Dynamic
Communication
and
Connectivity
in
Frontal
Networks
Bradley
Voytek1
and
Robert
T.
Knight1,2
1Helen
Wills
Neuroscience
Institute
and
2Department
of
Psychology
University
of
California,
Berkeley,
CA
94720
How
do
we
maintain
a
stable
percept
of
the
world
in
the
face
of
the
powerful
drive
of
neuroplasticity
in
both
health
and
disease?
This
dichotomy
forms
one
of
the
most
fundamental
unanswered
questions
in
neuroscience
concerning
the
balance
between
the
dynamic,
plastic
underpinnings
of
our
neurobiology
and
the
relative
stability
of
our
cognition.
The
brain
undergoes
massive
changes
in
size,
morphology,
and
connectivity
during
normal
development
(see
Fig.
1,
Gogtay
et
al.,
2004)
and
aging
(Sowell
et
al.,
2003)
as
well
as
in
response
to
brain
injury
(Alsott
et
al.,
2009;
Carmichael,
2003),
yet
we
can
maintain
a
relatively
stable
sense
of
cognition
and
self
during
the
lifespan.
Human
brains,
each
with
over
100
billion
neurons,
develop
similarly
despite
the
wide
variations
in
environment
and
experience.
However,
within
the
bounds
of
this
stability
there
exists
a
wide
range
of
variability
and
capacity
for
change.
Here
we
will
discuss
the
role
of
neuroplasticity
in
frontal
lobe‐ dependent
cognition
by
examining
the
localization
of
attention
and
memory
functions
in
the
brain
and
how
these
seemingly
fixed
locations
may
reflect
flexible
neural
networks
that
change
communication
properties
as
required
by
behavior.
Figure
1.
Changes
in
grey
matter
volume
with
normal
development
(Adapted
from
Gogtay
et
al.,
2004).
This
figure
illustrates
the
structural
plasticity
of
the
neocortex
in
the
developing
human
brain,
especially
in
association
cortex,
during
childhood.
Note
the
relative
stability
of
primary
sensorimotor
and
visual
areas
by
puberty
in
contrast
to
the
plasticity
of
the
childhood
frontal
and
temporal
association
cortices.
Localization
of
Cognitive
Functions
Localization
of
cognitive
functions
in
the
human
brain
poses
a
major
problem
in
modern
neuroscience
(Brett,
Johnsrude,
&
Owen,
2002;
Young,
Hilgetag,
&
Scannell,
2000).
First,
there
is
the
problem
of
comparing
localization
of
function
data
across
methodologies
and
across
subjects
and
rectifying
findings
from
various
neuroimaging
and
neuropsychological
methodologies—each
with
their
own
limitations
and
underlying
assumptions—with
computational,
lesion,
and
animal
studies.
This
presents
a
daunting
prospect
for
any
investigator.
Second,
neuroscientists
face
the
inherent
morphological
variability
across
subjects;
currently,
any
claims
to
cortical
functional
specificity
are
probabilistic
claims
in
that—barring
direct
cortical
stimulation
mapping—one
cannot
guarantee
that
a
specific
cortical
region
plays
a
specific
functional
role.
For
example,
direct
cortical
stimulation
mapping
suggests
frontal,
temporal,
and
parietal
sites
are
all
involved
in
language
functions,
yet
the
specific
neuroanatomy
of
these
sites
differs
widely
across
subjects
(Sanai,
Mirzadeh,
&
Berger,
2008).
These
problems
are
not
just
theoretical
or
didactic
issues:
neurosurgeons
performing
surgical
tissue
resections
must
use
intraoperative
cortical
stimulation
mapping
to
ensure
that
the
cortical
tissue
to
be
removed
is
not
“eloquent”
(language
or
motor)
cortex.
Such
stimulations
are
performed
while
the
patient
is
awake
and
performing
cognitive
and
behavioral
tasks.
During
this
testing
period
the
surgeon
electrically
stimulates
different
brain
regions
to
monitor
speech
or
motor
arrest.
This
method—although
decades
old—is
still
widely
employed
because
of
the
known
variability
in
functional
localization
and
cortical
morphology
across
subjects.
