Sunday, August 5, 2012

More on Carry the One

I apologize for the hiatus in blog posts, but The Gray Area is back with another shameless plug for Carry the One Radio! This month, we talk to Lisa Stowers, who is an Assistant Professor at the Scripps Research Institute in San Diego. Her lab uses mice to study how chemical signals known as pheromones activate particular groups of neurons, and how this activity produces instinctive behaviors of fear, attraction, and aggression. By studying this system, Dr. Stowers hopes to shed new light on how the brain processes senses and generates behavior. Check it out at the link below!

http://www.carrytheoneradio.com/2012/08/01/lisa-stowers/

Friday, June 29, 2012

Carry the One Radio


I recently joined a UCSF Neuroscience initiative called Carry the One Radio, a series of 10 minute long interviews with scientists from various backgrounds and institutions. Started two years ago by fellow graduate student Sama Ahmed, Carry the One aims to get high school and college students interested in science through relaying a scientist's story about he or she got interested in science, and "the one" project that creates the fire in their belly. I'm co-hosting the show with Sama, and we're now posting episodes on the web every month. This month, Sama talks to Cori Bargmann, a professor at the Rockefeller University and investigator at the Howard Hughes Medical Institute. Dr.Bargmann studies the neuronal circuitry underyling animal behavior using the humble worm, C.elegans, as a model system. She has also been featured on the Charlie Rose Brain Series and The New York Times. 

The website is still under construction, but please check out the latest episode here!:


Please also check out the Facebook page at: http://www.facebook.com/carrytheone

Tuesday, June 12, 2012

Bacteria that influences happiness




In a recent study from the Alimentary Pharmabiotic Center, scientists showed that the bacteria that live in our gut during development can affect adult brain function and emotional states. Specifically, these little microbes are able to affect levels of the chemical serotonin in our brains. Serotonin, a neurotransmitter, plays an important role in the regulation of mood and emotion. Research has found that serotonin levels are altered during stress, anxiety and depression and many antidepressant drugs are designed to target this neurotransmitter. 

In this study, the scientists were able to demonstrate that mice that were raised in a germ-free environment and therefore had very little gut flora or microbiota during early life. This early absence of gut bacteria significantly elevated concentrations of serotonin in the adult brain, specifically in the hippocampus, a neuronal structure that has important roles in episodic and emotional memory. Most importantly, these germ-free mice with increased levels of serotonin during development displayed less anxious behavior when tested as adults, as compared to mice that were raised in normal conditions and had normal gut flora. Interestingly, this effect seemed to be sex-specific; male mice with reduced gut flora and subsequent elevated levels of hippocampal serotonin showed a much more marked effect than female mice. 

Intriguingly, the neurochemical effect seems to be irreversible. When the scientists recolonized the young germ-free mice in a normal environment that would allow the restoration of intestinal microbiota, they found that hippocampal serotonin levels continued to be elevated in these mice. Paradoxically, the restoration of the gut flora was able to reverse the behavioral effect, such that the germ-free mice no longer showed reduced anxiety compared to the control animals. 
This study follows  earlier work from several groups, showing that a microbiome-gut-brain axis exists and that it is essential for maintaining normal health which can affect brain and behaviour. The research was carried out by Dr Gerard Clarke, Professor Fergus Shanahan, Professor Ted Dinan and Professor John F Cryan and colleagues at the Alimentary Pharmabiotic Centre in UCC.
“As a neuroscientist these findings are fascinating as they highlight the important role that gut bacteria play in the bidirectional communication between the gut and the brain, and opens up the intriguing opportunity of developing unique microbial-based strategies for treatment for brain disorders”, said Professor John F Cryan, senior author on the publication and Head of the Department of Anatomy & Neuroscience at UCC.
The results from this study have many implications, as it shows that manipulating the natural microbiota that exist in our body, whether it be through infection, antibiotics or diet, can profoundly affect other bodily functions, including brain function and behavior. “We’re really excited by these findings” said lead author Dr Gerard Clarke. “Although we always believed that the microbiota was essential for our general health, our results also highlight how important our tiny friends are for our mental wellbeing.”

Thursday, June 7, 2012

Vaccine trial for Alzheimer's Disease


A healthy brain slice is shown next to a very damaged brain slice.


Alzheimer’s disease (AD) is a complex neurological disease that is the most common form of dementia, or loss of brain function. Individuals suffering from Alzheimer's display impairments in learning and memory, as well as changes in personality and mood. According to the World Health Organisation, dementia is currently the fastest growing global health epidemic. AD is most often diagnosed in people that are older than 65, although there are a few rare cases of early-onset of the disease. The prevailing hypothesis about the cause of AD involves the protein amyloid precursor protein (APP), which is found in the outer membrane of nerve cells and that, instead of being broken down, forms a harmful substance called beta-amyloid. This noxious version of the protein can accumulate as plaques and kill brain cells. Needless to say, the disease is devastating to many all over the world, and a huge cost for society. 

Researchers around the world have been investigating genetic and environmental factors that may put individuals at risk, as well as how beta-amyloid can cause neurodegeneration. Moreover, other theories besides the APP theory exist to explain the cause of AD. While there is currently no cure for the disease, scientists have been trying different approaches to treat the disease; one of them has been vaccines. The first vaccination study conducted almost a decade ago, showed some efficiency in clearing up beta-amyloid plaques, but did not help with dementia at all. Furthermore, the vaccine caused too many adverse side effects, including an autoimmune reaction, and was soon abandoned. 

A recent study from researchers at the Karolinska Institutet in Stockholm points to the first successful attempt at a vaccine treatment for AD. The new treatment is an active vaccine and the idea is to use a type of vaccine designed to trigger the body's immune defence against beta-amyloid. In this set of clinical trials, the vaccine was modified such that it only affects the harmful form of APP, that is beta-amyloid. The investigators observed that 80 per cent of the participating patients developed protective antibodies against beta-amyloid, without suffering any side effects that were observed in previous trials of this study. The researchers believe that the treatnent, called CAD106 vaccine, could be an effective and tolerable way to treat patients with mild to moderade AD. More large-scale clinical trials have to be conducted to further determine the efficacy of CAD106, but the discovery is very encouraging for AD patients and their families.





Thursday, May 31, 2012

What's the buzz: Microglia


There is growing evidence demonstrating that immune cells and signaling molecules serve as carriers in an intricate network of bidirectional communication between the immune system and the brain. This occurs via peripheral immune pathways as well as through interactions between neurons and the resident immune cells in the brain known as microglia. It turns out that microglia are involved in a lot more than just protecting the brain from infections; it has been shown that microglia are capable of influencing the growth and activity of neighbouring neurons. This affects the plastic nature of neuronal networks, and thus microglia are able to affect cognitive and social behaviors. 

