Long term treatment and disease severity change brain responses to levodopa in Parkinson's disease

Hershey, Tamara; Black, Kevin J.; Carl, Juanita L.; McGee‐Minnich, Lori; Snyder, Abraham Z.; Perlmutter, Joel S.

doi:10.1136/jnnp.74.7.844

Cited by 74 publications

(76 citation statements)

References 48 publications

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“…Subjects were pretreated with 200 mg oral carbidopa, given at least 2 h before levodopa infusion [16,38]. TD subjects also completed a detailed self-report of lifetime symptoms and treatment [65].…”

Section: Protocolmentioning

confidence: 99%

“…First, levodopa is well tolerated in normal individuals and in TD [9,16], whereas dopamine antagonists such as haloperidol often cause akathisia or other distressing motor side effects. Second, when dopamine production outside the brain is adequately inhibited by a peripheral decarboxylase inhibitor like carbidopa, levodopa does not alter global cerebral blood flow [34,36,38]. This characteristic allows us to use qualitative measurements of blood flow such as blood oxygenation level-dependent (BOLD) signal in fMRI to determine the impact of levodopa on brain activity without misrepresenting an absolute change in local flow or neuronal activity [10,15,27].…”

Section: Introductionmentioning

confidence: 99%

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Dopaminergic modulation of response inhibition: an fMRI study

HERSHEY

2004

Cognitive Brain Research

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Dopamine has been hypothesized to modulate response inhibition. To test this hypothesis, we used functional magnetic resonance imaging (fMRI) to measure the effects of the dopamine prodrug levodopa on the brain responses to a well-validated response inhibition task (go/no-go, or GNG). Since abnormalities of response inhibition and dopamine have been thought to underlie tics and other symptoms of Tourette syndrome, we studied 8 neuroleptic-naive adults with tic disorders as well as 10 well-matched healthy controls. Subjects were pretreated with the peripheral decarboxylase inhibitor carbidopa, then scanned during GNG and control blocks, both before and during i.v. levodopa infusion. Both groups had similar task performance and task-related regional brain activity before and during levodopa infusion. Levodopa did not affect reaction times or accuracy, so fMRI findings can be interpreted without concern that they simply reflect a performance difference between conditions. Levodopa did affect the magnitude of GNG-related fMRI responses in the right cerebellum and right parietal cortex, significantly reducing both. Pre-levodopa activity in the right cerebellum correlated with reaction times (higher magnitudes associated with faster reaction times), and pre-levodopa activity in the right parietal cortex correlated with false alarm rate (higher magnitudes associated with higher error). In summary, right parietal and cerebellar regions important in mediating specific aspects of the GNG task were modulated by levodopa, suggesting a region-specific role for dopamine in response inhibition. D 2004 Elsevier B.V. All rights reserved.Theme: Neural basis of behavior Topic: Cognition

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Section: Protocolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dopaminergic modulation of response inhibition: an fMRI study

HERSHEY

2004

Cognitive Brain Research

Self Cite

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“…A dose 41 of levodopa estimated to fill each subject's volume of distribution at a target concentration of 1 600ng/mL was infused over 10 minutes, followed until the second PET scan of the day was 2 completed by a maintenance infusion at a rate estimated to compensate for elimination. In prior 3 work, these infusion rates produced a mean blood level across subjects of ~625ng/mL after 25 4 minutes of infusion (Black et al 2003 …”

Section: Levodopa Infusion 40mentioning

confidence: 94%

Levodopa-stimulated dopamine release in Tourette syndrome

Black

Piccirillo

Koller

et al. 2013

Preprint

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“…Other groups have also reported levodopa activation imaging studies in PD, as reviewed in part by Hershey et al (2003). An early PET study found no rCBF differences after levodopa in 10 motor fluctuators (Melamed et al, 1986).…”

Section: Regional Cbf Response To Levodopa In the Whole Samplementioning

confidence: 99%

Levodopa Challenge Neuroimaging of Levodopa-Related Mood Fluctuations in Parkinson's Disease

Black

Hershey

Hartlein

et al. 2004

Neuropsychopharmacol

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Some patients with advanced Parkinson's disease (PD) develop dose-related fluctuations in mood. This may reflect alterations in dopamine-influenced brain circuits that mediate emotion. However, there is no available information to localize which dopamineinfluenced neurons may be most affected. Eight patients with PD and clinically significant levodopa-related mood fluctuations (mania, depression, or anxiety) were compared to 13 patients with similarly severe PD and fluctuations of motor function but not of mood. Regional cerebral blood flow (rCBF) was measured with positron emission tomography before and after levodopa (in the presence of carbidopa). The rCBF response to levodopa in medial frontal gyrus and posterior cingulate cortex (PCC) significantly differed between mood fluctuators and control patients (corrected po0.02). Other regions with uncorrected po0.001 in this comparison were cortical Brodmann areas 22, 40, 13, 11, and 28, hippocampus, and claustrum. The levodopa activation paradigm detected group differences not evident in a comparison of resting rCBF. Abnormalities of dopamine innervation may produce mood fluctuations via effects on PCC, an area strongly linked to mood and anxiety and with known rCBF responsiveness to levodopa or D2-like dopamine receptor agonists. We speculate that mood fluctuations may arise in parkinsonian patients who have abnormal dopaminergic modulation of caudate nucleus, anterior cingulate cortex, or orbital frontal cortex, all of which innervate PCC. The findings require confirmation in larger and bettermatched groups.

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Long term treatment and disease severity change brain responses to levodopa in Parkinson's disease

Cited by 74 publications

References 48 publications

Dopaminergic modulation of response inhibition: an fMRI study

Dopaminergic modulation of response inhibition: an fMRI study

Levodopa-stimulated dopamine release in Tourette syndrome

Levodopa Challenge Neuroimaging of Levodopa-Related Mood Fluctuations in Parkinson's Disease

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