BackgroundIt is still unclear which underlying mechanisms are involved in cognitive deficits of psychotic disorders. Pro-cognitive effects of muscarinic M1 receptor agonists suggest alterations in M1 receptor functioning may modulate these symptoms. Post mortem studies in patients with schizophrenia have shown significantly reduced M1 receptor expression rates in the dorsolateral prefrontal cortex (DLPFC) compared to controls. To date no in-vivo examinations of M1 receptor binding in relation to cognitive impairments have been done. As cognitive deficits have similar course and prognostic relevance across psychotic disorders, the current study assessed M1 receptor binding in the DLPFC and hippocampus in relation to cognitive functioning.MethodsMuscarinic M1 receptor binding potential (BPND) was measured using 123I-IDEX, single photon emission computed tomography (SPECT) in 30 medication-free subjects diagnosed with a psychotic disorder. A computerized neuropsychological test battery was used to assess cognition, and the positive and negative syndrome scale (PANSS) to assess severity of psychotic symptoms.ResultsAssessment of cognitive domains showed that lower M1 BPND in the DLPFC was related to overall lower performance in verbal learning and memory. In addition, lower M1 BPND in the DLPFC was related to greater negative symptom severity. Lastly, lower M1 BPND in the hippocampus was related to worse delayed recognition of verbal memory.ConclusionThis is the first study to show that variation in M1 receptors in the DLPFC is related to cognitive and negative symptom outcome in psychotic disorders. The M1 receptor may be an important biomarker in biological stratification of patients with psychotic disorders.

Faces are important visual objects for humans and other social animals. A complex network of specialized brain areas is involved in the recognition and interpretation of faces. This network needs to strike a balance between being sensitive enough to distinguish between different faces with similar features, and being tolerant of low-level visual changes so that a given face is stably perceived as a particular individual. Such stability may require feedback from higher brain regions down to the level where details are represented. Here, we describe a phenomenon in which interocular competition between face features is stabilized and eliminated when observers attend high-level face characteristics. Two different face images presented to the individual eyes do not cause the perceptual fluctuations that are typically observed in binocular rivalry. Instead, they merge into a stable percept of an intermediate face that combines features from both eyes’ images. The stability of the intermediate face percept depends on the observer attending holistic face properties such as identity or gender. It disappears when observers explicitly attend facial features, suggesting a crucial role of top-down stabilizing feedback from high-level areas that represent holistic faces back to lower processing levels where detailed face features compete for conscious representation.

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