Welcome I'm Michelle McDonald and I'm the
executive director of Brain Injury
Canada. I'm thrilled to have Dr. John
Connolly with me today. Dr. Connolly is
the Chief Science Officer and co-founder
of VoxNeuro.
Dr. Connolly earned his PhD from the
Institute of Psychiatry, Psychology and
Neuroscience at King's College in London. He currently holds the Senator William
McMaster chair in cognitive neuroscience,
is the founding director of the Advanced
Research and Experimental and Applied
Linguistics Center and co-directs the
language, memory and brain lab, both at
McMaster University. He is an author of
over 330 articles, chapters and
presentations, most of which involve
cognition and health and brain pathology.
And I should mention that VoxNeuro is
our platinum sponsor and we thank them
for their dedication and support and for
all they do for those living with brain
injuries. So welcome Dr. Connolly. Thank
you very much thank you it's a pleasure
to be here. So let's just dive right in
we've got a lot to cover and let's then
there's you know we want to hear so much
from you so so a lot of your work over
your career has been focused on those in
coma or vegetative state. what do we know
now about coma that we did not know ten
years ago? That's a very good question
when I started looking at coma for
example I spoke to a few colleagues and
they said well if you ask ten
neurologists you'll get fifteen ideas so
it is it is a very complex condition and
also it is not one single condition it
looks the same and this may be a
recurring theme in the things that I
say, that how things look is not
necessarily what's going on. So to get to
your question in the last ten years I
think we have some sense - now I only see
this from my perspective I should point
that out I do what I do - but I think one
of the things that's most important is
that first of all the work of a
colleague in France her name is
Catherine Fisher, herself a neurologist,
she really was really the first person
to use what are called event related
brain potentials - brain responses - to to
particular types of auditory stimuli. It was
just very simple stuff but what happens
with this when you present auditory
stimuli to a person, in a coma or not, you
will get brain responses. Now if they're
in a coma they may show rudimentary
brain responses and stop there but what
she demonstrated was that many did not.
They showed a particular type of brain
response that she used to demonstrate
that the response could predict
emergence from the coma not what the
person would emerge like in terms of
whether it's a vegetative state a
locked-in state or just emerge and as
one of our patients did, say they were
hungry. So you get a range of responses
but she would say but they will emerge
and she demonstrated a 90% plus
specificity to this this response so in
other words when people were judged
again externally, behaviorally, to be non
awake that 90% over 90% of
those patients did not show this brain
response. Just for the record it's called
a mismatch negativity but we don't have
to get into that but they did not show
this response. Equally those who did
emerge 90% sorry
there was a predictive value that if you
showed the response in coma
you would emerge. So as a 90 plus percent. The problem with - and she wa- she was
very upfront about this the problem with
her work was that the sensitivity was a
problem that there were people emerging
who'd never showed the response and she
just thought that undermined some of the
work that she was doing in terms of how
specific could she be
about this is a very useful tool and one
of the ideas that we had quite some time
ago to about 20 years ago, 21
years ago and we had applied for funding
to do this work was to look at these
patients but for longer periods of time
so up to 24 hours because what I wondered
at the time was is it possible because
you see this in a lot of brain injuries
the person's there -  how much the person
is tuned in whether it's a conversation
or just two stimuli that are being
presented will wax and wane. And
certainly there were anecdotes about
coma patients that would indicate there
were times during their coma when they
had been aware of what was going on in
the ward, that they would say did
somebody - did something, was someone
pregnant? I had this dream that someone
was pregnant and that turned out to be
one of the nurses that was dealing with
the patient quite a bit and would have
conversations with her colleagues as she
was dealing with him and so I just had
it was all anecdote and so what we did
was we extended the testing of brain
responses for longer than the one like
25 minute 35 minute test. We extended we
tested the coma patients for up to 24
hours and we looked to see two things:
could we ever within that 24 hour period
record this brain response and if we did
was it a one-off occasion or was it in
fact waxing and waning? So I do think
that one of the advances over the last
ten years is that we've now published
several papers on this, that we find that
that many patients do show this response
and yes it does wax and wane so in other
words there will be times when they're
showing, times when they're not and in
fact in a very small study the first one
we published we just had a case study
two patients that we presented and we
demonstrated that that we saw this
response in them. It waxed and waned
so sometimes it was there, sometimes it
was not. Both of them emerged so the
positive predictive value that Catherine Fisher spoke about in some of her
patients we certainly saw. The thing is
when we did the traditional analysis
thing is this the way we did it was over
the extended period of time plus we used
machine learning to look at the
responses we can see them with much
greater resolution it was like switching
from just regular vision to a microscope.
