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1 ability dysfunctional beliefs affecting motivation and negative symptoms acetylcholine acetylcholinesterase inhibitors 272 adolescents, relevance of performance-based measures 262 affect recognition, studies of affect recognition training 300 neural mechanisms of affective saliency of stimuli, assessment issue 61 aging cognitive processing, changes in and dementia sensory functioning, changes in 112 see also older patients alertness-promoting agent, modafinil 275 Alzheimer s disease (AD) 117 amphetamine treatment 275 anhedonia 100 anterior cingulate cortex (ACC), error/conflict detection anticholinergic medication, negative effects on cognition 10, 309 antipsychotic medications dopamine D2 receptor blockade 267 dosing effects of addon compounds effect on cognition 9 10 and emotion recognition interference with effects of cognitive enhancers apathy 100 assessment affective saliency of tasks 61 of cognitive and functional skills cognitive neuroscience approach consensus batteries experiential negative symptoms 93 informant-based reports of functional performance 119 issues requiring further study 121 repeated testing, bipolar disorders 62 standard cognitive measures, criticism of see also performance-based measures of functioning assessment of cognition in schizophrenia treatment studies 231 cognitive outcome measures 240 computerized tests paper pencil batteries current status of clinical trials outcome measures and study designs 239 associative memory 208 attention attitudes, dysfunctional attributional style 86, bipolar disorder 56 training programs targeting 300 auditory (dys)function 180 behavioral studies neurophysiological approaches normative age-related changes predicting social cognition and outcome 88 auditory emotion recognition 181 auditory steady-state response (ASSR) 182 auditory training, Brain Fitness Program awareness of illness measurement of insight 150 measurement of neurocognition meta-analysis data analysis 145 discussion limitations of studies included in 150 methods used results studies included in AX-CPT task, executive processing/working memory 185 B-CATS (Brief Cognitive Assessment Tool for Schizophrenia) 241 BACS (Brief Assessment of Cognition in Schizophrenia) BCA (Brief Cognitive Assessment) 241 beliefs, dysfunctional BFP see Brain Fitness Program bipolar disorder functional impairment genetics 167 neuropsychological impairments 70 social cognition 54 56

2 317 bipolar disorder/schizophrenia comparison assessment issues clinical remission diagnostic criteria functional outcomes, predictors of and history of psychosis 59 negative symptoms 58 neurophysiological findings profile and course of cognitive deficit sex differences trans-disorder effects 167 blunted affect 100 brain-derived neurotrophic factor (BDNF), effect of training on levels 309 Brain Fitness Program (BFP) and improvements in neural operations during early auditory processes and increase in serum BDNF and D-serine levels 309 brain reserve capacity theory 72 brain volume loss, in persistent psychosis 118 Brief Assessment of Cognition in Schizophrenia (BACS) Brief Cognitive Assessment (BCA) 241 Brief Cognitive Assessment Tool for Schizophrenia (B-CATS) 241 brief version of UPSA 121, 257, CACNA1C gene 168 Cambridge Neuropsychological Test Automated Battery (CANTAB) 242 cannabinoid receptor agents 277 chronicity of illness, impact on cognition 10 clinical remission clinical trials on cognition co-primary measures of functional capacity design of early phase trials further cognitive outcome measures implementation issues 235 trials using cognitive neuroscience tests 238 interview-based measures 239 Cognitive Assessment Interview (CAI) 239 cognitive deficits/impairments course of effect sizes 4 5 heritability of 163 included as a dimension of psychosis 80 independence from psychosis profile of as stable traits in schizophrenia 163 see also generalized cognitive deficits cognitive domains, similarities and differences between schizophrenia and comparison groups Cognitive Drug Research (CDR) battery cognitive enhancement, pharmacological approaches compounds used in previous studies methodology negative results, reasons for neurotransmitter interventions Cognitive Enhancement Therapy (CET) 289 cognitive neuropsychiatry cognitive neuroscience 25 26, 194 models of episodic memory models of working memory 195 cognitive processing, normative age-related changes cognitive remediation and vocational rehabilitation see computerized cognitively intact schizophrenia explanations