selective deficits in prefrontal cortex function in medication- naïve patients with schizophrenia...
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Selective Deficits in Prefrontal Cortex Function in Medication-Naïve Patients with SchizophreniaDeanna 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
HypothesisThe dorsolateral prefrontal cortex
plays a role in the manipulation of information by recoding it into contextual representationsWorking 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
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