The insula – the brain’s cigarette addiction centre

By looking at smokers who have experienced brain damage, scientists have discovered a specific part of the brain that controls addiction to nicotine – the insula. If this area is damaged, a smoker completely loses the urge to smoke.

It is mid-February and we are six weeks into the new year. For most of us, our New Year’s resolutions have long been forgotten and our bad habits remain frustratingly habitual. The things that are bad for us often feel strongly compelling, be they high-fat foods, gambling or alcohol. And nowhere is the problem of addiction more widespread, serious and dangerous than the case of cigarette smoking.

Smoking is the biggest threat to the health of the developed world. Smoking is the leading preventable cause of death in the developed world, and every year it kills five times more people than drugs, suicide, murder, road accidents and HIV combined.

The dangers of smokers are both well-established and well-known, and surveys repeatedly show that the majority of smokers want to quit. But weaning oneself off a substance as addictive as nicotine is not easy.

People often view quitting smoking as a question of willpower – a problem of the mental world. But like all mental processes, addiction eventually boils down to physical matter, to our brains and the chemicals that reside within.

Neurological studies have found that smoking causes long-term changes to various parts of the brain including the dopamine system involved in feelings of pleasure, and the amygdala, involved in emotional responses.

Even cues associated with smoking such as the smell of smoke or the sight of a cigarette, can trigger distinctive patterns of activity in these areas, and are likely to contribute to the urges that smokers feel.

The insula is the brain's cigarette smoking addiction centreNow, Nasir Naqvi and colleagues from the University of Iowa have tracked down the neurons that control the addictive urges of smokers to a part of the brain called the insula.

Located deep inside the brain, the insula is involved in emotion. It collects and processes sensory information from the rest of the body, and translates them into conscious emotional experiences, such as cravings, hunger or pain. And in doing this, the insula could control cravings for cigarettes in response to smoking-related cues.

Naqvi found compelling evidence for this by looking at several smokers who had suffered brain damage, often because of a stroke. Many of these smokers successfully kicked their habits, but in those with damage to their insulas, something more unusual happened.

While most people find quitting a long and difficult process, those with insula damage quit easily and immediately. They never touched a cigarette again, and most importantly, never felt the urge to do so. They completely lost their addiction to smoking and were 22 times more likely to do so than smokers with other types of brain damage.

Naqvi believes that becoming addicted to nicotine causes the insula to change, making smoking just as necessary a bodily need as hunger or thirst. The insula processes information about sights, smells and feelings that relate to smoking and anticipates both the pleasurable effects of nicotine and the negative effects of nicotine withdrawal.

The end result is a strong and conscious urge to smoke, that disappears when the insula is damaged. As one patient said, his body just ‘forgot the urge to smoke’.

But can this knowledge be used to help smokers to quit? Directly changing the insula seems an unlikely step. The major worry is the direct treatments could have knock-on effects other aspects of a patient’s life.

However, Naqvi promisingly found that none of the patients with insula damage lost their urge to eat, or the pleasure of doing so. He suspects that urges like hunger, that are essential for our survival, are controlled by multiple brain networks that act as failsafes should any one fail.

Alternatively, the insula may only control bodily cravings that people develop over time, while other brain regions deal with more instinctive drives.

Nonetheless, the knowledge that the insula is the brain’s nicotine addiction centre could help in indirect ways. Scientists could look for drugs that target neurotransmitters active in the insula. And by monitoring brain activity in the insula, doctors could compare how effective some quitting methods are against others.

In the mean time, smokers should bear in mind that giving up can be difficult but millions of people have successfully done it. And in doing so, they have reduced their risk of cancer, heart disease and many other illnesses.

Reference: Naqvi, Rudrauf, Damasio & Bechara. 2006. Science 315 531-534.

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Of dogs and devils – the rise of contagious cancer

While human cancers cannot be transmitted from person to person, scientists have recently identified two types of contagious cancers in animals. In Tasmanian devils and domestic dogs, cancer cells have evolved into independent parasites, jumping from animal to animal like an infectious virus.

