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The impact of low-frequency stimulation of the pedunculopontine nucleus region on reaction time in parkinsonism
  1. Wesley Thevathasan1,2,
  2. Peter A Silburn3,4,
  3. Helen Brooker5,
  4. Terry J Coyne3,
  5. Sadaquate Khan6,
  6. Steven S Gill6,
  7. Tipu Z Aziz2,
  8. Peter Brown1
  1. 1Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, UK
  2. 2Nuffield Department of Surgery, University of Oxford, Oxford, UK
  3. 3St Andrews and Wesley Hospitals, Brisbane, Australia
  4. 4Centre for Clinical Research, Royal Brisbane and Women's Hospital, University of Queensland, Brisbane, Australia
  5. 5Cognitive Drug Research Ltd, Goring-on-Thames, UK
  6. 6Institute of Neurosciences, Frenchay Hospital, Bristol, UK
  1. Correspondence to Professor P Brown, Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, 33 Queen Square, London, WCIN 3BG, UK; p.brown{at}ion.ucl.ac.uk

Abstract

Objectives Attentional augmentation and enhanced motor function are potential mechanisms by which stimulation of the region of the pedunculopontine nucleus (PPN) may improve gait in parkinsonism. Here, the authors assess the impact of stimulation of this region on attentional and motor aspects of reaction task performance in patients with parkinsonism.

Methods Eleven patients implanted with PPN stimulators underwent computerised assessment of simple, choice and digit vigilance reaction tasks. Patients were assessed ‘off medication’ during stimulation at different frequencies (0 Hz, 5 Hz, 10 Hz and ‘therapeutic’ 20–35 Hz). There were two primary endpoints: ‘Speed of Reaction’ (sum of the mean task reaction times) and ‘Accuracy of Reaction’ (reflecting omissions and percentage of correct responses). Baseline performance was compared with age- and sex-matched healthy controls. Clinical effects of stimulation were assessed using the Unified Parkinson's Disease Rating Scale and a falls frequency scale.

Results Compared with healthy controls, subjects had significant deficits in ‘Speed of Reaction’ and in all mean task reaction times. ‘Accuracy of Reaction’ was not different from healthy controls and did not improve with stimulation. ‘Speed of Reaction’ significantly improved with stimulation at therapeutic frequencies (20–35 Hz). Of the individual tasks, only simple reaction time improved significantly. Simple reaction time distribution analysis revealed a general speeding of responses rather than a selective reduction in outliers. Acute PPN stimulation improved gait and balance but not akinesia scores. Chronic PPN stimulation significantly improved falls frequency. Falls score improvement significantly correlated with changes to simple reaction time with therapeutic stimulation.

Conclusion The pattern of reaction time improvement with stimulation of the PPN area suggests a benefit on motor performance, rather than augmentation of attention.

  • Pedunculopontine
  • deep brain stimulation
  • Parkinson's disease
  • reaction time
  • electrical stimulation
  • motor physiology

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Footnotes

  • Funding This work was supported by the Medical Research Council (UK), the Charles Wolfson Charitable Trust, the Norman Collisson Foundation and the Oxford Biomedical Research Centre.

  • Competing interests HB is an employee of Cognitive Drug Research Pty Ltd. PAS, PB, TZA, SSG and TJC have received honoraria from Medtronic.

  • Ethics approval Ethics approval was provided by local ethics committees in Oxford, Bristol and Brisbane.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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