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