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.