Giuseppe Castegnetti

Optimising a model-based approach to inferring fear learning from skin conductance responses.

Highlights • We validate a Psychophysiological model (PsPM) to infer anticipatory sympathetic arousal from changes in skin conductance.• We optimise the inversion of this PsPM in terms of a constrained non-linear dynamic causal model.• This method allows a quantification of fear memory in humans.

Modeling event-related heart period responses

Abstract Cardiac rhythm is generated locally in the sinoatrial node, but modulated by central neural input. This may provide a possibility to infer central processes from observed phasic heart period responses (HPR). Currently, operational methods are used for HPR analysis. These methods embody implicit assumptions on how central states influence heart period. Here, we build an explicit psychophysiological model (PsPM) for event‐related HPR. This phenomenological PsPM is based on three experiments involving white noise sounds, an auditory oddball task, and emotional picture viewing. The model is optimized with respect to predictive validity—the ability to separate experimental conditions from each other. To validate the PsPM, an independent sample of participants is presented with auditory stimuli of varying intensity and emotional pictures of negative and positive valence, at short intertrial intervals. Our model discriminates these experimental conditions from each other better than operational approaches. We conclude that our PsPM is more sensitive to distinguish experimental manipulations based on heart period data than operational methods, and furnishes a principled approach to analysis of HPR.

A linear model for event-related respiration responses

Highlights • We develop a novel method for analysing event-related respiratory responses.• This method is based on a Psychophysiological Model (PsPM) of interpolated time series.• We analyse respiration period (RP), amplitude (RA) and flow rate (RFR).• RA and RFR estimates distinguish different event types, and all three measures distinguish events from non-events.• The new method could be useful for fMRI experiments using respiration belts.

A pupil size response model to assess fear learning.

Abstract During fear conditioning, pupil size responses dissociate between conditioned stimuli that are contingently paired (CS+) with an aversive unconditioned stimulus, and those that are unpaired (CS‐). Current approaches to assess fear learning from pupil responses rely on ad hoc specifications. Here, we sought to develop a psychophysiological model (PsPM) in which pupil responses are characterized by response functions within the framework of a linear time‐invariant system. This PsPM can be written as a general linear model, which is inverted to yield amplitude estimates of the eliciting process in the central nervous system. We first characterized fear‐conditioned pupil size responses based on an experiment with auditory CS. PsPM‐based parameter estimates distinguished CS+/CS‐ better than, or on par with, two commonly used methods (peak scoring, area under the curve). We validated this PsPM in four independent experiments with auditory, visual, and somatosensory CS, as well as short (3.5 s) and medium (6 s) CS/US intervals. Overall, the new PsPM provided equal or decisively better differentiation of CS+/CS‐ than the two alternative methods and was never decisively worse. We further compared pupil responses with concurrently measured skin conductance and heart period responses. Finally, we used our previously developed luminance‐related pupil responses to infer the timing of the likely neural input into the pupillary system. Overall, we establish a new PsPM to assess fear conditioning based on pupil responses. The model has a potential to provide higher statistical sensitivity, can be applied to other conditioning paradigms in humans, and may be easily extended to nonhuman mammals.

Modeling fear-conditioned bradycardia in humans

Abstract Across species, cued fear conditioning is a common experimental paradigm to investigate aversive Pavlovian learning. While fear‐conditioned stimuli (CS+) elicit overt behavior in many mammals, this is not the case in humans. Typically, autonomic nervous system activity is used to quantify fear memory in humans, measured by skin conductance responses (SCR). Here, we investigate whether heart period responses (HPR) evoked by the CS, often observed in humans and small mammals, are suitable to complement SCR as an index of fear memory in humans. We analyze four datasets involving delay and trace conditioning, in which heart beats are identified via electrocardiogram or pulse oximetry, to show that fear‐conditioned heart rate deceleration (bradycardia) is elicited and robustly distinguishes CS+ from CS−. We then develop a psychophysiological model (PsPM) of fear‐conditioned HPR. This PsPM is inverted to yield estimates of autonomic input into the heart. We show that the sensitivity to distinguish CS+ and CS− (predictive validity) is higher for model‐based estimates than peak‐scoring analysis, and compare this with SCR. Our work provides a novel tool to investigate fear memory in humans that allows direct comparison between species.

Assessing fear learning via conditioned respiratory amplitude responses

Abstract Respiratory physiology is influenced by cognitive processes. It has been suggested that some cognitive states may be inferred from respiration amplitude responses (RAR) after external events. Here, we investigate whether RAR allow assessment of fear memory in cued fear conditioning, an experimental model of aversive learning. To this end, we built on a previously developed psychophysiological model (PsPM) of RAR, which regards interpolated RAR time series as the output of a linear time invariant system. We first establish that average RAR after CS+ and CS− are different. We then develop the response function of fear‐conditioned RAR, to be used in our PsPM. This PsPM is inverted to yield estimates of cognitive input into the respiratory system. We analyze five validation experiments involving fear acquisition and retention, delay and trace conditioning, short and medium CS‐US intervals, and data acquired with bellows and MRI‐compatible pressure chest belts. In all experiments, CS+ and CS− are distinguished by their estimated cognitive inputs, and the sensitivity of this distinction is higher for model‐based estimates than for peak scoring of RAR. Comparing these data with skin conductance responses (SCR) and heart period responses (HPR), we find that, on average, RAR performs similar to SCR in distinguishing CS+ and CS−, but is less sensitive than HPR. Overall, our work provides a novel and robust tool to investigate fear memory in humans that may allow wide and straightforward application to diverse experimental contexts.

Psychophysiological modeling: Current state and future directions

Psychologists often use peripheral physiological measures to infer a psychological variable. It is desirable to make this inverse inference in the most precise way, ideally standardized across research laboratories. In recent years, psychophysiological modeling has emerged as a method that rests on statistical techniques to invert mathematically formulated forward models (psychophysiological models, PsPMs). These PsPMs are based on psychophysiological knowledge and optimized with respect to the precision of the inference. Building on established experimental manipulations, known to create different values of a psychological variable, they can be benchmarked in terms of their sensitivity (e.g., effect size) to recover these values-we have termed this predictive validity. In this review, we introduce the problem of inverse inference and psychophysiological modeling as a solution. We present background and application for all peripheral measures for which PsPMs have been developed: skin conductance, heart period, respiratory measures, pupil size, and startle eyeblink. Many of these PsPMs are task invariant, implemented in open-source software, and can be used off the shelf for a wide range of experiments. Psychophysiological modeling thus appears as a potentially powerful method to infer psychological variables.