Although
the
functional
localization
story
appears
bleak
at
the
level
of
a
single
individual,
cerebral
regions
of
functional
localization
are
clearly
observed
when
averaged
across
a
group
of
subjects
with
neuroimaging
techniques
such
as
functional
magnetic
resonance
imaging
(fMRI)
and
positron
emission
tomography
(PET).
Most
studies
rely
upon
the
principle
of
cognitive
subtraction,
originally
established
in
reaction
time
studies
by
Franciscus
Donders
(Donders,
1869).
The
underlying
assumption
in
these
studies
is
that
activity
in
brain
networks
alters
in
a
task‐dependent
manner
that
becomes
evident
after
averaging
many
event‐related
responses
and
comparing
those
against
a
baseline
condition.
Deviations
from
this
baseline
reflect
a
change
in
the
neuronal
processing
demands
required
to
perform
the
task
of
interest.
Although
both
the
cognitive
subtraction
method
(Friston
et
al.,
1996)
and
assumptions
regarding
baseline
activity
(Gusnard
&
Raichle,
2001)
have
their
own
problems,
these
methods
provide
details
of
functional
localization
that
can
then
be
tested
and
corroborated
using
other
methodologies,
including
lesions
studies.
The
interpretation
of
these
localization
results
is
confounded,
however,
by
a
lack
of
clarity
in
what
is
meant
for
a
“function”
to
be
localized.
For
example,
Young
and
colleagues
(2000)
noted
that
for
a
given
function
to
be
localizable
that
function
“must
be
capable
of
being
considered
both
structurally
and
functionally
discrete”;
a
property
that
the
brain
is
incapable
of
assuming
due
to
the
intricate,
large‐scale
neuronal
interconnectivity.
Thus,
discussing
behavioral
functions
outside
of
the
context
of
the
larger
cortical
and
subcortical
networks
involved
with
that
function
is
a
poorly
posed
problem.
Therefore,
the
scientific
study
of
cognition
requires
detailed
neuroanatomical
and
connectivity
information
to
compliment
functional
activity
findings.
The
current
effort
to
map
a
human
connectome
(Sporns,
Tononi,
&
Kötter,
2005)
will
provide
researchers
with
the
neuroanatomical
roadmap
necessary
to
examine
changes
in
large‐scale
cortical
network
activity
during
cognition.
The
Lesion
Method
While
functional
neuroimaging
techniques
such
as
fMRI
and
PET
have
advanced
our
understanding
of
regional
specificity,
the
lesion
method
provides
the
strongest
case
in
the
argument
for
causality
in
functional
neuroanatomy;
i.e.,
brain
region
A
can
be
assumed
to
play
an
important
role
in
the
network
supporting
function
X
if
a
lesion
to
A
impairs
function
X.
Research
on
humans
with
focal
brain
lesions
(e.g.,
Fig.
2)
has
provided
seminal
information
with
regards
to
our
understanding
of
which
brain
regions
contribute
to
specific
behavioral,
sensory,
and
cognitive
functions
(Rorden
&
Karnath,
2004).
For
example,
because
prefrontal
(PFC)
and
basal
ganglia
lesions
lead
to
working
memory
deficits
(Voytek
&
Knight,
submitted;
Müller
&
Knight
2006;
Tsuchida
&
Fellows,
2009),
the
PFC
can
be
said
to
play
an
important,
if
not
necessary
role
in
working
memory
networks.
Figure
2.
Patient
lesion
reconstructions.
These
structural
MRI
slices
illustrate
the
lesion
overlap
across
six
patients
with
unilateral
PFC
lesions.
All
lesions
are
normalized
to
the
left
hemisphere
for
comparison
although
two
patients
had
right
hemisphere
lesions
(Adapted
from
Voytek
et
al.,
submitted).
Examining
groups
of
patients
with
stereotyped
lesions
allows
researchers
to
test
the
role
of
specific
regions
in
behavior.
Software
reconstructions
were
performed
using
MRIcro
(Rorden
&
Brett,
2000).
By
combining
lesion
studies
with
neuroimaging
techniques,
researchers
can
identify
other
brain
regions
associated
with
a
certain
behavior.
