Cognitive Neuroscience Treatment Research To Improve Cognition In Schizophrenia Research Articles

Cognitive [Computational] Neuroscience Test Reliability and Clinical Applications for Serious Mental Illness (CNTRaCS) Consortium: Progress and Future Directions.

The development of treatments for impaired cognition in schizophrenia has been characterized as the most important challenge facing psychiatry at the beginning of the twenty-first century. The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) project was designed to build on the potential benefits of using tasks and tools from cognitive neuroscience to better understanding and treat cognitive impairments in psychosis. These benefits include: (1) the use of fine-grained tasks that measure discrete cognitive processes; (2) the ability to design tasks that distinguish between specific cognitive domain deficits and poor performance due to generalized deficits resulting from sedation, low motivation, poor test taking skills, etc.; and (3) the ability to link cognitive deficits to specific neural systems, using animal models, neuropsychology, and functional imaging. CNTRICS convened a series of meetings to identify paradigms from cognitive neuroscience that maximize these benefits and identified the steps need for translation into use in clinical populations. The Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRaCS) Consortium was developed to help carry out these steps. CNTRaCS consists of investigators at five different sites across the country with diverse expertise relevant to a wide range of the cognitive systems identified as critical as part of CNTRICs. This work reports on the progress and current directions in the evaluation and optimization carried out by CNTRaCS of the tasks identified as part of the original CNTRICs process, as well as subsequent extensions into the Positive Valence systems domain of Research Domain Criteria (RDoC). We also describe the current focus of CNTRaCS, which involves taking a computational psychiatry approach to measuring cognitive and motivational function across the spectrum of psychosis. Specifically, the current iteration of CNTRaCS is using computational modeling to isolate parameters reflecting potentially more specific cognitive and visual processes that may provide greater interpretability in understanding shared and distinct impairments across psychiatric disorders.

INCF Workshop on Genetic Disease Models of Psychiatric and Neurological Diseases

This workshop was organized by the INCF Secretariat in collaboration with Martien Kas, Magali Haas and Rob Williams. It was held on February 14 - 16, 2013, in Utrecht, The Netherlands. Developing treatments for human diseases requires knowledge of the biological mechanisms underlying the disease states. This can only be gained through functional studies in which the course of disease is manipulated systematically using pharmacologic, environmental, and genetic interference. Experimental model systems are critical for resolving these scientific challenges, and researchers often select mice as the animal model. Brain disorders have a major societal and economic impact, but understanding these disease states is complicated because their underlying etiologies are not well characterized. This lack of knowledge about the mechanisms of brain disease has severely impeded the development and implementation of effective treatments using translational research approaches. Furthermore, brain disorders are complex and all factors, from genetic variation to disease development to environmental and behavioral influences, must be fully characterized to develop novel therapeutics. In 2009, the INCF held the 1 st INCF Workshop on Genetic Animal Models for Brain Diseases to address the potential role of Neuroinformatics in the development, evaluation, and use of genetic animal models for brain diseases. A key finding from this workshop was the increased need for standardized and interoperable database resources in which different modality phenotype data from available disease models and wild type animals can be integrated. To further explore the findings of the 1st INCF Workshop on Genetic Animal Models for Brain Diseases, INCF in association with One Mind for Research convened a second workshop that focused on genetic disease models of psychiatric and neurological diseases which was held in Utrecht, Netherlands on February 14-16, 2013. The workshop was organized around three disease states: traumatic brain injury (TBI), autism spectrum disorder (ASD), and Alzheimer’s disease (AD). For each disease state, the core disease phenotypes were clinically defined and available data from current animal models were evaluated. This information was then aligned with the genetic background based on animal models and the specific human genetic architecture. Next, the workshop examined the degree of agreement between basic science research and clinical outcome measures along with the impact this has on drug evaluation. The program concluded with efforts to bridge the translational gap between preclinical models and clinical trials, such as has been done with the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. Overall, the goals of the workshop were to: 1. Determine the criteria for core symptom definitions of brain diseases 2. Make recommendations for studying these core symptoms in mice based on current needs, limitations, and opportunities 3. Determine at what level human disease genetic architecture is critical for mouse models of brain diseases 4. Determine to what extent mouse and studies for brain diseases should be optimally aligned (e.g., in view of drug development)

Assessment of cognitive functions in animal models of schizophrenia.

