The validity and significance of normal range neurocognition in schizophrenia remain unclear and controversial. We assessed whether normal range patients and controls demonstrate evidence of decline relative to premorbid ability and differ in performance profiles across measures, including those external to the normality criterion. In addition, we compared below normal range healthy control participants with patients at the same ability level. Performance normality was defined as a MATRICS Consensus Cognitive Battery (MCCB) composite T score between 40 and 60. Patients (n = 17) and controls (n = 24) meeting the criterion were compared on MCCB domain scores and on independent measures of reading ability, probabilistic and social reasoning. Patients (n = 19) and controls (n = 20) scoring below 40 on the MCCB composite were compared on the same set of measures. Cognitively normal range patients and controls did not differ on estimated premorbid ability or decline and differed only on the Processing Speed domain of the MCCB. Performance did not differ across other domains or on social and probabilistic reasoning tasks. Cognitively below normal range patients and controls showed marked discrepancies between premorbid and current ability, but there were no group differences. In addition, below normal range groups did not differ on any MCCB domain score or in terms of external cognitive measures. Cognitively normal range schizophrenia patients may be largely indistinguishable from normal range controls, with the exception of processing speed performance. More typical schizophrenia patients below the normal range may be indistinguishable from low-performing controls even in terms of processing speed.

Objective: Although impaired general intellectual ability is a prevalent feature in schizophrenia, patterns suggesting preserved, deteriorated, and premorbidly impaired intellect have also been identified. The main purpose of this investigation was to examine the clinical, cognitive, and neuroanatomical characteristics of these intellectual subtypes, and to establish the value and validity of this approach for reducing the heterogeneity of schizophrenia. Methods: A total of 71 patients with a diagnosis of schizophrenia or schizoaffective disorder and 66 healthy controls were assessed. A 'preserved' performance pattern (n=29) was defined by average-range estimated premorbid and current IQ with no evidence of decline (premorbid-current IQ difference <10 points). A 'deteriorated' pattern (n=14) was defined by a difference between estimated premorbid and current IQ estimates of 10 points or more. A 'premorbidly impaired' pattern (n=14) was defined by below average estimated premorbid and current IQ and no evidence of decline greater than 10 points. The groups were compared on demographic,

Recent reports suggest that cognition is relatively preserved in some schizophrenia patients. However, little is known about the functional advantage these patients may demonstrate. The purpose of this study was to identify cognitively normal patients with a recently developed test battery and to determine the functional benefit of this normality relative to cognitively impaired patients. Average-range cognitive ability was defined by the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) composite score (T≥40) and applied to 100 patients with schizophrenia or schizoaffective disorder and to 81 non-psychiatric research participants. With group assignment adjusted for demographic variables, this procedure yielded 14 cognitively normal patients, 21 cognitively impaired patients, and 21 healthy adults with normal-range MCCB scores. Cognitively normal patients were indistinguishable from controls across all MCCB scales. Furthermore, their performance was superior to impaired patients on all scales except Social Cognition. Cognitively normal patients were also superior to impaired patients on a summary index of simulated life skills and functional competence. Nevertheless, both patient groups were equally disadvantaged relative to controls in independent community living. These findings suggest that normal-range cognition exists in schizophrenia, but fails to translate into enhanced community outcome.

This study assessed whether cortical thickness across the brain and regionally in terms of the default mode, salience, and central executive networks differentiates schizophrenia patients and healthy controls with normal range or below-normal range cognitive performance. Cognitive normality was defined using the MATRICS Consensus Cognitive Battery (MCCB) composite score (T = 50 ± 10) and structural magnetic resonance imaging was used to generate cortical thickness data. Whole brain analysis revealed that cognitively normal range controls (n = 39) had greater cortical thickness than both cognitively normal (n = 17) and below-normal range (n = 49) patients. Cognitively normal controls also demonstrated greater thickness than patients in regions associated with the default mode and salience, but not central executive networks. No differences on any thickness measure were found between cognitively normal range and below-normal range controls (n = 24) or between cognitively normal and below-normal range patients. In addition, structural covariance between network regions was high and similar across subgroups. Positive and negative symptom severity did not correlate with thickness values. Cortical thinning across the brain and regionally in relation to the default and salience networks may index shared aspects of the psychotic psychopathology that defines schizophrenia with no relation to cognitive impairment.

Prepulse inhibition (PPI) of startle occurs when intensity stimuli precede stronger startle-inducing stimuli by 10–1000 ms. PPI deficits are found in individuals with schizophrenia and other psychiatric disorders, and they correlate with other cognitive impairments. Animal research and clinical studies have demonstrated that both PPI and cognitive function can be enhanced by nicotine. PPI has been shown to be mediated, at least in part, by mesopontine cholinergic neurons that project to pontine startle neurons and activate muscarinic and potentially nicotine receptors (nAChRs). The subtypes and anatomical location of nAChRs involved in mediating and modulating PPI remain unresolved. We tested the hypothesis that nAChRs that are expressed by pontine startle neurons contribute to PPI. We also explored whether or not these pontine receptors are responsible for the nicotine enhancement of PPI. While systemic administration of nAChR antagonists had limited effects on PPI, PnC microinfusions of the non-α7nAChR preferring antagonist TMPH, but not of the α7nAChR antagonist MLA, into the PnC significantly reduced PPI. Electrophysiological recordings from startle-mediating PnC neurons confirmed that nicotine affects excitability of PnC neurons, which could be antagonized by TMPH, but not by MLA, indicating the expression of non-α7nAChR. In contrast, systemic nicotine enhancement of PPI was only reversed by systemic MLA and not by TMPH or local microinfusions of MLA into the PnC. In summary, our data indicate that non-α7nAChRs in the PnC contribute to PPI at stimulus intervals of 100 ms or less, whereas activation of α7nAChRs in other brain areas is responsible for the systemic nicotine enhancement of PPI. This is important knowledge for the correct interpretation of behavioral, preclinical, and clinical data as well as for developing drugs for the amelioration of PPI deficits and the enhancement of cognitive function.