BackgroundObsessive-compulsive disorder (OCD) is a psychiatric condition that typically manifests in compulsive urges to perform irrational or excessive avoidance behaviors. A recent account has suggested that compulsivity in OCD might arise from excessive stimulus-response habit formation, rendering behavior insensitive to goal value. We tested if OCD patients have a bias toward habits using a novel shock avoidance task. To explore how habits, as a putative model of compulsivity, might relate to obsessions and anxiety, we recorded measures of contingency knowledge, explicit fear, and physiological arousal.MethodsTwenty-five OCD patients and 25 control subjects completed a shock avoidance task designed to induce habits through overtraining, which were identified using goal-devaluation. The relationship between habitual behavior, erroneous cognitions, and physiological arousal was assessed using behavior, questionnaires, subjective report, and skin conductance responses.ResultsA devaluation sensitivity test revealed that both groups could inhibit unnecessary behavioral responses before overtraining. Following overtraining, OCD patients showed greater avoidance habits than control subjects. Groups did not differ in conditioned arousal (skin conductance responses) at any stage. Additionally, groups did not differ in contingency knowledge or explicit ratings of shock expectancy following the habit test. Habit responses were associated with a subjective urge to respond.ConclusionsThese data indicate that OCD patients have a tendency to develop excessive avoidance habits, providing support for a habit account of OCD. Future research is needed to fully characterize the causal role of physiological arousal and explicit fear in habit formation in OCD.

Objective-The goal of this study was to determine the neural correlates of excessive habit formation in obsessive-compulsive disorder (OCD). We aimed to (i) test for neurobiological convergence with the known pathophysiology of OCD and (ii) infer, based on abnormalities in brain activation, whether these habits arise from dysfunction in the goal-directed or habit system.Method-Thirty-seven OCD patients and 33 controls learned to avoid shocks while undergoing a functional Magnetic Resonance Imaging (fMRI) scan. Following 4 blocks of training, we tested if the avoidance response had become a habit by removing the threat of shock and measuring continued avoidance. We tested for task-related differences in brain activity in 3 ROIs, the caudate, putamen and medial orbitofrontal cortex at a statistical threshold of p<.05, family-wise error (FWE) corrected.Results-We observed excessive habit formation in OCD patients, which was associated with hyper-activation in the caudate. Activation in this region was also associated with subjective ratings of increased urge to perform habits. The OCD group, as a whole, showed hyper-activation in the medial orbitofrontal cortex (mOFC) during the acquisition of avoidance, however this did not relate directly to habit formation.Conclusions-OCD patients exhibited excessive habits that were associated with hyperactivation in a key region implicated in the pathophysiology of OCD, the caudate nucleus. Prior studies suggest that this region is important for goal-directed behavior, suggesting that habitforming biases in OCD may be a result of impairments in this system, rather than differences in the build up of stimulus-response habits themselves.

Different mnemonic outcomes have been observed when associative memories are reactivated by CS exposure and followed by amnestics. These outcomes include mere retrieval, destabilization-reconsolidation, a transitional period (which is insensitive to amnestics), and extinction learning. However, little is known about the interaction between initial learning conditions and these outcomes during a reinforced or nonreinforced reactivation. Here we systematically combined temporally specific memories with different reactivation parameters to observe whether these four outcomes are determined by the conditions established during training. First, we validated two training regimens with different temporal expectations about US arrival. Then, using Midazolam (MDZ) as an amnestic agent, fear memories in both learning conditions were submitted to retraining either under identical or different parameters to the original training. Destabilization (i.e., susceptibly to MDZ) occurred when reactivation was reinforced, provided the occurrence of a temporal prediction error about US arrival. In subsequent experiments, both treatments were systematically reactivated by nonreinforced context exposure of different lengths, which allowed to explore the interaction between training and reactivation lengths. These results suggest that temporal prediction error and trace dominance determine the extent to which reactivation produces the different outcomes.

RationalePrevious work has demonstrated a profound effect of N-methyl-d-aspartic acid receptor (NMDAR) antagonism in the infralimbic cortex (IL) to selectively elevate impulsive responding in a rodent reaction time paradigm. However, the mechanism underlying this effect is unclear.ObjectivesThis series of experiments investigated the pharmacological basis of this effect in terms of excitatory and inhibitory neurotransmission. We tested several pharmacological mechanisms that might produce the effect of NMDAR antagonism via disruption or dampening of IL output.MethodsDrugs known to affect brain GABA or glutamate function were tested in rats pre-trained on a five-choice serial reaction time task (5-CSRTT) following either their systemic administration or direct administration into the IL.ResultsSystemic lamotrigine administration (15 mg/kg), which attenuates excess glutamate release, did not counteract the ability of the intra-IL NMDAR antagonist 3-((R)-2-carboxypiperazin-4-yl)-propyl-l-phosphonic acid ((R)-CPP) to increase premature responding on the 5-CSRTT. Putative elevation of local extracellular glutamate via intra-IL infusions of the selective glutamate reuptake inhibitor dl-threo-β-benzyloxyaspartate as well as local α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor antagonism also had no effect on this task. However, intra-IL infusions of the GABAA receptor agonist muscimol produced qualitatively but not quantitatively comparable increases in impulsive responding to those elicited by (R)-CPP. Moreover, the GABAA receptor antagonist bicuculline blocked the increase in impulsivity produced by (R)-CPP when infused in the IL.ConclusionsThese findings implicate glutamatergic and GABAergic mechanisms in the IL in the expression of impulsivity and suggest that excessive glutamate release may not underlie increased impulsivity induced by local NMDA receptor antagonism.

