Macaque parvocellular mediodorsal thalamus: dissociable contributions to learning and adaptive decision‐making

Abstract

Distributed brain networks govern adaptive decision-making, new learning and rapid updating of information. However, the functional contribution of the rhesus macaque monkey parvocellular nucleus of the mediodorsal thalamus (MDpc) in these key higher cognitive processes remains unknown. This study investigated the impact of MDpc damage in cognition. Preoperatively, animals were trained on an object-in-place scene discrimination task that assesses rapid learning of novel information within each session. Bilateral neurotoxic (NMDA and ibotenic acid) MDpc lesions did not impair new learning unless the monkey had also sustained damage to the magnocellular division of the MD (MDmc). Contralateral unilateral MDpc and MDmc damage also impaired new learning, while selective unilateral MDmc damage produced new learning deficits that eventually resolved with repeated testing. In contrast, during food reward (satiety) devaluation, monkeys with either bilateral MDpc damage or combined MDpc and MDmc damage showed attenuated food reward preferences compared to unoperated control monkeys; the selective unilateral MDmc damage left performance intact. Our preliminary results demonstrate selective dissociable roles for the two adjacent nuclei of the primate MD, namely, MDpc, as part of a frontal cortical network, and the MDmc, as part of a frontal-temporal cortical network, in learning, memory and the cognitive control of behavioural choices after changes in reward value. Moreover, the functional cognitive deficits produced after differing MD damage show that the different subdivisions of the MD thalamus support distributed neural networks to rapidly and fluidly incorporate task-relevant information, in order to optimise the animals' ability to receive rewards.

Mediodorsal thalamus is critical for updating during extra-dimensional shifts but not reversals in the attentional set-shifting task

“…Both the SD and ED subtasks present online task changes that require rapidly altering response strategies. Therefore, impaired SD and ED performance would be consistent with the selective deficits in learning observed in other MD lesion rats (Hunt and Aggleton, 1998;Mitchell and Dalrymple-Alford, 2005), or in primates with damage to the magnocellular mediodorsal thalamic nucleus (MDmc: Browning et al, 2015;Chakraborty et al, 2016;Chakraborty et al, 2019;Mitchell, 2015;Mitchell et al, 2007a). We also predicted our MD lesion rats may show deficits during reversal subtasks given the reciprocal direct connectivity with the OFC (Groenwegen, 1988;Krettek and Price, 1977;Ray and Price, 1992).…”

“…Yet, it is becoming increasingly clear that the cortex does not function in isolation, but rather, relies heavily on subcortical and peripheral inputs supplied by the thalamus (Sherman and Guillery, 2002;Guillery and Sherman, 2011;Halassa and Kastner, 2017). Clearly, the mediodorsal thalamus (MD) has a critical role in functions of frontal cortex during higher order cognitive processes across mammalian species (Alcaraz et al, 2018;Browning et al, 2015;Chakraborty et al, 2016Chakraborty et al, , 2019DeNicola et al, 2020;Ferguson and Gao, 2018;Miller et al, 2017;Mitchell et al, 2007a;Mitchell et al, 2007b;Pergola et al, 2018;Parnaudeau et al, 2013;Schmitt et al, 2017). Monkeys with MD lesions were found to have deficits when required to rapidly update 'on-the-fly' task-relevant information during complex visuospatial associative tasks (Browning et al, 2015;Chakraborty et al, 2016;Mitchell et al, 2007a) but not during recognition of the visuospatial associations (Mitchell and Gaffan, 2008).…”

The Regulatory Role of the Human Mediodorsal Thalamus

“…Thus, varying temporal parameters, and/or switching demands or manipulating cognitive load will, in our view, provide insights into the influence of the MD on PFC functioning. Lastly, adapting animal tasks shown to identify PFC functioning after selective MD lesions 10 , 124 will be insightful. Importantly, we argue that the field will benefit most from hypothesis-driven tasks accompanied by accurate neuroimaging of the consequences of thalamic changes.…”

Confidence in Decision-Making during Probabilistic Tactile Learning Related to Distinct Thalamo–Prefrontal Pathways

“…Recently, evidence has emerged assigning the thalamus a central role in cognitive processes underpinning, for instance, learning (Mitchell 2015;Yamanaka et al 2018), memory (Van Groen et al 2002), attention (De Bourbon-Teles et al 2014Wright et al 2015), and decision-making (Mitchell 2015;Chakraborty et al 2019). The right thalamic cluster, involved in encoding the strength of individual prior belief through connections with vmPFC for an unchanged decision strategy, overlapped with the lateral and inferior pulvinar, whereas the left thalamic region, involved in updating the decision strategy through connections to the OFC, was located in the MD and nuclei within the anterior complex (Behrens et al 2003).…”