So we really could see the responses
with much greater acuity shall we say
and but when we did the usual procedure
that Catherine and we used prior to this,
we found that they would have fallen
into the category of emerging without
ever having shown this brain response.
So and I think the other thing that's
happened is there was there was for a
period of time and there still is but
it's it's really the game is over -  if you
show this brain response it means that
you were in a conscious state.
That is a very big deal I it doesn't
mean you are necessarily consciously
aware it just means it because there are
two different things there and the best
example I can use this for those of you
who wear glasses, I do, I very often might
be on the telephone or might be doing
something and I put my glasses down. I
then move to another room and I need my
glasses and I then have to figure out
where I left them. When I put them down
I was not unconscious. I was conscious. I
was just not consciously aware of
putting them down as I spoke to someone
on the telephone that's what we're
talking about here and I think at the
moment what we're doing thanks to a
federal government award but we're doing
work to see is there any point of which
patients that show this conscious, this
response that requires consciousness
doesn't mean their eyes open it just
means they are at some level aware of
what's going on in the environment but
not aware in the sense of I know where I
put my glasses, that do they ever break
into that other category where they
really are attending
to something. So we're running a variety
of other tests during that 24 hour
period
and we're still analyzing those so I I
don't know if we get that and that was
something that Catherine Fisher and I
would discuss not infrequently that it's
one thing to predict emergence it would
be quite another thing if we could
predict what they're going to come out
like because the intent there would be
the step-down clinic, the rehab people,
they could get ready for what this
patient was going to present. Furthermore
as as I discussed with some of the
people, we could actually begin some
types of therapy even while they were
still technically in the ICU and
technically in a coma. So it sounds very
outlandish but that's what we're doing
and that's that's really in my world
that's the that's the news of what in
the last 10 years has been found. That's
incredible it's fascinating so for those
families who are sitting with their
loved one is there anything that they
you know, not knowing that, that person is
not being monitored on your study, is
there anything that you know that you
can recommend for them that as they sit
vigil beside their loved one? I think
honestly and this is a response I have
to some television programs that I've
seen when when they still have an in
dialogue we can't tell if they can hear
you it's it's like yes we can but it
doesn't mean - they might just hear, they
might not respond but I will say as one
example that's, again Catherine Fisher
has and we're doing the same thing but
she has already published on if you have
someone's name spoken in the middle of
other types of stimuli they hear the
name Michelle or they hear the name John
and other names that are sex specific so
that we don't get that sort of confusion
going on. If it is spoken by someone they
don't know or if it's even a very
sophisticated artificial voice they
- they still show that brain
response if they are in that state.
