Fear Conditioning Deficits in Children and Adolescents with Psychopathic Traits: a Study in a Clinical Population

Deficits in fear conditioning related to psychopathy have been widely studied in adults. However, evidence in children and adolescents is scarce and inconsistent. This research aimed to expand knowledge about fear conditioning in psychopathy and its dimensions in child and early adolescent clinical populations. Participants were 45 boys (outpatients) aged 6–14 years (M = 10.59, SD = 2.04). They were assessed with the parents’ and teachers’ versions of the Child Problematic Traits Inventory (CPTI). A fear conditioning paradigm (Neumann et al., in Biological Psychology, 79(3), 337–342, 2008) for children and adolescents was used. Conditioned stimuli (CS+ and CS-) were geometric shapes and the unconditioned stimulus (US) was an unpleasant sound of metal scraping on slate (83 dB). Difference scores (CS+ minus CS-) in skin conductance responses (SCR) and self-reported cognitive and affective measures were considered as indices of fear conditioning. Results showed that: a) deficits in fear conditioning were related to some psychopathy dimensions but not to psychopathy as a unitary construct; b) the Impulsivity-Need for Stimulation dimension was a predictor of impaired fear conditioning at a cognitive level; c) the interaction of Callous-Unemotional and Impulsivity-Need for Stimulation dimensions was a significant predictor of impaired electrodermal fear conditioning; d) by contrast, the Grandiose-Deceitful dimension, was marginally associated with a greater electrodermal fear conditioning. In conclusion, psychopathy dimensions and their interactions, but not psychopathy as a whole, predicted deficits in fear conditioning as measured by SCR and cognitive indices. These findings confirm the notion that psychopathic traits are associated with deficits in fear conditioning in child and adolescent clinical populations and provide support for a multidimensional approach to youth psychopathy.

Mutants of the white ABCG Transporter in Drosophila melanogaster Have Deficient Olfactory Learning and Cholesterol Homeostasis

Drosophila’s white gene encodes an ATP-binding cassette G-subfamily (ABCG) half-transporter. White is closely related to mammalian ABCG family members that function in cholesterol efflux. Mutants of white have several behavioral phenotypes that are independent of visual defects. This study characterizes a novel defect of white mutants in the acquisition of olfactory memory using the aversive olfactory conditioning paradigm. The w1118 mutants learned slower than wildtype controls, yet with additional training, they reached wildtype levels of performance. The w1118 learning phenotype is also found in the wapricot and wcoral alleles, is dominant, and is rescued by genomic white and mini-white transgenes. Reducing dietary cholesterol strongly impaired olfactory learning for wildtype controls, while w1118 mutants were resistant to this deficit. The w1118 mutants displayed higher levels of cholesterol and cholesterol esters than wildtype under this low-cholesterol diet. Increasing levels of serotonin, dopamine, or both in the white mutants significantly improved w1118 learning. However, serotonin levels were not lower in the heads of the w1118 mutants than in wildtype controls. There were also no significant differences found in synapse numbers within the w1118 brain. We propose that the w1118 learning defect may be due to inefficient biogenic amine signaling brought about by altered cholesterol homeostasis.

Systematically investigating the role of context on effect replicability in reinstatement of fear in humans

Context is crucial in guiding behavior in an ever changing world and contextual information plays a crucial role in associative learning processes. For instance, the return of fear (RoF) after reinstatement (i.e, re-exposure the unconditioned stimulus (US) after successful fear extinction) is context dependent and is suggested to occur only when either extinction and test, or extinction and reinstatement context are identical, not when US re-exposure (i.e., reinstatement) occurs in a context different from extinction and test. Human adaptions of reinstatement paradigms have resulted in mixed findings: CS specific as well as unspecific RoF or unexpected “reinstated” conditioned responding in no reinstatement US control groups. Here, we systematically investigate the role of context on reinstatement-induced RoF in a human differential fear conditioning paradigm using subjective and psychophysiological measures in a large sample (N=212) including reinstatement and control groups. Overall, response patterns in reinstatement-groups mirrored results from single-cue rodent work. Yet, only generalized, not differential RoF was observed. Remarkably, depending on outcome measure RoF was also observed under identical experimental context conditions without US-re-exposure, underlining effects of contextual change beyond the reinstatement-US and challenging reinstatement research in human subjects and what we think we know about the mechanisms behind the reinstatement-phenomenon.

