Temporal Sensitivity for Achromatic and Chromatic Flicker across the Visual Cortex.

The retinal ganglion cells (RGCs) receive different combinations of L, M, and S cone inputs and give rise to one achromatic and two chromatic postreceptoral channels. The goal of the current study was to determine temporal sensitivity across the three postreceptoral channels in subcortical and cortical regions involved in human vision. We measured functional magnetic resonance imaging (fMRI) responses at 7 T from three participants (two males, one female) viewing a high-contrast, flickering, spatially uniform wide field (∼140°). Stimulus flicker frequency varied logarithmically between 2 and 64 Hz and targeted the L + M + S, L - M, and S - (L + M) cone combinations. These measurements were used to create temporal sensitivity functions of the primary visual cortex (V1) across eccentricity and spatially averaged responses from the lateral geniculate nucleus (LGN), and the V2/V3, hV4, and V3A/B regions. fMRI responses reflected the known properties of the visual system, including higher peak temporal sensitivity to achromatic versus chromatic stimuli and low-pass filtering between the LGN and V1. Peak temporal sensitivity increased across levels of the cortical visual hierarchy. Unexpectedly, peak temporal sensitivity varied little across eccentricity within area V1. Measures of adaptation and distributed pattern activity revealed a subtle influence of 64 Hz achromatic flicker in area V1, despite this stimulus evoking only a minimal overall response. The comparison of measured cortical responses to a model of the integrated retinal output to our stimuli demonstrates that extensive filtering and amplification are applied to postretinal signals.

Symptoms associated with headache in youth.

OBJECTIVE: To determine the underlying relationships between a broad range of headache-associated symptoms and how they relate to headache burden. BACKGROUND: Symptoms associated with head pain inform classification of headache disorders. However, many headache-associated symptoms are not included in the diagnostic criteria, which is largely based on expert opinion. Large symptom databases can assess headache-associated symptoms irrespective of pre-existing diagnostic categories. METHODS: We conducted a large single-center cross-sectional study on youth (6-17 years old) assessing patient-reported outpatient headache questionnaires between June 2017 and February 2022. Multiple correspondence analysis, an exploratory factor analysis, was applied to 13 headache-associated symptoms. RESULTS: 6662 participants (64% female; median age 13.6 years) were included. Multiple correspondence analysis dimension 1 (25.4% of the variance) captured the absence or abundance of headache-associated symptoms. A greater number of headache-associated symptoms correlated with greater headache burden. Dimension 2 (11.0% of the variance) revealed three symptom clusters: (1) cardinal features of migraine (light, sound, and smell sensitivity, nausea, and vomiting), (2) nonspecific global neurologic dysfunction symptoms (lightheadedness, trouble thinking, blurry vision), (3) vestibular and brainstem dysfunction symptoms (vertigo, balance problems, ear ringing, double vision). CONCLUSION: Assessing a broader range of headache-associated symptoms reveals clustering of symptomatology and a strong relationship with headache burden.

Comparison of continuous headache features in youth with migraine, new daily persistent headache, and persistent post-traumatic headache.

OBJECTIVE: To compare clinical features in youth with continuous headache from migraine, persistent post-traumatic headache, and new daily persistent headache to determine if they are similar, contrary to their distinction in the International Classification of Headache Disorders. METHODS: We pursued a single center age- and sex-matched observational study comparing the clinical characteristics of 150 youth (11 - 17 years old) with continuous headache from migraine, persistent post-traumatic headache, and new daily persistent headache. A diagnostic algorithm based on international classification of headache disorders criteria was used to identify those with migraine (headache features of migraine with gradual onset), and persistent post-traumatic headache and new daily persistent headache (based on the circumstances of headache onset regardless of headache features). Fifty participants each with migraine, persistent post-traumatic headache, and new daily persistent headache were matched by age and sex. Participant survey responses on headache characteristics were compared. RESULTS: Median usual headache severity was 6.0 [95%CI 6.0, 6.0] and was not different across diagnostic groups (H statistic = 1.2, p = 0.55). Headache exacerbation frequency, disability, associated symptoms, and most triggers were not significantly different across groups. The majority of persistent post-traumatic headache and new daily persistent headache had headache features consistent with a diagnose of migraine (72% and 62%, respectively). CONCLUSION: Our findings suggest that most persistent post-traumatic headache and new daily persistent headache may represent abrupt onset of migraine.

Patient headache questionnaires can improve headache diagnosis and treatment in children.

