we collected the complete data of four patients ( 1 woman , 3 men ) . mini - mental state examination ( 29.3  0.5 ) , hamilton depression rating scale ( 3  2 ) , fatigue severity scale ( 4.2  1.1 ) , and multidimensional fatigue inventory ( 57.8  15.0 ) were evaluated ( table 1 ) . we recruited patients from the national institute of neurological disorders and stroke ( ninds ) clinics . all patients gave written informed consent for this study protocol approved by the ninds institutional review board . the experimental details and analysis of the se were the same as in the previous study.3 we assessed the se as a progressive lengthening of peg movement time for successive peg movements , using a modified purdue pegboard test and a computer - based device ( part of the at - home testing device , intel , courtesy of the kinetics foundation).9 the pegboard test had a vertical line of eight holes on both the right and left sides . we asked patients to move individual pegs from the right to the left side as quickly as possible . the device could store the time of pulling - out and pushing - in of each peg . there were six runs , three with the right hand first , followed by three with the left hand . there was a 10-second pause between runs and each run began with a beep . to assess the se , we calculated differences between the times to move the first four pegs and the last four pegs for each hand . we did not calculate either the second run with the right hand or the fifth run with the left hand because the direction was opposite to the other two runs for each hand and we thought that the opposite direction might bias the data . we averaged the differences over the two runs , per hand , pegboard test , and patient . patients were asked to visit four times and to repeat the pegboard test during each visit . thus , we collected four sets of data . to know whether the se in both hands was statistically significant , differences were averaged across the four visits for each hand ( right , left , more affected , and less affected , respectively ) and evaluated using a wilcoxon signed rank test . we collected the complete data of four patients ( 1 woman , 3 men ) . mini - mental state examination ( 29.3  0.5 ) , hamilton depression rating scale ( 3  2 ) , fatigue severity scale ( 4.2  1.1 ) , and multidimensional fatigue inventory ( 57.8  15.0 ) were evaluated ( table 1 ) . we recruited patients from the national institute of neurological disorders and stroke ( ninds ) clinics . all patients gave written informed consent for this study protocol approved by the ninds institutional review board . the experimental details and analysis of the se were the same as in the previous study.3 we assessed the se as a progressive lengthening of peg movement time for successive peg movements , using a modified purdue pegboard test and a computer - based device ( part of the at - home testing device , intel , courtesy of the kinetics foundation).9 the pegboard test had a vertical line of eight holes on both the right and left sides . we asked patients to move individual pegs from the right to the left side as quickly as possible . the device could store the time of pulling - out and pushing - in of each peg . there were six runs , three with the right hand first , followed by three with the left hand . to assess the se , we calculated differences between the times to move the first four pegs and the last four pegs for each hand . we did not calculate either the second run with the right hand or the fifth run with the left hand because the direction was opposite to the other two runs for each hand and we thought that the opposite direction might bias the data . we averaged the differences over the two runs , per hand , pegboard test , and patient . patients were asked to visit four times and to repeat the pegboard test during each visit . thus , we collected four sets of data . to know whether the se in both hands was statistically significant , differences were averaged across the four visits for each hand ( right , left , more affected , and less affected , respectively ) and evaluated using a wilcoxon signed rank test . a wilcoxon signed rank test showed a strong statistical trend toward the se with the right hand , but no significance with the left hand ( right hand , 7745.3  513.7 ms . vs. 8082.8  455.7 ms , p = 0.068 ; left hand , 7797.3  887.8 ms . vs. 8144.8  937.5 ms , p = 0.465 ) ( figure 1a ) . a wilcoxon signed rank test did not show statistically significant se with either the more or less affected hands ( more affected hand , 7700.0  465.0 ms . vs. 8186.3  629.8 these results indicate that the se can be identified in drug - nave pd , as well as in advanced pd . additionally , the data show that the se is a feature in pd and is observed during the early - stage of the disease without medication . the se is well - known in pd.1,4,10,11 patients with pd were especially slow while they performed complex or repetitive movements.2,11 the patients needed considerably more time to perform one task and exhibited a longer pause between one task and the next , compared with healthy volunteers.2,11 patients with basal ganglia disorders also showed these abnormalities , but only pd patients needed progressively increased time to complete individual movements during repetitive movements.1 that is , the se was observed in only pd patients . to date , the se has only been measured in advanced pd with medication . in clinical practice , we can observe the se from several types of repetitive movements such as finger tapping , writing , and gait in early , drug - nave as well as advanced pd . thus , one can assume that the se would be measured during early , drug - nave pd . it might be asked why the se should be measured separately from other motor symptoms . it appears that the cause of all motor symptoms is not the same and dopaminergic medication does not improve all such symptoms.1214 the clinical significance of the se remains to be investigated . it has been suggested that it contributes to freezing of gait in pd.15 it was also postulated that the se may be related to cognition3,16 and fatigue.1 there are some limitations in this study . the mean value of the se was higher in the more affected hand than in the less affected hand , but there was no statistical significance . second , we did not provide data from healthy volunteers ; but because the se has been demonstrated in various types of sequential movements in pd , and not in healthy volunteers,11 it is less likely that the healthy volunteers would show the same se .
background and purposethe sequence effect ( se ) in parkinson s disease ( pd ) denotes progressive slowness in speed or progressive decrease in amplitude of repetitive movements . 
 it is a well - known feature of bradykinesia and is considered unique in pd . until now , it was well - documented in advanced pd , but not in drug - nave pd . 
 the aim of this study is to know whether the se can also be measured in drug - nave pd.methodswe measured the se with a computer - based , modified purdue pegboard in 4 drug - nave pd patients , which matched our previous study with advanced pd patients.resultswe observed progressive slowness during movement , that is , se . statistical analysis showed a strong statistical trend toward the se with the right hand , but no significance with the left hand . 
 there was no statistical significance of se with either the more or less affected hands.conclusionsthese results indicate that the se can be identified in drug - nave pd , as well as in advanced pd , with objective measurements and support the idea that the se is a feature in pd observed during the early stage of the disease without medication .