This two-part study will use transcranial magnetic stimulation, or TMS (see below), to
explore how the brain forms memories. People remember only some of the events they
experience every day, such as faces they perceive, words they read, speech they hear and
interpret, and so forth. The events remembered are those that have been saved or formed in
the brain. Part 1 of this study involves testing materials for Part 2, the TMS experiment.
Part 2 uses TMS to examine what parts of the brain are involved in forming memories.
Information gained from this study may be used in developing methods of enhancing memory in
both healthy people and in patients with memory impairments.
Healthy right-handed volunteers between 18 and 35 years of age may be eligible for this
study. Candidates may be screened with a medical interview and physical examination and a
brief test of short- and long-term visual and verbal memory. Eligible volunteers may
participate in Part 1 or Part 2 of the study, as follows:
Part 1 - Preparation of Words and Picture Materials
Participants look at several words or shapes that appear in random order on a computer
screen and try to remember them as well as possible for a memory test that will be given 20
minutes later. Each image appears on the screen for 3/4 of a second, with 1-1/4-second
intervals between them. For the test, words and shapes are again shown on the computer
screen at the same timing and intervals. When the items appear, the subject presses one of
three buttons as quickly as possible, determining if he or she has recognized the items with
a high or low level of confidence. The entire procedure lasts up to 1 hour, with breaks in
between. The purpose of this experiment is to find appropriate words and pictures to use as
stimuli in the TMS study described below.
Part 2 - TMS Experiment
For TMS, the subject sits in a comfortable chair. An insulated wire coil is placed on the
scalp, and brief electrical currents are passed through the coil, creating magnetic pulses
that stimulate the brain. The pulses may cause a pulling sensation on the skin under the
coil and twitching in muscles of the arm or leg. Electrodes are taped to the skin over some
muscles of the hands to record the electrical activity of the muscles. Pulses are delivered
in trains or short bursts of impulses, each lasting half a second. Participants receive 90
trains for a total of 900 pulses. TMS is applied during the first part of the memory study,
when the words and shapes are first presented on the computer screen, but not during the
second presentation for memory testing. The entire procedure takes up to 2 hours, with
breaks in between.
Before the TMS session, participants undergo magnetic resonance imaging (MRI) to determine
where to place the coil for TMS. For MRI, the subject lies still for up to 30 minutes at a
time on a table that slides into the scanner, a narrow metal cylinder surrounded by a strong
magnetic field. Earplugs are worn to muffle loud knocking sounds that occur while the
scanner takes pictures. Subjects can communicate with the MRI staff at all times and can
ask to stop the procedure at any time.
Recent functional imaging studies showed that memory retrieval is associated with activation
in the prefrontal cortex during the encoding process. However, a cause-effect link between
prefrontal activity and encoding has not been demonstrated. The purpose of this protocol is
to test the hypothesis that inhibitory repetitive transcranial magnetic stimulation (rTMS)
over left prefrontal cortex interferes with encoding of verbal items (words) into episodic
memory, thereby identifying this region as a substrate mediating verbal encoding.
Identification of the role of the prefrontal cortex in verbal memory encoding is the first
step to try to develop strategies to enhance such encoding processes in patients with memory
impairments, an issue of relevance in neurorehabilitation.
We plan to apply rTMS over left prefrontal cortex and over two control sites, during
encoding of verbal and nonverbal items into episodic memory. Normal, healthy volunteers
will be studied. The outcome measure will be performance on a subsequent memory test for
words presented during left prefrontal rTMS, as compared to performance for words presented
during rTMS over the control sites or without rTMS. This measure will indicate if left
prefrontal stimulation can disrupt memory encoding of words relative to other stimulation
sites or to no stimulation.
A secondary outcome measure will be performance on a subsequent memory test for words
presented during left prefrontal rTMS, as compared to performance for pictures presented
during left prefrontal rTMS. This measure will indicate if disruption of left prefrontal
function with TMS affects verbal and more than non-verbal memory encoding.
Healthy right handed volunteers, aged 18-35 years, will be included in this protocol.
Exclusion criteria for this study will be any current medical or surgical condition or
psychiatric or neurological illness. Furthermore, any individual who is on medication
with potential influence on nervous system function, who has a history of surgery with
metallic implants or known history of metallic particles in the eye, cardiac pacemaker,
neural stimulators, cochlear implants, pregnancy, or history of drug abuse, will be
excluded from the study.