Tired Brains Are More Excitable

By Neuroskeptic | February 14, 2012 7:37 am

An important new study shows how being awake causes progressive changes to the brain. This could shed light on the function of sleep – but it also raises warnings for neuroscientists.

Italian researchers Huber et al report that Human Cortical Excitability Increases with Time Awake. The experiment was conceptually simple – they measured cortical excitability when people were well rested and then looked to see how it changed as they were kept awake for over 24 hours.

The participants woke up at 7 am on Day 1 and were kept awake all of that day, all of the subsequent night, and all of Day 2. The excitability measurements spanned a period of 30 hours, from 9 am to 3 pm the next day. They were finally allowed to go to sleep on the next night and one final session took place on Day 3. I hope they got well paid for taking part.

The results showed a nice linear increase in excitability with increasing time spent awake. Sleep put this back to normal – mostly:

“Excitability” was measured using electroencephalography (EEG) combined with transcranial magnetic stimulation (TMS). Essentially, they zapped the brain (left frontal cortex) with a strong magnetic pulse, and measured the electrical activity that this provoked in the brain.

It was a small study but the findings look solid, with all six participants showing clearly higher stimulation-evoked potentials after sleep deprivation. EEG cortical theta band activity was also correlated with time spent awake, replicating previous findings.

The authors say that these data fit with the idea that the function of sleep is to prevent the brain from becoming too excitable. I previously described this as the “defragmentation” hypothesis of sleep.

The theory goes that while we’re awake, our brains are constantly forming new and stronger synaptic connections, as we learn and remember. Most of the new connections are excitatory. However this creates a problem because the brain must maintain a delicate balance between excitation and inhibition. Too much neural excitation and you’ll have a seizure, amongst other things. So some researchers believe that during sleep, the brain “prunes” the new excitatory connections in such a way that the information they store is preserved, but the overall excitability is reset.

These data are the first clear-cut human evidence in favor of the theory. Most of the previous work was in animals.

So sleep researchers will be very interested by this paper, but all neuroscientists should take note. If being awake changes cortical excitability, it means that the time of day that you conduct your experiments could have an impact on your results. EEG researchers should pay particular notice, but it could well be that these changes also affect the fMRI signal.

This could be a serious confounding factor in your data. Suppose, for example, that your healthy controls are more likely to have jobs than your patients with, say, autism or depression – which is sadly all too common. Now people with jobs would naturally prefer to attend your study later in the day, after work, leaving those with more flexible schedules to come in bright and early… you see the problem.

ResearchBlogging.orgHuber, R., Maki, H., Rosanova, M., Casarotto, S., Canali, P., Casali, A., Tononi, G., and Massimini, M. (2012). Human Cortical Excitability Increases with Time Awake Cerebral Cortex DOI: 10.1093/cercor/bhs014

CATEGORIZED UNDER: EEG, evopsych, mental health, papers
  • DS

    Sounds like a typical medical residency call night.

    I have not read the paper yet but I will comment anyhow based on Neuroskeptics post.

    TMS can have relatively long lasting effects on brain tissue- certainly on the order of hours. Was there a control group which received TMS but no sleep deprivation? If not then the reported results are worthless.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Mmm that's an interesting point. Well spotted.

    The authors do say “the induction of LTP-like modifications in human cortical circuits, by means of high frequency TMS protocols, results in a clear-cut increase of early-latency TEPs (starting from 5 to 15 ms)”

    However, they say that the TMS parameters they used do not cause this effect. They say

    “200-300 pulses were delivered… with an interstimulus interval randomly jittered between 600 and 750 ms. This stimulation rate does not induce significant reorganization/plasticity processes that might possibly interfere with the longitudinal measurements (Casarotto et al. 2010).”

    Casarotto et al is one of their own papers and it found very little change in the TMS evoked response between the start and the end of a TMS session lasting several hours with 5-8 stimulations (albeit not all in the same place).

    However, it could be that the effects of heavy stimulation are delayed i.e. there is little change on the day, but the brain becomes more excitable on the next day.

  • Ivana Fulli MD

    When I was a resident long ago , I was taught by one of my professors that when epilespia was suspected for an hospitalized client with a “clean EEG”, the client had to be asked to watch TV for hours, no nap allowed (and the nurses had to check on that )and the client was to be send to the EEG people's lab at the end of their working day.It was called “to lower the threshold of epilepsia”.

    I hope it is not off topic but, hormones like cortisol are known to have basal circadian fluctuations plus fluctuations due to the “stresses” in the life of the client. Plus I was told that the menstrual cycle gave women inter-individual fluctuations on the alpha wawes or whatever on the EEG.

    Decades ago the chronobiology was all the rage in pharmacologists circles although now tha cancer treating people seem to me (but I am not sure) the only researchers passionate about knowing the right time of the day to give drugs in order to maximize therapeutic effects and minimize the unwanted side effects.

  • DS

    I just took I very quick look at the paper. If they had kept the TEP/EEG sessions at every 6 hours throughout the entire experiment (baseline, sleep deprivation and recovery) then they could make a convincing argument but during sleep deprivation they did only one TEP/EEG session (18 hours after the last of three sessions separated by 6 hours each) and during sleep deprivation recovery (24 hours later) did only one TEP/EEG session.

    So, were the subjects recovering from TMS or sleep deprivation? I am not convinced that it was the latter. Yet.

  • David

    This sounds a lot like Tononi's synaptic homeostasis theory of sleep function. Neat stuff.

  • Martin

    @NS: I think it's a bit of an overstatement to conclude that this could be a huge confounding effect in neuroimaging (or behavioral) data. Of course wakefulness – independent of sleep deprivation – can have an effect, although I don't know the literature.

    But 30h of sleep deprivation is quite different to being measured in the morning or in the evening of a normal working day and comparing different states of wakefulness. The night-day cycle is just completely messed up in the former case. I think, there the difference in excitability would disappear or could not be measured anymore.

  • http://www.blogger.com/profile/06647064768789308157 Neuroskeptic

    Martin: It probably wouldn't be a confound in most studies, no, but it's something to think about. Especially because we don't know how this might affect the more subtle effects that are the focus of a lot of EEG interest at the moment (high frequency oscillations, connectivity, coherence) – the effect of excitability might be greater on those measures, that's just speculation though.

    On the other hand it might just be something that affects the response to TMS and nothing else.

  • http://www.blogger.com/profile/15579272589604671824 toodles mcgee

    How or does the “quality” of sleep play in this? Different med for insomnia can cause different sleep patterns, right? Are some better for alleviating this “excitability” issue?



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Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.


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