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The human circadian system can be phase shifted by flashes of dim light that last as little as 10 microseconds, results from a novel study showed.

Doug Brunk/MDedge News
Dr. Jamie M. Zeitzer

“This becomes a complementary way to help people with various kinds of circadian phase disorders,” the study’s first author, Jamie M. Zeitzer, PhD, said during an interview at the annual meeting of the Associated Professional Sleep Societies. “Right now under ideal laboratory circumstances, you can change someone’s circadian timing by about 3 hours. That’s not happening in the real world; that’s what you do in a lab. That’s with very bright light for 6 hours and very dim light the rest of the time.”

In an effort to build on previous literature related to circadian phase shifting and continuous light exposure in rodents and in humans, Dr. Zeitzer, of the department of psychiatry and behavioral sciences at Stanford (Calif.) University, and colleagues enrolled 56 healthy young men and women in their 20s and 30s to take part in two parallel 16-day studies. For the first 14 days, study participants maintained a regular sleep/wake cycle at home as confirmed through actigraphy and sleep logs. They spent the final 2 days in a specialized time-isolation laboratory, during which the phase of the circadian pacemaker (salivary melatonin onset) was determined in constant routine conditions on evening one and two; light exposure occurred between these two phase determinations on night one.

Light exposure consisted of 1 hour of a sequence of light flashes delivered through a pair of modified welding goggles during enforced wake starting 2 hours after habitual bedtime. Flashes were presented every 15 seconds and varied either by duration (from 10 microseconds to 10 seconds at a fixed intensity of 2,200 lux) or intensity (a range between 3 and 9,500 lux, with a duration fixed at 2 milliseconds).


Dr. Zeitzer and colleagues observed no significant difference in the phase shift created between flashes that were given at 10 microseconds and flashes that were given at 10 seconds. “That’s a six-log unit variation,” he said during a presentation of the results at the meeting. “There are a million times more photons given in 10-second flashes over the hour than there are in the 10-microsecond flashes. Despite the fact that there are a million more photons, you get the exact same phase shift in both of these conditions. You need very little light in order to generate these phase shifts. You’re talking about less than 1 second of light stretched out over 1 hour.”

 

 


The researchers also observed that flash intensity showed a sigmoidal relationship with phase shifting, with a half-maximal shift observed at 8 lux and 90% of the maximal shift occurring after exposure to flashes as dim as 50 lux. None of the flash sequences caused acute suppression of melatonin.

“We did not anticipate the invariance, that anything from 10 microseconds to 10 seconds gives us no difference [in phase shifting],” Dr. Zeitzer said. “That was surprising. I thought that more light would be slightly less effective in terms of photons but still give a bigger [phase] shift, but that didn’t happen. In the intensity response, we see things are more sensitive to light flashes than they are to continuous light, which is also surprising. It implies that a different part of the eye is responding to light flashes than it is to continuous light. It provides more information about how to minimize the amount of light we’re using and maximize the amount of shift.”

Which photoreceptors underlie the responses remains unclear, he continued, “but given the characteristics of photoreceptors, our hypothesis is that flashes are being mediated through a cone cell response, while the response to continuous light is being primarily mediated through a melanopsin response. A future question we plan to investigate is, can selective sequential simultaneous activation of different photoreceptors create enhanced phase shifts?”

The study was supported by the Department of Defense. Dr. Zeitzer reported having no financial disclosures.
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The human circadian system can be phase shifted by flashes of dim light that last as little as 10 microseconds, results from a novel study showed.

Doug Brunk/MDedge News
Dr. Jamie M. Zeitzer

“This becomes a complementary way to help people with various kinds of circadian phase disorders,” the study’s first author, Jamie M. Zeitzer, PhD, said during an interview at the annual meeting of the Associated Professional Sleep Societies. “Right now under ideal laboratory circumstances, you can change someone’s circadian timing by about 3 hours. That’s not happening in the real world; that’s what you do in a lab. That’s with very bright light for 6 hours and very dim light the rest of the time.”

In an effort to build on previous literature related to circadian phase shifting and continuous light exposure in rodents and in humans, Dr. Zeitzer, of the department of psychiatry and behavioral sciences at Stanford (Calif.) University, and colleagues enrolled 56 healthy young men and women in their 20s and 30s to take part in two parallel 16-day studies. For the first 14 days, study participants maintained a regular sleep/wake cycle at home as confirmed through actigraphy and sleep logs. They spent the final 2 days in a specialized time-isolation laboratory, during which the phase of the circadian pacemaker (salivary melatonin onset) was determined in constant routine conditions on evening one and two; light exposure occurred between these two phase determinations on night one.

Light exposure consisted of 1 hour of a sequence of light flashes delivered through a pair of modified welding goggles during enforced wake starting 2 hours after habitual bedtime. Flashes were presented every 15 seconds and varied either by duration (from 10 microseconds to 10 seconds at a fixed intensity of 2,200 lux) or intensity (a range between 3 and 9,500 lux, with a duration fixed at 2 milliseconds).


Dr. Zeitzer and colleagues observed no significant difference in the phase shift created between flashes that were given at 10 microseconds and flashes that were given at 10 seconds. “That’s a six-log unit variation,” he said during a presentation of the results at the meeting. “There are a million times more photons given in 10-second flashes over the hour than there are in the 10-microsecond flashes. Despite the fact that there are a million more photons, you get the exact same phase shift in both of these conditions. You need very little light in order to generate these phase shifts. You’re talking about less than 1 second of light stretched out over 1 hour.”

