals with PPTH attributed to mild traumatic brain injury, 39 with migraine, and 39 healthy controls were included. Participants completed a detailed headache characteristics questionnaire, the Migraine Disability Assessment Scale (MIDAS), Insomnia Severity Index (ISI), Hyperacusis Questionnaire (HQ), Allodynia Symptom Checklist, Photosensitivity Assessment Questionnaire, Beck Depression Inventory (BDI), State-Trait Anxiety Inventory, Post-Traumatic Stress Disorder (PTSD) checklist, Ray Auditory Verbal Learning Test, and the Trail Making Test A and B to assess headache characteristics, disability, insomnia symptoms, sensory hypersensitivities, and neuropsychological factors. Fisher’s test and one-way ANOVA or Tukey’s Honest Significant Difference were used to assess group differences of categorical and continuous data. Stepwise linear regression analyses were conducted to identify clinical variables associated with insomnia symptoms. Results Those with PPTH had significantly higher ISI scores (16.7 ± 6.6) compared to migraine patients (11.3 ± 6.4) and healthy controls (4.1 ± 4.8) ( p < 0.001). For those with PPTH, insomnia severity was most strongly correlated with the BDI (Spearman's rho ( Common.EditSubmissionSteps.Transform.EquationText ) = 0.634, p < 0.01), followed by Trait Anxiety ( Common.EditSubmissionSteps.Transform.EquationText = 0.522, p < 0.01), PTSD ( Common.EditSubmissionSteps.Transform.EquationText = 0.505, p < 0.01), HQ ( Common.EditSubmissionSteps.Transform.EquationText = 0.469, p < 0.01), State Anxiety ( Common.EditSubmissionSteps.Transform.EquationText = 0.437, p < 0.01), and MIDAS scores ( Common.EditSubmissionSteps.Transform.EquationText = 0.364, p < 0.01). According to linear regression models, BDI, headache intensity, and hyperacusis scores were significantly positively associated with insomnia severity in those with PPTH, while only delayed memory recall was negatively associated with insomnia severity in those with migraine. Conclusions Insomnia symptoms were more severe in those with PPTH compared to migraine and healthy control cohorts. Depression, headache intensity, and hyperacusis were associated with insomnia in individuals with PPTH. Future studies should determine the bidirectional impact of treating insomnia and its associated symptoms.

Abstract Background: Close associations between insomnia with other clinical factors have been identified in migraine, but there have been few studies investigating associations between insomnia and clinical factors in patients with persistent post-traumatic headache (PPTH). The study objective was to contrast the severity of insomnia symptoms in PPTH, migraine, and healthy controls, and to identify factors associated with insomnia in patients with PPTH vs. migraine. Methods: In this cross-sectional cohort study, 57 individuals with PPTH attributed to mild traumatic brain injury, 39 with migraine, and 39 healthy controls were included. Participants completed a detailed headache characteristics questionnaire, the Migraine Disability Assessment Scale (MIDAS), Insomnia Severity Index (ISI), Hyperacusis Questionnaire (HQ), Allodynia Symptom Checklist, Photosensitivity Assessment Questionnaire, Beck Depression Inventory (BDI), State-Trait Anxiety Inventory, Post-Traumatic Stress Disorder (PTSD) checklist, Ray Auditory Verbal Learning Test, and the Trail Making Test A and B to assess headache characteristics, disability, insomnia symptoms, sensory hypersensitivities, and neuropsychological factors. Fisher’s test and one-way ANOVA were used to assess group differences of categorical and continuous data. Stepwise logistic regression analyses were conducted to identify clinical variables associated with insomnia symptoms. Results: Those with PPTH had significantly higher ISI scores (16.72 ± 6.58) compared to migraine patients (11.28 ± 6.42) and healthy controls (4.05 ± 4.80) (p < 0.001). For those with PPTH, insomnia severity was most strongly correlated with the BDI (Spearman's rho (ρ) = 0.634, p < 0.01), followed by Trait Anxiety (ρ = 0.522, p < 0.01), PTSD (ρ = 0.505, p < 0.01), HQ (ρ = 0.469, p < 0.01), State Anxiety (ρ = 0.437, p < 0.01), and MIDAS scores (ρ = 0.364, p < 0.01). According to linear regression models, BDI, headache intensity, and hyperacusis scores were significantly positively associated with insomnia severity in those with PPTH, while only delayed memory recall was negatively associated with insomnia severity in those with migraine. Conclusions: Insomnia symptoms were more severe in those with PPTH compared to migraine and healthy control cohorts. Depression, headache intensity, and hyperacusis were associated with insomnia in individuals with PPTH. Future studies should determine the bidirectional impact of treating insomnia and its associated symptoms.

