Inhibitory Learning Research Articles

Basolateral amygdala inputs to the nucleus accumbens shell modulate the consolidation of cued-response and inhibitory avoidance learning

The basolateral amygdala (BLA) modulates different types of memory consolidation via distinct projections to downstream brain regions in multiple memory systems. Prior studies indicate that the BLA projects to the nucleus accumbens shell (NAshell) and that these regions interact to influence some types of behavior. Moreover, previous pharmacological work suggests the BLA and NAshell interact to influence memory. However, the precise role of the BLA-NAshell pathway has never been directly investigated in the consolidation of different types of memory including cued-response, spatial, or inhibitory avoidance (IA) learning. To address this, male and female Sprague-Dawley rats received optogenetic manipulations of the BLA or BLA-NAshell pathway immediately following training in different learning tasks. An initial experiment found that optogenetically inhibiting the BLA itself immediately after training impaired cued-response retention in a Barnes maze task in males and females, confirming earlier pharmacological work in males alone. Subsequent experiments found that BLA-NAshell pathway inhibition impaired retention of cued-response and IA learning but had no effect on retention of spatial learning. However, the present work did not observe any effects of pathway stimulation immediately after cued-response or IA learning. Together, the present findings suggest the BLA modulates the consolidation of cued-response and IA, but not spatial, memory consolidation via NAshell projections.

Pavlovian safety learning: An integrative theoretical review.

Safety learning involves associating stimuli with the absence of threats, enabling the inhibition of fear and anxiety. Despite growing interest in psychology, psychiatry, and neuroscience, safety learning lacks a formal consensus definition, leading to inconsistent methodologies and varied results. Conceptualized as a form of inhibitory learning (conditioned inhibition), safety learning can be understood through formal learning theories, such as the Rescorla-Wagner and Pearce-Hall models. This review aims to establish a principled conceptualization of 'Pavlovian safety learning', identifying cognitive mechanisms that generate safety and the boundary conditions that constrain it. Based on these observations, we define Pavlovian safety learning as an active associative process, where surprising threat-omission (safety prediction error) acts as a salient reinforcing event. Instead of producing merely neutral or nonaversive states, safety learning endows stimuli with active positive associations to 'safety'. The resulting stimulus-safety memories counteract the influence of fear memories, promoting fear regulation, positive affect, and relief. We critically analyze traditional criteria of conditioned inhibition for their relevance to safety and propose areas for future innovation. A principled concept of Pavlovian safety learning may reduce methodological inconsistencies, stimulate translational research, and facilitate a comprehensive understanding of an indispensable psychological construct.

Acute aerobic exercise modulates cognition and cortical excitability in adults with attention-deficit hyperactivity disorder (ADHD) and healthy controls

Evidence suggests aerobic exercise has beneficial effects on cognitive performance in adults with attention-deficit hyperactivity disorder (ADHD). The underlying mechanisms might depend on mechanisms of exercise-mediated brain physiology. The study aims to investigate the effects of acute aerobic exercise on cortical excitability and cognitive performance, and the correlation between these phenomena in adults with ADHD. Twenty-six drug-naïve ADHD adults, and twenty-six age-, and gender-matched healthy controls were assessed with respect to cortical excitability and cognitive performance before and after acute aerobic exercise (a single session for 30 min) or a control intervention. The results show significantly enhanced intracortical facilitation (ICF) and decreased short intracortical inhibition (SICI) after aerobic exercise in healthy subjects. In contrast, SICI was significantly enhanced following acute aerobic exercise in ADHD. In ADHD, furthermore inhibitory control and motor learning were significantly improved after the acute aerobic exercise intervention. Alterations of SICI induced by aerobic exercise, and inhibitory control and motor learning improvement were significantly positively correlated in the ADHD group. Aerobic exercise had partially antagonistic effects in healthy controls, and ADHD patients. Furthermore, aerobic exercise-induced cognition-enhancing effects in ADHD depend on specific alterations of brain physiology, which differ from healthy humans.

Approach and Conquer: Optimizing Fear Extinction by Adding Approach?