In a recent study from Jonathan Kipnis' lab at University of Virginia, School of Medicine, researchers showed that restoring microglial function in a mouse model of Rett Syndrome, a severe autism-spectrum disorder that affects 1 in 10,000-20,000 girls worldwide. The disease is caused by a mutation in the gene MECP2, which is carried on the X chromosome. Since males carry only one copy of the X chromosome, males with the mutation die very soon after being born, whereas girls with one copy of the mutation develop the disease. 

Signs of the disease typically set in between 6 and 18 months of age. Affected females often have trouble developing speech, walking and putting on weight. Many patients also develop breathing problems and apnoeas. They also display repeated behaviors such as hand washing and wringing. 

MECP2 is an important epigenetic regulator, meaning it is able to regulate the expression of genes by recruiting enzymes that modify the structure of chromatin network. How exactly a mutation in the gene is sufficient to cause Rett Syndrome is still a mystery, but researchers have been able to detect its expression widely in the brain. In fact, rescuing MECP2 expression in neurons in Rett Syndrome mice reverses some of the disease phenotypes. More recently however, researchers lie Kipnis began to look for MECP2 function in other cell types in the brain, like microglia. It is now known that microglia indeed do express MECP2, so Kipnis and colleagues began to ask whether restoring MECP2 function in microglia in a Rett Syndrome mouse would improve the symptoms. 

The researchers accomplished this by essentially replacing the immune system of the mutant mouse lacking MECP2. They first had to kill of the existing immune system using radiation, and then used a bone marrow transplant from a healthy wildtype mouse to the mutant mouse; thus the new microglia in the Rett Syndrome mouse now have MECP2 in them. In an unexpected result, the restoration of MECP2 function in microglia resulted in drastic improvements in the mutant mice; they began to breathe and walk better, and even gain weight more easily compared to the non-transplanted mutant mice. 

These findings, while exciting, are very preliminary in terms of bone marrow transplants being used in human Rett Syndrome patients.  At this point, Kipnis speculates that their results could be explained by the fact that microglia in mutant Rett Syndrome animals are unable to clear up and protect the neurons from cellular waste build up and potential pathogens, and thus neuronal function is impaired. More research is required to identify the mechanism of microglia function in Rett Syndrome. However, the study does provide a novel role for microglia in the brain, and a new target for treatment of Rett Syndrome.

Tuesday, May 22, 2012

Remember to remember


Joshua Foer: Feats of memory anyone can do

As someone who is studying neuroscience, I come across the topic of memory very often. Finding out how memories are formed and stored is after all a major impetus that drives research in neuroscience. This Ted Talk by Josh Foer, a science journalist who writes for a number of publications including National Geographic and The New York Times, gives an interesting perspective on how we make memories. In 2005, Josh went to cover the U.S Memory Championship, a competition of mental sports in which participants have to memorize as much information as possible within a given amount of time. There he met many extraordinary people with extraordinary memories, or so he thought, until he began training with some of the participants and realized the strategies they used basically came down to creating a visual and spatial framework to place memories. Called a 'memory palace', this context within your mind's eye allows you to extract memories more easily. But Josh points out that, this strategy is in fact not novel; before the advent of technological tools, strategies like the 'memory palace' was an effective way to memorize speeches and even academic material for tests. We've just forgotten how to use it because we have other places to store the memory palace besides our brain: our computers, our smartphones, and for the really old school people, photo albums. In other words, we've forgotten how to make memories, and therefore how to remember. What really drives the point home is that, after a year of training with the top European memorizer, Josh entered in the national Memory Championship in New York- and won. Because he remembered to remember. 

Check the talk out at:

http://www.ted.com/talks/joshua_foer_feats_of_memory_anyone_can_do.html

Thursday, May 17, 2012

Hmmm.....


[Suspicion] 
After a two week hiatus, The Gray Area is back with a post describing a study that investigated how the feeling of suspicion is created in our brains. One of my first posts was about researchers have been trying to study how person's brain activity is altered when he/she is telling a lie vs. telling a truth, that is, the neural basis of deception. This current study attempts to describe how brain activity may change when we think someone might be telling a lie, that is, the neural basis for the feeling of suspicion. 

Using the same technique of fMRI, these scientists at Virginia Tech Carilion Research have identified two regions that may be involved in creating the feeling of suspicion- the amygdala and parahippocampal gyrus. The amygdala is involved in processing fear and emotional memories, while the parahippocampal gyrus plays a central role in declarative memory. The task was this: There were 76 pairs of participants, each with a buyer and a seller. Each pair competed in 60 rounds of a bargaining game, while having their brains scanned by the fMRI machine. At the start of each round, the buyer was told the value of a hypothetical widget, and then they were asked to suggest a price to the seller. The seller was then asked to set a selling price; if the seller's price fellow below the stipulated widget, the trade would go through, with the seller receiving the selling price and the buyer receiving any difference between the selling price and the stipulated value. However, if the seller's value exceeded the stipulated price, the trade would not go through, and neither the buyer or seller would receive cash. 

The researchers found that the buyers fell into three categories: 42% were incrementalists, meaning they were actually quite honest about the stipulated value; 37% were conservatives, meaning they tended to withhold information; 21% were strategists, who intentionally deceived the sellers by pretending to be incrementalists (making higher value suggestions when the stipulated value was low, and vice versa). The sellers did have the monetary incentive to correctly predict the stipulated value, but they had no feedback about the buyer's accuracy. The investigators found that the more uncertain the seller was about the buyer's suggested price, the more active his or her amygdala and parahippocampal gyrus became. The activation of the amygdala was not very surprising to the authors, as suspicion is an emotional state. But Read Montague, the lead investigator 
and director of the Human Neuroimaging Laboratory and the Computational Psychiatry Unit at the Virginia Tech Carilion Research Institute, says the activation of the parahippocampal gyrus could be "an inborn lie detector" or a reminder of an untrustworthy person. 

While this study is not a great replication of real life situations in which we may encounter suspicious behaviors or people, it may be important in understanding the neurological basis of increased suspicion and distrust in neuropsychiatric disorders such as anxiety disorders and paranoia. 

