Why Brain Scanners Make Your Head Spin

Here at Neuroskeptic we see a lot of dizzyingly bad (and sometimes even good) neuroscience, but did you know that brain scanners can literally send your head into a spin? A new paper explains why, with implications for all MRI researchers.

MRI scanners rely on extremely powerful magnetic fields. This is why you can't take metal objects into the scanner room, as they'd be pulled into it. Yet the fields can also exert other kinds of effects on the body.

I'd always been told that static, unchanging magnetic fields are biologically inert. But moving through the field too quickly can cause side effects. When an object moves through a magnetic field, induction happens - electrical currents are produced.

In the case of the human body, these small currents can activate nerve cells. Depending on which cells they hit this can cause you to feel dizzy, see flashes of light, experience tingling sensations, and so on. Or so I thought.

However, a new paper from Dale Roberts et al of Johns Hopkins shows that just being in a powerful magnetic field can cause dizziness and vertigo - with no movement required. They noticed that lying still in or near an MRI scanner causes nystagmus, abnormal horizontal eye movements, and that the amount of eye movement is directly correlated with the angle at which the head is positioned relative to the field.

The nystagmus was caused by an automatic reflex in response to effects in the vestibular ("balance") system of the ear. Roberts et al realized that the static magnetic field causes electrical currents that activate vestibular cells, even when the head is perfectly still. It happens because there's a natural flow of electrically charged ions into these cells in a part of the ear called the semicircular canal. The magnetic field interacts with this ion current, in what's called a Lorentz force.

The semicircular canals normally allow us to sense when our head is moving. Our eyes automatically compensate for head movement to keep us looking in the same direction. The MRI magnet fooled the ear into thinking the head was rotating, and the eyes produced nystagmus as a result.

Two patients who had suffered damage to their semicircular canals were immune to the effect.

This has important implications for functional MRI studies of brain function. Many people are interesting in measuring eye movements during MRI scans. This finding suggests that these movements may be unusual, compared to normal eye movements outside the scanner. Worst, the vestibular stimulation could alter brain activity:

Vestibular stimulation induced by the magnetic field in healthy subjects simply lying in the bore could activate many brain areas related to vision, eye movements, and the perception of the position and motion of the body.

Roberts, D., Marcelli, V., Gillen, J., Carey, J., Della Santina, C., & Zee, D. (2011). MRI Magnetic Field Stimulates Rotational Sensors of the Brain Current Biology DOI: 10.1016/j.cub.2011.08.029

Schizophrenia And The Developing World Revisited

A major international study threatens to overturn what we thought we knew about schizophrenia.

People with schizophrenia are more likely to get better if they live in poor countries: that's been known for about 25 years. In the 1980s, a series of pioneering World Health Organization (WHO) studies looked at the prognosis for people diagnosed with schizophrenia around the world.

All of the data showed that people in developed countries were less likely to recover than those from poorer areas.

This paradoxical finding sparked no end of debate. What is it about these countries that makes them a better place to get schizophrenia? Patients in richer countries tend to have access to more and "better" psychiatric care, the latest drugs, and so on. Does this mean that those treatments are useless - worse, harmful? That's been the interpretation of some people.

But is it true? Not always, says a new study, W-SOHO. It's out in the British Journal of Psychiatry.

The authors compared schizophrenia outcomes in 37 countries. They recruited outpatients who were starting, or changing, antipsychotic medication. They found that in terms of "clinical" remission - i.e. improvement in the delusions, hallucinations, and other symptoms of schizophrenia - people in the developing world did indeed fare better than those from rich countries.

Over a 3 year period, 80-85% of patients from East Asia, the Middle East, and Latin America who started off ill, showed clinical remission, compared to 60-65% in Europe. That's not new: it confirms what the old WHO data showed.

But the new study also looked at "functional" remission - essentially, being able to participate in society:

having good social functioning for a period of 6 months. Good social functioning included those participants who had: (a) a positive occupational/vocational status, i.e. paid or unpaid full- or part-time employment, being an active student in university or housewife; (b) independent living; and (c) active social interactions, i.e. having more than one social contact during the past 4 weeks or having a spouse or partner.

For functional remission, Northern Europe (e.g. the UK, France, Germany) was the best place to get sick, with 35% achieving it. Not a very high figure, but better than elsewhere: it was just 18% in the Middle East and 25% in East Asia, despite these areas having the highest chances of clinical remission. Latin America did pretty well, however, at 29%.

This is a very important finding if it's true. Is it solid?

First off, were Northern European patients just less ill to start with? Not really. They had the highest rates of suicide attempts. They tended to be older, and to have been diagnosed at a later age, which was correlated with worse functional remission. Regression analyses confirmed that region was a predictor of remission controlling for all the other variables.