Exposure treatment involves systematic confrontation with fear-inducing stimuli, effectively reducing fear and anxiety. However, a significant number of clients still experience a return of fear (ROF) after treatment. This study investigates whether incorporating an approach component during fear extinction, a laboratory exposure analog, could mitigate this return of fear. Furthermore, we explored the underlying mechanisms by drawing on predictions from the inhibitory learning theory and the reflective-impulsive model of behavior. In a within-subjects design, we compared instructed active approach of a stimulus during extinction to more passive non-avoidance. Contrary to expectations, our findings revealed that performing approach behavior during extinction did not reduce ROF when compared to non-avoidance. Furthermore, valence and action tendencies, which were potential mechanisms based on the reflective-impulsive model of behavior, remained unaltered. Still, a noteworthy discovery emerged in the form of increased threat expectancies for the approached stimulus during extinction, suggesting a heightened level of expectancy violation, as predicted on the basis of the inhibitory learning theory. These findings offer valuable insights into the intricate relationship between approach behavior, ROF, and underlying mechanisms, highlighting the need for further research to assess the potential benefits of emphasizing approach in exposure treatment.

Effects of maternal age and environmental enrichment on learning ability and brain size.

It is well known that maternal age at reproduction affects offspring lifespan and some other fitness-related traits, but it remains understudied whether maternal senescence affects how offspring respond to their environments. Early environment often plays a significant role in the development of an animal's behavioral phenotype. For example, complex environments can promote changes in cognitive ability and brain morphology in young animals. Here, we study whether and how maternal effect senescence influences offspring plasticity in cognition, group behavior, and brain morphology in response to environmental complexity. For this, juvenile 3-spined sticklebacks from young and old mothers (i.e. 1-yr and 2-yr-old) were exposed to different levels of environmental enrichment and complexity (i.e. none, simple, and complex), and their behavior, cognitive ability, and brain size were measured. Exposing fish to enriched conditions improved individual learning ability assessed by a repeated detour-reaching task, increased the size of the whole brain, and decreased aggressive interactions in the shoal. Maternal age did not influence the inhibitory control, learning ability, and group behavioral responses of offspring to the experimental environmental change. However, maternal age affected how some brain regions of offspring changed in response to environmental complexity. In offspring from old mothers, those exposed to the complex environment had larger telencephalons and cerebellums than those who experienced simpler environments. Our results suggest that maternal effect senescence may influence how offspring invest in brain functions related to cognition in response to environmental complexity.

Synapse-type-specific competitive Hebbian learning forms functional recurrent networks

Cortical networks exhibit complex stimulus-response patterns that are based on specific recurrent interactions between neurons. For example, the balance between excitatory and inhibitory currents has been identified as a central component of cortical computations. However, it remains unclear how the required synaptic connectivity can emerge in developing circuits where synapses between excitatory and inhibitory neurons are simultaneously plastic. Using theory and modeling, we propose that a wide range of cortical response properties can arise from a single plasticity paradigm that acts simultaneously at all excitatory and inhibitory connections-Hebbian learning that is stabilized by the synapse-type-specific competition for a limited supply of synaptic resources. In plastic recurrent circuits, this competition enables the formation and decorrelation of inhibition-balanced receptive fields. Networks develop an assembly structure with stronger synaptic connections between similarly tuned excitatory and inhibitory neurons and exhibit response normalization and orientation-specific center-surround suppression, reflecting the stimulus statistics during training. These results demonstrate how neurons can self-organize into functional networks and suggest an essential role for synapse-type-specific competitive learning in the development of cortical circuits.

Exposure therapy tailored to inhibitory learning principles in a naturalistic setting: an open pilot trial in obsessive-compulsive outpatient care.

Inhibitory learning (IL) theory offers promising therapeutic strategies. However, more evidence is needed, especially regarding OCD treatment in routine care. The present pilot study investigated the positive and negative effects of IL-focused cognitive-behavioral therapy (CBT) in a university outpatient setting. A total of N = 21 patients (57.14% male, mean age 31.14, SD = 12.39 years) passed through manualized therapy delivered by licensed psychotherapists. Between the first and 20th IL-focused CBT session, obsessive-compulsive symptoms (Obsessive Compulsive Inventory-Revised, d = 3.71), obsessive beliefs (Obsessive-Beliefs Questionnaire, d = 1.17), depressive symptoms (Beck Depression Inventory, d = 3.49), and overall psychological distress (Global Severity Index, d = 3.40) decreased significantly (all ps < 0.01). However, individual patients reported some negative effects of therapy. The results underline the value of thorough investigations of novel therapeutic interventions in naturalistic settings.

