Assessing and Treating Anxiety in Individuals with Autism

Anxiety is a cluster of responses that can involve both operant and respondent behavior, which can be both public and/or private in nature, and occurs when an upcoming aversive stimulus is signaled. Despite the reported high comorbidity of autism and anxiety, there has been very limited research on how to directly assess and treat anxiety, especially with individuals who have limited communication skills. In Study 1, anxiety was assessed in five individuals with autism, ranging in age from 10 to 19 years old. Anxiety was assessed by measuring behavior during (1) a baseline (with no putative anxiety-provoking stimuli present), (2) signals for an upcoming aversive event, and (3) exposure to that aversive event. Anxiety presented in several different ways, as both conditioned activation and suppression, and both with and without problem behavior during the aversive event. In Study 2, individualized treatments involving differential reinforcement of alternative responses and stimulus fading were used to successfully reduce anxious responding in all four participants who displayed anxiety. These studies demonstrated a potentially useful means of assessing anxiety in individuals with autism which may not only help to measure anxious behavior and identify anxiety-provoking events, but may also lead to effective treatment.

Thought Conditioning: Inducing and Reducing Thoughts About the Aversive Outcome in a Fear-Conditioning Procedure

The human fear-conditioning paradigm is a widely used procedure to study anxiety. However, merely thinking about the aversive outcome is typically not measured in this procedure. This is surprising because thinking of an aversive event is of clinical relevance (e.g., in the form of intrusions) and theoretical interest. We present two preregistered studies that (a) included thinking of an aversive outcome as an additional dependent variable and (b) compared several interventions to reduce it. We found that mere thinking of an aversive outcome could be successfully conditioned. Among the participants who showed successful acquisition, extinction training was less successful in reducing it than counterconditioning. Presenting new additional outcomes also proved effective to reduce thoughts about the initial outcome when the new outcomes were positive stimuli. Including thinking of the aversive outcome as an additional dependent variable may serve to enhance the understanding of anxiety-related disorders and inform their treatment.

Pavlovian-to-instrumental transfer in subclinical obsessive–compulsive disorder

Pavlovian-to-instrumental transfer (PIT) refers to the effect of stimuli that have been associated with a pleasant or aversive event on instrumental behaviors. Given that obsessive–compulsive disorder (OCD) is linked to excessive compulsions, which in the laboratory can be tested via testing instrumental responses, we assessed PIT effects in individuals with subclinical levels of OCD. Participants from a nonclinical population were separated in groups with low (OC−) and high (OC+) levels of OCD. Participants learned to associate one button press ( R1) with the cancellation of an aversive outcome ( O1) and another button press ( R2) with the cancellation of another aversive outcome ( O2). Subsequently, they watched stimuli of five different colors ( S1– S5) that were followed by O1, O2, a novel negative outcome ( O3: video of a house on fire), or two neutral outcomes ( O4: plus sign; O5: caret symbol), respectively. In the last phase, participants saw S1– S5 while they were allowed to press the R1 or the R2 button. Contrary to predictions, the OC− compared to OC+ group showed somewhat stronger specific PIT effects, indicated by more R1 and R2 responses during the presentation of the S1 and S2, respectively. No reliable evidence was found for general PIT.

Different methods of fear reduction are supported by distinct cortical substrates

Understanding how learned fear can be reduced is at the heart of treatments for anxiety disorders. Tremendous progress has been made in this regard through extinction training in which the aversive outcome is omitted. However, current progress almost entirely rests on this single paradigm, resulting in a very specialized knowledgebase at the behavioural and neural level of analysis. Here, we used a dual-paradigm approach to show that different methods that lead to reduction in learned fear in rats are dissociated in the cortex. We report that the infralimbic cortex has a very specific role in fear reduction that depends on the omission of aversive events but not on overexpectation. The orbitofrontal cortex, a structure generally overlooked in fear, is critical for downregulating fear when novel predictions about upcoming aversive events are generated, such as when fear is inflated or overexpected, but less so when an expected aversive event is omitted.

Different forms of fear extinction are supported by distinct cortical substrates

Understanding how learned fear can be reduced is at the heart of treatments for anxiety disorders. Tremendous progress has been made in this regard through extinction training in which an expected aversive outcome is omitted. However, current progress almost entirely rests on this single paradigm, resulting in a very specialized knowledgebase at the behavioural and neural level of analysis. Here, we used a paradigm-independent approach to show that different methods that lead to reduction in learned fear are dissociated in the cortex. We report that the infralimbic cortex has a very specific role in fear reduction that depends on the omission of aversive events but not on overexpectation. The orbitofrontal cortex, a structure generally overlooked in fear, is critical for downregulating fear when fear is inflated or overexpected, but not when an aversive event is omitted.

Fear Without Context: Acute Stress Modulates the Balance of Cue-Dependent and Contextual Fear Learning

During a threatening encounter, people can learn to associate the aversive event with a discrete preceding cue or with the context in which the event took place, corresponding to cue-dependent and context-dependent fear conditioning, respectively. Which of these forms of fear learning prevails has critical implications for fear-related psychopathology. We tested here whether acute stress may modulate the balance of cue-dependent and contextual fear learning. Participants ( N = 72) underwent a stress or control manipulation 30 min before they completed a fear-learning task in a virtual environment that allowed both cued and contextual fear learning. Results showed equally strong cue- and context-dependent fear conditioning in the control group. Stress, however, abolished contextual fear learning, which was directly correlated with the activity of the stress hormone cortisol, and made cue-dependent fear more resistant to extinction. These results are the first to show that stress favors cue-dependent over contextual fear learning.

Transient acidosis while retrieving a fear-related memory enhances its lability

Attenuating the strength of fearful memories could benefit people disabled by memories of past trauma. Pavlovian conditioning experiments indicate that a retrieval cue can return a conditioned aversive memory to a labile state. However, means to enhance retrieval and render a memory more labile are unknown. We hypothesized that augmenting synaptic signaling during retrieval would increase memory lability. To enhance synaptic transmission, mice inhaled CO2 to induce an acidosis and activate acid sensing ion channels. Transient acidification increased the retrieval-induced lability of an aversive memory. The labile memory could then be weakened by an extinction protocol or strengthened by reconditioning. Coupling CO2 inhalation to retrieval increased activation of amygdala neurons bearing the memory trace and increased the synaptic exchange from Ca2+-impermeable to Ca2+-permeable AMPA receptors. The results suggest that transient acidosis during retrieval renders the memory of an aversive event more labile and suggest a strategy to modify debilitating memories.