However, Northern European patients did tend to have better function at baseline. They were more likely to be employed, living independently, and socially active when they entered the study. 63% were living independently which is much higher than anywhere else: it was 24% in Middle East and Latin America. 23% had a paid job compared to 17-19% in developing countries.


That's not a flaw in the study as such but it does suggest that the differences, whatever they are, are already in place before people get treated.

One concern I have is that the definition of "functional remission" may be North Europe-centric. "Living independently" is something we aspire to but in other places, with a strong tradition of the extended family household, the idea that it would be a bad thing for someone with schizophrenia to be living with their family might seem silly. If that means they'll be cared for and supported, what's wrong with it?

And in terms of paid employment, Northern Europe just has a stronger economy than most other places (erm... well, it did back in 2000 when these data were collected), so maybe it's no surprise that people with schizophrenia were more likely to have paid jobs.

In terms of the study itself, it was extremely large with over 17,000 patients enrolled. But here's the thing: this study was run by Lilly, the drug company who make olanzapine, an antipsychotic used in schizophrenia. Three of the authors on the paper are Lilly employees, and the lead author was a consultant for them. The study deliberately sampled lots of people taking olanzapine, presumably in order to find out whether they did better.

None of this necessarily means that the data aren't valid, but I'm just not sure I trust Lilly over the WHO.

Haro JM, Novick D, Bertsch J, Karagianis J, Dossenbach M, & Jones PB (2011). Cross-national clinical and functional remission rates: Worldwide Schizophrenia Outpatient Health Outcomes (W-SOHO) study. The British journal of psychiatry : the journal of mental science, 199, 194-201 PMID: 21881098

The Real "Contagion" Virus

Seen Contagion yet?

It's pretty scary. A new epidemic disease comes out of nowhere and starts killing everyone. It infects the brain - victims suffer seizures, or fall into a coma, and die. It spreads like wildfire. Humanity's only hope lies in Lawrence Fishburne and Kate Winslet.

Luckily, that's fiction. But only just.

In the movie, the killer bug is called "MEV-1", but it might as well have been called the Nipah virus, because it was closely based on a real disease of the same name. So much so that this post about Nipah contains movie spoilers.

The Nipah Virus came to the world's attention in late 1998. There was an outbreak of a severe fever accompanied in many cases by encephalitis (viral infection of the brain) in Malaysia and Singapore. 276 patients were recorded. 40% of them died.

In the initial outbreak, there was probably no person-to-person transmission of the virus. Rather, only people who came into contact with Malaysian pigs - mainly farmers and butchers - caught the disease. Over a million pigs were culled in 1999 to try and contain the outbreak, and this seemed to be effective.

But since then, there have been several other smaller Nipah outbreaks in Asia, one almost every year in fact. In some of these, person to person transmission has been detected, notably in Bangladesh and India. The fatality rate in these more recent outbreaks has also been higher (70-90%). Luckily, unlike in the movie, it doesn't seem to be very contagious - so far. Most years have seen only 10 or 12 cases. But who knows what the future holds?

The virus is distantly related to measles, but is much more severe. Symptoms can begin anywhere from 4 days to 2 months after infection, but generally within 1 to 2 weeks. More recent outbreaks seem to have a shorter incubation period. The symptoms include fever, headache, vomiting, seizures, muscular jerks, and altered consciousness (confusion, coma).

Even after the initial infection is over, a minority of patients (4-8%) later suffer a relapse encephalitis. The virus seems able to remain dormant in the body before re-emerging to infect the brain again. Survivors may suffer neurological problems such as epilepsy, movement disorders, fatigue, and others. This is especially common following relapse encephalitis.

Where did it come from? It turns out that various strains of Nipah-like viruses are common in certain bats that inhabit various Asian countries, specifically fruit bats of the Pteropus genus, aka "flying foxes". The bats don't get sick, but infected bats are highly contagious, excreting the virus in their urine.

The virus seems to have made the leap into humans not once but several times, from different kinds of bats. Each outbreak could represent a new crossover event. Often there was an intermediate animal host, such as the domestic pigs in Malaysia .

Nipah is a classic zoonotic disease - it jumps from animals to humans. Zoonoses are scary for two reasons. They're new to humans, so humans haven't had a chance to develop immunity. And they may be especially deadly, because they haven't evolved not to be deadly to us.

Viruses and bacteria don't actually want to kill you. They want you alive, so that you can keeping breathing, walking, having sex, and otherwise spreading them. So pathogens tend to evolve to be less lethal to their primary hosts. Unfortunately, that's only good news if you are the primary host, and in the case of zoonoses, we're not. Bats don't get sick, but we do.

