CNTRICS Imaging Biomarker Selections: Executive Control Paradigms

Neuroimaging Intermediate Phenotypes of Executive Control Dysfunction in Schizophrenia

“…Future research could be made more powerful, reproducible and resource-efficient by the use of larger datasets and standardized paradigms and methods across centers. Recommendations of research practices and clinically relevant paradigms have been made by expert groups (122)(123)(124), and the last few years have seen a number of high-powered imaging genetics studies with hundreds or even thousands of subjects (30, 38, 62, 73,80,119,120,125,126). Much of the problem of small sample sizes can be attributed to the expense of acquiring imaging data, which limits the number of subjects that individual groups can afford to use.…”

Blocking NMDAR Disrupts Spike Timing and Decouples Monkey Prefrontal Circuits: Implications for Activity-Dependent Disconnection in Schizophrenia

“…To investigate that question in this study, we (1) trained monkeys to perform a cognitive control task that measures specific deficits in schizophrenia (Barch et al, 2003; Carter et al, 2012; Jones et al, 2010; MacDonald et al, 2005; MacDonald et al, 2003), (2) administered drugs that block NMDA receptors to mimic some aspects of synaptic dysfunction in schizophrenia (Kirov et al, 2012; Timms et al, 2013; Umbricht et al, 2000), as well as to replicate the same pattern of cognitive control errors in monkeys that has been reported in patients (Blackman et al, 2013; Jones et al, 2010; MacDonald, 2008; MacDonald et al, 2005; MacDonald and Chafee, 2006), and (3) carried out multi-electrode recording in prefrontal cortex of monkeys to characterize how an NMDAR synaptic deficit distorted the spiking dynamics of prefrontal cortical circuits. This allowed us to test the hypothesis that changes in synaptic function, cognitive function, and network connectivity might be linked by an underlying defect in the relative timing with which prefrontal neurons generate action potentials with respect to one another.…”

Aligning physiology with psychology: Translational neuroscience in neuropsychiatric drug discovery

“…The field of schizophrenia has led the way with initiatives like MATRICS [Measurement and Treatment Research to Improve Cognition in Schizophrenia (Green and Nuechterlein, 2004)], and Clinical Antipsychotic Trials of Intervention Effectiveness [CATIE (McEvoy, 2006;Stroup et al, 2003)], Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia [CNTRICS (Carter and Barch, 2007)]. CNTRICS especially has prompted coordination of animal models and human clinical studies of cognition [e.g., (Barch et al, 2009;Harvey, 2008;Kerns et al, 2008) that integrates animal models Dudchenko et al, 2013;Lustig et al, 2012;Millan and Bales, 2013;Siegel et al, 2013;Young et al, 2013), imaging and biomarker research (Barch and Mathalon, 2011;Barch et al, 2012;Carter et al, 2012;Taylor et al, 2012).…”