 

 


The researchers also observed that flash intensity showed a sigmoidal relationship with phase shifting, with a half-maximal shift observed at 8 lux and 90% of the maximal shift occurring after exposure to flashes as dim as 50 lux. None of the flash sequences caused acute suppression of melatonin.

“We did not anticipate the invariance, that anything from 10 microseconds to 10 seconds gives us no difference [in phase shifting],” Dr. Zeitzer said. “That was surprising. I thought that more light would be slightly less effective in terms of photons but still give a bigger [phase] shift, but that didn’t happen. In the intensity response, we see things are more sensitive to light flashes than they are to continuous light, which is also surprising. It implies that a different part of the eye is responding to light flashes than it is to continuous light. It provides more information about how to minimize the amount of light we’re using and maximize the amount of shift.”

Which photoreceptors underlie the responses remains unclear, he continued, “but given the characteristics of photoreceptors, our hypothesis is that flashes are being mediated through a cone cell response, while the response to continuous light is being primarily mediated through a melanopsin response. A future question we plan to investigate is, can selective sequential simultaneous activation of different photoreceptors create enhanced phase shifts?”

The study was supported by the Department of Defense. Dr. Zeitzer reported having no financial disclosures.

The human circadian system can be phase shifted by flashes of dim light that last as little as 10 microseconds, results from a novel study showed.

Doug Brunk/MDedge News
Dr. Jamie M. Zeitzer

“This becomes a complementary way to help people with various kinds of circadian phase disorders,” the study’s first author, Jamie M. Zeitzer, PhD, said during an interview at the annual meeting of the Associated Professional Sleep Societies. “Right now under ideal laboratory circumstances, you can change someone’s circadian timing by about 3 hours. That’s not happening in the real world; that’s what you do in a lab. That’s with very bright light for 6 hours and very dim light the rest of the time.”

In an effort to build on previous literature related to circadian phase shifting and continuous light exposure in rodents and in humans, Dr. Zeitzer, of the department of psychiatry and behavioral sciences at Stanford (Calif.) University, and colleagues enrolled 56 healthy young men and women in their 20s and 30s to take part in two parallel 16-day studies. For the first 14 days, study participants maintained a regular sleep/wake cycle at home as confirmed through actigraphy and sleep logs. They spent the final 2 days in a specialized time-isolation laboratory, during which the phase of the circadian pacemaker (salivary melatonin onset) was determined in constant routine conditions on evening one and two; light exposure occurred between these two phase determinations on night one.

Light exposure consisted of 1 hour of a sequence of light flashes delivered through a pair of modified welding goggles during enforced wake starting 2 hours after habitual bedtime. Flashes were presented every 15 seconds and varied either by duration (from 10 microseconds to 10 seconds at a fixed intensity of 2,200 lux) or intensity (a range between 3 and 9,500 lux, with a duration fixed at 2 milliseconds).


Dr. Zeitzer and colleagues observed no significant difference in the phase shift created between flashes that were given at 10 microseconds and flashes that were given at 10 seconds. “That’s a six-log unit variation,” he said during a presentation of the results at the meeting. “There are a million times more photons given in 10-second flashes over the hour than there are in the 10-microsecond flashes. Despite the fact that there are a million more photons, you get the exact same phase shift in both of these conditions. You need very little light in order to generate these phase shifts. You’re talking about less than 1 second of light stretched out over 1 hour.”

 

 


The researchers also observed that flash intensity showed a sigmoidal relationship with phase shifting, with a half-maximal shift observed at 8 lux and 90% of the maximal shift occurring after exposure to flashes as dim as 50 lux. None of the flash sequences caused acute suppression of melatonin.

“We did not anticipate the invariance, that anything from 10 microseconds to 10 seconds gives us no difference [in phase shifting],” Dr. Zeitzer said. “That was surprising. I thought that more light would be slightly less effective in terms of photons but still give a bigger [phase] shift, but that didn’t happen. In the intensity response, we see things are more sensitive to light flashes than they are to continuous light, which is also surprising. It implies that a different part of the eye is responding to light flashes than it is to continuous light. It provides more information about how to minimize the amount of light we’re using and maximize the amount of shift.”

Which photoreceptors underlie the responses remains unclear, he continued, “but given the characteristics of photoreceptors, our hypothesis is that flashes are being mediated through a cone cell response, while the response to continuous light is being primarily mediated through a melanopsin response. A future question we plan to investigate is, can selective sequential simultaneous activation of different photoreceptors create enhanced phase shifts?”

The study was supported by the Department of Defense. Dr. Zeitzer reported having no financial disclosures.
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Key clinical point: When distributed as flashes, the human circadian system can be phase shifted by extraordinarily brief and dim light.

Major finding: The researchers observed no significant difference in the phase shift created between flashes that were given at 10 microseconds and flashes that were given at 10 seconds.

Study details: Two parallel 16-day studies involving 56 healthy men and women in their 20s and 30s.

Disclosures: The study was supported by the Department of Defense. Dr. Zeitzer reported having no financial disclosures.

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