1. Purpose of the Guidelines
These guidelines are instituted for members of the Society with respect to ethical
issues of the non-invasive studies of human brain functions. Examinations being
addressed herein are: magnetoencephalogram (MEG), transcranial magnetic stimulation
(TMS), positron emission tomography (PET), single-photon emission computed tomography
(SPECT), functional magnetic resonance imaging (fMRI) and neuropsychological
studies. Such methods do not affect research subjects invasively, thus research
using these methods are called "non-invasive studies". Each method,
however, has different ethical issues. These guidelines should be considered
as a reference guide of the Japan Neuroscience Society, and are not intended
to limit or constrain individual studies in each research organization or institute.
When planning a research project, it is desirable that the project be separately
approved by an ethical committee of the research@organization or institute.
It should be understood, however, that the submission policy of the official
journal of the Society should clearly state these guidelines, and studies to
be published in the journal are required to follow the guidelines. It should
be noted that the guidelines are not applicable to a clinical case where an
examination is conducted for the purpose of treatment or diagnosis which benefits
patients directly, and are only applicable to a case where a normal person or
a patient is subjected to an examination for the purpose of research.
2. Explanation to the Subject
Before examination, it is necessary to explain the general outline of the examination
to @the subject, and to obtain a written agreement from the subject. Such explanation
should include: the purpose of the examination; an outline of the examination;
anticipated risks and possible discomfort to be experienced by becoming the
subject; how and to what extent his/her personal information will be kept confidential;
the right to withdraw from the study or refuse to be the subject at any time;
and the fact that withdrawing will not result in a penalty or loss of benefits.
3. Informed Consent
When asking a person to participate as a research subject, it is necessary to
obtain written informed consent from him/her prior to the experiment. In particular,
if the research includes any unknowns about safety of the subjects during its
course of research, and if there is a possibility that the subject may be burdened
with excessive physical and/or psychological strains, informed consent must
be obtained with even more discretion. The documentation of informed consent
may differ among research organization or institutes, or research methods used.
However, it must comply with the international standard (Helsinki Declaration,
revised in Edinburgh in 2000.)
4. Examination Guidelines Specific for Each Non-invasive Study
A. MEG
When conducting an MEG, a physician in charge or a deputy thereof must attend
the examination. However, if the person responsible for the examination is a
medical doctor, a nurse in charge of the patient may attend the examination
in place of the doctor in charge. Particular caution is required when the patient
has epilepsy. If a seizure occurs during the examination, the examination must
be terminated immediately so as to administer an appropriate treatment to the
patient. Inside a shielded room the patient is monitored at all times during
the examination using a television camera. In some cases, a doctor or a nurse
may stay in the shielded room to observe the state of the patient. The subject
in the shielded room and the person responsible for the examination outside
the shielded room must be able to communicate closely with each other by means
of a microphone at all times, so that the@subject can clearly express his/her
feelings to the examiner outside the room.
B. TMS
In a case of single or double stimulation, the medical history of the subject,
even if he/she is a healthy person, must be obtained to ensure that the subject
does not have a past history of febrile convulsions or of diseases that can
deteriorate with stress such as@asthma or the like, whereby it is possible to
deal with any unforeseen situations. When repetitive magnetic stimulation of
high frequency is used, extra caution is needed. Prior to the experiment, it
is necessary to thoroughly explain to the subject that even a healthy person
might have a convulsive seizure under this stimulation. The explanation should
refer to the references given below. A doctor must attend the experiment and
must observe the subject during the course of the experiment, so that the doctor
can treat the subject if the subject develops a convulsive seizure. It is contraindicated
to use the following as a subject: patients having a metal piece within the
brain, patients with a cardiac pacemaker, children, and pregnant women.
[References]
1. Wassermann EM: Risk and safety of repetitive magnetic stimulation: report
and suggested guidelines from the international workshop on the safety of repetitive
transcranial magnetic stimulation, June 5-7, 1996. Electroenceph Clin Neurophysiol
108: 1-16, 1998.
2. Chen R, Gerloff C, Classen J, Wassermann EM, Hallett M, Cohen LG: Safety
of different inter-train intervals for repetitive transcranial magnetic stimulation
and recommendations for safe range of stimulation parameters. Electroenceph
Clin Neurophysiol 105: 415-421, 1997.
C. PET/SPECT
When using PET or SPECT, it is necessary to consider radiation exposure of the
subject and the examiner responsible for the experiment. Regarding the fundamental
principle for radiation protection, according to the recommendation made by
the International Commission on Radiological Protection (ICRP) with regard to
individual radiation dosage, the concept of justification is applied which reads
"the action should not be employed unless the introduction thereof generates
positive profit to the subject."1) Regarding the radiation exposure of
the subject, a standard different from the one for public exposure may be used
because the participant voluntarily becomes the subject of the experiment. Nonetheless,
there is no direct benefit to the subject by becoming one, and thus, the ethics
committee of each research organization or institute should set an upper limit
to the radiation exposure dosage when planning for the examination so as to
avoid radiation exposure as much as possible. When selecting a subject, the
following must be taken into consideration: health condition; symptoms; age;
sex; and fitness to consent, and the selection must be made carefully. Women
who are pregnant or are likely to be pregnant must not be subjects of the examination.
As a rule, children should also not be subjects, but if clinical benefits can
be expected, the examination may be conducted with an approval from the ethics
committee of the respective research organization or institute.
[Reference]
1. ICRP: 1990 Recommendations of the International Commission on Radiological
Protection. ICRP Publication 60, Pergamon Press, Oxford, England, 1990.
D. fMRI
Measurement at a static magnetic field of 2-4T may be conducted by obtaining
an approval from the ethics committee of each research organization or institute.
Measurement at a static magnetic field exceeding 4T must be conducted after
thorough discussion with the ethics committee that includes an expert on magnetic
field. Change in magnetic field intensity over time is measured by a method
determined by IEC for each gradient coil. Alternatively, by obtaining examination
data from a manufacturer, it is necessary to regulate the maximum value of the
time-rate-of-change in magnetic field intensity according to the IEC standard
or the US FDA viewpoint. With respect to the RF heat generation, in a case where
a volume coil whose output is distributed almost evenly is used, it should be
regulated only for an average value at the head. When a volume coil other than
that mentioned above or a surface coil is used, the relative spatial distribution
of an output at each coil must be obtained to regulate the local maximum. When
measuring at a value exceeding the range of the normal operation mode according
to the IEC standard, it is necessary to obtain an approval from the ethics committee
of each research organization or institute. The following people must not be
chosen as a subject: (1) a person with a cardiac pacemaker; (2) a person with
cardiac valves; (3) a person who has a metal piece within his/her body, that
cannot be confirmed whether it is nonmagnetic or not, (such as surgical clips);
and (4) a person with difficulty in communication.
E. Neuropsychological Study
A neuropsychological study itself is a method to test the cognitive process
of a subject or a patient by measuring his/her ability to answer questions or
to perform a task. Thus, collected data include verbal and behavioral data.
During the neuropsychological study, a person in charge of the study tends to
conduct a relatively large number of tests systematically, whereby there is
a risk of causing unnecessary psychological burden on the subject. Therefore,
such aspect should be given thoughtful consideration.