Monika Sobczak-Edmans1, Yu-Chun Lo2, Yung-Chin Hsu2, Yu-Jen Chen2, Fu Yu Kwok1, Kai-Hsiang Chuang3,4, Wen-Yih Isaac Tseng2,5,6,7, and SH Annabel Chen1,8
1Psychology, Nanyang Technological University, Singapore, Singapore, 2Institute of Medical Device and Imaging, National Taiwan University College of Medicine, Taipei, Taiwan, 3The Queensland Brain Institute, The University of Queensland, Brisbane, Australia, 4The Centre for Advanced Imaging, The University of Queensland, Brisbane, Australia, 5Institute of Brain and Mind Sciences, National Taiwan University College of Medicine, Taipei, Taiwan, 6Department of Radiology, National Taiwan University College of Medicine, Taipei, Taiwan, 7Molecular Imaging Center, National Taiwan University, Taipei, Taiwan, 8Centre for Research And Development in Learning, Nanyang Technological University, Singapore, Singapore
Synopsis
Diffusion spectrum imaging was employed to establish
structural connectivity between cerebro-cerebellar regions co-activated during
verbal working memory. IFG, IPL,
pons, thalamus, superior cerebellum and inferior cerebellum were used as seed
points to reconstruct the white matter cerebro-cerebellar circuitry.
The reconstructed pathways were examined further to establish the relationship
between structural and effective connectivity as well as the relationship
between structural connectivity and verbal working memory performance. It was
found that structural connectivity is indirectly related to effective
connectivity but does not predict it. Additionally, it was demonstrated that
the integrity of the ponto-cerebellar tract is an important
factor in explaining individual differences in verbal working memory. The
findings of the study furthered our understanding of the
relationship between structural and functional connectivity and provided insight to the variability in verbal working memory performance. Introduction
The cerebro-cerebellar
model of verbal working memory (VWM)[1] includes the inferior frontal-superior
cerebellum network and the inferior parietal-inferior cerebellum network as
demonstrated by functional neuroimaging and brain stimulation [1,2,3]. However
the structural connectivity for these networks has yet to be verified in
humans, therefore the current study aimed to clarify whether cerebro-cerebellar
co-activations observed during VWM have anatomical connectivity. We performed
anatomically-guided deterministic tractography that used a fiber tracking
algorithm with quantitative anisotropy to trace the following tracts: the left inferior
frontal gyrus (IFG) via pons to the right superior cerebellum (sCERE), the left
inferior parietal lobule (IPL) via pons to the right inferior cerebellum
(iCERE) and the cerebellar tracts via thalamus to the left IFG. Once we
reconstructed the connectivity for these tracts, we investigated if their
microstructure contributes to the individual differences in VWM performance. We
hypothesized that greater white matter integrity of the fronto-cerebellar tracts
will be associated with faster response times in VWM, whereas greater white
matter integrity of parieto-cerebellar tracts will be associated with higher
accuracy rates. In addition, we examined whether the white matter tracts
underlying cerebro-cerebellar networks are related to the functional dynamics
of the interactions between cerebro-cerebellar regions implicated in VWM. In
order to do this, we investigated if Bayesian model selection of DCM models
informed by the tractography results will have a higher degree of confidence in
model inference than uninformed models. Subsequently, we examined if structural
connectivity can predict effective connectivity within this network.
Methods
31 adults (mean
age=22.5±1.2 years) performed a VWM Sternberg task (Fig.1) in a 3T MRI scanner
with a 32 channel head coil. Participants were right-handed, did not
have a history of neurological or psychiatric conditions. Diffusion spectrum
imaging data were acquired using: TR=7200ms, TE=136ms, slice thickness=3mm, 45
slices, FOV=220mm. The diffusion weighting was distributed along the grid of
128 directions with a bmax=7000 s/mm
2. FMRI sequence parameters
were: TR=2.5s, TE=29ms, FoV=225mm, 48
slices, and 3.5x3.5x3.5mm
3 voxels. MPRAGE image was acquired
(1x1x1mm
3 resolution, TR=2.3s, TE=1.9ms, FoV=256mm, distance
factor=50%). Standard Dartel preprocessing was conducted in spm12. All DSI
analysis was conducted using DSI Studio. Tractography was performed for every
tract separately, resulting in 8 different tracts per subject. The tracts were
represented in MNI space. For each of the tracts, the mean tract GFA index was
generated. Effective connectivity analysis (Fig. 2) was conducted using DCM in
spm12 and correlational analysis between structural and modulatory connections
was performed.
Results
The reconstructed tracts
are presented in Fig.3. Comparison of Bayesian model selection results and the
most optimal model are shown in Fig.4. No significant relationship was found
between structural and modulatory connectivity for the tracts from
fronto-cerebellar and parieto-cerebellar loops. Pearson correlational analysis
for white matter tracts and VWM performance showed that only mean GFA for the pons-sCERE
tract positively correlated with the response time (r=0.47, p=0.004). None of the
other tracts were significantly correlated with the response time or accuracy,
but there was a tendency for significance between mean GFA of the IPL-pons
tract and accuracy rate (r=0.24; p=0.09).
Conclusion
To the best of our
knowledge, this is the first study to demonstrate in vivo structural tract
connectivity between the left IFG and the right sCERE, and between left IPL and
right iCERE via the pons and thalamus using diffusion spectrum imaging tractography.
This demonstrates that there are anatomical connections between
cerebro-cerebellar regions involved in VWM. We found that structural
connectivity of the reconstructed cerebro-cerebellar networks relates functionally
to VWM in two ways: First, constructed DCM models that resembled the underlying
anatomical pathways more closely had a higher degree of confidence in Bayesian
model selection. This suggests that structural connectivity is indirectly
related to the effective connectivity. Second, it was found that the increasing
connectedness of the ponto-cerebellar tract was correlated with increase VWM
efficiency, implying that the structure of ponto-cerebellar tract contributes
to individual differences in VWM.
Acknowledgements
This work was supported by
a grant from Singapore Ministry of Education AcRF Tier 2 grant
(MOE2011-T2-1-031) and Nanyang Technological University Start Up Grant.References
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Desmond, J. E. (2005). Temporal dynamics of cerebro-cerebellar network
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S. H., & Shieh, P. B. (2005). Cerebellar transcranial magnetic stimulation
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of Neurology,58(4), 553-560.
[3] Kwok F.Y, Ng, T.H.B.,
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