Instrumental Avoidance Learning Research Articles

Early-life stress is associated with a preponderance of habitual responding in a novel instrumental avoidance learning paradigm

There is substantial evidence linking early-life stress (ELS) to negative health outcomes in adulthood, including addiction. However, the neurocognitive and behavioral mechanisms through which ELS increases these risks remain unclear. To address this gap in knowledge, we developed a novel instrumental learning paradigm to explore the effects of ELS on the balance of habitual versus goal-directed learning. Habits efficiently reproduce repetitive behaviors but are inflexible whenreward contingencies related to those behaviors change. Persisting in performing a response after its outcome has been devalued is the hallmark of habitual behavior in instrumental learning. Participants with a history of higher ELS were significantly more likely to make habitual responses in this instrumental avoidance learning paradigm than individuals with a history of lower ELS. Logistic regression analysis showed that ELS is significantly related to habitual responding over and above the effects of retrospective socioeconomic status, trait and state anxiety, depression and recent levels of stress. Analysis of the differential impacts of the type of ELS suggested that these effects are largely driven by experiences of physical neglect.

Integration of social cues and individual experiences during instrumental avoidance learning.

Learning to avoid harmful consequences can be a costly trial-and-error process. In such situations, social information can be leveraged to improve individual learning outcomes. Here, we investigated how participants used their own experiences and others’ social cues to avoid harm. Participants made repeated choices between harmful and safe options, each with different probabilities of generating shocks, while also seeing the image of a social partner. Some partners made predictive gaze cues towards the harmful choice option while others cued an option at random, and did so using neutral or fearful facial expressions. We tested how learned social information about partner reliability transferred across contexts by letting participants encounter the same partner in multiple trial blocks while facing novel choice options. Participants’ decisions were best explained by a reinforcement learning model that independently learned the probabilities of options being safe and of partners being reliable and combined these combined these estimates to generate choices. Advice from partners making a fearful facial expression influenced participants’ decisions more than advice from partners with neutral expressions. Our results showed that participants made better decisions when facing predictive partners and that they cached and transferred partner reliability estimates into new blocks. Using simulations we show that participants’ transfer of social information into novel contexts is better adapted to variable social environments where social partners may change their cuing strategy or become untrustworthy. Finally, we found no relation between autism questionnaire scores and performance in our task, but do find autism trait related differences in learning rate parameters.

Regulation of striatal dopamine responsiveness by Notch/RBP-J signaling

Dopamine signaling is essential for reward learning and fear-related learning, and thought to be involved in neuropsychiatric diseases. However, the molecular mechanisms underlying the regulation of dopamine responsiveness is unclear. Here we show the critical roles of Notch/RBP-J signaling in the regulation of dopamine responsiveness in the striatum. Notch/RBP-J signaling regulates various neural cell fate specification, and neuronal functions in the adult central nervous system. Conditional deletion of RBP-J specifically in neuronal cells causes enhanced response to apomorphine, a non-selective dopamine agonist, and SKF38393, a D1 agonist, and impaired dopamine-dependent instrumental avoidance learning, which is corrected by SCH23390, a D1 antagonist. RBP-J deficiency drastically reduced dopamine release in the striatum and caused a subtle decrease in the number of dopaminergic neurons. Lentivirus-mediated gene transfer experiments showed that RBP-J deficiency in the striatum was sufficient for these deficits. These findings demonstrated that Notch/RBP-J signaling regulates dopamine responsiveness in the striatum, which may explain the mechanism whereby Notch/RBP-J signaling affects an individual’s susceptibility to neuropsychiatric disease.

Disrupted avoidance learning in functional neurological disorder: Implications for harm avoidance theories.