Generalization Between Perceptually Similar Stimuli Is Associated With Improvement in Social Anxiety Following Cognitive-Behavioral Therapy

Cognitive-behavioral therapy (CBT) for anxiety disorders requires that people learn to inhibit their fear during exposure to stimuli that no longer pose a threat. We investigate whether individual differences in this inhibitory learning ability, measured prior to treatment, can predict responsiveness to CBT for social anxiety disorder. Participants (N = 128) were randomized to CBT or a wait-list control and completed tests of fear generalization and extinction prior to and following the intervention period. Contrary to expectations, individual differences in extinction, measured at pretreatment, were not associated with treatment responses but there was evidence that these abilities changed over time due to treatment. Individual differences in fear generalization at pretreatment were associated with treatment responses. Weaker generalization between dangerous and perceptually similar but novel safe stimuli was associated with enhanced responding to CBT. These findings contribute to the development of a mechanistic approach to patient stratification where participants who are least likely to respond to CBT can be identified prior to treatment.

Daily-life stress reactivity and recovery following virtual-reality-based cognitive behavioral therapy in patients with a psychotic disorder.

Studies have consistently demonstrated increased stress sensitivity in individuals with psychosis. Since stress sensitivity may play a role in the onset and maintenance of psychosis, this could potentially be a promising target for treatment. The current study was the first to investigate whether reactivity to and recovery from daily-life stressors in psychosis change in response to treatment, namely virtual-reality-based cognitive behavioral therapy (VR-CBT). 116 patients were randomized to either VR-CBT or the waiting list control group (WL). Pre-treatment and post-treatment participants completed a diary ten times a day during six to ten days. Multilevel analyses were used to model the time-lagged effects of daily stressful events on negative affect (NA) and paranoia symptoms to examine reactivity and recovery. There was a significant difference in NA reactivity. VR-CBT showed higher NA at post-treatment compared to pre-treatment than WL (bpre=0.14; bpost=0.19 vs bpre=0.18; bpost=0.14). There was a significant difference in NA recovery and paranoia recovery between the groups at lag 1: VR-CBT showed relatively lower negative affect (bpre=0.07; bpost=-0.06) and paranoia (bpre= 0.08; bpost=-0.10) at post-treatment compared to pre-treatment than WL (bpre=0.08; bpost=0.08; bpre=0.04; bpost=0.03). Negative affect and paranoia recovery improved in response to treatment. Increased NA reactivity may be explained by a decrease in safety behavior in the VR-CBT group. The discrepancy between reactivity and recovery findings may be explained by the inhibitory learning theory that suggests that an original threat reaction may not erase but can be inhibited as a consequence of exposure therapy.

Paradigms and Practice Shifts: A Topical Narrative Review of the Evolving Face of Exposure-Based Treatment for Youth

Abstract: Exposure therapy is the gold standard treatment for anxiety and obsessivecompulsive disorders in children, adolescents, and adults. Inhibitory Learning Theory offers a nuanced and advanced perspective on exposure treatment positing that violating threat expectancies is more important than habituation. This paper highlights the effectiveness of inhibitory learning theory-guided exposure procedures for youth with anxiety and OCD, chronic pain, and eating disorders. A topical review focusing on the theoretical foundations of inhibitory learning theory, crucial augmentations of the approach, and outcomes with pediatric patients diagnosed with anxiety, eating, and pain disorders is presented. The literature review indicated that inhibitory learning theory-driven exposure produced beneficent outcomes in the identified populations. Various limitations and future directions were discussed. Limitations notwithstanding, inhibitory learning theory-led exposure represents a viable treatment option for pediatric patients with anxiety, eating, and chronic pain disorders.

