Transcript hnhnvg
Selective Deficits in Prefrontal
Cortex Function in MedicationNaïve Patients with
Schizophrenia
Deanna M. Barch, Cameron S. Carter, Todd S. Braver,
Fred W. Sabb, Angus Macdonald III, Douglas C. Noll and
Jonathan D. Cohen.
Background Info & Past
Research …
Schizophrenics were thought to have deficits in
working memory due to their use of antipsychotic
drugs (Carter et al. 1996)
Unknown which regions were disturbed
Working memory defined as the ability to
temporarily maintain and manipulate
information
Dorsolateral prefrontal cortex supports working
memory that maintains information contextually
Context meaning prior task relevant information that
supports an appropriate response
Purpose…
Assess
whether the dorsolateral
prefrontal cortex is specifically
responsible for the working memory
deficits in patients with
Schizophrenia
Hypothesis
The
dorsolateral prefrontal cortex
plays a role in the manipulation of
information by recoding it into
contextual representations
Working memory deficits in
Schizophrenic patients are due to
disturbed dorsolateral prefrontal cortex
function, so should fail to show
increased activation during task
Subjects
Experimental: 14 right handed, medication naïve,
first episode patients with Schizophrenia
Neuroleptic free, recruited after their psychotic
symptom (hallucination, delusions, etc)
Confirmed to have diagnosis of Schizophrenia 6
months after study (follow up)
Control: 12 right handed, healthy individuals
recruited through advertisements
All between ages of 14-50 years old
Method
Cognitive Task (A-X Continuous Performance
Test)
Single letters presented on a screen
Subjects respond with one button if the target (X)
follows a contextual cue (A), with adjacent button for
non targeted stimuli
10 second trial, including a cue, a delay period, a
target, and an intertrial interval.
Long delay or short delay
Produces a tendency to respond to letter X and an
expectancy to make a response to the letter A
Selects for contextual processing by…
Present with either A-X , B-X or A-Y with long/short
delay
Method con’t…
Image Acquisition (fMRI)
Whole body scanner
16 slices (3.75 mm^3 voxels) taken parallel to
anterior commissure-posterior commissure line
scans were coordinated so each stimulus yielded
4 images
Results
Schizophrenics showed deficits in dorsolateral
PFC activation during tasks requiring contextual
processing
Yellow indicates area of activation
Results
Both control and experimental group showed
intact posterior and inferior prefrontal cortex
activation
Yellow indicates areas of activation
Discussion
Conclude that dorsolateral prefrontal cortex
deficits are present at the onset of
Schizophrenia—not due to medication
Leads to inability to actively represent and maintain
context information
Prefrontal cortex disturbances in Schizophrenics
may be anatomically specific
Inferior/posterior prefrontal cortex activation still
intact, only dorsolateral impaired
Strengths and Limitations
Limitations
Discussion was poorly written, just stated results
over again
Organization of paper was messy
Method to test contextual working memory
inadequate
Unknown whether patients have deficits in contextual
working memory or just working memory in general
Strengths
Sheds light on anatomically specific regions that are
impaired in Schizophrenics
The Next Step…
Re-examine using a better method to accurately
test for contextual working memory
Does this only apply to Schizophrenics or all
patients with frontal lobe deficits?
Can begin to map out specific regions that
contribute to deficits found in Schizophrenic
patients
References
Barch, D.M., Carter, C.S., Braver, T.S., Sabb,
F.W., MacDonald, A., Noll, D.C. and
Cohen,
J.D. (2001). Selective Deficits in
Prefrontal Cortex Function in Medication-Naïve
Patients with Schizophrenia. Arch Gen
Psychiatry, 58, 280-281.
Carter, C., Robertson, L., Nordahl, T., Chaderjian,
M., Kraft, L. and O’Shora-Celaya, L. (1996).
Spatial Working Memory Deficits and Their
Relationship to Negative Symptoms in
Unmedicated Schizophrenia Patients. Biol
Psychiatry, 40, 930-932