Controllability estimation in Parkinson's disease: role of dopamine

Parkinson's disease (PD) is the second most common neurodegenerative disorder
and is marked by motor, cognitive, and affective dysfunction related to
pathology of the dopaminergic system. It is estimated that up to 50% of PD
patients suffer from depression at some point during the disease. The
depressive symptoms have been suggested to stem from maladaptive learning about
the consequences ones decisions have on the immediate environment. Indeed,
learned helplessness has been proposed as a model of depression which has been
shown to involve estimations of how much control one have over the environment.
Dopamine might act as an arbiter between modes of decision-making where
stimulus-response associations are formed from either passively (spectator)
observing or by actively exploring the environment (actor). A lack of
endogenous dopamine might thus bias patients into the passive mode of
decision-making causing them to erroneously perceive their environment as
uncontrollable. In this study we investigate the impact LDOPA has on how PD
patients estimate decision controllability.

This study aims to elucidate the relationship between subjective
controllability and dopamine in PD patients. We hypothesize that lower levels
of dopamine will be related to lower estimations of controllability. Using
fMRI, we will investigate the neural correlates of differences in
controllability. We hypothesize a difference in subcortical BOLD responses when
encountering prediction errors during the actor decision-making mode as a
function of dopaminergic innervation. Dopaminergic innervation will be
manipulated through measuring patients off and on L-DOPA.

A within-subjects repeated measure design will be used in this study. PD
patients will be tested twice, (1) on their regular L-DOPA medication, (2) off
their regular L-DOPA medication.

Participants will attend two identical study sessions on and off medication.
Participants will complete a series of questionnaires, structural and
functional MRI where the main task will be completed, out of scanner tasks to
independently measure associative learning and working memory capacity. Tremor
response will be measured during the functional MRI. There is no risk to the
patients concerning L-DOPA administration since it will be their normal dose.
Potential discomfort might be associated with the off medication session,
similar L-DOPA withdrawal designs in PD patients have been approved and
performed safely. Participating in this study is associated with minimal burden
and risk. The study can only be performed using this patient group due to the
unique disease profile of decreased dopaminergic innervation.