Tactile P300 to unpredictable electric shocks: Association with anxiety symptoms, intolerance of uncertainty, and neuroticism

Highlights

• Examined tactile P300 to predictable and unpredictable shocks.

• Measured anxiety symptoms, intolerance of uncertainty (IU), and neuroticism.

• P300 enhanced to unpredictable relative to predictable shocks.

• P300 enhancement associated with anxiety symptoms, IU, and neuroticism.

• Attentional engagement to unpredictable threat heightened in anxiety phenomena.

Abstract

The no, predictable, and unpredictable threat (NPU-threat) task is an experimental paradigm that delineates the anticipation of predictable vs. unpredictable threat. The current literature suggests that heightened defensive motivation in anticipation of unpredictable threat is associated with anxiety disorders and increased symptoms. Few investigations have examined whether a heightened response to actual threat is also associated with anxiety-related phenomenology. The present study examined the relationship between the tactile P300 to shock delivery during the NPU-threat task and individual differences in anxiety symptoms, intolerance of uncertainty, and neuroticism. Overall, the tactile P300 was enhanced in response to unpredictable shocks relative to predictable shocks. Greater tactile P300 enhancement to unpredictable shocks was associated with greater anxiety symptoms, intolerance of uncertainty, and neuroticism. The present study suggests that temporal unpredictability enhances attentional engagement to threat, which is greater in individuals characterized by narrow and broad anxiety constructs.

Introduction

Aversive stimuli have been shown to impact neural and physiological indicators of emotional and motivational reactivity. For example, the perception of threatening and unpleasant visual stimuli increase the startle reflex (an indicator of defense motivation), corrugator activity (an indicator of negative affect), and both event-related potentials (ERPs) and neural response in a number of different brain regions, including the amygdala, hippocampus, and prefrontal cortex (Aldhafeeri, Mackenzie, Kay, Alghamdi, & Sluming, 2012; Blau, Maurer, Tottenham, & McCandliss, 2007; Bradley, Codispoti, & Lang, 2006; Lang, Bradley, & Cuthbert, 1990; Lang, Greenwald, Bradley, & Hamm, 1993; Robinson, Charney, Overstreet, Vytal, & Grillon, 2012). Aversive imagery and scripts also impact reactivity, such that unpleasant, relative to pleasant, scenes potentiate the startle reflex, corrugator activity, and skin conductance response (an indicator of arousal) (Miller, Patrick, & Levenston, 2002). Finally, auditory and tactile stimuli, such as aversive sounds and CO₂-enriched air, heighten corrugator activity and heart rate (Bradley, Zack, & Lang, 1994; Forsyth, Lejuez, & Carlos., 2000). Overall, aversive stimuli elicit robust neural and physiological responses that are consistent with enhanced emotional and motivational reactivity.

There are several conceptual and theoretical models that implicate increased reactivity to threat as a potential etiological mechanism of anxiety disorders and symptoms (Engel, 1977; Fanselow & Lester, 1988; Mogg, Mathews, & Weinman, 1987; Seligman & Binik, 1977). Indeed, there is ample evidence supporting these models across multiple methodologies (Grillon & Baas, 2003; Vaidyanathan, Patrick, & Cuthbert, 2009). For example, individuals with specific and social phobia have been shown to exhibit an enhanced startle reflex to fear-relevant stimuli (De Jong & Merckelbach, 1996; Globisch, Hamm, Esteves, & Öhman, 1999; Hamm, Cuthbert, Globisch, & Vaitl, 1997; McTeague et al., 2009). Additionally, individuals at risk for anxiety, such as children with a maternal history of an anxiety disorder, show potentiation of the startle reflex when viewing unpleasant images (Kujawa, Glenn, Hajcak, & Klein, 2015). Anxiety disorders and symptoms have also been associated with elevated ERPs indicating enhanced attention towards threat. A number of anxiety disorders, including panic disorder, social phobia, and specific phobia, as well as trait anxiety have been associated with an increased late positive potential (LPP) in response to negative and unpleasant stimuli (MacNamara & Hajcak, 2010; MacNamara, Ferri, & Hajcak, 2011; Michalowski et al., 2009; Miltner et al., 2005; Moser, Huppert, Duval, & Simons, 2008; Pauli et al., 1997). The increased neural and physiological reactivity observed across multiple disorders and traits suggests that it may reflect a transdiagnostic mechanism of anxiety disorders.

Research has begun to identify particular features of aversive stimuli that may contribute to increased emotional and motivational reactivity. Predictability is one characteristic that has been shown to impact reactivity¹ . Unpredictability diminishes the ability to prepare for, respond to, or avoid danger and threat (Grupe & Nitschke, 2013). Thus, heightened emotional and motivational responding is adaptive in the context of unpredictable threat, but becomes maladaptive when the response exceeds the true danger of the threat (Rosen & Schulkin, 1998). A maladaptive response to ambiguous, uncertain, or unpredictable threat has been proposed as a key mechanism of multiple forms of psychopathology, most notably anxiety disorders (Carleton, 2016; Gentes & Ruscio, 2011).

