Zhihao Li1,2, CecĂlia N Prudente3,4, Randall Stilla3, Krish Sathian5,6, Hyder A Jinnah7, and Xiaoping Hu2
1Affective and Social Neuroscience, Shenzhen University, Shenzhen, China, People's Republic of, 2Biomedical Engineering, Emory University and Georgia Institute of Technology, Atlanta, GA, United States, 3Neurology, Emory University, Atlanta, GA, United States, 4Physical Medicine and Rehabilitation, University of Minnesota, Minneapolis, MN, United States, 5Neurology, Rehabilitation Medicine, Psychology, Emory University, Atlanta, GA, United States, 6Rehabilitation R&D Center for Visual & Neurocognitive Rehabilitation, Atlanta VA Medical Center, Decatur, GA, United States, 7Neurology, Human Genetics and Pediatrics, Emory University, Atlanta, GA, United States
Synopsis
Cervical
dystonia (CD) is a neurological movement disorder where the pathophysiology remains
to be characterized. The present rfMRI study explored CD-associated brain
alterations of (i) functional connectivity (FC), (ii) fractional amplitude of
low frequency fluctuation (fALFF), and (iii) regional homogeneity (ReHo). The
results revealed 25 significant regional alterations that confirm and extend
existing knowledge. Additionally, using these regional alterations as
diagnostic features, a support vector machine classifier identified 8 features
that together yielded a maximum classification accuracy of 97%.PURPOSE
Cervical dystonia (CD) is a neurological disorder characterized by
abnormal movements and postures of the head
1. To date, there have
been only 2 applications
2,3 of resting-state functional MRI (rfMRI) in
evaluating the associated pathophysiology; but these previous studies were not
specifically focused on the brain network underlying head movement and rfMRI
features other than functional connectivity (FC) were not explored. The present
study examined CD-associated alterations of FC by capitalizing on newly identified
brain regions underlying isometric head rotation
4. In addition to FC,
which only reflects inter-regional signal synchronization, local regional alterations
were also explored using measurements of the fractional amplitude of low
frequency fluctuation (fALFF)
5 and of regional homogeneity (ReHo)
6.
Finally, with alterations of FC, fALFF, and ReHo identified, a support vector
machine (SVM)
7 learning algorithm was implemented to identify rfMRI
features with the highest power in distinguishing the patient and control
participants.
METHOD
Thirty-two participants (controls: N=16, 10F6M, Age=57.1±12.7; patients:
N=16, 9F7M, Age=56.7±11.4) were scanned during rest (no specific task other
than eye fixation) with a 3T Siemens Trio scanner (EPI-BOLD, TR/TE/FA/FOV=2000ms/30ms/90
o/220cm,
volume=240, 30 axial slices, thickness/gap=4mm/0mm, matrix=64×64). AFNI (http://afni.nimh.nih.gov)
was used for the analysis with regular preprocessing steps of despiking, slice
timing correction, volume registration, noise reduction
8, band pass
filtering (0.08Hz<f<0.009Hz), spatial smoothing (FWHM=5mm), and spatial
normalization. For the analysis of FC, we used a compound seed that included 4
spheres (r=5mm) located in the precentral gyrus (Talairach coordinates: x=21/-15/30/-54,
y=-22/-22/-13/-1, z=52/49/46/31, LPI orientation) reported in a recent study of
isometric head movement
4. The voxel-wise measurements of FC, fALFF,
and ReHo were individually derived and then compared between groups (group t-test)
with potential confound of head motion modeled by a covariate of the maximum
pairwise displacement in the motion parameter. To identify the rfMRI features for
best group classification, the SVM analysis (radius basis function kernel) involved
the procedures of “recursive feature elimination” (RFE) and “leave-one-out
cross-validation” (LOOCV) (Fig.1); thus the highest classification accuracy was
achieved with the fewest but most important features.
RESULTS
At the corrected threshold of p<0.05 (p<0.01/voxel and 581mm
3
cluster), the CD participants exhibited both reduced (e.g. bilateral
postcentral gyrus) and enhanced (e.g. bilateral basal ganglia and thalamus) FC
in different brain regions (Fig.2). For the measurements of fALFF (Fig.3) and
ReHo (Fig.4), only reduced values were observed in CD individuals (e.g.
bilateral postcentral gyrus). Combining FC, fALFF, and ReHo, we have identified
25 alterations (Table.1). Feeding these 25 features into the SVM classifier
with RFE, 8 features survived (highlighted in Table 1) and a maximum group classification
accuracy of 97% was achieved.
DISCUSSION
Seeding in brain regions activated by isometric head rotation4,
the present study revealed FC alterations in a brain network specific to head
movements. FC alterations were confirmed at both the cortical and subcortical
level, which resolved limitations of the previous studies2,3. In
addition to the inter-regional FC, cortical (e.g. postcentral gyrus) and
subcortical (e.g. basal ganglia and thalamus) alterations were also identified
in local regional measurements; thus insights of pathophysiology in CD extended
to reduced power and regional homogeneity of the intrinsic neural fluctuation. The
rfMRI features identified here may have potential in future applications for
improving diagnostic and prognostic evaluations in CD.
Acknowledgements
This work was
supported by: National Center for Advancing Translational Sciences and NIH
(U54NS065701, U54NS06571-03S1), as well as the Emory University Research
Committee (UL1 RR025008).References
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