Cognitive Functioning in Schizophrenia: Leveraging the RDoC Framework

Preface
Cognition Is Vital to Living for People with Schizophrenia
Contents
The MATRICS Consensus Cognitive Battery: An Update
1 Background of the MATRICS Initiative and Its Consensus Cognitive Battery
2 Translation and Normative Data with the MCCB in Additional Languages
2.1 Translations
2.2 Community Norming in Other Languages
2.3 International Scoring System for the MSCEIT Managing Emotions Branch
3 Development of the Neurocognitive Composite Score
4 Website for Downloading the MCCB Computer Programs
5 Applications of the MCCB in Clinical Trials
5.1 Pharmacological Clinical Trials with the MCCB
5.2 Psychometric Properties of the MCCB
5.3 Clinical Trials with Training-Based Interventions
6 Applications of the MCCB within Psychopathology Research
6.1 Factor Analytic Studies of the MCCB
6.2 Profile of Cognitive Deficits in Schizophrenia
6.3 Sensitivity of MCCB to Cognitive Deficits in Biological Relatives and Familial Aggregation
7 Summary
References
Cognitive [Computational] Neuroscience Test Reliability and Clinical Applications for Serious Mental Illness (CNTRaCS) Consort...
1 Goal Maintenance
2 Relational Encoding and Retrieval in Episodic Memory
3 Gain Control
4 Visual Integration
5 CNTRaCS Phase Two
6 Working Memory
7 Positive Valence Systems
8 Future Directions of CNTRACS: Phase Three
References
Attention in Schizophrenia
1 Defining Attention
2 Global Alertness
3 Control of Attention in Schizophrenia
3.1 Control of Attention: Evidence from Salient Distractors
3.2 Control of Attention: Evidence from Implicit Priming
4 Selection in Schizophrenia: Impaired Focusing or Hyperfocusing?
4.1 Early Studies of Impaired Focusing
4.2 Hyperfocusing: Narrow But Intense Focusing of Attention
4.3 Hyperfocusing: Exaggerated Focusing on Partial Matches
4.4 Impaired Focusing or Hyperfocusing?
5 Open Questions and Future Directions
References
Perceptual Functioning
1 Anomalous Perceptual Experiences in Psychosis: Clinical Observations
2 Basic Mechanisms of Visual Perception and Methodological Issues
3 Different Models
3.1 Signal-to-Noise Ratio
3.2 A Disruption of the Magnocellular Pathway
3.3 Context-Modulation Model
3.4 Predictive Coding Model
4 Methodological Descriptions
4.1 Masking
4.2 Electroencephalographic Correlates of Masking Impairments
4.3 Spatial Vision
4.4 Retinal Function
4.5 Relationship Between Visual Impairments and Disruptions in the Neuronal Connectivity
4.5.1 Contour Integration Deficits
4.5.2 Visual Perception and Disruptions of Neuronal Connectivity
4.6 Dynamic Aspects of Perception
5 Conclusion
References
Episodic Memory and Schizophrenia: From Characterization of Relational Memory Impairments to Neuroimaging Biomarkers
