Unmedicated Parkinson's Disease Patients Research Articles

Antiparkinsonian medication masks motor signal progression in de novo patients

Patients not yet receiving medication provide insight to drug-naïve early physiology of Parkinson's Disease (PD). Wearable sensors can measure changes in motor features before and after introduction of antiparkinsonian medication. We aimed to identify features of upper limb bradykinesia, postural stability, and gait that measurably progress in de novo PD patients prior to the start of medication, and determine whether these features remain sensitive to progression in the period after commencement of antiparkinsonian medication.Upper limb motion was measured using an inertial sensor worn on a finger, while postural stability and gait were recorded using an array of six wearable sensors. Patients were tested over nine visits at three monthly intervals. The timepoint of start of medication was noted.Three upper limb bradykinetic features (finger tapping speed, pronation supination speed, and pronation supination amplitude) and three gait features (gait speed, arm range of motion, duration of stance phase) were found to progress in unmedicated early-stage PD patients. In all features, progression was masked after the start of medication.Commencing antiparkinsonian medication is known to lead to masking of progression signals in clinical measures in de novo PD patients. In this study, we show that this effect is also observed with digital measures of bradykinetic and gait motor features.

Dopamine replacement remediates risk aversion in Parkinson's disease in a value-independent manner

IntroductionClinical evidence suggests that Parkinson's Disease (PD) patients are risk averse. Dopaminergic therapy has been reported to increase risk tolerance, but the underlying mechanisms are unclear. Some studies have suggested an amplification of subjective reward value, consistent with the role of dopamine in reward value coding. Others have reported value-independent risk enhancement. We evaluated the value-dependence of the effects of PD and its therapy on risk using tasks designed to sensitively measure risk over a wide range of expected values. Method36 patients with idiopathic PD receiving levodopa monotherapy and 36 healthy matched controls performed two behavioural economic tasks aimed at quantifying 1) risk tolerance/aversion in the gain frame and 2) valuation of potential gains relative to losses. PD patients performed the tasks on and off their usual dose of levodopa in randomized order; controls performed the same tasks twice. ResultsRelative to the controls, unmedicated PD patients showed significant value-independent risk aversion in the gain frame, which was normalized by levodopa. PD patients did not differ from controls in their valuation of gains relative to losses. However, across both tasks and regardless of medication, choices of the patients were more determined by expected values of the prospects than those of controls. ConclusionDopamine deficiency in PD was associated with risk aversion, and levodopa promoted riskier choice in a value-independent manner. PD patients also showed an increased sensitivity to expected value, which was independent of levodopa and does not appear to result directly from dopamine deficiency.

Dopamine substitution alters effective connectivity of cortical prefrontal, premotor, and motor regions during complex bimanual finger movements in Parkinson's disease

Bimanual coordination is impaired in Parkinson's disease (PD), affecting patients' quality of life. Besides dysfunction of the basal ganglia network, alterations of cortical oscillatory coupling, particularly between prefrontal and (pre-)motoric areas, are thought to underlie this impairment. Here, we studied 16 PD patients OFF and ON medication and age-matched healthy controls recording high-resolution electroencephalography (EEG) during performance of spatially coupled and uncoupled bimanual finger movements. Dynamic causal modeling (DCM) for induced responses was used to infer task-induced effective connectivity within a network comprising bilateral prefrontal cortex (PFC), lateral premotor cortex (lPM), supplementary motor area (SMA), and primary motor cortex (M1). Performing spatially coupled movements, excitatory left-hemispheric PFC to lPM coupling was significantly stronger in controls compared to unmedicated PD patients. Levodopa-induced enhancement of this connection correlated with increased movement accuracy. During performance of spatially uncoupled movements, PD patients OFF medication exhibited inhibitory connectivity from left PFC to SMA. Levodopa intake diminished these inhibitory influences and restored excitatory PFC to lPM coupling. This restoration, however, did not improve motor function.Concluding, our results indicate that lateralization of prefrontal to premotor connectivity in PD can be augmented by levodopa substitution and is of compensatory nature up to a certain extent of complexity.

GPi Oscillatory Activity Differentiates Tics from the Resting State, Voluntary Movements, and the Unmedicated Parkinsonian State.

