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How the human brain generates conscious phenomenal experience is a fundamental problem. In particular, it is unknown how variable and dynamic changes in subjective affect are driven by interactions with objective phenomena. We hypothesize a neurocomputational mechanism that generates valence-specific learning signals associated with 'what it is like' to be rewarded or punished. Our hypothesized model maintains a partition between appetitive and aversive information while generating independent and parallel reward and punishment learning signals. This valence-partitioned reinforcement learning (VPRL) model and its associated learning signals are shown to predict dynamic changes in 1) human choice behavior, 2) phenomenal subjective experience, and 3) BOLD-imaging responses that implicate a network of regions that process appetitive and aversive information that converge on the ventral striatum and ventromedial prefrontal cortex during moments of introspection. Our results demonstrate the utility of valence-partitioned reinforcement learning as a neurocomputational basis for investigating mechanisms that may drive conscious experience.
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http://dx.doi.org/10.1101/2023.03.17.533213 | DOI Listing |
Nature
September 2025
Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, MA, USA.
Loss-of-function variants in the lipid transporter ABCA7 substantially increase the risk of Alzheimer's disease, yet how they impact cellular states to drive disease remains unclear. Here, using single-nucleus RNA-sequencing analysis of human brain samples, we identified widespread gene expression changes across multiple neural cell types associated with rare ABCA7 loss-of-function variants. Excitatory neurons, which expressed the highest levels of ABCA7, showed disrupted lipid metabolism, mitochondrial function, DNA repair and synaptic signalling pathways.
View Article and Find Full Text PDFJ Immunother Cancer
September 2025
Pharmaceutical Sciences, Washington State University, Spokane, Washington, USA
Prostate cancer (PC) is notoriously known for exhibiting an immunologically cold phenotype in the tumor immune microenvironment (TIME), leading to the need for interventions to enhance immunotherapy efficacy. Recent findings by Zhao in the identified stromal monoamine oxidase A (MAOA), a key enzyme that degrades monoamine neurotransmitters and plays a role in the neuroendocrine system, as a critical regulator of the immune response to PC. Altering MAOA levels in myofibroblastic cancer-associated fibroblasts, either genetically or pharmacologically, can reprogram PC's TIME to modulate CD8 T cell-mediated cytotoxicity through the WNT5A-Ca²-NFATC1 signaling axis, highlighting the stromal influences on CD8 T cell cytotoxic activity within the TIME.
View Article and Find Full Text PDFJ Safety Res
September 2025
Department of Civil, Construction and Environmental Engineering, The University of Alabama, Tuscaloosa, AL 35487, United States; Alabama Transportation Institute, The University of Alabama, Tuscaloosa, AL 35487, United States; Transportation Policy Research Center, The University of Alabama, Tuscalo
Introduction: Police officers are integral to enforcing traffic laws and providing assistance to motorists. While performing their duties on the road or roadside, they encounter significant hazards, many of which arise from the negligent or inappropriate behaviors of drivers. Despite the prevalence of these risks, there is a paucity of research specifically examining the outcomes of traffic crashes involving police officers or police vehicles, particularly in relation to the injury severity sustained by police officers in such incidents.
View Article and Find Full Text PDFJ Genet Genomics
September 2025
State Key Laboratory of Tropical Crop Breeding, Shenzhen Branch, Guangdong Laboratory of Lingnan Modern Agriculture, Key Laboratory of Synthetic Biology, Ministry of Agriculture and Rural Affairs, Agricultural Genomics Institute at Shenzhen, Chinese Academy of Agricultural Sciences, Shenzhen, Guangd
The genetic basis of early-stage salt tolerance in alfalfa (Medicago sativa L.), a key factor limiting its productivity, remains poorly understand. To dissect this complex trait, we integrate genome-wide association study (GWAS) and transcriptomics (RNA-seq) from 176 accessions within a machine learning based genomic prediction framework.
View Article and Find Full Text PDFJ Neurosci Methods
September 2025
Department of Computer Science and Engineering, IIT (ISM) Dhanbad, Dhanbad, 826004, Jharkhand, India. Electronic address:
Background: Interpretation of motor imagery (MI) in brain-computer interface (BCI) applications is largely driven by the use of electroencephalography (EEG) signals. However, precise classification in stroke patients remains challenging due to variability, non-stationarity, and abnormal EEG patterns.
New Methods: To address these challenges, an integrated architecture is proposed, combining multi-domain feature extraction with evolutionary optimization for enhanced EEG-based MI classification.