1 Preamble
2 Relational Memory Tasks in Schizophrenia Research
2.1 Associative Recognition Tasks
2.2 The Relational and Item-Specific Encoding Task (RISE)
2.3 Associative Inference Paradigm (AIP)
2.4 Transverse Patterning (TP) Tasks
2.5 The Semantic Encoding Memory Task (SEMT)
2.6 Eye-Tracking Tasks
3 Biomarkers of Episodic Memory Impairments in Schizophrenia
3.1 Paired-Associates Tasks
3.2 RISE
3.3 Transitive Inference
3.4 Transverse Patterning
3.5 SEMT
3.6 Overview of fMRI Biomarker Findings
4 Conclusion: Outstanding Questions on Memory Research in Schizophrenia and Related Psychoses
References
Working Memory in People with Schizophrenia
1 What Is Working Memory
2 How Is WM Measured?
3 WM and Broad Cognitive Performance
3.1 Origins of Impairment
3.2 Delay-Dependent Deficits?
4 Neural Systems Implicated in WM Dysfunction in Schizophrenia
4.1 Summary and Future Directions
References
Targeting Frontal Gamma Activity with Neurofeedback to Improve Working Memory in Schizophrenia
1 Introduction
2 Schizophrenia-Related DLPFC Microcircuit Abnormalities
3 Neural Oscillations During WM
4 Targeting DLPFC Gamma Activity to Improve WM in Patients with SCZ
5 Conclusions and Future Directions
References
Cognitive Dysfunction as a Risk Factor for Psychosis
1 Introduction
2 The Nature of the Relationship Between Cognition and Psychosis Risk
2.1 Cognitive Impairment as a Causal Mechanism for Psychosis
2.1.1 Data-Driven Classification of Psychosis Using Cognitive Performance
2.2 Cognition as an Intermediate Risk Factor
2.2.1 The Role of Genetics
2.2.2 The Role of Neural Metrics
2.3 Symptom Correlation Evidence
3 Specificity of Cognitive Deficits
4 Associations Between Cognitive Deficits with Symptom Severity
4.1 Psychotic-Like Experiences
4.2 High-Risk Populations
4.3 Transition from CHR to First Episode
4.4 Overall Limitations and Considerations
5 Summary
References
Environmental Risk Factors and Cognitive Outcomes in Psychosis: Pre-, Perinatal, and Early Life Adversity
1 Introduction
2 Obstetric Complications and Cognition in Psychosis
2.1 Prenatal Infection
2.2 Prenatal Maternal Stress
2.3 Hypoxia-Associated Obstetric Complications
2.4 Maternal Health Behaviors
2.5 Obstetric Complications and Cognition in Psychosis: Summary
3 Early Life Stress and Cognition in Psychosis
3.1 Childhood Trauma
3.2 Neighborhood-Level Adversity
3.3 Peer Victimization
3.4 Early Life Stress and Cognition in Psychosis: Summary
4 Discussion
4.1 Considerations Pertaining to Intersectionality
4.2 Gene x Environment Interactions
5 Conclusions and Recommendations
References
Developmental Manipulation-Induced Changes in Cognitive Functioning
1 Overview
1.1 Diagnostic Considerations
1.2 Developmental Origins
2 Commonly Used Animal Models of Schizophrenia-Related Behaviors
3 Prenatal Models
3.1 Maternal Immune Activation (MIA) Model
3.2 Maternal Methylazoxymethanol Acetate Exposure (MAM) Model
3.3 Prenatal Psychological Stress Models
3.4 Diet/Nutritional Deficiency
4 Early Postnatal Developmental Models
4.1 Neonatal Hippocampal Lesion Model
4.2 Psychosocial Stress in Neonates
4.3 Postnatal Drug Challenges
4.4 N-Methyl-D-Aspartate (NMDA) Receptor Antagonist Models (Phencyclidine, Ketamine, and MK-801)
5 Combination Models
6 Translational Approaches: From Bench to Bedside
6.1 Pharmacological Interventions
6.2 Environmental Enrichment Interventions
7 Conclusions
References
Genetic Influences on Cognitive Dysfunction in Schizophrenia
1 Schizophrenia: A Clinically and Genetically Heterogenous Disorder
2 The Value of Endophenotypes in Schizophrenia Research
3 Measures of Cognitive Dysfunction as Endophenotypes for Schizophrenia
4 The Genetics of Cognitive Dysfunction in Schizophrenia
5 Conclusions and Future Directions
References
Using Nonhuman Primate Models to Reverse-Engineer Prefrontal Circuit Failure Underlying Cognitive Deficits in Schizophrenia
