Baker MR

Baker SN

Banerjee S

Bayen AB

Choudhury S

Chowdhury MSJH

Islam N

Kumar H

Majumdar S

Schofield IS

Newcastle University E-Prints

1  Title Page: 1 Article Title: A Mobile Application to Measure the Ability to Stop in Movement Disorders 2  3 Authors’ names and affiliations: Supriyo Choudhury, MD 1, Suchismita Majumdar, Msc 1, 4 Nazrul Islam, MBBS2, Asit Baran Bayen, Msc 1, Sattwika Banerjee, Msc 1, Mohammad Shah 5 Jahirul Hoque Chowdhury, MD2, Ian S Schofield, BMedSci, MBBS, FRCP3, Mark R Baker, 6 PhD, FRCP3,4, Stuart N Baker, PhD3, Hrishikesh Kumar, MD, DM1  7 SC and SM has equal contribution as joint first author.  8 1 Institute of Neurosciences Kolkata, Kolkata, India 9 2 National Institute of Neurosciences and Hospital, Dhaka, Bangladesh 10 3 The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom 11 4 Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom 12  13 Joint correspondence information: 14 Dr Hrishikesh Kumar 15 Head, Department of Neurology 16 Director of Research 17 Vice Chairman 18 Institute of Neurosciences Kolkata 19 185/1 AJC Bose Road, Kolkata 20 West Bengal (India) 21 Postal code: 700017 22 Email address: rishi_medicine@yahoo.com 23 Ph: (033)240309982 24 2  Prof. Stuart N Baker 25 Faculty of Medical Science,  26 Newcastle University,  27 Newcastle upon Tyne,  28 NE2 4HH, UK 29 E-mail: stuart.baker@newcastle.ac.uk 30  31 Word Counts: 777 32  33 Running title: Mobile App for Measuring Ability to Stop  34  35 Key words: ocSSRT, Reaction Time (RT) 36  37 Disclosures: 38 Figure Permissions: All the required permissions have been taken for the use of the parts of 39 the figure: 1 (A-G) from Roy et al, Choudhury et al and Rahman et al published by the 40 same group after obtaining the necessary permissions 41 Funding Sources:   Institutional research fund of HK, Institute of Neurosciences Kolkata, 42 India. SNB received funding from UKRI/Medical Research Council Confidence in Concept 43 grant number MC/PC/17168 and project grant number MR/P012922/1for this research.   44 Conflict of Interest: No COI to disclose  45 Financial Disclosures for the previous 12 months: The authors declare that there are no 46 additional disclosures to report. 47  48 3  Main Text: 49 The ability to start and stop movements is impaired in movement disorders[1]. Measuring the 50 ability to respond to a cue is relatively easy; stopping is a more hypothetical concept which is 51 harder to quantify. One successful approach relies on the ‘horse race’ model. This 52 conceptualises a Go and Stop process which race in parallel towards a finish line. If the Go 53 process wins, the movement is executed; if the Stop process wins, movement is inhibited. 54 This theoretical concept was given mathematical expression by Logan and Cowan (1984), 55 leading to the stop signal reaction time (SSRT)[2]. We measured SSRT through a simple task 56 using a battery-operated portable box, ideal for bedside assessment. In the task, the subjects 57 were requested to release a button in response to intermittently flashing green LED (‘go 58 signal’) as fast as they could but cease to release the button in quarter of trials at random 59 when the ‘stop signal’ (red LED flashes) immediately followed the ‘go signal’. The stop 60 signals were delivered in four different delays, leading to different proportions of trials were 61 the button was released inappropriately. The probability of error and reaction time during a 62 stop-signal task are used to compute SSRT. Recently, we improved SSRT estimation 63 reliability using a Bayesian mathematical approach (optimum combination stop signal 64 reaction time, ocSSRT)[1]. Essentially, this measure was derived from mean posterior 65 probabilities of SSRTs in four different stop-signal delays and summarised as one mean and 66 95% confidence interval for individual subject. Subsequently, we applied ocSSRT to 67 movement disorders patients through a portable battery-operated box with a digital display. 