Tired Brains Are More Excitable

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.

Huber, 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

The Hidden Face Within

One of these two images contains a hidden picture of a face. Which one?

This was the question faced by participants in a remarkable psychology experiment just published, Measuring Internal Representations from Behavioral and Brain Data.

Five healthy volunteers were presented with a series of random black and white grid patterns. Each grid square was either black or white, and this was randomly determined on each trial.

There was no pattern to the images, they were completely random. But the subjects were told that half of the patterns contained a hidden face, and that their job was to work out which ones did. Each subject saw over 10,000 random images and they took about 1 second to judge each one.


The volunteers "detected" a face in 44% of the images. Somehow, all five of them convinced themselves that they were seeing faces in many of the grids. The authors say that

Upon completion of the experiment we debriefed observers, and all expressed shock that no face was ever presented.

That's strange enough in itself, but here's the really clever bit. The authors compared the patterns which were declared to contain a face, to the ones that were reported as empty. The image below shows the average "face" grid, minus the average "non face" grid, for each individual subject:

As you can see, this reveals...a face! Kind of. The top half shows the raw average; the bottom half shows the statistically significant differences from random noise.

In Subjects 1 and 2, the face is pretty clear, with eyes, a nose and a mouth. For 3 and 4, it's less coherent, but you might be able to see it if you look hard enough. For Subject 5, not really.

What this means is that people (at least, most of them) were not just seeing faces in any noise. They tended to see faces when the random patterns happened to resemble a kind of primitive face, but it was a different face for each person. The authors say that these strange faces correspond to the individual's internal representations, or models, of "a face", that each subject was "seeing" in the noise.

Finally, the whole experiment was conducted while EEG data was being recorded from the participant's brains. The EEG results revealed that there was a clear difference in the neural activity associated with "face" compared to "nonface" stimuli - except in Subject 5, who you'll remember had the least coherent "internal face".

What's exciting about this approach is that it investigates perception in a purely "top down" way. Normally, when we look at anything, what we end up perceiving is a product of "bottom up" influences - the raw data - and "top down" ones - what we expect to see. In this experiment, there was no real "bottom up" data; it was all "top down".

This is a form of pareidolia - perceiving familiar things in random stimuli. Seeing the face of Jesus in your sock, that kind of thing. It works for sounds too: in the famous White Christmas Experiment, people report "hearing" music in pure white noise - when told to expect it. Real-life examples of this include the "Islam Is The Light" doll, and my personal favorite, the singing paedophile Christmas mouse.

Finally, I wonder what embodied cognition theorists make of this paper. Because this paper claims to be "Measuring Internal Representations from Behavioral and Brain Data"; embodied cognition (at least the radical kind) is the theory that "internal representations" either don't exist, or at least don't explain anything about human cognition.

Smith, M., Gosselin, F., and Schyns, P. (2012). Measuring Internal Representations from Behavioral and Brain Data Current Biology DOI: 10.1016/j.cub.2011.11.061

Dream Action, Real Brain Activation

A neat little study has brought Inception one step closer to reality. The authors used fMRI to show that dreaming about doing something causes similar brain activation to actually doing it.

The authors took four guys who were all experienced lucid dreamers - able to become aware that they're dreaming, in the middle of a dream. They got them to go to sleep in an fMRI scanner. Their mission was to enter a lucid dream and move their hands in it - first their left, then their right, and so on. They also moved their eyes to signal when they were about to move their hands.

Unfortunately, only one of the intrepid dream-o-nauts succeeded, even though each was scanned more than once. Lucid dreaming isn't easy you know. Two didn't manage to enter a lucid dream. One thought he'd managed it, but the data suggested he might have actually been awake.

But one guy made it and the headline result was that his sensorimotor cortex was activated in a similar way to when he made the same movements in real life, during the lucid dream -  although less strongly. Depending on which hand he was moving in the dream, the corresponding side of the brain lit up:

EEG confirmed that he was in REM sleep and electromyography confirmed that his muscles were not in fact being activated. (During REM sleep, an inhibitory mechanism in the brain prevents muscle movement. If the EMG shows activity this is a sign that you're actually partially awake).

They also repeated the experiment with another way of measuring brain activation, NIRS. Out of five dudes, one made it. Interesting this showed the same pattern of results - weak sensorimotor cortex activation during movement - but it also showed stronger than normal supplementary motor area activation, which is responsible for planning movements.

This is rather cool but in many ways not surprising. After all, if you think about it, dreaming presumably involves all of the neural structures that are involved in really perceiving or doing whatever it is you're dreaming about. Otherwise, why would we experience it so clearly as being a dream about that thing?

