PowerPoint Slides - War Related Illness and Injury Study Center

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20 Οκτ 2013 (πριν από 4 χρόνια και 24 μέρες)

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Maheen M. Adamson, PhD

Director of Clinical Neuroscience,

War Related Illness and Injury Study Center (WRIISC)

VA Palo Alto Health Care System

Clinical Assistant Professor (Affiliated) of Psychiatry and
Behavioral Sciences

Stanford University School of Medicine, CA


Future Tools for Diagnosis and Monitoring of
mild TBI

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Disclaimer

The views expressed in this presentation are those of the authors
and DO NOT reflect the official policy of the


Department of Veterans Affairs

or

the United States Government

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Outline


Task
-
related Functional MRI


Resting State Functional MRI


Functional Connectivity


why is it important?


Combining
neuroimaging

methods


Promising future avenues for
mTBI

research


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Why Functional MRI

Common things heard in hallways:


fMRI is not clinical


Analysis takes a long time and is very confusing


Statistical significance = red/blue blobs?


Any task will show activation


what difference does
it make?


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MRI vs. fMRI

MRI studies brain anatomy

Functional MRI (
fMRI
)studies brain
function

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The meaning of CONTRAST

Stimulation

Control/baseline

An
example
using PET

Difference

-

=

fMRI measures Blood Oxygenation Level
Dependent (BOLD) signal indirect measure
of neural activity.


Neural activity Blood oxygen fMRI signal

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Developing fMRI literature on TBI


Task
-
induced changes that differentiate clinical and
healthy samples during cognitive, motor and sensory
tasks.


Working memory deficits after TBI: universal
observation of increased involvement of the regions
critical for WM, including prefrontal cortex (PFC) and
anterior cingulate cortex (ACC) and occasionally
parietal regions in TBI

(Christodoulou et al., 2001; Hillary et al., 2010, 2011; McAllister et al., 1999, 2001;
Medaglia

et al., 2011; Newsome et
al., 2007;
Scheibel

et al., 2007).

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Working Memory in
mTBI

McAllister et al., 2001

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Longitudinal fMRI in Severe TBI


Increased
activation observed after
6
-
month evolution in TBI patients
during the 3
-
back condition.


The
most striking changes were
seen in the bilateral prefrontal
cortex,
with left
hemisphere
predominance.


The
second region that showed
statistical significant changes was
the
bilateral parietal
posterior
region.


Both
regions are involved in
working
memory processes
.
Statistical Parametric Maps with left
as left.

Sanchez
-
Carrion et al., 2008

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Functional Brain changes with recovery of TBI


A recent study represents the first effort in systems
neuroscience to examine how
practice

of a
cognitive task influences BOLD signal change after
neurological compromise (
Medaglia

et al., 2011).


The goal of this study was to induce plasticity in PFC via
task practice using a well
-
established working memory
task in individuals with TBI to test that right PFC
recruitment represents a latent support system.

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N = 1 back task

N = 2 back task

Regions of interest show reduced activation following practice, including the anterior cingulate
and right prefrontal cortices. Neural recruitment in brain injury does not represent
reorganization but a natural extension of latent mechanisms that engage transiently and are
contingent upon cerebral challenge

Right BA 46 (DLPFC)

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What About Intrinsic Differences In Brain
Activity Irrespective Of Task?

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Conventional MRI and resting
-
state fMRI correlation analysis in a
21
-
year
-
old with verbal memory deficits following severe TBI

MacDonald et al., 2008


Conventional MRI (FLAIR) revealed bilateral superior frontal lesions but no abnormalities
that would explain the patient’s verbal memory deficit (left to right: transverse slices at the
level of hippocampus, thalamus, fornix,
cingulum
).


Volumetric MRI showed 18% loss of left hippocampus.