68 We observed that patients with movement disorders e.g. Parkinson’s Disease (PD), cervical 69 dystonia (CD), and writer’s cramp demonstrated significantly prolonged ocSSRT compared 70 to healthy control[1]. Thus, this neurophysiological index may have potential use for 71 classification of various types of movement disorders including psychogenic movement 72 disorders. The prolonged ocSSRT was partially normalised after intake of l-dopa in PD 73 4  patients and after one month of injecting therapeutic doses of botulinum toxin in the affected 74 muscles in CD patients. We also used this box to optimise the settings of Deep Brain 75 Stimulation (DBS) in our Movement Disorder clinic[3] and potentially this can be further 76 validated as an tool for DBS programming even remotely. We also showed that ocSSRT is 77 useful in discriminating between Alzheimer’s and Parkinson’s disease[4]. SSRT could thus 78 be used for screening and classification of neurodegenerative conditions. Against this 79 backdrop, there is a need for greater accessibility of this tool to movement disorder 80 neurologists and researchers interested in exploring the clinical utility of SSRT. We therefore 81 developed and validated an android application to measure simple visual reaction time (RT) 82 and ocSSRT.  83 For validation (criterion validity) we compared the RT and ocSSRT in a group of 31 healthy 84 subjects (mean age 35±10 years, 16 female), recorded through our previously validated 85 ocSSRT box and the new android application. The reliability of the estimates (ocSSRT and 86 RT) was confirmed by repeating the test through the same box and android application one 87 week later in a subset of the same individuals. We finally compared readings between the 88 android application and box in ten Parkinson’s disease patients (54±7 years, 3 female), to 89 provide a measure of accuracy.  90 The test-retest reliability (intra-class correlation coefficient, ICC) was 0.778 for ocSSRT in 91 the application in healthy people. The ICCs for box versus application (accuracy) for healthy 92 was 0.707 and for PD patients 0.748 (p<0.01).  The criterion validity (or accuracy) and test-93 retest reliability (or precision) for application were all ≥0.7 (p<0.01), showing that the 94 application is an accurate and precise tool for estimation of both RT and ocSSRT. The small 95 sample size of PD patients and relatively young control group may impact the generalisability 96 of this observation.  Although measures from the application and box were highly correlated, 97 ocSSRT measured with the box was 57±13ms shorter; a similar difference was seen in RT 98 5  (43±13ms; both mean±SEM). We performed electromechanical tests in which an artificial 99 finger was lifted from the response button of the box or the touch screen of the application at 100 a fixed time after detection of the cue by a photodiode. The application had a delay of 51ms 101 in registering the response compared to the box, compatible with the observed differences in 102 ocSSRT and RT. Data acquired with the application thus requires a 51ms correction 103 (subtraction) for comparison with our previous published data[1, 3, 4]. This is due to a delay 104 incurred because of touch screen technology.  105 We have made this application freely available via the Amazon play store[5]. We hope that 106 this will provide movement disorder neurologists with easy access to a quantitative tool to 107 measure the ability to start and stop in their patients. 108  109 Authors’ Roles:  110 1. Research project: A. Conception, B. Organization, C. Execution; 111 2. Statistical Analysis: A. Design, B. Execution, C. Review and Critique; 112 3. Manuscript Preparation: A. Writing of the first draft, B. Review and Critique;  113  114 SC: 1A, 1B, 1C, 2A, 2B, 2C, 3A, 3B, SM: 1A, 1B, 1C, 2B, 2C, 3B, NI: 1B, 1C, 2B, 2C, 3B, 115 ABB: 1B, 2B, 3C, SB: 1B, 2B, 3C, MHC: 1B, 3B, IS: 1A, 2A, 2C, 3B, MB: 1A, 1B, 1C, 116 2A, 2B, 2C, 3B SNB: 1A, 1B, 1C, 2A, 2B, 2C, 3B HK: 1A, 1B, 1C, 2A, 2B, 2C, 3B 117 Financial Disclosures: 118 Funding Sources and Conflict of Interest: HK received Institutional research fund of HK, 119 Institute of Neurosciences Kolkata, India. SNB received funding from UKRI/Medical 120 6  Research Council Confidence in Concept grant number MC/PC/17168 and project grant 121 number MR/P012922/1 for this research.  