Imagine you wake up one day and while slowly emerging from the groggy haze of sleep, you go to stretch your arms; nothing happens.  You try to move your legs, wiggle your toes; nothing happens.  You try to look around but you seem to only be able to stare at the ceiling.  You try to call for help but still nothing.  A wave of fear and panic surges through you.  Snapping awake in an instant, you realize that your whole body is entirely paralyzed and that you have somehow ended up in the hospital.  This is the experience that befell French fashion magazine editor, Jean-Dominique Bauby in 1995 when he suffered a massive stroke.  All his mental faculties remained intact despite being completely paralyzed and unable to speak.  He was left with just one ability: to blink his left eyelid.  With this sole connection from his mind to the outside world, he was able to write his memoir purely through blinking his eye in a sort of morse code dictation.  Needless to say, the book is short (although I highly recommend it!).

But what happens to people who are not left with any connection at all?  What if they are completely unable to move, stranded within their own mind?  What if they are still in there but they have no way of showing it, never able to find a bridge of communication?  Until we consider such a catastrophe, we cannot really comprehend how vital movement is to our everyday functioning.  When it is lost, the lines that define that which makes us conscious human beings begin to blur.  Now imagine that someone has not retained 100% of their cognitive functioning and they cannot move.  Doctors today would assess whether this individual can make any purposeful or voluntary response to various external stimuli and search for signs of any awareness.  If nothing could be observed, the person would be deemed in a vegetative state. Recovery would be thought to be unlikely.  But does this diagnosis tell the whole story?

In 2005, a 23 year old woman suffered severe trauma to her brain in a terrible car accident.  Five months later, she remained unresponsive and was diagnosed as being in a vegetative state.  Some time after this, Dr. Adrian Owen (no relation) now at Western University in Canada started to work with her.  He wanted to find out whether he could use neuroimaging techniques to assess her level of consciousness (if any remained) in a new way.  While in an fMRI scanner, the woman was given one of two instructions: either

1. imagine playing tennis, or

2. imagine walking through your home.

Characteristic and distinguishable patterns of neural activity are known to occur in healthy people when given one of these instructions.  The tennis imagery reliably activates a region called the supplementary motor area (SMA); the spatial task of walking through one’s home reliably activates other regions such as premotor cortex (PMC), posterior parietal cortex (PPC), and parahippocampal regions (PPA).

So what would it mean if this woman, who was thought to have no remaining awareness, could selectively modulate her brain activity to perform the given task?  What would it mean if the neural pattern shows that she could hear and respond to directions?  The image below shows the results from the study.  The top panel shows the characteristic responses elicited from a healthy individual.  The bottom panel displays what was observed in the patient.  Pretty similar, huh?

To follow this work, Dr. Owen took it a step further.  He started working with a man who had suffered severe head trauma in a car crash in 1999, at age 26.  When clinically evaluated, he could not open his eyes or produce any sound, and over the next 12 years his condition remained unchanged as persistent vegetative state.  In 2012, this young man had his first MRI scan where the same instructions were given to either imagine hitting a tennis ball or think about navigating around his house.

When his activity turned out to be roughly similar to that of controls (as in the previous example), researchers realized that this paradigm could be used to gain more information about the young man’s inner mental capabilities.  The distinct neural responses could be used to signify answers to yes/no questions.  When asked a question, imagining playing tennis would signify a “yes” response; imagining walking through the house would signify a “no” response.  Since the two neural patterns are clearly different, the answer could be clearly detected, but would he be able to answer verifiable questions correctly?

If asked “Is your name John?” (the correct answer was yes), he would have to imagine playing tennis to signify an answer of “yes”; if asked “Is your name Mike?”, he would have to imagine navigating his house to signify that his name was not Mike.  This task requires sustained attention, working memory, language comprehension and knowledge of the answer to the question, abilities traditionally thought unlikely to remain for someone in a vegetative state.

The researchers questioned the young man using this technique.  They wanted to assess whether he retained basic knowledge about the world by asking him if a banana was yellow.  They wanted to know if he knew who he was, so they asked him his name (John or Mike).  They wanted to know if he had orientation in time and space, so they asked him what year it was (1999 or 2012), and where he was (in a hospital or a supermarket).  They also wanted to know whether he had acquired any new information since the accident.  Finally, to determine this, they asked him what his caretaker’s name was (It was Sarah, see below for this result).  They successfully obtained answers to 12 different questions using this approach.