However when a
familiar voice for example the person's
partner speaks their name they show a
different response. They show a response
to that that that indicates a
recognition of a familiar voice. There
may be a range of low level
physiological reasons for that but I
think right now the the more
parsimonious result is that that there
is a level of recognition going on that
they they know who that voice belongs to
or they know about the voice and that's
a very significant result. The other
thing is that in in ICU it's one thing
in coma it's one thing but in vegetative
state theoretically vegetative state
that's another thing where really the
person should be tested, that somebody
should use some technique to see if
there is any response to external events
and and that really should be mandated
There's a man in New York,
Joseph Innes who's talked about the the
day of considering not doing that as
malpractice is not too far away so he's
quite vehement about it and I think it
really is the case we could tell if
there's something going on. A negative
result doesn't mean nothing is going on
it just means well we have to test maybe
more or do something more sophisticated
but I do think it is that that stage at
this point. That's so important for all
those families that are in that position
of wondering what's happening with their
loved one that's that's crucial
information yeah. So we're in the middle
of a pandemic hence why we're doing this
online so since the pandemic started
there have been some reports of
neurological effects of COVID-19 on
patients who have have recovered from
from the illness so can you talk a
little bit more about that and then also
how VoxNeuro and there you know the
objective health assessments that you do
how do they fit into the treatments for
those individuals?So it's a bit of a
two-pronged question.
The thing that I noticed, there were two
things that happened the very first
reports out of Wuhan, medical reports
we're talking about up to 64% of
the people they saw we're exhibiting
some signs of what they described as
neurological consequences of the virus. They were they were at what you might
describe as low level neurological but
neurological nonetheless. It was then
just days later because reports were
flying out from all over the place it
was a it was a anecdote from New York
then coincidentally or not actually not
coincidentally I was talking to a former student
who works out in Los Angeles, neurologist
but also got her PhD with me, uh
and she was she was working in LA and
she said a lot of them have frank
neurological symptoms and she said it
includes delirium and that's that's
where it becomes very interesting
because that comes with cognitive
symptomatology as well and as people
started to get more and more information
it became clear that there were memory
problems, there were language problems,
there were executive function problems
so and also especially in Italy they
really jumped on this right away so that
they were opening neuro clinics in
regards to to these patients, these COVID-19
patients that they were specifically targeting so
that these people who could go to
particular locations, to clinics that
were geared toward neurological and
neural cognitive consequences and that's
where I first saw the term maybe someone
else had used it already but I saw the
term used for the first time, neuro
invasive. And there's a very interesting
group at Laval University in Quebec who
has been looking at viruses
like this for some time and they had
talked about some elements of
neurological consequences to various
already existing strains and
they were they were saying they -
even givi- giving the mechanism of
how it it got into the brain and through
cranial nerves and that is why for
example another group talked about using
the fact that someone loses their sense
of smell or has very very bad headaches
this other group was talking about this
was the route by which the virus entered
the brain and I thought that was really
very very interesting because they were
talking about COVID-19 as being - they even
suggested that because one of the
targets let's call it that of the virus
once it got into the brain was the
medulla and the medulla has a very
strong representation in controlling
respiration. Everybody was talking about
respiratory problems at that stage and
this group suggested it could even be a
secondary consequence of the virus not a
primary consequence so I don't know that
that's been confirmed but it is
certainly a neuro invasive virus and and
the issue of where we're involved is
that in order to assess the cognition I
think one of the problems is that there
comes a time when you just have to stop
subjective opinion when you look at
someone and and vegetative state is a
classic example where historically
consensus diagnosis which is the
opinions of very skilled people
looking at something that's very
complicated and and saying I think this
is vegetative state and they agree and
that's the label the person gets and
even the people who developed one of the
best tests around the coma recovery
scale, the revised version, they found
even when they administered it the first
time around they were wrong 36% of the
time. So that is right in the ballpark
that's a very good behavioral test the
point is what you see in behavior maybe
is not really what's going on and that
is is just too common an occurrence. So I
think I think VoxNeuro's role here
is to when you talk about executive
function that is a very overarching term
it involves a range of different
cognitive functions. Which ones? And is it
memory, is it is it attention to detail,
is it concentratio? And and there's just
a range of things and I think that's
really what our contribution would be to
this because the other thing that the
Chinese and the Italians who had the
longest exposure to this have been
talking about is that these consequences
do not go away in many cases this is now
a person has in a sense recovered from COVID-19 in some respects but they
have lasting neurological consequences
it's not everyone but it's it's a
percentage and they had talked about the
rehabilitation pandemic that's going to
follow so I think that's where we come
in to, we could help by saying here's
what's really going wrong rather than
just generalizations about executive
function and the tension. Gets specific
and get some measures that you can rely
on day-in day-out. Wow oh I'm sure
there's going to be a lot more coming
out as we as see for the research
happens with COVID-19. So you talked a
bit about you know subjective versus
objective diagnosis and we - diagnosis and
prognosis are an ongoing challenge
and I know that that's one of the the
questions that families have when
they're you know what what's going to
happen with my my son, daughter, spouse,
mother, father, whatever but so how can
common diagnostic errors of catastrophic
brain injury be avoided? I think it is
again using biological measures I think
the and I think one of the things you
have to really look at then is a
point-of-care system.