Lo, M., & Rota, P. (2008). The emergence of Nipah virus, a highly pathogenic paramyxovirus Journal of Clinical Virology, 43 (4), 396-400 DOI: 10.1016/j.jcv.2008.08.007

Alice In Wonderland Syndrome

One pill makes you larger
And one pill makes you small
And the ones that mother gives you
Don't do anything at all
Go ask Alice
When she's ten feet tall

So sang Jefferson Airplane in their psychedelic classic White Rabbit. While this song seems sure to have been inspired by the use of certain unapproved medications, don't have to be dropping acid to feel ten feet tall.

A new paper from Germany reports on a case of "Alice In Wonderland Syndrome" associated with topiramate, an anti-epileptic drug also used to prevent migraines:

A 17-year-old girl presented with a 7-year history of migraine... she was put on 50 mg topiramate at night... after 4 months the dose was further increased to 75 mg/day, as she was still having three to four headache days/month.

She then reported previously unknown intermittent nocturnal distortions of her body image only on those occasions when she did not directly fall asleep after taking topiramate. She described that either her head would grow bigger and the rest of the body would shrink, or that her hand resting comfortably on her chest would increase in size and become heavier, while the remaining arm would become smaller. The patient denied any hallucinatory character of these perceptions and insisted on their unpleasant but unreal nature...

After reduction of topiramate to 50 mg/day, the nocturnal phenomena ceased within 2 weeks. The neurological and psychiatric examination was normal... We agreed with the patient to a rechallenge and increased the daily dose to 75 mg/day. Two weeks later the distortions reappeared again and the patient decided to discontinue the drug.

Alice In Wonderland Syndrome - the feeling that parts of the body have changed in size or shape - is a symptom known to be associated with various brain disorders, although it's not clear why it happens. It can occur in migraines. However in this case, the patient had never experienced such symptoms before she started on an anti-migraine drug.

The authors conclude that while topiramate is an "excellent" drug, it can cause unusual side effects and they say that "The prescribing physician should be aware that it has the ability to induce various adverse effects and should encourage patients to report them - even if they initially appear awkward to them."

Jürgens TP, Ihle K, Stork JH, & May A (2011). "Alice in Wonderland syndrome" associated with topiramate for migraine prevention. Journal of neurology, neurosurgery, and psychiatry, 82 (2), 228-9 PMID: 20571045

Antidepressants In The UK

Antidepressant sales have been rising for many years in Western countries, as regular Neuroskeptic readers  will remember.

Most of the studies on antidepressant use come from the USA and the UK, although the pattern also seems to hold for other European countries. The rapid rise of antidepressants from niche drugs to mega-sellers is perhaps the single biggest change in the way medicine treats mental illness since the invention of psychiatric drugs.

But while a rise in sales has been observed in many countries, that doesn't mean the same causes were at work in every case. For example, in the USA, there is good evidence that more people have started taking antidepressants over the past 15 years.

In the UK, however, it's a bit more tricky. Antidepressant prescriptions have certainly risen. However, a large 2009 study revealed that, between 1993 and 2005, there was not any significant rise in people starting on antidepressants for depression. Rather, the rise in prescriptions was caused by patients getting more prescriptions each. The same number of users were using more antidepressants.

Now a new paper has looked at antidepressant use over much the same period (1995-2007), but using a different set of data. Pauline Lockhart and Bruce Guthrie looked at pharmacy records of drugs actually dispensed, not just prescribed, and their data only covers a specific region, Tayside in Scotland. The 2009 study was nationwide.

So what happened?

The new paper confirmed the 2009 survey's finding of a strong increase in the number of antidepressant prescriptions per patient.

However, unlike the old study, this one found an increase in the number of people who used antidepressants each year. It went up from 8% of the population in 1995, to 13% in 2007 - an extremely high figure, higher even than the USA.

In other words, more people took them, and they took more of them on average - adding up to a threefold increase in antidepressants actually sold. The increase was seen across men and women of all ages and social classes.

There's no good evidence of an increase in mental illness in Britain in this period, by the way.

But why did the 2009 paper report no change in antidepressant users, while this one did? It could be that the increase was localized to the Tayside area. Another possibility is that there was an increase nationwide, but it wasn't about people with depression.

The 2009 study only looked at people with a diagnosis of depression. Yet modern antidepressants are widely used for other things as well - like anxiety, insomnia, pain, premature ejaculation. Maybe this non-depression-based use of antidepressants is what's on the rise.

Lockhart, P. and Guthrie, B. (2011). Trends in primary care antidepressant prescribing 1995–2007 British Journal of General Practice