A popular way to visualize the brain is to clench your fist and stick your thumb out and point it at the ground, as if you are a Roman emperor passing judgement on a defeated gladiator.* Your thumb is now the brain stem and the thumbnail the end of the spinal cord. Your fingers and hand represent the cortex, with the little finger the pre-frontal cortex. Now, do the same, but first squeeze a grape in the grip of your index finger. The grape contains the seat of our obsessions.
The relationship between the mind and the brain is one of the most mysterious in modern science. At their most basic, the thoughts that cause such mayhem in OCD are just electrical and chemical signals. But to say those physical elements alone define and confine the mind would be to say that the Mona Lisa is just some paint. There is a point at which this material pragmatism seems to give way to something greater, a frontier beyond which the sum is greater than the parts. In the brain, that is the moment at which the chemistry and electricity, the nuts and bolts, combine to form the mind, to give humans the sensation of consciousness.
Take the separation of brain and mind too far, and you hit the scientifically awkward idea of a soul – that the mind can and perhaps does exist in isolation of its physical basis. But, refuse to accept the notion of a mind−brain duality at all, and we struggle to explain the human experience. It’s a problem as much of philosophy and metaphysics as one of biology.
Biology has one clear advantage over philosophy and metaphysics: it can be measured. But it’s natural for scientists to measure either the mind or the brain. Even as modern science scoffs at the false premise of dualism, it inadvertently reinforces it. Neurologists work with brain tissue. Psychologists grapple with functions of the mind. Psychiatrists have a foot in both camps; they diagnose problems of the mind and treat them as problems of the brain, which is perhaps why psychiatry is sometimes regarded with suspicion by both sides.
Since the days of Esquirol and Freud, OCD has been viewed as a problem of the mind. Except, of course, OCD wasn’t viewed, not in the literal sense, it was conceived, modelled, reimagined. Modern technology, however, now allows the brain to be viewed in the literal sense. And that literal view, some neuroscientists believe, can show us the physical basis of OCD.
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Only a fool or a liar will tell you how the brain works. Even well into the twentieth century, while scientists in other fields could harness technology to split the atom and unravel the molecular structure of DNA, neuroscientists were largely restricted to two types of experiment. They could remove and look at a dead brain, or they could watch for the effects of brutal accidents and dreadful disease on a live brain. The nineteenth-century scientist Paul Broca famously unravelled how the brain processes language with the help of stroke victims who lost the ability to speak. By the 1960s, Canadian neurosurgeon Wilder Penfield made maps of cognitive function with electrical stimulation of the exposed brains of wide-awake epileptic patients he was poised to operate on, to see which part of their bodies activated – the patients might twitch their shoulder or report a memory.
Neuroscience became more high-tech in the 1970s with devices to analyse live brains – an alphabet soup of acronyms. First was the CAT scan, computed axial tomography – which combines X-ray images taken from various directions – and the PET scan, positron emission tomography, which maps radioactively labelled chemicals injected into the bloodstream. Most influential was MRI, magnetic resonance imaging, based on a tool that research chemists had long used to probe molecular structure. The chemists called the technique nuclear magnetic resonance, and one of the first things that doctors did when they started to point the machines at their patients was to drop the word ‘nuclear’ from the name. The patients preferred it that way.
MRI uses magnets and radio waves to detect blood. Particularly useful to neuroscientists is functional MRI, which takes lots of scans, one immediately after the other, and so shows how the blood moves. Blood flow in the brain means activity. If one part of the brain shows a greater demand for blood, or in the parlance of MRI studies, ‘lights up’, then neuroscientists believe it shows the ‘lit up’ part of the brain is more active. If the person whose brain is scanned is engaged in a task at the time, then neuroscientists can claim an association between the task and the region of the brain that lights up. In this way, functional MRI has been used to probe the brain regions associated with love, hate, racism, voting intention, response to adverts and chocolate, and why someone would prefer to drink Coke or Pepsi.