Objectives The hypothalamus plays a key role in both migraine and cluster headache (CH). As brain region‐to‐region structural correlations are believed to reflect structural and functional brain connectivity patterns, we assessed the structural covariance patterns between the volume of the hypothalamic region and vertex‐by‐vertex measurements of cortical thickness in patients with migraine and in those with CH relative to healthy controls (HC). Methods T1‐weighted images were acquired on a 3T MRI scanner for a total of 59 subjects including 18 patients with CH (age: mean = 43.8, SD = 12.4), 19 with migraine (age: mean = 40.1, SD = 12.2), and 22 HCs (age: mean = 39.1, SD = 8.2). Imaging was collected between attacks (migraineurs) and during out‐of‐bout phases (CH). Data were post‐processed using FreeSurfer version 6.0 and within‐group correlations between hypothalamic region volume with cortical thickness were explored using a whole‐brain vertex‐wise linear model approach. Between‐group differences in correlation slopes between hypothalamic region volume and vertex‐by‐vertex measurements of cortical thickness were interrogated using post‐hoc comparisons. Results There were no significant between‐group differences (migraine vs CH; migraine vs HC; or CH vs HC) for age, sex, total brain volume or volume of the left or right hypothalamic region. For each group, there were significant positive correlations ( P < .01) between right and left hypothalamic region volumes with cortical thickness measurements. HC had significant positive correlations between hypothalamic region volume and cortical thickness over large portions of the superior and rostral medial frontal, orbitofrontal cortex and rostral anterior cingulate, and smaller clusters in the superior and middle temporal, posterior cingulate, fusiform, and precentral cortex. Post‐hoc analysis showed significant differences in covariance patterns in those with migraine and CH relative to HC, with both migraine patients and CH having weaker structural covariance of hypothalamic region volume with frontal and temporal cortical thickness. Conclusion Recent evidence suggests hypothalamic region connectivity to frontal and temporal areas to be relevant for regulating pain perception. Thus, the diminished structural covariance in migraineurs and CH might suggest abnormal functioning of the pain control circuitry and contribute to mechanisms underlying central sensitization and chronification of pain.

Background and Objectives Migraine with aura (MwA) is associated with increased brain hyper‐responsiveness to visual stimuli and increased visual network connectivity relative to migraine without aura (MwoA). Despite this, prior studies have provided conflicting results regarding whether MwA is associated with higher photophobia symptom scores compared to MwoA. The relationships between MwA and other types of sensory hypersensitivity, such as phonophobia and cutaneous allodynia (CA), have not been previously investigated. The purpose of this cross‐sectional observational study was to investigate whether MwA is associated with greater symptoms of photophobia, phonophobia, and CA compared to MwoA. Methods This analysis included 321 migraine patients (146 MwA; 175 MwoA) who had been enrolled into the American Registry for Migraine Research. The diagnosis of either MwoA or MwA was determined by headache specialists using ICHD diagnostic criteria. Patients completed the Photosensitivity Assessment Questionnaire, the Hyperacusis Questionnaire, and the Allodynia Symptom Checklist. Mean or median values were compared between groups. Regression models were created to analyze the relationship between MwA with photophobia scores, hyperacusis scores, and the presence of interictal CA. Results Those with MwA had higher mean photophobia scores than those with MwoA (4.1 vs 3.0, P = .0003). MwA was positively associated with photophobia symptom severity ( B = 0.50 [SE = 0.14], P = .0003), after controlling for age, patient sex, and headache frequency. Aura was not associated with hyperacusis symptom severity ( B = 0.07 [SE = 0.08], P = .346) or the presence of interictal CA (OR 1.33 [95% CI 0.70‐2.53], P = .381). Conclusion MwA is associated with higher photophobia symptom scores compared to MwoA. Aura is not associated with greater hyperacusis or interictal allodynia scores. These findings complement prior imaging and neurophysiologic studies that demonstrated MwA to be associated with hyper‐responsiveness of brain visual processing regions. The findings suggest that MwA is associated specifically with visual hypersensitivity, as opposed to being associated with a general hypersensitivity to multiple types of sensory stimuli.

Objectives Often, persistent post-traumatic headache and migraine are phenotypically similar. However, the similarities and differences in the neuropathological underpinnings of persistent post-traumatic headache and migraine require further understanding. We used diffusion tensor imaging (DTI) and a novel method for detecting subtle changes in fibertract integrity by measuring node-by-node parameters along each tract to compare fibertract profiles between those with migraine and those with persistent post-traumatic headache, and compared both cohorts to a group of controls. Methods Eighteen fibertracts were reconstructed for 131 subjects, including 49 patients with persistent post-traumatic headache attributed to mild traumatic brain injury, 41 with migraine, and 41 controls. Node-by-node diffusion parameters of mean diffusivity and radial diffusivity were calculated along each tract. Mean diffusivity and radial diffusivity measurements were averaged along quartiles of each tract for statistical interpretation and group comparison. Using a post-hoc analysis, correlations between tract quartile measurements and headache frequency were calculated. Results There were significant differences between migraine and persistent post-traumatic headache cohorts for quartile measurements of mean diffusivity or radial diffusivity in the bilateral anterior thalamic radiations, cingulum (angular bundles and cingulate gyri), inferior longitudinal fasciculi, and uncinate fasciculi, the left corticospinal tract, and the right superior longitudinal fasciculi-parietal portion. For migraine patients, there was a significant positive correlation between headache frequency and forceps major mean diffusivity, whereas for persistent post-traumatic headache there was a positive correlation between headache frequency and cingulum angular bundle mean diffusivity and radial diffusivity. Conclusions Quartile measurements of radial diffusivity and mean diffusivity indicate unique differences in fibertract profiles between those with migraine vs. persistent post-traumatic headache. Although for both migraine and persistent post-traumatic headache there was a positive relationship between fibertract alterations and headache frequency, there were disease-specific differences between headache frequency and fibertract injury patterns. These findings might suggest potential differences in the neuropathological mechanisms underlying migraine and persistent post-traumatic headache.

Even when concussions are associated with prolonged physical and cognitive sequelae, concussions are typically “invisible” on diagnostic brain imaging, indicating that the neuropathology associated with concussion lies under the detection threshold of routine imaging. However, data from brain structural and functional research imaging studies using diffusion tensor imaging, resting‐state functional magnetic resonance imaging, and brain perfusion imaging indicate that these imaging sequences have a role in identifying concussion‐related neuropathology. These advanced imaging techniques provide insights into concussion neuropathology and might be useful for differentiating concussed patients from healthy controls. In this review article, we provide an overview of research findings from brain structural and functional imaging studies of concussion, and discuss the accuracy of classification models developed via machine‐learning algorithms for identifying individual patients with concussion based on imaging data.