Thalamocortical contributions to working memory processes during the n-back task.

Working memory allows individuals to temporally maintain and manipulate information that is no longer accessible from the sensorium. Whereas prior studies have detailed frontoparietal contributions to working memory processes, less emphasis has been placed on subcortical regions, in particular the human thalamus. The thalamus has a complex anatomy that consists of several distinct nuclei, many of which have dense anatomical connectivity with frontoparietal regions, and thus might play an important yet underspecified role for working memory. The goal of our study is to characterize the detailed functional neuroanatomy of the human thalamus and thalamocortical interactions during the n-back task. To that end, we analyzed an n-back fMRI dataset consisting of 395 subjects from the Human Connectome Project (HCP). We found that thalamic nuclei in the anterior, medial, ventral lateral, and posterior medial thalamus showed stronger evoked responses in response to higher working memory load. Activity in most thalamic nuclei were only modulated by working memory load, but not by categorical membership of the memorized stimuli, suggesting that thalamic function supports domain-general processing for working memory. To determine whether thalamocortical interactions contribute to cortical activity for working memory, we employed an activity flow mapping analysis to test whether thalamocortical interactions can predict cortical task activity patterns. In support, this data-driven thalamocortical interaction model explained a significant amount of variance in the observed cortical activity patterns modulated by working memory load. Our results suggest that the anterior, medial, and posterior medial thalamus, and their associated thalamocortical interactions, contribute to the modulations of distributed cortical activity during working memory.

Thalamocortical contributions to cognitive task activity.

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