Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

The overall goal of the following experiment is to observe and quantify the clinical effect of adaptive deep brain stimulation and compare it to standard stimulation. This is achieved by performing a passive recording from the deep brain stimulation or DBS electrodes of postoperative Parkinson's patients and performing spectral analysis on bipolar montages to identify the optimal contacts for simultaneous stimulation and recording. As a second step standard, continuous clinical monopolar stimulation is performed at the identified contact to determine the parameters that confer clinical improvements such as tremor suppression.

Next intermittent stimulation is performed according to beta amplitude in order to identify trigger thresholds appropriate for adaptive stimulation, which can then be tested against standard continuous stimulation. The results show improvements in clinical outcome with adaptive stimulation compared with standard high frequency stimulation, despite significant reductions in electrical charge delivery and time on stimulation. The main advantage of this technique over existing methods like conventional high frequency simulation is that in acute studies, it reduces overall stimulation and therefore saves the battery as well as improving motor performance.

The implications of this technique extend towards therapy of other neurological and neuropsychiatric disorders treated with DBS because other conditions such as tremor also fluctuate and therefore may be amenable to an adaptive stimulation approach. The idea for this method has developed slowly over time as a number of groups have recognized the importance of excessive synchronization, particularly beta oscillations in the pathophysiology of Parkinson's disease. Begin by obtaining informed consent for the experiment from a patient with medically refractory Parkinson's disease.

Following the implantation of DBS electrodes, there are 2D BS electrodes each having four contacts. A stimulus can be delivered to one contact, and recordings can be obtained from the two adjacent contacts. The contact being used to deliver the stimulus can be changed as desired the night before the experimental procedure stopped the patient's Parkinsonian medication the following morning when the patient arrives for testing, start by washing your hands.

Then gently remove the electrode wires from their protected cover. Next, connect the externalized DBS electrodes to the connector cable. Then connect the electrode to the amplifier.

Finally, connect the reference electrode over the patient's left clavicle. Then record the bipolar local field potential or LFP from contact zero and two contralateral to the worst affected side whilst the patient is at rest. Next, repeat the bipolar recording from contacts one and three.

Perform a power spectral analysis to identify the patient specific beta peak frequency and the bipolar contact pair with the highest beta amplitude for stimulation testing, which are the L zero L two electrodes. In this example, after determining the bipolar contact pair with the highest beta amplitude, which in this case would be zero and two, select the contact that is bridged by those two as the contact for monopolar stimulation. To connect the patient to the adaptive DBS setup.

Connect the analog amplifier to the A to D converter and to the portable computer running the signal analysis software. Second stage digitally filter the signal around the patient's specific beta peak with the four hertz pass band. The software monitors the beta amplitude and uses this to control the stimulation With a preset threshold, the beta amplitude is smooth with a smoothing window of 400 milliseconds.

Next, connect the D to a trigger to the stimulator. The next step is to turn on conventional high frequency stimulation with an initial voltage of zero. Then connect the stimulator to the patient through the amplifier optically, isolate all connections to the patient.

Apply the monopolar stimulation at the contact identified earlier. Monitor the stimulator readout continuously throughout the experiment to ensure that the expected stimulation is delivered slowly. Increase the stimulation voltage by 0.5 volt increments every few minutes.

Looking for the clinical effect threshold. For example, an improvement in tremor, stiffness, or slowness. Establish the clinically useful stimulation voltage, which is generally between 1.5 and three volts and has minimal or no side effects such as paresthesia with the stimulation at the clinically effective voltage.

Switch the stimulator off with a 250 millisecond ramp down. Then with the stimulation still at the clinically effective voltage, switch the stimulator on with a 250 millisecond ramp up. Ask the patient about paresthesia or any other side effects experienced upon switching off and on the stimulation if side effects are present.

Continue to reduce the voltage in steps of 0.25 volts and test for paresthesia by switching the stimulation off and on when no more paresthesia is reported. Set the voltage 0.1 volts below this threshold and turn on the stimulation. Next, increase the beta amplitude trigger threshold and ensure that the clinical effect remains continue to gradually increase the beta amplitude trigger threshold to a level that results in the minimum time on stimulation.

Whilst maintaining a clinical effect, aim for stimulation to be on at most 50%of the time. Adjusting the trigger threshold and stimulation parameters to ensure appropriate adaptive DBS without self triggering is a crucial step. Achieving this requires careful and slow titration of the threshold and stimulation voltages whilst closely monitoring the patient.

Once the trigger threshold and stimulation parameters are set, turn off the stimulation for 10 minutes to wash out the stimulation effect. Being sure to blind the patients to the test conditions. Begin to deliver adaptive DBS conventional DBS or no stimulation.

Allow the test condition to run for a five minute stabilization period. After five minutes, begin the clinical testing. Assess the patient using the unified Parkinson's Disease Rating Scale.

Objective assessment measures such as accelerometry or actigraphy could also be used. After finishing one test condition, turn off stimulation for another 10 minute rest period. Then trigger the next type of stimulation Again, beginning with a five minute stabilization period prior to performing the assessment.

Fix the voltage pulse width and stimulation frequency identically across test conditions so that the only difference relates to the timing of stimulation. With regard to beta amplitude throughout the clinical testing video, record the task so that an independent expert can perform a blinded assessment at a later time. The percent motor improvement from the unstimulated state as assessed by an unblinded observer during the experimental session is shown here for conventional DBS adaptive DBS and random stimulation Blinded assessments were also done by evaluating videos of the motor performance.

The motor scores were improved by 66%and 50%during adaptive DBS in the unblinded and blinded conditions respectively. Despite the reduced amount of total stimulation, the clinical outcome was 29%better unblinded and 27%better blinded in the adaptive DBS group compared with the conventional DBS group. While attempting this procedure, it's important to remember to continuously observe the patient for potential side effects or changes in clinical state Following this procedure.

Other approaches like triggering of different potential biomarkers or with different triggering levels or forms can be performed in order to explore the large variety of possible adaptive DBS paradigms.