Studying Movement Control in Parkinson's Disease Using Closed Loop Deep Brain Stimulation
Condition: Parkinson Disease
MeSH terms: Parkinson Disease
Study type: Interventional

Summary: 
      Parkinson's disease is a common, disabling, progressive condition characterised by severe
      problems with movement for which medical treatment in the longer term can be unsatisfactory.
      Deep brain stimulation is a treatment, which directly stimulates the nerve cells affected
      inside the brain to help overcome the difficulties with movement. Classically, deep brain
      stimulation stimulates in a manner that is constant and independent of a patients underlying
      condition as reflected in their brainwave activity. Recent research has suggested that
      adjusting deep brain stimulation in real time using analyses of brain signals recorded from
      deep brain stimulation electrodes (termed closed loop deep brain stimulation) nay be better
      than classical deep brain stimulation in alleviating difficulties with movement. However, it
      remains unclear whether closed-loop deep brain stimulation also leads to fewer unwanted side
      effects on movement control. In order to answer this question, the investigators will analyze
      deep brain stimulation activity and activity recorded from the surface of the head in
      Parkinson's disease patients undergoing deep brain stimulation surgery. During the recordings
      patients will perform different movement tasks. Deep brain stimulation has been found to
      reduce patients' ability to suppress inappropriate movements in certain tasks and performance
      in these tasks will be the core point of interest. The recordings will be conducted three
      times: During closed loop deep brain stimulation, classical deep brain stimulation and while
      the stimulator is turned off. This will allow the investigators to assess putative
      differences in the effect of closed loop and classical deep brain stimulation with regards to
      wanted and unwanted effects on movement control and to elucidate their correlates in the
      brain.
    

Detailed description: 
      Study Summary Patients will undergo standard 2 part deep brain stimulation implantation
      (electrode implantation day 1, battery and stimulator implantation approximately day 7, home
      approximately day 10). The experiments will be performed whilst the patients are inpatients
      between the two operations and will therefore not require any extra visits or delay in
      starting therapeutic deep brain stimulation. This paradigm is the standard method for
      conducting local field potential research in human and represents the paradigm by which the
      vast majority of previous research in this area has been conducted. Patients will be tested
      either at Oxford University Hospitals National Health Service Trust or University College
      London National Health Service Trust.

      At least 24h after electrode implantation (first of the two surgeries) patients will be
      approached about the study and left with the patient information sheet for 24 hours, before
      further discussion, and, if appropriate consent.

      Thereafter, the following procedures will be undertaken:

        1. The subjects will participate in a short assessment testing their cognitive function and
           fill out questionnaires regarding handedness and impulsiveness traits . Furthermore,
           they will be introduced to the three motor tasks, which they will perform during the
           definitive test. Together, these assessments will take approximately one hour.

           Prior to the next steps, which will be conducted on the same day or 1-3 days
           later(depending on the preferences of the participant), participants will be requested
           to withhold their usual medication overnight so that they are assessed off medication on
           the morning of the tests.

        2. Deep brain stimulation will be evaluated in order to find the best stimulation
           parameters ( the settings, which yield the best clinical benefit) for each individual
           patient. This will take approximately 1 hour and is part of the standard clinical
           procedure.

        3. Recordings will be made from the deep brain stimulation electrodes and electrodes placed
           on the surface of the head in order to assess activity and communication within the
           brain. During the recordings participants will perform three motor tasks using their
           hands. In the first two tasks they have to decide whether to press a button on a
           computer mouse or refrain from a response depending on the nature of some small dots
           moving in different directions on a computer screen. This will allow assessing patients'
           ability to perform and inhibit movements. In the third task they are asked to press a
           button depending on the direction of an arrow presented in the middle of the screen,
           while ignoring arrows around this central cue. This additional task will allow assessing
           patients' ability to control conflicting response tendencies. The recordings will be
           conducted three times: During closed loop deep brain stimulation, open loop deep brain
           stimulation and while the stimulator is turned off. The order of these sessions will be
           randomized and counter-balanced across participants. The experimental recordings will
           take approximately 2 hours.

      Prior to recordings we will assess motor impairment using a validated clinical score and
      patients will have the opportunity to familiarize themselves with the motor tasks.

      Completion of the recordings will mark the end of an individual's participation in the study.
      Given the overall duration of the study patients will be offered the opportunity to complete
      the recordings after overnight withdrawal of dopaminergic medication over two days or on one
      single day if preferred.

      Thereafter the patient will have their stimulator implanted as usual (most often 7 days after
      the first operation) and they will be discharged on day 9 - 10 according to their clinical
      recovery.

      For patients with already implanted pacemakers, suitable participants will be identified by
      the Functional Neurosurgery team who follow the clinical care of the patients. The invitation
      letter and information sheet will be provided by the clinical team on behalf of the
      researchers. If patients are interested, they would then be asked to contact the researchers.
      The same assessments as above (rating scales, motor tasks) will be conducted on one single
      day in the National Hospital for Neurology and Neurosurgery, London.

      Clinical intervention:

      Externalisation of electrode wires. The externalisation of the electrode wires will be
      performed by trained neurosurgeons. This will occur in the awake patient under local
      anaesthetic (or under a brief general anaesthetic if independent assessment of the patient's
      clinical state by an anaesthetist determines this to be necessary) in the neurosurgical
      department.

      Research intervention:

      Single blinded counterbalanced within-subject trial. Patients will undergo closed loop deep
      brain stimulation, open loop deep brain stimulation and a session without deep brain
      stimulation whilst performing motor tasks. Local field potential and electroencephalographic
      activity will be simultaneously recorded.

      Closed loop deep brain stimulation will be delivered through a portable battery operated
      electronic device connected to the externalised leads. This incorporates an amplifier that
      allows brain waves to be recorded during deep brain stimulation, a controller and a
      stimulator. The controller is a simple rectifier and level detector, which then operates a
      switch that allows stimulation. The level detector is adjusted so that deep brain stimulation
      is only allowed when a certain clinician determined threshold of pathological brain wave
      activity is exceeded. The stimulator supplies stimulation at a frequency of 130 Hertz and a
      voltage as used for standard clinical stimulation. The device weighs about 350 grams and is
      most simply carried in a small shoulder bag, or attached to a belt.
    

Intervention name(s): Deep Brain Stimulation applied through custom built external stimulator (Little et al., 2013, 2015); closed-loop Deep Brain Stimulation applied through custom built external stimulator (Little et al., 2013, 2015); Deep Brain Stimulation off; local field potentials and electroencephalography recordings
Intervention type(s): Procedure; Procedure; Procedure; Device
Intervention description(s): 'Classical' high-frequency Deep Brain Stimulation, which is applied irrespective of ongoing brain activity.; Deep Brain Stimulation, which is applied depending on ongoing brain activity.; Deep Brain Stimulation is turned off.; Simultaneous recordings of local field potentials from subthalamic nucleus and electroencephalography
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: blinded cross-over study of no deep brain stimulation, conventional deep brain stimulation and adaptive deep brain stimulation
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Basic Science
Keywords: Deep Brain Stimulation