scholarly journals Flanker Task-Elicited Event-Related Potential Sources Reflect Human Recombinant Erythropoietin Differential Effects on Parkinson’s Patients

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Maria L. Bringas Vega ◽  
Shengnan Liu ◽  
Min Zhang ◽  
Ivonne Pedroso Ibañez ◽  
Lilia M. Morales Chacon ◽  
...  

We used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson’s Disease patients. The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low resolution tomography (LORETA) inverse solution was employed to localize the neural generators. Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs. From our results rHuEPO seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus were evoked by incongruent stimuli differentiated PD and HCs.

2019 ◽  
Author(s):  
Maria L Bringas Vega ◽  
Shengnan Liu ◽  
Min Zhang ◽  
Ivonne Pedroso Ibañez ◽  
Lilia M. Morales Chacon ◽  
...  

AbstractWe used EEG source analysis to identify which cortical areas were involved in the automatic and controlled processes of inhibitory control on a flanker task and compared the potential efficacy of recombinant-human erythropoietin (rHuEPO) on the performance of Parkinson’ s Disease patients.The samples were 18 medicated PD patients (nine of them received rHuEPO in addition to their usual anti-PD medication through random allocation and the other nine patients were on their regular anti-PD medication only) and 9 age and education-matched healthy controls (HCs) who completed the flanker task with simultaneous EEG recordings. N1 and N2 event-related potential (ERP) components were identified and a low-resolution tomography (LORETA) inverse solution was employed to localize the neural generators.Reaction times and errors were increased for the incongruent flankers for PD patients compared to controls. EEG source analysis identified an effect of rHuEPO on the lingual gyri for the early N1 component. N2-related sources in middle cingulate and precuneus were associated with the inhibition of automatic responses evoked by incongruent stimuli differentiated PD and HCs.From our results rHuEPO, seems to mediate an effect on N1 sources in lingual gyri but not on behavioural performance. N2-related sources in middle cingulate and precuneus evoked by incongruent stimuli differentiated PD and HCs.


1992 ◽  
Vol 2 (9) ◽  
pp. 1405-1416
Author(s):  
A Besarab ◽  
K K Flaharty ◽  
A J Erslev ◽  
J B McCrea ◽  
P H Vlasses ◽  
...  

The clinical pharmacology of human recombinant erythropoietin (epoetin) was studied in order to compare the effectiveness of various routes and dosing schedules in dialysis patients. Thirty-six patients received epoetin beta three times a week i.v. for at least 12 wk. The mean dose needed to achieve target hemoglobin was 225 +/- 36 U/kg per week (median dose, 180 U/kg per week). Twenty-eight of 36 patients who were converted to a once-a-week i.v. schedule increased their requirements to 429 +/- 50 U/kg per week in order to maintain a target hematocrit of 33 to 40 vol%. Twelve of 28 patients could maintain their target hematocrit when dosed once a week s.c. at 84 +/- 10 U/kg. The other 16 patients required 137 +/- 15 U/kg per week divided into two doses. In the entire group of 28 patients, the weekly requirement for epoetin was reduced by 50% when the s.c. route was used two or three times a week. Pharmacokinetic studies performed during chronic therapy indicated rapid clearance of erythropoietin (t1/2 of 6.8 +/- 0.3 h). Single i.v. doses greater than 150 U/kg were required to increase basal erythropoietin by 30 mU/mL at 44 h postdosing. With s.c. dosing, such increments in erythropoietin levels frequently persisted beyond 60 h because of prolonged and slow absorption. Pharmacokinetic simulations in conjunction with clinical correlation of the erythropoietic response suggest that the duration that the erythropoietin levels are maintained, and not the absolute peaks, is the primary determinant of efficacy. This may result from nonlinearity in the dose response. Pharmacokinetic simulation also indicated that i.v. dosing could not maintain adequate interdialytic erythropoietin levels, whereas s.c. dosing could. Cost analysis indicated that the use of s.c. dosing two or three times a week at an average total weekly dose of 110 to 120 U/kg is effective treatment of anemia in most dialysis patients.


2001 ◽  
Vol 24 (6) ◽  
pp. 367-373 ◽  
Author(s):  
I. Stefanidis ◽  
P.R. Mertens ◽  
P. Wurth ◽  
R. Bach ◽  
W. Makropoulos ◽  
...  

