Prayer and Physic in Seventeenth-Century England

Historians have often represented prayer as an instrumental response to illness. We argue instead that prayer, together with physic, was part of larger regimes to preserve health and prevent disease. We focus on early modern England, through the philosophical writings of the physician, Robert Fludd, and the medical records of the clergyman, Richard Napier. Fludd depicted health as a fortress and illness as an invasion by demons; the physician counsels the patient in maintaining and restoring moral and bodily order. Napier documented actual uses of prayer. As in Fludd’s trope, through prayer, Napier and his patients enacted their aspiration for health and their commitment to a Christian order in which medicine only worked if God so willed it. Prayer, like physic, was a key part of a regime that the wise practitioner aimed to provide for his patients, and that they expected to receive from him.

Response-independent outcome presentations weakens the instrumental response-outcome association

The present paper explored the fate of previously formed response-outcome associations when the relation between R and O was disrupted by arranging for O to occur independently of R. In each of three experiments response independent outcome delivery selectively reduced the R earning that O. Nevertheless, in Experiments 1 and 2, the R continued to show sensitivity to outcome devaluation, suggesting that the strength of the R-O association was undiminished by this treatment. These experiments used a two-lever, two-outcome design introducing the possibility that devaluation reflected the influence of specific Pavlovian lever-outcome associations. In an attempt to nullify these incidental Pavlovian cues, Experiment 3 used a single bidirectional vertical lever that rats could press left or right for different outcomes. Again, response-independent outcome presentation selectively depressed the performance of the R that delivered the response-independent O. However, in this situation, the response independent O also reduced the sensitivity of R to outcome devaluation; whereas the non-degraded R was sensitive to devaluation, the degraded R was not. We conclude that selective degradation of the instrumental contingency can weaken a specific R-O association while leaving other R-O associations intact. Furthermore, the use of a bidirectional vertical lever in Experiment 3 revealed that instrumental manipulanda, such as levers or chains, produce Pavlovian cues capable of forming incidental associations with the instrumental outcome, obscuring the relative influence of R-O associations after various manipulations.

Intrinsic regulators of the action potential waveform control dopamine release to shape behavior

Despite the widely known role of dopamine in reinforcement learning, how the patterns of dopamine release that are critical to the acquisition, performance, and extinction of conditioned responses are generated is poorly resolved. Here, we demonstrate that the coordinated actions of two ion channels, Kv4.3 and BKCa1.1, control the pattern of dopamine release on different time scales to regulate separate phases of reinforced behavior in mice. Inactivation of Kv4.3 in VTA dopamine neurons increases pacemaker activity and excitability that is associated with increased ramping prior to lever press in a learned instrumental response paradigm. Loss of Kv4.3 enhanced performance of the learned response and facilitated extinction. In contrast, loss of BKCa1.1 increased burst firing and phasic dopamine release that enhanced learning of an instrumental response. Inactivation of BKCa1.1 increased the reward prediction error that was associated with an enhanced extinction burst in early extinction training. These data demonstrate that temporally distinct patterns of dopamine release are regulated by the intrinsic properties of the cell to shape behavior.

In search of the behavioural effects of fear: a paradigm to assess conditioned suppression in humans

Conditioned fear can substantially reduce the likelihood that an individual will engage in reward- related behaviour - a phenomenon coined conditioned suppression. Despite the unmistakable relevance of conditioned suppression for excessive fears and their adverse consequences, the phenomenon has primarily been observed in animal models and is not yet well understood. Here, we aimed to develop a conditioned suppression paradigm that enables a robust quantification of the effect of Pavlovian aversive stimuli on subsequent reward-related behaviour in humans and assess its potential relation to physiological measures of fear. In phase 1, an instrumental response was incentivized with monetary rewards. In phase 2, one of two conditioned stimuli (CS+) was reinforced with an aversive unconditioned stimulus (US, i.e., electric stimulus). During aversive Pavlovian learning we assessed differential skin conductance (SCR) and fear potentiated startle responses (FPS). Lastly, we tested the effect of the aversively conditioned CS+ on the response rate of the instrumental response in a transfer phase. Despite strong aversive Pavlovian conditioning, as indicated by large effect sizes in differential SCR and FPS, we did not find any evidence for conditioned suppression: i.e., there was no significant reduction of instrumental responding in the presence of the CS+ compared to a new control stimulus. This lack of conditioned suppression is in line with previous studies that reported difficulties inducing conditioned suppression and points towards a general challenge in investigating conditioned suppression in humans. Implications and directions for future research on the highly relevant behavioural effects of fear and anxiety are discussed.

