Headache medicine depends upon subjective reports of pain. For primary headache disorders such as migraine, no blood test, imaging, or other objective means accurately assesses either the burden of illness or its time course. This dependence on subjectivity persists from diagnosis, through evaluation of treatment efficacy, to determination of disability. Many patients with longstanding migraine underreport symptoms, explaining that they have a high pain tolerance or have simply become accustomed to their headaches. Others may exaggerate symptoms due to anxiety, pain catastrophizing, depression, or secondary gain issues. An objective, quantitative biological measurement of migraine would greatly improve diagnosis and treatment. Ideally, repeat testing would track changes in headache pain and/or chronification. This problem motivated us to develop an objective, quantitative, non-invasive method to assess changes in CNS information processing that occur with the type of systemic cortical alterations that have been suggested to occur with migraine sufferers. This system, which delivers tactile (skin) stimulation to the fingertips, takes advantag of dense innervation in the fingertips projecting to adjacent areas in the brain. Sensory percepts are highly influenced by interactions between these adjacent brain areas and effectively provide a non-invasive biopsy of brain function. The stimulation protocols were both designed and validated from our findings from in vivo studies of cerebral cortical dynamics in non-human primates. Thus, they provide cortical dynamic metrics, or cortical metrics- and while independently obtained cortical metrics are predominantly influenced by specific cortical mechanisms, combining the metrics generates an individual CNS profile that can be used to characterize an individual's neurological status.. Proof of concept, with pilot data, has been obtained for differentiating migraineurs from healthy subjects as well as individuals with concussion. This application proposes to not only fully validate that difference but to determine i there is a correlation between a subject's migraine related self-reported pain and their CNS profile. An additional innovative feature of this application is that it proposes to (1) determine subject's CNS profile before their initial physician visit, (2) track the response of the patient t the intervention prescribed by the clinician and (3) retrospectively determine the capacity of the initial CNS profile to predict treatment outcomes. RELEVANCE: The overall goal of the proposed work is to investigate the utility of novel sensory-based methodologies that are currently being used in both basic and clinical research to track recovery in headache patients post- treatment. Recently, utilizing state-of-the-art technology, we built a multi-site tactile stimulator that allows for investigation of central nervos system (CNS) health and advanced methods in sensory perceptual metrics. These metrics have been demonstrated to be sensitive to changes in centrally mediated mechanisms; and systemic alterations of cortical health (via neurodegenerational, neurodevelopmental, pharmacological or trauma induced changes) robustly change the measures. It is anticipated that clinicians will be able to utilize these measures to improve diagnostic performance and enable assessment of efficacy of treatment. The study itself will serve to validate the utility of a number of these measures in headache and eventually provide health workers with a means to detect when an individual is under-reporting or over-reporting pain symptoms, and to track the recovery of an individual from headache. Better methods for measuring the progression of headache and response to treatment could lead to better diagnostics and therapeutics. Additionally, the information from this study could aid in understanding centrally mediated mechanisms that undergo significant alterations with headache.