Background: Deep brain stimulation (DBS) is an emerging treatment strategy for severe, medication-refractory Tourette syndrome (TS). Thalamic (Cm-Pf) and pallidal (including globus pallidus interna, GPi) targets have been the most investigated. While the neurophysiological correlates of Parkinson's disease (PD) in the GPi and subthalamic nucleus (STN) are increasingly recognized, these patterns are not well characterized in other disease states. Recent findings indicate that the cross-frequency coupling (CFC) between beta band and high frequency oscillations (HFOs) within the STN in PD patients is pathologic.Methods: We recorded intraoperative local field potentials (LFPs) from the postero-ventrolateral GPi in three adult patients with TS at rest, during voluntary movements, and during tic activity and compared them to the intraoperative GPi-LFP activity recorded from four unmedicated PD patients at rest.Results: In all PD patients, we noted excessive beta band activity (13–30 Hz) at rest which consistently modulated the amplitude of the co-existent HFOs observed between 200 and 400 Hz, indicating the presence of beta-HFO CFC. In all 3TS patients at rest, we observed theta band activity (4–7 Hz) and HFOs. Two patients had beta band activity, though at lower power than theta oscillations. Tic activity was associated with increased high frequency (200–400 Hz) and gamma band (35–200 Hz) activity. There was no beta-HFO CFC in TS patients at rest. However, CFC between the phase of 5–10 Hz band activity and the amplitude of HFOs was found in two TS patients. During tics, this shifted to CFC between the phase of beta band activity and the amplitude of HFOs in all subjects.Conclusions: To our knowledge this is the first study that shows that beta-HFO CFC exists in the GPi of TS patients during tics and at rest in PD patients, and suggests that this pattern might be specific to pathologic/involuntary movements. Furthermore, our findings suggest that during tics, resting state 5–10 Hz-HFO CFC shifts to beta-HFO CFC which can be used to trigger stimulation in a closed loop system when tics are present.

Ipsilateral deficits of dopaminergic neurotransmission in Parkinson's disease.

The nigral lesion and the resulting contralateral motor signs of Parkinson's disease (PD) are remarkably asymmetric. This study investigated the prevalence of patients with "wrong-sided" lesions, that is, patients with symptoms on the side ipsilateral to the predominant dopaminergic nigrostriatal deficit. The analyzed sample included 434 early unmedicated PD patients from the Parkinson's Progression Markers Initiative database. Asymmetry indices of motor function and putamen [(123)I]FP-CIT SPECT were calculated from the screening visit data. Ipsilateral deficits were unexpectedly common even when only patients with clear motor and dopaminergic asymmetries were included in the analysis (8.1%, n = 24/295). When patients with any asymmetry were included in the analysis, the prevalence of ipsilateral deficits was 15.4% (n = 65/423). Wrong-sided symptoms were not associated with the PD motor subtype. However, the dataset was heavily biased toward tremor-dominant patients (85% of patients). Right-handed PD patients had predominantly right-sided motor symptoms and left-sided dopamine defects, whereas the effect was opposite in left-handed patients (P = 0.005 and 0.028, respectively). The results indicate that the side of the predominant motor symptoms and the corresponding side of the dopaminergic defects in PD are not random, but are directed by brain lateralization. Importantly, the traditional pathogenetic model of nigral degeneration causing primarily contralateral motor symptoms may be inadequate in many patients.

Neuropsychiatric and cognitive symptoms and body side of onset of parkinsonism in unmedicated Parkinson's disease patients.

The onset of motor symptoms is primarily unilateral in the majority of Parkinson's disease (PD) patients. Because of the lateralization of several cognitive and neuropsychiatric functions and the role of impaired dopaminergic transmission on non-motor symptoms in PD, the question raises whether body side of onset of parkinsonian motor symptoms might influence cognitive and/or neuropsychiatric domains in idiopathic PD. Here we investigated the prevalence and severity of neuropsychiatric and cognitive alterations in a cohort of 84 drug naïve PD patients, divided into two groups according to the body side of onset of motor symptoms (42 left onset PD patients-LPD and 42 right onset PD patients-RPD). Eighty-four age-, sex- and educational level-matched healthy subjects (HC) served as controls. Both LPD and RPD patients had higher prevalence and severity of neuropsychiatric and cognitive symptoms with respect to HC. There were no difference between LPD and RPD as to the pattern or severity of neuropsychiatric and cognitive symptoms. However, significantly higher percentage of LPD patients than RPD deviated more than 1.5 SD from mean values of HC at scales for depression. Our results indicate that in early PD patients side of onset of parkinsonian motor symptoms does not influence non-motor accompanying signs, at least at neuropsychiatric and neuropsychological domains, and suggest that differences reported by previous reports may be secondary to disease progression and/or dopamine replacement therapy.

