Elucidating the therapeutic mechanism of DBS by simultaneously stimulating and recording from the target brain region.

Deep Brain Stimulation (DBS) of the ventral part of the anterior internal
capsule (vALIC) is a promising option for patients with otherwise
treatment-refractory obsessive-compulsive Disorder (OCD) (Denys et al 2010).
However, the high variability among patients and clinical response patterns has
made it difficult to gain systematic insight into the optimal neurosurgical
target and stimulation settings. At present, stimulation parameters are based
on clinical feedback and previous experience with other patients, which is
time-consuming, inefficient and subjective. A quantitatively driven approach to
tailor stimulation parameters is urgently needed for more effective and
efficient clinical treatment. Preliminary work by our group indicates that
neural changes in the frontostriatal network are essential for efficacy of DBS.
Recently we acquired prototype bi-directional brain radio devices that not only
stimulate but also record activity from the targeted brain structure. We
propose to use these unique devices in select patients already implanted with
or eligible for DBS electrodes, in order to develop more effective and
systematic stimulation DBS parameters. Moreover, these devices will also afford
us the possibility to get a greater understanding of the neural pathophysiology
of OCD that can be targeted with DBS and other treatment modalities, by
allowing us to monitor the brain activity of patients as they experience
symptoms in daily life situations.

Our primary objectives are to decode **signatures** of activity from the
electrode that might prelude or accompany an OCD attack, by analyzing its
activity in an experimental setting and in real-life situations, and to
correlate symptom changes with corticostriatal response at different settings
by recording local neural activity (EEG oscillatory amplitude) and network
activity (EEG oscillatory phase stability and frontostriatal connectivity) at
the electrodes and the scalp.

Our second objective is to investigate DBS induced changes in corticostriatal
EEG oscillations that are associated with various cognitive and behavioral
paradigms and with cortisol levels.

Observational cohort study in 11 OCD patients that are in need of battery
replacement or are eligible for a first DBS implantation. Instead of a regular
neurostimulator, these patients will receive a bi-directional brain radio
device. We will use this device to record DBS-related neural changes which will
be correlated with relevant clinical changes.

The benefit for participants of this study will be indirect, as the results of
this study will allow more efficient DBS for other OCD patients. Patients
eligible for the study are in need of a stimulator replacement or a new DBS
system. As replacement of the stimulator or new implantation of a DBS device is
a surgery that will need to be performed anyhow, there is no additional
surgical risk. In addition to the possibilities for recording brain activity,
the experimental stimulators have exactly the same functional performance as
the regular stimulators, so that there will be no loss of therapeutic effect
for the patients. There are no risks associated with EEG acquisition and the
burden can be considered minimal. The treatment itself is not a point of
investigation in this study. We classify this study as having a low chance of
possible risks and a low degree of harm, leading to a moderate risk to
patients, since a DBS system is used outside of the intended use.
The main burden for the patient consists of a 15-20% shorter (1.5-2 months)
shorter interval between two stimulator replacement surgeries, as the
experimental stimulator has a shorter lifetime than a regular stimulator due to
the recordings. Additional burden will be the periods of symptom provocation
they will have to endure when the stimulators are turned off and during
provocation tasks, and the time and effort they are asked to invest in the
study visits and in recording their symptoms and daily activities at home,
according to the study protocol.