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Home Lab MRI-information Recruitment Publications Tasks Other Interests |
Paulus, Martin P.: Neural
substrates underlying behavioral organization
Abnormalities
of neural circuits and neurotransmitter systems has led scientists away from a
single locus, single neurotransmitter explanation of schizophrenia.
Instead, schizophrenia is more appropriately viewed as a “systems”
disorder, i.e. when different parts of the brain or different neurotransmitter
systems do not work together appropriately to generate behavior, thinking, or
feeling. One
approach to elucidate schizophrenia as a “systems” disorder is to use
experimental paradigms during functional neuroimaging to probe behavioral
processes and their underlying neural systems. Decision-making is important for
daily life and can be defined as the process of executing an action from a
number of alternatives with potentially uncertain outcomes.
Decision-making can be separated into different component processes that
include: assessment of the situation, execution of an appropriate action, and
evaluation of the outcome.
We have developed a neural systems model for decision-making and its
proposed dysfunctions in schizophrenia, which has been used to derive the basic
hypotheses. Based
on work by others and our own behavioral and neuroimaging studies in
schizophrenia patients we hypothesize that the integration of assessment,
execution and evaluation across trials to guide decision-making is disrupted in
schizophrenia patients.
In this
proposal we will use the two-choice prediction task and functional magnetic
resonance imaging (fMRI) to:
(1) to
examine whether assessment, execution or evaluation is dysfunctional in
schizophrenia patients;
(2) to
determine which neural substrate activation underlies altered assessment,
execution or evaluation processes during decision-making; and
(3) to
relate these dysfunctional processes to levels of functioning in daily living as
measured by a multi-dimensional assessment of health related quality of life.
The aims
of this research program parallel those of the Mental Illness, Research,
Education, and Clinical Center (MIRECC) of the VISN 22.
Thus, this program will be using the infrastructure that has been created
by the MIRECC. Achieving
these goals will help to answer the question “in what way do schizophrenia
patients make poor decisions and which brain systems are responsible?”
These goals are important because there is a growing concern about
schizophrenia patient’s decisional capacity yet the basic processes and neural
substrates underlying decision-making and their dysfunction are poorly
understood. Second,
quantifying the precise behavioral dysfunctions and underlying neural substrate
activation patterns during decision-making in schizophrenia patients will
provide us with new medication targets and help to develop remedial psychosocial
intervention strategies.
Third, the decision-making and neural substrate activation patterns may
be used to identify subtypes of schizophrenia patients with distinct
pathophysiology and treatment needs.
Murray B. Stein MD, MPH:
Emotional Processing in Female Victims of Intimate Partner Violence
This program
of research is a continuation of our MERIT-funded studies that have been ongoing
since 1997. The penultimate goal of
this research program is the delineation of the neurobiological effects of
severe psychological trauma in women, and the elucidation of mechanisms that
mediate this effect. Our initial period of MERIT funding focused on the
delineation of neuropsychological impairment and brain morphometric
abnormalities in women with and without posttraumatic stress disorder (PTSD)
related to intimate partner violence (IPV). The second period of MERIT funding,
which we are currently completing, focuses on brain functional abnormalities and
neuropsychological and symptomatic correlates thereof in women with PTSD related
to IPV and those without IPV exposure. This next period of anticipated funding
will focus on the delineation of neural substrates of emotional processing
dysfunction in women exposed to IPV, including those with and without PTSD and
those without IPV exposure. In the proposed study, Blood Oxygen Level Dependent
(BOLD) contrast functional Magnetic Resonance Imaging (fMRI) will be used to
measure cerebrovascular-mediated neural activation in response to a series of
tasks assessing emotional processing. For the first time, we will also provide
participants with a standardized, state-of-the-art psychotherapeutic treatment
for PTSD, with the aim of identifying pre-treatment emotional processing
differences that can predict outcome to this treatment.Our main hypothesis is
that a functional neurocircuitry involving processes in limbic (e.g., amygdala)
and cortical regulatory regions (e.g., inferior parietal lobule and medial
prefrontal cortex) can be identified that supports abnormalities in emotional
processing in women with IPV-related PTSD. An ancillary hypothesis is that
activity in these regions can predict response to psychotherapeutic treatment
for PTSD. The
corresponding specific research objectives of our study are: 1. To use affective probes in conjunction with functional MRI to
investigate the neural substrates of emotional processing (including emotional
salience and social-emotional judgment) in women exposed to intimate partner
violence (IPV), and to compare and contrast these processes to those in women
who have not experienced serious lifetime trauma. 2. To
evaluate whether mental disorders commonly seen in conjunction with exposure to
IPV (i.e., PTSD and major depressive disorder) account for differences in
emotional processing in a priori determined regions of interest among women with
IPV. A sub-aim is to determine whether history of childhood maltreatment
accounts for such differences. 3. To
determine the extent to which pre-treatment (baseline) abnormalities in
emotional processing in women with IPV-related PTSD predict outcome to a
standardized, evidence-based psychosocial therapy. Specific questions to be
addressed within this specific aim are: a. Is low baseline
prefrontal cortical and/or inferior parietal lobular activity predictive of poor
treatment outcome? b. Does exaggerated
amygdala activation in response to emotional tasks predict poor treatment
outcome? Subjects
will include approximately 150 female victims of domestic violence with or
without PTSD, and a control group of approximately 25 age-, ethnicity-, and
education-matched group of women without a lifetime history of serious (PTSD
Criterion “A”) trauma. We have a strong, ongoing collaborative relationship
with the San Diego Family Justice Center from which to recruit subjects.
Subjects will be administered a structured clinical interview of lifetime
psychiatric disturbances, a brief assessment of specific cognitive abilities,
self-report measures of current psychological functioning, and will be screened
thoroughly for past and current medical, neurological, and medication status.
Participants will take part in baseline assessment and 60-minute fMRI
session using several well-studied emotional processing tasks with which our
research group has considerable expertise. Subjects with PTSD who desire
treatment (estimated at ~ 40% of assessed subjects) will undergo an empirically
supported psychotherapy intervention for victims of domestic violence designed
to reduce the symptoms of PTSD and improve daily functioning. Predictors of
outcome based on the pre-treatment fMRI assessment will be evaluated. |
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Home Lab MRI-information Recruitment Publications Tasks Other Interests last edited: 07/28/2007 |