The Eyes Have It: Pupillary Dynamics Predict Arousal State in Mice
Kevin L. Turner, Kyle W. Gheres, and Patrick J. Drew
(see pages 949–964)
Behavioral experiments with rodents of all sorts require that the researchers know the arousal state of the animal, which is not always evident as rodents often sleep with open eyes, both in natural and experimental settings. Connections have been found between eye movement and blinking, neural activity and cortical blood flow, and arousal state. Now Turner et al. investigate these connections in more detail in nonanesthetized, head-fixed mice. The authors simultaneously tracked blinking and changes in pupil diameter via video while also recording electrophysiological activity in the somatosensory cortex and hippocampal CA1 [measured as local field potentials (LFPs)], neck muscle tone [measured with electromyography (EMG)], whisker movements, and cerebral blood volume (hemodynamic signals) during wakefulness, rapid-eye movement (REM) sleep, and non-REM sleep. Awake mice frequently moved their whiskers, which correlated with increased pupil diameter and high EMG power, while the LFP showed reduced low-frequency power and hemodynamic fluctuations were comparatively small. During non-REM sleep, whisker and muscle movements and pupil size predictably decreased, whereas low-frequency LFP and hemodynamic signals increased. During REM sleep, pupils remained constricted, while whisker movements increased and EMG signals were very low due to muscle atonia. Hemodynamic signals were at their highest during REM sleep with elevated theta-band power detected in the LFP. Across arousal states, pupil diameter was largest during periods of greatest arousal and smallest during sleep. When comparing pupillary changes with cortical neural and hemodynamic changes, the researchers observed that fluctuations in pupil and LFP gamma-band power were small in awake mice, but in sleeping mice both were substantially larger. Similarly, during awake states, pupil and hemodynamic changes were small. In REM and non-REM sleep states, pupils constricted about a second before cortical blood volume increased. The tight temporal correlation between fluctuations in blood volume and pupil constriction suggests that the process mediating arousal also controls cerebral blood flow. In terms of blinking, there was little correlation between blinking and cortical activity or blood flow during sleep, but in awake state the authors found that blinking may signal a sort of neural “resetting,” as it often occurred during processing of new or startling information. Together, the observations showed that pupil diameter and position alone could remarkably predict the arousal state as well as conventional—yet more invasive—measures, obviating the need for such measures as pupil diameter can be regularly tracked during such studies. Now researchers can depend on eye measurements as a reliable indicator of more intractable physiological signs.
Recovery of visual detection and localization depicted for patient J.M. See Rowland et al., Figure 2 for more detail.
Multisensory Training Restores Vision in Humans after Stroke
Benjamin A. Rowland, Cheryl D. Bushnell, Pamela W. Duncan, and Barry E. Stein
(see pages 1018–1026)
Hemianopia, a debilitating condition that often arises after stroke or trauma affecting the visual cortex, effectively causes blindness in half the visual field. Treatments such as visual retraining have had only limited success, though some people recover spontaneously over a period of months. But recent studies in a cat model showed striking results using multisensory training using paired audiovisual stimuli. (Visual or auditory cues alone did not lead to recovery.) Remarkably, the animal studies showed that the rehabilitation was effective even when animals were anesthetized, indicating that behavioral engagement or cognitive responses were not required, greatly expanding the potential for the treatment in nonresponsive patients. Now Rowland et al. show equally striking results in humans. In the current study, the authors recruited two men, aged 64 years (J.M.) and 72 years (C.W.), who suffered from hemianopia following stroke 14 and 8 months earlier. In addition to their visual impairment, which left them unable to detect flashes of light in the affected visual field, both subjects suffered from reduced mobility and cognitive deficits (presumably due in part to eye strain) that affected their ability to function independently. For the training, researchers repeatedly presented visual–auditory stimuli consisting of a brief flash of bright light simultaneously coupled with a brief burst of broadband noise, presented to the hemianopic field in blocks of 100 to 150 trials, with up to 600 trials per session. The subjects underwent weekly, 2 h sessions for 10 weeks. The patients also underwent assessment during the sessions, in which they responded to light flashes verbally and by pointing to its location as fast as possible. They were also asked to identify real objects, such as glasses or a water bottle, or virtual geometric shapes, which were either stationary or moving. Before training, both patients were totally blind to the stimuli. Both subjects made significant improvements in the first 4 to 5 weeks of training, but one made detectable gains as early as after the first session. Both patients reported marked improvements in their ability to navigate their environment and other functions including reading, and therefore in their quality of life. Interestingly, vision detection and localization improved first at the edge of the sighted field—rather than at the stimulus location, as might be expected—and then expanded to encompass the entire visual field. The mechanism for the improvement remains unknown, but the authors speculate that the overlapping visual and auditory topographic maps in the superior colliculus and their extensive connectivity to other brain regions may underlie the recovery. The study shows that this simple, noninvasive multisensory therapy could lead to sight recovery from a previously uncurable disability.
Footnotes
This Week in The Journal was written by Stephani Sutherland.
