Questionnaire and structural imaging data accurately predict headache improvement in patients with acute post-traumatic headache attributed to mild traumatic brain injury.

BACKGROUND: Our prior work demonstrated that questionnaires assessing psychosocial symptoms have utility for predicting improvement in patients with acute post-traumatic headache following mild traumatic brain injury. In this cohort study, we aimed to determine whether prediction accuracy can be refined by adding structural magnetic resonance imaging (MRI) brain measures to the model. METHODS: Adults with acute post-traumatic headache (enrolled 0-59 days post-mild traumatic brain injury) underwent T1-weighted brain MRI and completed three questionnaires (Sports Concussion Assessment Tool, Pain Catastrophizing Scale, and the Trait Anxiety Inventory Scale). Individuals with post-traumatic headache completed an electronic headache diary allowing for determination of headache improvement at three- and at six-month follow-up. Questionnaire and MRI measures were used to train prediction models of headache improvement and headache trajectory. RESULTS: Forty-three patients with post-traumatic headache (mean age = 43.0, SD = 12.4; 27 females/16 males) and 61 healthy controls were enrolled (mean age = 39.1, SD = 12.8; 39 females/22 males). The best model achieved cross-validation Area Under the Curve of 0.801 and 0.805 for predicting headache improvement at three and at six months. The top contributing MRI features for the prediction included curvature and thickness of superior, middle, and inferior temporal, fusiform, inferior parietal, and lateral occipital regions. Patients with post-traumatic headache who did not improve by three months had less thickness and higher curvature measures and notably greater baseline differences in brain structure vs. healthy controls (thickness: p < 0.001, curvature: p = 0.012) than those who had headache improvement. CONCLUSIONS: A model including clinical questionnaire data and measures of brain structure accurately predicted headache improvement in patients with post-traumatic headache and achieved improvement compared to a model developed using questionnaire data alone.

Thalamic subfield iron accumulation after acute mild traumatic brain injury as a marker of future post-traumatic headache intensity.

OBJECTIVE: To explore alterations in thalamic subfield volume and iron accumulation in individuals with post-traumatic headache (PTH) relative to healthy controls. BACKGROUND: The thalamus plays a pivotal role in the pathomechanism of pain and headache, yet the role of the thalamus in PTH attributed to mild traumatic brain injury (mTBI) remains unclear. METHODS: A total of 107 participants underwent multimodal T1-weighted and T2* brain magnetic resonance imaging. Using a clinic-based observational study, thalamic subfield volume and thalamic iron accumulation were explored in 52 individuals with acute PTH (mean age = 41.3; standard deviation [SD] = 13.5), imaged on average 24 days post mTBI, and compared to 55 healthy controls (mean age = 38.3; SD = 11.7) without history of mTBI or migraine. Symptoms of mTBI and headache characteristics were assessed at baseline (0-59 days post mTBI) (n = 52) and 3 months later (n = 46) using the Symptom Evaluation of the Sports Concussion Assessment Tool (SCAT-5) and a detailed headache history questionnaire. RESULTS: Relative to controls, individuals with acute PTH had significantly less volume in the lateral geniculate nucleus (LGN) (mean volume: PTH = 254.1, SD = 43.4 vs. controls = 278.2, SD = 39.8; p = 0.003) as well as more iron deposition in the left LGN (PTH: T2* signal = 38.6, SD = 6.5 vs. controls: T2* signal = 45.3, SD = 2.3; p = 0.048). Correlations in individuals with PTH revealed a positive relationship between left LGN T2* iron deposition and SCAT-5 symptom severity score at baseline (r = -0.29, p = 0.019) and maximum headache intensity at the 3-month follow-up (r = -0.47, p = 0.002). CONCLUSION: Relative to healthy controls, individuals with acute PTH had less volume and higher iron deposition in the left LGN. Higher iron deposition in the left LGN might reflect mTBI severity and poor headache recovery.

Developing multivariable models for predicting headache improvement in patients with acute post-traumatic headache attributed to mild traumatic brain injury: A preliminary study.