For
example,
research
using
scalp
electroencephalography
(EEG)
has
shown
that
unilateral
PFC
lesions
cause
lateralized
deficits
in
top‐down
modulation
of
activity
in
visual
extrastriate
cortex
during
attention
(Fig.
3,
Barceló,
Suwazano,
&
Knight,
2000;
Yago
et
al.,
2004)
and
working
memory
(Voytek
&
Knight,
submitted),
which
makes
EEG
a
powerful
tool
for
investigating
the
network
dynamics
subserving
cognition.
Figure
3.
Examining
the
effects
of
unilateral
PFC
lesions
on
attention
networks.
A,
Illustration
of
the
lateralization
of
early
visual
activity
modulated
by
attention.
For
healthy
control
subjects
(top),
lateralized,
attended
stimuli
lead
to
early
(~150ms)
activity
increases
in
visual
extrastriate
cortex
(orange
region).
For
patients
with
unilateral
PFC
lesions
(shaded
region,
bottom),
normal
attention‐related
activity
increases
are
seen
for
stimuli
presented
ipsilesionally
(orange),
however
when
stimuli
are
presented
contralesionally
patients
show
activity
deficits
compared
to
controls
(blue).
This
effect
is
seen
in
scalp
EEG
in
B
(Adapted
from
Barceló,
Suwazano,
&
Knight,
2000).
While
the
underlying
notion
of
brain
damage
disrupting
function
is
fairly
obvious—damaging
parts
of
a
machine
prevent
the
machine
from
working
optimally—the
specific
effects
of
brain
damage
are
neither
obvious
nor
always
predictable.
There
are
several
factors
that
prohibit
accurate
prediction
of
which
deficits
will
manifest
after
a
given
brain
lesion.
This
is
largely
due
to
the
fact
that
we
are
still
uncertain
with
regards
to
the
accuracy
of
regional
localization
of
function
and
the
poorly
posed
nature
of
the
functional
localization
question
in
general.
Because
the
probability
distribution
of
functional
localization
across
subjects
is
broad,
especially
across
cortical
association
areas
(Sanai,
Mirzadeh,
&
Berger,
2008),
the
importance
of
distributed
cortical
networks
in
behavior
and
subsequent
recovery
cannot
be
ignored.
Nevertheless,
working
with
patients
with
circumscribed
frontal
brain
lesions
provides
us
with
insight
into
how
frontal
cortex
interacts
with
the
rest
of
the
brain
to
give
rise
to
cognitive
functions.
When
combined
with
computational
and
behavioral
methodology
and/or
neuroimaging,
the
lesion
method
allows
researchers
to
examine
exactly
which
areas
are
critical
for
which
cognitive
functions.
For
example,
recent
work
by
Badre
and
colleagues
took
advantage
of
the
inherent
differences
in
lesion
size
and
extent
in
their
patient
populations
to
examine
the
rostral/caudal
organization
of
cognitive
and
action
control
in
the
frontal
cortex
(Badre
et
al.,
2009).
While
this
“messiness”
of
lesion
size,
extent,
and
location
has
traditionally
been
viewed
as
a
major
drawback
of
the
lesion
method,
it
is
the
cornerstone
of
voxel‐based
lesion‐symptom
mapping
(VLSM)
(Fig.
4,
Bates
et
al.,
2003).
This
method
requires
a
detailed
neuroanatomical
scan
of
every
patient;
t‐ tests
are
then
performed
at
every
voxel
on
a
variable
of
interest
(e.g.,
a
cognitive
task)
where
the
statistical
“groups”
are
defined
by
whether
the
patient
has
a
lesion
in
that
specific
voxel
or
not.
This
clever
technique
allows
researchers
to
map
voxel‐ by‐voxel
which
regions
are
most
important
for
a
cognitive
function.
Figure
4.
Example
of
VLSM
(Adapted
from
Bates
et
al.,
2003).
These
maps
show
speech
fluency
(AC)
and
language
comprehension
(DF)
in
101
aphasic
stroke
patients.
Color
represents
the
effect
of
lesion
on
behavior
with
large
t‐values
suggesting
a
significant
relationship
between
the
presence
of
a
lesion
and
a
behavioral
deficit.
