Characterization of Complex Pulse Shapes in Deep Brain Stimulation for Movement Disorders Using EEG and Local Field Potential Recordings
Condition: Parkinson Disease; Essential Tremor
MeSH terms: Parkinson Disease; Movement Disorders; Essential Tremor
Study type: Interventional

Summary: 
      Parkinson's disease and essential tremor are chronic movement disorders for which there is no
      cure. When medication is no longer effective, deep brain stimulation (DBS) is recommended.
      Standard DBS is a neuromodulation method that uses a simple monophasic pulse, delivered from
      an electrode to stimulate neurons in a target brain area. This monophasic pulse spreads out
      from the electrode creating a broad, electric field that stimulates a large neural
      population. This can often effectively reduce motor symptoms. However, many DBS patients
      experience side effects - caused by stimulation of non-target neurons - and suboptimal
      symptom control - caused by inadequate stimulation of the correct neural target. The ability
      to carefully manipulate the stimulating electric field to target specific neural
      subpopulations could solve these problems and improve patient outcomes. The use of complex
      pulse shapes, specifically biphasic pulses and asymmetric pre-pulses, can control the
      temporal properties of the stimulation field. Evidence suggests that temporal manipulations
      of the stimulation field can exploit biophysical differences in neurons to target specific
      subpopulations. Therefore, our aim is to evaluate the direct neurophysiological effects of
      complex pulse shapes in DBS movement disorder patients. This will be achieved using a
      two-stage investigation: stage one will study the neural response to different pulse shapes
      using electroencephalography (EEG) recordings. Stage two will study the neural responses to
      different pulse shapes using intra-operative local field potential (LFP) recordings. This
      study only relates only to the collection of EEG and LFP recordings in DBS patients. The
      protocol does not cover any surgical procedures, which already take place as part of the
      patient's normal clinical care.
    

Detailed description: 
      Parkinson's disease and essential tremor are chronic movement disorders for which there is no
      cure. When medication is no longer effective, deep brain stimulation (DBS) is recommended.
      Standard DBS is a neuromodulation method that uses a simple monophasic pulse, delivered from
      an electrode to stimulate neurons in a target brain area. This monophasic pulse spreads out
      from the electrode creating a broad, electric field that stimulates a large neural
      population. This can often effectively reduce motor symptoms. However, many DBS patients
      experience side effects - caused by stimulation of non-target neurons - and suboptimal
      symptom control - caused by inadequate stimulation of the correct neural target. The ability
      to carefully manipulate the stimulating electric field to target specific neural
      subpopulations could solve these problems and improve patient outcomes.

      It has been shown that modifying the electrical waveform (e.g. pulse duration, pulse
      polarity, etc.) determine the spatial selectivity in functional electrical stimulation. Also,
      a recent clinical study examined for the first time the acute effects of anodic compared to
      cathodic neurostimulation in 10 PD patients. They found that thresholds for anodic
      stimulation were significantly higher than thresholds for cathodic stimulation, which is in
      agreement with previous research in animal studies and model calculations. However, they also
      reported a better clinical effect of anodic compared to cathodic stimulation. Furthermore, a
      modeling study from Anderson et al. (2018) found that fiber orientations can be selectively
      targeted depending on the stimulus waveform (i.e. cathodic or anodic). Another recent study
      examined the effect of an active symmetric biphasic pulse in 8 PD and 3 ET patients. They
      found that this pulse shapes produced significant clinical improvements compared to the
      standard clinical pulse shape.

      Besides the symmetric biphasic pulse shape, the asymmetric pre-pulse shows great potential
      for the refinement of DBS therapy. If the pre-pulse is anodic, it has a hyperpolarizing
      effect and is therefore referred to as a hyperpolarizing pre-pulse. If it is cathodic, it has
      a depolarizing effect near the electrode and is therefore referred to as a depolarizing
      pre-pulse. Clinical studies focused on the use of asymmetric pulse shapes to improve the
      spatial selectivity by selectively exciting fibers in cochlear implant listeners13-16.
      Modeling studies indicate that a hyperpolarizing pre-pulse can actually decrease the
      threshold for axons and that the threshold is decreased more for axons close to the electrode
      than axons further away. This indicates that a hyperpolarizing pre-pulse may help focus the
      effects of stimulation to axons near the electrode, thus leading to an increase in the
      therapeutic window and potentially more efficient symptom control.

      Evidence suggests that temporal manipulations (i.e. the use of complex pulse shapes,
      specifically biphasic pulses and asymmetric pre-pulses) of the stimulation field can exploit
      biophysical differences in neurons to target specific subpopulations. Ultimately, this may
      lead to an increase in the therapeutic window and/or more efficient symptom control. In this
      study, we aim to understand the neural mechanism underpinning the clinical effects observed
      by manipulating the pulse shapes, by comparing neurophysiological responses to the standard
      clinical pulse shapes to the responses to the complex pulse shapes. This will be achieved
      using two approaches. The first approach will study neural responses to different pulse
      shapes using electroencephalography (EEG) recordings. The second approach will study neural
      responses to different pulse shapes using intra-operative local field potential (LFP)
      recordings. This study and research protocol relates only to the collection of EEG and LFP
      recordings in DBS patients. The protocol does not cover any surgical procedures, which will
      already take place as part of the patient's normal clinical care.
    

Intervention name(s): Boston Scientific: Study tool computer
Intervention type(s): Device
Intervention description(s): Compare clinical outcome measurements of complex pulse shapes to standard clinical pulse shape
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Randomized, crossover, blinded design
Masking: Single (Participant)
Primary purpose: Supportive Care