Impaired cognitive functioning is recognized as an integral feature of schizophrenia. These deficits have emerged not only as an important predictor of clinical and social outcomes but also as a target for schizophrenia therapeutics. Several cognitive functions have been identified as being commonly deficient in schizophrenia patients, including attention, working memory, reasoning and problem solving, visual learning and memory or social cognition. The selected neuropsychological tests measuring these specific domains were included in the MATRICS Consensus Cognitive Battery (MCCB) and in the Cambridge Neuropsychological Test Automated Battery (CANTAB). While the MCCB and the CANTAB are used in clinical trials of cognition-enhancing drugs for schizophrenia, there is a growing need for a translational test battery that can be used in animal models. To reduce the translational gap between preclinical and clinical studies, the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CINTRICS) programme has recommended animal tasks with construct validity for the evaluation of cognitive domains that are affected in schizophrenia. This review will overview rodent tests that are widely used to identify schizophrenia-like cognitive impairments, including CINTRICS's recommendations and novel touchscreen-based procedures.

Mice heterozygous for an inactivated allele of the schizophrenia associated Brd1 gene display selective cognitive deficits with translational relevance to schizophrenia

Schizophrenia is a debilitating brain disorder characterized by disturbances of emotion, perception and cognition. Cognitive impairments predict functional outcome in schizophrenia and are detectable even in the prodromal stage of the disorder. However, our understanding of the underlying neurobiology is limited and procognitive treatments remain elusive. We recently demonstrated that mice heterozygous for an inactivated allele of the schizophrenia-associated Brd1 gene (Brd1+/− mice) display behaviors reminiscent of schizophrenia, including impaired social cognition and long-term memory. Here, we further characterize performance of these mice by following the preclinical guidelines recommended by the ‘Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS)’ and ‘Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS)’ initiatives to maximize translational value. Brd1+/− mice exhibit relational encoding deficits, compromised working and long term memory, as well as impaired executive cognitive functioning with cognitive behaviors relying on medial prefrontal cortex being particularly affected. Akin to patients with schizophrenia, the cognitive deficits displayed by Brd1+/− mice are not global, but selective. Our results underline the value of Brd1+/− mice as a promising tool for studying the neurobiology of cognitive deficits in schizophrenia.

Memory deficit in patients with schizophrenia and posttraumatic stress disorder: relational vs item-specific memory.

It has been well established that patients with schizophrenia have impairments in cognitive functioning and also that patients who experienced traumatic events suffer from cognitive deficits. Of the cognitive deficits revealed in schizophrenia or posttraumatic stress disorder (PTSD) patients, the current article provides a brief review of deficit in episodic memory, which is highly predictive of patients’ quality of life and global functioning. In particular, we have focused on studies that compared relational and item-specific memory performance in schizophrenia and PTSD, because measures of relational and item-specific memory are considered the most promising constructs for immediate tangible development of clinical trial paradigm. The behavioral findings of schizophrenia are based on the tasks developed by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative and the Cognitive Neuroscience Test Reliability and Clinical Applications for Schizophrenia (CNTRACS) Consortium. The findings we reviewed consistently showed that schizophrenia and PTSD are closely associated with more severe impairments in relational memory compared to item-specific memory. Candidate brain regions involved in relational memory impairment in schizophrenia and PTSD are also discussed.

On Altered Patterns of Brain Activation in At-Risk Adolescents and Young Adults

On Altered Patterns of Brain Activation in At-Risk Adolescents and Young Adults

Cognitive Training in Schizophrenia: Golden Age or Wild West?

Cognitive Training in Schizophrenia: Golden Age or Wild West?

Revised associative inference paradigm confirms relational memory impairment in schizophrenia.

