This study will examine the underlying mental processes that determine how people understand
social behavior, remember information, and think. Language, planning, problem solving,
reasoning, social behavior, and memory are the critical parts of cognition that make up
daily life. This study will explore the association between performance on various
experimental tasks and day-to-day functioning.
Healthy normal volunteers and patients with certain kinds of brain damage (primarily focal
or degenerative lesions of the human prefrontal cortex) or psychiatric disorders may be
eligible for this study. Candidates with central nervous system trauma, disease or
dysfunction will be screened with a routine neurological examination and history.
Participants may be asked to complete written tests, sit in front of a computer monitor and
press a key to indicate a decision about what appears on the screen (for example, whether a
statement is accurate) and answer questions from a test examiner. A skin conductance
response (SCR) test may be done along with some of the cognitive tests. SCR uses electrodes
(pieces of metal attached to wires) placed on the fingers to measure the subject's emotional
reaction to a test. Participants may also do an evoked response test, in which the subject
watches words or scenes on a TV screen while his or her responses are recorded from
electrodes placed on the scalp (similar to an electroencephalogram). The tests will be
scheduled for an average of one session a week, with each session lasting from 30 minutes to
3 hours. Generally, 15 sessions will be scheduled over a 1-year period. Special arrangements
will be made to accommodate participants from out-of-town.
Participants may have a magnetic resonance imaging (MRI) scan of the brain. This test uses
radio waves and a strong magnetic field to picture structural and chemical changes in
tissue. For the procedure, the subject lies on a table in a space enclosed by a metal
cylinder (the scanner) for about 1 hour.
In addition, some study subjects will be invited to participate in a training study designed
to improve their planning or social behavior. Participation requires coming to NIH daily
over a 1- to 2-month period for 1 to 2 hours each visit.
The purpose of this protocol is to test a comprehensive model of the underlying knowledge
representations stored in the human prefrontal cortex developed by the principal
investigator. Utilizing a variety of standardized and experimental neuropsychological tasks
and techniques, we will investigate hypotheses regarding the role of the dorsolateral
prefrontal cortex in planning, problem-solving, and reasoning and the ventromedial
prefrontal cortex in social cognition and emotional processing. We will ascertain the
relationship between so-called "cold" cognitive processes such as planning and "hot" social
processes such as attitude formation and specific brain regions within the prefrontal
cortex. Besides cognitive paradigms, we will use skin conductance and event-related EEG
recording techniques when subjects are performing selected cognitive tasks in order to
determine the relationship between autonomic and central nervous system markers of emotional
modulation and speed/duration of processing and task performance. The data we collect in
this protocol will be of value in 1) Developing a model of the forms of knowledge
representation stored in the human prefrontal cortex; 2) Developing outcome measures for
drug and behavioral treatments for disorders of prefrontal cortex functions; and, 3)
Developing biologically plausible computer models of the cognitive sub-components stored in
the human prefrontal cortex that compose the complex skills referred to above.
- INCLUSION AND EXCLUSION CRITERIA:
Controls: Healthy normal controls matched to specific patient groups for age, education,
gender, and race to be recruited by advertisement from the community or from among friends
and relatives of the patient. Individuals with a neurological or psychiatric history or
medical condition that would compromise our interpretation of the test results will not be
Patients: Patients will be selected from referrals to the Cognitive Neuroscience Section,
the NIH Clinical Center, and from referrals recruited through approved advertisement in
appropriate media and medical journals.
All patients must have a diagnosed CNS disorder with lesions localization (when suspected)
verified by CT or MRI scanning available from the referring physician or completed at the
NIH Clinical Center. Subjects without neurological, neuropsychological, and imaging
evidence compatible with one of the recruited diagnoses will be excluded from the study as
will subjects who cannot cooperate with neuropsychological testing (based on family report
and the report of the referring healthcare professional).
The bulk of the patients recruited for this protocol will have focal or degenerative
lesions of the HPFC. We also will recruit patients with non-frontal lesions in order to
determine the specificity of the deficit we observe in patients with HPFC lesions. These
patients will undergo the same testing but are not expected to have marked cognitive
deficits on tests of frontal lobe function.
Patients with different basal ganglia disorders or limbic system lesions are included
because their lesions involve differing subsets of subcortical structures that are thought
to play an important role in the automatic activation of stored plans and social behavior.
Another prediction from the SEC model is that patients with basal ganglia disorders will
have deficits primarily on over-learned components of tasks that require visuomotor
interaction (e.g., a visuomotor serial reaction time task) but have spared performance on
higher level cognitive planning tasks that don't require simple visuomotor responses.
The bulk of the patients will be patients with focal penetrating head injuries who will be
seen here at the NIH as part of a newly funded study to be conducted primarily, but not
solely, at the National Naval Medical Center. Patients with dementing disorders (e.g.,
frontotemporal dementia) are suitable for assessment of the structure of knowledge, and in
particular, the systematic general breakdown of social and non-social SEC knowledge
representation. Patients with focal lesions (e.g., dorsolateral frontal) will be studied
to assess damage to specific sub-components of the structured event complex model.
Occasionally, single cases will be intensively studied due to a unique behavioral
presentation (see above for a lengthier description).
A durable power of attorney will be appointed if the patient is unable to make decisions
about any or all aspects of this protocol. In the past in our protocols, this has almost
always been the spouse.
The age range of the brain-damaged patients will be determined on entrance into the
protocol. An equal number of left and right unilateral lesions will be sought for
determination of laterality differences. Patients with lesions limited to (rather than
simply including) the frontal lobe will also be especially sought.
Minors (ages 6-17) are included in this protocol in order to examine 3 specific questions:
(1) What is the distinction in retrievable SEC knowledge (e.g., plans or social rules)
learned prior to adolescence from that subsequent to adolescence?; (2) Does learning and
development of all aspects of social cognition require an intact prefrontal cortex?; and
(3) Will some effects of early prefrontal cortex lesions only appear after the age of 14?
The first question will be addressed by studying healthy normal children before the age of
14 on experimental social cognition and planning tasks slightly modified from those used
with adults (see the six studies described above). The second question will be addressed
by studying single cases and groups of children with prefrontal cortex lesions on social
cognition tasks before and after the age of 14. The third question will be addressed by
studying children with prefrontal cortex lesions incurred before the age of 14 both before
and after the age of 14 on social cognition, meta-cognition, and planning tasks.