Contextual control of conditioned pain tolerance and endogenous analgesic systems: Evidence for sex-based differences in endogenous opioid engagement

The mechanisms underlying the transition from acute to chronic pain are unclear but may involve the persistence or strengthening of pain memories acquired in part through associative learning. Contextual cues, which comprise the surrounding environment where events occur, were recently described as a critical regulator of pain memory; both rodents and humans exhibit increased pain sensitivity in environments recently associated with a single painful experience. It is unknown, however, how repeated exposure to an acute painful unconditioned stimulus in a distinct context modifies pain sensitivity or the expectation of pain in that environment. To answer this question, we conditioned mice to associate distinct contexts with either repeated administration of a mild visceral pain stimulus (intraperitoneal injection of acetic acid) or vehicle injection over the course of three days. On the final day of experiments animals received either an acid injection or vehicle injection prior to being placed into both contexts. In this way, contextual control of pain sensitivity and pain expectation could be tested respectively. Both male and female mice developed context-dependent conditional pain tolerance, a phenomenon mediated by endogenous opioid signaling. However, when expecting the presentation of a painful stimulus in a given context, males exhibited conditional hypersensitivity whereas females exhibited endogenous opioid-mediated conditional analgesia. Successful determination of the brain circuits involved in this sexually dimorphic anticipatory response may allow for the manipulation of pain memories, which may contribute to the development of chronic pain states.

Horizontal connectivity in V1 : Prediction of coherence in contour and motion integration

This study demonstrates the functional importance of the Surround context relayed laterally in V1 by the horizontal connectivity, in controlling the latency and the gain of the cortical response to the feedforward visual drive. We report here four main findings : 1) a centripetal apparent motion sequence results in a shortening of the spiking latency of V1 cells, when the orientation of the local inducer and the global motion axis are both co-aligned with the RF orientation preference; 2) this contextual effects grows with visual flow speed, peaking at 150-250 degrees per second until matching the propagation speed of horizontal connectivity (0.15-0.25 mm/ms); 3) For this speed range, axial sensitivity of V1 cells is tilted by 90 degrees to become co-aligned with the orientation preference axis; 4) the modulation strength by the surround context correlates with the spatiotemporal coherence of the apparent motion flow. Our results suggest an internally-generated binding process, linking local (orientation /position) and global (motion/direction) features as early as V1. This long-range diffusion process constitutes a plausible substrate in V1 of the human psychophysical bias in speed estimate for collinear motion. Since demonstrated in the anesthetized cat, this novel form of contextual control of the cortical transfer function is a built-in property in V1, whose expression does not require behavioral attention and top-down control from higher cortical areas. We propose that horizontal connectivity participates to the propagation of an internal prediction wave, linking contour co-alignment and global axial motion at an apparent speed in the range of saccadic-like eye-movements.

Trial-wise exposure to visual appetitive cues increases physiological arousal but not temporal discounting.

Humans and many animals devalue future rewards as a function of time (temporal discounting). Increased discounting has been linked to various psychiatric conditions, including substance-use-disorders, behavioral addictions and obesity. Despite its high intra-individual stability, temporal discounting is partly under contextual control. One prominent manipulation that has been linked to increases in discounting is the exposure to highly arousing appetitive cues. However, results from trial-wise cue exposure studies appear highly mixed, and changes in physiological arousal were not adequately controlled. Here we tested the effects of appetitive (erotic), aversive and neutral visual cues on temporal discounting in thirty-five healthy male participants. The contribution of single-trial physiological arousal was assessed using comprehensive monitoring of autonomic activity (pupil size, heart rate, electrodermal activity). Physiological arousal was elevated following aversive and in particular erotic cues. In contrast to our pre-registered hypothesis, if anything, we observed decreased temporal discounting following erotic cue exposure. Aversive cues tended to increase decision noise. Computational modeling revealed that trial-wise arousal only accounted for minor variance over and above aversive and erotic condition effects, arguing against a general effect of physiological arousal on temporal discounting.

