44 / 198
(
p
cluster
<
0.005,
p
voxel
<
0.005). This resulted in spatially distinct
correlation patterns of amygdala connectivity with the Buckley cog-
nitive, affective and somatic factors of the Beck Depression In-
ventory-II. These results indicate that amygdala connectivity may be a
potentially effective neuroimaging biomarker for comorbid depressive
symptoms among chronic TBI individuals.
Keywords: Amgydala, fMRI, Resting-state, functional connectivity,
Depression, TBI
T1-17
SLOWED CALLOSAL FUNCTION IN TBI LINKED TO
IMPAIRED WHITE MATTER INTEGRITY
Emily Dennis
1
, Monica Ellis
2,9
, Sarah Marion
9
, Claudia Kernan
2
,
Talin Babikian
2
, Richard Mink
3
, Christopher Babbitt
4
, Jeffrey
Johnson
5
, Christopher Giza
6
, Paul Thompson
1,7
, Robert Asarnow
8
1
Keck SOM USC, IGC, NII, Los Angeles, USA
2
UCLA, Dept. Psychiatry Biobehav Sciences, Los Angeles, USA
3
Harbor-UCLA Medical Center & Los Angeles BioMedical Research
Institute, Torrance, USA
4
Miller Children’s Hospital, Long Beach, USA
5
LAC
+
USC Medical Center, Dept. Pediatrics, Los Angeles, USA
6
Mattel Children’s Hospital, UCLA Brain Injury Research Center,
Dept. Neurosurg, Div. Ped Neurol, Los Angeles, USA
7
USC, Dept. Neurology, Pediatrics, Psychiatry, Radiology, En-
gineering, and Ophthalmology, Los Angeles, USA
8
UCLA, Dept. Psychology, Los Angeles, USA
9
Fuller Theological Seminary, Grad School Psychology, Pasadena,
USA
The corpus callosum is the most widely reported area of disruption
in traumatic brain injury (TBI). Here we present data linking dis-
rupted corpus callosum (CC) integrity to slowed callosal function in
pediatric moderate/severe TBI in the post-acute phase (1–6 months
post injury). We examined 63 participants: 32 TBI (mean age
=
14.2,
9 female), and 31 controls (mean age
=
14.9, 14 female). We used
visual ERPs (event related potentials) to measure IHTT (inter-
hemispheric transfer time, msec). EEG was recorded during a visual
pattern matching task. To assess white matter integrity, we used a
method developed in our lab, autoMATE (automated multi-atlas
tract extraction), to generate along-tract measures of fiber integrity.
The distribution of IHTTs showed a bimodal distribution within the
TBI group: some had IHTTs within 1.5 SD from the control mean,
but others differed significantly (group cut-off
=
18 msec min). We
ran an element-wise linear regression testing for differences in FA
and MD between the IHTT-slow TBI group and controls, and the
IHTT-normal TBI group and controls. IHTT-slow and control
groups differed significantly: the IHTT-slow group had lower FA
and higher MD across large areas of the CC and beyond. There were
minimal differences in FA between the IHTT-normal and control
groups, and none in MD. Our results indicate that TBI can cause
damage to myelin integrity, impairing the function of those tracts.
Keywords: IHTT, ERP, DTI, pediatric, traumatic brain injury,
corpus callosum
T1-18
INTRANASAL INSULIN TREATMENT OF TRAUMATIC
BRAIN INJURY: EFFECTS ON MEMORY AND CEREBRAL
METABOLISM
Fiona Brabazon
1
, Colin Wilson
2
, Shalini Jaiswal
2
, William H. Frey
3
,
Kimberly Byrnes
1,4
1
USUHS, Neuroscience Graduate Program, Bethesda, USA
2
USUHS, Department of Radiology, Bethesda, USA
3
University of Minnesota, Department of Neurology, Oral Biology
and Neuroscience, Minneapolis, USA
4
USUHS, Department of Anatomy, Physiology, and Genetics, Be-
thesda, USA
Traumatic brain injury (TBI) is often followed by a period of ce-
rebral hypometabolism. Impaired cerebral glucose uptake directly
affects long term patient outcome and is associated with cognitive
and physical deficits. Intranasal insulin, which bypasses the blood
brain barrier (BBB) to directly treat the brain, increases cerebral
glucose uptake in Alzheimer’s disease patients, and significantly
improves memory function in these patients. Our preliminary data
has demonstrated that 7 days of intranasal insulin treatment in-
creased speed of completion of a beam walk task in a rodent model
of TBI and increased viability of neurons and the number of anti-
inflammatory microglia in the hippocampus. We therefore hypoth-
esized that intranasal insulin would rescue cerebral metabolic
function and cognitive deficit resulting from TBI in a chronic
treatment model.
Adult male Sprague Dawley rats were exposed to a moderate
controlled cortical impact (CCI) injury followed by intranasal insulin
or saline treatment beginning 4 hours post-injury and continuing with
daily administration for 14 days. Positron emission tomography (PET)
scanning of radioactively labeled glucose (FDG
18
) was performed
prior to injury and again at 48 hours and 10 days post-injury. A
significant depression in glucose uptake was observed in both insulin
and saline treated groups, but a trend towards returning to baseline
values was observed in the ipsilateral hippocampus and hypothalamus
of the insulin treated group at 10 days post injury. Cognitive testing
with the Morris water maze revealed that intranasal insulin signifi-
cantly increased memory function in comparison to saline treatment,
as measured by probe trial island crosses. An analysis of the search
strategy used during the probe trial revealed that the insulin treated
animals performed significantly better than saline treated animals.
Tissue was also collected for assessment of macrophage and astrocyte
activity and neuronal viability.
Overall, we now show that intranasal insulin increases memory
function and has the potential to increase cerebral glucose uptake after
TBI. These data support our hypothesis that intranasal insulin, a drug
approved for clinical trials for the treatment of Alzheimer’s disease, is
effective in improving outcome following TBI.
Keywords: memory, insulin, PET, FDG18
T1-19
THE ROLE OF THE ATP-SENSITIVE POTASSIUM CHAN-
NEL IN THE VASCULAR DYSFUNCTION ASSOCIATED
WITH REPETITIVE MILD TRAUMATIC BRAIN INJURY
Masaki Todani
1,2
, Enoch Wei
1
, John Povlishock
1
1
Virginia Commonwealth University, Anatomy and Neurobiology,
Richmond, USA
2
Yamaguchi University Hospital, Advanced Medical Emergency and
Critical Care Center, Ube, Japan
Traumatic brain injury (TBI) has been associated with impaired ATP-
sensitive potassium (K
ATP
) channel function in both the neuronal and
vascular compartments. Both L-arginine and L-lysine are required to
activate the K
ATP
channel and exert both neuronal and vascular pro-
tection. While these protective effects have been confirmed following
uncomplicated TBI, their potential beneficial effects following re-
petitive TBI have not been established. In this study, we investigated
A-8