Monday, April 30, 2012

Digital High

Having just watched 21 Jump Street a week ago, I had a strong sense of déjà vu when I read this story- a new drug that's been circulating among high school students and has got them raving about it on YouTube. This is no ordinary drug though; it's music. Called i-Doser, the "drug" is actually a new online service that sells musical tracks for prices between $1-$5 per track, with the promise that you will get high or experience the euphoria of ecstasy, marijuana or cocaine. Appropriately then, each track in their library is named after a particular drug, both legal and illegal. The site prides itself on providing a legal alternative to the illicit drugs that pervade society today. So the big question is...how does this thing work??

With the tag-line of 'Binaural Brainwave Simulated Experiences', the underlying principle behind the product is using binaural beats delivered through stereo headphones to create an otherworldly experience.  Binaural beats, is a phenomenon that occurs when two different tones are played in opposite ears, and a low-frequency beating sensation is created in the brain. The beating sensation is the effect of the conflicting electrical signals in your brain’s wiring. The binaural beat effect was discovered by Heinrich Wilhelm Dove, a Prussian physicist and meteorologist, in 1839. His discovery only earned greater public awareness in the late 20th century, when claims arose that binaural beats could help induce relaxation, meditation, creativity and other desirable mental states. While there have been very few controlled experiments to study this effect, the hypothesis is that bineural beats can induce changes in a person's psyche by creating differential patterns of brain wave activity.  There are four different sets of waves that are produced in our brain:  Alpha, Beta, Delta, and Theta. Alpha brain waves are associated more with a relaxed state, while beta brain waves are associated with alertness, and so on. Thus, when these brain waves are mixed and matched, it is purported that a person may experience another state of consciousness, much like a drug-induced high. 

So will i-Doser keep people from seeking drugs, and more importantly is it safe? I have to admit that I am skeptical of i-Doser replacing recreational drugs. On their website, i-Doser states that there are three classes of people: Susceptible to Binaural Beats, Originally Unsusceptible to Binaural Beats, and Immune to Binaural Beats. They also make the bold claim that drug addicts can use these tracks to supplement their drug addictions and even break them;  I do have a hard time believing that. As for safety, the general consensus is that the technology is completely safe. Apparently, the brain slowly adjusts itself back to reality when the track is done playing.  And since it doesn't actually affect your body in any physical way, there are no physiological side effects to worry about. However, since the tracks are said to mimic drug-like states, driving after listening to one of their tracks wouldn't be such a great idea.

There are numerous links on YouTube documenting reactions to i-Doser. You can always try it out yourself, if you're curious. Be careful though, they don't give you a refund. 

Tuesday, April 17, 2012

Profile:Who says scientists can't rhyme


Earlier this year, I wrote a post describing my rotation project in Allan Basbaum's lab. Here at UCSF, Allan Basbaum is affectionately known as 'the most interesting man in science'. This poem that Allan wrote a while ago is a great example of his passion for the spinal cord (and neuroanatomy in general) and his witty sense of humor. In fact, one of our other faculty members, Allison Doupe, often tells us stories about how she calls Allan for joke ideas when she's giving talks at other universities. So, here it is: Praise the Lord for the Spinal Cord. 


Monday, April 9, 2012

Mum's the word

In a recent study from the UC Davis MIND Institute, researchers demonstrated that pregnant mothers who are obese are 67% more likely to have a child with autism, compared to moms with a healthy weight and no diabetes or high blood pressure. It is well established that obesity is a major risk factor for diabetes and high blood pressure (also known as hypertension) and can increase insulin resistance in the body. The authors of this study suggest that in pregnant women with diabetes, unregulated sugar in the body can result in prolonged fetal exposure to high glucose levels. Doctors say that this prolonged exposure can affect brain development in unborn children. The findings of this study will help in the search for non-genetic triggers of autism and encourage pregnant moms to take extra caution regarding diet and exercise during their pregnancy. Check this article out at CNN Health:

http://thechart.blogs.cnn.com/2012/04/09/moms-weight-or-diabetic-condition-may-be-a-factor-in-autism/

Monday, April 2, 2012

What's the buzz: Neural Inertia


Getting your wisdom teeth removed? Most people wouldn't think twice about requesting general anaesthesia; in fact it is estimated that 25 million patients per year in the U.S undergo surgeries using general anaesthesia. However, we're still not sure how exactly anaesthesia interacts with the central nervous system to produce its effects. A group of researchers at the University of Pennsylvania School of Medicine, led by Dr. Max Kelz, MD, PhD, assistant professor of Anesthesiology and Critical Care recently conducted a study to try to understand how the brain comes out of its anaesthetized state and back to consciousness. 

The prevailing theory about how anaesthesia works is that going under- or the induction of anaesthesia- is commonly attributed to drug-induced modifications of neuronal function, while coming back up- or emergence from anaesthesia- is thought to be a passive process, as the drug is eliminated from its sites of action in the central nervous system. If this is the case, then it follows that induction and emergence are the same process, just in different directions. Consequently, one would expect that the concentrations of the anaesthetic in the central nervous system would be the same during induction and emergence. However, using dose response data from animal models, the group of researchers were able to demonstrate that induction and emergence are actually not identical; in fact the concentration of the anaesthetic is lower at emergence than at induction. More interestingly, the researchers observed  their animal subjects exhibited resistance when returning to the wakeful state during emergence. They explain this observation by introducing the concept of "neural inertia", which they describe as the tendency of the central nervous system to resist behavioral state transitions between conscious and unconscious states. 

Intuitively, neural inertia seems useful in terms of keeping the patient unconscious as the body recovers from a surgery. I was terrified to learn that 1 in 1000 cases of patients undergoing surgery under general anaesthesia report experiencing wakefulness during the procedure. At the other extreme however, patients with neurological disorders like narcolepsy can take hours to emerge from anaesthesia-induced unconsciousness. Thus, elucidating the actual circuits underlying neural inertia will give anaesthesiologists better control of the effects of anaesthesia on patient. 

The concept of neural inertia is also fascinating in terms of understanding how people wake up from comas. A recent report in the New York Times Magazine described a significant number of cases where doctors were able to wake up coma patients after years of unresponsiveness (find the article here). The first of such incidents happened in 1999 in South Africa. The patient, who had been in a coma for 3 years, was given a drug called zolpidem to improve sleep quality. Miraculously, just within a few hours of being given the drug, the patient began to stir and when he woke, he immediately recognized his mother, who was waiting eagerly by his bedside. Over the next few hours and days, his speech, movement and cognition all slowly revived. Since this case, there has been a growing number of successful 'awakenings' using zolpidem. No one really understands how this drug is working, but Kelz says that "this line of research may one day help us to develop novel anesthetic drugs and targeted therapies for patients who have different forms of sleep disorders or who have the potential to awaken from coma but remain stuck in comatose states for months or years."