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It has been suggested that, unlike pure extinction which typically results in the return of the fear response under a variety of circumstances, memory reactivation followed by extinction can attenuate the reemergence of conditioned fear. The reactivation-extinction procedure has attracted the attention of basic and clinical researchers due to its potential clinical value for the treatment of psychiatric conditions, such as anxiety and drug abuse disorders. However, mixed results have been achieved so far in replicating and understanding this paradigm. It has been proposed that memory destabilization could be critical in this sense. Using contextual fear conditioning in rats and midazolam as an amnesic agent, we first determined what reactivation conditions are necessary to destabilize the mnemonic trace. After establishing the conditions for memory destabilization, a series of experiments was conducted to determine if destabilization is critical for the success of the reactivation-extinction procedure. Data confirmed the importance of memory destabilization prior to extinction inside the reconsolidation window to attenuate spontaneous recovery and retard reacquisition of conditioned fear. The present report offers a candidate explanation of the discrepancy in results obtained with the reactivation -extinction procedure by different laboratories.

The present experiments addressed a fundamental discrepancy in the Pavlovian conditioning literature concerning responding to a target cue following compound reinforced training with another cue of higher salience. Experiment 1 identified one determinant of whether the target cue will be overshadowed or potentiated by the more salient cue, namely contiguity between compound CS termination and US presentation. Overshadowing and potentiation were observed with delay and trace procedures, respectively. Experiments 2-3 contrasted elemental and configural explanations of potentiation. Both experiments supported a configural account. Experiments 3 and 4, by manipulating prior learning experiences to bias subjects to encode the same compound elementally or configurally, demonstrated decreased potentiation and overshadowing, respectively. Overall, these experiments demonstrate potentiation with non-taste stimuli and identify one variable that determines whether overshadowing or potentiation will occur. Moreover, they show that prior experiences can determine how a compound is encoded and are compatible with the idea of flexible encoding as a principle of information processing. KeywordsPavlovian fear conditioning; potentiation; overshadowing; elemental encoding; configural encoding; transfer of learning; encoding flexibility A central focus in the study of Pavlovian conditioning since the 1970s has been to understand the mechanisms that underlie cue interactions during training. By cue interactions, we mean the changes in a target cues' (X) behavioral control that occur as a function of the copresentation during training of another cue, either simultaneously or serially. In other words, conditioned responding to X during test changes because a second cue (A) was trained simultaneously with X (e.g., AX→US), relative to a group that was trained in the absence of A (e.g., X→US). Importantly, much theorizing in the area of Pavlovian conditioning has been concerned with one form of cue interaction, namely cue competition. Cue competition is said to have occurred when during testing we observe less behavioral control by the target cue (X) because a second cue was also presented during training. The example we just provided (AX→US) is called overshadowing, and was documented early on by Pavlov (1927). Overshadowing is not an isolated phenomenon, but rather one of many examples in which behavioral control to a target cue is decreased by the co-presentation of a second cue during training. Blocking, the decreased responding to a target cue after it has been trained in the presence of an already established predictor of the outcome, is another example of cue competition (Kamin, 1968 NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptOvershadowing and blocking are two phenomena that are widely observed across tasks and species. That is, they are observed in appetitive conditioning with rats (Holland, 1999), aversive conditioning with rats (Wheeler & Miller, 2007), spatial learning with rats (Sánchez-...

Four experiments using rats in a Pavlovian lick-suppression preparation investigated the effects of combining 2 treatments known for their response-decrementing effects, namely, overshadowing and degraded contingency. Contrary to most contemporary learning theories, the extended comparator hypothesis predicts that these 2 treatments will counteract each other, and therefore, less of a decrement in conditioned responding should be observed than with either treatment alone. Experiments 1 and 2 confirmed this prediction in first-order conditioning and sensory preconditioning preparations, respectively. Experiment 3 demonstrated that posttraining extinction of the training context resulted in a recovery from degraded contingency and reversed the counteractive effect on overshadowing. Finally, Experiment 4 demonstrated that posttraining extinction of the overshadowing stimulus resulted in recovery from simple overshadowing and also reversed the counteractive effect on degraded contingency. These results are consistent with the extended comparator hypothesis but not traditional or recent acquisition-focused models.