Antisaccades and executive dysfunction in early drug-naive Parkinson's disease: The discovery study.

Cognitive impairment is well recognized in Parkinson's disease (PD), but when it begins to develop is unclear. The aim of this study was to identify early signs of cognitive impairment along with abnormalities in saccadic behavior in newly diagnosed unmedicated PD patients. Nineteen drug-naive PD patients and 20 controls were examined using a battery of tests, including an antisaccade task, phonemic and semantic verbal fluencies, and a switching and rule finding task. With simple tasks, no differences were found between the two groups. However, cognitive performance of the two groups diverged with more complex tasks, occurring independently of PD-related motor impairment. Patients exhibited higher antisaccadic error rates and switch costs in the task switching test, and performed significantly worse in the rule finding task. Certain cognitive domains and saccadic parameters are already significantly impoverished in newly diagnosed Parkinson's patients, even before the initiation of medication.

Factors underlying probabilistic and deterministic stimulus-response learning performance in medicated and unmedicated patients with Parkinson’s disease.

Prior studies have not tested individual differences or effects of medication dosage on stimulus-response learning in patients with Parkinson's disease (PD). In the current study, we investigated the effects of motor variables (including tremor, akinesia, and disease duration) as well as dopaminergic medication dosage on learning in unmedicated PD patients, medicated PD patients, and healthy controls. We tested all subjects on probabilistic and deterministic learning tasks, and also collected awareness measures data using postexperimental questionnaires. Importantly, we tested learning performance in tremor-dominant and akinesia-dominant PD patients, and further correlated learning performance with disease duration and medication dosage. Results show that akinesia-dominant patients were more impaired than tremor-dominant patients at probabilistic reward- but not punishment-based learning, which is in agreement with prior studies of the relationship between akinesia and basal ganglia dysfunction. We also found no difference between medicated and unmedicated PD patients in reward- or punishment-based deterministic learning, but medicated patients were better than unmedicated patients at reward-based probabilistic learning. Our results show that awareness measures explain differences among probabilistic and deterministic learning performance. Moreover, we found that disease duration and motor severity are inversely correlated, and medication dosage is positively correlated, with reward-based probabilistic learning. Our results suggest that stimulus-response learning performance in patients with PD depends on the type of learning (probabilistic vs. deterministic), medication status (on vs. off medication, dopaminergic medication dosage), disease duration as well as motor severity and subtype in PD patients (tremor- vs. akinesia-dominant).

Parkinson's disease cognitive network correlates with caudate dopamine

Prior evidence has suggested a link between caudate dopaminergic functioning and cognition in Parkinson's disease (PD). In this dual tracer study we analyzed the relationship between nigrostriatal dopaminergic dysfunction and the expression of the previously validated PD cognition-related metabolic pattern (PDCP). In this study, 17 non-demented PD patients underwent positron emission tomography (PET) imaging with [(18)F]-fluorodeoxyglucose to measure PDCP expression, and [(18)F]-fluoropropyl-β-CIT (FPCIT) to measure dopamine transporter (DAT) binding. Automated voxel-by-voxel searches of the FPCIT PET volumes were performed to identify regions in which DAT binding significantly correlated with PDCP expression values. The findings were validated using prespecified anatomical regions-of-interest (ROIs). Voxel-wise interrogation of the FPCIT PET scans revealed a single significant cluster in which DAT binding correlated with PDCP expression (p<0.05, corrected). This cluster was localized to the left caudate nucleus; an analogous correlation (r=-0.63, p<0.01) was also present in the "mirror" region of the right hemisphere. These findings were confirmed by the presence of a significant correlation (r=-0.67, p<0.005) between PDCP expression and DAT binding in caudate ROIs, which survived adjustment for age, disease duration, and clinical severity ratings. Correlation between caudate DAT binding and subject expression of the PD motor-related metabolic pattern was not significant (p>0.21). In summary, this study demonstrates a significant relationship between loss of dopaminergic input to the caudate nucleus and the expression of a cognition-related disease network in unmedicated PD patients. These baseline measures likely function in concert to determine the cognitive effects of dopaminergic therapy in PD.