The correction of anemia with human recombinant erythropoietin (rHuEPO) in end stage renal disease is associated with hypertension in about one third of hemodialysis patients. The pathogenesis of the rHuEPO-induced hypertension is still uncertain, though evidence of the involvement of endothelial cells has emerged. The aim of this study was to determine plasma endothelin-1 during hemodialysis and to compare the endothelin-1 levels in hemodialysis patients with and without rHuEPO substitution. Nineteen stable patients (13 male and 6 female, mean age 62 ± 11 years) with end stage renal disease were studied. Cuprophan dialysers (GFS 12®, Gambro, Lund, Sweden) were used for hemodialysis in all cases. rHuEPO (40U/kg s.c.) was administered to 10 patients. Blood pressure (BP; RR mmHg) and blood volume changes (ΔBV; hemoglobinometry %) were serially measured. Samples were taken before and every hour during hemodialysis. Plasma endothelin-1 was measured by ELISA (R&D Systems, Minneapolis, USA) and corrected for hemoconcentration. Endothelin-1 concentration was elevated before commencement of hemodialysis (1.16 ± 0.36 pg/ml) when compared to healthy controls (ref. 0.3 - 0.9) and increased to 1.47 ± 0.51 pg/ml by the end of the session (p<0.05). In patients under rHuEPO-substitution plasma endothelin-1 was higher when compared to patients without substitution before (1.25 ± 0.3 vs. 1.05 ± 0.3 pg/ml) and at the end of HD (1.62 ± 0.5 vs. 1.28 ± 0.3 pg/ml, p<0.05). There was no difference in BP and ΔBV between the two groups during treatment. Plasma endothelin-1 was higher in hemodialysis patients and there was a continuous rise in plasma endothelin-1 during a session. Comparison of two groups of hemodialysis patients with and without s.c. rHuEPO-replacement treatment revealed a significantly higher plasma endothelin-1 concentration in patients with s.c. rHuEPO treatment. However, the elevated endothelin-1 levels were not accompanied by arterial hypertension.


2019 ◽  
Vol 12 (1) ◽  
pp. 103-107
Author(s):  
Marta Ostrihoňová ◽  
Jana Adamíková ◽  
Tomáš Molnár ◽  
Monika Antošová ◽  
Milan Polakovič

Abstract This work deals with the capture of human recombinant erythropoietin (rhEPO) from a mixture of proteins in a concentrated postcultivation supernatant. Cation-exchange multimodal adsorbent Capto MMC ImpRes was selected as potential chromatographic separation material. Its equilibrium properties were investigated in batch adsorption experiments. The effect of pH in the range of 5.5—7.5 and NaCl concentration in the range of 0—300 mM on the adsorption of rhEPO and contaminant proteins was examined. Optimal conditions found in these equilibrium experiments were applied to rhEPO adsorption in a chromatographic column. Several experiments were carried out at different elution conditions to optimize the rhEPO yield and selectivity.


2005 ◽  
Vol 33 (5) ◽  
pp. 1129-1130 ◽  
Author(s):  
P.J. Coussons ◽  
S. Baig ◽  
C. Fanutti ◽  
R. Grant

rHuEPO (recombinant human erythropoietin) is a haemopoietic growth factor and a primary regulator of erythropoiesis that is used for the treatment of chronic anaemia associated with RA (rheumatoid arthritis). Erythropoietin also appears to modulate a broad array of cellular processes, including progenitor stem-cell development, cellular integrity, angiogenesis and oxidative damage. These diverse activities suggest the exciting possibility of multiple roles for rHuEPO therapy in a variety of disorders other than RA, including cerebral ischaemia, myocardial infarction, chronic congestive heart failure and cancer. Thus it appears that rHuEPO may be a pleiotropic agent, capable of influencing tissue remodelling independently of its established erythropoietic role. Whereas these effects may be largely beneficial, dose-related side effects could have implications for the safe therapeutic use of rHuEPO and its illegal use as a performance-enhancing agent in endurance sports.


1993 ◽  
Vol 79 (4) ◽  
pp. 600-602 ◽  
Author(s):  
Steven J. Schiff ◽  
Steven L. Weinstein

✓ The use of perioperative human recombinant erythropoietin is described in a Jehovah's Witness patient. Despite significant anemia, the child's hematocrit was sufficiently increased by the use of erythropoietin so that a two-stage hemispherectomy could be performed without blood transfusion.


2020 ◽  
Author(s):  
Mattia F. Pagnotta ◽  
David Pascucci ◽  
Gijs Plomp

AbstractBrain mechanisms of visual selective attention involve both local and network-level activity changes at specific oscillatory rhythms, but their interplay remains poorly explored. Here, we investigate anticipatory and reactive effects of feature-based attention using separate fMRI and EEG recordings, while participants attended to one of two spatially overlapping visual features (motion and orientation). We focused on EEG source analysis of local nested oscillations and on graph analysis of connectivity changes in a network of fMRI-defined regions of interest, and characterized a cascade of attentional effects and their interplay at multiple spatial scales. We discuss how the results may reconcile several theories of selective attention, by showing how β rhythms support anticipatory information routing through increased network efficiency and β-γ coupling in functionally specialized regions (V1 for orientation, V5 for motion), while reactive α-band desynchronization patterns and increased α-γ coupling in V1 and V5 mediate stimulus-evoked processing of task-relevant signals.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S647-S647
Author(s):  
Rachel Scrivano ◽  
Paul Kieffaber

