Nothing to fear but asphyxiation?

Think of the scariest movie you’ve ever seen (for me it’s The Ring). How did you feel when the group of teenagers popped in that video, or the girl climbed out of the TV? When the phone rang and the killer was on the other end? Or when the babysitter was home alone and a shadow passed across the screen? Even though you know it’s just a movie, you still experience that knot in your stomach, pounding heart, sweaty palms and building anxiety that comes with a real stressful or frightening encounter.

These visceral, gut reactions are physiological fear responses our brain and body automatically initiate when in a perceived threatening situation. These experiences are thought to be subserved by the amygdala, an old and deeply rooted part of the brain that is essential in processing emotion, particularly fear. This is partly through connections the amygdala has to the sympathetic nervous system, which controls our basic ‘fight-or-flight’ reactions to danger–preparing us to either stand and fight or flee as fast as we can.

However, some people don’t experience this sensation of fear. Individuals who have undergone damage to the amygdala, either through a stroke or head injury, or from the rare genetic condition Urbach-Wiethe disease, report an inability to feel this emotion. One famous example of this absence is in the patient SM, who reported no feelings of fear when faced with snakes, spiders, horror films, or haunted houses. Even after being threatened with a real life knife attack, SM had no experience of fear sensations. However, there was one thing that was able to instill in her these feelings of anxiety and terror–asphyxiation.

Researchers at the University of Iowa have been studying SM over the last decade to try to find something, anything, that would scare her. After exhausting all the typical psychological stressors to no avail, they decided to try a physical stressor that can elicit the same reactions. Published last month in Nature Neuroscience, the researchers had SM and two other people with similar amygdala lesions inhale carbon dioxide for several seconds, cutting off their oxygen flow and essentially suffocating them. This experience typically causes panic attacks and fear responses in people, including extreme distress, pounding heart, and an immediate desire to escape the situation. All three participants–none of whom had previously experienced fear–had these exact same panicky reactions to the CO2. In fact, when compared with normal healthy individuals, the amygdala patients had significantly greater fear responses, both physically and psychologically, than those with intact amygdalas.

So what’s behind this phenomenon? The researchers believe that these panic reactions are distinct from learned fear responses, such as phobias of snakes or spiders. Instead, there appears to be a unique pathway involved in panic from inherent physiological stressors that passes through the amygdala. In fact, this response may be inhibited in the amygdala, as the control participants experienced less dramatic reactions to the carbon dioxide than the amygdala patients. However, learned fears or perceived outside dangers rely on the amygdala to integrate these scary sensory situations—such as seeing someone with a gun—as a threat. Thus, those with amygdala lesions do not learn and incorporate the proper fear associations with these triggers, but they do still have the capacity to experience these dramatic panic responses to internal physical stressors.

So the next time you’re watching a scary movie, you could try reminding yourself that it’s not real, or you could try hyperventilating—it may actually reduce your panic (assuming your amygdala is still intact).*

Boo!

*I do not actually recommend this as a fear-coping mechanism.

Billions of dollars to map billions of neurons

A lot of money is being spent right now to ‘map the human brain’. In the last month, both the European Commission and U.S. president Barack Obama have pledged to give billions of dollars to fund two separate projects geared towards creating a working model of the human brain, all 100 billion neurons and 100,000 billion synapses.

The first, the Human Brain Project, is being spearheaded by Prof Henry Markram of École Polytechnique Fédérale de Lausanne. Together, with collaborators from 86 other European institutions, they aim to simulate the workings of the human brain using a giant super computer.

To achieve this, they will work to compile information about the activity of tons of individual neurons and neuronal circuits throughout the brain in a massive database. They then hope to integrate the biological actions of these neurons to create theoretical maps of different subsystems, and eventually, through the magic of computer simulation, a working model of the entire brain.