Patients with schizophrenia have widespread cognitive impairments, with selective deficits in relational memory. We previously reported a differential relational memory deficit in schizophrenia using the Associative Inference Paradigm (AIP), a task suggested by the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative to examine relational memory. However, the AIP had limited feasibility for testing in schizophrenia because of high attrition of schizophrenia patients during training. Here we developed and tested a revised version of the AIP to improve feasibility. 30 healthy control and 37 schizophrenia subjects received 3 study-test sessions on 3 sets of paired associates: H-F1 (house paired with face), H-F2 (same house paired with new face), and F3-F4 (two novel faces). After training, subjects were tested on the trained, noninferential Face-Face pairs (F3-F4) and novel, inferential Face-Face pairs (F1-F2), constructed from the faces of the trained House-Face pairs. Schizophrenia patients were significantly more impaired on the inferential F1-F2 pairs than the noninferential F3-F4 pairs, providing evidence for a differential relational memory deficit. Only 8% of schizophrenia patients were excluded from testing because of poor training performance. The revised AIP confirmed the previous finding of a relational memory deficit in a larger and more representative sample of schizophrenia patients.

CNTRICS Imaging Biomarkers Final Task Selection: Long-Term Memory and Reinforcement Learning

Functional imaging paradigms hold great promise as biomarkers for schizophrenia research as they can detect altered neural activity associated with the cognitive and emotional processing deficits that are so disabling to this patient population. In an attempt to identify the most promising functional imaging biomarkers for research on long-term memory (LTM), the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative selected "item encoding and retrieval," "relational encoding and retrieval," and "reinforcement learning" as key LTM constructs to guide the nomination process. This manuscript reports on the outcome of the third CNTRICS biomarkers meeting in which nominated paradigms in each of these domains were discussed by a review panel to arrive at a consensus on which of the nominated paradigms could be recommended for immediate translational development. After briefly describing this decision process, information is presented from the nominating authors describing the 4 functional imaging paradigms that were selected for immediate development. In addition to describing the tasks, information is provided on cognitive and neural construct validity, sensitivity to behavioral or pharmacological manipulations, availability of animal models, psychometric characteristics, effects of schizophrenia, and avenues for future development.

CNTRICS Imaging Biomarkers Selection: Working Memory

The sixth meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) consortium was focused on selecting promising imaging biomarker measures for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of working memory (WM), the 2 constructs of interest were "goal maintenance" and "interference control." CNTRICS received 7 task nominations for goal maintenance and 3 task nominations for interference control. For goal maintenance, the breakout group for WM recommended the AX Continuous Performance Test/Dot Pattern Expectancy (DPX) and the Switching Stroop task for translation and further development for use in clinical trial contexts in schizophrenia research. Notably, these same 2 paradigms were recommended for "rule generation and selection" in executive control, a highly related construct. For interference control, the breakout group recommended the Suppress Task and the Sternberg Item Recognition Paradigm for translation for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used by the breakout group to recommend tasks for further development. In addition, the group revisited the construct of WM capacity. Since the initial CNTRICS meeting, a growing body of work has emerged on the neurobiological substrates of WM capacity, making measure of this construct ready for translation. The group suggested a promising imaging biomarker measure for capacity, a version of the change detection task that measures delay activity over posterior parietal and occipital cortex.

Brain Mapping Biomarkers of Socio-Emotional Processing in Schizophrenia

The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative has formed with the expressed intent of identifying constructs and paradigms that would identify biomarkers of psychosis. The manipulation of these biomarkers would serve as targets for treatment interventions. The second phase of CNTRICS consisted of critical discussions evaluating brain mapping (functional neuroimaging and brain electrical activity) paradigms as biomarkers to measure specific constructs. Among the constructs identified in, CNTRICS I was socio-emotional processing, specifically focused on affect recognition. Here, we provide a critical appraisal of the ability of candidate socio-emotional tasks to identify putative biomarkers and recommendations for future directions in this rapidly moving research domain.