BackgroundFunctional neurological disorder (FND) is an elusive disorder characterized by unexplained neurological symptoms alongside aberrant cognitive processing and negative affect, often associated with amygdala reactivity.MethodsWe examined the effect of negative conditioning on cognitive function and amygdala reactivity in 25 FND patients and 20 healthy volunteers (HV). Participants were first conditioned to stimuli paired with negative affective or neutral (CS +/CS −) information. During functional MRI, subjects then performed an instrumental associative learning task to avoid monetary losses in the context of the previously conditioned stimuli. We expected that FND patients would be better at learning to avoid losses when faced with negatively conditioned stimuli (increased harm avoidance). Multi-echo resting state fMRI was also collected from the same subjects and a robust denoising method was employed, important for removing motion and physiological artifacts.ResultsFND subjects were more sensitive to the negative CS + compared to HV, demonstrated by a reinforcement learning model. Contrary to expectation, FND patients were generally more impaired at learning to avoid losses under both contexts (CS +/CS −), persisting to choose the option that resulted in a negative outcome demonstrated by both behavioural and computational analyses. FND patients showed enhanced amygdala but reduced dorsolateral prefrontal cortex responses when they received negative feedback. Patients also had increased resting state functional connectivity between these two regions.ConclusionsFND patients had impaired instrumental avoidance learning, findings that parallel previous observations of impaired action-outcome binding. FND patients further show enhanced behavioural and neural sensitivity to negative information. However, this did not translate to improved avoidance learning. Put together, our findings do not support the theory of harm avoidance in FND. We highlight a potential mechanism by which negative contexts interfere with adaptive behaviours in this under-explored disorder.

Amygdala Activity, Fear, and Anxiety: Modulation by Stress

Amygdala Activity, Fear, and Anxiety: Modulation by Stress

Amygdala Neurons Mediate Acquisition But Not Maintenance of Instrumental Avoidance Behavior in Rabbits

Whereas the amygdala is generally understood to be involved in aversively motivated learning, the specific associative function of the amygdala remains controversial. This study addressed the amygdalar role in mediation of discriminative instrumental avoidance learning of rabbits. Bilateral microinjection of the GABA receptor agonist muscimol centered in the basolateral nucleus of the amygdala was given to inactivate amygdalar neurons at each of three stages of acquisition. The absence of behavioral learning in rabbits trained immediately after amygdalar inactivation confirmed previous results with electrolytic lesions. The absence of savings during training after muscimol had become ineffective indicated an amygdalar role in the establishment of acquisition-relevant neural plasticity, not simply in the expression of the learned response. A time-limited role of the amygdala in instrumental avoidance learning was indicated by the finding that intra-amygdalar muscimol failed to disrupt performance of the well-established avoidance response. The passage of time alone (with no training trials) was sufficient to reduce amygdalar involvement in response performance. These results and demonstrations that other limbic system areas make time-limited contributions to learning indicate that the amygdala is part of a larger intermediate memory system that supports learning and performance before habit consolidation.

Limbic thalamic, cingulate cortical and hippocampal neuronal correlates of discriminative approach learning in rabbits

Previous research employing lesions and recording of neuronal activity has implicated cingulothalamic and hippocampal circuitry in the mediation of discriminative instrumental avoidance learning in rabbits. This study was directed at the question of whether the cingulothalamic circuitry is specialized for avoidance learning, or whether it is also involved in appetitively motivated learning. Multi-unit neuronal recordings in the aforementioned areas were obtained as adult New-Zealand white rabbits learned to approach and orally contact a drinking spout for water reward after a tone conditional stimulus (CS+), and to ignore the spout after a different, non-predictive tone conditional stimulus (CS-). As during avoidance learning, excitatory and discriminative training-induced neuronal activity (TIA) developed during the course of approach learning. Discriminative TIA refers to development of greater neuronal firing response to the CS+ than to the CS-. Excitatory TIA refers to increased neuronal discharge magnitude during training compared to the activity elicited before training, when CS presentations were unpaired with foot-shock presentations. As during avoidance learning, TIA in anterior cingulate cortical and interconnected mediodorsal (MD) thalamic neuronal records preceded TIA in posterior cingulate cortical and interconnected anterior ventral thalamic records. Delayed changes also occurred in area CAI of the hippocampus in parallel with changes in the posterior cingulate cortex and the anterior thalamic nuclei. In contrast to the avoidance-related activity, the changes in the thalamic areas preceded or occurred concurrently with changes in the related cingulate cortical areas. This difference is hypothesized to be due to a reduced or absent contribution of amygdaloid efferents to the approach learning-related TIA. The overall magnitude of the elicited training-induced neuronal responses was reduced, relative to the discharges during avoidance conditioning. The discharge magnitude differences suggested a greater recruitment of limbic circuit functions during avoidance learning, possibly due to the aversiveness and high arousal associated with the avoidance task. In general, the results indicate that the circuitry formed by interconnected cingulate cortical, limbic thalamic and hippocampal neurons has fundamentally similar functions in both approach and avoidance learning.