OBJECTIVES/BACKGROUND: Post-traumatic headache (PTH) is a common symptom after mild traumatic brain injury (mTBI). Although there have been several studies that have used clinical features of PTH to attempt to predict headache recovery, currently no accurate methods exist for predicting individuals' improvement from acute PTH. This study investigated the utility of clinical questionnaires for predicting (i) headache improvement at 3 and 6 months, and (ii) headache trajectories over the first 3 months. METHODS: We conducted a clinic-based observational longitudinal study of patients with acute PTH who completed a battery of clinical questionnaires within 0-59 days post-mTBI. The battery included headache history, symptom evaluation, cognitive tests, psychological tests, and scales assessing photosensitivity, hyperacusis, insomnia, cutaneous allodynia, and substance use. Each participant completed a web-based headache diary, which was used to determine headache improvement. RESULTS: Thirty-seven participants with acute PTH (mean age = 42.7, standard deviation [SD] = 12.0; 25 females/12 males) completed questionnaires at an average of 21.7 (SD = 13.1) days post-mTBI. The classification of headache improvement or non-improvement at 3 and 6 months achieved cross-validation area under the curve (AUC) of 0.72 (95% confidence interval [CI] 0.55 to 0.89) and 0.84 (95% CI 0.66 to 1.00). Sub-models trained using only the top five features still achieved 0.72 (95% CI 0.55 to 0.90) and 0.77 (95% CI 0.52 to 1.00) AUC. The top five contributing features were from three questionnaires: Pain Catastrophizing Scale total score and helplessness sub-domain score; Sports Concussion Assessment Tool Symptom Evaluation total score and number of symptoms; and the State-Trait Anxiety Inventory score. The functional regression model achieved R = 0.64 for modeling headache trajectory over the first 3 months. CONCLUSION: Questionnaires completed following mTBI have good utility for predicting headache improvement at 3 and 6 months in the future as well as the evolving headache trajectory. Reducing the battery to only three questionnaires, which assess post-concussive symptom load and biopsychosocialecologic factors, was helpful to determine a reasonable prediction accuracy for headache improvement.

T2* reduction in patients with acute post-traumatic headache.

OBJECTIVES: Although iron accumulation in pain-processing brain regions has been associated with repeated migraine attacks, brain structural changes associated with post-traumatic headache have yet to be elucidated. To determine whether iron accumulation is associated with acute post-traumatic headache, magnetic resonance transverse relaxation rates (T2*) associated with iron accumulation were investigated between individuals with acute post-traumatic headache attributed to mild traumatic brain injury and healthy controls. METHODS: Twenty individuals with acute post-traumatic headache and 20 age-matched healthy controls underwent 3T brain magnetic resonance imaging including quantitative T2* maps. T2* differences between individuals with post-traumatic headache versus healthy controls were compared using age-matched paired t-tests. Associations of T2* values with headache frequency and number of mild traumatic brain injuries were investigated using multiple linear regression in individuals with post-traumatic headache. Significance was determined using uncorrected p-value and cluster size threshold. RESULTS: Individuals with post-traumatic headache had lower T2* values compared to healthy controls in cortical (bilateral frontal, bilateral anterior and posterior cingulate, right postcentral, bilateral temporal, right supramarginal, right rolandic, left insula, left occipital, right parahippocampal), subcortical (left putamen, bilateral hippocampal) and brainstem regions (pons). Within post-traumatic headache subjects, multiple linear regression showed a negative association between T2* in the right inferior parietal/supramarginal regions and number of mild traumatic brain injuries and a negative association between T2* in bilateral cingulate, bilateral precuneus, bilateral supplementary motor areas, bilateral insula, right middle temporal and right lingual areas and headache frequency. CONCLUSIONS: Acute post-traumatic headache is associated with iron accumulation in multiple brain regions. Correlations with headache frequency and number of lifetime mild traumatic brain injuries suggest that iron accumulation is part of the pathophysiology or a marker of mild traumatic brain injury and post-traumatic headache.

Seroprevalence of anti-SARS-CoV-2 antibodies among staff at primary healthcare institutions in Prishtina.