Feeling more confident to encounter negative emotions: The mediating role of distress tolerance on the relationship between self-efficacy and outcomes of exposure and response prevention for OCD

BackgroundWhile exposure and response prevention (ERP) is the first-line treatment for obsessive-compulsive disorder (OCD), up to half of patients do not effectively respond. In an effort to better understand the mechanisms behind ERP, the inhibitory learning model emphasizes the roles of increasing perceived self-efficacy and distress tolerance. While self-efficacy and distress tolerance have separately been shown to predict OCD symptoms and treatment outcomes, no studies have assessed their joint effects in ERP. The current study examined distress tolerance as a mediator of the relationship between self-efficacy and ERP outcomes. MethodsPatients in an intensive ERP-based treatment program (N = 116) completed weekly self-report measures. ResultsOver the course of treatment, as OCD symptoms reduced, self-efficacy and distress tolerance both significantly increased. Importantly, increases in self-efficacy and distress tolerance mediated each other in explaining symptom reduction, suggesting a possible bi-directional effect. LimitationsThe temporal relationship between changes in self-efficacy and distress tolerance is worthy of further investigation. In addition, the current sample had limited racial diversity and might not be representative of patients receiving lower levels of care. Findings merit replication to be ascertained of their reliability. ConclusionsFindings suggest that during ERP, patients gain confidence in their abilities both to cope with general challenges and to withstand distress, potentially helping them engage with exposures and overcome initial fears. These findings provide support for the inhibitory learning model and highlight the mechanistic roles of self-efficacy and distress tolerance in ERP. Clinical implications to target both in treatment are discussed.

Effectiveness of exposure-based treatment for childhood anxiety disorders: An open clinical trial to test its relation with indices of emotional processing and inhibitory learning

Background and objectivesThe current study examined how effectiveness of exposure-based CBT was related to indices of emotional processing and inhibitory learning during exposure exercises. MethodsAdolescents with anxiety disorder(s) (N = 72; age 11–19; 85% girls) received a group-based, intensive two-week treatment of which effectiveness was indexed by the SCARED and by ratings of anxiety and approach towards individualized goal situations. To index emotional processing, subjective units of distress (SUDs) were used to indicate both initial and final fear level, and absolute, relative, and total dose of fear reduction. To index inhibitory learning, subjective threat expectancies (STEs) were used to indicate initial and final threat expectancy, and absolute, relative, and total dose of expectancy change. ResultsFrom pre-treatment to follow-up, there was a large-sized reduction of anxiety symptoms, small-sized decrease of subjective anxiety and a large-sized increase in subjective approach towards individual treatment goals. Higher fear levels prior to exposure were related to a larger decrease of symptoms. Higher threat expectancies after exposure exercises were independently associated with less decrease of anxiety and increase of approach towards treatment goals. Total dose of experienced fear reduction and total dose of experienced expectancy change were (partly) independently related to more increase in approach towards individualized goal situations. LimitationsAs patients also received other treatment elements, the results cannot be interpreted unequivocally. ConclusionsThe pattern of findings seems to indicate that emotional processing (as indexed by fear reduction) and inhibitory learning (as indexed by expectancy change) are both relevant in exposure-based CBT.

Conditioned inhibition, inhibitory learning, response inhibition, and inhibitory control: Outlining a conceptual clarification.

Inhibition can be defined as a phenomenon in which an agent prevents or suppresses a behavioral state that would otherwise occur. Associative learning studies have extensively examined how experiences shape the acquisition of inhibitory behavioral tendencies across many species and situations. Associative inhibitory phenomena can be studied at various levels of analysis. One could focus on the trajectory of behavioral change involved in learning from negative statistical associations between discrete events (inhibitory learning). Alternatively, one could be interested in the effects of accumulated experience with those negative associations (conditioned inhibition). One could rather be interested in how organisms implement what they learn through experiences involving negative associations (response inhibition). Yet, one could inquire into how the capacity of learning negative associations and performing accordingly varies between individuals and along time for the same individual (inhibitory control). This article presents a tentative taxonomy addressing different levels of analysis of associative inhibitory phenomena by using different terms for each. In addition, recent evidence and certain unresolved issues at each level are thoroughly scrutinized and contrasted with prior findings. The empirical and theoretical advances made by modeling inhibition as an associative learning phenomenon have provided scaffolds for the current knowledge and emerging accounts of the topic. Some of those emerging accounts have the potential to bridge different levels of analysis and foster "cross-pollination" of ideas among broad fields beyond associative learning. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Increased Generalization, Stronger Acquisition, or Reduced Extinction? Investigation of the Mechanisms Underlying the Acquisition-in-Multiple-Contexts Effect