Based on these results, it seems that this man was able to show evidence of focused attention, language comprehension, and working memory. He was able to provide information about personal preference (did he like watching hockey on TV) as well as his bodily state (was he in pain).  Despite these astonishing findings, his diagnosis of being in a persistent vegetative state was not technically incorrect as it is based on his ability to produce observable behavior at the bedside.  These results left his diagnosis unchanged, yet, this clinical assessment does not accurately capture his inner mental capabilities.  So where does this leave us?

Of course, these examples are exceptions.  They should not be used as evidence that all vegetative state patients exist in a horrific prison of the mind without the ability to communicate due to paralysis.  It is more complicated than that.  In a study of 54 patients in either persistent vegetative state or minimally conscious state, only 5 showed evidence of being able to modulate their neural activity in this way, and some skeptics would argue that this small number are not showing true evidence of consciousness.  More work is clearly needed to smooth out the wrinkles of these first unusual observations to determine where vegetative state sits on the spectrum of consciousness. That having been said, this patient has persisted in a vegetative state for over 12 years, qualifying him as being in a permanent vegetative state.  Because of this, it is possible that he could become the subject of a legal petition to withdraw life support (nutrition and hydration).  Would this new imaging work influence such a decision?

The determination of a vegetative state diagnosis is made by searching for external observable behaviors, the only signs that clinicians can currently detect at the bedside.  The work of Dr. Owen demonstrates that advances in imaging technology might allow us to peek inside the brain of a person in such a vegetative state and observe his or her internal neural activity.  Could this new internal behavior count as an observable behavior to be included in a diagnosis consideration?  Although it is not my goal to insert my personal beliefs here, I think this neuroscience suggests that we need to think carefully about what it really means for someone to be classified as being in a vegetative state.

The linguistic implications of the word “vegetative” are that people in this condition have the same mental capabilities as a vegetable: none.  This work suggests that perhaps in a small subset of patients, this may not be the case.

All of this naturally brings up questions regarding quality of life of these patients, and the early potential of communicating about it using imaging techniques.  If you had a family member who had a clear order to turn off life support in such a circumstance, would you want these tests done first?  Should they be included in diagnosis?  How should this early research be communicated to family members in the most sensitive and ethical ways?  Dr. Owen and his team are working through some of these issues in some fascinating recent publications.  My purpose here is not to make any kind of philosophical arguments about how these very special patients should be viewed or treated, but rather to provide some science to help inform your own beliefs on the subject.

Owen believes that one day perhaps we will perfect this approach to assess whether a patient in a vegetative state has desires, and the use of neuroimaging in this area has the potential to greatly enhance diagnosis accuracy and treatment outcomes.  We could also use it to communicate with these individuals as Jean-Dominique Bauby used blinking his eye as his sole access to the external world.  Although there are still scientists who remain skeptical of this work and claim there is no evidence of consciousness, Owen responds with, “in the end if they say they have no reason to believe the patient is conscious, I say ‘fine, but I have no reason to believe you are either’.”  I will look forward to see where this work takes us in the future.

Citations:

http://www.nature.com/nrn/journal/v14/n11/full/nrn3608.html

http://www.sciencemag.org/content/313/5792/1402.abstract

http://www.nejm.org/doi/full/10.1056/NEJMoa0905370

http://www.nature.com/news/neuroscience-the-mind-reader-1.10816

Henry was a seemingly normal boy growing up in Hartford, Connecticut in the 1930’s.  After a bicycle accident in childhood, he started to suffer from terrible seizures.  Despite being on high levels of anti-convulsant medication, these seizures became severely debilitating into adulthood.  You can imagine it might be hard to hold a job when you could start foaming at the mouth, biting your tongue and convulsing uncontrollably at any minute.  As a solution to this, his neurosurgeon decided to drill into his skull and remove a melon ball sized chunk of neural tissue from the back of each side of his brain.  Although the surgery succeeded in the goal of preventing seizures, it left Henry with a strange problem.  For the rest of his life, he could no longer form new memories.  If you have ever seen the movie Memento (and if you haven’t, you should), it was like the condition the main character suffers from.  He could no longer remember when he had eaten; he would read the same magazine over and over again; he had to leave himself countless notes about everything. Every day, his doctor would have to introduce himself as if they had never met before, and he would react with the same distress each time he was informed that his father had died many years before.  Despite this strange condition, Henry’s IQ was above average, and he was able to show evidence of other types of learning.  He just could not remember having learned it.  Henry Molaison died in 2008, and he is possibly one of the most studied and fascinating individuals in the history of neuroscience.