BACKGROUND: Many studies examined the spread of SARS-CoV-2 within populations using seroprevalence. Healthcare workers are a high-risk population due to patient contact, and studies are needed to examine seroprevalence of SARS-CoV-2 antibodies among healthcare workers. Our study investigates the seroprevalence of anti-SARS-CoV-2 antibodies among staff at primary healthcare institutions in Prishtina, and factors associated with seroprevalence. METHODS: We carried out a cross-sectional survey including SARS-CoV-2 serological testing and questionnaires with primary healthcare workers from primary healthcare facilities in the Prishtina, the capital city of Kosovo. We calculated prevalence of anti-SARS-CoV-2 antibodies, and of self-reported positive PCR test among primary healthcare workers, as well as crude and adjusted ORs for explanatory factors. RESULTS: Eighty-three of the healthcare workers (17.47%) tested positive for SARS-CoV-2 antibodies IgG or IgM, while 231 (48.63%) either had antibodies or a previous positive PCR test. Odds of seropositivity were affected by male gender (OR 2.08, 95% CI 1.20, 3.61), and infected family members (OR 3.61, 95% CI 2.25, 5.79) of healthcare workers. Higher education, being part of larger families and having infected family members gave higher odds of positive PCR test and seropositivity. Other healthcare workers had lower odds of positive PCR test and seropositivity than physicians. CONCLUSION: Over 17% of healthcare workers were seropositive for SARS-CoV-2 antibodies and close to half of them were either seropositive or PCR self-reported positive test. Several factors are associated with decreased and increased odds for such outcomes. These findings should be explored further and addressed to Kosovo policy makers, and assist them to intensify vaccination efforts, and maintain control measures until we achieve herd immunity.

Distinguishing persistent post-traumatic headache from migraine: Classification based on clinical symptoms and brain structural MRI data.

BACKGROUND: Persistent post-traumatic headache most commonly has symptoms that overlap those of migraine. In some cases, it can be clinically difficult to differentiate persistent post-traumatic headache with a migraine phenotype from migraine. The objective of this study was to develop a classification model based on questionnaire data and structural neuroimaging data that distinguishes individuals with migraine from those with persistent post-traumatic headache. METHODS: Questionnaires assessing headache characteristics, sensory hypersensitivities, cognitive functioning, and mood, as well as T1-weighted magnetic resonance imaging and diffusion tensor data from 34 patients with migraine and 48 patients with persistent post-traumatic headache attributed to mild traumatic brain injury were included for analysis. The majority of patients with persistent post-traumatic headache had a migraine/probable migraine phenotype (77%). A machine-learning leave-one-out cross-validation algorithm determined the average accuracy for distinguishing individual migraine patients from individual patients with persistent post-traumatic headache. RESULTS: Based on questionnaire data alone, the average classification accuracy for determining whether an individual person had migraine or persistent post-traumatic headache was 71.9%. Adding imaging data features to the model improved the classification accuracy to 78%, including an average accuracy of 97.1% for identifying individual migraine patients and an average accuracy of 64.6% for identifying individual patients with persistent post-traumatic headache. The most important clinical features that contributed to the classification accuracy included questions related to anxiety and decision making. Cortical brain features and fibertract data from the following regions or tracts most contributed to the classification accuracy: Bilateral superior temporal, inferior parietal and posterior cingulate; right lateral occipital, uncinate, and superior longitudinal fasciculus. A post-hoc analysis showed that compared to incorrectly classified persistent post-traumatic headache patients, those who were correctly classified as having persistent post-traumatic headache had more severe physical, autonomic, anxiety and depression symptoms, were more likely to have post-traumatic stress disorder, and were more likely to have had mild traumatic brain injury attributed to blasts. DISCUSSION: A classification model that included a combination of questionnaire data and structural imaging parameters classified individual patients as having migraine versus persistent post-traumatic headache with good accuracy. The most important clinical measures that contributed to the classification accuracy included questions on mood. Regional brain structures and fibertracts that play roles in pain processing and pain integration were important brain features that contributed to the classification accuracy. The lower classification accuracy for patients with persistent post-traumatic headache compared to migraine may be related to greater heterogeneity of patients in the persistent post-traumatic headache cohort regarding their traumatic brain injury mechanisms, and physical, emotional, and cognitive symptoms.

Headache Characteristics and Psychological Factors Associated with Functional Impairment in Individuals with Persistent Posttraumatic Headache.

