The marriage
between basic science research and clinically relevant research is necessary
for extending our understanding of both the former and the latter. Just as
studying the natural course of development can shed much light on mechanisms of
disease, investigations on such disorders can also tell us much about basic
development: since disorders are often manifestations of a “natural process”
gone wrong, they often clue us in on the workings of essential processes in
normal development. For instance, as this week’s articles suggest, research on
attention disorders often informs basic research on attention. In practice,
however, these two practices are not really isolated; it’s more of a continuous
cycle in which knowledge from basic research (or clinical research) is used to
examine diseases (or developmental processes) through the lens of the other
discipline. However, there are important pitfalls to this approach. For one,
while studying the diseased state can often point to a certain brain region or
process involved in maintaining balance in the natural state, it doesn’t
necessarily shed light on the exact workings found in the natural state. Rather,
it essentially builds an image from negative space: it tells us what should not happen, but not necessarily what does happen.
Bonnelle et. al. (2011) investigated the role of the functional
connections in the default mode network (DMN) in predicting attention deficits
after traumatic brain injury (TBI). Using neuroimaging techniques, they found
that impairments in sustained attention are associated with increased
activation of the DMN (shown in figure 1 below). More importantly, the
interaction of the precuneus with the rest the default network was predictive
of future attention impairments. Here’s the punch line: “predictive
information” is present before any
behavioral manifestation of attention impairment! By using diffusion tensor
imaging (TMI), Bonnelle and his team also found that structural
disconnection/low functional connections in the DMN are also predictive of
sustained attention deficits (shown in figure 2 below).
FIGURE 1
FIGURE 2
Thus, the authors
suggest that abnormalities in DMN function as well as certain functional
connections can serve as reliable markers of attention impairments. This
conjecture and this study provide a good example of the relationship between
basic research and clinically relevant research in the study of attention. By
studying patients with attention disorders (TBI patients) and comparing their
DMN activation patterns with those of healthy, control patients, we are able to
find a potentially new strategy of predicting sustained attention impairments
(clinically relevant) using markers in DMN (a natural state process).
Berman
et. al. (2011)’s
study expanded upon the then current knowledge of functional connectivity in
the DMN and its impact on neurological disorders such as Major Depressive Disorder
(MDD). Specifically, they analyzed the connectivity of the DMN in the subgenual
cingulate both on and off-task to examine the relationship between connectivity
and rumination. The authors found patients with MDD demonstrated more
functional connectivity between the posterior-cinguate cortex and the
subgenual-cingulate cortex compared to healthy individuals during rest periods, but not during tasks. Importantly, this
functional connectivity was correlated with rumination and brooding. The figure
below shows this phenomenon. As one can see, the MDD group differs notably from
the HC group only during off-task periods, just as the relationship between
rumination and connectivity exists only during off-task periods.
Personally,
this was my favorite paper this week because I think it really sheds light on
the workings of depression and potentially new targets and treatment options
for patients with MDD. I don’t have any experience with MDD personally, so I
can only imagine what it must be like for these patients. I do remember reading
Kay Redfield Jamison’s memoir, An Unquiet
Mind, in which she recounts her battle with bipolar disorder, and I will
never forget her description of depression:
In
its severe forms, depression paralyzes all of the otherwise vital forces that
make us human, leaving instead a bleak, despairing, desperate, and deadened
state…Life is bloodless, pulseless, and yet present enough to allow a
suffocating horror and pain. All bearings are lost; all things are dark and
drained of feeling. The slippage into futility is first gradual, then utter.
Thought, which is as pervasively affected by depression as mood, is morbid,
confused, and stuporous. It is also vacillating, ruminative, indecisive, and
self-castigating. The body is bone-weary; there is no will; nothing is that is
not an effort, and nothing at all seems worth it. Sleep is fragmented, elusive,
or all-consuming. Like an unstable, gas, an irritable exhaustion seeps into
every crevice of thought and action.
I truly hope the authors take this study
further and work towards a future treatment option for patients with major
depressive disorder.
Saytte et. al. (2009)’s study involves (almost) every college
student’s best friend. It usually comes in a red plastic cup and having the
first one makes having the second and third ones seem like a really good idea.
Saytte and his team investigated the effects of alcohol consumption on
consciousness and meta-consciousness. Specifically, fifty-four male social
drinkers were given either alcohol (0.82g alcohol/kg of body weight) or a
placebo beverage and subsequently asked to perform a mind-wandering reading
task. The key aspect of this experiment was the fact that both self-caught and
probe-caught “zone-outs” were utilized, thus allowing the authors to
differentiate between mind-wandering “inside and outside of awareness.” The
authors found that subjects given the alcohol exhibited more probe-caught
zoning out episodes compared to subjects given the placebo drink. Thus,
subjects given alcohol not only demonstrated a greater degree of mind
wandering, but also had a reduced probability of catching themselves. Indeed,
the experimental group engaged in mind wandering without awareness 25% of the
time. Based on these results, the authors conclude that alcohol impairs
individuals’ meta-awareness of their current thoughts. I think this study was
really well designed because it provided a true experiment on human subjects in
an area of study where such real experiments often cannot be done due to
obvious ethical reasons. For instance, the two previous studies examined
patient groups and compared them with control groups. Thus, their studies,
while rigorous and informative, do not constitute true experiments. In this
study, Saytte and colleagues were actually able to manipulate a variable and
examine the effects of that manipulation in an ethical way to provide important
information on mind-wandering and consciousness.
Manly
et. al. (2001) provide
a new battery of tests, namely the Test of Everyday Attention for Children
(TEA-Ch), for evaluating children’s attention. TEA-Ch is composed of nine
subsets taken and modified from adult attentional measures. By evaluating the
performance of 293 healthy children in TEA-Ch, the authors evaluated the
reliability of TEA-Ch in predicting attention in children. The second part of
this study involved evaluating the performance of 24 children with ADHD on
TEA-Ch. While results from TEA-Ch indicated that these children had deficits in
performance on all of the TEA-Ch measures (except the Sky Search task), they
did not shed much light on the extent to which attention skills were impaired. The
authors conclude that the subsets of the TEA-Ch are in fact not measures of attention, but of
auditory and visual detection, counting and response speed, etc.
I
think the main interest this article had for me was noting the differences
between children and adults in their attention patterns and thus the need for
specialized tests for children, which should be different from those for
adults, in diagnosing attention disorders such as ADHD and ADD. While I
recognize that severe forms of these diseases need treatment and medication,
there have been too many cases of extremely young children who were diagnosed
with ADD or ADHD being unnecessarily drugged due to flaws in the diagnosis
system. Most children are naturally more active; it is important to develop a
specialized test sequence for children and thus be absolutely sure that a child
needs mediation before prescribing one.
Some
Further Comments/Possible Future Investigations
When I read about the possible role of
DMN’s interaction with the rest of the brain in promoting a “coordinated
balance between internally and externally directed thought,” I was reminded of
schizophrenia. Although we know very little about schizophrenia, we do know
that a hallmark of this disease is uncontrolled internal thoughts. For
instance, patients report hearing voices that compel them to perform certain
actions. I would be extremely interested to see the role that the DMN plays in
schizophrenia and the different activation patterns and functional connections in
the DMN in healthy individuals and patients with schizophrenia.
References
Image
References
What is a Hangover? http://gizmodo.com/tequila/. Accessed 03/10/2013.
http://clinica2m.ru/news.html. Accessed 03/10/2013.
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