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Psychosis spectrum illnesses are characterized by impaired goal-directed behavior and significant neurophysiological heterogeneity. To investigate the neurocomputational underpinnings of this heterogeneity, 75 participants with Early Psychosis (EP) and 68 controls completed a dynamic decision-making task. Consistent with prior studies, EP exhibited more choice switching, not explained by reward learning deficits, but instead by increased transition to exploration from exploitation. Bayesian modeling implicated elevated uncertainty intolerance and decision noise as independent contributors to suboptimal transition dynamics across individuals, which identified three computational subtypes with unique cognitive and symptom profiles. Replicating prior studies, a high decision-noise subtype emerged showing learning deficits and worse negative symptoms; our analyses further uncovered a normative subtype with worse mood symptoms and a novel uncertainty-intolerance subtype with higher hospitalization rates. These specific microcognitive disruptions underlying the distinct neurocomputational subtypes are individually measurable and may have the potential for targeted interventions.
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http://dx.doi.org/10.1101/2025.04.29.25326698 | DOI Listing |
EMBO J
September 2025
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan.
During a critical period of postnatal brain development, neural circuits undergo significant refinement coincident with widespread alternative splicing of hundreds of genes, which undergo altered splice site selection for the generation of isoforms essential for synaptic plasticity. Here, we reveal that neuronal activity-dependent phosphorylation of paxillin at its serine 119 (p-paxillin) acts as a molecular switch in the nucleus for the control of alternative splicing during this period. We show that following NMDA receptor activation, nuclear p-paxillin is recruited to nuclear speckles, where it interacts with splicing factors, such as U2AFs.
View Article and Find Full Text PDFExp Neurobiol
August 2025
Department of Biological Sciences, Konkuk University, Seoul 05029, Korea.
This study investigated the learning strategy preferences of 11-month-old APP/PS1 double transgenic (Tg) mice, a well-established murine model of Alzheimer's disease (AD). APP/PS1 Tg and non-Tg control mice were serially trained in visual and hidden platform tasks in the Morris water maze. APP/PS1 Tg mice performed poorly in visual platform training compared with non-Tg mice but performed as well as non-Tg mice in hidden platform training.
View Article and Find Full Text PDFMed Eng Phys
October 2025
University of Missouri, Department of Physical Therapy, Columbia, MO, USA. Electronic address:
Measurable neuromotor control deficits during functional task performance could provide objective criteria to aid in concussion diagnosis. However, many tools which measure these constructs are unidimensional and not clinically feasible. The purpose of this study was to assess the classification accuracy of a machine learning model using features measured by a clinically feasible movement-based assessment system (Mizzou Point-of-care Assessment System (MPASS) between athletes with and without concussion.
View Article and Find Full Text PDFJ Affect Disord
September 2025
Peking University Sixth Hospital, Peking University Institute of Mental Health, NHC Key Laboratory of Mental Health (Peking University), National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, China. Electronic address:
Background: This study aimed to examine associations between age of onset and domain-specific cognitive deficits in major depressive disorder (MDD).
Methods: We assessed 582 MDD patients (389 first-episode [FED], 193 recurrent [RMD]) and 280 healthy controls (HCs) using five cognitive domains from the MATRICS Consensus Cognitive Battery. Of these patients, 289 were reassessed after 8 weeks of antidepressant treatment.
Neurol Res
September 2025
Electrophysiology Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Objectives: This study aimed to investigate the effects of repeated exposure to sevoflurane as an anesthetic agent during various developmental stages, namely neonatal, preadolescent, and adult, on behavioral, synaptic, and neuronal plasticity in male and female Wistar rats.
Methods: Rats were exposed to sevoflurane during three developmental stages: neonatal (PN7), pre-adolescence (PN28), and adulthood (PN90). Behavioral performance was evaluated with the Morris Water Maze.