Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT05406349 |
| Other study ID # |
K99NS126715 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 6, 2022 |
| Est. completion date |
April 2027 |
Study information
| Verified date |
November 2023 |
| Source |
University of California, Los Angeles |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Spatial navigation is a fundamental human behavior, and deficits in navigational functions
are among the hallmark symptoms of severe neurological disorders such as Alzheimer's disease.
Understanding how the human brain processes and encodes spatial information is thus of
critical importance for the development of therapies for affected patients. Previous studies
have shown that the brain forms neural representations of spatial information, via
spatially-tuned activity of single neurons (e.g., place cells, grid cells, or head direction
cells), and by the coordinated oscillatory activity of cell populations. The vast majority of
these studies have focused on the encoding of self-related spatial information, such as one's
own location, orientation, and movements. However, everyday tasks in social settings require
the encoding of spatial information not only for oneself, but also for other people in the
environment. At present, it is largely unknown how the human brain accomplishes this
important function, and how aspects of human cognition may affect these spatial encoding
mechanisms. This project therefore aims to elucidate the neural mechanisms that underlie the
encoding of spatial information and awareness of others. Specifically, the proposed research
plan will determine how human deep brain oscillations and single-neuron activity allow us to
keep track of other individuals as they move through our environment. Next, the project will
determine whether these spatial encoding mechanisms are specific to the encoding of another
person, or whether they can be used more flexibly to support the encoding of moving inanimate
objects and even more abstract cognitive functions such as imagined navigation. Finally, the
project will determine how spatial information is encoded in more complex real-world
scenarios, when multiple information sources (e.g., multiple people) are present. To address
these questions, intracranial medial temporal lobe activity will be recorded from two rare
participant groups: (1) Participants with permanently implanted depth electrodes for the
treatment of focal epilepsy through responsive neurostimulation (RNS), who provide a unique
opportunity to record deep brain oscillations during free movement and naturalistic behavior;
and (2) hospitalized epilepsy patients with temporarily implanted intracranial electrodes in
the epilepsy monitoring unit (EMU), from whom joint oscillatory and single-neuron activity
can be recorded.
Description:
This research study is based upon a unique opportunity to work with neurosurgical patients,
who already have electrodes implanted in deep brain structures for clinical reasons (i.e.,
for the monitoring and treatment of pharmaco-resistant epilepsy). Research procedures will
only be performed with patients who already have such electrodes implanted for clinical
reasons; no electrodes will be implanted for research purposes, and the researchers will not
have any influence on the implantation procedures of these electrodes. Two groups of
participants will be asked to participate in the research study: 1. Hospitalized patients who
have electrodes implanted temporarily (typically for up to two weeks) for epilepsy monitoring
in the epilepsy monitoring unit (EMU participants). 2. Patients who have
chronically/permanently implanted electrodes as part of the NeuroPace RNS System for the
treatment of epilepsy (RNS participants). Independent from and prior to the research study,
the patient's clinical care team (neurologists, neurosurgeons, etc.) decide whether
electrodes or the RNS System will be implanted based solely on clinical criteria. If
electrodes or the RNS System are implanted, patients will then be offered to participate in
the research study; however, the decision whether or not to participate in the research study
will not have any effect on the patient's treatment or clinical care.
Screening, recruitment, and consent procedures for EMU participants:
If the clinical care team decides - independent from the research study - that a patient's
clinical condition merits implantation of temporary electrodes and hospitalization in the
epilepsy monitoring unit (EMU), the patient's neurologists or neurosurgeons will invite the
patient to participate in the research study. The neurosurgeons and neurologists make it
clear to the patient that the decision to participate in the research is entirely voluntary
and that the patient's medical needs will not be affected in any way by this decision. For
patients who are interested in participating in the research study, the principal
investigators meet with the patient to discuss the consent form. Subsequently the principal
investigator also ensures that the patient fully understands the consent form and emphasizes
again to the patient that participation is entirely voluntary and that the patient's decision
whether to participate or not will have no effect on their medical care. If the patients are
local, the research team meets with the patient at UCLA before or after pre-surgical tests.
This is commonly done a 1-3 weeks before the surgery. For patients traveling long distance,
the discussion may take place the day before the surgery. After discussion the patient signs
the consent form to participate in the research study and it is countersigned by the
principal investigator.