Abstract It is unclear whether or not older adults experience more difficulty managing cognitive conflict by inhibiting distracting stimuli and/or ignoring irrelevant information than younger adults. A common procedure used to measure inhibitory function is through the use of congruent and incongruent stimuli. Specifically, past literature that used tasks like the Simon and flanker have found differing effects on reaction times and various event-related potential (ERP) amplitudes and latencies, suggesting that either inhibitory function is a unitary mechanism or multifaceted. Moreover, research exhibits uncertainty for whether or not age influences deficits to inhibitory function. Therefore, the present study sought to investigate these research questions by combining the Simon and flanker tasks into one unique task. The study’s behavioral results indicate that older adults have greater difficulty with cognitive conflict in both Simon and flanker tasks due to significantly prolonged reaction times during incongruent trials. Furthermore, reaction time data posits that there are no significant age-related differences between the Simon and flanker task. This finding indicates that through the use of these tasks, inhibitory function is a unitary mechanism. In addition, preliminary electroencephalogram data shows that younger and older adults process the task’s information similarly. These initial findings can further inhibition research through its use as benchmarks for the measurement of cognitive change and deficit identification in older adults.


2017 ◽  
Vol 31 (4) ◽  
pp. 167-178 ◽  
Author(s):  
Xenija Weißbecker-Klaus ◽  
Peter Ullsperger ◽  
Gabriele Freude ◽  
Sergei A. Schapkin

Abstract. Neuronal mechanisms of error processing under multitasking and their impact on the processing of a concurrent task were examined. Twenty-one younger and twenty older healthy adults performed a visual-motor flanker task or an auditory-vocal semantic task or both tasks simultaneously. During task performance the electroencephalogram (EEG) was continuously recorded. The event-related potential (ERP) was derived from the EEG, and ERP components associated with error processing (Ne and Pe) and semantic processing (N400) were analyzed. Older participants responded more slowly than younger ones in the flanker task regardless of the multitasking condition, while accuracy was equal in both groups. In the flanker task, multitasking led to an increase of error rates, a reduction of reaction times, and a disappearance of post-error slowing (PES). Error detection (Ne) was delayed and error awareness (Pe) attenuated in the single flanker task relative to the multitasking condition. In the semantic task, multitasking led to an increase of reaction times and a delay of the N400 in particular when an error in the flanker task occurred. First, these results indicate that multitasking impaired error processing, in particular conscious error perception (Pe) and abolished post-error adjustments of performance (PES) which may have resulted in a more risky response tendency in the flanker task. Second, multitasking impaired semantic processing, in particular after an error in the concurrent flanker task. Hence, multitasking compromised error processing and error prevention in one of the tasks, and semantic processing in the other task. Consequently, multitasking should be avoided at workplaces with error-prone job assignments or where poor understanding of communication may have serious consequences.


2021 ◽  
Vol 12 ◽  
Author(s):  
Kathrin Mayer ◽  
Marina Krylova ◽  
Sarah Alizadeh ◽  
Hamidreza Jamalabadi ◽  
Johan van der Meer ◽  
...  

Background: Stress adversely affects the attentional focus, the active concentration on stimuli, and increases susceptibility to distraction. To experimentally explore the susceptibility to distraction, the Attention Modulation by Salience Task (AMST) is a validated paradigm measuring reaction times (RT) for processing auditory information while presenting task-irrelevant visual distractors of high or low salience. We extended the AMST by an emotional dimension of distractors and an EEG-based evaluation. We then investigated the effect of the stress-relieving medication Neurexan (Nx4) on the participants' susceptibility to distraction.Methods: Data from a randomized, placebo-controlled, crossover trial (NEURIM study; ClinicalTrials.gov: NCT02602275) were exploratively reanalyzed post-hoc. In this trial, 39 participants received a single dose of placebo or Nx4 immediately before the AMST. Participants had to discriminate two different tone modulations (ascending or descending) while simultaneously perceiving task-irrelevant pictures of different salience (high or low) or valence (negative or positive) as distractors. Using EEG recordings, RT and the event-related potential (ERP) components N1, N2, and N3 were analyzed as markers for susceptibility to distraction.Results: In the placebo condition, we could replicate the previously reported task effects of salient distractors with longer RT for high salient distractors on the behavioral level. On the electrophysiological level, we observed significantly increased amplitudes of the N2 and N3 ERP components for positive emotional pictures. In terms of drug effect, we found evidence that Nx4 reduced distractibility by emotional distractors. The effect was shown by significantly reduced amplitudes of N2 and N3 ERP components and reduced RT for the positive valence domain under Nx4 compared to placebo. The Nx4 effects on RT and ERP components also showed a significant correlation.Conclusion: Emotional distractors in addition to the previously used salience distractors and the EEG based evaluation of ERPs valuably complement the AMST. Salient distractors were affecting attentional processes earlier, while valent distractors show modulatory effects later. Our results suggest that Nx4 has beneficial effects on attention by inhibiting the effect of task-irrelevant information and reducing susceptibility to emotionally distracting stimuli. The observation of a beneficial impact of Nx4 on attention regulation is supportive of Nx4's claim as a stress-relieving medication.


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