An fMRI investigation of Pavlovian Instrumental Transfer and Avoidance Learning with Primary Reinforcement in Psychopathy

Unlike many other neuropsychiatric disorders, psychopathy is characterized by
instrumental or proactive aggression. Previous research on psychopathy has
focused on impairments in various learning tasks and aversive processing, and
associated abnormalities in the ventromedial prefrontal cortex (vmPFC) and
amygdala respectively. This will be the first study to assess interactions
between aversive (Pavlovian) processes and instrumental decision making by
making use of a Pavlovian Instrumental Transfer (PIT) paradigm and a
reinforcement learning paradigm. In addition, we will assess not only neural
activity in the vmPFC and the amygdala, but critically also connectivity
between the amygdala and the vmPFC.
PIT refers to the phenomenon that Pavlovian cues (that predict reward or
punishment) influence instrumental responding. For instance, aversive cues
(that predict punishment) inhibit appetitive instrumental behaviours (such as
approach), while potentiating aversive instrumental behaviours (such as active
withdrawal and passive avoidance). The paradigm enables us to assess a new
hypothesis on the pathophysiology of psychopathy in the context of alternative
leading hypotheses on psychopathy: the violence inhibition model in the
integrated emotion system, the somatic marker theory, and the response set
modulation hypothesis.
Specifically, we hypothesise that psychopathy is characterized not just by a
failure of aversive processing per se, nor by impaired instrumental decision
making per se, but rather by a failure to adjust instrumental (goal-directed)
decision making based on aversive, but not appetitive Pavlovian cues (i.e.
stimuli that predict reward or punishment). Thus PPs are expected to exhibit
disinhibited approach, but impaired withdrawal and avoidance, only in the
context of aversive Pavlovian cues. Performance of PPs will be compared with
that of healthy controls, as well as people with antisocial personality
disorder (ASPD) without psychopathy (ASPD-P). In contrast to PPs, the latter
group is mostly characterized by reactive aggression, and not proactive
aggression and are predicted to exhibit exaggerated rather than disrupted
modulation of instrumental behaviour by Pavlovian cues.
Complementarily we will employ an integrated reinforcement learning and
Go/NoGo paradigm, enabling us to assess influences of reward and punishment
cues on a different dimension of responding, i.e. inhibition vs. activation. We
hypothesize that psychopathy does not modulate the processing of appetitive or
aversive cues per se, nor the activation or inhibition of responding by itself,
but rather will influence the interaction between affective processing and
response activation. Accordingly we expect that psychopathy will be accompanied
by disruption of passive punishment avoidance while not affecting the other
conditions. Finally, we expect that the fMRI experiments will localize these
neuromodulatory effects to activity changes in subcortical brain regions
associated with appetitive and aversive processing and in cortical brain
regions that regulate descending behavioral control mechanisms. Specifically,
changes in activity are predicted to occur in the striatum, amygdala,
lateral/medial (orbito)frontal cortex and their connectivity.

The main objective is to elucidate the role of Pavlovian cues in instrumental
behaviour in PPs and PASPD-Ps and its neural underpinnings. To this end we will
acquire fMRI data from PPs, PASPD-Ps, and healthy controls during the
performance of two tasks. Based on prior literature, we predict that abnormal
task performance in PPs and PASPD-Ps is accompanied by, respectively, reduced
and enhanced connectivity between the amygdala, the ventromedial prefrontal
cortex (vmPFC), and/or the striatum.

A cross-sectional design will be employed with a healthy control group
matched to the patient groups (PPs and PBPDs) on age, sex and intelligence. We
will use liquid outcomes - sucrose and citric acid for reward, and magnesium
sulfate for punishment. Prior to each fMRI session, a short calibration (simple
choice) task to titrate the magnesium sulfate concentration. During scanning,
subjects will complete two tasks. The first task enables the assessment of
reward and punishment predictive cues on active approach versus active
withdrawal. The second task enables the assessment of such cues on active
approach versus passive avoidance. Heart rate and pupil dilation (eyetracking)
measurements will be obtained to assess autonomic responsiveness to the cues.
Pre- and post-scanning different questionnaires and neuropsychological tests
will be filled out and performed to control a.o. for attentional deficits.

Participants will get two appointments: during and before the first appointment
participants will receive information and have to fill out some questionnaires
and will participate in diagnostic interviews. During a second appointment,
participants will participate in several experimental tasks during which
functional imaging data will be collected. Collection of data will be done at
the Donders Centre for Cognitive Neuroimaging. This does not involve any
special risks (see also Appendix C).