Cognitive slowing in Parkinson's disease is related to frontostriatal dopaminergic dysfunction

BackgroundFrontostriatal and cognitive dysfunctions in Parkinson's disease (PD) are hypothesized to be linked predominately to dopaminergic dysfunction within neural networks linking dorsal striatum to dorsolateral prefrontal cortex. MethodsThe authors evaluated the relationship between frontostriatal dopaminergic function and cognitive performance, especially cognitive processing speed by performing [18F]fluorodopa PET and computerized tests of automatic and controlled cognitive processing speed (CogniSpeed) in 23 newly diagnosed and unmedicated PD patients and 14 controls. ResultsPD patients were slower than the controls in all the CogniSpeed measures studied. The Fdopa uptake in caudate nucleus correlated negatively with slowing on all the tests. Slower performance in relatively automatic processes measured by choice reaction tasks as well as in more controlled processes measured by a calculation task was related to reduced Fdopa uptake in the anterior cingulate gyrus. The reduced dopaminergic function in the thalamus was associated with the slower performance in the subtraction test. ConclusionOur study indicates that dopaminergic dysfunction within neural networks linking striatum to prefrontal cortex is involved in the slowing of both automatic and controlled cognitive processing in PD patients.

Reduced Striatal Dopamine Synthesis Capacity is Associated with Symptoms of Depression in Patients with de novo Unmedicated Parkinson's Disease

Previous studies have suggested that impaired striatal dopamine function might be independently related to depression in patients with Parkinson's disease (PD), but the results are not uniform. In this study, we investigated de novo unmedicated and medicated PD patients with more advanced disease using 18F-fluorodopa-PET. In unmedicated de novo patients, but not in medicated patients, higher depression scores were associated with lower striatal 18F-fluorodopa uptake. These results indicate that impaired striatal dopaminergic function in PD is related to depressive symptoms and that these effects can be observed in de novo patients without the confounding effects of advanced neurodegeneration and medications.

Dissociation between Active and Observational Learning from Positive and Negative Feedback in Parkinsonism

Feedback to both actively performed and observed behaviour allows adaptation of future actions. Positive feedback leads to increased activity of dopamine neurons in the substantia nigra, whereas dopamine neuron activity is decreased following negative feedback. Dopamine level reduction in unmedicated Parkinson’s Disease patients has been shown to lead to a negative learning bias, i.e. enhanced learning from negative feedback. Recent findings suggest that the neural mechanisms of active and observational learning from feedback might differ, with the striatum playing a less prominent role in observational learning. Therefore, it was hypothesized that unmedicated Parkinson’s Disease patients would show a negative learning bias only in active but not in observational learning. In a between-group design, 19 Parkinson’s Disease patients and 40 healthy controls engaged in either an active or an observational probabilistic feedback-learning task. For both tasks, transfer phases aimed to assess the bias to learn better from positive or negative feedback. As expected, actively learning patients showed a negative learning bias, whereas controls learned better from positive feedback. In contrast, no difference between patients and controls emerged for observational learning, with both groups showing better learning from positive feedback. These findings add to neural models of reinforcement-learning by suggesting that dopamine-modulated input to the striatum plays a minor role in observational learning from feedback. Future research will have to elucidate the specific neural underpinnings of observational learning.

Elevation of oxidized DJ-1 in the brain and erythrocytes of Parkinson disease model animals

DJ-1, the causative gene of a familial form of Parkinson's disease (PD), has been reported undergo oxidation preferentially at the 106th cysteine residue (Cys-106) under oxidative stress. Recently, it has been found that the levels of oxidized DJ-1 in erythrocytes of unmedicated PD patients are markedly higher than those in medicated PD patients and healthy subjects. In the present study, we examined the changes in oxidized DJ-1 levels in the brain and erythrocytes of PD animal models using specific antibodies against Cys-106-oxidized DJ-1. Treatment with PD model compounds such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 6-hydroxydopamine significantly elevated the levels of oxidized DJ-1 in erythrocytes. Immunohistochemical analysis also revealed that the number of oxidized DJ-1 antibody-positive cells in the substantia nigra of MPTP-treated mouse increased in a dose-dependent manner. These results suggest that the oxidative modification of DJ-1 in the brain and erythrocytes is involved in the pathogenesis of PD in animal models.

