Slowed Movement Stopping in Parkinson’s Disease and Focal Dystonia is Improved by Standard Treatment

Abstract

Patients with Parkinson’s disease and focal dystonia have difficulty in generating and preventing movement. Reaction time (RT) and stop signal reaction time (SSRT) measure the speed to initiate and stop a movement respectively. We developed a portable device to assess RT and SSRT. This incorporated a novel analysis to measure SSRT more efficiently (optimal combination SSRT, ocSSRT). After validation ocSSRT was measured in Parkinson’s disease patients without dyskinesia (PD), cervical dystonia (CD) and writer’s cramp. We also assessed how ocSSRT responded to L-dopa in PD patients and botulinum toxin injections in CD patients. Participants were instructed to release a button following a green LED flash on the device. On 25% of trials, a red LED flashed 5–195 ms after the green LED; participations were instructed to abort the button release on these trials. ocSSRT and RT were significantly prolonged in patients with Parkinson’s disease and focal dystonia (one-way ANOVA p < 0.001). Administration of L-dopa significantly improved ocSSRT and RT in PD patients (p < 0.001). Administration of botulinum toxin significantly improved ocSSRT, but not RT, in CD patients (p < 0.05). ocSSRT is an easily-administered bedside neuro-physiological tool; significantly prolonged ocSSRT is associated with PD and focal dystonia.

Effects of Diazepam on Reaction Times to Stop and Go

“…Robbins ( 2000 ) noted that in marmosets manipulations of dopamine and noradrenaline tend to produce effects on tasks predominantly engaging the dorsolateral prefrontal cortex, but manipulations of the serotonergic system tend to alter performance in tests sensitive to orbitofrontal dysfunction. Interestingly, a recent study from our group (Choudhury et al, 2019 ) showed a significant reduction in SSRT after treatment with the dopamine precursor levodopa in Parkinson’s patients, potentially supporting the contention that movement stopping is mediated by circuits involving the dorsolateral prefrontal cortex.…”

“…In this study, we used our recently-developed method exploiting portable equipment and an analytical approach which incorporates knowledge of the likely reliability of the response probability estimates. We have shown that this provides rapid SSRT measurements with high reproducibility (Choudhury et al, 2019 ). Regardless of any methodological differences, we can have high confidence in our results since this was a double-blind placebo-controlled trial, in which we demonstrated a significant difference between placebo and 10 mg diazepam.…”

“…We used a custom-built battery-powered device housed in a plastic case, which the subject held comfortably in two hands (Choudhury et al, 2019 ). One red and one green light-emitting diode (LED, 5 mm diameter) mounted on the front of this box indicated Stop and Go respectively; a press button (2 cm diameter) positioned beneath the LEDs was depressed and held or released by the subject depending on the instructions encoded by the sequence of LED flashes.…”

“…Mathematical details of the calculation of ocSSRT are provided in Choudhury et al ( 2019 ), which should be consulted for a full description. Briefly, for a given stop-signal delay (SSD), the number of inappropriate responses M and the total number of trials tested with that delay N was determined.…”

“…Recently we have developed an improved index by applying Bayesian statistics to SSRT estimation. This index, which appears to have significantly higher reproducibility (Choudhury et al, 2019 ), is known as optimum combination SSRT (ocSSRT).…”