Mediodorsal thalamus regulates task uncertainty to enable cognitive flexibility

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 18, 2025

The mediodorsal (MD) thalamus is a critical partner for the prefrontal cortex (PFC) in cognitive control. Accumulating evidence has shown that MD regulates task uncertainty decision making and enhance flexibility. However, computational mechanism of this process remains unclear. Here we trained biologically-constrained models to delineate mechanistic role context-dependent making. We show addition feedforward structure recurrent PFC increases robustness low cueing signal-to-noise ratio, enhances working memory, enables rapid context switching. Incorporating genetically identified thalamocortical connectivity interneuron cell types into model replicates key neurophysiological findings task-performing animals. Our reveals mechanisms geometric interpretations regulating cue switching enable makes experimentally testable predictions linking deficits with disrupted connectivity, excitation-inhibition imbalance dysfunctional inhibitory types. by which activity flexibility not fully understood. authors build incorporating Together experimental testing, circuit

Language: Английский

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Thalamocortical contributions to cognitive task activity

eLife, Journal Year: 2022, Volume and Issue: 11

Published: Dec. 20, 2022

Thalamocortical interaction is a ubiquitous functional motif in the mammalian brain. Previously (Hwang et al., 2021), we reported that lesions to network hubs human thalamus are associated with multi-domain behavioral impairments language, memory, and executive functions. Here, show how task-evoked thalamic activity organized support these broad cognitive abilities. We analyzed magnetic resonance imaging (MRI) data from subjects performed 127 tasks encompassing range of representations. first investigated spatial organization found basis set patterns evoked processing needs each task. Specifically, anterior, medial, posterior-medial exhibit hub-like profiles suggestive participation. These task overlapped interlinking cortical systems. To further determine relevance thalamocortical connectivity, built data-driven model test whether can be used predict activity. The predicted task-specific patterns, outperformed comparison models on cortical, hippocampal, striatal regions. Simulated low-dimensional, multi-task hub regions impaired prediction. This simulation result was supported by neuropsychological patients focal lesions. In summary, our results suggest general organizational principle system supports

Language: Английский

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The thalamus in psychosis spectrum disorder

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: April 13, 2023

Psychosis spectrum disorder (PSD) affects 1% of the world population and results in a lifetime chronic disability, causing devastating personal economic consequences. Developing new treatments for PSD remains challenge, particularly those that target its core cognitive deficits. A key barrier to progress is tenuous link between basic neurobiological understanding clinical phenomenology. In this perspective, we focus on opportunity combines innovations non-invasive human neuroimaging with insights into thalamic regulation functional cortical connectivity. The thalamus an evolutionary conserved region forms forebrain-wide loops critical transmission external inputs as well construction update internal models. We discuss our perspective across four lines evidence: First, articulate how symptomatology may arise from faulty network organization at macroscopic circuit level playing central coordinating role. Second, recent animal work has mechanistically clarified properties circuits relevant regulating dynamics function more generally. Third, present evidence support alterations PSD, propose similar "thalamocortical dysconnectivity" seen pharmacological imaging (under ketamine, LSD THC) healthy individuals phenotype common set symptoms idiopathic drug-induced psychosis. Lastly, synthesize work, lay out translational path biomarker therapeutic development.

Language: Английский

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Thalamocortical architectures for flexible cognition and efficient learning

Trends in Cognitive Sciences, Journal Year: 2024, Volume and Issue: 28(8), P. 739 - 756

Published: June 17, 2024

The brain exhibits a remarkable ability to learn and execute context-appropriate behaviors. How it achieves such flexibility, without sacrificing learning efficiency, is an important open question. Neuroscience, psychology, engineering suggest that reusing repurposing computations are part of the answer. Here, we review evidence thalamocortical architectures may have evolved facilitate these objectives flexibility efficiency by coordinating distributed computations. Recent work suggests prefrontal cortical networks compute with flexible codes, mediodorsal thalamus provides regularization promote efficient reuse. Thalamocortical interactions resemble hierarchical Bayesian computations, their network implementation can be related existing gating, synchronization, hub theories thalamic function. By reviewing recent findings providing novel synthesis, highlight key research horizons integrating computation, cognition, systems neuroscience.

Language: Английский

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Thalamic regulation of frontal interactions in human cognitive flexibility

PLoS Computational Biology, Journal Year: 2022, Volume and Issue: 18(9), P. e1010500 - e1010500

Published: Sept. 12, 2022

Interactions across frontal cortex are critical for cognition. Animal studies suggest a role mediodorsal thalamus (MD) in these interactions, but the computations performed and direct relevance to human decision making unclear. Here, inspired by animal work, we extended neural model of an executive frontal-MD network trained it on decision-making task which neuroimaging data were collected. Using biologically-plausible learning rule, found that MD compressed its cortical inputs (dorsolateral prefrontal cortex, dlPFC) underlying stimulus-response representations. Through feedback dlPFC, this thalamic operation efficiently partitioned activity patterns enhanced switching different contingencies. To account interactions with other regions, expanded compute higher-order strategy signals outside offered more efficient route such switch dlPFC patterns. Human fMRI provided evidence engaged had routing orbitofrontal when subjects switched behavioral strategy. Collectively, our findings contribute emerging regulation brain.