Wednesday, March 14, 2012

Are you in love?

Yet another rather reductionist approach to interpreting brain activity- an article outlining the brain regions and neurotransmitters that are engaged when a person is in love. Appropriately, this article was published on Valentine's day.

http://www.scientificamerican.com/article.cfm?id=your-brain-in-love-graphsci 

Wednesday, March 7, 2012

Too many PhDs?

When Eric Kandel visited UCSF, one of the professors asked him if we (graduate schools in this country) are training too many scientists. Kandel shook his head firmly and simply said that we are always in need of new ideas and therefore new scientists. However, this recent article in Nature Medicine indicates that there is not a sustainable number of jobs in the biomedical industry because too many students are being trained to be scientists. Thoughts anyone?

http://www.nature.com/nm/journal/v18/n3/full/nm0312-329b.html?WT.ec_id=NM-201203

Tuesday, February 28, 2012

Tunes from the Brain





















Tokyo musician Masaki Batoh, designed an instrument to pick up brain waves from the parietal and frontal lobes and turn them into radio waves, which is in turn converted into a wave pulse that is output as sound. The result? Music! Or at least a semblance of it. Read the article to find out more:

http://www.wired.com/underwire/2012/02/masaki-batoh-brain-waves-music/

Sunday, February 26, 2012

Sweet dream or beautiful nightmare?



First off, thanks to Beyonce for inspiring the title of this article. And to Pandora really for introducing me to the song.

On to more serious matters. Dreams have always been a mystifying topic; no one really knows what the purpose of dreams are, or how they come to manifest parts of our reality and subconscious. There has been research into when dreams occur, and several independent studies have suggested that specific types of electrical activity that occur during particular stages of sleep correlate with the occurrence of dreams. This article from one of my favorite neuroscience blogs describes a study that identified patterns of brain activity that may predict the likelihood that dreams will be recalled upon waking. Check it out:

http://scienceblogs.com/neurophilosophy/2011/05/sleepy_brain_waves_predict_dream_recall.php#more

Wednesday, February 15, 2012

What's the buzz: Connectome



Earlier this week, I went to a talk by Sebastian Seung, a professor of Computational Neuroscience at MIT, at the Commonwealth Club of California. I mention the venue because it ended up influencing the demographic of the audience- many non-scientists and a noticeable majority of elderly individuals. Dr.Seung talked about his new book, Connectome, and the underlying science behind the Connectome. In his book, he defines the Connectome as a map of connections between a brain's neurons and asserts the idea that "your personal identity is encoded in the pattern of connections between your neurons. If this hypothesis is true, then any kind of personal change is ultimately about changing your connectome." Dr.Seung explained the four R's that form the basis of the dynamic nature of the Connectome: 

Reweighting means changes in the strengths of synapses.

Reconnection is the creation and elimination of synapses.
Rewiring is the creation and elimination of neural branches.
Regeneration is the creation and elimination of neurons.


Despite my initial reservations about attending this talk, I'm glad I went for several reasons. Firstly, while 'Connectome' has been a buzzword for a few years, it was enlightening to see the developments being made in the field. I, personally, am not sure if I buy the argument that "we are our connectome". I strongly believe that the way our neurons are wired up manifests itself greatly in how we behave, but I don't think it's the sole basis for "who we are". Other factors that I think should be considered are the nature of these connection, the morphology of the neurons, and the molecular cascades that might be unique to one set of neurons and not the other. Thus, if anything, Dr.Seung made me question his science, which we, as graduate students, are trained to do. Secondly, it was interesting to see a scientist communicating to a lay audience, and the analogies he tried to draw between neuronal processes and real-life situations (a particularly interesting one was equating the release of neurotransmitter at synapses to "neurons spitting on each other.") There were times when I felt frustrated by the oversimplified, dramaticized, descriptions of the scientific concepts, and had to remind myself of the nature of the audience; I was perhaps one of a handful of scientists in the audience. By the same token, it also made me think about how I would communicate my science to my friends and family who do not have a science background (something I am trying to do with this blog). As Dr.Seung showed us some, frankly breathtaking, images of the Connectome that he and his lab are trying to build, it was interesting to observe the audience's reactions and it made me think how much the term 'Connectome' and the science behind meant to the people around me. I also found out about a really cool initiative that undergraduates at MIT have undertaken- Eyewire. It encourages laymen to help contribute to research about the connections in the retina. The website has a brief background about neurons and the retina, and then participants can start exploring these connections through a game interface. Its a really interesting concept, and a little hard to describe, but definitely check it out at eyewire.org

Tuesday, February 14, 2012

Profile: Eric Kandel



Eric Kandel is an American neuropsychiatrist, professor of biochemistry and biophysics at Columbia University, and a recipient of the 2000 Nobel Prize in Physiology or Medicine and colloquially known as one of the 'Founding Fathers of Neuroscience'. My encounters with Dr.Kandel had always been through my classes and textbooks and quirky anecdotes from my undergraduate research mentor, who was a postdoctoral fellow in the Kandel Lab (for fans of Neurotree, I guess that makes Dr.Kandel my scientific grandfather!). Three years after I first came across his name, I met Eric Kandel at my graduate school interview at Columbia University. With his characteristic bow-tie, flyaway hair and Brooklyn accent, Dr.Kandel makes an unforgettable first impression. He was present at a reception during the interview weekend, and prospective students (myself included) were clamoring over each other to get the chance to talk to him. With admirable ease, Dr.Kandel made his way around the room introducing himself to students, talking about everything from the weather and science to the movie that was made depicting his journey to Neuroscience (In Search of Memory). When he finally came around to the small table I was standing at with a few of my fellow interviewees, I remember my throat sticking as I introduced myself and almost dropping my drink when he laughed at a passing comment (those who have met or heard Dr.Kandel talk will know that he has a very distinct laugh that gives the impression that he is choking on a rather large object. My roommate actually does a remarkably accurate impression). We talked briefly about my undergraduate mentor, and then with a benign pat on my shoulder, he excused himself to move on to the next group of interviewees. Predictably, I hurriedly pulled out my phone and texted my friend and made the appropriate update to my Facebook status. 

