Search bioRxiv⌕ Search

bioRxiv · 10.1101/2020.10.06.327775

Impulsivity as Bayesian inference under dopaminergic control

Abstract

Bayesian models successfully account for several of dopamine (DA)s effects on contextual calibration in interval timing and reward estimation. In these models, tonic levels of DA control the precision of stimulus encoding, which is weighed against contextual information when making decisions. When DA levels are high, the animal relies more heavily on the (highly precise) stimulus encoding, whereas when DA levels are low, the context affects decisions more strongly. Here, we extend this idea to intertemporal choice and probability discounting tasks. In intertemporal choice tasks, agents must choose between a small reward delivered soon and a large reward delivered later, whereas in probability discounting tasks, agents must choose between a small reward that is always delivered and a large reward that may be omitted with some probability. Beginning with the principle that animals will seek to maximize their reward rates, we show that the Bayesian model predicts a number of curious empirical findings in both tasks. First, the model predicts that higher DA levels should normally promote selection of the larger/later option, which is often taken to imply that DA decreases impulsivity, and promote selection of the large/risky option, often taken to imply that DA increases risk-seeking. However, if the temporal precision is sufficiently decreased, higher DA levels should have the opposite effect--promoting selection of the smaller/sooner option (higher impulsivity) and the small/safe option (lower risk-seeking). Second, high enough levels of DA can result in preference reversals. Third, selectively decreasing the temporal precision, without manipulating DA, should promote selection of the larger/later and large/risky options. Fourth, when a different post-reward delay is associated with each option, animals will not learn the option-delay contingencies, but this learning can be salvaged when the post-reward delays are made more salient. Finally, the Bayesian model predicts correlations among behavioral phenotypes: Animals that are better timers will also appear less impulsive.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mikhael, J. G., Gershman, S. J.. 2020-10-07. Impulsivity as Bayesian inference under dopaminergic control. https://doi.org/10.1101/2020.10.06.327775

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