Recent
work
has
expanded
the
lesion
method
into
computational
modeling.
Using
a
cortically‐plausible
network
architecture
researchers
have
shown
the
effects
of
lesions
on
functional
connectivity
(Alstott
et
al.,
2009;
Young,
Hilgetag,
&
Scannell,
2000)
and
on
oscillatory
dynamics
(Honey
&
Sporns,
2008)
demonstrating
activity
changes
in
remote
brain
areas
(Reggia,
2004)
not
directly
connected
to
the
lesioned
brain
region
(Young,
Hilgetag,
&
Scannell,
2000).
These
findings
suggest
that
lesions
to
highly
connected
critical
hubs—including
frontal
and
parietal
regions—result
in
widespread
changes
in
functional
connectivity
and
oscillatory
communication.
Recovery
and
Compensation
Predicting
the
course
of
recovery
from
brain
damage
is
confounded
by
a
lack
of
understanding
about
the
extent
and
time
course
of
recovery
possible
across
different
regions
of
the
central
nervous
system.
Neural
plasticity
is
critical
for
functional
recovery
after
brain
damage
with
improvement
possible
even
20
years
after
the
initial
injury
(Bach‐y‐Rita,
1990).
There
are
several
theories
of
recovery
of
function
(Grafman,
2000),
including:
cortical
compensation
by
perilesion
and
intact
homologous
brain
regions
(Wundt,
1902)
or
subcortical
(Van
Vleet
et
al.,
2003)
structures;
diaschisis
reversal
(von
Monakow,
1969);
unmasking
(Lytton,
Williams,
&
Sober,
1999);
distributed
cortical
representations
(Jackson,
1958);
and
axonal
sprouting
and
neurogenesis
(Carmichael
et
al.,
2001).
Many
of
these
theories
predate
neuroimaging
and
were
based
on
clinical
observations
of
patients
with
brain
damage.
In
1902,
Wilhelm
Wundt
noted
that,
…in
both
simple
and
complex
disturbances,
there
is
usually
a
gradual
restoration
of
the
functions
in
the
course
of
time.
This
is
probably
effected
by
the
vicarious
functioning
of
some,
generally
a
neighboring
cortical
region
in
place
of
that
which
is
disturbed
(in
disturbances
of
speech,
perhaps
it
is
the
opposite,
before
untrained,
side
that
comes
into
play).
This
latter
point
was
proved
in
a
recent
paper
wherein
Blasi,
et
al.
demonstrated
that
patients
who
have
recovered
from
Broca’s
aphasia
due
to
left
frontal
stroke
show
fMRI
activation
in
the
right
frontal
Broca’s
area
homologue
(Fig.
5A,
Blasi
et
al.,
2002).
The
fact
that
the
brain
is
not
a
static
machine,
but
rather
a
fluctuating
(plastic),
self‐repairing
organ
(Cramer,
2008),
provides
an
important
confound
to
lesion‐based
research.
For
example,
most
lesion
studies
that
demonstrate
behavioral
deficits
in
humans
are
performed
on
patients
who
have
had
sudden
(acute)
brain
damage
(e.g.,
stroke
or
trauma)
precisely
because
these
patients
show
the
strongest
behavioral
deficits.
In
contrast,
patients
who
have
undergone
surgical
resections
to
remove
cancerous
cerebral
tissue
tend
to
show
fewer
deficits
before
and
after
their
surgeries
(Desmurget,
Bonnetblanc,
&
Duffau,
2006)
compared
to
a
patient
with
a
comparably
size
lesion
from
a
stroke.
This
phenomenon
is
interpreted
as
recovery
processes
resulting
from
compensation
by
other
brain
regions
in
cases
of
slow‐growing
lesions.
Because
the
lesions
are
slow‐growing
rather
than
rapidly‐occurring
(such
as
from
stroke),
the
hypothesis
is
that
the
deficits
resulting
from
the
lesion
are
minimized
due
to
the
incrementally
slow
rate
of
growth
permitting
compensatory
processes
to
mask
those
deficits.