Perceptual Measurement in Schizophrenia: Promising Electrophysiology and Neuroimaging Paradigms From CNTRICS

The sixth meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) focused on selecting promising imaging paradigms for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of perception, the 2 constructs of interest were "gain control" and "visual integration." CNTRICS received 6 task nominations for imaging paradigms for gain control and 3 task nominations for integration. The breakout group for perception evaluated the degree to which each of these tasks met prespecified criteria. For gain control, the breakout group believed that one task (mismatch negativity) was already mature and was being incorporated into multisite clinical trials. The breakout group recommended that 1 visual task (steady-state visual evoked potentials to magnocellular- vs parvocellular-biased stimuli) and 2 auditory measures (an event-related potential (ERP) measure of corollary discharge and a functional magnetic resonance imaging (fMRI) version of prepulse inhibition of startle) be adapted for use in clinical trials in schizophrenia research. For visual integration, the breakout group recommended that fMRI and ERP versions of a contour integration test and an fMRI version of a coherent motion test be adapted for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used in the breakout group to evaluate and recommend tasks for further development.

CNTRICS Final Biomarker Selection: Control of Attention

Attention is widely believed to be dysfunctional in schizophrenia. The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) group previously concluded that the processes involved in the top-down control of attention are particularly impaired in schizophrenia and should be the focus of future research. These processes determine which sources of input should be attended, linking goal representations in prefrontal cortex with more posterior regions that implement the actual selection of attended information. A more recent meeting of the CNTRICS group assessed several paradigms that might be useful for identifying biomarkers of attentional control and that could be used for treatment development and assessment. Two types of paradigms were identified as being particularly promising. In one approach, neural activity is measured (using electroencephalography or functional magnetic resonance imaging) during the period between an attention-directing cue and a target. In a second approach, neural activity is measured under low- and high-distraction conditions. These approaches make it possible to identify the goal representations that guide attention and the interactions between these goal representations and the implementation of selection. Although more basic science research with healthy volunteers and preclinical research with schizophrenia patients is needed before these paradigms will be ready to provide clinically useful biomarkers, they hold substantial promise for aiding in the development and assessment of new treatments.