No COI to disclose.  122 Financial Disclosures for the previous 12 months: The authors declare that there are no 123 additional disclosures to report. 124  125 Ethical Compliance Statement: 126 Institutional Ethics Committee approved the research and informed consent was obtained 127 before participation. 128 We confirm that we have read the journal’s position on issues involved in ethical publication 129 and affirm that this work is consistent with those guidelines.  130  131 References:  132 1. Choudhury, S., et al., Slowed movement stopping in Parkinson’s disease and focal 133 dystonia is improved by standard treatment. Scientific reports, 2019. 9(1): p. 1-9. 134 2. Logan, G.D. and W.B. Cowan, On the ability to inhibit thought and action: A theory 135 of an act of control. Psychological review, 1984. 91(3): p. 295. 136 3. Roy, A., et al., Stop Signal Reaction Time measured with a portable device validates 137 optimum STN-DBS programming. Brain Stimulation: Basic, Translational, and 138 Clinical Research in Neuromodulation, 2020. 13(6): p. 1609-1611. 139 4. Rahman, S., et al., Comparing Stop Signal Reaction Times in Alzheimer’s and 140 Parkinson’s Disease. Canadian Journal of Neurological Sciences, 2021: p. 1-26. 141 7  5. Kolkata, I.o.N. Stop Signal Reaction Timer. [Mobile application ] 2021 October 11, 142 2021 [cited 2022 30 Nov 2022]; Available from: 143 https://www.amazon.com/dp/B09HYKM45H/ref=apps_sf_sta. 144  145 All the required permissions have been taken for the use of the parts of the figure: 1 (A-G) 146 from Roy et al, Choudhury et al and Rahman et al published by the 147 same group after obtaining the necessary permissions 148  149  150  151 All the required permissions have been taken for the use of the parts of the figure: 1 (A-G) 152 from Roy et al, Choudhury et al and Rahman et al published by the 153 same group after obtaining the necessary permissions 154  155  156  157 Legends for Figures:  158 Figure 1: Starting and stopping ability of patients with movement disorders and validation of 159 the android application  160 A. Schematic description of the stop signal task. Stop signals (illumination of red LED at one 161 of four intervals after the Go cue) occur in a pseudorandom order, comprising 25% of trials; 162 the remaining 75% of trials have a Go cue only (illumination of green LED). Participants 163 were instructed to release the button in response to Go trials but to keep pressing the button if 164 the Go signal was followed by a Stop signal. B. Previously-developed battery operated box 165 8  for estimation of Reaction time (RT) and optimum combination Stop Signal Reaction Time 166 (ocSSRT) C. RT and ocSSRT were significantly prolonged in patients with movement 167 disorders (WC= Writer’s cramp, CD= Cervical dystonia, PD= Parkinson’s Disease) [1]. D. 168 RT and ocSSRT are partially corrected in Parkinson’s disease patients after intake of L-dopa 169 (from OFF to ON phase)[1]. E, F. The motor signs (UPDRS III) worsened and ocSSRT was 170 prolonged after turning off an implanted Deep Brain Stimulation (DBS) device. Both 171 measures improved after optimising DBS settings[3]. G. A cumulative probability plot for 172 ocSSRT differentiated healthy people from those with Alzheimer’s or Parkinson’s disease[4]. 173 H. The difference between ocSSRT measured through the novel application and existing box 174 at day 1 and day 7 in healthy participants. Dotted line shows a difference of 51ms, expected 175 from electromechanical tests. I. The correlation between ocSSRT measured through the 176 application at day 1 and day 7. The dotted line plots the line of identity (y=x; i.e. perfect 177 equality between the ocSSRT measured at Day 1 and Day 7). J. Screenshot of the welcome 178 screen and the main trial screen of the android application.  179 9   180  181 

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A Mobile Application to Measure the Ability to Stop in Movement Disorders

A Mobile Application to Measure the Ability to Stop in Movement Disorders

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