Is there anybody in there?

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?

1*

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.

2*

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

 

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2 thoughts on “Is there anybody in there?

  1. This is my favorite. I remember reading The Diving Bell and the Butterfly and thinking, the character Noirtier de Villefort in The Count of Monte Cristo has come to real! And studies here are probably the closest people ever get to the question of the level of consciousness, experimentally. Just free-associating: is sensation and motivation even separable? can a person feel and understand the world while unable to initiate even thought of movements?

    Like

  2. Pingback: Gray Matters

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