Medicina, Vol. 59, Pages 29: Fitts’ Tapping Task as a New Test for Cognition and Manual Dexterity in Multiple Sclerosis: Validation Study

Author Contributions

Conceptualization, K.D.G., B.W.-G. and D.J.; methodology, K.D.G., B.W.-G., G.V., I.V.I., N.Š., T.J.C. and D.J.; software, K.D.G., G.V., I.V.I. and N.Š.; validation, K.D.G., B.W.-G. and D.J.; formal analysis, D.J.; investigation, K.D.G., G.V., I.V.I. and N.Š.; resources, K.D.G., G.V., I.V.I. and N.Š.; data curation K.D.G., G.V., I.V.I. and N.Š.; writing—original draft preparation, D.J.; writing—review and editing, K.D.G., B.W.-G., G.V., I.V.I., N.Š., T.J.C. and D.J.; visualization, K.D.G. and D.J.; supervision, K.D.G. and B.W.-G.; project administration, K.D.G., G.V., I.V.I. and N.Š.; funding acquisition, K.D.G. All authors have read and agreed to the published version of the manuscript.

Conflicts of Interest

Klaudia Duka Glavor received honoraria as a speaker/consultant from Biogen, Novartis, Teva and Merck. Dejan Jakimovski, Gorka Vuletic, Iva Vranić Ivanac, Nataša Šimić and have nothing to disclose. Thomas J Covey has received honoraria as a speaker/consultant for Biogen. Bianca Weinstock-Guttman received honoraria as a speaker and/or as a consultant for Biogen Idec, Sanofi & Genzyme, Genentech, Novartis, BMS, Bayer, Horizon, and Janssen. Weinstock-Guttman received research funds from Biogen Idec, Genentech and Novartis.

Figure 1. Example of Fitts’ Tapping Task applied in a real-world setting. Legend: The subject is instructed to alternate and touch the strip-targets using the stylus. Trials included different difficulties based on the target widths of 0.5 cm, 1.0 cm, 2.0 cm, and 4.0 cm, and movement amplitudes of 4.0 cm, 8.0 cm, 16.0 cm, respectively.

Figure 1. Example of Fitts’ Tapping Task applied in a real-world setting. Legend: The subject is instructed to alternate and touch the strip-targets using the stylus. Trials included different difficulties based on the target widths of 0.5 cm, 1.0 cm, 2.0 cm, and 4.0 cm, and movement amplitudes of 4.0 cm, 8.0 cm, 16.0 cm, respectively.

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Figure 2. Bland–Altman plots depicting the reproducibility of the FTT including all measures (6 Fitts’ difficulties) and the average FTT score (average of the 12 trials together). Legend: FTT—Fitts’ Tapping Task. Left—absolute difference in Fitts’ Tapping Tasks within the people with multiple sclerosis over 1-week follow-up, Right—percent difference in Fitts’ Tapping Tasks within the people with multiple sclerosis over 1-week of follow-up. Each dot represents the difference between the two timepoints over 1-week. The green lines represent the lower and upper 95% confidence intervals and the red line represents the mean value.

Figure 2. Bland–Altman plots depicting the reproducibility of the FTT including all measures (6 Fitts’ difficulties) and the average FTT score (average of the 12 trials together). Legend: FTT—Fitts’ Tapping Task. Left—absolute difference in Fitts’ Tapping Tasks within the people with multiple sclerosis over 1-week follow-up, Right—percent difference in Fitts’ Tapping Tasks within the people with multiple sclerosis over 1-week of follow-up. Each dot represents the difference between the two timepoints over 1-week. The green lines represent the lower and upper 95% confidence intervals and the red line represents the mean value.

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Figure 3. Bland–Altman plots depicting the reproducibility of total FTT time and individual FTT difficulties. Legend: FTT—Fitts’ Tapping Task. Left—absolute difference in Fitts’ Tapping Tasks within the people with multiple sclerosis over 1-week follow-up, Right—percent difference in Fitts’ Tapping Tasks within the people with multiple sclerosis over 1-week of follow-up. Each dot represents the difference between the two timepoints over 1-week. The green lines represent the lower and upper 95% confidence intervals and the red line represents the mean value.

Figure 3. Bland–Altman plots depicting the reproducibility of total FTT time and individual FTT difficulties. Legend: FTT—Fitts’ Tapping Task. Left—absolute difference in Fitts’ Tapping Tasks within the people with multiple sclerosis over 1-week follow-up, Right—percent difference in Fitts’ Tapping Tasks within the people with multiple sclerosis over 1-week of follow-up. Each dot represents the difference between the two timepoints over 1-week. The green lines represent the lower and upper 95% confidence intervals and the red line represents the mean value.

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Figure 4. Box plot illustrating psychomotor performance between the three study groups. Legend: FTT—Fitts’ Tapping Task. The FTT performance measured at each difficulty level is shown in the first panel (left), whereas the reaction and decision times are shown in the second panel (right). Data are shown as the mean and error bars depict two standard errors.

