**Lasker Forum on Ethical Challenges in Biomedical Research and
Practice**

**[Neuroimaging]{.underline}**

**Case Study**

**For Discussion Only**

**May 2003**

***Background***: It is the year 2008, and Dr. Jerome Golda is seeing
the first person of the day at the Cabeza Psychiatric Clinic, a private
group practice that has been designed to bring multiple disciplines to
the treatment of mental health problems. Dr. F. is a neuropsychiatrist;
his colleagues include psychologists, transactional analysts,
radiologists, and pharmacologists. Modern psychiatric practice is
increasingly employing brain imaging technologies to assist the more
traditional psychiatric methods to diagnose and treat mental illness.
Accordingly, the clinic has for some years had a state-of-the-art fMRI
facility[^1], which is now often used in patient evaluation and in
monitoring treatment. Since fMRI images produce what is believed to be
objective understanding of how brain function affects or determines
emotions, including temperament, personality and mood, Dr. Golda often
relies on fMRI to tell him how the brains of his patients are
malfunctioning and whether various interventions restore normal
function.

***The Patient***

That is what is under way in Dr. Golda's examination of John Patton, an
engaging and energetic 18 year old who has been under treatment for
symptoms that have been disturbing Patton and his family. He is given to
bouts of sudden, apparently inexplicable rage; these have not resulted
in violence to others, but on two recent occasions he has damaged
objects -- in one instance destroying a television set following an
upset loss on the part of his favorite NFL team, and in another case
smashing some expensive china during a family holiday gathering.

John Patton had been diagnosed by his primary psychiatrist as having
antisocial personality disorder. Before being referred to Dr. Golda,
Patton had been seen over a number of sessions by a psychoanalyst, Dr.
Hyde. Patton's family history is considered pertinent to his current
behavior in that he comes from a long line of military men, several of
whom attended military schools and were early volunteers for combat
during times of war. The men in his family have a favorable reputation
for aggressiveness, boldness, and leadership but there is also some
suggestion of a tendency towards verbal (and possibly physical)
abusiveness in these men. When Dr. Hyde had probed Patton's childhood,
he found evidence of an unusual level of hostility about his treatment
by his mother, apparently a very strict parent. Patton volunteered that
he rarely experienced uncontrollable anger during his frequent arguments
with his mother. Dr. Hyde also learned that beginning in his first year
in high school, Patton began to display fits of temper, to the extent
that school authorities occasionally called his parents and once
suspended Patton for a short time. Patton has admitted that such
episodes have become increasingly frequent in his life -- enough to
worry his family seriously.

With this information and assessment in hand, Patton was turned over to
Dr. Golda for an evaluation of the neurobiological basis for his
emotional problems. Dr. Golda had already conducted MRI studies of the
boy and found some structural changes in the brain (smaller intracranial
and cerebral volumes) that have been associated with post traumatic
stress disorder (PTSD), possibly resulting from past mistreatment. To
assess any functional component to Patton's behavior, Dr. Golda decided
that it would be useful to create video scenarios for Patton to view
while fMRI studies were being conducted, to perform fMRI studies during
an interview with Patton's therapist, and to combine these techniques in
some sessions. The technical staff at Cabeza has borrowed photographs of
Patton's parents and others who were important in his childhood, and
used these to create computer-generated scenarios which could be played
on a miniature TV flat screen fitted within the fMRI mount in the
examination room while fMRI measurements were being taken.

In one of these scenarios, the simulated video shows Patton's mother and
father engaged in a disagreement so intense that his mother strikes his
father, an incident that Patton had previously reported in detail to Dr.
Hyde as one that had triggered what Patton characterized as typical of
his anger reaction towards his mother. Watching the scenario, Patton
reports anger at his mother, and the fMRI study shows intense activity
in an area of his brain (the amygdala) which is known to be involved in
responding to and producing anger, avoidance, defensiveness, and fear.
This neural reaction was expected but what is troubling about the image
is that the areas of the brain responsible for regulating anger
responses (orbitofrontal cortices) do not "light up" appropriately.
Together, these findings suggest that young Patton has functional brain
patterns that predispose him to react strongly to anger stimuli with a
diminished ability to control his behavior in response to anger. Patton
is therefore considered to be at high risk for violent behavior in the
future. While this kind of prognosis had typically been imprecise, based
only on traditional psychiatric evaluations and behavior tests, studies
had shown that obtaining consistent fMRI data greatly enhanced the
confidence with which such a prognosis can be made.

1.  Is this imaging manipulation justified? Is it ethical? Is this an
    evaluation scenario that would, were it done in the research
    setting, have required IRB[^2] approval? What validation standards
    should exist for this kind of diagnostic use of neuroimaging?

2.  What standards should be in place before fMRI is used to diagnose
    behavior disorders? Who should be involved in developing them?

3.  Assume that, if they know in advance that such scenarios will be
    presented, patients will be able to modify their reactions to them.
    Therefore, Dr. Golda wants to avoid giving patients a precise
    advance description of the assessment scenarios. In clinical
    practice, how should a psychiatrist obtain consent for this kind of
    assessment? Are warnings required?

4.  Did the psychiatrist have obligations to Patton's parents when he
    created a video that "reinvents" the past and puts the parents in a
    negative light?