It’s a lot easier to look for these regions than to find them. Despite the way these studies are sometimes presented, most don’t prove that a certain part of the brain is responsible for a specific activity, thought or intention. The most they can say is that the scan images showed increased activity in that part of the brain at the time, but the pictures say little about cause and effect – whether the area that lit up drives the mental activity under investigation, or if it activates as a consequence of the activity.
There are other weaknesses with this kind of research. Most parts of the brain do different things at different times – the amygdala, for example, plays a role in both sexual arousal and terror – but an MRI scan cannot differentiate between passion and panic. It only tells us when a region is active, or more accurately, more active than normal. So what should we think when the amygdala lights up on an MRI scan when we are shown a picture of Cameron Diaz or Brad Pitt – that we are afraid of them? And then there is the dead fish problem.
In 2005, neuroscientists in California put an Atlantic salmon bought from a local fishmonger into their MRI machine. They showed the dead fish a series of photographs and scanned for its response. ‘The salmon’, the scientists later reported, ‘was asked to determine what emotion the individual in the photo must have been experiencing.’ It sounds silly, but it’s a common and necessary step to calibrate MRI machines and check all is good before human volunteers are introduced. The California scientists tried it with a pumpkin too, because one is about the same size and weight as a human head.
The test samples – animal or vegetable – of course are not supposed to yield results. Yet, when the neuroscientists looked at the output of the scans of the salmon, they found a curious thing. The results appeared to show the salmon thinking. Shown the photographs, parts of its fishy brain had lit up. The rogue signal was down to a technical and statistical glitch, random noise in the way the scanner’s computer software processed the signals. The scientists knew this, but rather than throw the scans away, they decided to publish them to alert others to the problem. MRI studies performed without certain statistical precautions, they said, could give out false positive results.
All of this is not meant to undermine the power and usefulness of MRI scans in research, just to show that the results are often not as clear-cut as they might appear. Neuroscientists get cross when journalists ignore the caveats and exaggerate the potential of brain scans to determine how we think and behave, but neuroscientists do it themselves. Some sell MRI scans they claim can help companies market their products, or detect liars.
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It’s pretty grim inside an MRI machine. In 2003, as science correspondent for The Guardian, I had my brain scanned by MRI as part of a research study at University College London into the way we process information. The scientists were interested in how people can find themselves unable to pronounce certain words. It was nothing to do with my OCD. I wanted to write for the newspaper about how it felt to have a scan, and to take part was the only way they would let me through the doors. Time on those machines is too precious to waste on a tourist.
I remember most the sense of entombment; the metal cage to hold my head still and the magnet itself seemed to brush the end of my nose. And the noise – like I was trapped next to someone who typed a chapter of this book on an old-fashioned clickety-clack typewriter and blew an air horn each time they finished a sentence. Given that experience, I have great admiration for the people with OCD who have agreed to venture into these machines in the name of science, and then allowed scientists to poke their obsessions with a sharp stick.
Strapped inside MRI tubes, people with obsessive fears of contamination have had their hands sprayed with (harmless) water they are told contains drugs. Women with a compulsive need for symmetry have had nail varnish unevenly removed from their fingers. In other experiments, people with OCD have been asked to identify the words that set them off the most – ‘scissors’ say, for a mother who feared she would stab her child – and then been forced to listen as the scientists repeat the words back to them over and over again through the loudspeakers of the MRI scanner. All the time, the machines record their torment in pixels.
Hundreds of OCD patients have been MRI scanned over the last decade or so, and had their brains compared to those of normal people, schizophrenics and hoarders. They have been scanned before and after treatment, and while they rest or wrestle with deliberately planted intrusive thoughts. Again and again a consistent picture of OCD emerges – unusual activity in and around a brain region called the basal ganglia.
The basal ganglia is the grape held in your crooked index finger. It is a tightly packed and knotty cluster of tissue at the base of the forebrain. Like most of the brain, exactly what the basal ganglia does, and how, remains largely unknown. But the basal ganglia does seem to play a role in ritual, compulsion and OCD. This was first shown almost a century ago with the work of an Austrian medic called Constantin von Economo, the original flying doctor.