OBJECTIVE: Persistent posttraumatic headache (PPTH), one of the most common symptoms following mild traumatic brain injury, is often associated with substantial functional disability. The objective of this study was to assess the contribution of demographics, headache characteristics, and psychological symptoms to disability associated with PPTH. METHODS: Participants completed the State-Trait Anxiety Inventory (STAI), the Beck Depression Inventory (BDI), the Pain Catastrophizing Scale (PCS), and the Migraine Disability Assessment (MIDAS) questionnaire. Two linear regression models were formulated to interrogate the relationships between 1) demographics and headache characteristics with the MIDAS questionnaire and 2) demographics, headache characteristics, and psychological symptoms with the MIDAS questionnaire. A two-way stepwise regression using the Akaike information criterion was performed to find a parsimonious model describing the relationships between demographics, headache characteristics, and psychological measures with the MIDAS questionnaire. RESULTS: Participants included 58 patients with PPTH and 39 healthy controls (HCs). The median MIDAS score among those with PPTH was 48.0 (first quartile [1Q] = 20.0, third quartile [3Q] = 92.0), indicative of severe disability. Compared with the HCs, those with PPTH had higher scores on the BDI, STAI, and PCS. Older age predicted lower MIDAS scores (age: B=-0.11, P<0.01), whereas higher headache frequency, greater headache intensity, and higher trait anxiety scores predicted higher MIDAS scores in individuals with PPTH (headache frequency: B=0.07, P<0.001; headache intensity: B=0.51, P=0.04; trait anxiety score: B=1.11, P=0.01). CONCLUSIONS: Individuals with PPTH had substantial psychological symptoms and headache-related disability. Disability was partially explained by age, headache frequency and intensity, and trait anxiety. Holistic management of patients with PPTH to address headaches and psychological symptoms might reduce headache-associated disability.

Altered speech patterns in subjects with post-traumatic headache due to mild traumatic brain injury.

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 3 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 yet more precise 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 production may have been more effortful resulting in slower speaking rates and more precise vowel articulation during headache vs. when they were headache-free, suggesting that speech alterations were related to PTH and not solely due to the underlying mTBI.

Clinical correlates of insomnia in patients with persistent post-traumatic headache compared with migraine.

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 (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.

Altered speech with migraine attacks: A prospective, longitudinal study of episodic migraine without aura.

BACKGROUND AND OBJECTIVE: Some individuals with migraine report the presence of speech changes during their migraine attacks. The goal of this study was to compare objective features of speech during the migraine pre-attack, the migraine attack, and during the interictal period. METHODS: This was a prospective, longitudinal, observational study of adults with episodic migraine and healthy non-migraine controls. Participants provided speech samples three times per day using a speech elicitation tool included within a mobile app. Six complementary speech features that capture articulation and prosody were extracted from speech samples. Participants with migraine maintained a daily headache diary using the same app. A mixed effects model and t-tests were used to investigate differences in speech features between controls, the migraine pre-attack phase, the migraine attack, and the interictal period. RESULTS: In total, 56,767 speech samples were collected, including 43,102 from 15 individuals with migraine and 13,665 from matched healthy controls. Significant group-level differences in speech features were identified between those with migraine and healthy controls and within the migraine group during the pre-attack vs. attack vs. interictal periods (all p < .05). Most consistently, speech changes occurred in the speaking rate, articulation rate and precision, and phonatory duration. Within-subject analysis revealed that seven of 15 individuals with migraine showed significant change in at least one speech feature when comparing the migraine attack vs. interictal phase and four showed similar changes when comparing the pre-attack vs. interictal phases. CONCLUSIONS: Changes in speech occurred in almost half of the individuals during migraine attacks. Once confirmed in subsequent studies, speech changes could be considered a feature of the migraine attack.

Differences in fibertract profiles between patients with migraine and those with persistent post-traumatic headache.

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.

Static and dynamic functional connectivity differences between migraine and persistent post-traumatic headache: A resting-state magnetic resonance imaging study.

