Renewal of fear and avoidance in humans to escalating threat: Implications for translational research on anxiety disorders.

Exposure-based treatment for threat avoidance in anxiety disorders often results in fear renewal. However, little is known about renewal of avoidance. This multimodal laboratory-based treatment study used an ABA renewal design and an approach-avoidance (AP-AV) task to examine renewal of fear/threat and avoidance in twenty adults. In Context A, 9 visual cues paired with increases in probabilistic money loss (escalating threats) produced increases in ratings of feeling threatened and loss expectancies and skin-conductance responses (SCR). During the AP-AV task, a monetary reinforcer was available concurrently with threats. Approach produced the reinforcer or probabilistic loss, while avoidance prevented loss and forfeited reinforcement. Escalating threat produced increasing avoidance and ratings. In Context B with Pavlovian extinction, threats signaled no money loss and SCR declined. During the AP-AV task, avoidance and ratings also declined. In a return to Context A with Pavlovian threat extinction in effect during the AP-AV task, renewal was observed. Escalating threat was associated with increasing ratings and avoidance in most participants. SCR did not show renewal. These are the first translational findings to highlight renewal of avoidance in humans. Further research should identify individual difference variables and altered neural mechanisms that may confer increased risk of avoidance renewal.

"Watch out!": Effects of instructed threat and avoidance on human free-operant approach-avoidance behavior.

Approach-avoidance paradigms create a competition between appetitive and aversive contingencies and are widely used in nonhuman research on anxiety. Here, we examined how instructions about threat and avoidance impact control by competing contingencies over human approach-avoidance behavior. Additionally, Experiment 1 examined the effects of threat magnitude (money loss amount) and avoidance cost (fixed ratio requirements), whereas Experiment 2 examined the effects of threat information (available, unavailable and inaccurate) on approach-avoidance. During the task, approach responding was modeled by reinforcing responding with money on a FR schedule. By performing an observing response, participants produced an escalating "threat meter". Instructions stated that the threat meter levels displayed the current probability of losing money, when in fact loss only occurred when the level reached the maximum. Instructions also stated pressing an avoidance button lowered the threat level. Overall, instructions produced cycles of approach and avoidance responding with transitions from approach to avoidance when threat was high and transitions back to approach after avoidance reduced threat. Experiment 1 revealed increasing avoidance cost, but not threat magnitude, shifted approach-avoidance transitions to higher threat levels and increased anxiety ratings, but did not influence the frequency of approach-avoidance cycles. Experiment 2 revealed when threat level information was available or absent earnings were high, but earnings decreased when inaccurate threat information was incompatible with contingencies. Our findings build on prior nonhuman and human approach-avoidance research by highlighting how instructed threat and avoidance can impact human AA behavior and self-reported anxiety.

The tipping point: Value differences and parallel dorsal-ventral frontal circuits gating human approach-avoidance behavior.

Excessive avoidance and diminished approach behavior are both prominent features of anxiety, trauma and stress related disorders. Despite this, little is known about the neuronal mechanisms supporting gating of human approach-avoidance behavior. Here, we used functional magnetic resonance imaging (fMRI) to track dorsal anterior cingulate and medial prefrontal (dACC/dmPFC) activation along an approach-avoidance continuum to assess sensitivity to competing appetitive and aversive contingencies and correspondence with behavior change. Behavioral and fMRI experiments were conducted using a novel approach-avoidance task where a monetary reward appeared in the presence of a conditioned stimulus (CS), or threat, that signaled increasing probability of unconditioned stimulus (US) delivery. Approach produced the reward or probabilistic US, while avoidance prevented US delivery, and across trials, reward remained fixed while the CS threat level varied unpredictably. Increasing the CS threat level (i.e., US probability) produced the desired approach-avoidance transition and inverted U-shaped changes in decision times, electrodermal activity and activation in pregenual ACC, dACC/dmPFC, striatum, anterior insula and inferior frontal regions. Conversely, U-shaped changes in activation were observed in dorsolateral and ventromedial prefrontal cortex and bimodal changes in the orbitofrontal and ventral hippocampus. These new results show parallel dorsal-ventral frontal circuits support gating of human approach-avoidance behavior where dACC/dmPFC signals inversely correlate with value differences between approach and avoidance contingencies while ventral frontal signals correlate with the value of predictable outcomes. Our findings provide an important bridge between basic research on brain mechanisms of value-guided decision-making and value-focused clinical theories of anxiety and related interventions.

Not so bad: avoidance and aversive discounting modulate threat appraisal in anterior cingulate and medial prefrontal cortex.

The dorsal anterior cingulate (adACC) and dorsal medial prefrontal cortex (dmPFC) play a central role in the discrimination and appraisal of threatening stimuli. Yet, little is known about what specific features of threatening situations recruit these regions and how avoidance may modulate appraisal and activation through prevention of aversive events. In this investigation, 30 healthy adults underwent functional neuroimaging while completing an avoidance task in which responses to an Avoidable CS+ threat prevented delivery of an aversive stimulus, but not to an Unavoidable CS+ threat. Extinction testing was also completed where CSs were presented without aversive stimulus delivery and an opportunity to avoid. The Avoidable CS+ relative to the Unavoidable CS+ was associated with reductions in ratings of negative valence, fear, and US expectancy and activation. Greater regional activation was consistently observed to the Unavoidable CS+ during avoidance, which declined during extinction. Individuals exhibiting greater aversive discounting-that is, those more avoidant of immediate monetary loss compared to a larger delayed loss-also displayed greater activation to the Unavoidable CS+, highlighting aversive discounting as a significant individual difference variable. These are the first results linking adACC/dmPFC reactivity to avoidance-based reductions of aversive events and modulation of activation by individual differences in aversive discounting.

The functional analysis of problematic verbal behavior.

This study describes procedures and outcomes in a functional analysis of problem behavior of 2 public school students. For a 13-year-old honors student, bizarre tacts (labeled as psychotic speech by school staff) were maintained by attention. For a 15-year-old with autism, the functional analysis revealed that perseverative mands for toileting were controlled by attention; mands for edible items were controlled by access to any food item; and mands for nonedible items were maintained by access to the specific item manded. The "problematic" aspects of the verbal behavior differed-the bizarre speech was problematic based on its content, but the perseverative verbalizations resulted in high response cost for classroom staff. Research in the area of problematic verbal behavior is sparse and warrants further attention from behavior analysts who work in public school settings. This research demonstrates the applicability and relevance of functionally analyzing problematic verbal behavior in public school settings.