Measuring tFUS-dependent changes in behaviour (in our target tasks) when targeting deep brain regions [Behavioral Objective]
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
The experiment is conducted on healthy participants. Using the proposed technique we aim at understanding the neural substrate of empathy
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary outcome of the study will be participant performance in our task.
(Behavioural Outcome)
Secondary outcome
-
Background summary
The discovery of mirror neurons in the macaque premotor cortex (di Pellegrino
et at., 1992), active while the monkey performs an action and vicariously while
viewing similar actions performed by others, was a game changer. It suggested
that we process what goes on in other people not only by abstract thoughts, but
also by mapping their states onto our bodily states (Rizzolatti and Sinigaglia,
2010; Gallese and Sinigaglia, 2011). In humans, using fMRI, we showed that
somatosensory cortices, normally active while we sense our bodies move or be
touched, are also vicariously activated while witnessing others move (Gazzola
et al., 2006; Gazzola and Keysers, 2009) or experience neutral (Keysers et al.,
2004) or painful (Meffert et al., 2013) sensations on their skin. The anterior
insula (AI), and the mid- to anterior cingulate cortex (abbreviated ACC),
normally active while we experience emotions, are also vicariously activated
while witnessing the emotions of others (Carr et al., 2003; Singer et al.,
2004, 2006; Jackson et al., 2005; Lamm et al., 2007, 2011; Meffert et al.,
2013; Morrison et al., 2013).
That people reporting more empathy show stronger vicarious activations in
primary somatosensory cortex (SI) (Gazzola et al., 2006) and AI (Singer and
Lamm, 2009), led many to consider vicarious activations (VA) as the neural
basis for empathy (Engen and Singer, 2013). Recently, this line of research has
become the target of criticism: although no one now doubts humans have
vicarious activations, the function of these activations (Hickok, 2013), and
how they influence empathy is the topic of many speculations and few hard
facts. All there is, is encouraging correlational evidence. We now must
directly tackle the function of these systems, by going beyond correlation into
causation. The biggest obstacle to this approach so far is that the key
vicarious pain regions (AI and ACC), lie centimetres below the surface of the
brain, beyond the reach of traditional non-invasive tools including
transcranial Direct Current Stimulation (tDCS) or Transcranial Magnetic
Stimulation (TMS). Transcranial focused ultrasound (tFUS) is a new and very
promising non-surgical low-energy technique for modulation neural activity with
high spatial resolution, adjustable focus and low tissue attenuation. tFUS has
been used safely and effectively for neural stimulation in mouse, rabbit and
monkey (Tufail et al., 2010; Yoo et al., 2011; Deffieux et al., 2013), and has
recently been shown to also be a safe and effective method of transient
cortical modulation in humans (Legon et al., 2014; Mueller et al., 2014;
Sanguinetti et al., 2014; Lee et al., 2015).
We will therefore aim to selectively modulate activity within brain regions
vicariously activated during observation of others* emotions. In order to
achieve this goal, we will use transcranial focused ultrasound stimulation
(tFUS).
The scientific benefit of US as neuromodulation tool is enormous: the
scientific community will finally be able to test causality between deep brain
activity and behaviour, opening a new era of knowledge. Transcranial focused
ultrasound could additionally replace deep brain stimulation, offering a cheap
and safe method for the treatment of brain disorders such as essential tremor
or Parkinson's disease. There is currently no way to affect brain tissue deep
to the cortex without surgery, genetic alteration or viral vectors (the latter
two are not approved for human use). This technology is non-surgical and as
invasive as any diagnostic ultrasound exam. With success, transcranial focused
ultrasound could become useful world-wide as a cheap, portable and effective
tool for human brain mapping efforts as well as for the diagnosis and potential
treatment of a broad range of psychiatric and neurological disorders. The
anticipated risk is minimal; the immediate benefit is zero, though the
potential future benefits for the academic and medical community at large
justify the low risk and limited immediate benefit.
Study objective
Measuring tFUS-dependent changes in behaviour (in our target tasks) when
targeting deep brain regions [Behavioral Objective]
Study design
A total of 40 healthy neurologically intact voluntary participants will be
recruited.
During the recruitment phase participants will be informed of all the
procedures they will undergo. Moreover, they will be screened for tFUS
stimulation.
The experimental session will start by positioning, through neuronavigation,
the tFUS transducer. The optimal location will be chosen in order to target
either the anterior Insula or the cingulate cortex. The specific target will be
selected based on a fMRI study performed before this project. In the
preliminary fMRI study, participants will be shown a set of emotional facial
expressions and their brain activity will be recorded, this will instruct us on
the specific region to target with tFUS.
After positioning the transducer, participants will be asked to watch short
video-clips depicting emotional facial expressions. After observation they will
be asked to rate the emotional facial expressions.
The full set of video-clips will include: 25 painful, 25 disgusted and 25 happy
facial expressions. Each clip used in the study has a duration of 2 seconds.
During observation, a short ultrasound burst (0.5 seconds) will be applied to
the target region. In counterbalanced blocks we will also include sham trials,
in which the transducer is turned upside down and NO ultrasound stimulation is
applied. Sham trials will be included to control for possible unspecific
placebo-like effects on brain activity (possibly caused by vibration on the
skin produced by the transducer or the chirping noises at times present).
Participants will thus undergo 75 active trials and 75 sham trials.
Using this design, we can investigate the effect of tFUS on participants*
rating of the emotional facial expressions (behavioural objective). The session
will also include an anatomical scan, which will facilitate post-processing.
Study burden and risks
No burden is associated with our study. Risks are minimized by our screening
procedure.
Meibergdreef 47
Amsterdam 1105 BA
NL
Meibergdreef 47
Amsterdam 1105 BA
NL
Listed location countries
Age
Inclusion criteria
healthy participants, age 18-35
Exclusion criteria
A potential subject who does not meet any of the following criteria will be
excluded from participation in this study:
- Proficiency with the English language
- Potential participants will be asked to fill a standard questionnaire for
neuromodulation studies (TMS/tDCS) to exclude any participant with
contraindications to brain stimulation/neuromodulation.
* EXAMPLE OF SAFETY SCREENING
* Have you ever:
Had an adverse reaction to neuromodulation or ultrasound?
Had a seizure?
Had an EEG?
Had a stroke?
Had a head injury (include neurosurgery)?
* Do you have any metal in your head (outside of the mouth,) such as shrapnel,
surgical clips, or fragments from welding or metalwork?
* Do you have any implanted devices such as cardiac pacemakers, medical pumps,
or intracardiac lines, cochlear implants, implanted brain stimulators,
implanted defibrillator?
* Do you suffer from frequent or severe headaches?
* Have you ever had any other brain-related condition?
* Have you ever had any illness that caused brain injury?
* Are you taking any medications? (e.g. Tricyclic anti-depressants, neuroleptic
agents, and other drugs that lower the seizure threshold)
* If you are a woman of childbearing age, are you sexually active, and if so,
are you using a reliable method of birth control?
* Does anyone in your family have epilepsy?
* Do you need further explanation of the technique and its associated risks?
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL74100.018.20 |