In the predictive coding framework, mismatch negativity (MMN) is regarded a correlate of the prediction error that occurs when top-down predictions conflict with bottom-up sensory inputs. Expression-related MMN is a relatively novel construct thought to reflect a prediction error specific to emotional processing, which, however, has not yet been tested directly. Our paradigm includes both neutral and emotional deviants, thereby allowing for investigating whether expression-related MMN is emotion-specific or unspecifically arises from violations of a given sequence. Twenty healthy participants completed a visual sequence oddball task where they were presented with (1) sequence deviants, (2) emotional sequence deviants, and (3) emotional deviants. Mismatch components were assessed at ventral occipitotemporal scalp sites and analyzed regarding their amplitudes, spatiotemporal profiles, and neuronal sources. Expression-related MMN could be clearly separated from its neutral counterpart in all investigated aspects. Specifically, expression-related MMN showed enhanced amplitude, shorter latency, and different neuronal sources. Our results, therefore, provide converging evidence for a quantitative specificity of expression-related MMN and seems to provide an opportunity to study prediction error during preattentive emotional processing. Our neurophysiological evidence ultimately suggests that a basic cognitive operator, the prediction error, is enhanced at the cortical level by processing of emotionally salient stimuli.

Recent large-scale, genome-wide association studies (GWAS) have identified hundreds of genetic loci associated with general intelligence. The cumulative influence of these loci on brain structure is unknown. We examined if cortical morphology mediates the relationship between GWAS-derived polygenic scores for intelligence (PSi) and g-factor. Using the effect sizes from one of the largest GWAS meta-analysis on general intelligence to date, PSi were calculated among 10 P value thresholds. PSi were assessed for the association with g-factor performance, cortical thickness (CT), and surface area (SA) in two large imaging-genetics samples (IMAGEN N = 1651; IntegraMooDS N = 742). PSi explained up to 5.1% of the variance of g-factor in IMAGEN (F1,1640 = 12.2–94.3; P < 0.005), and up to 3.0% in IntegraMooDS (F1,725 = 10.0–21.0; P < 0.005). The association between polygenic scores and g-factor was partially mediated by SA and CT in prefrontal, anterior cingulate, insula, and medial temporal cortices in both samples (PFWER-corrected < 0.005). The variance explained by mediation was up to 0.75% in IMAGEN and 0.77% in IntegraMooDS. Our results provide evidence that cumulative genetic load influences g-factor via cortical structure. The consistency of our results across samples suggests that cortex morphology could be a novel potential biomarker for neurocognitive dysfunction that is among the most intractable psychiatric symptoms.

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Even today, patients with schizophrenia often have an unfavorable outcome. Negative symptoms and cognitive deficits are common features in many patients and prevent recovery. In recent years, aerobic endurance training has emerged as a therapeutic approach with positive effects on several domains of patients’ health. However, appropriately sized, multicenter randomized controlled trials that would allow better generalization of results are lacking. The exercise study presented here is a multicenter, rater-blind, two-armed, parallel-group randomized clinical trial in patients with clinically stable schizophrenia being conducted at five German tertiary hospitals. The intervention group performs aerobic endurance training on bicycle ergometers three times per week for 40–50 min/session (depending on the intervention week) for a total of 26 weeks, and the control group performs balance and tone training for the same amount of time. Participants are subsequently followed up for 26 weeks. The primary endpoint is all-cause discontinuation; secondary endpoints include psychopathology, cognition, daily functioning, cardiovascular risk factors, and explorative biological measures regarding the underlying mechanisms of exercise. A total of 180 patients will be randomized. With currently 162 randomized participants, our study is the largest trial to date to investigate endurance training in patients with schizophrenia. We hypothesize that aerobic endurance training has beneficial effects on patients’ mental and physical health, leading to lower treatment discontinuation rates and improving disease outcomes. The study results will provide a basis for recommending exercise interventions as an add-on therapy in patients with schizophrenia.The study is registered in the International Clinical Trials Database (ClinicalTrials.gov identifier [NCT number]: NCT03466112) and in the German Clinical Trials Register (DRKS-ID: DRKS00009804).