Prior research has demonstrated that conducting acquisition in multiple contexts results in more responding to the point that it can even nullify the benefit of subsequent extinction in multiple contexts on reducing renewal of excitatory responding. The underlying mechanism to explain why this happens has not been systematically examined. Using self-reported expectancy of the outcome, the current study investigates three mechanisms that potentially explain why acquisition in multiple contexts results in more responding—greater generalization, stronger acquisition learning, or slower extinction learning. Participants (N = 180) received discriminative training with a conditioned stimulus (CS+) and outcome pairing and a CS− → noOutcome pairing in either one or three contexts. This was followed by either extinction treatment in a novel context or no extinction. Finally, testing occurred in the acquisition context, the extinction context, or a novel context. Stronger renewal of extinguished conditioned expectation was observed for participants who received CS+ → Outcome pairings in three contexts relative to one context. There was no effect of the number of contexts on the strength of the excitatory CS+ → Outcome association or degree of inhibitory learning that occurred during extinction. This suggests that generalization is the mechanism responsible for the adverse impact to extinction learning when acquisition is conducted in multiple contexts.

The herbicide glyphosate inhibits hippocampal long-term potentiation and learning through activation of pro-inflammatory signaling

Glyphosate, a herbicide marketed as Roundup, is widely used but there are concerns this exposure could impair cognitive function. In the CA1 region of rat hippocampal slices, we investigated whether glyphosate alters synaptic transmission and long-term potentiation (LTP), a cellular model of learning and memory. Our hypothesis is that glyphosate alters neuronal function and impairs LTP induction via activation of pro-inflammatory processes. Roundup depressed excitatory synaptic potentials(EPSPs) in a dose-dependent manner with complete suppression at 2000 mg/L. At concentrations ≤ 20 mg/L Roundup did not affect basal transmission, but 4 mg/L Roundup administered for 30 min inhibited LTP induction. Acute administration of 10–100 μM glyphosate also inhibited LTP induction. Minocycline, an inhibitor of microglial activation, and TAK-242, an inhibitor of toll-like receptor 4 (TLR4), both overcame the inhibitory effects of 100 µM glyphosate. Similarly, lipopolysaccharide from Rhodobacter sphaeroides (LPS-RS), a different TLR4 antagonist, overcame the inhibitory effects. In addition, ISRIB (integrated stress response inhibitor) and quercetin, an inhibitor of endoplasmic reticulum stress, overcame the inhibitory effects. We also observed that in vivo glyphosate injection (16.9 mg/kg i.p.) impaired one-trial inhibitory avoidance learning. This learning deficit was overcome by TAK-242. These observations indicate that glyphosate can impair cognitive function through pro-inflammatory signaling in microglia.

Threshold plasticity of SOI-GST microring resonators.

Spiking Neural Networks, also known as third generation Artificial Neural Networks, have widely attracted more attention because of their advantages of behaving more biologically interpretable and being more suitable for hardware implementation. Apart from using traditional synaptic plasticity, neural networks can also be based on threshold plasticity, achieving similar functionality. This can be implemented using e.g. the Bienenstock, Cooper and Munro rule. This is a classical unsupervised learning mechanism in which the threshold is closely related to the output of the post-synaptic neuron. We show in simulations that the threshold characteristics of the nonlinear effects of a microring resonator integrated with Ge2Sb2Te5 demonstrate some complex dependencies on the intracavity refractive index, attenuation, and wavelength detuning of the incident optical pulse, and exhibit class II excitability. We also show that we are able to modify the threshold power of the microring resonator by the changes of the refractive index and loss of Ge2Sb2Te5, due to transitions between the crystalline and amorphous states. Simulations show that the presented device exhibits both excitatory and inhibitory learning behavior, either lowering or raising the threshold.

