Cognitive Neuroscience Treatment Research

1
CNTRICS
Cognitive Neuroscience Treatment Research to
Improve Cognition in Schizophrenia
2
Cognitive Constructs and Goals For this Meeting

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

3
The Challenges

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

4
The Goals For This Meeting

• 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
• Identify ways of improving homology, either in
  existing paradigms or in new paradigms
• With the goal of being able to improve predictive
  utility
• Our goal is NOT to identify best paradigm or
  task
• Use tasks to illustrate points
• Next CNTRICS II Animal meeting will focus on
  paradigms

5
TASKS
6
How did we select tasks in humans?

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

7
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.
• Nominated Tasks
• Contrast-Contrast Effect (CCE) Task
• Contrast Sensitivity Steady state visual evoked
  potentials to magnocellular vs. parvocellular
  biased stimuli.
• Mismatch Negativity 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.
• Nominated Tasks
• Coherent Motion Detection Task
• Contour Integration Task
• Babble Task Construct Unclear

8
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.
• Nominated Tasks
• AX-CPT/Dot Pattern Expectancy Task
• 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.
• Nominated Tasks
• Operation Span/Symmetry Span
• Recent Probes Task
• Ignore Suppress Task Interesting, but in need of
  more development
• Inhibition of Currently Irrelevant Memories Task
  Different Construct

9
Attention

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

10
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.
• Nominated Tasks
• 1-2 AX-CPT
• ID-ED Task
• Groton Maze Learning Test (GMLT) Construct
  Unclear
• 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.
• Nominated Tasks
• Stroop Task
• Stop Signal Task
• Simon Task Interesting, but in need of more
  development
• Attention Networks Task Different Construct

11
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.
• Nominated Tasks
• Associative Inference
• Relational and Item Specific Encoding and
  Retrieval Task (RiSE)
• Transitive Inference
• Item Encoding and Retrieval The processes
  involved in memory for individual stimuli or
  elements irrespective of contemporaneously
  presented context or elements.
• Nominated Tasks
• Relational and Item Specific Encoding and
  Retrieval Task (RiSE)
• Inhibition of Currently Irrelevant Memories Task
  Different Construct

12
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.
• Nominated Tasks
• PIzzagalli Reward Task
• Probabilistic Reversal Learning
• Probabilistic Selection Task
• Weather Prediction Task Does Not always Elicit
  Deficits in Schizophrenia, depending on how you
  look at it

13
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.
• Nominated Tasks
• Facial Affect Recognition and the Effects of
  Situational Context
• Penn Emotion Recognition Task
• Multimorph Task 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