Age-related differences in the electrophysiological and hemodynamic signatures of arousal

2586 

Abstract Submission 

Sydney Bailes^1,2, Stephanie Williams^1,2, Baarbod Ashenagar^1,2, Dabriel Zimmerman³, Laura Lewis⁴

¹Boston University, Boston, MA, ²Massachusetts Institute of Technology, Cambridge, MA, ³University of Philadelphia, Philadelphia, PA, ⁴Massacusetts Institute of Technology, Cambridge, MA

Sydney Bailes  
Boston University|Massachusetts Institute of Technology
Boston, MA|Cambridge, MA

Stephanie Williams  
Boston University|Massachusetts Institute of Technology
Boston, MA|Cambridge, MA

Baarbod Ashenagar  
Boston University|Massachusetts Institute of Technology
Boston, MA|Cambridge, MA

Dabriel Zimmerman  
University of Philadelphia
Philadelphia, PA

Laura Lewis, Ph.D.  
Massacusetts Institute of Technology
Cambridge, MA

Sleep plays a crucial role in maintaining brain health and cognition, yet as we age our ability to initiate and maintain sleep is impaired [1]. Changes in sleep architecture are typical even in healthy aging, but greater sleep impairment has been linked to occurrences of neurodegenerative diseases [2]. Transitions in behavioral arousal state have previously been shown to follow a distinct sequence of thalamic activation followed by cortical deactivation [3]. Additionally, older adults have been shown to have increases in thalamocortical connectivity not observed in younger individuals paired with a reduced capacity to functionally disconnect regions related to attentional, sensory, and higher cognitive functions during NREM sleep [4]. The thalamus is a hub for sensory integration and modulation of arousal state with profuse connections to the cortex, thus, investigating differences in thalamocortical interactions could provide insight towards understanding age-related sleep impairments. We used simultaneous EEG-fMRI to investigate age-related differences in electrophysiological and hemodynamic changes around transitions in behavioral arousal state.

We simultaneously measured BOLD fMRI and EEG in 30 human subjects (16 female) during sleep. Participants were sorted into two age groups: young (N=11, 18-39 years) and older (N=19, 60-80 years). BOLD fMRI data was acquired at 3 Tesla (TR=378 ms, 2.5mm isotropic voxels). EEG data was acquired using a 32-channel MR compatible EEG cap. Subjects closed their eyes and performed a self-paced breathing task – pressing a button on every breath in. We identified behavioral arousals, defined as the first button press after 30 seconds of inactivity, and rejected arousals with excessive motion (>0.3mm). We calculated the EEG spectrogram around each arousal and calculated occipital alpha power (8-13 Hz) and frontal delta power (0.5-4 Hz). The fMRI time series 10 s before and 20 s after each arousal were also extracted to calculate the mean fMRI response for each group.

Occipital alpha power increased following arousal, visible on both an individual event level and on a group level, as expected (Fig. 1). In the young group the alpha power peaked before the moment of arousal, while it continued to rise post-arousal in the older group (Fig 1B). Delta power dynamics were also distinct between the groups: in the young group, delta power began to decrease before arousal, whereas in the older group, it decreased after arousal (Fig. 1C). These results showed that older adults exhibited a mixed state after arousal, reflecting EEG signatures of both sleep and wakefulness. We next investigated the fMRI activity linked to arousal and observed cortical deactivation following and thalamic activation before arousal, consistent with prior work [3]. Notably, the thalamus reached its peak earlier in the older group (Fig. 2B). To spatially characterize age-related changes, we extracted 32 cortical regions of interest (ROIs) and estimated their time to peak. Most regions reached their peak deactivation earlier in the older group while a minority of cortical regions reach their peak deactivation earlier in the young group (Fig. 2C).

We found that despite sharing a general pattern of dynamics that unfold around arousal, the timing of the EEG and fMRI changes differs between the age groups. Older adults exhibited a mixed electrophysiological state following arousal containing EEG signatures of both wakefulness and sleep that was not observed in the young group. Conversely, the older adults had faster changes in the fMRI signatures of arousal compared to the young group. These results demonstrate that the mechanisms controlling arousal state transitions are occurring on different time scales for the two groups. Furthermore, we found slower electrophysiological arousals and faster hemodynamics in aging, suggesting an alteration of arousal circuitry in the older brain.

Aging ²

Sleep and Wakefulness ¹

Aging

Cortex

Electroencephaolography (EEG)

FUNCTIONAL MRI

Sleep

Thalamus