Wave of the future: Using anesthesia to detect neurodegeneration

Author: Samantha Payne, 01/03/17

Most people have experienced being put to sleep for a surgical procedure, whether it is relatively minor like the removal of a tooth, or major heart surgery. In fact, every day 60 000 people will undergo general anesthesia in the U.S. You may have noticed a lot of stories sound similar: “I was completely awake talking to the surgeon and then, suddenly, the next thing I knew I was waking up in the recovery room and the surgery was over!”

While it may seem like a simple procedure – you are given a drug that makes you “fall asleep” – regulating anesthesia is one of the most complicated aspects of a surgery. The anesthesiologist must predict how much drug to give you so that you will remain unconscious for the duration of the surgery and still allow you to regain consciousness once it’s over.

Charting the unconscious mind

The fine balance between unconscious and conscious that anesthesiologists are able to achieve is due, in part, to careful monitoring of various physiological outputs, such as heart rate and blood pressure. Aside from basic physiological functioning, brain activity is increasingly being employed as a useful tool to measure a patient’s anesthetized state. The activity of your brain is monitored using an electroencephalogram (EEG), which measures voltage fluctuations produced by firing neurons. A normal resting-state brain will produce a certain pattern of waves at a defined amplitude, and this will change when unconsciousness is induced in a patient. Anesthesiologists can use EEG patterns to determine the level of unconsciousness a patient is experiencing during surgery and adjust the delivery of anesthetics accordingly.

EEG patterns and age

In addition to their importance during general anesthesia, it’s known that EEG signatures change as we age; the EEG trace from a child looks vastly different than that of an adult. Recently, researchers have begun to wonder if we can use this information to predict the onset of neurodegenerative disease. The drugs that are used for general anesthesia, e.g., profonol, act on the same areas of the brain that are affected by diseases such as Alzheimer’s or dementia. Interestingly, neuroanatomical changes in these regions of the brain, such as a decrease in white matter of the cortex, are directly correlated with changes in the EEG readout. By characterizing what EEG signatures look like as we age, we can determine if an individual’s brain activity is typical of their age and, if not, if there is an underlying pathology at work.

Image caption: Electroencephalogram (EEG) spectrogram of individual administered the general anesthetic propofol. The drug is given at the 20 minute mark (x-axis) and elicits a detectable change in frequency and power (y-axes). EEG pattern changes similar to those seen with propofol administration are also detectable in patients with reduced white matter of the cortex (not shown). Reproduced from Valencia et al. British Journal of Anesthesia 2014 (open access).

Opening a therapeutic window for regenerative strategies

It is the link between the areas of the brain affected by anesthetic drugs and neurodegenerative diseases that can allow us to use EEG as a tool for predicting abnormal brain changes. Current methods of diagnosing neurodegenerative diseases like Alzheimer’s rely on the detection of clinical symptoms, such as memory loss or language deficits. However, once these symptoms manifest, there has already been extensive damage to the brain that is difficult to reverse. Detecting degeneration in the brain earlier means that we can implement regenerative strategies sooner, increasing the effectiveness of treatment. For example, allopregnanolone, a neurosteroid known to boost neuron regeneration and reduce Alzheimer’s pathology in mice, is more effective when administered to animals with preclinical disease compared to animals with later-stage degeneration. Due to these encouraging results, allopregnanolone is currently being tested clinically for safety in human patients with early stage Alzheimer’s.

Although not yet in clinical use, our unconscious brain waves could one day be used as a first-pass screening for neurodegeneration, allowing us to intervene with regenerative medicine to halt and even reverse the damage.

 

 

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Samantha Payne

Samantha Payne

Samantha is a PhD student in the Chemical Engineering and Applied Chemistry department at the University of Toronto. She has previously investigated regeneration in a non-mammalian gecko model during an MSc program, and now currently combines stem cell biology and biomaterials to encapsulate and deliver therapeutic cells to the stroke-injured brain. Samantha became interested in scientific communication as a means to combine her love of writing and science to share exciting scientific discoveries to a broader community. Follow Samantha on Twitter @samantha_lpayne
Samantha Payne

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