Test of A Model of Representational Knowledge Stored in the Human Prefrontal Cortex
Test of A Model of Representational Knowledge Stored in the Human Prefrontal Cortex
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
 included.

 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.