For several decades the National Institute of Mental Health (NIMH) has supported basic and translational research into cognitive impairment in schizophrenia. This article describes the Institute\'s ongoing commitment to cognitive assessment and intervention research, as reflected by three signature initiatives-Measurement and Treatment Research to Improve Cognition in Schizophrenia; Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia; and Research Domain Criteria-and related funding announcements that span basic experimental studies, efficacy and comparative effectiveness trials, and implementation research designed to promote cognitive healthcare in real-world treatment settings. We discuss how trends in science and public health policy since the early 2000s have influenced NIMH treatment development activities, resulting in greater attention to (1) inclusive teams that reflect end-user perspectives on the utility of proposed studies; (2) measurement of discrete neurocognitive processes to inform targeted interventions; (3) clinical trials that produce useful information about putative illness mechanisms, promising treatment targets, and downstream clinical effects; and (4) \"productive urgency\" in pursuing feasible and effective cognitive interventions for psychosis. Programs employing these principles have catalyzed cognitive measurement, drug development, and behavioral intervention approaches that aim to improve neurocognition and community functioning among persons with schizophrenia. NIMH will maintain support for innovative and impactful investigator-initiated research that advances patient-centered, clinically effective, and continuously improving cognitive health care for persons with psychotic disorders.

UNASSIGNED: The aim of this study was to characterise long-term neurological and neurocognitive sequelae after tick-borne encephalitis (TBE) in adults.
UNASSIGNED: 98 prospective consecutive TBE patients, classified by disease severity, were included. Immediate outcomes were evaluated with Glasgow Outcome Scale (GOS) and Rankin Scale (RS). After 6 and 18 months, long-term disability was evaluated using Modified Rankin Scale (MRS) and neurocognitive assessment was performed with Matrics Consensus Cognitive Battery (MCCB), measuring processing speed, attention/vigilance, working memory, verbal learning, visual learning, reasoning/problem solving and social cognition. The MCCB results were compared to healthy age, gender and education-matched controls.
UNASSIGNED: Mild, moderate, and severe TBE was diagnosed in 53.1%, 38.8%, and 8.2% of cases, respectively. At discharge, 25.5% of the patients had major or moderate impairments (GOS) and various levels of disability in 34.7% (RS). Up to 18 months from the onset of TBE, over 20% remained with slight to moderate disability (MRS). GOS, RS and MRS scores correlated with disease severity. At 6 months after the onset, TBE patients scored significantly lower than controls in processing speed, verbal, and visual learning. Two latter domains were significantly more impaired in patients with mild TBE. Patients aged 18-39 performed significantly worse in attention/vigilance and working memory, whereas aged 60+ in verbal learning. A year later, significant improvement was observed in six of seven cognitive domains.
UNASSIGNED: Long-term neurological sequelae persist in a substantial proportion of TBE patients with significant impairment in several cognitive domains, especially in younger patients and even after mild TBE.

Cognitive deficits in visuospatial learning (VSL) are highly associated with an increased risk of developing psychosis among populations with clinical high risk (CHR) for psychosis. Early interventions targeting VSL enhancement are warranted in CHR but remain rudimentary. We investigated whether personalized transcranial magnetic stimulation (TMS) over the left parieto-hippocampal network could improve VSL performance in CHR patients and if it could reduce the risk of psychosis conversion within 1 year.
Sixty-five CHR patients were randomized to receive active or sham TMS treatments using an accelerated TMS protocol, consisting of 10 sessions of 20 Hz TMS treatments within 2 days. TMS target was defined by individual parieto-hippocampal functional connectivity and precisely localized by individual structural magnetic resonance imaging. VSL performance was measured using Brief Visuospatial Memory Test-Revised included in measurement and treatment research to improve cognition in schizophrenia consensus cognitive battery (MCCB). Fifty-eight CHR patients completed the TMS treatments and MCCB assessments and were included in the data analysis.
We observed significant VSL improvements in the active TMS subgroup (Cohen\'s d = 0.71, P < .001) but not in the sham TMS subgroup (Cohen\'s d = 0.07, P = .70). In addition, active TMS improved the precision of VSL performance. At a 1-year follow-up, CHR patients who received active TMS showed a lower psychosis conversion rate than those who received sham TMS (6.7% vs 28.0%, χ2 = 4.45, P = .03).
Our findings demonstrate that personalized TMS in the left parieto-hippocampal network may be a promising preventive intervention that improves VSL in CHR patients and reduces the risk of psychosis conversion at follow-up.

