Closed-loop Deep Brain Stimulation (DBS) for treatment of movement disorders

Participants will be admitted to hospital as part of the standard clinical management for their prescribed DBS procedure. As appropriate, the participant’s involvement will proceed in three stages; electrode lead externalisation, study period and procedure completion. In the electrode lead externalisation stage, participants will be routinely implanted with commercial DBS electrodes (e.g. Medtronic) as part of their prescribed DBS implantation procedure. A routine lead externalisation procedure will then be performed using a commercial externalisation kit (e.g. Medtronic Externalisation Lead Kit). In some cases, only a brief intraoperative externalisation period will be used. This will allow a subset of experiments to be conducted in a reduced timeframe, minimising the burden to participants and providing key data that will optimise subsequent experiments performed over extended externalisation periods. The study period will last for approximately 20 minutes, during which time different forms of stimulation will be applied and assessed. Stimulation with different pulse width, shape and rate parameters will be tested. The amplitude of stimulation will be progressively stepped up over a period of 5-10 minutes whilst clinical effects are monitored. A washout period of up to 5 minutes will be observed between conditions, depending on the duration of applied stimulation and when symptoms return. In Intra-operative procedures, typically 2-4 conditions will be tested for 5-10min each depending on the time available, the condition of the patient and the research hypothesis being tested. In each condition the stimulation amplitude will be typically stepped from a starting level (e.g. 0.5mA) to a predefined maximum. The starting and maximum amplitude levels, as well as the stimulus parameters, will be selected at the discretion of the research team depending on the stimulation target, the patient’s condition and the research hypothesis being tested. Stimulation parameters tested will include symmetric and asymmetric biphasic pulses, stimulation rates up to 250pps (130Hz typical) and pulse widths up to 1ms (60microseconds typical). Intraoperative assessment is possible as it is standard clinical practice for the patient to be awake during electrode implantation surgery. The experimental session in intraoperative procedures will be administered by our Neurologist and research engineers. When using extended externalisation, the study period will commence after an appropriate recovery period and will typically occur over 5-6 days. The recovery period will depend on the participant and appraised by our Neurologist. This recovery period can be anywhere between 1 to 2 days after stage 1 surgery. During this period experimental sessions will be scheduled for 2 hours twice per day, depending on each participant’s condition. Within each day, sessions will be conducted both off- and on- the participants' standard movement disorder medications, with appropriate wash-out/-in times allowed (varying between 5 and 30 minutes depending on prior stimulation and when symptoms return). The experimental sessions in the extended externalisation procedure will be primarily administered by our research engineers with the Neurologist attending the first session if possible. Where possible, two forms of stimulation will be applied to the implanted electrodes using the externalised leads, conventional open-loop stimulation and biomarker-controlled closed-loop stimulation. Initially, conventional open-loop DBS will be used to evaluate stimulation parameter settings and to identify suitable biomarkers. Based on published data and comparable studies, a subset of approximately 12 stimulation parameter sets (determined by time available, eg a two hour session equals 120 minutes, thus 12 lots parameters can be tested over 10 minutes depending on the time available and the discretion of our neurologist and or Research Engineers). These parameters will be applied in a random order at intervals of about 10 minutes (including a wash-out period). Conditions may make testing of all 12 parameters not feasible in which case a subset will be chosen. The subset of stimulation conditions tested will be chosen by the research team depending on the time available, the implanted location of the DBS electrodes and the condition of the patient. Stimulation with different pulse width, shape and rate parameters will be tested. The stimulating electrode configuration will also be varied. During stimulation, objective measures of participant state (e.g. finger tapping ability, rigidity and/or speech quantification) will be recorded along with conventional clinical assessments (e.g. UPDRS) and subjective observations. Bioelectric signals, such as local field potentials, may also be recorded during stimulation and will be subsequently analysed to seek correlations between each participant’s clinical state and oscillatory activity in various frequency bands. At all times within these procedures wash-out/-in times allowed will vary between 5 and 30 minutes depending on prior stimulation and when Participants' symptoms return. Closed-loop stimulation controlled using the identified biomarkers will then be employed when feasible. Closed-loop stimulation testing would last at the discretion of the Research Team and dependant upon the Participant's comfort. The testing sessions may last between 30min to over several hours (or even days if considered safe to do so by our Neurologist and Research Team). Objective measures of participant state, conventional clinical assessments and subjective observations will be recorded during stimulation to determine the effectiveness of closed-loop DBS. Different stimulation parameter sets (e.g. time-varying patterned stimulation) that were found to be effective for open-loop stimulation may be evaluated using closed-loop stimulation. Following the study period, the participants prescribed DBS procedure will be completed and clinical management will proceed as usual.