It may be, however, that lucid dreaming is different, and that the motor cortex isn't activated in this way in normal dreams. I suppose it depends what the dream was about.

That raises the interesting question of what someone with brain damage would dream about. On the theory that dream experiences come from the same structures as normal experiences, you shouldn't be able to dream about something that you couldn't do in real life... I wonder if there's any data on that?

Dresler M, Koch SP, Wehrle R, Spoormaker VI, Holsboer F, Steiger A, Sämann PG, Obrig H, & Czisch M (2011). Dreamed Movement Elicits Activation in the Sensorimotor Cortex. Current biology : CB PMID: 22036177

Life With Low Serotonin, Revisited

Last year I covered the case of a young man born with a genetic disorder which caused him to suffer low levels of the monoamine neurotransmitters - serotonin, dopamine, and noradrenaline.

These are the chemicals that are widely thought to be deficient in depression, and they're the target of antidepressant drugs (especially serotonin).

If low monoamines cause depression, you'd expect someone with low monoamines to be depressed, at least on the simplest view. But the case from last year had no reported mood problems, although he did show appetite, sleep and concentration problems that were cured by serotonin replacement therapy.

Now a new case report has just appeared that tells a different story. Gabriella Horvath and colleagues from British Columbia describe two sisters. Both had a normal birth and childhood, but at the ages of 11 and 15 respectively, began to suffer severe migraines and other symptoms. Sister 1:

started having hemiplegic migraine at age 11 years, initially occurring every 3–8 weeks, lasting 4–48 hours, presenting with right or left-sided numbness and paralysis, no visual disturbances, but slurred speech, associated with vomiting, headache, and confusion, followed by weakness lasting up to 7 days, and then complete recovery. The frequency of her migraine increased slowly with age up to twice a month...

Between 12 and 20 years she had developed progressive spastic paraparesis; sensory loss in stocking distribution... urinary and bowel incontinence; bladder instability... irritable bowel syndrome; sleep problems; depressed mood; and anxiety. She needed to use a wheelchair for most of the time by the age of 17.

Sister 2 had a rather different course:

The older sister originally presented at the age of 15 years with a history of hemiplegic migraine and seizures and myoclonic jerks. EEG showed generalized spike-and-wave activity, and polyspikes with photoconvulsive [light-induced seizures] response, in keeping with juvenile myoclonic epilepsy. Her seizures were brief and infrequent and not associated with the migraine episodes...

She subsequently developed progressive weakness, frequent falls, depression, and mild bladder instability...

Various blood and genetic tests failed to get to the bottom of it. MRI scans showed abnormalities in the spinal cord and parts of the brainstem in both cases, but why?

Spinal tap studies in Sister 1 revealed very low levels of 5HIAA, which is a by-product of brain serotonin (5HT). This suggested low 5HT levels. So doctors started her on 5HTP to try to boost it.

They report that 5HTP treatment caused "improvement" in all symptoms, including the migraines, slurred speech, depression, and movement, but not immediately. She gradually went from being in a wheelchair to being able to walk around the house on crutches, although she used a wheelchair outside. However, after 3 years of treatment, at age 20, she suddenly fell into a coma lasting 2 months. She is now recovering.

Sister 2 also had low 5HIAA, and was given 5HTP. She also reported symptomatic improvement.

Blood tests reported very low platelet serotonin levels. 5HTP treatment increased this but they were still below normal. Platelet 5HT reuptake rate was also low, suggesting a problem with the 5HT reuptake transporter protein 5HTT.

But the 5HTT gene (famously known as "The Happiness Gene" although that's questionable) seemed entirely normal in these patients. The authors say however that the symptoms are, in some ways, reminiscent of mice who lack the 5HT reuptake protein (5HTT knockout mice), who also show low serotonin. Also, if it were genetic, that wouldn't explain why there were no problems at all during childhood.

So this case is a mystery. The low serotonin has no known cause, and it might just be a side effect of a deeper underlying problem, but serotonin has long been linked to migraines so it might account for some of the symptoms. The fact that 5HTP helped supports this, though it wasn't a controlled trial so we can't know for sure.

As for the depression and anxiety, improved by 5HTP, this could have been a result of low serotonin, but it could also have been a psychological reaction to the severe medical problems. It's impossible to know.

Horvath GA, Selby K, Poskitt K, Hyland K, Waters PJ, Coulter-Mackie M, & Stockler-Ipsiroglu SG (2011). Hemiplegic migraine, seizures, progressive spastic paraparesis, mood disorder, and coma in siblings with low systemic serotonin. Cephalalgia : an international journal of headache PMID: 22013141