for 72 and symptom severity 11 CogPack, computerized training CogRehab software, computerized training 288 CogState schizophrenia battery 242 community functioning 87, contribution of social cognition performance-based assessment competence see functional capacity; social competence computational modeling and ph-fmri computerized cognitive training 284 important future directions neurobiological effects of 304 prior meta-analytic work programs 287 BPF (Brain Fitness Program) CogPack exercises, studies using CogRehab exercises, studies using comparative effects of NEAR (Neuropsychological & Educational Approach to Remediation) psychophysical findings 308 serum biomarker and genetic findings computerized social cognitive training neurobiological effects of

3 318 computerized social cognitive training (cont.) with social cognitive group treatment 300 summary of computerized testing COMT polymorphisms and cognitive improvement after training and pharmacological issues 279 conflict detection, executive control context processing Continuous Performance Tasks (CPT), inheritance of attentional deficits control, proactive and reactive control task issues in experimental designs copy number variants (CNVs), rare variation 161, cortical disinhibition, ketamine effects cross-cultural relevance of performance-based measures 262 CTNRICS (Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia) cultural differences in generalized cognitive deficits 35 performance-based measures 262 D-serine, training increasing levels of 309 davunetide, neurogenesis promoting 277 declarative memory, ketamine effects 178 default mode network (DMN) 204 defeatist beliefs 92 delusions interference with work see also persecutory delusions dementia , dementia praecox, symptoms 2 demographic issues age of clinical trial samples sex differences, comparison studies depressive symptoms diagnostic criteria Direct Assessment of Functional Status scale (DAFS) direct observation of functional tasks, problems with 251 disorganization/disorganized symptoms links to cognitive domains relationship to executive functions relationship to ToM abilities 128 distraction, suppression of, WM tasks , dopamine D1 agonists, administration problems 279 disruption by glutamatergic dysregulation 269 dorsolateral prefrontal cortex (DLPFC) and ACC activity, executive control deficits 212 inverted-u hypothesis, working memory post-mortem studies and proactive control 211 reduced activation during WM tasks 200 role in distraction suppression, WM tasks 204 role in episodic memory 208 dose of medications drugs see medication; pharmacological approaches to cognitive enhancement DTNBP1 gene studies dual process vs. standard model of schizophrenia 6 dysfunctional beliefs and negative symptoms educational attainment and work functioning 99 EFB (Everyday Functioning Battery) 259 effect size, funnel plot Emotion Trainer, computerized program emotional processing/ emotional intelligence 86, bipolar disorder computerized training in face processing tasks, methodological issues link to community functioning 132 oxytocin improving 134 prosodic-level impairments visual deficits, contribution of 185 empathy, bipolar disorder 56 employment see work functioning encoding in episodic memory, neural correlates encoding deficits, working memory and interference control deficits 199 neural evidence for role of default mode network (DMN) 204 endophenotype approach, genetics research 162 Enriched Supportive Therapy (EST) 289 episodic memory (EM) cognitive neuroscience models genetic studies impairments and neural correlates error monitoring, executive control

4 319 event-related potentials (ERP) assessment of early auditory processing 89 bipolar disorder/ schizophrenia comparison Everyday Functioning Battery (EFB) 259 exceptionality and verbal superiority 8 versus normality 5 7 executive control dysfunction 209 conflict detection/error monitoring context processing proactive and reactive control experiential negative symptoms 93 experimental designs, control task issues externalizing attributional bias 13, eye movement, deficits in smooth pursuit face processing tasks, methodological issues facial emotion recognition computerized training in early visual deficits impairing 185 factor analyses bipolar disorder and schizophrenia comparison of cognitive domains social cognition and neurocognition 87 88, 131 false beliefs see delusions; theory of mind (ToM) familial pattern of deficits filtering deficits, working memory 199, first episode psychosis (FEP) attrition rates in computerized tests cognitive