Phasic inhibition of dopamine neurons is an instrumental punisher

It is well established that the activity of VTA dopamine neurons is sufficient to serve as a Pavlovian reinforcer but whether this activity can also serve as instrumental reinforcer is less well understood. Here we studied the effects of optogenetic inhibition of VTA dopamine neurons in instrumental conditioning preparations. We show that optogenetic inhibition of VTA dopamine neurons causes a response-specific, contingency-sensitive suppression of instrumental responding. This suppression was due to instrumental response, not Pavlovian stimulus, learning and could not be attributed to deepened instrumental extinction learning. These effects of optogenetic inhibition of VTA dopamine neurons on instrumental responding are formally similar to the effects of aversive events in instrumental preparations and show that optogenetic inhibition of VTA dopamine neurons is sufficient to serve as an instrumental punisher.

Calibration

In the context of chemical metrology, calibration is the process of relating a known quantity of an analyte to the corresponding measured instrumental response through a mathematical relationship. Calibration permits the assignment of analyte levels in unknown samples based on the known levels of the calibrants. Details of the calibration model are important to achieve accurate results. Several common approaches are used in calibrating methods. Most frequently, calibration models are based on linear instrumental response, with mathematical models that include zero intercept, fixed intercept, unconstrained (fitted), and bracketed models. When instrumental response is nonlinear, a linear model may still provide accurate results if the calibration range is sufficiently limited. This presentation will provide an overview and application of various calibration models, with recommendations of ways to improve measurement accuracy. Examples are presented that illustrate advantages and disadvantages for each of these models as applied to low level samples and to unknowns with levels that span several orders of magnitude.

Novel reference-free methods for the determination of the instrumental response of Laue-type bent crystal spectrometers

This paper presents two novel reference-free methods for the determination of the instrumental resolution of Laue-type crystal spectrometers.

Effects of Scopolamine on Conditioning of Lever Pressing

The aim of this work was to determine the effects of scopolamine, a cholinergic antagonist, on the conditioning of an instrumental response and the contextual conditioning of this response. Five groups of rats were trained to lever-press on a Variable Interval 30 s schedule in context A. Scopolamine was administered 15 min before each conditioning session to AB 0.01 mg/kg, AB 0.10 mg/kg and AB 1.00 mg/kg groups. The AA Saline and AB Saline groups received saline injections.Contextual conditioning of the lever-pressing response was assessed in one extinction session. The AA group received this extinction session in the conditioning context (A), while the AB groups received this session in a different context (B). Results showed that scopolamine impaired the conditioning of the lever-pressing response but no effects on contextual conditioning were found.

Automaticity and cognitive control: Effects of cognitive load on cue-controlled reward choice

The extent to which human outcome–response (O-R) priming effects are automatic or under cognitive control is currently unclear. Two experiments tested the effect of cognitive load on O-R priming to shed further light on the debate. In Experiment 1, two instrumental responses earned beer and chocolate points in an instrumental training phase. Instrumental response choice was then tested in the presence of beer, chocolate, and neutral stimuli. On test, a Reversal instruction group was told that the stimuli signalled which response would not be rewarded. The transfer test was also conducted under either minimal (No Load) or considerable (Load) cognitive load. The Non-Reversal groups showed O-R priming effects, where the reward cues increased the instrumental responses that had previously produced those outcomes, relative to the neutral stimulus. This effect was observed even under cognitive load. The Reversal No Load group demonstrated a reversed effect, where response choice was biased towards the response that was most likely to be rewarded according to the instruction. Most importantly, response choice was at chance in the Reversal Load condition. In Experiment 2, cognitive load abolished the sensitivity to outcome devaluation that was otherwise seen when multiple outcomes and responses were cued on test. Collectively, the results demonstrate that complex O-R priming effects are sensitive to cognitive load, whereas the very simple, standard O-R priming effect is more robust.