By
definition,
acute
lesions,
on
the
other
hand,
result
in
rapid
tissue
damage
that
cannot
be
(immediately)
compensated
for.
Thus,
though
patient
work
is
invaluable,
the
temporality
of
the
lesion
(both
onset
time
and
time
since
damage)
should
not
be
discounted.
Given
the
number
of
brain
regions
needed
to
support
cognitive
functions,
it
is
not
unreasonable,
given
the
variety
of
recovery
theories,
to
hypothesize
that
cognitive
recovery
could
be
supported
by
any
part
of
the
cognitive
network.
The
PFC
however
plays
an
important
role
in
cognitive
networks
by
biasing
information
flow
in
other
regions
to
favor
positive
behavioral
outcomes
(Miller
&
Cohen,
2001).
Therefore,
the
PFC
may
play
a
privileged
role
in
cognitive
compensation.
For
example,
although
patients
with
lateral
PFC
lesions
have
lasting
attention
and
working
memory
deficits
(e.g.,
Voytek
&
Knight,
submitted;
Barceló,
Suwazano,
&
Knight,
2000),
cognitive
functions
can
recover
somewhat
over
time
(Voytek
et
al.,
submitted).
Numerous
studies
suggest
that
the
PFC
plays
a
diverse
role
in
a
wide
range
of
cognitive
functions
involved
in
the
allocation
and
control
of
visual
attention
and
working
memory.
One
hypothesis
is
that
the
PFC
maintains
an
association
between
endogenous
elements
in
working
memory
while
an
unknown
neuronal
mechanism
compares
these
endogenous
representations
to
exogenous
visual
information
as
it
is
processed
in
extrastriate
visual
areas
(Barceló,
Suwazano,
&
Knight,
2000;
Kimberg
&
Farah,
1993).
It
is
important
to
note
that
neuropsychological
testing
alone
can
be
misleading
concerning
the
extent
of
recovery
after
PFC
damage.
For
example,
if,
during
an
attention
task,
visual
stimuli
are
presented
full‐field,
that
is,
presented
in
the
center
of
the
visual
field
and
with
unrestrained
eye‐movements,
patients
with
unilateral
PFC
lesions
do
not
show
obvious
visual
attention
deficits.
However,
if
visual
stimuli
are
lateralized
to
the
left
or
right
visual
hemifield
by
a
matter
of
a
few
degrees
and
central
fixation
is
maintained,
then
deficits
in
visual
working
memory
(Voytek
&
Knight,
submitted)
and
attention
(Barceló,
Suwazano,
&
Knight,
2000)
are
clearly
evident.
Visual
stimulus
lateralization
takes
advantage
of
the
neuroanatomy
of
the
mammalian
visual
system
such
that
stimuli
presented
to
the
right
visual
hemifield
preferentially
activate
the
left
visual
cortex
(and
vice
versa)
before
that
information
is
then
transferred
to
the
opposite
visual
cortex
via
the
corpus
callosum.
Such
lateralized
designs
increase
statistical
power
in
that
patients
can
serve
partially
as
their
own
controls
(i.e.,
“good”
hemifield
vs.
“bad”
hemifield;
see
Fig.
3A),
thus
allowing
for
a
within‐subjects
comparison
of
the
effects
of
the
brain
lesion
on
a
cognitive
function
for
contralesionally‐
versus
ipsilesionally‐presented
stimuli.
Nevertheless,
even
in
lateralized
visual
attention
and
working
memory
paradigms
patients
with
unilateral
PFC
damage—though
worse
than
control
subjects
when
stimuli
are
presented
contralesionally—still
perform
well
above
chance
levels.
This
finding
is
somewhat
in
contrast
to
what
is
observed
in
lesion
and
neuroimaging
studies
of
primary
cortical
functions.
Neuroimaging
studies
of
movement
or
visual
processing
localize
these
processes
to
motor
and
visual
cortex,
respectively.
Lesions
to
primary
motor
or
primary
visual
cortex
lead
to
striking
and
permanent
deficits
(hemiparesis
or
cortical
blindness,
in
these
specific
cases).
