CHDR uses computer-based driving simulators made by Green Dino to safely measure the effects of pharmacological compounds and/or diseases on driving performance. These tests can be performed repeatedly, yielding highly reproducible data and allowing researchers to establish doseeffect curves for a number of CNS functions.

Highlights

  • The driving simulator is a safer version of the standard driving test, providing a robust measure of a drug’s effects on attention and motor control.
  • The simulator can be programmed to measure specific effects, impairments, and other disabilities that may affect driving performance, for example decision-making, motor control, risk-taking behaviour, and spatial memory.
  • The results are recorded automatically and can be correlated with blood values and other physiological parameters.
  • The simulator is a standardised testing environment with sufficient variations to minimise learning effects in cross-over experiments.
  • The tests can be repeated frequently, allowing the researcher to measure the time course of driving performance during dosing.
  • The effects of a new compound can be compared to benchmark compounds such as alcohol intoxication or medications known to impair driving ability.

Validation and clinical relevance

The effects of alcohol on driving performance have been measured extensively at CHDR using our validated ‘ethanol clamp’ method. With this protocol, the subject receives an intravenous infusion of ethanol. The infusion rate is adjusted continuously based on breath alcohol samples in order to maintain (‘clamp’) the subject’s blood alcohol concentration. The researcher then measures the effect of intoxication (in the Netherlands, the legal limit is defined as 0.5 g/L alcohol) on driving performance in the simulator. The effects of a new drug can then be compared to the effects of alcohol intoxication. In addition, the reaction profile has been established in subjects following a 1-mg dose of alprazolam, a widely prescribed anxiolytic drug often taken during the day, potentially before getting behind the wheel; the results revealed that taking a dose of alprazolam has a more severe effect on driving performance than alcohol intoxication

Using the driving simulator in patients with Huntington’s disease

In a recent trial CHDR studied how Huntington’s disease affects driving skills, as well as the effects of presymptomatic patients identified with genetic testing. A standard set of tasks in the driving simulator and NeuroCart is applied to presymptomatic patients and early-stage patients, and the results are compared against a control group of healthy subjects who are not carriers of the Huntington mutation.

One of the goals of this study was to objectively measure the effect of developing Huntington’s disease on driving ability, which is an important first step to helping patients drive safely, allowing them to keep their licence as long as possible. It shows the clinical relevance of using the more practical driving simulator compared to the basic tests used in NeuroCart. It is possible now to evaluate new drugs for treating Huntington’s disease, as we have a baseline score for comparison.