Over the last decade or two, the field of neuroscience has exploded.  After the great success of the human genome project, many people considered the brain to be the final frontier, the last unexplored territory and even the holy grail of science.  I became fascinated by the subject in college during my Introduction to Cognitive Science class where I was introduced to examples of strange neurological cases like Henry.  I read about people who lost the ability to recognize faces, who could no longer perceive motion, or who had developed uncharacteristic obsessions with drawing or religion after brain injury.  I became intrigued by how that clump of cells in your head gives rise to everything one experiences as well as the bizarre and surprising consequences that pop up when things go wrong.  Since college, I have whole heartedly pursued the subject not only in my career but in my free time as well.

I have been known to devour books by Oliver Sacks and Eric Kandel and rave to people about the stories in them.  I have become transfixed by stories of religious auditory hallucinations in temporal lobe epilepsy or a man who became obsessed with piano music after being struck by lightning.  There is the example of the autistic savant, known as “the living camera,” who is able to draw the entirety of Rome from memory after flying over it in a helicopter, perfecting details down to the number of windows on each major building.  The brain is a powerful and mysterious organ, and these stories of its strange intricacies will always fascinate me.      

My academic training as a Neuroscientist requires that I complete a highly specialized project, which takes up the majority of my time, but the rigorous coursework, teaching and independent study required in the earlier years of the PhD have given me something arguably more valuable.  They have taught me to speak science.  Yes, science can often seem like it is its own language.  I remember reading academic journal articles when I first decided to dive into research and thinking to myself “this may as well be written in french!” (a language that I definitely do not speak).  After years of dedicated perseverance, I have transformed into a novice speaker of neuroscience.  I now have the ability to read most any kind of journal article and understand the gist of what the scientists did and why it matters.

Once I reached this level, I discovered a whole body of work that often shifts my perspective on life.  I am constantly amazed by new research and hot avenues of exploration in the field.  When faced with conflict as a child, my mother always told me that I had a choice, that I could get upset or choose to do something more useful.  At the time, I was not able to escape the grips of powerful emotion and dismissed the advice as empty words aimed to comfort, however, as I’ve grown up and used neuroscience to inform my approach to conflict, I have been able to better see the insight in her advice.  I suppose I’m a bit biased, but I truly believe that knowledge of the emerging findings in neuroscience can inform your every day life, and how you view the world.  It can empower you and allow you to see things more clearly.  Charles Darwin said, “the highest possible stage in moral culture is when we recognize that we ought to control our thoughts.”  I have found this incredibly powerful, and I want to share it with you.

Of course, the fun is always in sharing ideas and discussing them with others; however, with science, often times the language barrier becomes a problem and those who do not speak the language get left out.  Academic papers contain jargon and require background knowledge, becoming inaccessible to those without it.  I have sat through countless lectures at top universities and international conferences where I became lost and had to go back and find ways to teach myself the material.  At first, I assumed it was because I was just not as bright or not able to keep up, but over the years I realized it was mainly due to bad teaching and ineffective communication.  When I went through the material in a more accessible way, I realized how exciting it was.  If only the lecturer had just said that!

 My goal with Gray Matters is to shed this barrier completely by translating the science into more accessible nuggets that people can appreciate.  I want to share my enthusiasm and show people why this subject is so amazing!  Over the last few years, I have gained experience teaching neuroscience spanning from explaining a sheep’s brain to a fascinated 10 year old to demonstrating cell respiration to a high schooler to teaching cranial nerves to advanced graduate students.  Despite the various ages and levels of my students, one thing always remains the same: the science needs to be translated.  I have found that simple drawings, explanations and analogies have helped tremendously, and I hope to use these tools to communicate the newest and hottest topics in the field.

My aim is to make Gray Matters accessible to people from any background.  I have friends who work in areas such as marketing, tech and even opera singing, but there is not one person who hasn’t found something I’ve told them about neuroscience relevant to their field and/or just plain cool.  To my artistic friends, I send articles about creativity, genius, musical hallucinations, and using art in recovery; to my tech friends, I send articles about new devices, innovative technologies and the future of communication; to my doctor friends I send articles about the importance of treating the mind and body, new case studies and connections between the brain and other organs; to my friends in banking, I advise them to read Daniel Kahneman’s work and be cautious to avoid the pitfalls of loss aversion.  There is something for everyone!   Now, instead of pummeling friends and family with these little specialized tidbits, I thought I’d find a place to write them all down.  That way, people can read them at their own leisure (or choose to opt out completely!).  I hope that this blog will enrich your neuroscientific knowledge and that you can take it with you in your future endeavors , whatever they may be.