INTRODUCTION: Although migraine and persistent post-traumatic headache often share phenotypic characteristics, few studies have interrogated the pathophysiological differences underlying these headache types. While there is now some indication of differences in brain structure between migraine and persistent post-traumatic headache, differences in brain function have not been adequately investigated. The objective of this study was to compare static and dynamic functional connectivity patterns in migraine versus persistent post-traumatic headache using resting-state magnetic resonance imaging. METHODS: This case-control study interrogated the static functional connectivity and dynamic functional connectivity patterns of 59 a priori selected regions of interest involved in pain processing. Pairwise connectivity (region of interest to region of interest) differences between migraine (n = 33) and persistent post-traumatic headache (n = 44) were determined and compared to healthy controls (n = 36) with ANOVA and subsequent t-tests. Pearson partial correlations were used to explore the relationship between headache burden (headache frequency; years lived with headache) and functional connectivity and between pain intensity at the time of imaging and functional connectivity for migraine and persistent post-traumatic headache groups, separately. RESULTS: Significant differences in static functional connectivity between migraine and persistent post-traumatic headache were found for 17 region pairs that included the following regions of interest: Primary somatosensory, secondary somatosensory, posterior insula, hypothalamus, anterior cingulate, middle cingulate, temporal pole, supramarginal gyrus, superior parietal, middle occipital, lingual gyrus, pulvinar, precuneus, cuneus, somatomotor, ventromedial prefrontal cortex, and dorsolateral prefrontal cortex. Significant differences in dynamic functional connectivity between migraine and persistent post-traumatic headache were found for 10 region pairs that included the following regions of interest: Secondary somatosensory, hypothalamus, middle cingulate, temporal pole, supramarginal gyrus, superior parietal, lingual gyrus, somatomotor, precentral, posterior cingulate, middle frontal, fusiform gyrus, parieto-occiptal, and amygdala. Although there was overlap among the regions demonstrating static functional connectivity differences and those showing dynamic functional connectivity differences between persistent post-traumatic headache and migraine, there was no overlap in the region pair functional connections. After controlling for sex and age, there were significant correlations between years lived with headache with static functional connectivity of the right dorsolateral prefrontal cortex with the right ventromedial prefrontal cortex in the migraine group and with static functional connectivity of right primary somatosensory with left supramarginal gyrus in the persistent post-traumatic headache group. There were significant correlations between headache frequency with static functional connectivity of left secondary somatosensory with right cuneus in the migraine group and with static functional connectivity of left middle cingulate with right pulvinar and right posterior insula with left hypothalamus in the persistent post-traumatic headache group. Dynamic functional connectivity was significantly correlated with headache frequency, after controlling for sex and age, in the persistent post-traumatic headache group for one region pair (right middle cingulate with right supramarginal gyrus). Dynamic functional connectivity was correlated with pain intensity at the time of imaging for the migraine cohort for one region pair (right posterior cingulate with right amygdala). CONCLUSIONS: Resting-state functional imaging revealed static functional connectivity and dynamic functional connectivity differences between migraine and persistent post-traumatic headache for regions involved in pain processing. These differences in functional connectivity might be indicative of distinctive pathophysiology associated with migraine versus persistent post-traumatic headache.

Less Cortical Thickness in Patients With Persistent Post-Traumatic Headache Compared With Healthy Controls: An MRI Study.

OBJECTIVE: To investigate differences in cortical thickness in patients with persistent post-traumatic headache (PPTH) relative to healthy controls and to interrogate whether cortical morphology relates to headache burden (headache frequency, years with post-traumatic headache, PTH) in patients with PPTH. BACKGROUND: PTHs are one of the most common symptoms following concussion. In some patients, PTHs continue for longer than three months and are classified as PPTH. This study has two main goals: (1) To delineate the neuropathology of PPTH, by interrogating differences in cortical thickness in patients with PPTH relative to healthy controls. (2) To interrogate potential associations between brain morphology and headache burden in patients with PPTH by examining whether cortical thickness relates to frequency of headaches or years lived with PTH. METHODS: Adults with PPTH diagnosed according to ICHD 3 beta diagnostic criteria and healthy controls underwent brain MRI on a 3 Tesla scanner. Vertex-by-vertex whole brain estimates of cortical thickness were automatically calculated using FreeSurfer v5.3. Differences in cortical thickness in patients with PPTH relative to healthy controls were determined using a general linear model design. Associations were explored between regional clusters where patients with PPTH showed cortical thickness differences compared with healthy controls with headache frequency and years lived with PPTH. RESULTS: This study included 33 patients with PPTH and 33 healthy control subjects (healthy controls: median age = 33.0, IQR = 15.5; patients with PPTH: median age = 36.0, IQR = 20.5; P = .56). Patients with PPTH had less cortical thickness relative to healthy controls in the left and right superior frontal, caudal middle frontal, and precentral cortex as well as less cortical thickness in the right supramarginal, right superior and inferior parietal, and right precuneus region (P < .05, Monte Carlo corrected for multiple comparisons). There were no regions where patients with PPTH had more cortical thickness relative to healthy controls. A correlation analysis of regions that showed less cortical thickness in patients with PPTH demonstrated a negative correlation between left and right superior frontal thickness with headache frequency (P < .05). There was no association between regional cortical thickness and years lived with PPTH. CONCLUSION: Compared with healthy controls, patients with PPTH had less cortical thickness in bilateral frontal regions and right hemisphere parietal regions. For patients with PPTH, more frequent headaches were related to less thickness in the left and right superior frontal regions, potentially indicating that brain morphology changes in the superior frontal regions in patients with PPTH are modified by headache frequency.