Songbirds can learn flexible contextual control over syllable sequencing

The flexible control of sequential behavior is a fundamental aspect of speech, enabling endless reordering of a limited set of learned vocal elements (syllables or words). Songbirds are phylogenetically distant from humans but share both the capacity for vocal learning and neural circuitry for vocal control that includes direct pallial-brainstem projections. Based on these similarities, we hypothesized that songbirds might likewise be able to learn flexible, moment-by-moment control over vocalizations. Here, we demonstrate that Bengalese finches (Lonchura striata domestica), which sing variable syllable sequences, can learn to rapidly modify the probability of specific sequences (e.g. ‘ab-c’ versus ‘ab-d’) in response to arbitrary visual cues. Moreover, once learned, this modulation of sequencing occurs immediately following changes in contextual cues and persists without external reinforcement. Our findings reveal a capacity in songbirds for learned contextual control over syllable sequencing that parallels human cognitive control over syllable sequencing in speech.

Songbirds can learn flexible contextual control over syllable sequencing

The flexible control of sequential behavior is a fundamental aspect of speech, enabling endless reordering of a limited set of learned vocal elements (i.e. syllables or words). Songbirds are phylogenetically distant from humans, but share the capacity for vocal learning as well as neural circuitry for vocal control that includes direct cortical-brainstem projections. Based on these similarities, we hypothesized that songbirds might likewise be able to learn flexible, moment-by-moment control over vocal production. Here, we demonstrate that Bengalese finches, which sing variable syllable sequences, can learn to rapidly modify the probability of specific sequences (e.g. ‘ab-c’ versus ‘ab-d’) in response to arbitrary visual cues. Moreover, once learned, this modulation of sequencing occurs immediately following changes in contextual cues and persists in the absence of external reinforcement. Our findings reveal a capacity in songbirds for learned contextual control over syllable sequencing that parallels aspects of human cognitive control over speech.

Postprint BuckfieldSinclairGlautier (2020) Slow associative learning in alcohol dependence and the Alcohol Cue Exposure Treatment Paradox

The published version is available at: https://onlinelibrary.wiley.com/doi/epdf/10.1111/add.15210 AimsTo examine two explanations for the observation that cue-exposure treatment has not been clearly effective in the treatment of alcohol dependence: do alcohol dependent individuals have either 1) slower extinction and/or 2) greater contextual specificity of extinction than non-dependent individuals? DesignIn two exploratory laboratory experiments we used mixed factorial designs with two-group between-subjects factors and within-subjects factors corresponding to performance in different parts of a computer-based learning task.SettingUniversity of Southampton psychology research laboratories and two addiction treatment services in the city of Southampton, UK.ParticipantsExperiment 1: Seventy-four (54 female) undergraduates from the University of Southampton (age M=20.4 years). Experiment 2: One-hundred and two (40 female) participants from the University of Southampton, the local community, and from two Southampton alcohol treatment services (age M=41.3 years). MeasurementsThe Alcohol Use Disorders Identification Test, a 1-week time-line follow-back alcohol consumption questionnaire, the Barratt Impulsiveness Scale (11th Ed), and a computerised learning task. Experiment 2 additionally used the 44-item Big Five Inventory, a drug use history checklist, and the Hospital Anxiety and Depression Scale. FindingsExperiment 1: light and heavy drinkers did not differ significantly in extinction (extinction block x drinking status interaction, p=.761, η_p^2=.005, 95% confidence interval (0,.028)) or on contextual control of extinction (recovery block x drinking status interaction, p=.514, η_p^2=.009, 95% confidence interval (0,.084)). Experiment 2: slower extinction in abstinent alcohol dependent participants compared with light drinkers (extinction block x drinking status interaction, p=.023, η_p^2=.031, 95% confidence interval (0,.069)) but no significant difference on contextual control of extinction (recovery block x drinking status interaction, p=.069, η_p^2=.033, 95% confidence interval (0,.125)). ConclusionAbstinent alcohol dependent people may have slower extinction learning for alcohol-related cues, than non-dependent light drinkers.