Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia

Cognitive Constructs and Goals For this Meeting Facilitate the use and/or development of animal models: Facilitate the use and/or development of animal models: Of the types of cognitive constructs identified as relevant to schizophrenia in CNTRICS I Of the types of cognitive constructs identified as relevant to schizophrenia in CNTRICS I That are well grounded in construct validity That are well grounded in construct validity That will HAVE good predictive utility in developing novel pharmacological agents for use in individuals with schizophrenia That will HAVE good predictive utility in developing novel pharmacological agents for use in individuals with schizophrenia

The Challenges Humans, primates, and rodents have similar capabilities in some areas, and not others… Humans, primates, and rodents have similar capabilities in some areas, and not others… What do we mean by homologous? What do we mean by homologous? Why isn’t predictive utility better? Why isn’t predictive utility better? How do you know when you are measuring a homologous process or construct? How do you know when you are measuring a homologous process or construct?

The Goals For This Meeting Understand how and why constructs have been operationalized differently across species Understand how and why constructs have been operationalized differently across species Develop a consensus on what it means to be measuring a homologous process or construct Develop a consensus on what it means to be measuring a homologous process or construct Identify ways of improving homology, either in existing paradigms or in new paradigms Identify ways of improving homology, either in existing paradigms or in new paradigms With the goal of being able to improve predictive utility With the goal of being able to improve predictive utility Our goal is NOT to identify “best” paradigm or task Our goal is NOT to identify “best” paradigm or task Use tasks to illustrate points Use tasks to illustrate points Next CNTRICS II Animal meeting will focus on paradigms Next CNTRICS II Animal meeting will focus on paradigms

TASKS

How did we select tasks in humans? Surveyed the field for potential tasks Surveyed the field for potential tasks Solicited widely for nominations Solicited widely for nominations Developed a database for review Developed a database for review Selected 1-3 tasks for each construct Selected 1-3 tasks for each construct Construct validity (psychological and neural) Construct validity (psychological and neural) Reliability Reliability Psychometric characteristics Psychometric characteristics Animal model Animal model Studied in schizophrenia (good, but not a deal breaker) Studied in schizophrenia (good, but not a deal breaker)

Perception Gain control: The processes whereby neurons adapt their response levels to take into account their immediate context, in order to make best use of a limited dynamic signaling-range. Gain control: The processes whereby neurons adapt their response levels to take into account their immediate context, in order to make best use of a limited dynamic signaling-range. Nominated Tasks: Nominated Tasks: Contrast-Contrast Effect (CCE) Task Contrast-Contrast Effect (CCE) Task Contrast Sensitivity + Steady state visual evoked potentials to magnocellular vs. parvocellular biased stimuli. Contrast Sensitivity + Steady state visual evoked potentials to magnocellular vs. parvocellular biased stimuli. Mismatch Negativity [ALREADY WELL DEVELOPED] Mismatch Negativity [ALREADY WELL DEVELOPED] Prepulse Inhibition of Startle [ALREADY WELL DEVELOPED] Prepulse Inhibition of Startle [ALREADY WELL DEVELOPED] Integration: The processes linking the output of neurons – that individually code local (typically, small) attributes of a scene - into global (typically, larger) complex structure, more suitable for the guidance of behavior. Integration: The processes linking the output of neurons – that individually code local (typically, small) attributes of a scene - into global (typically, larger) complex structure, more suitable for the guidance of behavior. Nominated Tasks: Nominated Tasks: Coherent Motion Detection Task Coherent Motion Detection Task Contour Integration Task Contour Integration Task Babble Task [Construct Unclear] Babble Task [Construct Unclear]

Working Memory Goal Maintenance: The processes involved in activating task related goals or rules based on endogenous or exogenous cues, actively representing them in a highly accessible form, and maintaining this information over an interval during which that information is needed to bias and constrain attention and response selection. Goal Maintenance: The processes involved in activating task related goals or rules based on endogenous or exogenous cues, actively representing them in a highly accessible form, and maintaining this information over an interval during which that information is needed to bias and constrain attention and response selection. Nominated Tasks: Nominated Tasks: AX-CPT/Dot Pattern Expectancy Task AX-CPT/Dot Pattern Expectancy Task Probabilistic Reversal Learning [Does not isolate construct] Probabilistic Reversal Learning [Does not isolate construct] Interference Control: The processes involved in protecting the contents of working memory from interference from either other competing internal representations or external stimuli. Interference Control: The processes involved in protecting the contents of working memory from interference from either other competing internal representations or external stimuli. Nominated Tasks: Nominated Tasks: Operation Span/Symmetry Span Operation Span/Symmetry Span Recent Probes Task Recent Probes Task Ignore Suppress Task [Interesting, but in need of more development] Ignore Suppress Task [Interesting, but in need of more development] Inhibition of Currently Irrelevant Memories Task [Different Construct] Inhibition of Currently Irrelevant Memories Task [Different Construct]

