Human perceptual learning is delayed by the N-methyl-D-aspartate receptor partial agonist D-cycloserine

Background: The optimisation of learning has long been a focus of scientific research, particularly in relation to improving psychological treatment and recovery of brain function. Previously, partial N-methyl-D-aspartate agonists have been shown to augment reward learning, procedural learning and psychological therapy, but many studies also report no impact of these compounds on the same processes. Aims: Here we investigate whether administration of an N-methyl-D-aspartate partial agonist (D-cycloserine) modulates a previously unexplored process – tactile perceptual learning. Further, we use a longitudinal design to investigate whether N-methyl-D-aspartate-related learning effects vary with time, thereby providing a potentially simple explanation for apparent mixed effects in previous research. Methods: Thirty-four volunteers were randomised to receive one dose of 250 mg D-cycloserine or placebo 2 h before tactile sensitivity training. Tactile perception was measured using psychophysical methods before and after training, and 24/48 h later. Results: The placebo group showed immediate within-day tactile perception gains, but no further improvements between-days. In contrast, tactile perception remained at baseline on day one in the D-cycloserine group (no within-day learning), but showed significant overnight gains on day two. Both groups were equivalent in tactile perception by the final testing – indicating N-methyl-D-aspartate effects changed the timing, but not the overall amount of tactile learning. Conclusions: In sum, we provide first evidence for modulation of perceptual learning by administration of a partial N-methyl-D-aspartate agonist. Resolving how the effects of such compounds become apparent over time will assist the optimisation of testing schedules, and may help resolve discrepancies across the learning and cognition domains

Hydrocortisone as an adjunct to brief cognitive-behavioural therapy for specific fear: endocrine and cognitive biomarkers as predictors of symptom improvement

Background: Glucocorticoid (GC) administration prior to exposure-based cognitive-behavioural therapy (CBT) has emerged as a promising approach to facilitate treatment outcome in anxiety disorders. Further components relevant for improved CBT efficacy include raised endogenous GCs and reductions in information-processing biases to threat. Aims: To investigate hydrocortisone as an adjunct to CBT for spider fear and the modulating role of threat bias change and endogenous short-term and long-term GCs for treatment response. Methods: Spider-fearful individuals were randomized to receiving either 20 mg of hydrocortisone (n = 17) or placebo (n = 16) one hour prior to single-session predominantly computerised exposure-based CBT. Spider fear was assessed using self-report and behavioural approach measures at baseline, 1-day and 1-month follow-up. Threat processing was assessed at baseline and 1-day follow-up. Cortisol and cortisone were analysed from hair and saliva samples at baseline. Results/outcomes: Self-report, behavioural and threat processing indices improved following CBT. Hydrocortisone augmentation resulted in greater improvement of self-report spider fear and stronger increase in speed when approaching a spider, but not on threat bias. Neither threat bias nor endogenous GCs predicted symptom change, and no interactive effects with hydrocortisone emerged. Preliminary evidence indicated higher hair cortisone as predictor of a stronger threat bias reduction. Conclusions/interpretation: Our data extend earlier findings by suggesting that GC administration boosts the success of exposure therapy for specific fear even with a low-level therapist involvement. Future studies corroborating our result of a predictive hair GC relationship with threat bias change in larger clinical samples are needed

D-Cycloserine as adjunct to brief computerised CBT for spider fear: Effects on fear, behaviour, and cognitive biases

Abstract In anxiety disorders, cognitive behavioural therapy (CBT) improves information-processing biases such as implicit fear evaluations and avoidance tendencies, which predicts treatment response, so they might constitute important treatment targets. This study investigated (i) whether information-processing biases changed following single-session computerised CBT for spider fear, and (ii) whether this effect could be augmented by administration of D-cycloserine (DCS). Spider-fearful individuals were randomized to receiving 250mg of DCS (n=21) or placebo (n=17) and spider fear was assessed using self-report, behavioural, and information-processing (Extrinsic Affective Simon Task & Approach Avoidance Task) measures. Linear mixed-effects analyses indicated improvements on self-report and behavioural spider fear following CBT, but not on cognitive bias measures. There was no evidence of an augmentation effect of DCS on any outcome. Cognitive biases at 1-day were not predictive of 1-month follow-up spider fear. These findings provide no evidence for information-processing biases relating to CBT response or augmentation with DCS

D-cycloserine as adjunct to brief computerised CBT for spider fear: effects on fear, behaviour, and cognitive biases

