1. Control of Attention in schizophrenia 1.Advance understanding of schizophrenia. Move from description of deficits to explanation of specific mechanisms and neural systems implicated in the illness. 1.Advance understanding of how attention works in the normal brain by studying how these processes break down with disease. James Gold, MPRC & Steven Luck, University of Iowa A program of translational research, teaming a clinical and basic researcher, with two goals:

2. What is schizophrenia? Prevalence: Approx. 1% of the population. Age of Onset:Most cases late adolescence. Duration:Usually lifetime Disability: 4 th leading cause of disability 70-80% of patients are unemployed.

3. Major Symptoms Hallucinations Delusions Loss of motivation, social interest Cognitive impairment Current treatments are not effective for cognitive deficits, the major hurdle for reducing the disability of schizophrenia.

4. Processing Speed and Employment in SC Of those subjects who scored below 85 on the WAIS-III PSI, only 30.0% were employed; of those who scored 85 or greater, 73.0% were employed. Digit Symbol Sample Items Symbol Search Sample Items PSI by Employment Group

5. Cognitive impairment in Schizophrenia There is clear evidence that SC patients demonstrate impairments on standard clinical measures of attention and short term memory. Clinical measures are too complex to isolate the actual brain mechanisms that are responsible for the observed deficits. The goal of our work is to bring recent advances in the basic cognitive neuroscience of attention and short term memory into the clinic.

6. What is Attention for ? The brain is frequently overloaded with too many… –Sensory inputs to perceive –Perceptions and thoughts to remember The role of selective attention is to focus the brain’s resources on the most important information, reducing the impact of overload.

7. Multiple Attention Mechanisms New research indicates that we have separate attention mechanisms for different cognitive systems. This raises the possibility that SC may differentially impact specific attention mechanisms.

8. Attention in Perception and ST Memory In perception: The visual system first processes the basic features (color, shape) of a scene in separate brain areas. Attention is needed to accurately locate and combine these basic features into separate objects. Overload: complex scenes with overlapping features In short term memory: The STM system has very limited storage capacity. Attention is needed to select the relevant items to store. Overload: too many items to store

9. Feature Search or Target = Response = Left button press if the red rectangle is on the left and right button press if the red rectangle is on the right

10. or Target = Response = Left button press if the red rectangle is on the left and right button press if the red rectangle is on the right Feature Search

11. or Target = Response = Left button press if the red rectangle is on the left and right button press if the red rectangle is on the right Conjunction Search

12. or Target = Response = Left button press if the red rectangle is on the left and right button press if the red rectangle is on the right Conjunction Search

13. Reaction Time for Feature and Conjunction Search Tasks Slowing in conjunction search reflects the time required for spatially focused attention to scan each item

14. Experimental Paradigm Sample Array (100 or 500ms) Test Array: Change in Orientation Test Array: Change in Color 2000ms Delay

15. Sample Trial #1: Set Size 6 + This bar was previously horizontal

16. Percent Accuracy by Condition O = C: Patients with SC show normal feature binding.

17. k-Scores for Set Sizes 4 and 6

18. 1.Provide strong evidence that attention may function normally binding features in support of visual perception. The demonstration of intact function is critical to meet the goal of isolating specific impairments. 2.Provide evidence that memory-level attention is impaired. The need to use attention to select for storage actually impaired performance. In the same experiment, with the same stimuli, we have shown that these two forms of attention may operate independently, one normally, one abnormally. Initial Results

19. The Promise of Translational Research 1.We have shown that it is possible to bring basic cognitive neuroscience methods into the study of schizophrenia. 2.Our initial results strongly support the hypothesis that schizophrenia involves a breakdown of specific forms of attention, providing important clues about the underlying neural systems involved in the illness. 3.Our initial results in patients have stimulated new basic science experiments on the control of attention in normal subjects. The results of these experiments will then inform the next generation of patient experiments.