Dopamine Effect on Inhibitory Control
Condition: Idiopathic Parkinson's Disease
MeSH terms: Parkinson Disease
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): PD patients H&Y=1.5-2 Medications ON; PD patients H&Y=1.5-2 Medications OFF; Healthy age-matched controls; PD patients H&Y=3 Medications OFF; PD patients H&Y=3 Medications ON
Intervention type(s): Drug; Drug; Behavioral; Drug; Drug
Intervention description(s): Parkinson's patients will be allowed to the first-morning dose of levodopa medicament (levodopa, dopamine agonists, anticholinergic drugs, or a combination of levodopa and an anticholinergic drug) which normally allowed the patient to attain the best control of symptoms one hour before being tested (19). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients.; Parkinson's patients will not take medications overnight prior to the study (20). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients. This intervention will be given on a different day with respect to the Medication ON intervention. The order of intervention will be counterbalanced across subjects; Healthy controls will perform the stop signal task and the go-only task in the same day. The order of administration will be counterbalanced.; Parkinson's patients will not take medications overnight prior to the study (20). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients. This intervention will be given on a different day with respect to the Medication ON intervention. The order of intervention will be counterbalanced across subjects; Parkinson's patients will be allowed to the first-morning dose of levodopa medicament (levodopa, dopamine agonists, anticholinergic drugs, or a combination of levodopa and an anticholinergic drug) which normally allowed the patient to attain the best control of symptoms one hour before being tested (19). Patients will perform both the stop-signal task and the go-only task. Experimental conditions will be counterbalanced across patients.
Allocation: Non-Randomized
Intervention model: Factorial Assignment
Intervention model description: Both groups of patients will perform the stop-signal task and the go-only task under two conditions: a) ON Levodopa medication state calculated after the first-morning dose which normally allowed the patient to attain the best control of symptoms (4) b) OFF Levodopa medication state. i.e patients did not take medications overnight prior to the study (19). Experimental conditions will be counterbalanced across patients and administered in two different experimental sessions occurring on different days.
Healthy controls will perform the stop signal task and the go-only task in the same day. The order of administration will be counterbalanced.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Levodopa medication; stop signal task; inhibitory control; Parkinson's Disease; stop signal reaction time; proactive inhibition