Figure 4. Box plot illustrating psychomotor performance between the three study groups. Legend: FTT—Fitts’ Tapping Task. The FTT performance measured at each difficulty level is shown in the first panel (left), whereas the reaction and decision times are shown in the second panel (right). Data are shown as the mean and error bars depict two standard errors.

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Figure 5. Correlation matrix between psychomotor performance and PROs in pwMS and HCs. Legend: pwMS—people with multiple sclerosis, HCs—healthy controls, PROs—patient-reported outcomes. The correlation matrix depicts the correlation coefficients (r) derived from Pearson’s correlations. (A)—correlations between psychomotor performance and PROs in people with multiple sclerosis, (B)—correlations between psychomotor performance and PROs in healthy controls.

Figure 5. Correlation matrix between psychomotor performance and PROs in pwMS and HCs. Legend: pwMS—people with multiple sclerosis, HCs—healthy controls, PROs—patient-reported outcomes. The correlation matrix depicts the correlation coefficients (r) derived from Pearson’s correlations. (A)—correlations between psychomotor performance and PROs in people with multiple sclerosis, (B)—correlations between psychomotor performance and PROs in healthy controls.

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Figure 6. Change in psychomotor (FTT) and physical hand (dynamometer) performance over 2-year follow-up in eight pwMS. Legend: FTT—Fitts’ Tapping Task, pwMS—people with multiple sclerosis. Paired t-test was used to calculate the intraindividual change in Fitts’ Tapping Task and dynamometer measures. Each line represents one pwMS that was followed over 2-years.

Figure 6. Change in psychomotor (FTT) and physical hand (dynamometer) performance over 2-year follow-up in eight pwMS. Legend: FTT—Fitts’ Tapping Task, pwMS—people with multiple sclerosis. Paired t-test was used to calculate the intraindividual change in Fitts’ Tapping Task and dynamometer measures. Each line represents one pwMS that was followed over 2-years.

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Table 1. Demographic and patient-based outcomes in the study groups.

Table 1. Demographic and patient-based outcomes in the study groups.

Demographic and PRO MeasuresPwMS (n = 30)Migraine (n = 30)HCs (n = 30)Across Groups p-ValueMS vs. HCs p-ValueFemale, n (%)22 (73.3)22 (73.3)22 (73.3)1.0001.000Age, mean (SD)37.3 (9.7)39.9 (7.5)37.5 (6.8)0.3891.000Formal years of education, n (%)High school completed21 (70.0)15 (50.0)14 (46.7)0.3330.185Bachelor’s degree completed6 (20.0)12 (40.0)11 (36.7)Postgraduate degree completed3 (10.0)3 (10.0)5 (16.7)36-Item Short Form Survey (SF-36), median (IQR)Physical functioning70 (43.8–96.3)90 (65.0–100.0)97.5 (83.8–100.0)0.0180.005Role limitations due to physical health75 (25–100)75 (25.0–100.0)100 (100.0–100.0)0.0010.002Role limitations due to emotional problems83.3 (33.3–100)100 (33.3–100.0)100 (66.7–100.0)0.2590.087Energy/fatigue57.5 (40.0–70.0)55 (35.0–66.3)52.5 (45.0–75.0)0.720.829Emotional well-being70 (59.0–80.0)68 (55.0–77.0)68 (59.0–81.0)0.7190.917Social functioning75.0 (62.5–100.0)75 (37.5–87.5)81.3 (59.4–100.0)0.2940.934Pain70 (38.8–72.0)60 (37.5–72.5)80 (60.0–90.0)0.0190.271General health perception56 (38.8–72.0)63.5 (45.8–77.0)77 (69.3–87.8)<0.001<0.001Physical health67.8 (41.6–83.3)68 (41.4–82.1)85.9 (74.3–91.8)<0.0010.001Mental health69.9 (49.5–82.8)72.1 (48.2–82.1)74.4 (62.2–86.8)0.4860.506

Table 2. Intrarater and interrater reproducibility of the FTT in healthy controls.

Table 2. Intrarater and interrater reproducibility of the FTT in healthy controls.

FTT PerformanceTestRaterMean (SD)1st difficultyTest 1Rater 17.53 (0.99)Rater 27.48 (0.99)Test 2Rater 17.52 (0.34)Rater 27.41 (0.36)2nd difficultyTest 1Rater 19.7 (0.99)Rater 29.73 (0.93)Test 2Rater 19.66 (1.12)Rater 29.62 (1.04)3rd difficultyTest 1Rater 112.72 (1.83)Rater 212.81 (1.75)Test 2Rater 113.77 (3.12)Rater 213.59 (2.99)4th difficultyTest 1Rater 117.73 (1.52)Rater 217.71 (1.53)Test 2Rater 118.18 (2.58)Rater 218.21 (2.58)5th difficultyTest 1Rater 126.41 (3.69)Rater 226.43 (3.55)Test 2Rater 125.42 (3.25)Rater 225.48 (3.18)6th difficultyTest 1Rater 130.11 (3.37)Rater 229.78 (3.13)Test 2Rater 130.98 (3.32)Rater 230.93 (3.23)

Table 3. Short-term reproducibility of Fitts’ Tapping Task in five pwMS over one week.