deficits in 10 psychosis studies 70 symptom dimensions and cognitive functioning fmri (functional magnetic resonance imaging) computerized cognitive training, improved activation following computerized social cognition training pharmacological fmri (ph-fmri) working memory (WM) Food and Drug Administration (FDA), approval criteria for cognitive enhancing drugs functional capacity co-primary measures informant-based reports 119 interview-based measures 239 link to defeatist beliefs 92 performance-based measures role in identifying determinants of disability self-report measures, biases in functional milestones, limited responsiveness of functional outcome and neurocognition bipolar disorder schizophrenia comparison cognitive ability as key predictor of 4, contribution of social cognition to integrating perception, ability and motivation perceptual processes predicting 88 role of negative symptoms social cognition as mediator between funnel plot, publication bias GABA (gamma-aminobutyric acid) and cortical disinhibition interventions 277 reduced signaling levels 269 general intelligence, heritability of 166 generalized cognitive deficits 24 27, 32, 194 around the globe 35 factor analyses of cognitive domains general discussion and conclusion meta-analysis findings over past three decades pattern within families treatment issues vs. specific impairments genetic association studies COMT polymorphism and cognitive improvement after training genetic factors attention cognitive deficits as candidate endophenotype heritability of 42, 163 as stable traits 163 episodic memory general intelligence 166 working memory global cognitive impairment see generalized cognitive deficits glutamatergic interventions glutamatergic neurotransmission, disturbance of and higher cognitive dysfunction and impaired sensory processing group treatment, social cognitive skills training 300

5 320 hallucinations, effect on work functioning 99 heritability of cognitive deficits 163 of schizophrenia see also genetic factors hierarchical model of cognitive domain structure hippocampus learning and declarative memory 178 preservation of gray matter following CET 307 role in episodic memory and visual dysfunction and ZNF804A risk variant hospitalization, impact on functional outcome 118 illness awareness see awareness of illness Independent Living Scales (ILS) informant-based reports of functional performance 119 variation in informant validity 250 in-person observation of functional activity, problems with 251 see also awareness of illness intelligence, heritability of 166 interference control deficits, WM interview-based measures 239, 261 inverted U hypothesis, prefrontal recruitment in WM JTC (jumping to conclusions) effect ketamine behavioral effects 214 neurobiological effects specificity of response 178 task-switching performance in monkeys Kraepelin, E., dementia praecox, symptoms 2 lamotrigine treatment 274 learning and declarative memory, ketamine response 178 long-term memory magnetoencephalography (MEG) studies magnitude/severity of impairment magnocellular pathway, visual dysfunction maintenance deficits, working memory mechanisms contributing to neuroimaging evidence Maryland Assessment of Social Competence (MASC) 254 MATRICS Consensus Cognitive Battery (MCCB) MATRICS CT study 261 MATRICS (Measurement and Treatment Research to Improve Cognition in Schizophrenia) project 61 62, 119, 231, 233, 271 medial prefrontal cortex, activation during reality-monitoring training 307 medication administration problems 279 doses, effect on efficacy effect on cognition 9 10, 309 and emotion recognition interference with cognitive enhancers 278 Medication Management Ability Assessment (MMAA) 258 memory Bleuler s work 1 2 effect of medication on 10 normative age-related changes see also episodic memory (EM); working memory (WM) mental state attribution 87 see also theory of mind (ToM) meta-analyses, cognitive deficit findings comparative findings 4 5 global cognition meta-analysis, insight cognition link studies included in analysis meta-analytic studies of Micro-Expressions Training Tool (METT) Micro-Module Learning Test (MMLT) mild cognitive impairment (MCI) 114 mismatch negativity (MMN) 89, 182 missing data, computerized tests MK-0777 treatment 277 modafinil treatment 275 motion detection deficits 183 motivation, ability and negative symptoms muscarinic receptor systems N-methyl-D-aspartate (NMDA) see NMDA receptor dysfunction NEAR (Neuropsychological and Educational Approach to Remediation) negative symptoms 58 ability and motivation correlation with cognitive domains and dysfunctional beliefs experiential, reduced motivation 93 interference with work neurobiological determinants of cognition 176 glutamatergic contributions to impaired sensory processing 178