Symptoms of Autonomic Dysfunction Among Those With Persistent Posttraumatic Headache Attributed to Mild Traumatic Brain Injury: A Comparison to Migraine and Healthy Controls.

BACKGROUND: Most persistent posttraumatic headaches (PPTH) have a phenotype that meets diagnostic criteria for migraine or probable migraine. Although symptoms of autonomic dysfunction have been well described among those with migraine, the presence and relative severity of such symptoms among those with PPTH have yet to be reported. OBJECTIVE: The objective of this study was to assess and compare symptoms of autonomic dysfunction among those with PPTH attributed to mild traumatic brain injury (mTBI) vs migraine vs healthy controls using Composite Autonomic Symptom Score 31 (COMPASS-31) questionnaire scores. METHODS: Individuals with PPTH (n = 56) (87.5% of whom had a migraine/probable migraine phenotype), migraine (n = 30), and healthy controls (n = 36) were prospectively assessed in this cross-sectional cohort study using the COMPASS-31 questionnaire. Total COMPASS-31 scores and individual domain scores (bladder, gastrointestinal, orthostatic intolerance, pupillomotor, secretomotor, vasomotor) were compared between subject groups. RESULTS: COMPASS-31 mean total weighted score was 37.22 ± 15.44 in the PPTH group, 27.15 ± 14.37 in the migraine group, and 11.67 ± 8.98 for healthy controls. COMPASS-31 mean weighted total scores were significantly higher in those with PPTH vs migraine (P = .014), for PPTH vs healthy controls (P = .001), and for migraine vs healthy controls (P = .001). Those with PPTH had numerically higher scores for all COMPASS-31 domains compared to those with migraine, and the domain scores were significantly higher for orthostatic intolerance (PPTH = 4.80 ± 2.47 vs migraine = 3.33 ± 2.31, P = .027) and bladder (PPTH = 1.14 ± 1.45 vs migraine = 0.47 ± 0.73, P = .020). Among individuals with PPTH, post hoc correlations indicated a positive association between number of total lifetime TBIs with total weighted COMPASS-31 scores (rho = 0.32, P = .020), between years lived with headache and vasomotor domain subscores (rho = 0.27; P = .044), and between headache frequency with vasomotor domain subscores (rho = 0.27; P = .041). CONCLUSIONS: Symptoms of autonomic dysfunction were greatest among those with PPTH compared to migraine and healthy controls. Among individuals with PPTH, number of lifetime TBIs was associated with greater symptoms of autonomic dysfunction, while greater headache burden was associated with higher vasomotor domain autonomic dysfunction subscores, potentially indicating that PPTH patients with higher disease burden have an increased risk for having autonomic dysfunction. Symptoms of autonomic dysfunction should be ascertained during the clinical management of patients with PPTH and might be a characteristic that helps differentiate PPTH from migraine.

Acoustic and perceptual speech characteristics of native Mandarin speakers with Parkinson's disease.

This study examines acoustic features of speech production in speakers of Mandarin with Parkinson's disease (PD) and relates them to intelligibility outcomes. Data from 11 participants with PD and 7 controls are compared on several acoustic measures. In speakers with PD, the strength of association between these measures and intelligibility is investigated. Speakers with PD exhibited significant differences in fundamental frequency, pitch variation, vowel space, and rate relative to controls. However, in contrast to the English studies, speech rate was consistently slow and most strongly correlated with intelligibility. Thus, acoustic cues that strongly influence intelligibility in PD may vary cross-linguistically.

Persistent post-traumatic headache vs. migraine: an MRI study demonstrating differences in brain structure.

