Dopamine effects on frontal cortical blood flow and motor inhibition in Parkinson's disease

Abstract

Parkinson's disease (PD) is characterized by dysfunction in frontal cortical and striatal networks that regulate action control. We investigated the pharmacological effect of dopamine agonist replacement therapy on frontal cortical activity and motor inhibition. Using Arterial Spin Labeling MRI, we examined 26 PD patients in the off-and on-dopamine agonist medication states to assess the effect of dopamine agonists on frontal cortical regional cerebral blood flow. Motor inhibition was measured by the Simon task in both medication states. We applied the dual process activation suppression model to dissociate fast response impulses from motor inhibition of incorrect responses. General linear regression model analyses determined the medication effect on regional cerebral blood flow and motor inhibition, and the relationship between regional cerebral blood flow and motor inhibitory proficiency. We show that dopamine agonist administration increases frontal cerebral blood flow, particularly in the pre-supplementary motor area (pre-SMA) and the dorsolateral prefrontal cortex (DLPFC). Higher regional blood flow in the pre-SMA, DLPFC and motor cortex was associated with better inhibitory control, suggesting that treatments which improve frontal cortical activity could ameliorate motor inhibition deficiency in PD patients.

Self‐reported rates of impulsivity in Parkinson’s Disease

“…Furthermore, while previous studies focus on PD patients with and without ICB, we included analyses that self‐assess behavioral symptoms in a healthy cohort. Findings regarding increased motor impulsivity are less consistent, with some studies showing increased motor impulsivity in ICB patients, 15,61 There are no elevations in BIS‐11 motor impulsivity scores and this is consistent with previous studies that show intact behavioral motor inhibitory control in ICB patients 63‐65 and lower self‐reported ratings of motor impulsivity in PD patients with addictions 27 …”

Transcranial Direct Current Stimulation for the Treatment of Parkinson's Disease: Clinical and Regional Cerebral Blood Flow SPECT Outcomes

“…Previous studies suggested that PD was involved in the frontoparietal and frontostriatal network and showed cortical thinning of the middle and superior frontal areas and inferior parietal area on neuroimaging study. 15,16 Therefore, our findings are consistent with the results of these previous studies, because the rCBF of the frontal and parietal areas was changed.…”

“…Cerebral function was evaluated via changes in rCBF on cerebral perfusion SPECT, and the follow‐up images demonstrated significantly increased rCBF in the frontal medial and parietal areas when compared to baseline images. Previous studies suggested that PD was involved in the frontoparietal and frontostriatal network and showed cortical thinning of the middle and superior frontal areas and inferior parietal area on neuroimaging study . Therefore, our findings are consistent with the results of these previous studies, because the rCBF of the frontal and parietal areas was changed.…”

Subcortical Intermittent Theta-Burst Stimulation (iTBS) Increases Theta-Power in Dorsolateral Prefrontal Cortex (DLPFC)

“…The prescribed target was identified according to standard techniques. To localize the DLPFC, we identified the mid-portion of the middle frontal gyrus along its longitudinal axis anterior to the pre-motor area (Trujillo et al, 2019), and designated this point as the midpoint for the subdural electrode. A radiopaque marker (18G needle) was placed at this point using the stereotactic headframe for localization.…”

“…The DLPFC has direct connections to the STN (Haynes and Haber, 2013) and GPi (Middleton and Strick, 2002), as well as widespread connections to the caudate nucleus and to the orbitofrontal, cingulate, premotor, and pre-supplementary motor cortices (Ridderinkhof et al, 2004). In PD patients, functional magnetic resonance imaging (fMRI) studies reveal reduced DLPFC activity during inhibitory control tasks, with increased activity after administration of anti-Parkinsonian medications correlating to improved inhibitory control task performance (Trujillo et al, 2019). Furthermore, EEG studies show that theta-frequency activity is decreased in PD patients performing these tasks (Singh et al, 2018).…”