6 321 auditory function visual dysfunction glutamatergic determinants of higher cognitive dysfunction PCP/NMDA model of schizophrenia 176 summary 186 Neurocognitive Enhancement Therapy (NET) 290 neurocognitive measures neurodegenerative disorders 114, 117 neurodevelopmental hypotheses cognitive impairment 41 cognitively intact schizophrenia 72 neurogenesis-promoting compounds 277 neuroimaging magnetoencephalography (MEG) studies voxel-based morphometry (VBM) 307 see also fmri (functional magnetic resonance imaging) neurophysiological findings 56 57, visual dysfunction 183 working memory abnormalities neuroplasticity and decreased BDNF functioning 309 Neuropsychological and Educational Approach to Remediation (NEAR) neurotransmitters acetylcholine dopamine GABA 269 glutamate non-viable as cognitive enhancers 279 nicotinic agonists nicotinic receptor density, alteration of 269 NMDA receptor dysfunction and auditory deficits and cognitive deficits hypo-function hypothesis, ketamine effects and visual deficits non-transmitter interventions 277 noradrenergic interventions normality 6 8 novel relational information, encoding and retrieval of, role of hippocampus older patients , 121 assessment of cognitive and functional skills and dementia functional performance hospitalization 118 see also aging oxytocin, improving emotion recognition 134 paper pencil test batteries parvocellular pathway, visual dysfunction PCP (phencyclidine)/nmda model of schizophrenia perception integrating with ability and motivation perceptual closure, visual function 184 as predictor of social cognition and outcome 88 see also social perception performance-based measures of functioning , 248 advantages of over other modalities future directions limitations of 251 role in identifying determinants of disability selected measures Direct Assessment of Functional Status scale (DAFS) Everyday Functioning Battery (EFB) 259 Independent Living Scales (ILS) Maryland Assessment of Social Competence (MASC) 254 Medication Management Ability Assessment (MMAA) 258 Micro-Module Learning Test (MMLT) Social Skills Performance Assessment (SSPA) Test of Adaptive Behavior in Schizophrenia (TABS) UCSD Performance-Based Skills Assessment (UPSA) 255 UPSA-Brief 257 summary and conclusions 263 use of in treatment studies 261 performance normality, definition and prevalence of 6 8 persecutory delusions and attributional style 56, 86, JTC (jumping to conclusions) effect personalizing attributional bias 56, pharmacokinetics 279 pharmacological approaches to cognitive enhancement 266 cognitive enhancement methodology mechanisms of action studied acetylcholinesterase inhibitors 272 amphetamine 275 cannabinoid receptor agents 277 GABA-based interventions 277

7 322 pharmacological approaches to cognitive enhancement (cont.) glutamatergic interventions modafinil 275 nicotinic agonists non-transmitter interventions 277 noradrenergic interventions serotonergic medications negative results, reasons for transmitter manipulations pharmacological models of psychosis behavioral effects of ketamine 214 integration with computational models neurobiological effects of ketamine phencyclidine (PCP) model positive symptoms see psychotic symptoms prefrontal cortex (PFC) and episodic memory 207, 208 NMDA dysfunction premorbid functioning and vocational success 99 prevalence of impairment 9, 51 proactive and reactive control problem solving training prosodic-level impairments prospective and procedural memory psychiatric rehabilitation studies psychological testing, challenges of 235 psychosis and cognition features in bipolar disorder 59 future typology 80 persistent, link to poor outcome 118 psychotic symptoms classification and cognitive deficits and cognitive functioning interference with work see also persecutory delusions publication bias 145, quality of life improvements 15 RBANS (Repeatable Battery for the Assessment of Neuropsychological Status) 240 reactive and proactive control reading measures, effect sizes of paragraphs, impact of early visual deficits 185 premorbid performance level issue 8 real-world functioning see performance-based measures reality-monitoring, effects of computerized training on 307 rehabilitation see computerized relational memory evidence for impaired DLPFC function 208 role of hippocampus remission of symptoms bipolar disorders persistence