Research on the influence of neurocognitive factors on suicide risk, regardless of the diagnosis, is inconsistent. Recently, suicide risk studies propose applying a trans-diagnostic framework in line with the launch of the Research Domain Criteria Cognitive Systems model. In the present study, we highlight the extent of cognitive impairment using a standardized battery in a psychiatric sample stratified for different degrees of suicidal risk. We also differentiate in our sample various neurocognitive profiles associated with different levels of risk.
We divided a sample of 106 subjects into three groups stratified by suicide risk level: Suicide Attempt (SA), Suicidal Ideation (SI), Patient Controls (PC) and Healthy Controls (HC). We conducted a multivariate Analysis of Variance (MANOVA) for each cognitive domain measured through the standardized battery MATRICS Consensus Cognitive Battery (MCCB).
We found that the group of patients performed worse than the group of healthy controls on most domains; social cognition was impaired in the suicide risk groups compared both to HC and PC. Patients in the SA group performed worse than those in the SI group.
Social cognition impairment may play a crucial role in suicidality among individuals diagnosed with serious mental illness as it is involved in both SI and SA; noteworthy, it is more compromised in the SA group fitting as a marker of risk severity.

UNASSIGNED: Persons with schizophrenia exhibit greater neurocognitive test score dispersion. Here, we seek to characterize dispersion on the Neurocognitive Composite subtests of the Measurement of Treatment Research to Improve Cognition in Schizophrena Consensus Cognitive Battery (MCCB) and determine the relative effects of different antipsychotic formulations on dispersion and mean performance.
UNASSIGNED: In this post hoc analysis of the DREaM study (NCT02431702), which compared treatment with paliperidone palmitate (PP) long-acting injectable with oral antipsychotic (OAP) treatment over 18 months, dispersion in MCCB neurocognitive subtest performance was calculated for each participant by visit (test occasion).
UNASSIGNED: Over 18 months, mean neurocognitive performance improved in a manner consistent with the expected effects of practice in both groups (p < 0.05); this improvement was observed during the first 9 months (PP: p < 0.05, OAP: p < 0.001), followed by stable performance over the second 9 months (PP: p = 0.821, OAP: p = 0.375). Rates of change did not differ between groups (treatment-by-visit interaction: p = 0.548). In contrast, analyses of dispersion focusing on contrasts between baselines and end points of the first and second 9 months revealed different patterns. Over the first 9 months, dispersion in both groups lessened to a similar extent. However, over the second 9 months, dispersion remained stable in the PP group, whereas neurocognitive performance became significantly more variable in the OAP group (p < 0.01).
UNASSIGNED: Dispersion of neurocognitive test scores provides a different index of cognitive change than that provided by composite scores. Long-term maintenance of therapeutic levels provided by PP over time may limit (relative to oral AP) the extent to which cognitive performance becomes more variable.

Impairments in cognitive functions are one of the main features of schizophrenia. A variety of factors can influence the extent of cognitive deficits. In our study, we examined the severity of cognitive deficits at different stages of the disease and the relationship between psychopathological symptoms and cognitive functions. We recruited 32 patients with first-episode psychosis (FEP), 70 with chronic schizophrenia (CS), and 39 healthy controls (HC). Psychopathological symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS) and cognitive functions were measured with the MATRICS Cognitive Consensus Battery (MCCB). Cognitive deficits were present in both FEP and CS participants. CS individuals had lower overall scores and poorer working memory; however, clinical variables appeared to play a significant role in these scores. In FEP, disorganization correlated negatively with verbal and visual learning and memory, social cognition, and overall score; negative symptoms negatively correlated with social cognition. In CS participants, disorganization correlated negatively with speed of processing, reasoning, problem solving, and overall score; negative symptoms were negatively correlated with speed of processing, visual learning, memory, and overall score; positive symptoms were negatively correlated with reasoning and problem solving. Our findings indicate that psychopathological symptoms have a significant impact on cognitive functions in FEP and CS patients.

BACKGROUND: The MATRICS consensus cognitive battery (MCCB) is the gold standard for neuropsychological assessment in psychotic disorders but is rarely used in low resource settings. This study used the MCCB to determine the prevalence, profile and associations of various exposures with cognitive impairment in Ugandan first-episode psychosis patients.
METHODS: Patients and matched healthy controls were recruited at Butabika Hospital in Uganda. Clinical variables were first collated, and after the resolution of psychotic symptoms, a neuropsychological assessment of seven cognitive domains was performed using the MCCB. Cognitive impairment was defined as two standard deviations (SD) below the mean in one domain or 1SD below the mean in two domains. Descriptive statistics determined the prevalence and profile of impairment while regression models determined the association between various exposures with cognitive scores while controlling for age, sex and education.
RESULTS: Neuropsychological assessment with the MCCB found the burden of cognitive impairment in first-episode psychosis patients five times that of healthy controls. The visual learning and memory domain was most impaired in first-episode psychosis patients, while it was the working memory domain for the healthy controls. Increased age was associated with impairment in the domains of the speed of processing (p < 0.001) and visual learning and memory (p = 0.001). Cassava-rich diets and previous alternative and complementary therapy use were negatively associated with impairment in the visual learning (p = 0.04) and attention/vigilance domains (p = 0.012), respectively. There were no significant associations between sex, history of childhood trauma, or illness severity with any cognitive domain.
CONCLUSIONS: A significant burden of cognitive impairment in Ugandan first-episode psychosis patients is consistent with prior data from other contexts. However, the profile of and risk factors for impairment differ from that described in such work. Therefore, interventions to reduce cognitive impairment in FEP patients specific to this setting, including dietary modifications, are required.