Similarly, the Brain Activity Map Project, or BAM! (exclamation added because it’s exciting), is a proposed initiative that would be organized through the United States’ National Institutes of Health and carried out in a number of universities and research institutes throughout the U.S. BAM will attempt to create a functional model of the brain – a ‘connectome’ – mapping its billions of neuronal connections and firing patterns. This would enable scientists to create both a ‘static’ and ‘active’ model of the brain, mapping the physical location and connections of these neurons, as well as how they work and fire together between and within different regions. At the moment, we have small snap-shots into some of these circuits but on only a fraction of the scale of the entire brain. This process would first be done on much smaller models, such as a fruit fly and a mouse, before working up to the complexities of a human brain version.

BAM proposes to create this model by measuring the activity of every single neuron in a circuit. At the moment, this is done using deep brain techniques, a highly invasive process that involves opening up the skull to implant electrodes onto individual cells to read and record their outputs. Understandably, this is only done in patients already undergoing brain surgery, and is a slow and expensive process. Thus, the first task of BAM would be to develop better techniques to acquire this information. Research into this field is already underway, and exciting proposals have included nanoparticles and lasers that could measure electrical outputs from these cells less invasively, or even using DNA to map neural connections.

Neither project has directly acknowledged the other, but it is thought that the recent announcement of the U.S. proposal is a response to the initial European scheme launched earlier this year. And while there are distinct differences between the two initiatives in how they will acquire and store the raw information, as well as how they plan to build their subsequent models, the two projects overlap significantly. Both have the potential to better illuminate how exactly the brain works, and each ultimately hopes to provide us with a clearer picture of not only normal brain functioning, but also what happens when these processes are disrupted. Scientists and doctors could then use computer models to simulate dysfunction involved in neurological or psychiatric disorders, such as Alzheimer’s or schizophrenia. This would also open up possibilities for investigating better treatment options, as well as drastically cutting down on the expense and risk currently involved in clinical drug trials for psychiatric and neurological disorders.

However, there is a long list of obstacles these projects must overcome before we get too excited, not the least of which are the 100,000,000,000,000 connections that need to be measured and modeled. That’s over one million times as many neurons as there were genes to map in the Human Genome Project, the closest approximation to the current endeavors. Additionally, while there was a clear end to the human genome, the ambition of making a human connectome is both much larger and much less well-defined. Indeed, neither proposal yet has a definitive end-goal, and no one is clear on what the final product will look like.

For the Human Brain Project, the collaboration of over 80 different labs across Europe will also be a significant challenge. By collaborating rather than competing, the capacity for productivity and innovation in this and future projects is far higher. However, it will be extremely difficult to manage differences in laboratory methods and communication, not to mention egos, between these institutions.

Another major concern for the American proposal is funding. With the financial crisis, fiscal cliff and federal sequestration of recent months, the U.S. economy (and Congress) do not have a very good track record at the moment. And it is hard to believe they are going to approve a multi-billion dollar project when they cannot even agree to continue funding for health care, education and military spending. Private companies including Google and Microsoft, as well as charities such as the Howard Hughes Medical Institute and Allen Institute for Brain Science have signed on to the project, but the bulk of funding will still have to be provided by government institutions.

In his State of the Union address, President Obama alluded to the Brain Activity Map Project, and tried to head-off the inevitable financial protests to it by invoking the Human Genome Project, which cost $2.7 billion to complete but has reportedly produced a return of $140 to every dollar spent. This was manifested through pharmaceutical and biotechnology developments, as well as subsequent start-up companies. This turnover has the potential to grow even further through future reductions in health care spending from medical developments, and the hope is that BAM will produce similar high returns. However, the question remains as to whether this investment could be better spent elsewhere, such as improving the medical system, research for drug treatment developments, or health education and prevention programs. Some in the scientific community are also worried that already limited funding to other fields of research will be slashed in order to subsidize the project.

Despite these concerns, it is undeniable that if these programs were to succeed they would be spectacular achievements in scientific research, not unakin to the discovery of the Higgs Boson or even the first space expeditions of the 1960s. Many believe that the human brain is the final frontier for medical research, and it will remain to be seen whether these brain-mapping projects will enable us to finally understand the wild and intricate workings of our own minds.

(Originally posted on King’s Review)

(And an updated version has been published on The Atlantic)