A lot of these patients early in their
condition really can't go elsewhere to
be tested and I think that's one of the
real pluses of electroencephalography.
That and again we really concentrate on
one side of it but I won't go into that
unless it becomes essential but but we
do look at particular types of it and
these are responses these are not this
is not novel science these are measures
that have been around in some cases one
response that we look at was first
published about in 1965, another one
1978, another one 1980 so these are very
very well established responses we know
what they're about. So I think the the
real issue is putting a behavioral test
on an iPad is just putting it on an iPad.
That doesn't make it objective it just
makes it easier to collect the data and
that's not trivial. I think one of the
most - when I got my PhD as you
mentioned it was in a medical federation
I was with doing this within the
Hospital Federation of England and
London and medical histories are
absolutely critical but then if you look
at other disorders, other diseases, the
first thing they then want is can we get
some CTs? Can we get some blood work?
It's it's common practice well it's - it should be common practice that
when you see a patient in a coma or in
what you think might be a vegetative
state in other words if there is some
problem communicating with the person
it's either impossible or it's very very
laborious and you don't trust -  not it's
not that you don't trust the patient, you
don't trust your ability to get reliable
responses then I think you should switch
to a biological measure because you
can't fake those. Just for the record
I could but you if you were skilled
you'd know that I was doing it and so
effectively you cannot fake these these
are robust, they're reliable, the
reliability of these responses is very
very high
so I just think that the subjective
opinion as the developers of the CRSR, the coma recovery scale revised version
as they demonstrated themselves it it is
problematic.
They made error rates of up to 36% so it is simply you're looking
at a patient and you make assumptions
there may be a lot going on where we
tested a man who is diagnosed as in a
vegetative state by a world-class
neurologist who has since passed away
unfortunately Jane Gillette, she tested
and she said classic vegetative state
and then she also added your turn and
this man he showed he went right up to
showing speech comprehension responses.
He was thoroughly there when we - and he
received treatment and he made a
wonderful recovery and when we
interviewed him and we we've kept in
touch it's been ten years now since we
first tested him even longer possibly
but he remembers being tested and he
remembers what we said to him and he
remembers one time when we ran one test
in particular faster than usual because
we thought it was too laborious for him
and he couldn't do it and he he was
upset. He said I remember that I panicked
because I knew what you were trying to
do and I thought if I fail this test
they were going to make assumptions about
my state and it unfortunately was a month
later when we tested him again so he had
to go through that agony for a month
because we tested him and I said I think
last time we might have run this too
quickly so we're going to run this more
slowly. Responses came back so he needed time to
do things but he was doing them and and
so like I say he's made a very very
strong recovery so it was not vegetative
state. Jane - Dr. Gillett - was very
excited about this so so at any rate I
think that's the difference between
subjective views even if they're skilled
versus objective evidence.
