1. Cerebellar White Matter Integrity
and Depression in Chronic TBI
Deborah M. Little PhD
Patrick Glang
Michelle Pennington BA
Baylor Scott & White Health
University of Oregon
Texas A&M Health Sciences
College of Medicine

2. Funding and Disclosure
There are no financial conflicts of interest related to the
specific topic of this lecture.
Funding - TBI
Department of Defense W81XWH-08-1-0732 (Little)
Veterans Administration RR&D 1I01RX000394 (Little)
Veterans Administration RR&D 1I01RX000304 (Morissette)

3. Scope of the Problem
Population based retrospective, self report studies have repeatedly
found and reported an increased risk of MDD in persons who also
report a history of TBI. However, these studies lack many controls
needed to assess the true prevalence and incidence of these comorbid
conditions and do not address the primary question as to whether TBI
results in increased risk of MDD.
TBI traumatic brain injury (mild, moderate, severe/traumatic)
Known:
1. Holsinger and colleagues found an increased lifetime prevalence of MDD in veterans (~18%;
WWII) than in combat controls (~14%)
2. Surveillance (Jorge et al 1993; Seel et al 2003; Kreutzer et al 2001), Jorge et al, 2004) studies show
an increased rate of dx of MDD in those with a recent history of TBI
• Case control studies, Hospital based recruitment
• Patient history of premorbid depression, anxiety disorders increased risk of depression post-
TB
3. Depressive symptoms in Chronic TBI have been shown to have neuroanatomical correlates that
include those in the fronto cerebellar circuit.

4. Why look at the cerebellum?
- Preliminary data from our lab using voxel based morphometric
analyses identified the cerebellum as the region most related to
current depressive symptoms

5. Why look at the cerebellum?
- Preliminary data in combat-related TBI has shown that white
matter injury in the cerebellum may be more specific and sensitive
to depressive symptoms when compared to PTSDUncinate Fasciculus
H
C
TBI
PTSDTBI+PTSD
TBI+D
epression
FractionalAnisotropy
0.30
0.35
0.40
0.45
0.50
0.55

6. Why look at the cerebellum?
- Biomechanical modelling highlights sensitivity of the cerebellum as
a position structure of high vulnerability to shear and strain injury
- The cerebellum has been demonstrated to be related to MDD in
non-TBI pediatric and adult patients including localized ischemic
insult
- Cognitive Cerebellar Affective Syndrome, Schmahmann 1998

7. Methods
 A total of 24 patients with a history of non-combat,
single, closed-head type TBI (24mild, 24mod) and 24
demographically matched controls participated
 For the TBI patients, the index injury was required to
have occurred after age 17 and at least 12 months prior
to the study. All subjects were required to be native
speakers of English.
 Detailed neuropsychological testing was also performed
to characterize executive function, memory, and
attention.

8. Methods
 Imaging was conducted using parallel imaging together
with an 16-channel phased-array head coil
 Fractional anisotropy (FA) was extracted from regions
of interest in the pontine cross tracts, middle and
superior cerebellar peduncles, portions of the cortico-
spinal tract and medial lemniscus (bilaterally when
appropriate).
 Three regions of interest
were placed on each tract.
 Regions were drawn
independently by two
raters (PG, MP) and
exceeded reliability of 0.91

9. Results
Inf CSTMedial lemniscus Pontine crossing tracts
• The moderate to severe TBI group had reduced FA – relative to
controls – in all ROIs
• The moderate to severe TBI group differed from the mild TBI
group in all ROIs
• The mild TBI differed from controls for regions of interest in the
medial lemniscus, pontine crossing tracts and inferior portions of
the CST (p<0.01 for all)

10. Results
Correlations between cerebellar FA and BDI II
• No significant correlations between FA and BDI on any measures
for controls
• For the mild TBI, BDI II total score was associated with reduced
FA in the medial lemniscus (p=0.006)
• For moderate to severe, depressive symptoms were associated
with reduced FA in the pontine fibers (p=0.04), cortico-spinal
tract (p=0.02) and superior cerebellar peduncles (p=0.04)

11. Conclusions
Damage to the cerebellar white matter appears to have a relationship
with depressive symptoms in chronic TBI
Those tracts that cross or traverse from the spine up through
superior cortical areas appear to be more affected by non-combat
acceleration-deceleration injury
Preliminary investigations into volumetric alterations also appear to
be altered in mild and moderate TBI which is not consistent with
other studies of mild TBI
FA of the caudate and SN also show similar relationships raising the
question of the role of the dopaminergic network in TBI
Finally, cerebellar integrity appears to account for depressive
symptoms along the same magnitude as gross measures of cortical
white matter integrity.

12. Acknowledgements
• Deborah M. Little PhD
• Ulrich Mayr PhD
• Michelle Pennington BA
• Jane Gillett
• University of Oregon
• Baylor University
• Scott & White Healthcare
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