My second encounter with Dr.Kandel was a few weeks ago when he visited UCSF; my fellow graduate students and I were lucky to have a very candid discussion (once we got past the awkward pregnant pauses) with him. The talk was titled "Animal Models of Neurological Disorders", but he ended up talking about his life, how he got into science, and his views on the world of biomedical research today. I thought I'd share some of what he recounted to us rather than focus on his research; his life story is not only fascinating, but also gave us some interesting insights into the journey of becoming a scientist: how historical, cultural and personal circumstances can affect one's entry into science, the challenges one faces as a graduate student, and the importance of risk-taking, creativity and collaboration in scientific research.  

Eric Kandel was born in Vienna, Austria to middle-class Jewish parents, in November 1929, eleven years after the Austro-Hungarian Empire collapsed following its defeat in World War I. Dr.Kandel described to us, that even at a young age, he recognized the cultural richness of Vienna, which was home to some of the greatest intellectuals such as psychoanalyst Sigmund Freud, writer and doctor Arthur Schnitzler, painter Gustav Klimt among many others. Many of these intellects were Austrian Jews, and they flourished despite the early traces of anti-semitism. This however changed after the Anschluss in 1938, and Dr.Kandel noted that this "final flowering of the Austrian Jewish intellectual activity" greatly shaped his early childhood. He even gave us a glimpse into the early violence against Jews. He explained to us that the one year he experienced under Nazi rule influenced his later interests in the mind, the unpredictable nature of human behavior and motivation, and the persistence of memory. 

Dr.Kandel and his family fled Austria right before the outbreak of World War II and arrived in the United States in April 1939. His family settled in Brooklyn, where he attended elementary school and later Erasmus Hall High School. He explained to us that his high school history teacher at the time- John Campagna, a Harvard University alumnus- encouraged him to apply to Harvard for college and he was one of two students from his graduating class to be admitted. He joined Harvard in 1948 with the intent of studying European intellectual history, although he sheepishly admitted to us that his "path was changed by love". As we all chuckled, he hastily explained that this was not the woman he married, but a woman who had a powerful impact on his future nonetheless- Anna Kris. Anna had also emigrated from Vienna with her parents, Ernst and Marianne Kris who were influential psychoanalysts. Frequent interactions with Anna and her family swayed his interests from history to psychoanalysis and thus began his study of the mind. 

Pacing around the room, he continued his narration: in order to solidify his study of the mind, he enrolled in medicine school at NYU Medical School in 1952, where he interacted with three influential psychoanalysts -Lawrence Kubie, Mortimer Ostow, and Syndney Margolin, who introduced him to the biology of the mind. Keen on finding more about the biological basis of mental processes, he decided to join Harry Grundfest's lab at Columbia University. Grundfest had made significant contributions to the field of neurophysiology, and was one of the only neurobiologists in the New York area at the time. In  Grundfest's lab, Dr.Kandel told us he learned the value of electrophysiological techniques and the importance of having a good preparation to test hypotheses. This is in fact where Dr.Kandel's interest in invertebrate neurobiology began (this would later lead him to his favored model system- the Aplysia). Grundfest nominated Dr.Kandel for a position at the NIH in Bethesda, which fortunately excluded him from being drafted into the military during the years following the Korean War. 


"I couldn't have joined the NIH at a better time" Dr.Kandel explained to us. There had been many breakthroughs in the field of neurosciences. Researchers including Wade Marshall had characterized a topographical map of sensory inputs from the body surface in the somatosensory cortex of the brain. Also at this time, Brenda Milner and William Scoville had described the now famous patient H.M. These findings in the field pushed Dr.Kandel to the study of learning and memory and during his time at the NIH, Dr.Kandel began looking for the perfect model system to study the neurobiology of learning. At the same time that Dr.Kandel joined Wade Marshall's lab, a budding post doctoral fellow Alden Spencer also joined with similar interests in the neurobiology of learning. Together, they decided to use the hippocampus, a neuronal structure that we now know to be essential for learning and memory, as their model system. At this point in   his story, Dr.Kandel interjected some advice: "It is important to take risks in your scientific career, but also know when to listen to others around you, especially those are more experienced". And that's exactly what happened with Dr.Kandel and Spencer; they were what Dr.Kandel described as "brash and naive" but  their risky experiments caught the interest of more experienced scientists around them and they were able to contribute some information about the physiological properties and wiring of neurons in the hippocampus.  


While his work on the hippocampus was enlightening, Dr.Kandel continued to look for a simpler model to investigate the neurobiology of memory; he believed that in a simpler circuit of neurons he could probe the actual cellular changes that occur as a result of learning. While looking for his ideal model system, Dr.Kandel told us that he faced some harsh criticisms from some very established neuroscientists (including John Eccles) for wanting to move away from mammals. He however stood by his rationale that "any insight into the modification of behavior by experience, no matter how simple the animal or the task, would prove to be highly informative"Dr.Kandel took his search with him through his residency at Harvard and a postdoctoral fellowship in Paris at Ladislav Tauc's lab, where he was first introduced to the Aplysia, the giant marine snail. The rest, as they say, is history. Dr.Kandel's work on the Aplysia characterized the neurobiology underlying the now famous gill-withdrawal reflex and introduced concept such as 'short-term memory', 'long-term memory' and sensitization, while describing the cellular basis of these phenomena. These initial studies formed the basis of learning and memory research that would later find many pioneers spread all over the world. 


Dr.Kandel was an exceptional narrator, and hearing about his journey from the perspective of a new, impressionable graduate student was a very enlightening experience. It gave me a lot of insight into how much of one's interest in science is circumstantial and made me appreciate the fact that we are surrounded by so many great scientists at UCSF who are invested in our training. When asked what advice he had for us, Dr.Kandel simply said "Never stop asking questions. And don't be afraid to take risks". With one last guttural chuckle, he ended his talk and I think all of my fellow graduate students and I left feeling a little wiser. 

Tuesday, February 7, 2012

Real Talk

I came across an interesting article from the Dana Foundation, a private organization that supports neuroscience research through grants and aims to educate the public about the successes and potential of research on the brain. The Foundation produces free publications, coordinates the International Brain Awareness Week campaign, and supports the Dana Alliances, a network of neuroscientistsand. Find out more at www.dana.org


This article talks about how neuroscientists need to find efficient ways of communicating their research to the public. This will probably be more useful for my fellow grad students and other scientists who might come across my blog, but its still useful to think about the communication gap that exists between scientists and their community. Check it out!


http://www.dana.org/news/features/detail.aspx?id=28910

Wednesday, February 1, 2012

Echo!