1 How Does Schizophrenia Alter the Function of Prefrontal Neurons and Synapses, and Can These Changes Be Reversed?
2 An Emerging Theory of the Failure Cascade Leading to Prefrontal Circuit Collapse in Schizophrenia
3 Schizophrenia: Convergent Causal Trajectories
4 Using Nonhuman Primate Models to Test the Causal Theory
5 Limitations of Nonhuman Primate Models in Schizophrenia Research
6 Neural Basis of Cognitive Functions Disrupted in Schizophrenia: Macaque Prefrontal Delay Neurons and Working Memory
7 Spatial Working Memory Deficits Following Manipulation of Prefrontal Cortex
8 Distributed Network Basis of Spatial Working Memory
9 Plasticity of Prefrontal Working Memory Activity
10 Changes in Persistent Working Memory Activity Between Adolescence and Adulthood
11 ``Silent´´ Mechanisms of Working Memory
12 Dendritic Spines, and Synaptic Mechanisms of Persistent Working Memory Activity in Recurrent Prefrontal Circuits
13 Neural Basis of Cognitive Functions Disrupted in Schizophrenia: Prefrontal Activity and Cognitive Control
14 Blocking NMDAR in Monkeys to Replicate Cognitive Control Deficits in Schizophrenia
15 Combining NMDAR Antagonists and the AX-CPT to Translate Cognitive Control Deficits in Schizophrenia to Monkeys
16 NMDAR Antagonists and Spiking Timing in Prefrontal Local Circuits
17 Convergent Impacts of Genetic Risk and NMDAR Blockade on Prefrontal Circuit Dynamics
18 Developmental NHP Models
19 Future Potential of Nonhuman Primate Models
20 Do We Need to Understand Schizophrenia at a Cellular Level to Cure It?
References
Olfactory Dysfunction in Schizophrenia: Evaluating Olfactory Abilities Across Species
1 Olfactory Dysfunction in Schizophrenia: Evaluating Olfactory Abilities Across Species
1.1 Odor Sensitivity
1.2 Odor Discrimination
1.3 Odor Identification
1.4 Odor Memory
2 Conclusions
References
Cholinergic Functioning, Cognition, and Anticholinergic Medication Burden in Schizophrenia
1 Introduction
2 Abnormalities of Central Nervous System Cholinergic Functioning in Schizophrenia
3 Attempted Cholinergic-Based Treatment Strategies in SZ
4 Clinical Evidence Linking Anticholinergic Medication Burden to Cognitive Outcomes in Schizophrenia
5 Measuring and Accounting for Anticholinergic Medication Burden: Limitations and Implications for Translational Biomarker Dev...
6 Summary and Future Directions
References
An Update on Treatment of Cognitive Impairment Associated with Schizophrenia
1 Introduction
2 Pharmacological Treatments
2.1 Background
2.2 Why Did These Trials Fail?
2.3 Clinical Trials Since 2018
3 Cognitive Remediation
3.1 Background
3.2 Fundamental Elements
3.3 Meta-Analyses of Efficacy for Cognitive Remediation
3.4 Variability of Treatment Response
3.4.1 Patient-Associated Moderators
3.4.2 Treatment-Associated Moderators
3.5 Current Limitations and Future Directions
4 Transdiagnostic Considerations for Clinical Trials
4.1 Looking Across Diagnoses
4.2 Looking Within Schizophrenia
5 Conclusions
References
The Relationship Between Cannabis, Cognition, and Schizophrenia: It´s Complicated
1 Cannabis Use in Schizophrenia Patients
2 Cannabis and Cognition in Healthy Individuals
2.1 Effects of Cannabis on Attention
2.2 Effects of Cannabis on Working Memory
3 Effects of Cannabinoids on Attention and Memory in Schizophrenia Patients
4 Cognition-Related Effects of Cannabinoids in Animal Models
4.1 Effects of THC on Cognition in Rodents
4.2 Effects of CBD on Cognition in Rodents
5 Future Directions
6 Conclusions
References
Sex Differences in Cognition in Schizophrenia: What We Know and What We Do Not Know
1 Introduction
2 Sex Differences in Cognition in Schizophrenia: Preserved Sexual Dimorphism or Not?
3 Sex Differences in Cognition in Schizophrenia Across Phase of Illness
4 Outstanding Questions About Sex Differences in Cognition in Schizophrenia
5 Concluding Remarks
References
Rethinking Immunity and Cognition in Clinical High Risk for Psychosis
1 Cognition and the Emergence of Psychosis from Risk
1.1 Overview
1.2 Assessment of Cognitive Function
1.3 Cognitive Impairment in CHR-P
1.4 Cognitive Performance in CHR-P Predicts Onset of Psychosis
1.5 CHR-P: Cognition, Grey Matter and Polygenic Risk
2 The Immune System and Its Role in the Pathogenesis of Psychosis
2.1 Overview of the Immune System
2.2 The Brain and the Periphery: The Role of Cytokines
2.3 Neuroinflammation and Psychosis: The `Two-Hit´ Vulnerability-Stress Hypothesis
2.4 Role of Cytokines: Correlation or Causation?
2.5 Cytokine Profiles and Clusters in Established Psychosis
3 Inflammatory Profiles in the Prodrome
3.1 Inflammatory Profiles and Onset of Psychosis
3.2 Inflammatory Profiles and Grey Matter and Cognitive Performance
4 Rethinking Immunity and Cognition: A Paradigm Shift
References