Temporal predictability of threat has been demonstrated to be particularly effective in eliciting defensive responses in the laboratory relative to other features such as occurrence uncertainty (Bennett, Dickmann, & Larson, 2018). The impact of temporal predictability on emotional and motivational reactivity has often been studied using the no, predictable, and unpredictable threat (NPU-threat) task. In the NPU-threat task, participants complete three within-subject conditions; no aversive stimulus is delivered in the no threat (N) condition, a signaled threat is delivered in the predictable threat (P) condition, and an unsignaled threat is delivered in the unpredictable threat (U) condition (Schmitz & Grillon, 2012). Numerous studies have demonstrated that the startle reflex is potentiated in anticipation of both predictable and unpredictable threat relative to no threat, with more recent evidence suggesting that startle potentiation is greater in anticipation of unpredictable threat relative to predictable threat (Ferry & Nelson, 2020; Gorka, Lieberman, Shankman, & Phan, 2017; Nelson & Hajcak, 2017b). Previous literature has also demonstrated that the type of threat administered during the task may impact the measurable response and that electric shock is consistently shown to be a potent aversive stimulus (Ferry & Nelson, 2020; Grillon, Baas, Lissek, Smith, & Milstein, 2004; Nelson & Hajcak, 2017b).

A growing number of studies have examined the relationship between startle potentiation during the NPU-threat task and anxiety disorders, symptoms, and clinical traits. For example, increased startle potentiation in anticipation of unpredictable (but not predictable) threat has been associated with a number of different anxiety disorders and symptoms, including panic attacks and panic disorder (Burani & Nelson, 2020; Grillon et al., 2008, 2017; Lieberman, Gorka, Shankman, & Phan, 2017) and specific phobia and social phobia (Gorka et al., 2017; Nelson & Hajcak, 2017a). In addition, increased startle potentiation in anticipation of unpredictable threat has been linked to clinical traits that are risk factors for the development of anxiety disorders, such as intolerance of uncertainty (IU) (Nelson & Shankman, 2011; Nelson, Liu, Sarapas, & Shankman, 2016). Finally, at least one investigation has found that increased startle potentiation in anticipation of unpredictable threat was associated with neuroticism (Craske et al., 2009). Overall, increased startle potentiation in anticipation of unpredictable threat has been associated with both narrow (disorders, symptoms) and broad (clinical and personality traits) individual difference measures of anxiety.

As previously mentioned, there is compelling evidence supporting increased emotional reactivity to threat as a potential mechanism of anxiety disorders and symptoms (Grillon & Baas, 2003; Vaidyanathan et al., 2009). Yet, few studies have examined whether this relationship is due to an element of uncertainty or unpredictability in the aversive stimulus. For example, it is possible that the content of aversive stimuli involves more uncertainty and unpredictability relative to neutral content, which at least partially contributes to the increased reactivity observed in individuals with anxiety disorders and symptoms. Uncertainty and unpredictability have both been shown to enhance ERP responses to the delivery of actual aversive stimuli. Indeed, pictures following uncertain relative to certain cues have been shown to elicit greater P2 and LPP responses in a community sample (Dieterich, Endrass, & Kathmann, 2016), and an enhanced P2, N2, and LPP in patients with obsessive-compulsive disorder relative to a control group (Dieterich, Endrass, & Kathmann, 2017). A separate investigation found an enhanced tactile P300 in response to the delivery of unpredictable relative to predictable shocks during the NPU-threat task (Nelson & Hajcak, 2017b). Together, these results suggest that unpredictability can enhance attentional engagement in response to the actual threat. However, it is still unclear whether increased reactivity to unpredictable threat is associated with individual difference measures of anxiety.

Sex differences in the prevalence of anxiety disorders has been well-documented, with women experiencing higher rates of lifetime diagnoses of almost all anxiety disorders (McLean, Asnaani, Litz, & Hofmann, 2011). A growing number of studies have begun to examine potential mechanisms of the sex difference in anxiety disorders. Recent psychophysiological evidence has also indicated potential sex differences in sensitivity to unpredictable threat, with women demonstrating greater reactivity relative to men (Burani & Nelson, 2020; Grillon, 2008). Notably, these studies have investigated sex differences in anticipatory reactivity, but have not examined reactivity to the actual aversive stimulus.

The present study examined the tactile P300 to the delivery of electric shocks during the NPU-threat task and individual differences in anxiety-related constructs. Specifically, participants completed self-report questionnaires measuring anxiety symptoms, intolerance of uncertainty, and neuroticism. We hypothesized that the tactile P300 would be enhanced in response to unpredictable relative to predictable threat. We also hypothesized that greater tactile P300 enhancement to unpredictable threat would be associated with greater anxiety symptoms, intolerance of uncertainty, and neuroticism. Finally, we hypothesized that women would show greater tactile P300 enhancement to unpredictable threat relative to men.