Echolocation is the process of detecting the location of objects by sensing echoes from those objects. A variety of animals echolocate, including bats, whales, dolphins, shrews and even flying squirrels. An interesting, albeit brief, discussion of echolocation in my systems neuroscience class got me scouring the internet for articles on human echolocation. I came across these two articles from a fellow blogger, check them out below. Plus, this will be a welcome change from my more (for lack of a better word) elaborate posts.

A story about a boy who has learned to echolocate so well, he plays basketball, skateboards among other things:
http://scienceblogs.com/neurophilosophy/2007/10/seeing_with_sound_the_boy_who.php

What brain areas are involved in echolocation?:
http://scienceblogs.com/neurophilosophy/2010/06/neural_basis_of_spatial_navigation_in_the_congenitally_blind.php

Monday, January 30, 2012

Ow do we itch?



Trust me, there is a point to the quirky title. I just started my second rotation in Allan Basbaum's lab, whose mantra is 'Pain is in the brain'. The lab studies the neurological basis of pain and its control, with an emphasis on changes in the central circuitry in the spinal cord and the brain. The spinal cord is a fascinating, yet somehow glossed over component of the central nervous system; the few lectures we had on the anatomy of the spinal cord did not do it justice.As my rotation progresses, I am discovering a whole new area of highly complex plastic molecules and circuits and their importance in mediating our ability to detect a range of thermal, mechanical and chemical stimuli and how they are changed in the setting of nerve or tissue injury. More importantly, I am gaining new insight and appreciation of chronic pain as a physiologically and psychologically debilitating condition and the need to elucidate the molecules and cells that are involved in pain processing. 

Before I delve into the actual topic of my post, I just want to give a very brief description of the primary afferents bringing sensory information to the spinal cord (and show off my new found knowledge of neuroanatomy). Firstly, the process by which intense thermal, mechanical or chemical stimuli are detected is called nociception. The population of peripheral nerve fibers that carry this sensory information are appropriately called nociceptors   The cell bodies of nociceptors are located in the trigeminal ganglion for the face and the dorsal root ganglia (DRG) for the body, and have both a peripheral and central axonal branch that innervates their target organ and the spinal cord, respectively. Nociceptors are excited only when stimulus intensities reach a noxious threshold; this suggests that they possess biophysical and molecular properties that enable them to selectively detect and respond to potentially injurious stimuli. There are two major classes of nociceptors. The first includes medium diameter myelinated (Aδ) afferents that mediate acute, well-localized “first” or fast pain. These myelinated afferents differ considerably from the larger diameter and rapidly conducting Aβ fibers that respond to innocuous mechanical stimulation (i.e. light touch). The second class of nociceptor includes small diameter unmyelinated “C” fibers that convey poorly localized, “second” or slow pain. These fibers carry information up to supraspinal structures via distinct pathways; pain is carried by the C fibers and Aδ fibers travel via the spinothalamic tract, while non-painful stimuli are carried by the Aβ fibers  via the dorsal lateral lemniscus. 

A burgeoning interest in the field of pain research is the neuronal basis of itch. That's right, itch; I did a double take too when I found that was my rotation project. Itch was defined more than 340 years ago by the German physician Samuel Hafenreffer as an "unpleasant sensation that elicits the desire or reflex to scratch". The sensation of itch, formally known as pruritus, is most commonly associated with chemical irritants like histamine and a variety of skin diseases. Itch can also result from systemic disorders such as liver and renal dysfunctions. The discovery of neuropathic itch, or itch resulting from nerve damage, spurred investigators to determine specific mediators and neural pathways related to the central processing of itch. These studies have been essential in illustrating the interaction between itch and pain. Think about it, what do we do when we itch? We scratch, sometimes in a manner that causes pain. Animal and human studies have shown that scratch-induced pain can abolish itch, and pain-relieving opioids like morphine generate itch; this hints at an antagonistic interaction. So, what's going on? 

The antagonistic interaction between itch and pain supports the 'specificity theory', which stipulates that  distinct sets of neurons mediate itch and pain. This replaced initial theories on itch that indicated that itch and pain were closely related; weak activation of nociceptors results in itch while strong activation of nociceptors results in pain. This theory, termed as the 'intensity theory' underlined a common central pathway of itch and pain. However, observations that seemingly itch-specific neurons can respond, albeit weakly, to painful stimuli like capsaiscin has prompted researchers to abandon both the 'specificity theory' and 'intensity theory'  in favor of a more plastic 'selectivity theory'. Thus, while there may be distinct set of neurons for pain and itch, more and more studies are suggesting an astonishingly broad overlap between downstream mechanisms of itch and pain signaling. Protease-activated receptor 2 (PAR2) and members of the transient receptor potential (TRP) family have been implicated as targets for both pain and itch receptors, and sensitization of peripheral nerve endings by the protein nerve growth factor (NGF) is a known pathophysiological mechnanism in both chronic itch and pain. Parallels between pain and itch processing are even more evident in the pattern of central sensitization, or the changes that occur in the central nervous system that lead to enhanced responses and/or lower thresholds to a painful or itch-inducing stimulus. fMRI and PET have also identified certain common brain areas like the anterior cingulate cortex and the thalamus that are activated by both pain and itch. 

These similarities and differences in mechanisms of itch and pain sensitization are already being translated into therapeutic approaches to chronic pain and itch. However, as with the studies dealing with chronic pain, it will be important to identify molecules and circuits that are involved in the detection of acute itch in order to treat conditions of chronic itch. That is what I hope to do in my rotation project; aren't you itching to know what I end up finding out? Sorry, I couldn't resist. 

Monday, January 16, 2012

The Synapses of Religion



A couple of years ago when I was scouring topics to research as part of my independent study for Anthropology, I came across Andrew Newberg, director of research at the Myrna Brind Center of Integrative Medicine at Thomas Jefferson University and Hospital in Philadelphia and Adjunct Professor of Religious Studies and Radiology at the University of Pennsylvania. Dr. Newberg has spearheaded the field of neurotheology, the study of the neurobiology behind religion. My fascination with Dr.Newberg's research admittedly did not outlive the duration of my independent study, but a recent article in Scientific American about recent findings in the field rekindled my interest and I thought I would post an abridged version of my anthropological study, in an effort to shed light on the history and potential future of neurotheology. Enjoy! 

