The Hypothalamus

When we wake up every morning and open our eyes, an immediate and very important electro-chemical chain reaction begins. The eyes open and light streams onto the retina. A cascade of electro-chemical signals flows from the eyes to a nuclear center within the hypothalamus, two paired tissues in the midline called the suprachiasmatic nuclei (SCN).

The suprachiasmatic center is one of the body's two major biological clocks. It not only regulates hormones related to the day/night cycle, but orchestrates the activities of many other internal clocks. In numerous experiments, it has been shown that, when the SCN is not innervated, the human body clocks free-run; they set their own time.

The body is awash with internal clocks. Researchers know of over one hundred clocks so far (Carol Orlock; from the book "Inner Time"). The human body has inner clocks in nearly every organ, every type of tissue, and inside many cells. All of these clocks have to be synchronized, and all are controlled (and influence) the body's two master clocks, the SCN inside the hypothalamus, and a second unidentified clock that regulates body temperature and alertness. (the activities of the second clock are well known, but its locale within the brain is unknown)

Chronobiologists divide the clocks into three areas: ultradian rhythms (those shorter than a day); circadian rhythms (24 hour cycles); and infradian rhythms (those cycling in intervals greater than 24 hours). Heart beats, body temperature, breathing patterns, and blink rates are examples of ultradian rhythms. The day/night cycle is circadian. A woman's menstrual cycle is infradian. All of these cycles are governed by hormones released by internal body clocks.

Our seven-day weeks, our calendar year, our day divided into 24 hours, all may seem like inventions of modern society. But they are not. Nature imposes rhythms that are weekly, monthly, and daily on all forms of animal and insect life. We fashioned our time pieces on the model that nature provided for us. How well we perform, how long we endure, our mood, our ability to remember, to feel and express emotions, how well we sense and perceive the world, how alert we are, how safe or accident prone, on and on, all these things are affected by internal clocks. Anything that disrupts these systems has a far reaching impact on the entire human body. It makes sense then to ask what impact occurs when a major, master time piece like the suprachiasmatic nucleus, is "shut down by" blindness. Epidemiological studies of sleep disturbance among the visually impaired all report a higher than normal (for the population at large) incidence of sleep problems (see the July, 1998 issue of the Journal of Visual Impairment and Blindness, Volume 92, number 7).

In the March, 1998 issue of the Journal of Visual Impairment and Blindness, Sack, Blood, Hughes and Lewy discuss the characteristics and impact of "Circadian-Rhythm Sleep Disorders in Persons Who are Totally Blind." They write "People who are totally blind are prone to a cyclic form of insomnia, designated in medical terminology as non-24-hour sleep-wake syndrome......Because they lack photic input to the circadian time keeping system, people who are totally blind have body rhythms that are not necessarily synchronized to the 24 hour solar and social day."

Insomnia is the most common sleep complaint of people who are blind. Although insomnia can be caused by a variety of factors (stress, depression, medications, sleep disorders, and aging), it is a logical result of an internal clock mechanism that "runs free" (as is theoretically proposed to be happening with blind individuals). A system that runs free is in and out of phase with the day/night cycle, ie. sometimes it is in phase (harmony) with the sighted world, and sometimes it is not. A free-running clock goes by a 24 hour, plus thirty minute cycle daily. It is an additional 30 minutes off with each successive day. Eventually, the clock is entirely "100 degrees" out of phase (going to bed when everyone else is getting up), before it starts back toward a normal cycle.

This alternation between in phase and out of phase makes diagnosis (and differentiation from other causes) difficult. Some days the patients have symptoms and other days there is no problem. When out of phase, the sleep cycle becomes dissociated from other body rhythms, and patients show typical sleep disorder symptoms: falling asleep during the day; difficulty getting to sleep at night; difficulty concentrating; erratic emotional periods; etc. "Most patients attempt to sleep and arise at conventional social times. This produces progressively less sleep, with secondary daytime sleepiness interfering with functioning at work or at school. In addition, sleep may be skipped for 24 to 40 hours, followed by sleeping for 14 to 24 hours without awakening."

Since body temperature is regulated by body clocks that respond to the day, night cycle, there is a connection between temperature and sleep patterns. "If people fall asleep when their body temperature is falling, they will have long bouts of sleep, but, if they go to sleep when their body temperature is rising, their sleep will be short.

Treatment follows two strategies. Medications can be used to attempt to set the master clock, or behavioral approaches are used to "disconnect the clock". "Moderate exercise (for example) at certain times of the day can shift circadian rhythms.

The easiest and most promising method used to set the master clock is the use of melatonin at bedtime. Although melatonin's efficacy and safety when used for sleep disorder treatment with blind individuals is unproved, there is anecdotal evidence that it is safe and effective. "Two reports have indicated that melatonin may be useful for blind children with sleep-rhythm disorders (Espezel, 1996, Journal of Visual Impairment and Blindness, 90, 43-50; and Jan, 1994, Developmental Medicine and Child neurology, 36, 97-107).

The suprachiasmatic nuclei are connected to and stimulate the pineal gland which secretes the hormone melatonin at night. There are reciprocal nerve fibers that run from the pineal gland back to the hypothalamus providing a feedback (homeostatic) loop. This feedback loop is the reason that melatonin is used to reset the master clock after jet lag, and it has important implications for treating disorders experienced by blind individuals.

In the January, 1998 issue of the magazine Science, Scott Campbell and Patricia Murphy of Cornell University Medical College in White Plains, New York, report on a study using light therapy applied to the backs of people's knees. This therapy apparently was effective in setting the body's clocks. Although controversial, this therapy is promising as a treatment for the blind, and suggests that areas of the skin may be able to set the body's clocks (this may help explain why blind individuals have varying degrees of "body clock symptoms" (little if any insomnia, no problems with hormonal cycles, etc.). In the July 11th Science News magazine, John Travis says:

"Despite the recent back-of-the-knee studies, eyes still seem to be the primary route by which the mammalian circadian system senses light. If scientists cut the optic nerve conveying information from the retina to the brain, mice lose their normal circadian rhythms. To resolve this seemingly contradictory evidence, investigators argue that retinas must contain light sensitive proteins other than the traditional opsins."

The implication is that there are cells in the retina that are not rods or cones, but that are specialized circadian photoreceptors. Aziz Sancar of the University of North Carolina School of Medicine contends that he has found such a photoreceptor. The chemical in this light sensitive receptor is made in the human retina as well as in human skin. This would explain why both the skin and the eyes affect the biological clocks of humans.

There are some interesting thoughts that follow from this. First, light therapy on the skin (backs of knees, etc.) may be worth trying with blind children when parents do not wish to experiment with drug therapies like melatonin. It might also be interesting to know if blind individuals from sunny climates have more or less sleep disorders than those from more overcast conditions (shorter days, etc.). There might also be evidence to show that individuals with no eyes or with eyelids that are closed could have more sleep problems than those with low vision or those with open eyes and normal retinas (cortical or higher brain level vision loses. This is all speculation on my part.

In the July, 1998 Journal of Visual Impairment and Blindness, there is an article entitled "Sleep Disturbances Among People Who Are Visually Impaired: A Survey of Guide Dog Users". In this study, one in five respondents reported sleep problems. Exercise was related to better sleep, depression with poorer sleep. The degree of visual acuity did not relate to sleep quality.


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