Pasquereau, B. | Search bioRxiv

bioRxiv2026

CM/Pf contribution to mesocircuit dynamics underlying awareness in non-human primates

BackgroundIn acute disorders of consciousness following severe brain injury, the heterogeneity and multiplicity of brain lesions make it difficult to infer a direct causal link between lesion patterns and impaired consciousness. As a result, neuroimaging analyses performed in intensive care settings can inform theories of consciousness mainly through correlational, rather than causal, evidence. The mesocircuit hypothesis proposes that interactions between the thalamus, basal ganglia, and cortex support the neural mechanisms underlying awareness. Among its key components, the intralaminar thalamic nuclei are thought to play a central role, yet their respective contributions to mesocircuit dynamics remain poorly understood. MethodsIn two macaque monkeys, we combined causal perturbations of three thalamic nuclei (the centromedian-parafascicular complex (CM/Pf), central lateral nucleus (CL), and mediodorsal nucleus (MD)) with a cue-guided behavioural task requiring the processing of multisensory information. Electrical microstimulation was first used to compare the behavioural consequences of perturbing each target. Reversible pharmacological inactivation using muscimol was subsequently performed in the CM/Pf and CL. Finally, the large-scale metabolic effects of CM/Pf inactivation (muscimol) and disinhibition (bicuculline) were assessed using [18F]FDG PET imaging. ResultsPerturbation of the intralaminar nuclei disrupted behavioural performance, with the strongest and most reproducible effects observed following CM/Pf manipulation. CM/Pf inactivation reduced correct responses and increased omissions and wrong responses, particularly under conditions requiring greater behavioural engagement. Importantly, these deficits occurred without evidence of major wakefulness impairment, as animals remained responsive throughout testing and showed no substantial increase in eye-closure probability. In contrast, CL perturbation produced weaker behavioural effects, suggesting distinct functional contributions of the two intralaminar nuclei. [18F]FDG PET imaging revealed that CM/Pf disinhibition increased glucose metabolism across thalamic, striatal, pallidal, and frontal cortical territories, whereas CM/Pf inactivation induced a broadly reciprocal pattern of metabolic pattern. These findings identify the CM/Pf as a major modulator of both thalamo-striatal and thalamo-cortical components of the mesocircuit. ConclusionsOur results show that a unilateral intralaminar nucleus perturbation is not sufficient to affect wakefulness, suggesting that this function is mediated by a bilateral network at the thalamus level within the mesocircuit. The CM/Pf emerged as the intralaminar nucleus exerting the strongest influence on goal directed behaviours requiring the mesocircuit dynamics. Our findings also support the existence of partially distinct intralaminar pathways contributing differentially to global state regulation of awareness-related functions, and identify the CM/Pf as a key thalamo-striatal hub within the mesocircuit.

neuroscience↗

bioRxiv2022

Neural dynamics underlying self-control in the primate subthalamic nucleus

The subthalamic nucleus (STN) is hypothesized to play a central role in neural processes that regulate self-control. Still uncertain, however, is how that brain structure participates in the dynamically evolving representation of value that underlies the ability to delay gratification and wait patiently for a gain. To address that gap in knowledge, we studied the spiking activity of neurons in the STN of monkeys during a task in which animals were required to remain motionless for varying periods of time in order to obtain food reward. At the single-neuron and population levels, we found a cost-benefit integration between the desirability of the expected reward and the imposed delay to reward delivery, with STN signals that dynamically combined both attributes of the reward to form a single integrated estimate of value. This neural representation of subjective value evolved dynamically across the waiting period that intervened between instruction cue and reward delivery. Moreover, this representation was gradually distributed along the antero-posterior axis of the STN such that the most posterior-placed neurons represented the temporal discounting of value most strongly. These findings highlight the selective involvement of the posterior STN in a dynamic internal process that dynamically estimates the ongoing cost-benefit balance of the current context. Such a process is essential for self-control, promoting goal pursuit and the willingness to bear the costs of time delays.

neuroscience↗