Conversely,
while
functional
neuroimaging
studies
show
task‐dependent
PFC
activation
during
attentional
control
and
working
memory,
lesions
to
the
PFC
lead
to
an
incomplete
loss
of
those
functions.
This
discrepancy
may
have
any
number
of
underlying
causes,
including
any
combination
of
the
following:
1.
Research
paradigms
used
to
assess
cognitive
deficits
may
be
less
sensitive
and
less
specific
than
those
used
to
examine
motor
or
sensory
deficits;
2.
Cognitive
processes
dependent
on
association
cortex
may
be
more
widely
distributed
across
a
broader
network
than
those
dependent
on
primary
cortex,
making
cognitive
processes
more
resilient
to
a
single
focal
lesion;
3.
Compensatory
mechanisms
may
be
facilitating
damaged
cognitive
functions
more
than
primary
functions.
In
order
for
neuronal
activity
differences
to
be
considered
“compensatory”,
Davis
et
al.
(2008)
have
outlined
at
least
two
criteria
that
must
be
met.
First,
novel
activity
increases
not
seen
in
normal
controls
(but
seen
in
e.g.,
lesion
patients)
must
be
associated
with
correct
behavioral
outcomes.
Second,
deficits
in
processing
by
one
region
must
be
associated
with
increases
in
activity
in
the
putative
compensatory
region.
These
criteria
are
important
because
activity
increases
interpreted
as
“compensatory”
may
in
fact
more
simply
reflect
a
global
increase
in
cortical
activity
due
to
increases
in
difficulty
in
performing
a
task
for
lesion
patients
compared
to
control
subjects
(Hillary
et
al.,
2006).
That
is,
because
of
the
lesion,
more
cognitive
resources
are
recruited
in
order
to
correctly
perform
the
task
compared
to
controls.
In
the
context
of
unilateral
PFC
damage
and
its
effects
on
attention
and
working
memory,
Voytek
et
al.
(submitted)
hypothesized
that
the
intact,
undamaged
PFC
compensates
for
the
damaged
cortex
in
a
load‐dependent
manner
as
required
by
task
demands.
What
was
observed
(Fig.
5B),
consistent
with
the
first
criterion
for
compensation,
was
that
increases
in
activity
over
the
intact
PFC
are
enhanced
on
correct
trials
when
the
damaged
PFC
is
challenged
with
lateralized
visual
working
memory
or
attention
demands.
With
regards
to
the
second
criterion,
their
experimental
designs
preferentially
challenged
the
damaged
hemisphere
in
patients
with
unilateral
PFC
damage,
and
increases
in
activity
over
the
intact
PFC
were
seen
in
conjunction
with
top‐down
deficits
in
the
visual
extrastriate
cortex
of
the
damaged
hemisphere.
It
is
important
to
highlight
that
the
decreased
posterior
extrastriate
responses
seen
in
cognitive
experiments
with
patients
with
unilateral
PFC
damage
(Voytek
&
Knight,
submitted;
Barceló,
Suwazano,
&
Knight,
2000)
are
only
seen
when
stimuli
are
presented
to
the
contralesional
hemifield.
If
we
are
to
assume
that
these
posterior
responses
normally
index
behavior
and
performance— and
PFC
patients
show
attenuated
extrastriate
responses
even
when
correctly
performing
the
task—then
logically
there
must
be
some
other
brain
regions
compensating
for
the
lesioned
cortex.
Figure
5.
Examples
of
compensatory
activity
after
frontal
damage.
A,
Compared
to
healthy
control
subjects,
patients
with
damage
to
left
inferior
frontal
gyrus
who
have
recovered
from
speech
deficits
show
increased
activation
in
the
homologous
area
in
the
intact
hemisphere
(blue
arrow)
and
decreased
activation
in
the
damaged
region
(red
arrows;
Adapted
from
Blasi
et
al.,
2002).
B,
Using
lateralized
visual
stimulus
designs,
Voytek
et
al.,
(submitted)
showed
that
patients
with
unilateral
PFC
lesions
(shaded
regions)
show
increased
activity
over
the
intact
PFC
only
when
the
damaged
hemisphere
was
directly
challenged
with
visual
stimuli.
This
activity
was
not
seen
in
control
subjects
and
it
scaled
with
cognitive
demands.