Standardization, Integration, and Sharing—Leveraging Research Investments

Cognitive impairment has been recognized as a significant cause of disability in schizophrenia for more than 20 years ( 1 Green M.F. What are the functional consequences of neurocognitive deficits in schizophrenia?. Am J Psychiatry. 1996; 153: 321-330 PubMed Google Scholar , 2 Green M.F. Kern R.S. Braff D.L. Mintz J. Neurocognitive deficits and functional outcome in schizophrenia: Are we measuring the “Right Stuff”?. Schizophr Bull. 2000; 26: 119-136 Crossref PubMed Scopus (2398) Google Scholar ), but the development of effective treatments for cognitive impairment in schizophrenia has been slow to advance. The National Institute of Mental Health (NIMH) Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative ( 3 Marder S.R. Fenton W. Measurement and treatment research to improve cognition in schizophrenia: NIMH MATRICS initiative to support the development of agents for improving cognition in schizophrenia. Schizophr Res. 2004; 72: 5-9 Abstract Full Text Full Text PDF PubMed Scopus (327) Google Scholar ) brought together members of academia, the pharmaceutical industry, and the US Food and Drug Administration to increase the viability of drug development by establishing consensus guidelines for study methodology, identifying promising targets for further investigation, and developing a standardized cognitive battery for use as end points in clinical trials. The resulting MATRICS Consensus Cognitive Battery (MCCB; 4 Nuechterlein K.H. Green M.F. Kern R.S. Baade L.E. Barch D.M. Cohen J.D. et al. The MATRICS Consensus Cognitive Battery, part 1: Test selection, reliability, and validity. Am J Psychiatry. 2008; 165: 203-213 Crossref PubMed Scopus (1544) Google Scholar , 5 Kern R.S. Nuechterlein K.H. Green M.F. Baade L.E. Fenton W.S. Gold J.M. et al. The MATRICS Consensus Cognitive Battery, part 2: Co-norming and standardization. Am J Psychiatry. 2008; 165: 214-220 Crossref PubMed Scopus (496) Google Scholar ) is a valuable tool that has been rapidly adopted and implemented in clinical research. However, instruments included in the MCCB are based on traditional neuropsychological measures developed more than 3 decades ago and tend to engage multiple cognitive functions simultaneously. This presents a significant disadvantage when testing treatments aimed at discrete cognitive processes, where “signal” for improved functioning might be obscured within a multi-component test of cognitive performance. With the revolution in cognitive science over the past decade ( 6 Cohen J.D. Insel T.R. Cognitive neuroscience and schizophrenia: Translational research in need of a translator. Biol Psychiatry. 2008; 64: 2-3 Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar ), the time is right to translate experimental cognitive neuroscience tasks into finer-grained clinical measures for use in the development of procognitive drugs. Transcranial Magnetic Stimulation: A Neuroscientific Probe of Cortical Function in SchizophreniaBiological PsychiatryVol. 70Issue 1PreviewTranscranial magnetic stimulation (TMS) is a neuropsychiatric tool that can serve as a useful method to better understand the neurobiology of cognitive function, behavior, and emotional processing. The purpose of this article is to examine the utility of TMS as a means to measure neocortical function in neuropsychiatric disorders in general, and schizophrenia in particular, for the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia initiative. When incorporating TMS paradigms in research studies, methodologic considerations include technical aspects of TMS, cohort selection and confounding factors, and subject safety. Full-Text PDF Using Brain Imaging Measures in Studies of Procognitive Pharmacologic Agents in Schizophrenia: Psychometric and Quality Assurance ConsiderationsBiological PsychiatryVol. 70Issue 1PreviewThe first phase of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICs) initiative focused on the identification of cognitive constructs from human and animal neuroscience that were relevant to understanding cognitive deficits in schizophrenia, as well as promising task paradigms that could be used to assess these constructs behaviorally. The current phase of CNTRICs has the goal of expanding this initial work by including measures of brain function that can augment these behavioral tasks as biomarkers to be used in drug development processing. Full-Text PDF Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia II: Developing Imaging Biomarkers to Enhance Treatment Development for Schizophrenia and Related DisordersBiological PsychiatryVol. 70Issue 1PreviewThe Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative, funded by an R13 from the National Institute of Mental Health, seeks to enhance translational research in treatment development for impaired cognition in schizophrenia by developing tools from cognitive neuroscience into useful measures of treatment effects on behavior and brain function. An initial series of meetings focused on the selection of a new set of tasks from cognitive neuroscience for the measurement of treatment effects on specific cognitive and neural systems. Full-Text PDF

CNTRICS Final Task Selection: Control of Attention

The construct of attention has many facets that have been examined in human and animal research and in healthy and psychiatrically disordered conditions. The Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) group concluded that control of attention-the processes that guide selection of task-relevant inputs-is particularly impaired in schizophrenia and could profit from further work with refined measurement tools. Thus, nominations for cognitive tasks that provide discrete measures of control of attention were sought and were then evaluated at the third CNTRICS meeting for their promise for future use in treatment development. This article describes the 5 nominated measures and their strengths and weaknesses for cognitive neuroscience work relevant to treatment development. Two paradigms, Guided Search and the Distractor Condition Sustained Attention Task, were viewed as having the greatest immediate promise for development into tools for treatment research in schizophrenia and are described in more detail by their nominators.

Perception Measurement in Clinical Trials of Schizophrenia: Promising Paradigms From CNTRICS

The third meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) focused on selecting promising measures for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of perception, the 2 constructs of interest were gain control and visual integration. CNTRICS received 5 task nominations for gain control and three task nominations for visual integration. The breakout group for perception evaluated the degree to which each of these tasks met prespecified criteria. For gain control, the breakout group for perception believed that 2 of the tasks (prepulse inhibition of startle and mismatch negativity) were already mature and in the process of being incorporated into multisite clinical trials. However, the breakout group recommended that steady-state visual-evoked potentials be combined with contrast sensitivity to magnocellular vs parvocellular biased stimuli and that this combined task and the contrast-contrast effect task be recommended for translation for use in clinical trial contexts in schizophrenia research. For visual integration, the breakout group recommended the Contour Integration and Coherent Motion tasks for translation for use in clinical trials. This manuscript describes the ways in which each of these tasks met the criteria used by the breakout group to evaluate and recommend tasks for further development.