Physicians would never send you for
blood tests if they were just going to
judge you by what they think is going on,
Wow that's an incredible story. Okay
so talk we talked about catastrophic
brain, now talking about more
mild traumatic brain injury concussion
how can diagnosis of MTBI concussion be
improved? That's a good question and I
think diagnosis with cases like
vegetative state as to whether it really
is it's still risky I would hate to on
the basis of our results even say that
someone is absolutely not there. There
may be better ways that we haven't
discovered yet but but concussion I
think the diagnosis is very problematic. What we do is we just provide objective
assessment of the person's state. If the
person again medical records and history
taking if the person has been in a
hockey game mm-hmm excuse me and was
checked into the boards from behind and
was really injured and is now reporting
feeling slow the family says the same
thing and we test them and they show
clear abnormalities in their brain
responses then we would say well
certainly he has cognitive dysfunction.
Given the history it probably came from
the hockey game and it probably was a
concussion. I think the real issue is
what we offer is that here's the
condition, here are the different
symptoms because again we see some
people that can't concentrate but their
memory for things is pretty good not
around the injury I just mean generally.
Other people we see they also have
trouble with memory so what we do is we
say here are the targets or problematic - 
here are the dysfunctions and it's where
a rehab person may want to focus some of
their attention but also what we can do
with these same techniques in the VoxNeuro repertoire is we follow them.
We can see as you begin to work with
them are they showing signs of
improvement?And and we have done that
and we are we can we contract these
responses and and I think that's really
where we'd fit in with a concussion
profile is is diagnosis. I feel sometimes
I'm almost trying to avoid the response
because it is really complicated. These
are very very difficult things to make a
strict diagnosis about and especially if
somebody has had concussions before and
you didn't get a baseline from them but
we are baseline free that is one of the
features. We have a normative
database and also we can look and just
say that is well below what this person
this 25 year old fellow or woman should
look like so let's just track them to
see how they change over time and we
have seen people come right back
especially younger people. The CFL
players they are where they are because
there are last time the average age is
sorry the average number of years
between when we tested them and their
last concussion was 29 years and they
still showed differences that were very
different from never concussed
age-matched controls. Okay so you did
touch on a bit on neuro rehabilitation
so how does neurocognitive health
assessments inform rehabilitation for
those with brain injury? I think we
talked we talked a lot to clinicians and
one of the things that they struggle
with is that they make they oftentimes
feel that even with the assessment tests
which are - they are the ones that are
always described as subjective, when
they're then doing their treatment they
hope they're targeting the right area, it
might take them some time to find that
wasn't the right area and they move to
another domain another cognitive domain
I think the big advantage that they have
said that we provide is we give a full
range evaluation we don't look at one
thing we look at a range of things and
we can then say this
part of this person's functional profile is
actually okay. There is a problem with
this other area there is a problem for
example in memory. But they can
concentrate, they can pay attention to
things, but they do have a memory problem.
And there are different types of memory.
Everyone knows about short-term and
long-term and also this type of memory
called working memory and we can look at
all of those things and then we get
again objective evidence both in terms
of the strength of the brain response
but also its timing like the man I
mentioned Dr. Gillett's patient. He
showed the responses but they were very
very late so he was not okay but he was
not vegetative. So I think I think with
all of these cases its we can help
target the rehab. We can say look at this
area and we have had very positive
feedback from people saying that is
really what's happened and the patients'
themselves especially concussion
patients they often have a lot of
insight and they they get some training
some intervention with particular areas
and they can really see the improvement.
So I think that's where contribute. Well it
sounds like the objective health
assessment really leads to a more indi-
individualized approach to treatment and
recovery and that's what every
individual strives for in their recovery
from brain injury. You're right yeah. So I
do want to let you get back to all the
important work you're doing so I do
thank you so much for being with me
today this has been fascinating and
eye-opening and I do also want to thank
the VoxNeuro team for all the hard work
that they're doing and for their support
of Brain injury Canada and it has been
an absolute pleasure speaking with you
today  thank you so much Dr. Connolly
Thank you very much it was a pleasure meeting with you
