Levodopa influences striatal activity but does not affect cortical hyper‐activity in Parkinson’s disease

Martinu, Kristina; Degroot, Clotilde; Madjar, Cécile; Strafella, Antonio P.; Monchi, Oury

doi:10.1111/j.1460-9568.2011.07979.x

Cited by 29 publications

(47 citation statements)

References 41 publications

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“…In accordance with these results, we have recently indicated that even within a motor task that solicits both motor and cognitive CBG regions, levodopa has an effect on the motor CBG circuit, but not the cognitive one (Martinu et al, 2012). Although the effect of levodopa on motor symptoms is beneficial, improvement can be seen in some tasks whereas performance on others worsens (Gotham, Brown, & Marsden, 1988;Cooper et al, 1992).…”

Section: Levodopa Treatmentsupporting

confidence: 56%

Cortico-basal ganglia and cortico-cerebellar circuits in Parkinson's disease: Pathophysiology or compensation?

Martinu¹,

Monchi²

2013

Behavioral Neuroscience

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The basal ganglia and the cerebellum are anatomically and functionally linked to the cerebral cortex through a series of well-established circuits. The disruption of dopaminergic projections in Parkinson's disease (PD) leads to an imbalance within these circuits, leading to motor and cognitive symptoms. The cortico-cerebellar (CC) network has often been viewed as a compensatory network, helping the dysfunction of the cortico-basal ganglia (CBG) circuits in PD. However, evidence for this compensatory role is scarce; most changes in cerebellar activity could equally be attributed to pathophysiological changes underlying PD. This paper will review the anatomy, interaction and function of the CBG and CC circuits, the pathophysiological, metabolic, and functional changes observed in PD, as well as the effect of levodopa and deep brain stimulation on these changes. We will use this framework to discuss the pathophysiological and compensatory mechanisms behind CBG and CC circuit activity in PD.

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Section: Levodopa Treatmentsupporting

confidence: 56%

Cortico-basal ganglia and cortico-cerebellar circuits in Parkinson's disease: Pathophysiology or compensation?

Martinu¹,

Monchi²

2013

Behavioral Neuroscience

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“…All patients came for two counterbalanced scanning sessions (one OFF medication, one ON levodopa), and were asked to withdraw from all anti-parkinsonian medications for a minimum of 12 hours prior to each appointment (see [11]). Participants remained off medications for the OFF session.…”

Section: Methodsmentioning

confidence: 99%

“…Participants performed SI, ET and control (CTL) finger movements using left and right hands separately during functional MRI acquisitions in a pseudo-randomised order across runs, in both ON and OFF conditions (previously described in [11]). Each block began with written instructions, displayed for 2.5s, followed by the appearance of five squares oriented in a horizontal row on the screen, each corresponding to a button on the response box.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously shown that the effect of levodopa in PD leads to an increase in activity in the putamen whether movements are SI or ET [11]. We did not, however, investigate the differences in the effect of levodopa on the neural patterns linked to asymmetrically affected hands.…”

Section: Introductionmentioning

confidence: 96%

“…Although patients with PD can also reach movement automaticity, they show greater increases in cortical and cerebellar activity than healthy controls when doing so [9]. We have previously shown that regions implicated in the motor cortico-striatal circuit (putamen, thalamus and premotor cortex) are involved in both SI and ET movements [10], [11]. More specifically, in young healthy adults, we have shown that activity of the putamen increases during repetitive control, ET and SI movements performed with the right hand.…”

Section: Introductionmentioning

confidence: 99%

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Asymmetrical Effect of Levodopa on the Neural Activity of Motor Regions in PD

et al. 2014

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Parkinson's disease (PD) is a neurodegenerative illness often characterized by asymmetrical symptoms. However, the reason for this asymmetry and the cerebral correlates underlying symptom asymmetry are still not well understood. Furthermore, the effects of levodopa on the cerebral correlates of disease asymmetry have not been investigated. In this study, right-handed PD patients performed self-initiated, externally triggered and repetitive control finger movements with both their right and left hands during functional magnetic resonance imaging (fMRI) to investigate asymmetrical effects of levodopa on the hemodynamic correlates of finger movements. Patients completed two experimental sessions OFF and ON medication after a minimum of 12 hours medication withdrawal. We compared the effect of levodopa on the neural activation patterns underlying the execution of both the more affected and less affected hand for self-initiated and externally triggered movements. Our results show that levodopa led to larger differences in cerebral activity for movements of the more affected, left side: there were significant differences in activity after levodopa administration in regions of the motor cortico-striatal network when patients performed self-initiated and externally triggered movements with their left hand. By contrast, when patients used their right hand, levodopa led to differences in cerebellar activity only. As our patients were affected more severely on their left side, we propose that levodopa may help provide additional dopaminergic input, improving movements for the more severely affected side. These results suggest that the impact of reduced dopamine in the cortico-striatal system and the action of levodopa is not symmetrical.

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Frequency-dependent neural activity in Parkinson's disease

Hou

Hallett

et al. 2014

Hum. Brain Mapp.

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The brainstem and basal ganglia are important in the pathophysiology of Parkinson's disease (PD). Reliable and sensitive detection of neural activity changes in these regions should be helpful in scientific and clinical research on PD. In this study, we used resting state functional MRI and amplitude of low frequency fluctuation (ALFF) methods to examine spontaneous neural activity in 109 patients with PD. We examined activity in two frequency bands, slow-4 (between 0.027 and 0.073 Hz) and slow-5 (0.010-0.027 Hz). Patients had decreased ALFF in the striatum and increased ALFF in the midbrain, and changes were more significant in slow-4. Additionally, changes in slow-4 in both basal ganglia and midbrain correlated with the severity of the parkinsonism. The ALFF in the caudate nucleus positively correlated with the dose of levodopa, while the ALFF in the putamen negatively correlated with the disease duration in both slow-4 and slow-5 bands. In addition, the ALFF in the rostral supplementary motor area negatively correlated with bradykinesia subscale scores. Our findings show that with a large cohort of patients and distinguishing frequency bands, neural modulations in the brainstem and striatum in PD can be detected and may have clinical relevance. The physiological interpretation of these changes needs to be determined.

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Levodopa influences striatal activity but does not affect cortical hyper‐activity in Parkinson’s disease

Cited by 29 publications

References 41 publications

Cortico-basal ganglia and cortico-cerebellar circuits in Parkinson's disease: Pathophysiology or compensation?

Cortico-basal ganglia and cortico-cerebellar circuits in Parkinson's disease: Pathophysiology or compensation?

Asymmetrical Effect of Levodopa on the Neural Activity of Motor Regions in PD

Frequency-dependent neural activity in Parkinson's disease

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