Selecting Paradigms From Cognitive Neuroscience for Translation into Use in Clinical Trials: Proceedings of the Third CNTRICS Meeting

This overview describes the goals and objectives of the third conference conducted as part of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. This third conference was focused on selecting specific paradigms from cognitive neuroscience that measured the constructs identified in the first CNTRICS meeting, with the goal of facilitating the translation of these paradigms into use in clinical trials contexts. To identify such paradigms, we had an open nomination process in which the field was asked to nominate potentially relevant paradigms and to provide information on several domains relevant to selecting the most promising tasks for each construct (eg, construct validity, neural bases, psychometrics, availability of animal models). Our goal was to identify 1-2 promising tasks for each of the 11 constructs identified at the first CNTRICS meeting. In this overview article, we describe the on-line survey used to generate nominations for promising tasks, the criteria that were used to select the tasks, the rationale behind the criteria, and the ways in which breakout groups worked together to identify the most promising tasks from among those nominated. This article serves as an introduction to the set of 6 articles included in this special issue that provide information about the specific tasks discussed and selected for the constructs from each of 6 broad domains (working memory, executive control, attention, long-term memory, perception, and social cognition).

CNTRICS final task selection: executive control.

The third meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) was focused on selecting promising measures for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of executive control, the 2 constructs of interest were "rule generation and selection" and "dynamic adjustments in control." CNTRICS received 4 task nominations for each of these constructs, and the breakout group for executive control evaluated the degree to which each of these tasks met prespecified criteria. For rule generation and selection, the breakout group for executive control recommended the intradimensional/extradimensional shift task and the switching Stroop for translation for use in clinical trial contexts in schizophrenia research. For dynamic adjustments in control, the breakout group recommended conflict and error adaptation in the Stroop and the stop signal task for translation for use in clinical trials. This article describes the ways in which each of these tasks met the criteria used by the breakout group to recommend tasks for further development.

CNTRICS final task selection: working memory.

The third meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) was focused on selecting promising measures for each of the cognitive constructs selected in the first CNTRICS meeting. In the domain of working memory, the 2 constructs of interest were goal maintenance and interference control. CNTRICS received 3 task nominations for each of these constructs, and the breakout group for working memory evaluated the degree to which each of these tasks met prespecified criteria. For goal maintenance, the breakout group for working memory recommended the AX-Continuous Performance Task/Dot Pattern Expectancy task for translation for use in clinical trial contexts in schizophrenia research. For interference control, the breakout group recommended the recent probes and operation/symmetry span tasks for translation for use in clinical trials. This article describes the ways in which each of these tasks met the criteria used by the breakout group to recommend tasks for further development.

Measurement issues in the use of cognitive neuroscience tasks in drug development for impaired cognition in schizophrenia: a report of the second consensus building conference of the CNTRICS initiative.

This overview describes the goals and objectives of the second conference conducted as part of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. This second conference was informed by a series of online surveys and brought together basic and clinical scientists from academia and industry to address the concerns central to each field of research. Our goal was to develop recommendations for future research addressing the psychometric and practical challenges involved in translating paradigms from cognitive neuroscience into tasks that are feasible for use in the treatment discovery and development process. In this overview article, we describe the series of talks that were presentations at the conference. This article serves as an introduction to the set of articles included in this special issue that provide overviews and discussions of the issues raised and the recommendations made in these talks and in the subsequent discussions at the meeting. In addition, we describe the online surveys conducted in the month before the conference that were used to obtain suggestions from the field as to important task selection criteria and to generate initial benchmark goals for psychometric development for cognitive neuroscience tasks.