Patients with schizophrenia have shown widespread white matter microstructural abnormalities and cognitive deficits, but the definitive relationship between white matter and cognitive performance remains unclear. In this study, we investigated the possible associations between white matter integrity and cognitive deficits in drug-naive first-episode schizophrenia (dn-FES) using diffusion tensor imaging (DTI). A total of 96 participants, including 46 dn-FES patients and 50 healthy individuals, underwent 3.0 T magnetic resonance diffusion-weighted imaging and cognitive assessments using the Chinese version of the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB). Group differences were tested using tract-based spatial statistics (TBSS). Compared with the control group, the dn-FES group exhibited reduced white matter integrity, as indexed using fractional anisotropy (FA) metrics, in the right-hemispheric cluster comprising the posterior thalamic radiation, posterior corona radiata, superior longitudinal fasciculus, retrolenticular part of the internal capsule, tapetum, splenium of the corpus callosum, sagittal stratum, and inferior longitudinal fasciculus. We found that social cognitive deficit is significantly correlated with reduced FA in these white matter regions, except the sagittal stratum and inferior longitudinal fasciculus. Furthermore, we found that speed of processing is positively correlated with reduced FA in the right superior longitudinal fasciculus of dn-FES patients. In summary, white matter deficits were validated in dn-FES patients and could be associated with speed of processing and social cognition, providing clues about a neural basis of schizophrenia and a potential biomarker for clinical studies.

OBJECTIVE: Working memory impairments represent a core cognitive deficit in schizophrenia, predictive of patients\' daily functioning, and one that is unaffected by current treatments. To address this, working memory is included in the MATRICS Consensus Cognitive Battery (MCCB), a standardized cognitive battery designed to facilitate drug development targeting cognitive symptoms. However, the neurobiology underlying these deficits in MCCB working memory is currently unknown, mirroring the poor understanding in general of working memory deficits in schizophrenia.
METHODS: Twenty-eight participants with schizophrenia were administered working memory tests from the MCCB and examined with resting-state functional MRI. Intrinsic connectivity networks were estimated with independent component analysis. Each voxel\'s time series was correlated with each network time series, creating a feature vector for voxel-level connectivity analysis. This feature vector was associated with working memory by using the distance covariance statistic.
RESULTS: The neurobiology of MCCB working memory tests largely followed the multicomponent model of working memory but revealed unexpected differences. The dorsolateral prefrontal cortex was not associated with working memory. The central executive system was instead associated with delocalized right and left executive control networks. The phonologic loop within the multicomponent model, a subsystem involved in storing linguistic information, was associated with connectivity to the left temporoparietal junction and inferior frontal gyrus. However, connections to the language network did not predict working memory test performance.
CONCLUSIONS: These results provide supporting evidence for the multicomponent model of working memory in terms of the biology underlying MCCB findings.

Electroconvulsive therapy is an effective treatment for bipolar depression, but there are concerns about whether it causes long-term neurocognitive impairment.
In this multicenter randomized controlled trial, in-patients with treatment-resistant bipolar depression were randomized to either algorithm-based pharmacologic treatment or right unilateral electroconvulsive therapy. After the 6-week treatment period, all of the patients received maintenance pharmacotherapy as recommended by their clinician guided by a relevant treatment algorithm. Patients were assessed at baseline and at 6 months. Neurocognitive functions were assessed using the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery, and autobiographical memory consistency was assessed using the Autobiographical Memory Interview-Short Form.
Seventy-three patients entered the trial, of whom 51 and 26 completed neurocognitive assessments at baseline and 6 months, respectively. The MATRICS Consensus Cognitive Battery composite score improved by 4.1 points in both groups (P = .042) from baseline to 6 months (from 40.8 to 44.9 and from 41.9 to 46.0 in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively). The Autobiographical Memory Interview-Short Form consistency scores were reduced in both groups (72.3% vs 64.3% in the algorithm-based pharmacologic treatment and electroconvulsive therapy groups, respectively; P = .085).
This study did not find that right unilateral electroconvulsive therapy caused long-term impairment in neurocognitive functions compared to algorithm-based pharmacologic treatment in bipolar depression as measured using standard neuropsychological tests, but due to the low number of patients in the study the results should be interpreted with caution.
ClinicalTrials.gov: NCT00664976.