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REHOVOT, ISRAEL—April 30, 2020—If an unconscious person responds to smell through a slight change in their nasal airflow pattern, they are likely to regain consciousness. This is the conclusion from a new study conducted by Weizmann Institute scientists and colleagues at Israel’s Loewenstein Rehabilitation Hospital. According to the findings, published in the journal Nature, 100% of the unconscious brain-injured patients who responded to a “sniff test” developed by the researchers regained consciousness during the four-year study period.

The scientists think that this simple, inexpensive test can aid doctors in accurately diagnosing brain injury and determining treatment plans according to the patient’s degree of damage. The team concludes that this finding once again highlights the primal role of the sense of smell in human brain organization. The olfactory system is the most ancient part of the brain, and its integrity provides an accurate measure of overall brain integrity.
Following severe brain injury, it is often difficult to determine whether the person is conscious or unconscious, and current diagnostic tests can lead to incorrect diagnosis in up to 40% of cases. “Misdiagnosis can be critical as it can influence the decision of whether to disconnect patients from life-support machines,” says Dr. Anat Arzi, who led the research. “In regard to treatment, if it is judged that a patient is unconscious and doesn’t feel anything, physicians may not prescribe them painkillers that they might need.”
Dr. Arzi commenced this research during her doctoral studies in the group of Prof. Noam Sobel of the Weizmann Institute’s Department of Neurobiology and continued it as part of her postdoctoral research in the University of Cambridge’s Department of Psychology.
The “consciousness test,” developed in collaboration with Dr. Yaron Sacher, head of the Department of Traumatic Brain Injury Rehabilitation at Loewenstein Rehabilitation Hospital, is based on the principle that nasal airflow changes in response to odor; for example, an unpleasant odor will lead to shorter and shallower sniffs. In healthy humans, the sniff-response can occur unconsciously in both wakefulness and sleep.
The study included 43 brain-injured patients at Loewenstein Rehabilitation Hospital. The researchers briefly placed jars containing various odors under the patients’ noses, including a pleasant scent of shampoo, an unpleasant smell of rotten fish, or no odor at all. At the same time, the scientists precisely measured the volume of air inhaled through the nose in response to the odors. Each jar was presented to the patient 10 times in random order during each testing session, and each patient participated in several such sessions. “Astonishingly, all patients who were classified as being in a ‘vegetative state,’ yet responded to the sniff test, later regained consciousness, even if only minimal. In some cases, the result of the sniff test was the first sign that these patients were about to recover consciousness – and this reaction was observed days, weeks, and even months prior to any other signs,” says Dr. Arzi. Moreover, the sniff response not only predicted who would regain consciousness, it also predicted with about 92% accuracy who would survive for at least three years.
“The fact that the sniff test is simple and potentially inexpensive makes it advantageous,” explains Dr. Arzi. “It can be performed at the patient’s bedside without the need to move them – and without complicated machinery.”
A mindful tennis game
After a severe head injury, patients may fall into a comatose state – their eyes are closed and they do not have sleep-wake cycles. A coma usually lasts for about two weeks, after which there may be rapid improvement and return to consciousness, deterioration leading to death, or a condition defined as “disorder of consciousness.”
When spontaneous eye opening occurs but there is no evidence that the patients are aware of themselves or their surroundings, they are then diagnosed as being in a “vegetative state.” Alternatively, if a patient displays consistent signs of awareness, even if those signs are minimal and unstable, the person will be classified as being in a “minimally conscious state.” The gold standard diagnostic tool for assessing level of consciousness is the Coma Recovery Scale (Revised), which examines responses to various stimuli: eye movements while tracking an object, turning the head toward a sound, and response to pain, among others. Since the rate of diagnosis errors may reach up to 40%, it is recommended to repeat the test at least five times.
However, misdiagnosis may also occur when the test is conducted repeatedly. “In a well-known study, a patient diagnosed as being in a vegetative state following a car accident was scanned in an MRI machine. While in the scanner, the researchers asked the patient to imagine that she was playing tennis, and observed that her brain activity was similar to the brain activity of healthy people when they also imaged playing a tennis game. Suddenly, they realized: ‘hold on a minute, she’s there. She hears us and is responding to our requests. She simply has no way of communicating,’” says Dr. Arzi. “There are also known cases of people who were diagnosed as being in a vegetative state, but when they regained consciousness, they were able to recount in detail what was occurring while supposedly vegetative. Diagnosing the level of consciousness of a patient who has suffered a severe head injury is a major clinical challenge. The sniff test we have developed may provide a simple tool to tackle this challenge.”

Prof. Noam Sobel is head of the Azrieli National Institute for Human Brain Imaging and Research. His research is supported by the Norman and Helen Asher Center for Human Brain Imaging; the Nadia Jaglom Laboratory for Research in the Neurobiology of Olfaction; the Adelis Foundation; and the Rob and Cheryl McEwen Fund for Brain Research. Prof. Sobel is the incumbent of the Sara and Michael Sela Professorial Chair of Neurobiology.


The American Committee for the Weizmann Institute of Science, founded in 1944, develops philanthropic support for the Weizmann Institute of Science in Rehovot, Israel, one of the world’s premier scientific research institutions. The Weizmann Institute is a center of multidisciplinary scientific research and graduate study, addressing crucial problems in medicine and health, technology, energy, agriculture, and the environment. For additional information, please visit www.weizmann-usa.org.

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