Serotonergic neurotransmission in early Parkinson's disease: A pilot study to assess implications for depression in this disorder

Objectives. Depression, a disease usually accompanied by a serotonergic deficit, has been observed in about 40% of patients suffering from Parkinson's disease (PD). Thus, a serotonergic dysfunction in PD can be assumed. We aimed to investigate the interaction between serotonergic (5-HT) and dopaminergic activity in early PD. We hypothesized a serotonergic as well as a dopaminergic deficit in PD patients. We also assumed a correlation between these neurotransmitters indicating a relationship between dopaminergic and serotonergic function in PD. Methods. Nine unmedicated PD patients before and 12 weeks after l-dopa treatment and nine healthy subjects were examined using the loudness dependence of auditory evoked potentials (LDAEP), a promising indicator of central serotonergic function. Dopaminergic transporters (DAT) were collected using 123I-FP-CIT and single photon emission computer tomography (SPECT). LDAEP values were correlated with 123I-FP-CIT SPECT data. Results. A significant difference between LDAEP of controls and patients (P= 0.05) suggested lower serotonergic activity in PD. Twelve weeks after initiation of l-dopa treatment this difference was lost between patients and controls (P= 0.20). There was a trend towards a correlation between LDAEP and DAT (r= 0.65; P = 0.057) of the unmedicated patients, suggesting a low serotonergic activity may be related to a dopamine deficit in PD. Conclusions. Our results support the hypothesis that serotonergic neurotransmission is decreased in untreated PD and suggest that a low serotonergic activity may be related to the dopamine pathology in PD. This could be related to the high prevalence of depression in PD.

Preparation and application of monoclonal antibodies against oxidized DJ-1. Significant elevation of oxidized DJ-1 in erythrocytes of early-stage Parkinson disease patients

DJ-1 was initially identified as a novel oncogene and has recently been found to be a causative gene for a familial form of Parkinson's disease (PD), viz, PARK7. Cysteine residue at position 106 (Cys-106) in DJ-1 was found to be oxidized preferentially under oxidative stress. In the present study, we developed specific antibodies against Cys-106-oxidized DJ-1 using baculovirus particles displaying the surface glycoprotein gp64-fusion protein as the immunizing agent. Western blot analysis combined with two-dimensional gel electrophoresis revealed that these antibodies specifically recognized oxidized DJ-1. Furthermore, we developed a competitive enzyme-linked immunosorbent assay (ELISA) for detecting oxidized DJ-1 and measured blood levels of oxidized DJ-1 in PD patients ( n = 15). It was observed that the levels of oxidized DJ-1 in erythrocytes of unmedicated PD patients were markedly higher without overlap than those of medicated PD patients and healthy subjects. No significant difference was observed in DJ-1 levels between mediated and unmediated PD patient. These results suggest the oxidative modification of DJ-1 in PD patients and the potential application of the antibody for diagnosis of PD at early-stage.

Dopaminergic Suppression of Brain Deactivation Responses during Sequence Learning

Cognitive processing is associated with deactivation of the default mode network. The presence of dopaminoceptive neurons in proximity to the medial prefrontal node of this network suggests that this neurotransmitter may modulate deactivation in this region. We therefore used positron emission tomography to measure cerebral blood flow in 15 Parkinson's disease (PD) patients while they performed a motor sequence learning task and a simple movement task. Scanning was conducted before and during intravenous levodopa infusion; the pace and extent of movement was controlled across tasks and treatment conditions. In normal and unmedicated PD patients, learning-related deactivation was present in the ventromedial prefrontal cortex (p < 0.001). This response was absent in the treated condition. Treatment-mediated changes in deactivation correlated with baseline performance (p < 0.002) and with the val(158)met catechol-O-methyltransferase genotype. Our findings suggest that dopamine can influence prefrontal deactivation during learning, and that these changes are linked to baseline performance and genotype.

The recognition of facial emotion expressions in Parkinson's disease

A limited number of studies in Parkinson's Disease (PD) suggest a disturbance of recognition of facial emotion expressions. In particular, disgust recognition impairment has been reported in unmedicated and medicated PD patients. However, the results are rather inconclusive in the definition of the degree and the selectivity of emotion recognition impairment, and an associated impairment of almost all basic facial emotions in PD is also described. Few studies have investigated the relationship with neuropsychiatric and neuropsychological symptoms with mainly negative results. This inconsistency may be due to many different problems, such as emotion assessment, perception deficit, cognitive impairment, behavioral symptoms, illness severity and antiparkinsonian therapy. Here we review the clinical characteristics and neural structures involved in the recognition of specific facial emotion expressions, and the plausible role of dopamine transmission and dopamine replacement therapy in these processes. It is clear that future studies should be directed to clarify all these issues.

