Selective Deficits in Prefrontal Cortex Function in Medication- Naïve 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 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, 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,