Dopamine Effect on Inhibitory Control
Dopamine Effect on Inhibitory Control
The effect of Levodopa medication on inhibitory control in Parkinson's patients is extremely
 debated despite the fact that this has potential clinical and therapeutic implications. A key
 confounding factor of many previous studies is that they did not take the disease duration in
 consideration. In fact, in moderate-to-advanced stages of Parkinson dopaminergic drugs could
 not produce a clear effect because too few dopaminergic cells for the drugs to operate on
 survived. Hence, in this study, we will compare the performance in the stop signal task in
 early-stage versus moderate-to-advanced stages Parkinson's patients both in ON and in OFF
 medication. In addition, to have a baseline measure of inhibitory control we will compare
 patient's performances with that of age-matched subjects.
The ability to stop a pending action is fundamental for survival in a natural environment
 where events cannot be fully predicted. Sudden events, such as the appearance of a physical
 obstacle, often require a quick change of the planned motor strategy and the first step
 toward this goal is to suppress the pre-programmed actions. Thus voluntary inhibition plays a
 crucial role in cognitive control and behavioral flexibility (1, 2). It has been shown that
 Parkinson's patients suffer from a specific deficit in this functions (3, 4, 5). However, it
 is extremely debated whether and how Levodopa medication (levodopa, dopamine agonists,
 anticholinergic drugs, or a combination of levodopa and an anticholinergic drug) affects
 response inhibition. A number of studies measuring inhibitory control via the stop signal
 task in Parkinson's patients seem to indicate that dopaminergic medications do not influence
 this executive function (5, 6, 7). However, a recent study (8) found that Levodopa medication
 does not affect specifically inhibitory control or movement readiness, but the balance
 between them. In fact, Parkinson's patients in the OFF medication state were able to maintain
 response latencies in the same range as healthy controls, but they showed a significant
 reduction in the ability to stop reactions abruptly. In contrast, patients' performance
 shifted significantly when taking dopaminergic medications. They move slower but stopping
 improved relative to the off dopamine state. This pattern suggests a role for dopamine in
 modulating the tradeoff between the two action control processes. In addition, studies of
 other specific populations and healthy adults suggest that dopaminergic medications deserve
 reconsideration in response inhibition. For instance, positron emission (PET) studies have
 found that higher levels of striatal D1 and D2/D3 receptor availability predict better
 performance on the stop signal task (9, 10) and that response inhibition performance evokes
 dopamine release in prefrontal, parietal, and temporal cortex in healthy adults (11). Even
 more importantly, a few recent studies provided evidence that early-stage Parkinson's
 patients with response inhibition impairment seem to beneﬁt from dopaminergic treatment
 (12,13). Therefore, a plausible hypothesis is that the absence of a clear effect of
 dopaminergic medications could be ascribed to the fact that in most previous studies included
 Parkinson's patients in the moderate-to-advanced stages. In those patients, the diminished
 efﬁcacy of dopaminergic drugs could be a consequence that too few dopaminergic cells for the
 drugs to operate on survived (14).

 Hence, the aim of the present work is to re-assess the impact of dopaminergic medications on
 inhibitory control on Parkinson's patients using a reaching version of the stop signal task
 (e.g. 4, 15, 16, 17, 18) taking the disease duration in consideration. To this aim, the
 investigators will compare the performance in the stop signal task in early-stage versus
 moderate-to-advanced stages Parkinson's patients both in ON and in OFF medication. Finally,
 to have a baseline measure of inhibitory control the investigators will compare patients'
 performances with those of age-matched subjects.
Inclusion Criteria:

 1. Right-handedness (as assessed by the Edinburgh Handedness Inventory)

 2. Being in stable treatment with the administration of L-dopa and dopamine agonists
 (i.e. not having motor fluctuations and/or dyskinesia)

 3. Having a Hoehn & Yahr score between 1.5 and 3

 Exclusion Criteria:

 1. Presence of severe sensory deficits

 2. Presence of overt signs of dementia (a. mini-mental state examination, MMSE must be
 ≥24; b. intelligence quotient ≥75).

 3. Comorbidity with other psychiatric disorders that might interfere with task execution
 (i.e. attentional disorders).

 4. Presence of severe tremor or rigidity of the right arm in the OFF medication state.