OBJECTIVE: To examine trends in diagnosis of headache and migraine in a large pediatric neurology cohort, and test whether an electronic health record (EHR)-integrated headache questionnaire can increase specificity of diagnosis and likelihood of prescribing migraine treatment. BACKGROUND: Under-diagnosis of migraine contributes to the burden of disease. As we founded our Pediatric Headache Program in 2013, we recognized that the proportion of patients with headache who were given a diagnosis of migraine was much lower than expected. METHODS: We developed a patient headache questionnaire, initially on paper (2013-2014), then in an electronic database (2014-2016), and finally integrated into our electronic health record (pilot: 2016, full: May 2017). We compared diagnoses and prescribed treatments for new patients who were given a headache diagnosis, looking at trends in the proportion of patients given specific diagnoses (migraine, etc.) versus the non-specific diagnosis, "headache." Next, we conducted a prospective cohort study to test for association between provider use of the form and the presence of a specific diagnosis, then for an association between specific diagnosis and prescription of migraine treatment. RESULTS: Between July 2011 and December 2022 the proportion of new headache patients who were given a diagnosis of migraine increased 9.7% and non-specific headache diagnoses decreased 21.0%. In the EHR cohort (June 2017-December 2022, n = 15,122), use of the provider form increased the rate of specific diagnosis to 87.2% (1839/2109) compared to 75.5% (5708/7560) without a patient questionnaire, nearly doubling the odds of making a specific diagnosis (odds ratio [OR] 1.90, 95% confidence interval [CI]: 1.65-2.19). Compared to those given only a non-specific headache diagnosis who were prescribed a migraine therapy 53.7% (1766/3286) of the time, 75.3% (8914/11836) of those given a specific diagnosis received a migraine therapy, more than doubling the odds of prescription (OR 2.39, 95% CI: 2.20-2.60). CONCLUSIONS: Interventions to improve specificity of diagnosis were effective and led to increased rates of prescription of migraine treatments. These results have been sustained over several years. This headache questionnaire was adapted into the Foundation system of EpicCare, so it is broadly available as a clinical and research tool for institutions that use this EHR software.

Neurophysiological Effects of Repeated Soccer Heading in Youth.

Repeated head loading in sports is associated with negative long-term brain health, and there is growing evidence of short-term neurophysiological changes after repeated soccer heading. The objective of this study was to quantify the head kinematics and effects of repetitive soccer headers in adolescents using an instrumented mouthguard. Adolescent soccer players aged 13-18 years were randomly assigned to a kicking control, frontal heading, or oblique heading group. Participants completed neurophysiological assessments at three-time points: immediately prior to, immediately after, and approximately 24 h after completing 10 headers or kicks. The suite of assessments included the Post-Concussion Symptom Inventory, visio-vestibular exam, King-Devick test, modified Clinical Test of Sensory Interaction and Balance with force plate sway measurement, pupillary light reflex, and visual evoked potential. Data were collected for 19 participants (17 male). Frontal headers resulted in significantly higher peak resultant linear acceleration (17.4 ± 0.5 g) compared to oblique headers (12.1 ± 0.4 g, p < 0.001), and oblique headers resulted in significantly higher peak resultant angular acceleration (frontal: 1147 ± 45 rad/s2, oblique: 1410 ± 65 rad/s2, p < 0.001). There were no neurophysiological deficits for either heading group or significant differences from controls at either post-heading timepoint, and therefore, a bout of repeated headers did not result in changes in the neurophysiological measures evaluated in this study. The current study provided data regarding the direction of headers with the goal to reduce the risk of repetitive head loading for adolescent athletes.

Acute and chronic management of posttraumatic headache in children: A systematic review.

OBJECTIVES: The goal of this paper is to provide a compilation of the evidence for the treatment of posttraumatic headache (PTH) in the pediatric population. Headache features and timing of therapy were considered. BACKGROUND: Headache is the most common symptom following mild traumatic brain injury (mTBI), affecting more than 80% of children and adolescents. It is unclear whether treatment for PTH should be tailored based on headache characteristics, particularly the presence of migraine features, and/or chronicity of the headache. METHODS: Systematic literature searches of PubMed, Embase, Scopus, and Cochrane databases (1985-2021, limited to English) were performed, and key characteristics of included studies were entered into RedCAP® (Prospero ID CRD42020198703). Articles and conference abstracts that described randomized controlled trials (RCTs), cohort studies, retrospective analyses, and case series were included. Participants included youth under 18 years of age with acute (<3 months) and persistent (≥3 months) PTH. Studies that commented on headache improvement in response to therapy were included. RESULTS: Twenty-seven unique studies met criteria for inclusion describing abortive pharmacologic therapies (9), preventative pharmacotherapies (5), neuromodulation (1), procedures (5), physical therapy and exercise (6), and behavioral therapy (2). Five RCTs were identified. Studies that focused on abortive pharmacotherapies were completed in the first 2 weeks post-mTBI, whereas other treatment modalities focused on outcomes 1 month to over 1-year post-injury. Few studies reported on migrainous features (7), personal history of migraine (7), or family history of migraine (3). CONCLUSIONS: There is limited evidence on the timing and types of therapies that are effective for treating PTH in the pediatric population. Prospective studies that account for headache characteristics and thoughtfully address the timing of therapies and outcome measurement are needed.

The intersection of COVID-19, school, and headaches: Problems and solutions.