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Von Economo married a princess but he had two passions: psychiatric medicine and aviation. He piloted one of the first fighter aircraft above the Italian front of the First World War in 1916, before he moved to a hospital in Vienna to care for soldiers with head injuries. It was there he saw his first cases of a bizarre disease that would go on to make him famous. Between 1915 and 1926, nearly a million people across the world died in a largely forgotten epidemic. Millions more were left as living statues in a catatonic state, unable to move or speak. Whatever infectious agent caused the disease (and it has yet to be pinned down with any certainty) seemed to attack and inflame the brain, and specifically, post-mortems of victims revealed, the region around the basal ganglia.
Von Economo reported how some patients with the condition – now known formally as encephalitis lethargica and less formally as von Economo’s disease or sleepy sickness – reported a strange sensation. They felt compelled to carry out odd movements. In his write-up of 1920, he said: ‘These patients do not say I have a twitch in my hand, but rather as a rule, I have got to move my hand that way.’* He saw a range of tic-like behaviours too. His patients would cluck, hiss and yell. These disturbances, he said ‘were reminiscent of compulsive movements and compulsive actions, with frequently ensuing utterances of speech and trends of thought of a compulsive character’.
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Our brains evolved from the inside out. The clever stuff at the edge, the cortex with its ability to reason, is new in evolutionary terms. The deepest bits of the brain are the oldest. They evolved in some ancestor long before we did and we share these brain units with all the subsequent species that developed later. The basal ganglia is among the deepest and oldest bits of the brain. Birds have a basal ganglia, and so do ugly eels called lampreys, which have been around for more than half a billion years.
Half a billion years is a long time to get something right, and the basal ganglia has its act perfect. It holds set programmes for repetitive, automatic and ritualistic behaviours, any of which a creature can press into service at a moment’s notice. A quick response – run! − is usually critical to such situations, so the higher parts of our brain – the middle management, which tend to mull on the pros and cons and just slow everything down – are sidelined. That makes the behaviour directed by the basal ganglia easy to activate and difficult to turn off. When people say that a pattern of behaviour is hardwired into the brain, it’s often something that is stored in the basal ganglia.
In that context, it makes sense that OCD could be a problem with the basal ganglia. OCD could be what happens when these programmes go haywire; when they can’t be turned off or when they activate at an inappropriate time. That would explain the quasi-instinctive drive in OCD to perform compulsive behaviour. Time and again, scientists see how damage to the basal ganglia can cause OCD-like symptoms. Injuries and diseases such as rheumatic fever, Huntingdon’s and Parkinson’s can bring on obsessions and compulsions, and so can something as benign as a wasp sting.
Mr V was French. He was 41 in 1968, when he was stung and suffered an extreme reaction. He had immediate convulsions and fell into a coma for twenty-four hours. He recovered, but scans showed he had suffered damage to the basal ganglia. Two years after he was stung, life began to get strange for Mr V. He started to feel an urge to count inside his head, usually to twelve or a multiple of twelve, though he performed more difficult calculations. Sometimes he wagged his finger as he did so; other times he was compelled to switch a light on and off for an hour or more. His psychiatrist noted: ‘When asked about his behaviour he answered that he had to count … that he could not stop … that it was stronger than him.’ Once Mr V was found on his knees as he pushed a stone along the ground with his hands – he simply had to push it, he explained.
Then there was Mr E, a 42-year-old Dutchman who suffered a heart attack in 1992, which choked off the oxygen to the base of his brain around the basal ganglia. He survived but started to compulsively whistle, for up to eight hours a day, always the same tune. He wanted to stop, but when he did he felt annoyed and anxious. After listening to him for almost sixteen years, Mrs E sent her husband for treatment.
