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dependent on dorsolateral prefrontal-striatal circuitry,

potentially disrupted following damage to the SVZ.

Motor speed

was assessed using Purdue Pegboard

, 36

which measures the time it takes to place pegs into a

board with 25 parallel holes. The 2-Hand trial was ana-

lyzed for the present study. Measures of motor speed are

considered to be dependent on frontostriatal circuitry in-

volving the motor circuit including the putamen, which

may be disrupted secondary to damage to the SVZ.

Visual perception

37

required the participants to

match 2-dimensional line drawings to a model.

Performance on the visual perception test has been

shown to be associated with temporal lobe volumes

. 38

Data Analysis

Linear mixed effect (LME) regression analyses were used

to examine differences in neuropsychological test scores

between patients and controls (“group”), withmoderating

variables including age at the time of the baseline visit

(“age

0

”) and time since baseline (“time”). Main effects

and their 2- and 3-way interactions were used in the anal-

yses of the raw scores of the neuropsychological tests.

Two-way interaction terms included Age

0

×

Time,

which examined the change in test score with age over

time; Group

×

Age

0

, which examined differences in test

scores with age between the groups; and Group

×

Time,

which examined differences in test scores with time

between the groups. A 3-way interaction term (Group

×

Age

0

×

Time) was used to examine whether the neuropsy-

chological scores changed differently with age and over

time between patients and controls. For LME analyses

showing a significant term “time,” a general linear

model ANOVA with Fisher’s least significant difference

was used as a post-hoc test to evaluate the differences in

neuropsychological performance between patients and

controls at individual time points (visits 1–4).

In patients, LME analyses were also used to evaluate

the overall relationship between the raw scores of the

neuropsychological tests and regional radiation doses

(“dose”) to SVZ, hippocampus, temporal lobes, and

cerebrum. The analyses controlled for age at the time

of irradiation (age

RT

) and for the presence or absence

of concurrent chemotherapy. For presentation of the

results in the Figures,

Z

-scores were used to account for

the effect of age on neuropsychological performance.

Because we hypothesized that higher radiation doses to

specific brain regions in patients would result in a more

pronounced impairment on specific neuropsychological

tests, no corrections for multiple comparisons were

performed. Statistical significance was set to

P

,

.05.

Fig. 1. Representative contours of the hippocampus on an axial (top image) T1-weighted MRI postgadolinium contrast and on the sagittal

(bottom left) and coronal reconstructions (bottom right). The T1 postgadolinium and FLAIR-sequence MRIs were fused to the RT-planning

CT scan to allow calculation of the doses to contoured structures.

Redmond et al.: Radiation to neural progenitor niches and neurocognitive outcomes

362

NEURO-ONCOLOGY

M A R C H 2 0 1 3

at Universitaet Leipzig, Institut fuer Informatik/URZ, Bibliothek on August 25, 2014

http://neuro-oncology.oxfordjournals.org/

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