As
previously
stated,
research
indicates
that
the
perilesion
cortex
and
the
homologous
intact
contralateral
cortex
may
both
be
involved
in
recovery
and
that
there
is
long‐range,
intracortical
reorganization
of
behaviorally‐
and
recovery‐ relevant
pathways
(Nudo,
2007;
Dancause,
2006).
Thus,
Voytek
et
al.
proposed
that
the
visual
information
delivered
to
the
contralesional
hemisphere
is
transferred
trans‐callosally
to
the
intact
hemisphere
where
the
intact
PFC
then
assumes
task
control
as
needed
on
a
trial‐by‐trial
basis.
Support
for
this
contention
is
provided
by
studies
in
non‐human
primates
revealing
that
top‐down
PFC
control
over
visual
cortex
during
memory
retrieval
relies
on
callosal
information
transfer
(Hasegawa
et
al.,
1998;
Tomita
et
al.,
1999).
Thus,
if
transcallosal
information
transfer
could
be
blocked,
then
behavioral
deficits
should
be
enhanced.
As
discussed
previously,
in
contrast
with
cognitive
deficits,
primary
motor
and
sensory
functions
rarely
recover
in
adults
who
suffer
cortical
damage,
although
other
modalities
may
take
over
intact
sensory
cortex
deprived
of
input
due
to
peripheral
damage
(Sadato
et
al.,
1996).
Unlike
adults
with
primary
cortical
damage,
children
who
have
had
a
surgical
hemispherectomy,
for
example,
can
regain
motor
control
of
the
affected
limbs
(Benecke
1991);
such
recovery
can
be
seen
even
in
children
with
massive
and
severe
cortical
damage
(e.g.,
Distelmaier
et
al.,
2007).
In
contrast,
others
have
observed
a
surprising
normality
among
patients
missing
massive
amounts
of
their
cortical
tissue
(Lewin,
1980).
While
deficits
caused
by
lesions
to
PFC
are
more
likely
to
recover
if
lesions
occur
later
in
life—and
this
recovery
may
be
dependant
upon
having
some
amount
of
intact
PFC
(Kolb
&
Gibb,
1990)—
children
with
PFC
damage
may
have
lasting
cognitive
impairment
(Kolb
&
Gibb,
1990).
The
interaction
between
age
and
location
of
lesion
with
behavioral
recovery
may
reflect
a
deeper
relationship
with
the
evolution
of
cognitive
and
sensory
functions
in
primates
(Anderson,
2007)
wherein
cognitive
functions,
having
evolved
more
recently,
are
more
distributed
across
cortex
and
thus
more
resistant
to
focal
brain
damage
once
those
functions
have
developed
in
adulthood.
Integrating
all
of
the
prior
points
it
may
be
that
the
farther
away
from
primary
cortical
areas
a
region
is,
the
less
predictable
the
function
becomes.
This
phenomenon
may
help
explain
why
we
have
fairly
robust
sensory
and
motor
homunculi
in
the
primary
(“lower”)
cortical
areas,
but
no
reliable
mapping
in
the
“higher”
sensory
and
motor
association
cortices.
This
is
illustrated
by
example
from
clinical
observations:
a
patient
with
damage
to
the
premotor
cortex
is
more
likely
to
recover
motor
functions
than
a
patient
with
a
lesion
of
primary
motor
cortex,
who
in
turn
is
more
likely
to
naturally
recover
than
a
person
with
a
lower
motor
neuron
lesion
in
the
spinal
cord.
A
network
theoretic
view
of
this
phenomenon
would
suggest
that
differences
between
the
focal
networks
of
primary
regions
and
distributed
networks
of
the
functions
subserved
by
association
cortex
may
account
for
these
differences
in
recovery.
Given
the
above
caveats,
in
order
to
study
human
cortical
recovery
of
function
one
must
carefully
balance
recovery
likelihood
with
probability
of
functional
localization.
That
is,
in
theory,
one
is
more
likely
to
find
a
reliable
deficit
across
subjects
with
damage
to
primary
cortical
regions,
but
less
likely
to
observe
recovery
in
these
patients.
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