Background and objectives In anxiety disorders, cognitive behavioural therapy (CBT) improves information-processing biases such as implicit fear evaluations and avoidance tendencies, which predicts treatment response. Thus, these cognitive biases might constitute important treatment targets. This study investigated (i) whether information-processing biases could be changed following single-session computerised CBT for spider fear, and (ii) whether this effect could be augmented by administration of D-cycloserine (DCS). Methods Spider-fearful individuals were randomized to receiving either 250 mg of DCS (n = 21) or placebo (n = 17). Three hours after drug administration, they received single-session computerized CBT, characterized by psychoeducation and exposure elements. Spider fear was assessed using self-report, behavioural, and information processing (Extrinsic Affective Simon Task & Approach Avoidance Task) measures at baseline (before drug administration), post-treatment, 1-day, and 1-month follow-up. Results Linear mixed-effects analyses indicated significant improvements on self-report and behavioural spider fear indices following CBT, but not on cognitive bias measures. There was no evidence of an augmentation effect of DCS on any outcome. Cognitive bias measures at 1-day were not predictive of 1-month follow-up spider fear in adjusted linear regression analyses. Limitations Results might be biased by limited representativeness of the sample (high education and intelligence, largely Caucasian ethnicity, young age). The study was also only powered for detection of medium-sized DCS effects. Conclusions These findings do not provide evidence for information-processing biases relating to treatment outcome following computerised CBT for spider fear or augmentation with DCS

Investigating d-cycloserine as a potential pharmacological enhancer of an emotional bias-learning procedure

The partial NMDA receptor agonist d-cycloserine (DCS) may enhance psychological therapies. However, its exact mechanism of action is still being investigated. Cognitive Bias Modification (CBM) techniques allow isolation of cognitive processes and thus investigation of how they may be affected by DCS. We used a CBM paradigm targeting appraisals of a stressful event (CBM-App) to investigate whether DCS enhanced the modification of appraisal, and whether it caused greater reduction in indices of psychopathology. Participants received either 250mg of DCS (n = 19) or placebo (n = 19). As a stressor task, participants recalled a negative life event, followed by positive CBM-App training. Before and after CBM-App, appraisals and indices of psychopathology related to the stressor were assessed. CBM-App successfully modified appraisals, but DCS did not affect appraisals post-training. There were no post-training group differences in frequency of intrusions. Interestingly, DCS led to a greater reduction in distress and impact on state mood from recalling the event, and lower distress post-training was associated with fewer intrusions. Therefore, DCS may affect emotional reactivity to recalling a negative event when combined with induction of a positive appraisal style, but via a mechanism other than enhanced learning of the appraisal style

D-cycloserine as adjunct to brief computerised CBT for spider fear: Effects on fear, behaviour, and cognitive biases

Contains fulltext : 214596pub.pdf (Publisher’s version ) (Closed access) Contains fulltext : 214596pre.pdf (Author’s version preprint ) (Open Access)Background and objectives: In anxiety disorders, cognitive behavioural therapy (CBT) improves information-processing biases such as implicit fear evaluations and avoidance tendencies, which predicts treatment response. Thus, these cognitive biases might constitute important treatment targets. This study investigated (i) whether information-processing biases could be changed following single-session computerised CBT for spider fear, and (ii) whether this effect could be augmented by administration of D-cycloserine (DCS). Methods: Spider-fearful individuals were randomized to receiving either 250 mg of DCS (n = 21) or placebo (n = 17). Three hours after drug administration, they received single-session computerized CBT, characterized by psychoeducation and exposure elements. Spider fear was assessed using self-report, behavioural, and information processing (Extrinsic Affective Simon Task & Approach Avoidance Task) measures at baseline (before drug administration), post-treatment, 1-day, and 1-month follow-up. Results: Linear mixed-effects analyses indicated significant improvements on self-report and behavioural spider fear indices following CBT, but not on cognitive bias measures. There was no evidence of an augmentation effect of DCS on any outcome. Cognitive bias measures at 1-day were not predictive of 1-month follow-up spider fear in adjusted linear regression analyses. Limitations: Results might be biased by limited representativeness of the sample (high education and intelligence, largely Caucasian ethnicity, young age). The study was also only powered for detection of medium-sized DCS effects. Conclusions: These findings do not provide evidence for information-processing biases relating to treatment outcome following computerised CBT for spider fear or augmentation with DCS.10 p

Human perceptual learning is delayed by the NMDA receptor partial agonist D-cycloserine

Background: The optimisation of learning has long been a focus of scientific research, particularly in relation to improving psychological treatment and recovery of brain function. Previously, partial NMDA agonists have been shown to augment reward learning, procedural learning and psychological therapy, but many studies also report no impact of these compounds on the same processes. Aims: Here we investigate whether administration of an NMDA partial agonist (D- cycloserine) modulates a previously unexplored process – tactile perceptual learning. Further, we use a longitudinal design to investigate whether NMDA-related learning effects vary with time, thereby providing a potentially simple explanation for apparent mixed effects in previous research. Methods: Thirty-four volunteers were randomised to receive one dose of 250mg D-cycloserine or placebo two hours before tactile sensitivity training. Tactile perception was measured using psychophysical methods before and after training, and 24/48 hours later. Results: The placebo group showed immediate within-day tactile perception gains, but no further improvements between-days. In contrast, tactile perception remained at baseline on day one in the D-cycloserine group (no within-day learning), but showed significant overnight gains on day two. Both groups were equivalent in tactile perception by the final testing – indicating NMDA effects changed the timing, but not overall amount of tactile learning. Conclusions: In sum, we provide first evidence for modulation of perceptual learning by administration of a partial NMDA agonist. Resolving how the effects of such compounds become apparent over time will assist the optimisation of testing schedules, and may help resolve discrepancies across the learning and cognition domains.</p