Cancer cells are, for all intents and purposes, immortal. Having broken free of the rules and strictures that govern other cells, they are free to grow and divide as they please. In a short space of time, a lone cancer cell can form a mass of identical clones – a tumour. Theoretically, cancers could exist indefinitely, but as always, there is a catch. Those that spread quickly and aggressively do so at the expense of their host, who usually ends up dying, taking the tumour with it.

But there is one way a cancer could escape this fate and carry on its selfish reproduction – by finding another host. It could become contagious.

In humans, cancers are definitely not contagious. You can’t catch cancer from someone who has it. At most, you can inherit a higher risk of developing cancer, because of faulty genes passed on from your parents. But recently, scientists have found some startling exceptions to this rule.

Even devils get cancerTasmanian devils are plagued by a contagious facial cancer

Earlier this year, Australian researchers Anne-Marie Pearse and Kate Swift found that a facial cancer plaguing the local Tasmanian devils (right) was caused by contagious cancers.

The condition, known as devil facial tumour disease, is spread when an infected devil bites another. The devils’ boisterous temperaments and their propensity for squabbling over carcasses mean that such bites are common.

Once infected, the animals develop grotesque tumours that stop them from feeding properly, and they usually die of starvation within six months. As a result, the cancer is decimating the already small population.

Going to the dogs

At University College London, Robin Weiss and Claudio Murgia have found another example of an infectious cancer – a disease called canine transmissible venereal tumour (CTVT), or Sticker’s sarcoma.

CTVT is transmitted through sex or close contact between infected dogs. It was first described 130 years ago by a German scientist called Novinski and its origins have been debated ever since. Some scientists suggested that it was caused by a virus, much like human papillomavirus (HPV) causes cervical cancer in humans today.

But in a study published this month, Weiss and Murgia have put these theories to rest. They and their colleagues analysed tumour samples from 40 dogs across five continents. All these samples shared identical and distinctive genetic markers that uninfected tissues from the same dogs did not.

The explanation was clear – these cancers had not developed in the usual way from the cells of the host animals. The cancer cells themselves were spreading from dog to dog.

Becoming contagious

CTVT evolved in an old Asian dog line, like the huskyThese rogue cells have become parasites in their own right, evolving from a single ancestor into a dynasty that has colonised the globe aboard canine vessels. How this process began is still a mystery, but Weiss’s analysis provides some hints as to where and when.

The original cancer cell must have developed in either a wolf or an old Asian dog lineage, such as a Husky (left). It evolved anywhere between 200 and 2500 years ago and may well have been around for even longer.

In fact, the CTVT cancer cell is very likely to be the oldest lineage of mammalian cells still in existence. The cells that Weiss is studying today are most probably direct clone descendants of the same cells that Novinski identified 130 years ago – genetically identical great-granddaughters of the original tumour.

To kill or not to kill

When that original cell gained independence, it became truly immortal, long outliving its original body and lasting for centuries. So far, we don’t know of any human cancer cells that have pulled off a similar trick. But Weiss feels that if they did, the best place to look for them would be in people with weaker immune systems including transplant patients and those with HIV.

His group have found evidence that evading the host’s immune defences is a key part of CTVT’s strategy for finding another dog to infect. The cells accomplish this by switching off some key immune system players – a group of genes collectively called dog leukocyte antigens (DLAs). They also secrete a protein called TGF-β1 that strongly blocks any immune responses.

But slipping past immune sentries would do the cells no good if the host died before infecting another dog. Infection requires sex, which may not happen for some time. So CTVT is a merciful parasite.

At the start of infection, it grows rapidly, but within 3-9 months, it regresses of its own accord. By never killing its carrier, the cells ensure that they can spread to as many new hosts as possible.

The Tasmanian devils are not so lucky. Their cancers are spread through biting, a more frequent event than sex, and as such, they can afford to be more aggressive. But the devils’ population is small and their genetic diversity is low. This combination may spell the end for both devils and cancer cells, unless some vaccine can be found.

 

Reference: Pearse & Swift. 2006. Nature 439: 549.
Murgia, Pritchard, Kim, Fassati & Weiss. 2006. Cell 126: 477-487.

 

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The insula – the brain’s cigarette addiction centre