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Rituals stored in the basal ganglia have been used to explain some of the most puzzling cases of OCD: children who go to bed fine and wake up the next morning with severe obsessions and compulsions. It’s a controversial area, but if the scientists and doctors who have investigated these cases are correct then it presents a startling conclusion – OCD can be passed from person to person as easily as a sore throat.
In early 1991, a 10-year-old boy was brought to the US National Institute of Mental Health in Maryland after he seemed to develop OCD overnight. He woke one day with severe obsessive concerns about Aids and other germs, as well as compulsions to clean and hoard. Within two days the boy could not face school, or anything else. He had developed a spitting tic alongside the obsessive thoughts, and jerky, abrupt movements. But the night before his symptoms arrived, his mother said, he had been completely healthy. Well, almost.
She was a medical technologist and she pointed out to the NIMH doctors that, just a couple of weeks before, the boy had been diagnosed with a throat infection; specifically, he had pharyngitis caused by streptococcal bacteria. What’s more, the boy’s older brother suffered from a tic disorder that waxed and waned, and his most recent bad days, the woman realized, had come after he had been ill with the same throat infection as his younger brother. ‘There had to be a connection,’ she said.
When the scientists tested the younger boy’s blood, they found that levels of antibodies – a sign of the severity of the strep infection – tracked his OCD symptoms. As the antibodies dropped, so his obsessions and compulsions weakened. When his antibodies spiked to indicate renewed strep infection, his OCD symptoms became worse.
The psychiatrists started to track down other similar cases. They advertised nationally and at big medical conferences. Reports of cases started to trickle in, slowly at first, just one or two each month, but as word spread the team would investigate four or five a week. They kept the idea of a possible link to streptococcus to themselves, until they had fifty children who showed a similar pattern: a strep throat infection closely followed by a surge in obsessive-compulsive symptoms or tics. By 1998, the psychiatrists had enough to go public. They published a report in the American Journal of Psychiatry that described the fifty cases, and coined a term for what was wrong with them: ‘Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections’; ‘Pandas’ for short.
The important word in that long title is ‘autoimmune’. Scientists think Pandas is down to the strep infection because it makes the body release antibodies against the foreign bacteria that in some people go on to mistakenly attack their own brain cells, probably in the basal ganglia. The exact mechanism, and its contribution to the OCD symptoms in the children, remains unclear and somewhat controversial, given that the idea suggests that common bacteria could provoke infectious outbreaks of OCD and perhaps other psychiatric disorders too.
The 1998 academic paper on Pandas caused a sensation. Patients and anxious parents of children with mysterious obsessions were handed an easy-to-understand explanation, and a possible cure: the scientists successfully treated some of the children by sucking out and replacing the plasma from their blood, so ridding them of the anti-brain antibodies. But the Pandas hypothesis left too many doctors and medical experts sceptical. Disagreement was bitter and polarized the field of child psychiatry for years. It still does. Some said the NIMH team was plain wrong and insisted they scrap the whole idea. A flurry of academic papers attacked and offered support to both camps. The biggest losers were acutely ill children and their parents, who did not know which experts to believe. The research and the controversy continue.
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It is not just studies of humans that link damage to the basal ganglia to ritualized and compulsive actions. Experiments with green anoles, a lizard sometimes called the American chameleon, have highlighted the crucial role of the basal ganglia in ritual in reptiles. Male anoles square off with each other for territory with a series of displays and repetitive actions; chiefly they strut and push themselves up and down on their front legs. We do this when we fight over territory too; look how a boxer behaves in the ring when he paces around a downed opponent.
In 2003, brain scientists at the University of Florida showed that anole territorial display routines associate with increased activity in distinct parts of their basal ganglia. The basal ganglia of the reptiles, they observed, seemed to activate to release the behaviour in the appropriate context. And while one part of the basal ganglia seemed to control dominant behaviour – the squats and struts – a separate part appeared to associate with a separate routine of submissive behaviour shown by the weaker anoles, which squeeze flat to the floor. The results of the Florida experiments supported other research on anoles in the 1970s, which showed that damage to their basal ganglia appeared to switch off control of these territorial rituals, but leave other behaviours intact.