OBJECTIVE: To equip clinicians with recommendations specific to concerns related to the novel coronavirus disease 2019 (COVID-19), which impact the physical, emotional, and social health of youth with headache disorders. BACKGROUND: COVID-19 has affected societies on a global scale including children and youth with chronic headache disorders. Many concerns are predicted to arise in the 2020-2021 school year, whether classes are conducted in-person or virtually. METHODS: Clinical impressions were combined with a review of the literature, although limited due to the recent nature of this issue. RESULTS: We describe recommendations to support caregivers and youth as they face changes expected with the return to school in the fall of 2020. CONCLUSION: Although there are significant concerns for caregivers and youth with migraine given the context of changes related to the pandemic, there are many recommendations that can help minimize exacerbations of the physical, emotional, and social health of youth with chronic migraine.

A neural correlate of visual discomfort from flicker.

The theory of "visual stress" holds that visual discomfort results from overactivation of the visual cortex. Despite general acceptance, there is a paucity of empirical data that confirm this relationship, particularly for discomfort from visual flicker. We examined the association between neural response and visual discomfort using flickering light of different temporal frequencies that separately targeted the LMS, L-M, and S postreceptoral channels. Given prior work that has shown larger cortical responses to flickering light in people with migraine, we examined 10 headache-free people and 10 migraineurs with visual aura. The stimulus was a uniform field, 50 degrees in diameter, that modulated with high-contrast flicker between 1.625 and 30 Hz. We asked subjects to rate their visual discomfort while we recorded steady-state visually evoked potentials (ssVEPs) from early visual cortex. The peak temporal sensitivity ssVEP amplitude varied by postreceptoral channel and was consistent with the known properties of these visual channels. There was a direct, linear relationship between the amplitude of neural response to a stimulus and the degree of visual discomfort it evoked. No substantive differences between the migraine and control groups were found. These data link increased visual cortical activation with the experience of visual discomfort.

Relationship between Visually Evoked Effects and Concussion in Youth.

Increased sensitivity to light is common after concussion. Viewing a flickering light can also produce uncomfortable somatic sensations like nausea or headache. We examined effects evoked by viewing a patterned, flickering screen in a cohort of 81 uninjured youth athletes and 84 concussed youth. We used Multiple correspondence analysis and identified two primary dimensions of variation: the presence or absence of visually evoked effects and variation in the tendency to manifest effects that localized to the eyes (e.g., eye watering) versus more generalized neurological effects (e.g., headache). Based on these two primary dimensions, we grouped participants into three categories of evoked symptomatology: no effects, eye-predominant effects, and brain-predominant effects. A similar proportion of participants reported eye-predominant effects in the uninjured (33.3%) and concussed (32.1%) groups. By contrast, participants who experienced brain-predominant effects were almost entirely from the concussed group (1.2% of uninjured, 35.7% of concussed). The presence of brain-predominant effects was associated with a higher concussion symptom burden and reduced performance on visio-vestibular tasks. Our findings indicate that the experience of negative constitutional, somatic sensations in response to a dynamic visual stimulus is a salient marker of concussion and is indicative of more severe concussion symptomatology. We speculate that differences in visually evoked effects reflect varying levels of activation of the trigeminal nociceptive system.

Developmental Effects on Pattern Visual Evoked Potentials Characterized by Principal Component Analysis.

Purpose: Peak amplitude and peak latency in the pattern reversal visual evoked potential (prVEP) vary with maturation. We considered that principal component analysis (PCA) may be used to describe age-related variation over the entire prVEP time course and provide a means of modeling and removing variation due to developmental age. Methods: PrVEP was recorded from 155 healthy subjects ages 11 to 19 years at two time points. We created a model of the prVEP by identifying principal components (PCs) that explained >95% of the variance in a "training" dataset of 40 subjects. We examined the ability of the PCs to explain variance in an age- and sex-matched "validation" dataset (n = 40) and calculated the intrasubject reliability of the PC coefficients between the two time points. We explored the effect of subject age and sex upon the PC coefficients. Results: Seven PCs accounted for 96.0% of the variability of the training dataset and 90.5% of the variability in the validation dataset with good within-subject reliability across time points (R > 0.7 for all PCs). The PCA model revealed narrowing and amplitude reduction of the P100 peak with maturation, and a broader and smaller P100 peak in male subjects compared to female subjects. Conclusions: PCA is a generalizable, reliable, and unbiased method of analyzing prVEP. The PCA model revealed changes across maturation and biological sex not fully described by standard peak analysis. Translational Relevance: We describe a novel application of PCA to characterize developmental changes of prVEP in youths that can be used to compare healthy and pathologic pediatric cohorts.

The Changing Landscape of Pediatric Migraine Therapy: A Review.

Importance: Migraine is a disabling and prevalent condition that affects the pediatric and adolescent population. This review describes current acute and preventive migraine pharmacologic therapies for the pediatric and adolescent population. Observations: Multiple pharmacotherapies that have been used in the treatment of acute headache and prevention in pediatric migraine are reviewed. There have been recent advances in the management of migraines among pediatric and adolescent patients, including US Food and Drug Administration approval of triptans for acute management in children as young as 6 years, and the first prospective, randomized, double-blind, placebo-controlled comparative study of preventive pharmacotherapy in pediatric migraine. A major challenge of evidence-based research in pediatric and adolescent migraine is the significant placebo effect. Conclusions and Relevance: Although progress is being made in the management of migraines among pediatric and adolescent patients, there remains much work to be done.