Language: Английский

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Changes in both top-down and bottom-up effective connectivity drive visual hallucinations in Parkinson’s disease

Brain Communications, Journal Year: 2022, Volume and Issue: 5(1)

Published: Dec. 12, 2022

Abstract Visual hallucinations are common in Parkinson’s disease and associated with a poorer quality of life higher risk dementia. An important influential model that is widely accepted as an explanation for the mechanism visual other Lewy body diseases these arise due to aberrant hierarchical processing, impaired bottom-up integration sensory information overweighting top-down perceptual priors within system. This hypothesis has been driven by behavioural data supported indirectly observations derived from regional activation correlational measures using neuroimaging. However, until now, there was no evidence neuroimaging differences causal influences between brain regions measured patients hallucinations. part because previous resting-state studies focused on functional connectivity, which inherently undirected nature cannot test hypotheses about directionality connectivity. Spectral dynamic modelling Bayesian framework allows inference effective connectivity—defined directed (causal) influence one region exerts another region—from MRI data. In current study, we utilize spectral estimate connectivity network our cohort 15 hallucinators 75 non-visual hallucinators. We find display decreased lateral geniculate nucleus primary cortex increased left prefrontal medial thalamus, compared Importantly, pattern predictive presence their severity hallucinating group. first study provide evidence, support processing disease.

Language: Английский

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Distinct roles of monkey OFC-subcortical pathways in adaptive behavior

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Aug. 28, 2024

Primates must adapt to changing environments by optimizing their behavior make beneficial choices. At the core of adaptive is orbitofrontal cortex (OFC) brain, which updates choice value through direct experience or knowledge-based inference. Here, we identify distinct neural circuitry underlying these two separate abilities. We designed behavioral tasks in male macaque monkeys updated values certain items, either directly experiencing changes stimulus-reward associations, inferring unexperienced items based on task's rules. Chemogenetic silencing bilateral OFC combined with mathematical model-fitting analysis revealed that monkey involved updating item both and In vivo imaging chemogenetic receptors positron emission tomography allowed us map projections from rostromedial caudate nucleus (rmCD) medial part mediodorsal thalamus (MDm). OFC-rmCD pathway impaired experience-based updating, while OFC-MDm inference-based updating. Our results thus demonstrate dissociable contributions different strategies, provide new insights into basis value-based decision-making primates.

Language: Английский

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Rapid context inference in a thalamocortical model using recurrent neural networks

Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)

Published: Sept. 27, 2024

Language: Английский

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Chronic restraint stress induces depression-like behaviors and alterations in the afferent projections of medial prefrontal cortex from multiple brain regions in mice

Brain Research Bulletin, Journal Year: 2024, Volume and Issue: 213, P. 110981 - 110981

Published: May 21, 2024

The medial prefrontal cortex (mPFC) forms output pathways through projection neurons, inversely receiving adjacent and long-range inputs from other brain regions. However, how afferent neurons of mPFC are affected by chronic stress needs to be clarified. In this study, the effects restraint (CRS) on distribution density dendrites/dendritic spines projections subcortical regions were investigated.

Language: Английский

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CCK+ interneurons contribute to thalamus-evoked feed-forward inhibition in prelimbic prefrontal cortex

Journal of Neuroscience, Journal Year: 2024, Volume and Issue: 44(23), P. e0957232024 - e0957232024

Published: May 2, 2024

Interneurons in the medial prefrontal cortex (PFC) regulate local neural activity to influence cognitive, motivated, and emotional behaviors. Parvalbumin-expressing (PV+) interneurons are primary mediators of thalamus-evoked feed-forward inhibition across mouse cortex, including anterior cingulate where they engaged by inputs from mediodorsal (MD) thalamus. In contrast, adjacent prelimbic (PL) we find that PV+ scarce principal thalamorecipient layer 3 (L3), suggesting distinct mechanisms inhibition. To identify mediate MD-evoked PL, combine slice physiology, optogenetics, intersectional genetic tools mice both sexes. We expressing cholecystokinin (CCK+) abundant L3 with cells exhibiting fast-spiking (fs) or nonfast-spiking (nfs) properties. MD make stronger connections onto fs-CCK+ interneurons, driving them fire more readily than nearby pyramidal other interneurons. CCK+ turn inhibitory, perisomatic cells, exhibit cannabinoid 1 receptor (CB1R) mediated modulation. Moreover, inhibition, but not direct excitation, is also sensitive CB1R Our findings indicate contribute revealing a mechanism which cannabinoids can modulate MD-PFC communication.

Language: Английский

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