We should be careful not to draw too many comparisons between lizard and human brains, but the anole study does raise an important question. We saw earlier how a capacity, or instinct, for ritual seems hardwired into the human brain, and how the contents of common human rituals are similar to the themes of OCD. We know from the work of van Economo – on sleepy sickness – and others that damage to the basal ganglia can force some people to perform involuntary and repetitive – ritualistic – movements. And now we see that the basal ganglia relates to ritualistic behaviour, fixed action patterns, in other species too. Is OCD what happens when a fault in the brain leads the basal ganglia to deploy ritual at the wrong time, in an inappropriate context?
Some neuroscientists think that it is. Those who study the basal ganglia, and the brain tissue that surrounds and interacts with it, have developed a model of how the OCD-brain might go wrong. Like all models of the brain, it’s massively simplistic to a neuroscientist and maddeningly complex to almost everybody else. It goes something like this:
The basal ganglia works closely with the brain’s orbitofrontal cortex (OFC), which sits just behind the eyebrows. The OFC processes sensory information from the eyes and elsewhere and passes signals to a region of the basal ganglia called the striatum. From there, the message goes to a separate brain structure called the thalamus, which controls motor systems. In response, the thalamus passes signals back to the OFC.
This happens in a non-stop loop, and it might help us respond to external threats. Told about events in the world by the OFC, the striatum and thalamus select the appropriate motor response, the right programme, and tell the OFC to make it happen. I see a lion. Yikes. Run away. When the circumstances change, the danger passes, the OFC signals the all-clear and the thalamus stands down.
What’s important for the model of OCD is that the OFC can pass these signals to the thalamus in two different ways. The signal to switch on passes through the striatum, and is called direct. The stand-down is indirect; it is sent to the thalamus through the striatum and then via other parts of the basal ganglia.
In this model of obsessive behaviour, OCD occurs when the thalamus runs out of control and sends inappropriate instructions back to the OFC. The instructions and the behaviour no longer suit the circumstance, and this puts the OFC in a bind. Information from the senses, updates from the outside world, indicates everything is fine. Yet signals from the thalamus suggest not. The consequent motor behaviour, the ritual, continues even while the senses tell the OFC that there is no danger, and no need for the behaviour. That’s the paradox of OCD right there. The water shrew jumps the removed stone. The clean hands are washed. I check the fresh paper towel for blood.
That’s a stripped-down version of the, itself simplified, model of the OCD brain. But here’s an even more simplified one: The direct route that excites the thalamus is an accelerator pedal. The indirect route is a brake. In normal function, the accelerator and brake work together to control speed. In OCD, the brake fails.
From this model of the way an obsessive brain works it’s clear why a common response from others − that someone with OCD just should not be so ridiculous − does not and will never work. Don’t you think we might have tried that? You merely tell us what we can see with our own eyes, that our hands are clean, that the towel is free of blood. We see and yet we can’t stop. A driver who points out that a speeding car is going too fast does not slow it down. We need to fix the brake.
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One way to try to fix the brake is to use drugs. The Leeds psychiatrist who gave me the rubber band had also convinced me to take Prozac. It was still a wonder drug back then, and Elizabeth Wurtzel’s bestselling account of her depression, Prozac Nation, had made those little green and cream pills almost a fashion accessory. Prozac didn’t help me much. I wasn’t depressed, just unhappy. I told the psychiatrist that I didn’t feel any better. He offered me an alternative drug. I don’t remember what it was called, just that he said it would turn me into a happy zombie. I wasn’t sure whether that was an endorsement or a warning. I still don’t know. I turned it down.
Some fifteen years later, the first thing that the psychiatrists I went to see at the specialist OCD unit did was to put me back on drugs. Not Prozac, but something similar. This time, the chance they would turn me into a happy zombie wasn’t discussed.