Parkinson's disease (PD) is identified by a series of motor abnormalities caused by dopaminergic disruption in the basal ganglia. Also, the basal ganglia have many diverse connections with several brain regions, including frontal cortical areas responsible for executive function and other cognitive processes. Therefore, patients with PD can develop a wide range of cognitive difficulties (eg, dementia, psychosis, depression), and imaging shows that patients with PD tend to have decreased activity in the prefrontal cortex.1,2
The cardinal medicinal treatment of PD, levodopa/carbidopa, helps replenish the lack of dopamine and reduces tremor, rigidity and other common motor
symptoms, but what effect does levodopa have on cognition
? Recent work has shown that levodopa has both deleterious and beneficial effects on cognition in patients with PD.3,4,5,6,7
Some researchers conclude that dopaminergic medication may improve certain types of neuropsychological performance and hinder others because the brain regions involved are differentially affected by dopamine.3
A reasonable hypothesis is that brain regions have an optimal dopamine level, and shifts from the norm can impair some tasks/measures while benefiting others. Therefore, the present study measured the effect of levodopa on two saccade tasks with dissociable neural substrates.
The analysis of saccades is increasingly used for studying cognition and memory.8
Saccade circuitry is clearly understood, and saccades possess dynamic properties that are easily measured non‐invasively.9,10
It is clear from recent imaging studies that the physiological substrates for saccades (overt orienting) and spatial attention (covert orienting) overlap in many brain regions.11
Moreover, recent work has shown a similar pattern of dysfunction across overt and covert orienting in various clinical populations, suggesting saccades may be a useful tool to evaluate higher cognitive functions.12,13
Our Tonic Inhibition Model of orienting proposes that there is a voluntary system (prefrontal cortex and basal ganglia) exerting tonic inhibition on a reflexive system (superior colliculus and brainstem); the voluntary system modulates reflexive saccades and attention.14
Typical paradigms that test this model are the prosaccade (reflexively look at the stimulus) and the antisaccade (inhibit the reflexive response and voluntarily look away
from the stimulus). In the Tonic Inhibition Model, a deficit in the voluntary system would predict both impaired performance in voluntary saccades and decreased inhibition of reflexive saccades (eg, more direction errors in an antisaccade task and/or shorter latencies for reflexive saccades). Such a baseline pattern has been found in pathologies that involve frontal dysfunction, such as schizophrenia, PD, autism and attention deficit hyperactivity disorder.8,15,16,17,18,19,20
Saccades have rarely been used to test the effects of levodopa in PD. Therefore, we tested patients with PD in a moderately advanced stage of the disease on a voluntary antisaccade (AS) task and a reflexive prosaccade (PS) task to measure the effects of levodopa on executive function. Furthermore, each task contained both gap and overlap trials to maximise task sensitivity.12
The present study had two main hypotheses: (1) levodopa would improve performance on the AS task because of improved frontal lobe function; and (2) levodopa would enhance the tonic inhibition of the reflexive system, consequently slowing performance on the reflexive PS task. Finally, a control group was included to evaluate the ability of levodopa to normalise voluntary and reflexive performance.