***We Can Diagnose But We Can't Treat***

Although researchers and pharmaceutical company scientists had
translated MRI and fMRI information about different brain structure and
circuitry into new treatments for panic disorder and anxiety syndromes,
there is as yet no proven therapy to help young Patton. That is, no
treatments are available that can moderate the abnormal brain responses
to anger that are triggered by neural activity in the amygdala and
orbitofrontal cortex. In addition, anger management therapy has been
only inconsistently effective in the type of neural reactions seen here.
The findings and lack of treatment options all lead to the conclusion
that Patton will exhibit an increasing tendency to react angrily to less
provocative stimuli. As a consequence, despite the fact that the neural
findings are not completely determinative, the physicians are fairly
certain that Patton's abnormal behavior will continue and worsen over
time.

1.  What should Patton be told about his brain imaging studies and their
    prognostications?

2.  What are the likely consequences of patients being told that their
    brain functions in ways that are destructive? What are the
    implications of thinking that brain physiology is responsible for
    aberrant behavior rather than perceiving behavior as something
    controlled by the will? Should we hold people completely responsible
    for their actions given that they appear to be at a physiological
    disadvantage?

3.  Would it be legitimate to use neural imaging to classify people as
    aggressive or non-aggressive? What positive and negative uses could
    be made of such a classification?

4.  What are the implications of classifying as medical a condition
    (here, aggressiveness) that was previously attributed primarily to
    social influences?

5.  Would the power of functional brain imaging justify requiring
    Patton's mental health treaters to warn people who would closely
    associate with Patton?

6.  What conditions should exist to justify functional neuroimaging in
    people who have not exhibited mental health or behavioral problems?
    If the imaging is powerfully predictive of behavior, can it be used
    to sort people for characteristics such as aptitude? If so, what
    consequences might flow from this use? And who is entitled to this
    information?

***Now There Is Treatment***

Later, some neurosurgeons develop what is believed to be a very precise
way to create a lesion in the part of the brain that will dampen the
reaction to anger stimuli. Patton's psychiatrist wonders whether Patton
is a candidate for the procedure. He is now 31 years of age and had been
arrested once for violent behavior. Also in the offing is a drug that
can be used to enhance the ability of the brain to modulate aggression.

1.  Would it be appropriate to treat Patton with these therapies? What
    are legitimate bases for making the choice between them?

2.  Does the precision with which fMRI can monitor the physiologic
    responses to these therapies make them different from existing brain
    stimulators or drugs that control behavior?

3.  At what point does the use of such therapies become a disturbing
    form of social control? Might there be a tendency, even if behavior
    is similar, to recommend the treatment for patients who are from the
    ghetto as opposed to an upper class military family?

4.  How much aberration is needed to employ these therapies and how much
    alteration in mental function can be justified, especially if the
    alteration changes personal identity or personality or changes how
    people experience life?

***Additional Issue***

While in his twenties, Patton becomes involved in an abusive incident,
in which his girlfriend sustains injuries sufficient to require
emergency care. This incident was seemingly unprovoked (or provoked by
very little) and was consistent with the psychiatric and biologic
prognosis that Patton was at risk for this type of behavior. The
District Attorney of Patton's jurisdiction, having read the police
report and the warrant for Patton's arrest, has decided to prosecute him
for assault and battery. In the course of the legal proceeding, Patton's
attorney asks that the records of his treatment including the fMRI
images be introduced as exculpatory evidence in his behalf.

1.  What do we think about the use of biological evidence (genotype,
    brain images, etc) as exculpatory evidence in a criminal matter?
    Should we hold people completely responsible for their actions given
    that they appear to be at a physiological disadvantage? How should
    the personal autonomy interest of people like Patton be balanced
    against public safety?

2.  If fMRI evidence can be exculpatory, are all prisoners entitled to
    brain scans as part of their defense?

3.  A proposed amendment to Great Britain's Mental Health Act would
    allow the detention of individuals who have not yet committed a
    crime but are deemed a potential threat to public safety. Is this a
    reasonable response to learning that the brain functions of certain
    people predispose them to violence? Should people with abnormal
    brain images be reported to law enforcement authorities? The U.S.
    Supreme Court has ruled that violent sex offenders can be jailed
    beyond their prison term if it can be shown that they have a mental
    or personality disorder that makes it difficult for them to control
    dangerous behavior. Is this an area where fMRI information can be
    put to good use for prisoners in general?

[^1]: fMRI is functional magnetic resonance imaging, which employs
    powerful magnetic fields to non-invasively monitor the rate of blood
    flow to the various parts of the brain. Since increased blood flow
    correlates with brain activity, the images produced with fMRI reveal
    which parts of the brain are active at the time. fMRI had been used
    since the mid 1990's to understand the neurobiological basis for our
    behavior, such as the regions of the brain that control or are
    responsible for learning, memory, and emotion. fMRI can be combined
    with more conventional MRI studies to provide simultaneous
    information on both brain structure and function. Enough research
    had been done with both forms of imaging to produce structural and
    functional brain images that are considered classic for many types
    of mental illness.

[^2]: An IRB is an Institutional Review Board whose purpose is to review
    and monitor biomedical research involving human subjects. An IRB has
    the authority to approve, require modifications to, or disapprove
    research. The fundamental purpose of an IRB review is to ensure that
    subjects are given the opportunity to provide informed consent, that
    the risks to subjects is minimized, and that the rights and welfare
    of human research subjects are otherwise protected.