Implementation and Preliminary Outcomes of an Exposure-Based Summer Camp for Pediatric OCD and Anxiety

Despite the high prevalence of anxiety disorders in children and adolescents and the existence of effective evidence-based treatments for them, access to psychological care remains a major public health concern. Summer camps may provide an effective treatment avenue for youth who might not otherwise have access to care. This study describes the design and implementation of Fear Facers, a semistructured, 5-day, daytime exposure-therapy-based summer camp designed for youth with a primary diagnosis of obsessive-compulsive disorder (OCD), social anxiety, separation anxiety, or a specific phobia. Preliminary data regarding feasibility and patient outcomes is also reported. Among 52 children and adolescents aged 7 to 16 who attended one of six camp sessions between 2018 and 2021, significant reductions in anxiety (d = 0.54) and OCD symptoms (d = 0.57) were observed from pre-camp to immediately post-camp. A subset of campers who were followed for an additional 3 months post-camp (n = 22) showed maintenance of treatment gains. Retention rates for the intervention were high. Our investigation provides further support for the use of a camp-based design for cognitive-behavioral approaches, and may provide a unique setting to maximize elements of inhibitory learning in exposures. We also discuss a number of elements regarding feasibility that need consideration for those hoping to develop similar interventions.

The Impact of Exposure Therapy on Cancer-Related Future Cognitions in Severe Health Anxiety

Individuals with illness anxiety disorder (IAD) experience a preoccupation with having or acquiring a serious illness despite having mild or absent physical symptoms. Formerly hypochondriasis, individuals with IAD experience high rates of disability, contribute to elevated annual health care costs, and experience multiple comorbidities. IAD has been historically difficult to treat for both medical and mental health providers. Research suggests cognitive behavior therapy has mixed results for individuals with IAD. In this fictitious case presentation, we describe a course of successful exposure therapy for IAD drawing on the principals of inhibitory learning theory. Thus, through this example we demonstrate how to overcome common obstacles to successful treatment for IAD, such as willingness to participation, comorbid depression, and therapeutic alliance.

Position Sensorless Drive With Online Parameters Estimation for Magnetic Suspension Centrifugal Compressor

With the advantages of a high power-to-weight ratio and oil-free bearings, a magnetically Suspension centrifugal compressor (MSCC) equipped with active magnetic bearings (AMB) operates more efficiently than traditional mechanical compressors over a wide speed range by precisely controlling a high-speed permanent-magnet synchronous motor (PMSM). However, owing to the harsh working environment, the motor parameters, including the resistor, inductance and flux linkage, vary significantly. This degrades the rotor position observer performance, which is crucial for controlling a high-speed PMSM. Hence, this article proposes an improved sensorless control method combined with novel motor parameter identification. First, an improved position sliding mode observer using a novel super-twisting algorithm (STA) is designed to achieve higher precision and better transient performance. Second, the influence of parameter mismatch is analyzed. To overcome the problems of rank deficiency and system matrix uncertainties, a novel identification strategy based on recursive total least squares excitatory and inhibitory learning (RTLS EXIN) is developed to identify inductance and resistance in two-time scales. Meanwhile, the back electromotive force (EMF) in static coordinates is employed to estimate the flux linkage. Third, the results are adopted to update the control parameters immediately. Finally, the proposed method is tested on an MSCC prototype experimental platform, and the results verify its validity and feasibility.

Evidence of Altered Fear Extinction Learning in Individuals with High Vaccine Hesitancy During Covid-19 Pandemic.

A relevance of fear and concerns about vaccine development and its side effects are suggested to explain COVID-19 vaccine hesitancy. However, evidence supporting the phobic origin hypothesis of hesitancy for COVID-19 and other vaccinations remains indirect and elusive. We addressed this issue by investigating the existence of a relationship between fear conditioning, extinction, and the respective vaccination hesitancy and anxiety scores in a group of 25 individuals. Overall, we show that the general mechanism of fear extinction learning is impaired in individuals with high vaccine hesitancy. State and trait anxiety scores do not account for this result. These findings suggest that attitudes against vaccination could be linked to an altered inhibitory learning process.