Table 3. Short-term reproducibility of Fitts’ Tapping Task in five pwMS over one week.

Longitudinal FTT Change (n = 5)Median Total Time (msec)ICC
p-Value aMean (Median) Raw Change (msec)Mean (Median) % ChangeMin–Max Range of
Change (%)Average of all 4 trials at Visit 119.2 (17.9–19.6)0.0010.31 (0.34)1.66 (1.77)−0.11–3.1Average of all 4 trials at Visit 219.7 (18.3–19.7)

Table 4. Psychomotor performance in the study groups.

Table 4. Psychomotor performance in the study groups.

Psychomotor TestsPwMS (n = 30)PwMig (n = 30)HCs (n = 30)Across Groups p-ValueEffect Size for pwMS vs. HCsPwMS vs. HCs p-ValueAverage Fitts’ Tapping Task time (seconds)18.2 (16.0–19.7)14.8 (12.4–17.2)15.6 (12.3–17.0)<0.0010.476<0.0011st difficulty time8.9 (7.2–9.8)7.1 (5.7–9)7.2 (6.1–8.3)0.0050.3870.0032nd difficulty time10.8 (9.4–12.5)8.3 (6.7–11.1)8.6 (6.8–10.0)0.0010.456<0.0013rd difficulty time13.8 (12.1–15.8)11.1 (9.6–13.8)11.4 (9.5–13.0)0.0020.4110.0014th difficulty time18.2 (16.9–19.7)14.3 (12.375–17)15.2 (12.8–16.6)<0.0010.58<0.0015th difficulty time25.1 (20.1–27.7)19.4 (16.1–23.6)20.6 (15.9–23.2)0.0010.3890.0036th difficulty time33.3 (25–35.2)27.7 (21.9–30)28.6 (22.3–31.8)0.0020.3260.011Average O’Connor Dexterity (seconds)201.4 (177.9–248.0)174.5 (165.2–197.9)173.7 (161.9–194.0)<0.0010.499<0.0011 peg88.5 (82.5–98.9)82.4 (76.3–92.9)80.4 (74.9–86.5)0.0070.4070.0023 pegs312.4 (270.1–378.1)267.2 (255.6–307.9)263.7 (248.9–300.7)<0.0010.457<0.001Average dynamometer (kP)33.3 (28.3–44.4)37.7 (30.2–46.7)37.3 (32.3–46.9)0.2470.2170.0931st attempt33 (29.0–43.5)38.5 (31.5–49.5)39 (31.8–47)0.2330.2070.1082nd attempt33 (28.0–44.3)38 (29.8–45.5)36.5 (32.0–48.0)0.2840.2140.0973rd attempt32 (26.8–45.0)37.5 (30.0–45.8)36 (33.8–46.5)0.2920.1910.139Average reaction time (ms)303.9 (243.9–361.6)236.9 (218.3–286.1)223.7 (198.8–254.2)0.0010.468<0.0011 stimulus291.3 (230.6–361.2)226.2 (202.6–271.7)218.4 (200.2–252.2)0.0010.4370.0012 stimuli311.8 (248.9–386.1)233.5 (211.5–283.1)225.1 (194.7–260.7)0.0010.4430.0014 stimuli310.3 (254.6–367.3)245.8 (227.3–312.5)229.1 (195.8–274.6)0.0030.4140.001Average decision time (ms)381.8 (359.8–413.5)373.6 (339.4–392.1)347.9 (314.4–363.7)0.0070.3890.0031 stimulus365.25 (338.2–389.1)338.4 (320.1–381.1)327.7 (304.5–354.7)0.020.3550.0062 stimuli385.25 (336.8–407.4)363.9 (343.9–384.5)350.4 (313.9–374.9)0.030.3230.0124 stimuli402.75 (367.1–442.1)394.4 (355.5–420.9)352.4 (331.1–382.0)0.0080.3730.004

Table 5. Hypothesis-driven hierarchical binary regression model for differentiation between pwMS and HCs.

Table 5. Hypothesis-driven hierarchical binary regression model for differentiation between pwMS and HCs.

Predictor AddedBS.E.Waldp-ValueExp(B)Step 1Age0.0810.0532.3340.1271.084Sex−0.130.8420.0240.8770.878Step 2Average FTT time−0.270.1383.8460.0490.763Step 3Average O’Connor time−0.0370.0165.5380.0190.964Step 4Average reaction time−0.0070.0043.2690.0710.993Step 5Average decision time−0.0090.0071.5520.2130.991

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