Only healthy volunteer subjects will be recruited and studied for this project. Volunteer
subjects will undergo transcutaneous stimulation of the auricular branch of the vagus
nerve (ABVN) to determine whether this modality will also produce cervical vagus nerve
compound action potentials. Ear Stimulation Group
Another part of the study is to measure the vagal response to maneuvers which are known
to stimulate the vagus nerve. The implementation of these vagal maneuvers will allow
comparison of ABVN stimulation to traditional methods of vagal stimulation.- Vagal
Maneuver Group
EAR STIMULATION GROUP:
This is a onetime visit only that involves baseline and test procedures.
Two MRI compatible electrodes will be placed in the auricle of the left ear, fixed by a
plastic armature that wraps around the ear. The leads from the electrodes are connected
to a stimulator.
A pneumatic belt may be placed around the lower thorax. Pneumatic tubes connect this belt
to a pressure transducer that in turn sends signal to a laptop-controlled device that
acquires the signals.
Two ECG electrodes are placed on both sides of the neck overlying the area near the
carotid artery where the vagus nerve is superficial. This is to measure the vagal action
potentials in the neck. Two ECG electrodes are placed one on each arm and one on the
chest for measurement of the electrocardiogram (ECG ). Three ECG electrodes are placed on
the abdomen in a line parallel to the longitudinal axis of the stomach to record the
electrogastrogram (EGG). Electrical stimulation of the electrodes placed in the ear is
provided by a current-constant stimulator. The stimuli consist of rectangular pulses with
450 µs pulse width, delivered at 30 Hz, and pulse train duration of 0.5 seconds.
Stimulation is gated, with 0.5-second delay, after peak inhalation (i.e., during
exhalation) or after peak exhalation (i.e., during inhalation).
Baseline procedure:
During the baseline recording the stimulating electrodes are placed in the auricle of the
subject but no current is delivered. Cervical neck electrodes are placed over the right
and left vagus nerve to record any electrical activity that might occur during the
baseline period. Baseline ECG and EGG recordings are also performed during this interval.
Test procedure:
Stimuli consisting of rectangular pulses with 450 µs pulse width, delivered at 30 Hz, and
pulse train duration of 0.5 seconds are then delivered to the subject. Current intensity
is set to achieve moderate to strong (but not painful) sensation, and pulse
frequency/duration is set following pilot testing to achieve a subjectively comfortable
stimulus sensation. This level of current stimulation is designated "100 per cent." The
current is then reduced to 10 per cent and ABVN is continued for 60 seconds. The current
amplitude is then increased again by 10 per cent and ABVN is applied again for 60
seconds. This sequence is repeated until the "100 percent" level is reached. These
stimuli are delivered during expiratory phase of respiration as investigations have shown
this to be most effective in producing vagal stimulation (8).
Once the target stimulus intensity has been achieved, stimuli are delivered during the
expiratory phase for a total of two minutes. Stimuli are then delivered at 50% and 25% of
the original amplitude for 2 minutes, respectively.
ECG and EGG recordings are continued during auricular branch vagal nerve stimulation.
VAGAL MANEUVER GROUP:
Healthy volunteers will be recruited initially to see the effect of these maneuvers on
the vagal activity.
A total of 30 healthy volunteers will be recruited. At the beginning of the study, a
baseline recording of 10 minutes will be made following which the maneuvers will be
conducted. Cervical neck electrodes are placed over the right and left vagus nerve to
record any electrical activity that might occur during the baseline period. Baseline ECG
and EGG recordings are also performed during this interval by placing the electrodes over
the chest and over the stomach area for ECG and EGG recordings.
After 10 seconds of each maneuver, another 8 minutes of recording will be made before
doing the next maneuver.
For the eating maneuver there is no time restriction and the subject will drink it as per
their capacity. After drinking the Ensure, a 20 minute recording will be made.
Investigators will include the following maneuvers:
Cough; Each subject will be asked to generate approximately 6 to 8 forceful and sustained
coughs over 5 to 10 seconds.
Cold stimulus to face: This technique involves submerging a patient's face in ice cold
water. We propose to place an ice pack or a washcloth soaked in ice water on each
subject's face for about 10 seconds. This creates a physiological response to a person
being submerged in cold water (Diver's Reflex) Carotid Massage: This technique is
performed with the subject's neck in an extended position, the head turned away from the
side being massaged. Only one side is massaged at a time. Pressure is applied underneath
the angle of the jaw in a gentle circular motion for about 10 seconds. The subject is
monitored throughout.
Gagging: A tongue depressor is briefly inserted into the subject's mouth touching the
back of the throat, which causes the person to reflexively gag. The gag reflex stimulates
the Vagus nerve.
Valsalva maneuver: The subject is instructed to bear down as if they were having a bowel
movement. The subject is asked to blow through a mouthpiece that is hooked to a device
used in clinical spirometry until the pressure reaches 10mmHg. Alternatively, we can have
the subject blow through the barrel of a 10 ml syringe for 15-20 seconds. This maneuver
increases intrathoracic pressure and stimulates the Vagus nerve.
Eating: Subjects will be asked to drink Ensure Original that has 220 calories after
fasting overnight to see that effect on vagal activity during eating.
All the maneuvers described above will be conducted for duration of 10 seconds each
except wherever stated otherwise and the recordings will be made for duration of 8
minutes after each maneuver. If it is not possible to all the maneuvers in one visit then
they will be conducted over two visits. Sometimes not all maneuvers will be conducted and
this will depend on the discretion of the investigator.