Attention Control of Attention: The ability to guide and/or change the focus of attention in response to internal representations. Control of Attention: The ability to guide and/or change the focus of attention in response to internal representations. Nominated Tasks: Nominated Tasks: Guided Search Guided Search McGaughy & Sarter Sustained Attention Task McGaughy & Sarter Sustained Attention Task Attention Networks Task [Multiple Constructs] Attention Networks Task [Multiple Constructs] Attention Capture Task [Different Construct] Attention Capture Task [Different Construct] Posner Spatial Cueing [Does Not Elicit Clear Deficits in Schizophrenia] Posner Spatial Cueing [Does Not Elicit Clear Deficits in Schizophrenia]

Executive Control Rule Generation and Selection: The processes involved in activating task related goals or rules based on endogenous or exogenous cues, actively representing them in a highly accessible form, and maintaining this information over an interval during which that information is needed to bias and constrain attention and response selection. Rule Generation and Selection: The processes involved in activating task related goals or rules based on endogenous or exogenous cues, actively representing them in a highly accessible form, and maintaining this information over an interval during which that information is needed to bias and constrain attention and response selection. Nominated Tasks: Nominated Tasks: 1-2 AX-CPT 1-2 AX-CPT ID-ED Task ID-ED Task Groton Maze Learning Test (GMLT) [Construct Unclear] Groton Maze Learning Test (GMLT) [Construct Unclear] Switching Stroop (task switching asymmetric or symmetric) Switching Stroop (task switching asymmetric or symmetric) Dynamic Adjustments of Control: The processes involved in detecting the occurrence of conflict or errors in ongoing processing, identifying the type of control adjustments needed, and recruiting additional control processes. Dynamic Adjustments of Control: The processes involved in detecting the occurrence of conflict or errors in ongoing processing, identifying the type of control adjustments needed, and recruiting additional control processes. Nominated Tasks: Nominated Tasks: Stroop Task Stroop Task Stop Signal Task Stop Signal Task Simon Task [Interesting, but in need of more development] Simon Task [Interesting, but in need of more development] Attention Networks Task [Different Construct] Attention Networks Task [Different Construct]

Long Term Memory Relational Encoding and Retrieval: The processes involved in memory for stimuli/elements and how they were associated with coincident context, stimuli or events. Relational Encoding and Retrieval: The processes involved in memory for stimuli/elements and how they were associated with coincident context, stimuli or events. Nominated Tasks: Nominated Tasks: Associative Inference Associative Inference Relational and Item Specific Encoding and Retrieval Task (RiSE) Relational and Item Specific Encoding and Retrieval Task (RiSE) Transitive Inference Transitive Inference Item Encoding and Retrieval: The processes involved in memory for individual stimuli or elements irrespective of contemporaneously presented context or elements. Item Encoding and Retrieval: The processes involved in memory for individual stimuli or elements irrespective of contemporaneously presented context or elements. Nominated Tasks: Nominated Tasks: Relational and Item Specific Encoding and Retrieval Task (RiSE) Relational and Item Specific Encoding and Retrieval Task (RiSE) Inhibition of Currently Irrelevant Memories Task [Different Construct] Inhibition of Currently Irrelevant Memories Task [Different Construct]

Motivation (was part of LTM) Reinforcement Learning: Acquired behavior as a function of both positive and negative reinforcers, including the ability to (a) associate previously neutral stimuli with value, as in Pavlovian conditioning; (b) rapidly modify behavior as a function of changing reinforcement contingencies and (c) slowly integrate over multiple reinforcement experiences to determine probabilistically optimal behaviors in the long run. Reinforcement Learning: Acquired behavior as a function of both positive and negative reinforcers, including the ability to (a) associate previously neutral stimuli with value, as in Pavlovian conditioning; (b) rapidly modify behavior as a function of changing reinforcement contingencies and (c) slowly integrate over multiple reinforcement experiences to determine probabilistically optimal behaviors in the long run. Nominated Tasks: Nominated Tasks: PIzzagalli Reward Task PIzzagalli Reward Task Probabilistic Reversal Learning Probabilistic Reversal Learning Probabilistic Selection Task Probabilistic Selection Task Weather Prediction Task [Does Not always Elicit Deficits in Schizophrenia, depending on how you look at it] Weather Prediction Task [Does Not always Elicit Deficits in Schizophrenia, depending on how you look at it]

Social and Emotional processing Affective Recognition and Evaluation: The ability to detect, recognize and judge the affective value of both linguistic (e.g., seen or spoken words and their prosodic contour) and nonlinguistic (e.g., images of people, facial expressions, eye gaze, scenes) stimuli. Affective Recognition and Evaluation: The ability to detect, recognize and judge the affective value of both linguistic (e.g., seen or spoken words and their prosodic contour) and nonlinguistic (e.g., images of people, facial expressions, eye gaze, scenes) stimuli. Nominated Tasks: Nominated Tasks: Facial Affect Recognition and the Effects of Situational Context Facial Affect Recognition and the Effects of Situational Context Penn Emotion Recognition Task Penn Emotion Recognition Task Multimorph Task [Interesting, but in need of more development] Multimorph Task [Interesting, but in need of more development] Perceiving Emotion Using Point Light Walkers [Interesting, but in need of more development] Perceiving Emotion Using Point Light Walkers [Interesting, but in need of more development] Reading the Mind in the Eyes Task [Interesting, but in need of more development] Reading the Mind in the Eyes Task [Interesting, but in need of more development]