Cortico-thalamocortical interactions for learning, memory and decision-making

Abstract

The thalamus and cortex are interconnected both functionally and anatomically and share a common developmental trajectory. Interactions between the mediodorsal thalamus (MD) and different parts of the prefrontal cortex are essential in cognitive processes, such as learning and adaptive decision-making. Cortico-thalamocortical interactions involving other dorsal thalamic nuclei, including the anterior thalamus and pulvinar, also influence these cognitive processes. Our work, and that of others, indicates a crucial influence of these interdependent cortico-thalamocortical neural networks that contributes actively to the processing of information within the cortex. Each of these thalamic nuclei also receives potent subcortical inputs that are likely to provide additional influences on their regulation of cortical activity. Here, we highlight our current neuroscientific research aimed at establishing when cortico-MD thalamocortical neural network communication is vital within the context of a rapid learning and memory discrimination task. We are collecting evidence of MD-prefrontal cortex neural network communication in awake, behaving male rhesus macaques. Given the prevailing evidence, further studies are needed to identify both broad and specific mechanisms that govern how the MD, anterior thalamus and pulvinar cortico-thalamocortical interactions support learning, memory and decision-making. Current evidence shows that the MD (and the anterior thalamus) are crucial for frontotemporal communication, and the pulvinar is crucial for frontoparietal communication. Such work is crucial to advance our understanding of the neuroanatomical and physiological bases of these brain functions in humans. In turn, this might offer avenues to develop effective treatment strategies to improve the cognitive deficits often observed in many debilitating neurological disorders and diseases and in neurodegeneration.

Keywords: anterior thalamus; behaviour; decision making; mediodorsal thalamus; neuroimaging; neurophysiology; prefrontal cortex; pulvinar.

Figure 1. Cortico‐thalamocortical connections

Schematic representations of the main cortical and subcortical connections of the three mediodorsal thalamus (MD) subdivisions [magnocellular MD (MDmc), parvocellular MD (MDpc) and lateral MD (MDl)] in macaque coronal plates. Overlapping frontal and temporal cortex connections to and from the pulvinar are highlighted, but not all neuroanatomical connectivity of the pulvinar is shown. Overlapping frontal cortex connections of the anterior thalamus (ATN) are shown (for complete details, please refer to Perry et al., 2021). The anterior–posterior position of each coronal section is given relative to the anterior commissure (ac) based on Paxinos, Huang and Toga (2000). The relative position of these coronal plates in the macaque brain is indicated on the sagittal plane in the top right illustration (A–E). The anatomical connectivity of the MD is based on the work of several laboratories (e.g. Aggleton & Mishkin, ; Russchen et al., ; Saunders et al., ; Schwartz et al., ; Timbie et al., 2020). It is apparent across species, but especially in the macaque, that the MDmc forms part of a distinct frontotemporal circuit receiving inputs from the perirhinal (PRh) and entorhinal (ERh) cortex and the amygdala (basomedial [BL], basomedial [BM], corticomedial [Co], medial [Me] and centromedial [Ce]), in addition to more ventral and ventromedial regions of prefrontal (areas 25, 32 and orbital periallocortex [OPAL]) and orbitofrontal cortex [areas 11, 13, 14 and 47(12)]. In contrast, the MDpc and MDl subdivisions tend to interact with more dorsolateral frontal regions (areas 9, 45 and 46). Interestingly, in the macaque, the anterior cingulate cortex (areas 24A, B and C) and the frontal pole (areas 10D and 10M) appear to be convergence points for connections with all three MD subdivisions, perhaps indicating a special role for these regions in integrating thalamocortical and corticocortical information. NB The pulvinar sends inputs to the amygdala and temporal cortex structures and has reciprocal connectivity with layer VI of the frontal cortex (e.g. Elorette et al., ; Jones & Burton, ; Rafal et al., ; Shipp, 2003). ^**The ATN does not connect directly to the amygdala or the perirhinal cortex. However, it is interconnected to the entorhinal cortex (refer to Perry et al., 2021).

Figure 2. Visuospatial discrimination task

For each neurophysiological recording session, the monkeys have to learn, for each trial, which one of two small coloured typographical characters embedded in a unique complex colourful background that includes one large typographical character presented on a touchscreen computer leads to receiving a small amount of fruit smoothie (correct; reward) and which one does not (incorrect; no reward). For a correct choice, the reward is delivered 1.8 s after a screen touch, whereas for an incorrect choice nothing happens for 1.8 s. Up to 30 new, unique visuospatial discriminations are generated for each recording session (depending on the ability of the monkey), and the monkey has to touch the correct typographical character, which they learned by trial and error (i.e. for the first exposure of each discrimination, the monkey has a 50/50 chance of making a correct choice). Each discrimination is presented consecutively and is repeated 16 times within the recording session. Subsequent exposures to each discrimination should result in rapid acquisition of the correct typographical character and a drastic reduction in errors. After the completion of a trial, the screen goes blank, and the monkey receives a 5 s intertrial interval (ITI) for a correct choice or 10 s for an incorrect choice. The black square at the top right‐hand corner of each discrimination indicated to a photocell monitoring light intensity that the trial had started and ended.