Local norepinephrine depletion and learning-related neuronal activity in cingulate cortex and anterior thalamus of rabbits

Multi-unit neuronal activity was recorded in posterior cingulate cortex (area 29) and the anterior ventral (AV) thalamic nucleus during discriminative instrumental avoidance learning wherein a response (stepping in an activity wheel) to a 0.5-s tone (CS+) prevented a foot-shock 5 s after CS+ onset. Presentations of a different tone (CS-) on 50% of the conditioning trials in an irregular sequence with the CS+ did not predict shock and thus required no response. Two groups of rabbits received intracranial micro-injections of 6-hydroxydopamine (6-OHDA) to locally deplete the NE in area 29 or the AV nucleus. Vehicle was injected in the non-depleted area in each group and a third group received vehicle injections in both areas. Dopamine neurons in subjects that received 6-OHDA were protected by pre-treatment with GBR-12909. Neuronal data were collected during two pre-training sessions in response to the tones only and when the tones and shock were presented unpaired. Thalamically depleted rabbits made more, and cortically depleted rabbits made fewer, avoidance responses than controls during the early stages of behavioral acquisition, and cortically depleted rabbits made fewer responses than controls and thalamically depleted rabbits during extinction testing administered after the completion of acquisition. One effect of NE depletion on neuronal activity was entirely local: elimination of neuronal sensitization effects (enhanced discharges elicited by tones during the unpaired tone-shock pre-training treatment relative to pre-training with tones only). Other neuronal effects of NE depletion were system-wide, i.e., they occurred whether the depletion was cortical or thalamic.(ABSTRACT TRUNCATED AT 250 WORDS)

Graded acquisition of an instrumental avoidance response by the spinal rat

Eight pairs of spinal rats were exposed to an instrumental conditioning paradigm in which one animal served as the experimental and the other as a yoked control animal. An electrode, inserted into the experimental animal's foot, contacted an aqueous solution delivering shock to both animals. Leg flexion terminated the shock. Following two consecutive min without shock, the experimental animal's solution was raised an additional millimeter and training was re-instated. This procedure was repeated 4 times, or until the experimental animal failed to reach the 2 min criterion. In Run 1, one leg was trained; during Run 2, the contralateral leg was used. In addition, the animal which served as the experimental in Run 1 served as the yoked control in Run 2 and vice versa. The results indicate that the spinal rat is capable of acquiring successively higher criteria in an instrumental conditioning routine. In conjunction with previous results, these findings suggest that instrumental avoidance learning can occur in the spinal cord.

Facilitation of instrumental avoidance learning by amphetamine: an analysis.

d-Amphetamine sulfate (1 mg/kg) was studied for its effect on acquisition (learning) of a conditioned avoidance response. Acquisition consisted of a single session of 700 trials in a Skinner box. A light and a noise (CS—conditioned stimulus) were presented for 15 sec ending in a brief shock (UCS—unconditioned stimulus) thus completing one trial. Avoidance responses, incorrect responses (when the CS was off) and wrong lever responses were recorded in blocks of 50 trials. The increase in the somatic motor activity (SMA) after amphetamine in different animals was also measured.