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Response monitoring in de novo patients with Parkinson's disease.

ABSTRACT: BACKGROUND: Parkinson's disease (PD) is accompanied by dysfunctions in a variety of cognitive processes. One of these is error processing, which depends upon phasic decreases of medial prefrontal dopaminergic activity. Until now, there is no study evaluating these processes in newly diagnosed, untreated patients with PD ("de novo PD"). METHODOLOGY/PRINCIPAL FINDINGS: Here we report large changes in performance monitoring processes using event-related potentials (ERPs) in de novo PD-patients. The results suggest that increases in medial frontal dopaminergic activity after an error (Ne) are decreased, relative to age-matched controls. In contrast, neurophysiological processes reflecting general motor response monitoring (Nc) are enhanced in de novo patients. CONCLUSIONS/SIGNIFICANCE: It may be hypothesized that the Nc-increase is at costs of dopaminergic activity after an error; on a functional level errors may not always be detected and correct responses sometimes be misinterpreted as errors. This pattern differs from studies examining patients with a longer history of PD and may reflect compensatory processes, frequently occurring in pre-manifest stages of PD. From a clinical point of view the clearly attenuated Ne in the de novo PD patients may prove a useful additional tool for the early diagnosis of basal ganglia dysfunction in PD.

SUBMITTER: Willemssen R

PROVIDER: S-EPMC2657830 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Response monitoring in de novo patients with Parkinson's disease.

Willemssen Rita R Müller Thomas T Schwarz Michael M Falkenstein Michael M Beste Christian C

PloS one 20090327 3

<h4>Background</h4>Parkinson's disease (PD) is accompanied by dysfunctions in a variety of cognitive processes. One of these is error processing, which depends upon phasic decreases of medial prefrontal dopaminergic activity. Until now, there is no study evaluating these processes in newly diagnosed, untreated patients with PD ("de novo PD").<h4>Methodology/principal findings</h4>Here we report large changes in performance monitoring processes using event-related potentials (ERPs) in de novo PD- ...[more]

PMID: 19325909

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Project description:BackgroundParkinson's disease (PD) manifests with the appearance of non-motor symptoms before motor symptoms onset. Among these, dysfunctioning visual structures have recently been reported to occur at early disease stages.ObjectiveThis study addresses effective connectivity in the visual network of PD patients.MethodsUsing functional MRI and dynamic causal modeling analysis, we evaluated the connectivity between the superior colliculus, the lateral geniculate nucleus and the primary visual area V1 in de novo untreated PD patients (n = 22). A subset of the PD patients (n = 8) was longitudinally assessed two times at two months and at six months after starting dopaminergic treatment. Results were compared to those of age-matched healthy controls (n = 22).ResultsOur results indicate that the superior colliculus drives cerebral activity for luminance contrast processing both in healthy controls and untreated PD patients. The same effective connectivity was observed with neuromodulatory differences in terms of neuronal dynamic interactions. Our main findings were that the modulation induced by luminance contrast changes of the superior colliculus connectivity (self-connectivity and connectivity to the lateral geniculate nucleus) was inhibited in PD patients (effect of contrast: p = 0.79 and p = 0.77 respectively). The introduction of dopaminergic medication in a subset (n = 8) of the PD patients failed to restore the effective connectivity modulation observed in the healthy controls.InterpretationThe deficits in luminance contrast processing in PD was associated with a deficiency in connectivity adjustment from the superior colliculus to the lateral geniculate nucleus and to V1. No differences in cerebral blood flow were observed between controls and PD patients suggesting that the deficiency was at the neuronal level. Administration of a dopaminergic treatment over six months was not able to normalize the observed alterations in inter-regional coupling. These findings highlight the presence of early dysfunctions in primary visual areas, which might be used as early markers of the disease.

Project description:BACKGROUND:Commonly used neuroimaging biomarkers in Parkinson's disease (PD) are useful for diagnosis but poor at predicting outcomes. We explored whether an atrophy pattern from whole-brain structural MRI, measured in the drug-naïve early stage, could predict PD prognosis. METHODS:362 de novo PD patients with T1-weighted MRI (n = 222 for the main analysis, 140 for the validation analysis) were recruited from the Parkinson's Progression Markers Initiative (PPMI). We investigated a previously identified PD-specific network atrophy pattern as a potential biomarker of disease severity and prognosis. Progression trajectories of motor function (MDS-UPDRS-part III), cognition (Montreal Cognitive Assessment (MoCA)), and a global composite outcome measure were compared between atrophy tertiles using mixed effect models. The prognostic value of the MRI atrophy measure was compared with 123I ioflupane single photon emission computed tomography, the postural-instability-gait-disturbance score, and cerebrospinal fluid markers. FINDINGS:After 4.5 years follow-up, PD-specific atrophy network score at baseline significantly predicted change in UPDRS-part III (r = -0.197, p = .003), MoCA (r = 0.253, p = .0002) and global composite outcome (r = -0.249, p = .0002). Compared with the 3rd tertile (i.e. least atrophy), the tertile with the highest baseline atrophy (i.e. the 1st tertile) had a 3-point annual faster progression in UPDRS-part III (p = .012), faster worsening of posture-instability gait scores (+0.21 further annual increase, p < .0001), faster decline in MoCA (-0.74 further annual decline in MoCA, p = .0372) and a + 0.38 (p = .0029) faster annual increase in the global composite z-score. All findings were replicated in a validation analysis using 1.5T MRI. Receiver operating characteristic analysis confirmed the superiority of the MRI biomarker, although it had modest AUC values (0.63). By comparison, the other biomarkers were limited in their ability to predict prognosis either in the main or validation analysis. INTERPRETATION:A PD-specific network atrophy pattern predicts progression of motor, cognitive, and global outcome in PD, and is a better predictor of prognosis than any of the other tested biomarkers. Therefore, it has potential as a prognostic biomarker for clinical trials of early PD.

Dataset Information

Response monitoring in de novo patients with Parkinson's disease.

Publications

Response monitoring in de novo patients with Parkinson's disease.

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