DTI revealed subtle abnormalities in the left and right
cingulum

bundles as well as left and
right
fornices
. Relative anisotropy in the
cingulum

and fornix were lower than the mean of
10 control subjects matched in age, gender, and handedness. Relative anisotropy was not
more than 2 SD below the mean in any of the regions
-

cannot be considered definitively
abnormal.

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Resting State fMRI

MacDonald et al., 2008



Resting state
fMRI

correlation analysis clearly demonstrates disruption of the normal
connectivity of the left
hippocampal

network



Analysis revealed that the BOLD fluctuations in the left hippocampus correlated poorly
with those in several other structures implicated in memory including anterior thalamus
and the ventral anterior cingulate cortex (
vACC
)



In contrast, the fluctuations in the right hippocampus were normally correlated with
those in these structures. No such left
-
right asymmetry in the hippocampal
-
anterior
thalamic and
hippocampal
-
vACC

correlations was seen in 10 age
-
matched controls.

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What Is This ‘RESTING STATE” Business?


Why do a Resting State FMRI?


INTRINSIC CONNECTIVITY NETWORK
(ICN) is another
way to refer to Resting State.


Functional connectivity (FC)
: is the correspondence over
time (co
-
activation) between spatially distinct
neurophysiological

events without implying directionality


May be observed from the spontaneous activity of the
resting brain.

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What Does the Data Look Like?


Synchronous low frequency fluctuations (LFF) signals
within blood oxygen level
-
dependent fMRI data
can be useful for investigating the functional
connections of brain cortices.


Brain cortices are characterized by LFF frequencies
less than 0.1 Hz, distinct from respiratory and
cardiac effects, with a frequency spectrum ranging
from 0.1 to 0.5 Hz and 0.6 to 0.12 Hz,
respectively.

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Methods of Analysis


Seed Analysis


Connectivity between the seed of right hippocampus and
a set of regions was disrupted in the early stage of
Alzheimer’s Disease (AD), whereas the seed of left
hippocampus showed increased connectivity with some
other regions (Wang et al. 2006)


Independent Component Analysis (ICA)


In mild AD, FC is deficient between the PCC and left
hippocampus or other regions within default (
Greicius

et
al., 2004)

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Most Common Networks


Default Mode Network


Significant resting
-
state
coactivation

of Posterior
Cingulate Cortex (PCC), bilateral inferior parietal
cortex, left
inferolateral

temporal cortex, & ventral
anterior cingulate cortex. Abnormal changes in
Alzheimer’s
(Li et al., 2002)



Salience Network



Anterior cingulate cortex and fronto
-
insula, amygdala
and striatum

disrupted in behavioral variant
frontotemporal dementia.


How Many Networks?

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Terms used


The
synchrony
of LFF implies that within neural
networks, the nodes function together


Task “on” vs. Task “off” and brain at rest.


“Co
-
activation” of task “on” regions with task “off”
regions
: Those regions activated during task “on”
period (e.g.,
visuo
-
spatial task) are deactivated when
the task is “off” (e.g., fixation)

Goal Directed
networks


Inward or self
-
reflected network


resting state or ICN


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Task
-
on and Task
-
off


It is not that these networks are reciprocal so that at
moments where goal
-
directed behavior is necessary,
the “inward” or self
-
reflective default mode network
remits, giving way to neural activity relevant to task.


Default mode activity plays a role in task and the
magnitude of deactivation in default mode regions
contribute to task performance
(Cole et al., 2010;
Hampson

et al., 2010)


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Changes in Resting Connectivity During
Recovery in TBI

Hillary et al., 2011

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Change in Connectivity in TBI

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FA/ICN Combined for
mTBI

Investigations


DTI/FA values (seed regions).


fMRI resting state, network analysis


Mayer et al., 2011


What the future holds?

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Real
-
world Performance

http://www.huffingtonpost.com/2008/12/01/army
-
bases
-
brace
-
for
-
surg_n_147360.html

Brain Function During Real
-
world
Performance

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Thank you!



Questions?