Impaired dimensional selection but intact use of reward feedback during visual discrimination learning in Parkinson's disease

It has been suggested that Parkinson's disease (PD) impairs the ability to learn on the basis of reward or reinforcing feedback i.e., by trial-and-error. In many learning tasks, particular ‘dimensions’ of stimulus information are relevant whilst others are irrelevant; therefore, efficient performance depends on identifying the dimensions of these ‘compound’ stimuli and selecting the relevant dimension for further processing. We investigated the ability of patients with PD, as well as patients with Huntington's disease and patients with frontal or temporal lobe lesions, to learn visual discriminations which required either a number of associations to be learned concurrently (the ‘eight-pair’ task) or the selection of information from compound stimuli (the ‘five-dimension’ task), both tasks being learned by trial-and-error. None of the basal ganglia disorder patient groups was impaired on the eight-pair task, militating against a crucial role for these brain structures in trial-and-error learning per se. Patients with mild, medicated PD, but not unmedicated PD patients, were impaired at identifying all five feature dimensions in the five-dimension task, implying dopaminergic ‘overdosing’ of the ability to analyse compound stimuli in terms of their component dimensions. Temporal lobe lesion patients performed similarly, suggesting that the temporal lobe may be the site of the medication overdose effect. Patients with severe, medicated PD were impaired at compound discrimination learning on the five-dimension task in the absence of an underlying impairment in identifying component stimulus dimensions; this pattern resembled that seen in Huntington's disease and frontal lobe lesion patients, implying that fronto-striatal circuitry is involved in the formation of rules based upon selected stimulus dimensions.

Personality traits and brain dopaminergic function in Parkinson's disease.

A distinctive personality type, characterized by introversion, inflexibility, and low novelty seeking, has been suggested to be associated with Parkinson's disease. To test the hypothesis that Parkinson's disease is associated with a specific dopamine-related personality type, the personality structures of 61 unmedicated Parkinson's disease patients and 45 healthy controls were examined. Additionally, in 47 Parkinson's disease patients, the dopaminergic function in the brain was directly measured with 6-[(18)F]fluoro-l-dopa ((18)F-dopa) positron emission tomography (PET) with MRI coregistration. The novelty-seeking personality score, supposedly associated with the parkinsonian personality, was slightly lower in the Parkinson's disease group compared with controls, but it did not have a significant relationship with (18)F-dopa uptake in any of the brain regions studied (r = -0.12 to 0.11, P > 0.15). The harm-avoidance personality score, associated with anxiety and depression, was clearly increased in patients with Parkinson's disease and it had a paradoxical, highly significant positive correlation with the (18)F-dopa uptake in the right caudate nucleus (r = 0.53, P = 0.04, Bonferroni corrected for 220 comparisons). Although the results of this study are not in disagreement with the concept of low-novelty-seeking personality type in Parkinson's disease, the personality type does not seem to be dopamine dependent. The correlation between the personality trait of harm avoidance and (18)F-dopa may reflect a specific feedback circuitry of neurotransmitters that is associated with negative emotionality in Parkinson's disease.

Preprogramming and control activity of bimanual self-paced motor task in Parkinson's disease

Objective: The authors investigated programming (Bereitschaftspotential or BP) and control activity (Skilled Performance Positivity or SPP) of a bimanual, sequential, skilled motor act in off-therapy Parkinson's disease (PD) patients.Methods: We recorded Movement Related Potentials (MRPs) in 12, non-demented, off-therapy parkinsonian patients and in 17 control subjects who were performing a skilled, time-locked motor act, which was not routine in their everyday life but had to be learned: the Skilled Performance Task (SPT). BP, SPP and correct performances were evaluated in grand average waveforms and in sequential blocks.Results: The analysis of correct performances showed that accuracy in PD patients was significantly lower than in the control group and this accuracy did not improve throughout the blocks. A significantly low level of performances was associated with an increased BP amplitude (P<0.05) and decreased SPP amplitude (P<0.05) in PD patients.Conclusion: Our findings suggest that skill motor learning is impaired in non-demented unmedicated PD patients. We discuss the view that PD patients may allocate more attentional resources, as suggested by the increased BP amplitude, the decreased SPP amplitude and the low correct performances, in order to perform a new skilled motor act.