of cognitive impairment following 13 Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) 240 research on cognition in schizophrenia, early pioneers 1 3 retrieval-related processes episodic memory, neural correlates working memory 203 role playing, measures using 254, schizophrenia as a cognitive disorder schizophrenia and bipolar disorder comparison 50 assessment issues course of cognitive deficits diagnostic criteria functional outcomes future directions moderating variables neurophysiological findings profile of cognitive deficits social cognition in bipolar disorder treatment of cognitive deficits 62 Schizophrenia Cognition Rating Scale (SCoRS) 239 self-appraisal/self-processing 143 self-report measures of functioning, avoidance of biases in sensory functioning glutamatergic contribution normative age-related changes 112 see also auditory (dys) function; visual (dys) function sensory gating deficits 57, 304 serotonergic medications serum biomarkers of traininginduced changes 309 set concept, early research by Shakow 3 gender differences, comparison studies siblings, unaffected, comparison of cognitive deficits skills training, tests assessing smoking, effects of 269 social cognition 126 in bipolar disorder definition of

8 323 domains of and functional outcome future directions and neurocognition perception as correlate and predictor of 88 role of ZNF804A risk variant 168 and work problems 100 see also computerized social Social Cognitive Interaction Training (SCIT) 300 Social Cognitive Skills Training (SCST) 300 social competence assessment of 254 deficits, and work problems 100 social perception 86 bipolar disorder 55 computerized training see also social cognition Social Skills Performance Assessment (SSPA) specific/core cognitive deficits 194 standard vs. dual process models 6 Standards for Educational and Psychological Testing (APA) 235 standards for psychological testing 235 stimulants and alertness agents 267 amphetamines 275 modafinil 275 nicotinic agonists Subtle Expressions Training Tool (SETT) symptom dimensions in psychosis 69, and neuropsychological functioning psychotic disorders schizophrenia studies summary and conclusion symptoms interference with work severity of, and cognition see also negative symptoms targeted pro-cognitive treatments task switching, neural correlates of temporal differences in generalized deficits Test of Adaptive Behavior in Schizophrenia (TABS) theory of mind (ToM) 128 bipolar disorder 55 cognitive basis of persecutory beliefs 13 link to insight mental state attribution 87 tone-of-voice, impaired discrimination tone matching training see computerized Training of Affect Recognition (TAR) 299 translational cognitive neuroscience 193 neural correlates of cognitive dysfunction episodic memory executive control working memory working memory example computational modeling and ph-fmri pharmacological neuroimaging (ph-fmri) treatment of cognitive deficits 62 twin studies cognitive deficits 42, 163 working memory two pathway model UCSD Performance-Based Skills Assessment (UPSA) 255 use in older patients 117, unaffected siblings, comparison of cognitive deficits UPSA-Brief (UPSA-B) 121, 257, Validation of Intermediate Measures (VIM) study validity of cognitive measures as outcome predictors of self-reports 250 of symptom dimensions verbal learning and memory, training program verbal memory processes Brain Fitness Program improving neural activation following computerized training verbal superiority study 8 visual contour integration 89, 185 visual (dys)function cognitive consequences of early normative age-related changes predicting social cognition and outcome 88 visual training, improving visual memory 308 vocational rehabilitation , 295, 297 voxel-based morphometry (VBM) 307 work functioning cognitive remediation and vocational rehabilitation effect of cognitive impairments 101 premorbid functioning and educational attainment 99 psychotic and negative symptoms social competence problems 100

9 324 work functioning (cont.) summary and conclusions supported employment working memory (WM) behavioral findings 196 encoding/maintenance deficits maintenance phase, interference control/ decay deficits cognitive neuroscience models 195 computational modeling and ph-fmri context processing role heritability of neurocognitive enhancement therapy improving neuroimaging findings 200 neural deficits across phases of WM prefrontal recruitment summaries , 218 younger people greater potential neuroplasticity 232 relevance of current test measures 262 ZNF (zinc finger protein) 804A gene