Skip to content

Fast fMRI Detects Specific Cascade of Thalamic Activity at Transitions in Behavioral Arousal State

Key findings

  • In this study, fast functional MRI at ultra-high field was used to investigate the thalamocortical dynamics underlying behavioral arousal state transitions—specifically, the moment of awakening
  • In subjects spontaneously transitioning between sleep and wakefulness, behavioral arousal was preceded by a sequence of activity across thalamic nuclei and the cingulate cortex, followed by widespread deactivation throughout the thalamus and cortex
  • A consistent temporal pattern emerged across individual thalamic nuclei at the moment of state transitions, and this thalamic activity was linked to the subsequent maintenance of behavioral arousal
  • Fast, ultra-high field functional MRI shows broad potential to determine the function of subcortical structures

Arousal from sleep is accompanied by striking behavioral changes that reflect a fundamental shift in neural dynamics throughout thalamocortical networks. The many diverse nuclei of the thalamus have unique structural and functional properties, but their activity isn't well understood because conventional imaging can't capture their fast dynamics.

Using high temporal resolution (fast) functional MRI at ultra-high field (7T), Laura Lewis, PhD, an affiliated faculty member at the Martinos Center for Biomedical Imaging at Massachusetts General Hospital, first author Beverly Setzer, a PhD student, and colleagues have mapped a precise sequence of neural activity that unfolds as the brain switches between behavioral arousal states. They describe the cascade of events in Nature Communications.


To track behavioral arousal state without a stimulus that would influence arousal directly, the researchers invited healthy young adults to fall asleep in an MRI scanner, but to press a button with every breath while they were awake. Arousal during the night was defined as the first button-press after at least 20 seconds of unresponsiveness.

The study included two sets of data on button-pushing:

  • Experiment 1—Data were analyzed on six subjects who participated in a previous study published in NeuroImage by Dr. Lewis and colleagues in which 3T fMRI was used to investigate the moment of arousal and detect thalamic activation before arousal
  • Experiment 2—13 new subjects were imaged with 7T fast fMRI to delineate activity within nine individual thalamic nuclei with sub-second resolution

The researchers also performed a control experiment. Eight new subjects (including three who participated in experiment 2) were imaged with 7T fast fMRI split into eight-minute periods while they performed a breathhold task. The purpose was to confirm that the activity sequence observed across thalamic nuclei was not driven by vascular dynamics.

Principal Findings

The major findings about spontaneous behavioral arousals were that:

  • The thalamus activated long before arousal, whereas the cortex deactivated afterwards
  • The centromedian nucleus, an intralaminar nucleus that receives input from the reticular activating system as well as sensorimotor information, is consistently activated first
  • Activity then spread to other thalamic nuclei, and the ventral posterolateral nucleus (VPL) was consistently the second nucleus that activated early; this finding was unexpected because VPL is a first-order somatosensory nucleus not previously implicated in arousal-state changes
  • Activity in most of the cortex declined at arousal, but the anterior and posterior cingulate cortex, like the thalamus, showed a large increase in activity before arousal
  • The thalamic activity was linked to subsequent maintenance of behavioral arousal

A Valuable New Research Approach

Subcortical structures play fundamental roles in modulating cognition, wakefulness, and consciousness. These results suggest a broad potential for fast, ultra-high field fMRI to be useful in studying their function.

Learn more about the Martinos Center

Learn more about research in the Department of Radiology

Related topics


Massachusetts General Hospital researchers have associated lower novelty-related locus coeruleus (LC) function with steeper amyloid-related cognitive decline in clinically normal older adults, suggesting functional MRI of the LC might distinguish between individuals at risk of vs. resistant to Alzheimer's disease.


Kuan-Cheng (Tony) Wu, Marco Renna, PhD, Maria Angela Franceschini, PhD, and others at Massachusetts General Hospital have developed and built a low-cost, wireless, and wearable cerebral oximeter that can track individual cerebral health and is also suitable for use at the community level and in telehealth visits.