Headache Triggers as Surprise

Dana P. Turner, MSPH, PhD; Adriana D. Lebowitz, BA; Ivana Chtay, BS; Timothy T. Houle, PhD

Disclosures

Headache. 2019;59(4):495-508. 

In This Article

Abstract and Introduction

Abstract

Objectives: To examine the hypothesis that surprising experiences of headache triggers are associated with daily headache activity.

Background: Little is known about the specific environmental or behavioral interactions that might trigger a headache attack in a prone individual. We propose that headache trigger exposures can be usefully characterized, not only by their mechanisms of action, but also on the degree of "surprise" they present to the individual. This hypothesis is based on elements of information theory: that unusual events and experiences carry more information than common events and experiences and that headache attacks are associated with reactions to uncommon or unexpected biopsychosocial exposures.

Methods: A secondary analysis of the Headache Prediction Study, this prospective cohort study followed N = 95 individuals with episodic migraine who contributed 4195 days of diary data. Information was collected on daily levels of several common headache triggers: number of caffeinated beverages, number of alcoholic beverages, stress (Daily Stress Inventory), and mood disturbance (Profile of Mood States). The probability of observing variations in each trigger was used to estimate the "surprisal" of experiencing each trigger, and this information, measured in bits, was used to predict headache attacks.

Results: Participants experienced a headache attack on 1613 of 4195 days (38.5%). Each of the triggers was modestly related to the probability of experiencing a future headache in a complex manner that involved interactions between current headache status, current levels of the trigger, and lagged (previous) levels of the trigger. However, when expressed as a surprisal, the associations were simplified and strengthened. For example, each of the individual trigger surprisals exhibited a meaningful association with the development of a future headache attack (expressed as a 1 SD change in surprisal), with odds ratios ranging from a low of 1.11 (95%CI: 1.00 to 1.24) for alcohol to a high of 1.30 (95%CI: 1.14 to 1.46) for stress. The individual surprisals could be summed for total trigger surprise and exhibited a reliable association with new onset headache, OR 1.35 (95%CI: 1.17 to 1.49). This score exhibited superior discrimination between headache and non-headache days from all of the individual triggers (ignoring base rate, AUC: 0.61; AUC: 0.71 with base rate).

Conclusions: Diverse headache triggers can be uniformly described using their probability distributions. Rare values of headache triggers, or surprising values, were found to have consistent associations with headache activity across a variety of triggers. This finding, if validated in external data using other triggers, has potential to be used to conceptualize the influence of a wide range of headache triggers.

Introduction

Despite our general understanding of the pathophysiological and neurobiological cascades underlying the initiation of headache attacks,[1] little is known about the specific environmental or behavioral interactions that might trigger an attack in a prone individual.[2] Since the time of Hippocrates, a vast array of headache trigger candidates has been hypothesized ranging from foods, activities, behaviors, environmental conditions, and many others.[3] Potency beliefs in these diverse factors vary considerably across individuals.[4,5] Therefore, conceptualizing a common pathway to causing or initiating an attack is difficult. Nevertheless, several elegant hypotheses have been proposed to unify the causal influence of these triggers.

Martin[6–9] and colleagues[10–13] have proposed a fear-conditioning model that postulates that a trigger factor creates anxiety, and avoidance of this trigger reinforces this anxiety. Future (accidental) exposures to the feared trigger then elicit a fear response, and the physiological responses to this fear trigger the attack. In this model, virtually anything can be conditioned to be a trigger, but careful exposure to the trigger extinguishes the fear response and corresponding potency of the trigger.[11,12] Borkum has expounded a very different model based on oxidative stress.[14,15] This model postulates that trigger factors all increase oxidative stress, either directly or indirectly, and the physiological response to this stress initiates a migraine attack. Borkum credits observations of Blau[16] and Benemi[17] in that migraine triggers can be uniformly characterized by their oxidative challenges to the brain and that migraine attacks are a defensive response to such challenges.[15] A third model proposed by Burstein and Jakubowski organizes headache triggers by their inputs to the central nervous system.[18] This model proposes that the diverse set of triggers activates a correspondingly diverse set of brain regions, but these regions all share projections to the superior salivatory nucleus. These projections, when activated, cascade to reduce activation of parasympathetic neurons in the meninges, and this leads to increased activation of the meningeal nociceptors. Each of these hypotheses enjoys considerable face validity based on biological plausibility, and none are mutually exclusive or require the others to be untrue based on their own validity.

In this manuscript, we describe the evaluation of a new model to unify the conceptualization of headache triggers. We propose that headache trigger exposures can be usefully characterized, not only by their mechanism of action, but also on the degree of "surprise" they present to the individual. By "surprise" we do not imply a change in conscious awareness (ie, shock or alarm) that is related to the exposure, but rather the rarity or unexpectedness in relation to past exposures. In this way, an exposure or trigger can be surprising even if it escapes conscious awareness. This hypothesis is entirely based on elements of information theory: that unusual events and experiences carry more information than common events and experiences and that headache attacks are triggered by reactions to uncommon or unexpected biopsychosocial challenges. Unlike existing theories, this model is agnostic about the exact biological mechanisms responsible for this proposed association. Rather than focusing on the proposed mechanisms that are initiated after exposure to a trigger, the model simply describes the amount of "information" being conveyed to an individual through this person's interaction with the world. If supported, this trigger surprise model would have immediate implications for the assessment of daily headache risk based on the summation of trigger surprise.

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