[tt] Implant boosts activity in injured brain

[Hughes, James J.]

http://www.nature.com/nature/journal/v448/n7153/full/448522a.html

Nature 448, 522 (2 August 2007) 

Michael Hopkin

Deep-brain stimulation offers hope for minimally conscious patients.
Implant boosts activity in injured brain

Deep-brain stimulation might help trauma patients regain consciousness.

Brain function has been improved in a patient who was in a minimally
conscious state, by electrically stimulating a specific brain region
with implanted electrodes. The achievement raises questions about the
treatment of other patients who have been in this condition for years,
the researchers say.

Patients in a minimally conscious state, often the result of severe
brain trauma, show only intermittent evidence of awareness of the world
around them. Typically, they are assumed to have little chance of
further recovery if they show no improvement during their initial
12-month rehabilitation programme.

In the latest case study, neuroscientists describe how they implanted
electrodes in the brain of a 38-year-old man who had been in a minimally
conscious state for more than six years following a serious assault. By
electrically stimulating a brain region called the central thalamus,
they were able to help him name objects on request, make precise hand
gestures, and chew food without the aid of a feeding tube (see page
600). The thalamus is involved in motor control, arousal and in relaying
sensory signals - from the visual systems, for example - to the cerebral
cortex, the part of the brain involved in consciousness.

Nicholas Schiff of Weill Cornell Medical College in New York, and his
colleagues chose the patient because they believed his condititon was
due to impairment of the arousal system, and that despite considerable
damage to his cerebral cortex, many essential areas were preserved.

"There will be a subset of patients who are responsive to this
approach," says Schiff. But he adds that patients with different brain
injuries may not benefit from electrostimulation. "Not every patient in
a minimally conscious state will fit this profile," Schiff says, and it
is difficult for neurologists to identify those patients who will show
recovery.

Nevertheless, the case shows that many patients currently seen as beyond
hope of rehabilitation might benefit from the results of further
research. "Severe brain injury is not an uncommon problem, and the
number of people doing research on this is shockingly small," Schiff
says. "It's very rare to find a programme that will take a patient in a
minimally conscious state even straight out of acute care. If they don't
respond in a lively enough way and can't communicate and interact with
people at the bedside, they go to a nursing home directly."

"The report does not suggest that deep-brain stimulation [DBS] 'cures'
the minimally conscious state," says Paul Matthews, a clinical
neuroscientist at Imperial College, London. "Although based on a study
of only a single patient, it suggests that DBS may be adapted to benefit
at least some patients in the minimally conscious state. And it
emphasizes that improvements can be made by patients even long after an
injury.

"Although we do not know precisely which brain connections are
important, we may expect that some specific connections must be intact
for DBS to have a beneficial effect."


http://www.nature.com/nature/journal/v448/n7153/full/448539a.html

Nature 448, 539-540 (2 August 2007) 

Neurology: An awakening

Michael N. Shadlen1 & Roozbeh Kiani1

Abstract

Neuroscientists and engineers are developing ways to help patients
overcome paralysis and stroke. But what about mental function itself?
Can medical intervention restore consciousness?

Jean-Paul Sartre wrote1: "In one sense choice is possible, but what is
not possible is not to choose." To the neurologist, however, gaining
consciousness is a decision of the unconscious brain to make choices.
Philosophers and scientists may argue about the definition of
consciousness2, 3, but neurologists have little trouble identifying its
absence. Now, physicians are beginning to understand how it can be
restored in some patients with severe brain damage. A case report by
Schiff et al. (page 600 of this issue4) raises hope in this area, and
sheds light on the neurobiological underpinnings of consciousness.
Schiff and his colleagues treated a patient who had been in a 'minimally
conscious state' (Box 1) for several years after a serious brain injury.

Sadly, the vast majority of coma patients do not recover consciousness.
The prognosis is determined by the type of injury to the brain, its
extent, and the findings from serial neurological examinations5. For
example, a trained neurologist can predict with near certainty that
meaningful recovery will not occur for many patients who remain in a
coma for days after a cardiac arrest, in which the brain is deprived of
blood flow and oxygen. For other patients, however, the outcome is less
certain.

Even after severe brain injury, some patients retain enough of the
cerebral cortex to raise hopes that some degree of organized mental
function might one day recover. Indeed, some show intermittent signs
that are clearly distinguishable from coma, despite an overall level of
function that is effectively unresponsive. For these patients, we do not
have reliable indicators of prognosis, and we lack treatments that might
help the brain restore consciousness.

But advances in basic neuroscience are beginning to reveal the brain
systems that are responsible for monitoring and sustaining engagement
with the world around us. A key component is the thalamus, which lies
between the brainstem and the cerebral hemispheres, and forms the
gateway to the brain's cortex.


The thalamus is organized as a set of nuclei. The best understood of
these nuclei are those containing the neurons that relay information
from the eyes, ears and skin to the appropriate sensory cortex. But much
of the thalamus is poorly understood. Anatomical studies in non-human
primates have identified a class of thalamic neuron that might operate
more generally in activating cortical networks6. These neurons, which
stain positively for the calcium-binding protein calbindin, are found in
all thalamic nuclei. Although we know little about the physiological
properties of these calbindin-positive cells, they tend to exhibit a
different pattern of connections with the cortex compared with the relay
cells. Their axons terminate more broadly both across cortical areas and
in layers that the relay cells miss. These calbindin-positive cells
comprise a large percentage of the intralaminar nuclei of the thalamus -
nuclei that have long been thought to have a role in arousal.