A dramatic crescendo of violins and soulful soprano voices greets viewers of the webpage of the European Society of Neurotheology. A pantheon of images of Gods from various religions emerges, with the message “Choose your Guide”. This guide subsequently takes you through the teachings of neurotheology, a concept first coined by the English writer Aldous Huxley in his novel Island. What Huxley used in somewhat of a satirical sense, at least for the purposes of his novel, soon attracted a mass following and a robust research field was evoked in order to find a physiological basis for religious or cosmic experiences. The field came into its own with the first book on the principles of neurotheology by Lawrence McKinney in 1994, titled Neurotheology: Virtual Religion in the 21st Century. In this book, Mckinney- the director at the American Institute of Mindfulness- attempts to create a working definition for the term neurotheology: the study of the physiological bases of religious experiences. Since then, neurotheology has garnered more attention in trying to answer some important questions regarding the validity of trying to find neurological underpinnings for religion: How is it that man’s purely physical brain has evolved the ability to connect with mystical events and the religious world? What neuronal systems or areas of the brain play a role in religious or spiritual experiences? Is religion indeed hardwired in the nerve connections in our brain? How does one go about measuring religiosity or spirituality?

WHAT IS NEUROTHEOLOGY?

Neurotheology, also known as biotheology or spiritual neuroscience, aims to study the activity of the brain during spritirual or religious experiences, thereby attempting to delineate neurological mechanisms for religiosity and religion. As such, neurotheologists believe strongly that all spiritual experiences are the result of neural impulses and brain patterns; the field favors this explanation over the converse possibility that spiritual experiences may be actually causing the neural impulses. While neurotheologists have been attacked for this somewhat reductionist approach to religion, it is important to understand the roots of these beliefs. In the early history of neurotheology, Mckinney postulated that pre-frontal development of the human brain occurs in a manner whereby the necessary connections to document the passage of time or chronicle events generally forms after the age of three. The inability of the adult brain to retrieve earlier images experienced by an infantile brain creates questions such as "Where did I come from?" and "Where does it all go?” which McKinney and other neurotheologists suggests led to the creation of various religious explanations. Neurotheologists like Andrew Newberg, have hypothesized that very specific neuronal structures and systems are involved in establishing these religious explanations and subsequent behaviors. Newberg and others describe repetitive, rhythmic stimulation of these neuronal systems which contribute to the experience of transcendental feelings of connection to a higher power. These researchers posit, however, that physical stimulation alone is not sufficient to generate cosmic experiences; there must be a blending of the rhythmic stimulation with philosophical ideas or psychological. This combination of the biological and psychological or philosophical ideas leads to the visceral experience of religiosity. Which neuronal systems are implicated in religious experiences and what are the ways in which to measure religiosity?

THE SCIENCE BEHIND NEUROTHEOLOGY

The Limbic System

According to Newberg and his colleague D’Aquili, the limbic system of the brain is highly implicated in the experience or induction of mystical states. The limbic system, sometimes also known as the emotional brain, is comprised of several brain structures, including the amygdala, hypothalamus, hippocampus, as well as the right frontal and right temporal lobes. The hypothalamus is concerned with all rudimentary aspects of emotion, homeostatic control of food and water intake, and controls the hormonal and related aspects of violent behavior and sexual activity. The amygdala also plays a highly significant role in sexual and violent behavior, and acting as a sensory filter to the various stimuli that we receive.  The hippocampus, which is contained in the temporal lobe, is a central structure in learning and memory, and relays essential contextual information to the amygdala. The right and left temporal lobes together control auditory, speech and language functions. According to Newberg and colleagues, the rich connections between the amygdala, hypothalamus, hippocampus, and temporal lobe enables a human to have religious, spiritual and mystical experiences.

Is the Temporal Lobe the ‘God Spot’?

What exactly is happening in the temporal lobe that elicits these spiritual or mystical experiences? One hypothesis is that during limbic hyperactivation, there is a resulting imbalance such that there is too much activity in the lower brain regions such as the limbic system and low activity in higher brain regions such as the cortices. Since areas of the cortex are important in controlling consciousness, the reduced activity leads to a lack of consciousness and the agitation of the limbic system leads to sensory arousal. This dichotomy persists because the higher regions of the brain are no longer able to interpret the information from the lower regions, and this uncertainty lends itself well to rationalization by way of spiritual and religious explications.

Another hypothesis proposed by the famous neuroscientist V.S Ramachandran, is that during seizures, the hyperactivity in the temporal lobes causes alterations in neuronal connections, either adding new ones or modifying existing ones. This process is referred to as kindling. Kindling was developed as a model to explain how it is that repeated stimulation of a specific area in the brain would cause the onset of epileptic seizures even after controlled stimulation ended in some cases. In this same manner it can be inferred that repeated stimulation of other parts of the brain can affect behaviors other than seizures. Ramachandran therefore postulates that religiosity is one such behavior that can be attributed to a kindling effect.

CURRENT RESEARCH

In their early research, Newberg and D’Aquili turned to a specific analysis of components of the central nervous system as crucial contributors to the religious experience. Firstly, there is the sympathetic system which is responsible for the arousal states that mediate activities such as hunting and mating. This system is also known as the ‘arousal’ system. The converse system is the parasympathetic system, responsible for activities such as sleeping, digestion, and cell growth. Appropriately, this system is known also called the ‘quiescent’ system. Newberg has found that while these ‘arousal’ and ‘quiescent’ systems normally act in an antagonistic fashion, maximal functioning in one system may spill over into the other system, thus leading to simultaneous activations of both systems. The investigators postulate that mystical experiences are most likely to occur during this ‘spill over’ effect. For example, mediation leads to a ‘hyperquiescent’ state of the ‘quiescent’ system, and this may in fact trigger the activation of the arousal system; this leads to a ‘burst of energy’ that leads to the feeling of being absorbed by an outside object. Buddhists refer to this notion as Appana samahdi. Literally meaning ‘fixed concentraion’. Conversely, the researchers assert that a state of ‘hyperarousal’ induced by ritualistic activity in the sympathetic system might spill over into the parasympathetic system; this breakthrough may contribute to the trancelike condition achieved in many religious experiences.

In addition to these systems, Newberg and colleagues found another neural complex that they called the Orientation Association Area (OAA) situated within the posterior parietal lobe, is also associated with such religious moments. The OAA is the area which enables us to orient ourselves in space and time and gives our bodies a sense of physical boundary. This physical boundary is used to give the self a sense of separateness from the rest of the uni­verse.  Using SPECT (single photon emission computed tomography) studies, Newberg and D’Aquili claim to capture the breakdown of these physical boundaries. Briefly, a radioactive tracer was injected into the arm of the subject, in this experiment, a Buddhist monk, on cue as they entered into deep meditative state. The tracer detected areas of the brain where there was an increase in neuronal activity and blood concentration. The imaging demonstrated minimal activity in the delineated OAA during peak meditation times. At the same time however, due to the intense concentration or appanna samadhi on a chant or prayer, the prefrontal cortex- termed as the Attention Association Area (AAA) - is strongly acti­vated; the AAA essentially takes over from the OAA as the brain’s new experiential center. This transfer of attention, Newberg claims, gives rise to another level of consciousness.

