Monday, April 13, 2009

Amygdala Medial Prefrontal Cortex Disconnect

A great amount of research has been conducted exploring how sleep deprivation weakens systems such as the immune system, weight control, cognitive processing (memory and learning) but there has been little inquiry into how sleep loss effects our emotional brain. Sleep deprivation has been commonly associated with several psychiatric disorders. It is thought that psychiatric and mood disorders, such as bi polar disorder, cause sleep loss. However, Mathew Walker and colleagues new study show that this isn’t necessarily the case as sleep deprivation, as the results from their study indicate, can itself be the cause of psychological instability.

The Study:
The study involved 26 healthy participants ages 18-30. The 26 subjects were divided in two groups: 12 were assigned to a sleep control group and the other 14 to a sleep deprivation group. All subjects had to refrain from ingesting caffeinated and alcoholic beverages for a total of 72 hours and followed a normal sleep/wake pattern for one week prior to the study (7 to 9 hours of sleep per night, waking hours: 6am -9pm). Their sleep/wake pattern was monitored by an actigraphy, a wristwatch movement sensor.

Pre-Study:

The sleep control group subjects had a normal night of sleep the night before the scanning. The sleep deprivation group remained awake for the entire night and the entire day before the scanning at 5pm (total of 35 hours of sleep deprivation).

Study/ fMRI Scanning:

The subjects were shown 100 images ranging from neutral to gruesome (i.e. basket on table to images of burn victims). Each image was shown for 10 seconds and the subjects were asked to quickly rate their emotional response through a button system, this was also to insure that all subjects remained awake and alert during the experiment. The subjects were in fMRI scanners during this whole process. Mathews and his colleagues were particularly looking for reactions in the amygdala, and curious to see if there were any significant differences between the sleep control group and the sleep deprivation group.

Results:
Both groups had similar emotional responses to the neutral images, but as the images became more and more aversive the fMRI scans showed that there were indeed great differences in how the brains were firing in the sleep-deprived subjects. In both groups the amygdala, as hypothesized, showed greater activity in response to the intense images, yet the sleep deprived subjects amygdala’s were 60% more active than the sleep control group subjects. Not only were the sleep deprived subjects amygdalas showing a stronger activation but also the volume of the amygdala that was activated (greater amount of neurons being activated) was three times that of the sleep control subjects.


It also became evident when observing the fMRI scans that there was a difference in the brain wiring of the control subjects and the sleep control subjects. The control subjects amygdalas maintained normal communication with the medial-prefrontal cortex (MPFC), however; the sleep deprivation participants amygdalas appeared to have lost connectivity with the MPFC and were instead communicating with regions of the autonomic nervous system.



Why is this loss of connectivity with the MPFC significant?

The MPFC communicates with the amygdala as it sends connections to the amygdalas central nucleus and brain stem outputs of the central nucleus. The MPFC serves as an “inhibitory, top-down control of amygdala function, resulting in contextually appropriate emotional responses.”

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Image and video hosting by TinyPic


Maria Morgan, working in Joseph LeDoux’s lab, researched damaged MPFC and found that some lesions of MPFC resulted in exaggerated fear reactions. When the amygdala is reacting to fear the MPFC remains inactive and vice versa. When the MPFC is damaged increased anxiety occurs as the amygdala is left “unchecked” by the MPFC. This often leads to a difficulty with decision making in emotional situations. This research supports Mathews and colleagues’ findings. However, in their case study a lack of connectivity between the MPFC and amygdala wasn’t caused by lesions in the MPFC but rather by a lack of sleep.

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The heightened emotional state occurs when threatening or in this case disturbing stimuli goes unchecked by the MPFC, and this greater activation of the amygdala communicates with the autonomic nervous system that in turn can lead to fight or flight responses.

Stimuli that activate the fight or flight response trigger the brains periventricular system PVS, commonly known as the brains punishment circuit. The PVS is composed of the hypothalamus, the thalamus, and the gray substance around the Sylvius. Acetylcholine activates emission of a hormone known as adrenal cortico-trophic ACTH which activate the adrenal glands to release adrenalin that prepares the body for fight or flight response.

This case study highlights the great importance of sleep. While more research must be done on the connection of sleep deprivation and mood disorders it is clear that sleep loss affects those without symptoms of psychiatric disorders as well. Most of us have experienced the altered state after pulling an all nighter. Now there is evidence that our brains are literally rewiring to create a heightened emotional state. As more research is conducted sleep might be taken more seriously in terms of psychological instabilities. Perhaps certain careers that often keep employees awake for hours on end who’s decision making is crucial will be reconsidered. For example, medical workers.

Sources:

LeDoux, Joseph. Synaptic Self: How Our Brains Become Who We Are. New York: Penguin Books, 2002.

Swaminathan Nikhil. “Can a Lack of Sleep Cause Psychiatric Disorders? Study shows that sleep deprivation leads to a rewiring of the brain’s emotional circuitry” Scientific American. October 23 2007. Get link

Walker, Mathew P. et al. “The human emotional brain without sleep- a prefrontal amygdala disconnect.” Current Biology. Vol 17 No 20.

Walker, Mathews P. et al “ Supplemental Data: The human emotional brain without sleep- a prefrontal-amygdala disconnect” Current Biology. Vol 17 No 20.

“The Amygdala and its Allies.” The Brain from Top to Bottom
http://thebrain.mcgill.ca/flash/i/i_04/i_04_cr/i_04_cr_peu/i_04_cr_peu_1a.jpg

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