Interfering with contextual fear memories by post-reactivation administration of propranolol in mice: a series of null findings

Post-reactivation amnesia of contextual fear memories by blockade of noradrenergic signaling has been shown to have limited replicability in rodents. This is usually attributed to several boundary conditions that gate the destabilization of memory during its retrieval. However, how these boundary conditions can be overcome, and what neural mechanisms underlie post-reactivation changes in contextual fear memory remain largely unknown. Here, we report a series of experiments in a contextual fear conditioning paradigm in mice, that were aimed at elucidating these matters. Towards this overarching goal, we first attempted to obtain a training paradigm that would consistently result in a contextual fear memory that could be destabilized upon reactivation, enabling robust amnesia by administration of propranolol. Unexpectedly, our attempts were unsuccessful to this end. Specifically, over a series of 11 experiments (including replicates) in which we varied different parameters of the fear acquisition procedure and administered propranolol or anisomycin, at best small and inconsistent effects were observed. These null findings are surprising, given that the training paradigms we implemented were previously shown to be vulnerable to post-reactivation amnestic agents. Additionally, we found that propranolol did not alter memory retrieval-induced neural activity, as measured by the number of c-Fos+ cells in the hippocampal dentate gyrus. Together, our findings illustrate the elusive nature of reactivation-dependent changes of non-human fear memory and underscore the need for better control over genetic and environmental factors that may influence behavioral outcomes of commonly used mouse strains.

Honey bees can store and retrieve independent memory traces after complex experiences that combine appetitive and aversive associations

Real-world experiences do often mix appetitive and aversive events. Understanding the ability of animals to extract, store and use this information is an important issue in neurobiology. We used honey bees as model to study learning and memory after a differential conditioning that combines appetitive and aversive training trials. First of all, we describe an aversive conditioning paradigm that constitutes a clear opposite of the well known appetitive olfactory conditioning of the proboscis extension response. A neutral odour is presented paired with the bitter substance quinine. Aversive memory is evidenced later as an odour-specific impairment in appetitive conditioning. Then we tested the effect of mixing appetitive and aversive conditioning trials distributed along the same training session. Differential conditioning protocols like this were used before to study the ability to discriminate odours, however they were not focused on whether appetitive and aversive memories are formed. We found that after a differential conditioning, honey bees establish independent appetitive and aversive memories that do not interfere with each other during acquisition or storage. Finally, we moved the question forward to retrieval and memory expression to evaluate what happens when appetitive and the aversive learned odours are mixed during test. Interestingly, opposite memories compete in a way that they do not cancel each other out. Honey bees showed the ability to switch from expressing appetitive to aversive memory depending on their satiation level.

Reducing the Soleus Stretch Reflex With Conditioning: Exploring Game- and Impedance-Based Biofeedback