BACKGROUND: The majority of individuals with post-traumatic headache have symptoms that are indistinguishable from migraine. The overlap in symptoms amongst these individuals raises the question as to whether post-traumatic headache has a unique pathophysiology or if head trauma triggers migraine. The objective of this study was to compare brain structure in individuals with persistent post-traumatic headache (i.e. headache lasting at least 3 months following a traumatic brain injury) attributed to mild traumatic brain injury to that of individuals with migraine. METHODS: Twenty-eight individuals with persistent post-traumatic headache attributed to mild traumatic brain injury and 28 individuals with migraine underwent brain magnetic resonance imaging on a 3 T scanner. Regional volumes, cortical thickness, surface area and curvature measurements were calculated from T1-weighted sequences and compared between subject groups using ANCOVA. MRI data from 28 healthy control subjects were used to interpret the differences in brain structure between migraine and persistent post-traumatic headache. RESULTS: Differences in regional volumes, cortical thickness, surface area and brain curvature were identified when comparing the group of individuals with persistent post-traumatic headache to the group with migraine. Structure was different between groups for regions within the right lateral orbitofrontal lobe, left caudal middle frontal lobe, left superior frontal lobe, left precuneus and right supramarginal gyrus (p < .05). Considering these regions only, there were differences between individuals with persistent post-traumatic headache and healthy controls within the right lateral orbitofrontal lobe, right supramarginal gyrus, and left superior frontal lobe and no differences when comparing the migraine cohort to healthy controls. CONCLUSIONS: In conclusion, persistent post-traumatic headache and migraine are associated with differences in brain structure, perhaps suggesting differences in their underlying pathophysiology. Additional studies are needed to further delineate similarities and differences in brain structure and function that are associated with post-traumatic headache and migraine and to determine their specificity for each of the headache types.

The relationship between perceptual disturbances in dysarthric speech and automatic speech recognition performance.

State-of-the-art automatic speech recognition (ASR) engines perform well on healthy speech; however recent studies show that their performance on dysarthric speech is highly variable. This is because of the acoustic variability associated with the different dysarthria subtypes. This paper aims to develop a better understanding of how perceptual disturbances in dysarthric speech relate to ASR performance. Accurate ratings of a representative set of 32 dysarthric speakers along different perceptual dimensions are obtained and the performance of a representative ASR algorithm on the same set of speakers is analyzed. This work explores the relationship between these ratings and ASR performance and reveals that ASR performance can be predicted from perceptual disturbances in dysarthric speech with articulatory precision contributing the most to the prediction followed by prosody.

Modeling listener perception of speaker similarity in dysarthria.

The current investigation contributes to a perceptual similarity-based approach to dysarthria characterization by utilizing an innovative statistical approach, multinomial logistic regression with sparsity constraints, to identify acoustic features underlying each listener's impressions of speaker similarity. The data-driven approach also permitted an examination of the effect of clinical experience on listeners' impressions of similarity. Listeners, irrespective of level of clinical experience, were found to rely on similar acoustic features during the perceptual sorting task, known as free classification. Overall, the results support the continued advancement of a similarity-based approach to characterizing the communication disorders associated with dysarthria.

The role of stress and word size in Spanish speech segmentation.

In English, the predominance of stressed syllables as word onsets aids lexical segmentation in degraded listening conditions. Yet it is unlikely that these findings would readily transfer to languages with differing rhythmic structure. In the current study, the authors seek to examine whether listeners exploit both common word size (syllable number) and stress cues to aid lexical segmentation in Spanish. Forty-seven Spanish-speaking listeners transcribed two-word Spanish phrases in noise. As predicted by the statistical probabilities of Spanish, error analysis revealed that listeners preferred two- and three-syllable words with penultimate stress in their attempts to parse the degraded speech signal. These findings provide insight into the importance of stress in tandem with word size in the segmentation of Spanish words and suggest testable hypotheses for cross-linguistic studies that examine the effects of degraded acoustic cues on lexical segmentation.

Empirically Estimable Classification Bounds Based on a Nonparametric Divergence Measure.

Information divergence functions play a critical role in statistics and information theory. In this paper we show that a non-parametric f-divergence measure can be used to provide improved bounds on the minimum binary classification probability of error for the case when the training and test data are drawn from the same distribution and for the case where there exists some mismatch between training and test distributions. We confirm the theoretical results by designing feature selection algorithms using the criteria from these bounds and by evaluating the algorithms on a series of pathological speech classification tasks.