Schiff et al.4 hypothesized that their patient might express a minimal
level of consciousness because of a primary impairment of the arousal
system itself. The patient had suffered irreparable damage to much of
the cerebral cortex, but many essential areas were preserved. By
stimulating the intralaminar nuclei, the authors hoped to switch on the
undamaged areas of cortex. Neurologists and neurosurgeons have
previously used electrodes to monitor brain activity in patients with
epilepsy and to stimulate deep-brain regions in the treatment of severe
Parkinson's disease. Because the brain itself lacks sensory receptors
(after all, it is normally protected by a cranium), these electrodes
cause no discomfort. This insight, and extensive experience with
stimulation electrodes in animal experiments7, made the procedure
feasible and relatively safe. Such considerations probably helped to
guide the complex ethical debate preceding this experimental trial on a
human patient.

The results were dramatic. Within 48 hours of the surgery to place the
electrodes, the patient, who had remained in a minimally conscious state
for 6 years, demonstrated increased arousal and sustained eye-opening,
as well as rapid bilateral head-turning to voices. Schiff and colleagues
allowed 50 days of post-operative recovery before activating the
stimulating electrodes again to ascertain that the stimulation by the
implanted electrodes - not some unknown aspect of the surgery - was the
source of the improvements.

An 18-week 'titration' phase, which involved finding the most effective
patterns of stimulation, followed. During this phase, the previously
non-verbal patient became capable of naming objects and using objects
with his hands - for example, bringing a cup to his mouth. Moreover, he
could swallow food and take meals by mouth, meaning he was no longer
dependent on a gastrostomy tube.

After the titration phase, the authors turned the stimulation on and off
systematically for a better assessment of its effects. The highest state
of arousal and the ability to perform functional limb movements were
associated with periods of stimulation. But compared with the
pre-surgical period, many functions remained improved even without
stimulation, indicating carry-over of the stimulation effects to
no-stimulation periods.

These results raise hope for some patients with brain injury, but there
are two caveats. First, this is a single case report; a carefully
controlled clinical trial is needed to answer the remaining questions.
What is the spectrum of brain injury that will benefit from thalamic
stimulation? What are the clinical, anatomical and functional
(neuroimaging) predictors of improvement?

Second, not all patients with disorders of consciousness will benefit
from thalamic stimulation. This patient had shown clear signs of
interactive behaviour and preservation of many of the important cortical
structures before the surgery. Thalamic stimulation presumably increased
both the level and consistency of activity in the preserved cortical
structures, leading to arousal and behavioural improvements. Such
stimulation would not benefit patients who have already lost the
critical cortical structures; the condition of persistent vegetative
state that often follows deprivation of the brain of oxygen and blood
flow (hypoxia and ischaemia) falls into this category.

But besides the hope that this study furnishes for some patients, the
observations of Schiff et al. may provide clues about the
neurobiological underpinnings of consciousness. Cognitive neuroscience
is beginning to expose the architecture of information processing that
is directed towards goals and actions; we refer to this as an
'intentional framework', but it flies under various banners, including
'affordances' and 'embodied cognition'8, 9, 10.

In essence, the brain does not process information in the abstract but
instead consults information acquired through the senses and in memory
insofar as it bears on the decisions made about potential actions and
strategies. Our brains allow us to decide among possible options - that
is, how and in what context to engage with the world around us. The
brain makes many such decisions unconsciously. Indeed, the decision to
engage at all is, in effect, an unconscious decision to be conscious.
Thus, the brain of the sleeping mother queries the environment for the
cry of her newborn. We suspect that the normal unconscious brain
monitors the environment for cues that prompt it to decide whether to
awaken and engage. This mechanism may be disrupted in various disorders
of consciousness, including the minimally conscious state,
hypersomnolence, concussion, abulia (lack of will) and possibly severe
depression.

Previous theories of consciousness have relied on a central executive
and magical physiological phenomena (for example, synchronized
reverberations) to elevate the subconscious functions of the brain to
consciousness. However, viewed as a decision to engage, consciousness
can instead be studied in the same framework as other types of decision
and the allocation of attention11. Rather than a central executive,
there seems to be a network of brain regions that organize the resting
state and maintain overall orientation towards context12, 13. It is
quite possible that they make decisions about whether or not to engage
and in what way. They do what Sartre considered impossible: they choose
whether to choose or not.

How these networks relate to intralaminar nuclei or the matrix of
calbindin-positive thalamic neurons is another question. However, the
idea that these areas need to be turned on for consciousness leads us to
wonder whether stimulation of the intralaminar thalamus in this patient4
worked through the activation of calbindin-positive neurons and these
circuits. If so, then the work of Schiff et al.4 could point the way
towards interventions that are more refined than stimulation with
electrodes.

These are loose strands, but neuroscience is beginning to stitch
together the neurologist's and the philosopher's ideas of consciousness.
It is wonderful to see the fruits of this research help one patient. We
hope that further studies will advance our knowledge and help more
patients. Meanwhile, our advice is: treat your blood pressure, wear a
helmet and read the existentialists.

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