Screening, recruitment, and consent procedures for RNS participants:
For the proposed study, the investigators have already identified a number of patients for
other ongoing studies that received NeuroPace RNS System at the UCLA medical center with RNS
devices implanted in medial temporal lobe regions. These patients have been identified
through their neurosurgeon or neurologist, who are part of the study team. These
neurosurgeons and neurologists will inform their patients about the opportunity to
participate in this research study. The neurosurgeons and neurologists make it clear to the
patient that the decision to participate in the research is entirely voluntary and that the
patient's medical needs will not be affected in any way by this decision. Potential subjects
external to the UCLA medical center may have preliminary contact from their treating
physician from a referring institution. If patients indicate interest in the study, the
principal investigator, faculty sponsor, or the study coordinator will make initial direct
contact via phone in a private secure location to introduce and describe the study after
which further information and copy of consent form can be sent for review via secure
encrypted e-mail and/or mail, if necessary. The principal investigators also ensure that the
patient fully understands the consent form and emphasize again that participation is entirely
voluntary and that the patient's decision whether to participate will have no effect on their
medical care. Potential participants will be approached no earlier than 3 months after their
RNS system placement to see if the patient would be interested in volunteering for the study.
Consent may be obtained over the phone or internet for participants necessitating extended
travel arrangements and accommodations. Participants, particularly those consented over the
phone or via the internet, will be provided with a physical copy of the consent form and
asked to sign it before performing any research procedures.
Behavioral tasks:
RNS participants will complete both freely moving and stationary view-based spatial
navigation and observation tasks whereas EMU participants will complete only stationary
view-based spatial navigation and observation tasks. Intracranial electroencephalographic
(iEEG) activity in RNS participants, and joint single-neuron activity and local field
potentials (LFP) in EMU participants will be recorded while participants complete variants of
self-navigation and observation tasks, similar to our previous work. All spatial navigation
and observation tasks will have the basic structure as follows:
- Self-navigation task: RNS participants will navigate an experimental room (size about
19.4 × 17.1 feet) in which 20 unique signs (combinations of a single color per wall with
numbers 1 to 5) are mounted along the 4 room walls. In addition, several predefined
target locations (each named with a letter) will be randomly distributed throughout the
room, but not visible to participants. Participants will be repeatedly asked to navigate
to one of the visible signs (e.g., "Go to sign yellow-4") or to find and learn one of
the invisible target locations (e.g., "Find target location T"). EMU participants will
be asked to perform the self-navigation tasks in a virtual environment, which is an
exact virtual replica of the real experimental room. To ensure a maximally immersive
experience, the participant will see this room from first-person perspective via a
head-mounted display, and the participant will be able to virtually walk around in this
room using wireless controllers. In the case of any discomfort, tasks can also be
performed on a desktop computer screen.
- Observation task: RNS participants will sit in the corner of the experimental room and
observe another person (i.e., an experimenter) that walks around within the room in a
seemingly random trajectory (in fact, the trajectory will be pre-defined and controlled,
but unknown to participants). Participants will be asked to press a button whenever the
experimenter hits one of the previously-learned invisible target locations. EMU
participants will also perform this task; however, EMU participants will watch the room
and the other person in a video that was recorded from a corner of the room. This video
will be shown in the head-mounted display, in order to mimic the experience from an
observer's first-person perspective (as if the participant would actually sit in the
real room corner). In the case of any discomfort, tasks can also be performed on a
desktop computer screen. For different study aims, participants will be asked to perform
slightly modified versions of the observation task: Instead of another person,
participants will be asked to observe the movements of an inanimate object (an electric
remote-controlled platform, similar to a remote-controlled toy car), or to observe not
one but multiple other people that move through the experimental room. And participants
will be asked to just imagine movements of other individuals and objects throughout the
room, while no other individuals/objects are physically present.
Electrophysiological recordings in EMU participants during task performance:
For participants with temporarily implanted electrodes in the epilepsy monitoring unit (EMU)
at UCLA, the Neuroport System (Blackrock Microsystems, Salt Lake City, UT) will be used for
data acquisition, which records single-unit and LFP neuronal activity alongside the
simultaneously recording clinical systems for epilepsy monitoring.
Electrophysiological recordings in RNS participants during task performance:
Participants have the chronically/permanently implanted FDA-approved RNS System for clinical
reasons (i.e., treatment of epilepsy), which is designed to treat epileptic seizures by
continuously recording electrophysiological activity from the patient's brain during everyday
life activities, and delivering electrical stimulation when abnormal activity patterns (e.g.,
epileptic seizure-like activity) are detected. For the research study, the study team will
use the regular recording capabilities of the RNS System, while participants perform the
described navigation and memory tasks.
Motion tracking during behavioral tasks:
For RNS participants, the location of participants within the experimental room will be
continuously tracked with sub-millimeter resolution using the OptiTrack motion tracking
system (Natural Point Inc.). Motion tracking will not be performed for EMU participants, as
these participants perform only stationary view-based tasks.
Eye tracking during behavioral tasks:
RNS participants' eye movements will be recorded using a mobile eye tracking headset, which
also allows mapping of the participant's gaze (i.e., their visual focus) onto the video of an
integrated 'world camera' that captures the environment from the participant's point of view.
EMU participants' eye movements will be recorded with a built-in eye tracker within the
head-mounted display, providing eye movement as well as gaze position data.
