Uncertainty during Anticipation Modulates Neural Responses to Aversion in Human Insula and Amygdala

Abstract

Uncertainty about potential negative future outcomes can cause stress and is a central feature of anxiety disorders. The stress and anxiety associated with uncertain situations may lead individuals to overestimate the frequency with which uncertain cues are followed by negative outcomes, an example of covariation bias. Using functional magnetic resonance imaging, we found that uncertainty-related expectations modulated neural responses to aversion. Insula and amygdala responses to aversive pictures were larger after an uncertain cue (that preceded aversive or neutral pictures) than a certain cue (that always preceded aversive pictures). Anticipatory anterior cingulate cortex (ACC) activity elicited by the cues was inversely associated with the insula and amygdala responses to aversive pictures following the cues. Nearly 75% of subjects overestimated the frequency of aversive pictures following uncertain cues, and ACC and insula activity predicted this uncertainty-related covariation bias. Findings provide the first evidence of the brain mechanisms of covariation bias and highlight the temporal dynamics of ACC, insula, and amygdala recruitment for processing aversion in the context of uncertainty.

Brain dynamics of upstream perceptual processes leading to visual object recognition: A high density ERP topographic mapping study

“…Importantly, here perceptual evidence remains partial or incomplete at the time of overt decision (Response 1, see Methods). This situation could potentially generate a mild conflict, expressed by the urge to make a rapid decision while the actual accumulation of evidence is not complete yet (Hayden, Pearson, & Platt, 2009;Sarinopoulos et al, 2010;Scheffers & Coles, 2000). Thus, whereas the PCC/PHG complex may be involved in updating contextual information about the scene (based on the rapid extraction and accumulation of LSF information; see Bar, 2009) as SMA to a smaller degree.…”

Uncertainty is associated with increased selective attention and sustained stimulus processing

“…Indeed, this has been demonstrated for various levels of emotional responding, including self-reported mood, valence, or pain intensity (Bar-Anan, Wilson, & Gilbert, 2009;Grupe & Nitschke, 2011;Ploghaus et al, 2001;Yoshida, Seymour, Koltzenburg, & Dolan, 2013) and autonomic reactivity (Grupe & Nitschke, 2011). Similarly, functional magnetic resonance imaging (fMRI) studies have revealed increased uncertainty-related activity in the amygdala and insula (Dunsmoor, Bandettini, & Knight, 2008;Ploghaus et al, 2001;Sarinopoulos et al, 2010;Yoshida et al, 2013), brain regions associated with the processing of emotional salience (Davis & Whalen, 2001;Straube & Miltner, 2011). Moreover, evidence from threat-of-shock paradigms has suggested that uncertainty elicits defensive motivation, which is associated with increased physiological reactivity and hypervigilance.…”

“…Conditions of unpredictable negative events are associated with sustained anxiety and apprehension (Davis, Walker, Miles, & Grillon, 2010;Grillon, 2008;Grupe & Nitschke, 2013) and give rise to the search for strategies to reduce uncertainty-for example, by correctly assessing contingencies (Alloy & Tabachnik, 1984). However, the ability to assess contingencies is impaired, as is indicated by research demonstrating illusory correlations between cues ambiguously signaling potential threat and subsequent aversive events (Grupe & Nitschke, 2011;Sarinopoulos et al, 2010;Wiemer, Mühlberger, & Pauli, 2014). Sarinopoulos and colleagues utilized a passive picture-viewing paradigm in which a cue indicated whether a subsequent picture would be neutral or aversive (certain conditions), or either of the two (uncertain condition).…”

“…Defensive emotional responding, as indicated by fMRI and autonomic measures (Grupe & Nitschke, 2011;Sarinopoulos et al, 2010;Williams et al, 2015), implies that uncertainly cued targets elicit sustained elaboration (Amrhein, Mühlberger, Pauli, & Wiedemann, 2004;Cuthbert, Schupp, Bradley, Birbaumer, & Lang, 2000;Liu, Huang, McGinnis-Deweese, Keil, & Ding, 2012), contrasting with the aforementioned early responses to uncertainty-independent neutral stimuli (Baas et al, 2006;Cornwell et al, 2007;Nelson et al, 2015;Shackman et al, 2011). Therefore, we utilized event-related potentials (ERPs), exploiting their excellent temporal resolution and sensitivity to attentional processes, to investigate the uncertainty-related dynamics in attentional allocation and sustained stimulus elaboration in a cued-picture paradigm (Grupe & Nitschke, 2011;Sarinopoulos et al, 2010).…”

Anterior Insula Integrates Information about Salience into Perceptual Decisions about Pain

“…The prestimulus state of brain areas involved in perceptual decisions may therefore also reflect information about the significance of an impending stimulus. For instance, Sarinopoulos et al (2010) recently showed that uncertainty-related expectations lead to an overestimation of the frequency by which uncertain cues are followed by negative outcome and amplified neural responses to aversion. Importantly, it is the subjective interpretation of available information that influences perceptions and actions, regardless of whether it is factually true or not.…”