PROJECT SUMMARY
Cognitive control is an umbrella term that describes processes that regulate cognitive, perceptual, and
motor functions needed to perform adaptive, goal-directed behaviors. Patients with neurological and psychiatric
disorders, for example schizophrenia, attention-deficit hyperactivity disorder (ADHD), traumatic brain injury and
stroke, suffer from impairments in cognitive control. Although the function of frontoparietal and striatal circuits in
cognitive control have been extensively studied, increasing evidence suggests a role for the thalamus. Thalamic
nuclei have reciprocal and non-reciprocal connections with multiple cortical regions, integrate modulatory inputs
from other subcortical structures, and innervate both excitatory and inhibitory cortical neurons. Despite this
prominent connectivity profile, the role of the human thalamus in cognitive control and effects of its dysfunction
are not well understood. The objective of the proposed research is to determine the cognitive control functions
of the human thalamus. Our central hypothesis, based on our extensive preliminary data and anatomical
properties of thalamocortical circuits in animal models, is that thalamic nuclei support cognitive control by
modulating cortical activities that include evoked responses, cortical network interactions, and neural oscillations.
These cortical activities instantiate neurocognitive processes that select or maintain task-relevant information,
and they can be selectively amplified through targeted increases in thalamocortical interactions. Consequently,
thalamocortical dysfunction can lead to cognitive rigidity, increased distraction, and poor planning. To test our
hypothesis, we propose a novel approach that integrates cognitive behavioral tasks that specifically manipulate
processes that select and maintain task-relevant information (for example, working memory and set switching),
multimodal neuroimaging (fMRI and EEG), and human thalamic lesions studies. We will first determine the
functional organization (topography) of thalamocortical functional connectivity for cognitive control (Aim 1), which
has not yet been systematically mapped in humans. We will then determine how thalamocortical interactions
select and maintain task-relevant information by examining its relationship with, and modulatory effects on, task-
related cortical activities (Aims 2 and 3). For all studies, we will recruit healthy individuals, patients with focal
thalamic lesions, and control patients from a lesion comparison group. By collecting multimodal neuroimaging
data from patients with focal thalamic lesions, we will determine how the disruption of thalamocortical interactions
affects task-related cortical neural activities and behavior. Results from our proposed research will establish how
the distribution of thalamocortical connectivity enables thalamic nuclei to participate in multiple cognitive control
functions, and specify the cognitive and neural repercussions of thalamocortical dysfunction observed in patients
with thalamic stroke, as well as other disorders such as ADHD and schizophrenia.