Impaired Visuospatial
Processing in Young Adult Male
Fragile X Premutation Carriers
Ling M. Wong, Naomi J. Goodrich-Hunsaker,
Yingratana (Bella) McLennan, Flora Tassone,
Danielle Harvey, Susan M. Rivera, Tony J. Simon
Cognitive Analysis and Brain Imaging Lab
http://cabil.mindinstitute.org
lmewong@ucdavis.edu
Funding: NIDCF UL1 DE019583, NIA RL1 AG032119, NINDS RL1
NS062412, NIDA TL1 DA024854.
What is visuospatial
processing?
Desimone & Duncan (1995)
Adapted from Mishkin et al (1983)
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Adult fXPCs exhibit intact function in pathways involved in
color and object recognition
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Impaired function in pathways involved in motion
perception, detection of spatial location, and visuomotor
coordination (Kéri & Benedek 2009, 2010, 2012)
‣
Adult male fXPCs have intact perception, but impaired
visuospatial performance (Hocking et al, 2012)
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Where in the processing stream is the root of impairment?
Aims of the Current Study
‣
Aim 1: Investigate whether adult male fXPCs
asymptomatic for FXTAS exhibit impaired visuospatial
functioning or visuospatial attention
‣
‣
Aim 2: Examine whether genetic “dosage” (e.g. CGG
repeat length, gender) modulates behavior
‣
‣
Results might provide a basis for a biomarker for
later neurodegeneration
Compare male and female performance
Aim 3: Examine whether performance declines w/age
Study Design
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Participants included 48 adults (aged 18 - 45)
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21 male fXPCs
27 HCs
5 Behavioral tasks
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Psychomotor speed (manual and oral)
Magnitude Comparison (distance effect)
Enumeration (numerical spatial attention)
Spatial cuing
1
Wong et al. Under Review, 2Goodrich-Hunsaker et al. J Int Neuropsychol Soc 2011:1-5
Psychomotor Speed Task
“Press the button as soon as you see the alien”
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HCs replicate published
population values, as do
male fXPCs1
Adult male fXPCs, unlike
females show similar
psychomotor speed
compared to HCs1
Manual
200
n=26
n=21
HC
fXPC
n=27
n=41
100
0
MALE
500
Median RT (in ms) ± S.E.
‣
Median RT (in ms) ± S.E.
300
HC
fXPC
FEMALE
Oral
400
300
200
n=27
n=21
HC
fXPC
n=26
n=42
HC
fXPC
100
0
MALE
FEMALE
1
Wong et al. Under Review, 2Goodrich-Hunsaker et al. Brain Cogn 2011;75:255-60
Magnitude Comparison Task
“Which of the two blue bars is longer?”
Expected Performance
Used RT from 2- to 1-cm
to determine the intercept
600
550
500
450
1
‣
2
3
4
5
Distance (in cm)
6
7
2.6
2.4
20%
2.2
15%
2.0
10%
1.8
1.6
5%
1.4
Male fXPCs are slower
1
2
3
5
Distance (in cm)
Intercept
(1- to 3- cm)
Performance relates to CGG
6
HC female
HC male
5
‣
Percent Error ± S.E.
RT (in ms)
650
Median RT / Manual Motor RT ± S.E.
Intercept was calculated
for each participant
700
30%
HC female (n=29)
fXPC female (n=44)
HC male (n=26)
fXPC male (n=21)
25%
2.8
0%
7
fXPC female
fXPC male
r = .31
4
3
2
1
20
25
30
35
Age (in yrs)
40
50
100
150
CGG Repeats
200
1
Wong et al. Under Review, 2Goodrich-Hunsaker et al. Front Hum Neurosci 2011;5:63
Enumeration Verbal Task
“How many green items do you see in the red square?”
Expected Performance
1500
RT (in ms)
Counting Range
(> 250 ms / item)
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1000
Subitizing Range
(< 100 ms / item)
500
3
4
5
6
Number of Items
7
8
HC female (n=29)
fXPC female (n=39)
HC male (n=26)
fXPC male (n=21)
40%
4
30%
3
20%
2
10%
1
2
3
4
5
Numerosity
6
7
8
0%
Subitize
(1 to 3 items)
50%
5
1
HC female
HC male
Count
(5 to 8 items)
6
2
Percent Error ± S.E.
Median RT / Oral Motor RT ± S.E.
1
Male fXPCs are slower
in counting
fXPC female
fXPC male
.4
.3
.2
.1
0
-.1
-.2
r = -.00
2
r = -.23
1.5
1
.5
0
20
25
30
35
Age (in yrs)
40
50
100
150
CGG Repeats
200
1
Wong et al. unpublished data, 2Hahn et al., Neuroimage 2006;32:842-53
Spatial Cuing
“Use the clues to find the target”
Cue
Target
ITI
1
3
2
4
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70
Cue effect
HC (n = 17)
fXPC (n = 16)
2.0
1.9
50
30
10
10
30
r HC = -.31
r fXPC = -.0.01
20
1.8
1.7
1.6
30
40
Age (yrs)
Cue effect
median RT / SRT
2.1
Male fXPCs perform
similarly to HCs
1
2
3
# cued locations
4
70
50
30
10
10
30
r = .05
50
70
90
CGG
110
130
Summary of Results
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Adult male fXPCs do not show enhanced psychomotor
speed, unlike female fXPCs.
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Adult male fXPCs are slower in magnitude comparison
and numerical spatial attention.
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Magnitude comparison performance worsens with
increased CGG.
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Results suggest visuospatial processing is impacted in
fXPCs, but attentional orienting is not affected.
Implications & Future Plans
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Results support previous findings of impaired
performance in visuospatial tasks in fXPCs.
‣
They add to a growing body of literature characterizing
the phenotypic spectrum produced by FMR1 gene
dosage.
‣
Lack of robust effects or associations may be due to
limited age and CGG sampling range. (c.f. Hocking et al,
2012 and Cornish et al, 2011)
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Data from fXPC boys will help determine whether
performance progressively declines or remains stable.
Thank you
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Thanks to all those who
participated in our study!
Contact:
lmewong@ucdavis.edu
CABIL Lab members:
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Tony J. Simon
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Thanks to:
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Susan M. Rivera
Flora Tassone
Danielle Harvey
Paul Hagerman
Randi Hagerman
Robert Berman
Naomi Goodrich-Hunsaker
Bella McLennan
Funding: NIDCF UL1 DE019583, NIA
RL1 AG032119, NINDS RL1
NS062412, NIDA TL1 DA024854.