When the OAA is shut down the physical boundaries of the body and the resulting sense of separation disappears. The brain can no longer create a boun­dar­y between the self and the external world, or locate itself in physical reality. As a result, Newberg says, the brain is forced to perceive the self as infinite and coalesced with everyone and everything in the external environment. This is the state Newberg calls Absolute Unitary Being: the point at which we ‘feel’ God. The SPECT studies led Newberg and D’Aquili to believe that they had found the common biological root to all religious experience: “We believe that we were seeing colorful evidence on the SPECT's computer screen of the brain's capacity to make spiritual experience real. After years of scientific study, and careful consideration of our results, Gene and I further believe that we saw evidence of a neurological process that has evolved to allow us humans to transcend material existence and acknowledge and connect with a deeper, more spiritual part of ourselves perceived of as an absolute, universal reality that connects us to all that is.”

While these imaging studies need to be replicated and executed on a bigger scale, this data could explain the notions of God and ‘mingling’ with God that people described in the early experiments. Newberg’s data also implicates structures outside the limbic system, such as the prefrontal cortex and the parietal lobe, in the experience of religious or spiritual sentiments. Thus, their studies have broadened the so-called ‘God Circuitry’ in the brain and have added to Venkatraman’s theory of the temporal lobe and the kindling effect.

CAN NEUROTHEOLOGY BRIDGE THE GAP BETWEEN SCIENCE AND RELIGION?

The results from these various studies have been a double edged sword; it has encouraged neurotheologists to continue with their research, but it has also given fuel to atheists to assert that God is ‘all in our heads’. Not surprisingly, neurotheologists have faced a lot of heat from philosophers, theologists, scientists and religious practitioners. The approach that neurotheologists use has been considered highly reductionist; more specifically, individuals have questioned whether it is at all informative or necessary to characterize a subjective trait such as religion in objective or scientific terms?
Challenging the notion that religious beliefs are rooted in any specific neural substrate or function, David L. Smith, a Roman Catholic priest and clinical psychologist, questions: "If 'God neurons' or 'God neurotransmitters' actually exist in the brain, are they defective in the agnostic and absent in the atheist?"4 Indeed, Smith is holding neurotheologians to the same standard that neuroscientists would pursue when proposing a connection between a neural structure and some behavioral phenomenon: the neurons and neurotransmitters implicated in these connections must be shown to exist. Thus far, no neurotheologist has come forward to make confident claims of "God neurons" and "God neurotransmitters." Smith concludes that neurotheology is "a pseudoscience cloaked in the mantle of Cartesian dualism.”
There are some theologists who believe that neurotheology does hold some good in bridging the gap between science and religion. Ilia Deli is a member of the Roman Catholic Franciscan Order and holds doctoral degrees in pharmacology and historical theology. She appreciates how neurotheologists combine theology and neuroscience to make the case for a religious neural substrate. "It is tempting to speculate that there is a 'God module' in the brain and that such a module is located in the area of the limbic system; however, such speculation needs to be made cautiously. What these findings do point to, however, is that spirituality involves the brain. For the first time in human history we are beginning to understand spiritual experience not as something apart from the physical human but rather bound up with the matter of the brain. Thus, matter and spirit are no longer seen to be indeed mutually related, if not one and the same." 
One of the biggest criticisms of neurotheology addresses the fact that how and why we believe in God or religion are two very different questions. While researchers in the field have generated a lot of data, it is often hard to tell which question neurotheology is aiming to answer. Moreover, the media, the publishing industry, and the researchers themselves acknowledge the fact that the world at large wants the answers to both questions. While, the ‘how’ question traditionally belongs to scientists, and the ‘why’ to theologists, an answer that combines both types of information in a comprehensible manner is what the general public, the ultimate target audience of neurotheologists, wants. Furthermore, as most branches of science, neuroscience has experienced the phenomenon of sensationalism (termed "neuro-sensationalism"), exaggerated and sensationalized reports of neuroscientific findings have portrayed neuroscience as the key to understanding all of human thought and behavior. As a consequence, the field of neurotheology becomes caught in the conflicts between genuine science and hype.

Newberg cites this problem in his own work. "Skeptics have used my findings to conclude that religious experience was nothing more than a neural confabulation within the brain, and religious practitioners cited my work to confirm that human beings are biologically 'hardwired for God.'" However, Newberg seems relatively unphased by such comments and views the heated debates between believers and skeptics as more fuel for the field and the idea that "making our brains experience certain beliefs as real. When I take a brain scan of someone who says that they were in God's presence, the scan tells me what happens in the brain when they experience being in God's presence; it doesn't tell me if God was or was not actually there." In his book, Newberg professes himself as a "seeker," or one who is intrigued by the possibility of a transcendent reality underpinning everyday life. However, in recent years he has distanced himself from proposing conclusive answers to the "why" questions of human belief. This doesn't mean that he and other neurotheologists can't keep asking them or initiate conversations about them. However, in the eyes of steadfast critics, even the questioning is useless in the face of the perceived irreconcilability between science and spirituality.

The field of neurotheology has also faced criticisms of methodology, primarily from scientists. Their skepticism lies in the fact that it hard to use objective methods to quantify or qualify such a subjective notion as religion. Critics concede that neurotheologists are rational in the sense that if we discover how the brain informs us of reality, then this should help us understand how the brain differentiated between real experiences and virtual or ethereal experience. However, critics insist, with good reason, that the evidence thus far is not conclusive. Firstly, as a caveat to the field of neuroimaging, the statistical methods used in neuroimaging analysis can lead to false positives and also often provides correlations rather than causations. With that caveat in mind, critics also state that the types of experiences being studied are not homogeneous. Each person has a different type of experience; some feel the presence of God while others don’t. Ultimately, the applicability of neurotheology does not extend beyond the physical world: fMRI and SPECT scans can inform us of how the brain creates religious experiences, but not where these experiences come from. The search for neuronal markers exemplifies how consumers of popular science, like me, are interested in the ‘how’ and the ‘why’, but ultimately we want to know how the science can be applied to us as creatures of cultural, political and economic circumstance.