People with spasticity, i.e., stretch hyperreflexia, have a limited functional independence and mobility. While a broad range of spasticity treatments is available, many treatments are invasive, non-specific, or temporary and might have negative side effects. Operant conditioning of the stretch reflex is a promising non-invasive paradigm with potential long-term sustained effects. Within this conditioning paradigm, seated participants have to reduce the mechanically elicited reflex response using biofeedback of reflex magnitude quantified using electromyography (EMG). Before clinical application of the conditioning paradigm, improvements are needed regarding the time-intensiveness and slow learning curve. Previous studies have shown that gamification of biofeedback can improve participant motivation and long-term engagement. Moreover, quantification of reflex magnitude for biofeedback using reflexive joint impedance may obtain similar effectiveness within fewer sessions. Nine healthy volunteers participated in the study, split in three groups. First, as a reference the “Conventional” group received EMG- and bar-based biofeedback similar to previous research. Second, we explored feasibility of game-based biofeedback with the “Gaming” group receiving EMG- and game-based biofeedback. Third, we explored feasibility of game- and impedance-based biofeedback with the “Impedance” group receiving impedance and game-based biofeedback. Participants completed five baseline sessions (without reflex biofeedback) and six conditioning sessions (with reflex biofeedback). Participants were instructed to reduce reflex magnitude without modulating background activity. The Conventional and Gaming groups showed feasibility of the protocol in 2 and 3 out of 3 participants, respectively. These participants achieved a significant Soleus short-latency (M1) within-session reduction in at least –15% in the 4th–6th conditioning session. None of the Impedance group participants showed any within-session decrease in Soleus reflex magnitude. The feasibility in the EMG- and game-based biofeedback calls for further research on gamification of the conditioning paradigm to obtain improved participant motivation and engagement, while achieving long-term conditioning effects. Before clinical application, the time-intensiveness and slow learning curve of the conditioning paradigm remain an open challenge.

Unconscious Knowledge Produces Adaptive Decisions via Conscious Judgments in a Novel Instrumental Conditioning Paradigm

The demonstration of unconscious instrumental conditioning (i.e., unconsciously learning to choose stimuli that lead to rewards) is central for the tenet that unconscious learning supports human adaptation. Recent studies, using reliable subliminal conditioning procedures, have found evidence against unconscious instrumental conditioning. The present preregistered study proposes an alternative paradigm, in which unconscious processing is stimulated not by the subliminal exposure of the predictive (conditioned) stimuli, but by employing predictive regularities that are complex and difficult to detect consciously. Participants (N = 211) were exposed to letter strings that, unknown to them, were built from two complex artificial grammars: an “rewarded’’ or a “non-rewarded” grammar. On each trial, participants memorized a string, and subsequently had to discriminate the memorized string from a distractor. Correct discriminations were rewarded only when the identified string followed the rewarded grammar, but not when it followed the non-rewarded grammar. In a subsequent test phase, participants were presented with new strings from the rewarded and from the unrewarded grammar. Their task was now to directly choose the strings from the rewarded grammar, in order to collect more rewards. Employing a trial-by-trial awareness measure widely used in implicit learning, we found that participants accurately choose novel strings from the rewarded grammar when they had no conscious knowledge of the grammar. The awareness measure also showed that participants were accurate only when the unconsciously learned grammar led to conscious judgments. The present study provides an alternative to subliminal conditioning paradigms and shows evidence for unconscious instrumental conditioning.

Cognitive Reserve and Anxiety Interactions Play a Fundamental Role in the Response to the Stress

The aims of the present study were to assess the possible interaction between Cognitive Reserve (CR) and State Anxiety (SA) on adrenocortical and physiological responses in coping situations. Forty healthy, middle-aged men completed the Cognitive Reserve Scale and the State-Trait Anxiety Inventory. We used an Observational Fear Conditioning (OFC) paradigm in order to assess emotional learning and to induce stress. Electrodermal activity (EDA) and salivary cortisol concentrations were measured throughout the conditions. Our results indicate that those who indicated having higher state anxiety showed a lower capacity for learning the contingency, along with presenting higher salivary cortisol peak response following the observational fear-conditioning paradigm. The most prominent finding was the interaction between cognitive reserve and state anxiety on cortisol response to the post observational fear-conditioning paradigm. Thus, those who showed a high anxiety-state and, at the same time, a high cognitive reserve did not present an increased salivary cortisol response following the observational fear-conditioning paradigm. Given these results, we postulate that the state anxiety reported by participants, reflects emotional activation that hinders the attention needed to process and associate emotional stimuli. However, cognitive reserve has an indirect relation with conditioning, enabling better emotional learning. In this context, cognitive reserve demonstrated a protective effect on hormonal response in coping situations, when reported anxiety or emotional activation were high. These findings suggest that cognitive reserve could be used as a tool to deal with the effects of stressors in life situations, limiting development of the allostatic load.