0018-9294 (c) 2013 IEEE. Personal use is permitted, but republication/redistribution requires IEEE permission. See
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This article has been accepted for publication in a future issue of this journal, but has not been fully edited. Content may change prior to final publication. Citation information: DOI
10.1109/TBME.2014.2385151, IEEE Transactions on Biomedical Engineering
TBME-01084-2014-R1
1
Abstract— Goal: The aim of this study was to investigate the
normalization of the intrinsic functional activity and connectivity
of TS adolescents before and after the cranial electrotherapy
stimulation (CES) with alpha stim device. Methods: We
performed resting-state functional magnetic resonance imaging
on eight adolescents before and after CES with mean age of about
nine years old who had Tourette’s syndrome with moderate to
severe tics symptom. Independent component analysis (ICA) with
hierarchical partner matching method was used to examine the
functional connectivity between regions within cortico-striato-
thalamo-cortical (CSTC) circuit. Granger causality was used to
investigate effective connectivity among these regions detected by
ICA. We then performed pattern classification on independent
components with significant group differences which served as
endophenotype markers to distinguish the adolescents between TS
and the normalized ones after CES. Results: Results showed that
TS adolescents after CES treatment had stronger functional
activity and connectivity in anterior cingulate cortex (ACC),
caudate and posterior cingulate cortex while had weaker activity
in supplementary motor area within the motor pathway
compared with TS before CES. Conclusion: The results suggest
that the functional activity and connectivity in motor pathway was
suppressed while activities in the control portions within CSTC
loop including ACC and caudate were increased in TS adolescents
after CES compared with adolescents before CES. Significance:
The normalization of the balance between motor and control
portions of the CSTC circuit may result in the recovery of TS
adolescents.
Index Terms—Tourette’s syndrome, resting-state fMRI,
cranial electrotherapy stimulation, independent component
analysis, machine learning
Manuscript received September 3, 2014; revised November 14, 2014;
accepted December 13, 2014. This work was supported by National Natural
Science Foundation of China under Grant 11271232 and 61301253. (Jianping
Qiao and Shenhong Weng contributed equally to this work.)(Corresponding
author: Zhishun Wang)
Jianping Qiao is with the College of Physics and Electronics, Shandong
Normal University, Jinan 250014 China. Shenhong Weng is with the
Department of Psychiatry, Wuhan University People Hospital, Wuhan 430060
China. Pengwei Wang is with the School of Information Science and
Engineering, Shandong University, Jinan 250100, China. Jun Long is with the
School of Information Science and Engineering, Central South University,
Changsha 410083 China.
*
Zhishun Wang is with the Department of Psychiatry,
Columbia University, New York, NY 10032 USA. (correspondence e-mail:
wangz@nyspi.columbia.edu, qiaojianpingdsp@gmail.com).
Copyright (c) 2014 IEEE. Personal use of this material is permitted.
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I. INTRODUCTION
OURETTE’S syndrome (TS) is a neurological disorder
characterized by repetitive, stereotyped, involuntary
movements and uncontrollable vocal tics. These symptoms
typically appear before the age of 18 and the condition occurs in
all ethnic groups with males affected three to four times more
often than females [1]. The cortico-striato-thalamo-cortical
(CSTC) circuit has been verified as an underlying
neurobiological correlate of TS [2-3]. High-resolution
structural magnetic resonance imaging has shown that children
and adult TS subjects displayed extensive brain abnormalities,
including cortical thickness [4-5] and changes in gray or white
matter volumes in brain regions involved in prefrontal,
sensorimotor, cingulate cortices and basal ganglia within CSTC
circuit [6-7]. Diffusion tensor imaging demonstrated that TS
patients had decreased fractional anisotropy and increased
radial diffusivity in the corticospinal tract, the corpus callosum
and long association fibre tracts compared with normal controls
[8-9]. In another study, the diffusion indices and tic severity of
TS was reported to have a positive correlation in the amygdale,
nucleus accumbens, globus pallidus and putamen [10].
Functional neuroimaging studies have revealed brain activation
and connection alterations in TS subjects during a variety of
tics and non-tics tasks [11-12], including an increased
functional interaction between primary motor cortex and
supplementary motor cortex (SMA) during tics than intentional
movements [13], different neuronal networks and connectivity
patterns when performing increasingly demanding finger-
tapping tasks [14], reduced activity in precentral gyrus, caudate
and increased activity in medial frontal gyrus during finger-
tapping task [15], frontal cortex and striatum during eye
blinking inhabitation [16], altered connectivity of the ventral
striatum in TS individuals with analyzing the functional
coupling based on positron emission tomography [17].
Moreover, our previous study has investigated spontaneous and
simulated tics in TS individuals with revealing that tics were
caused by the combined effects of excessive activity in motor
pathway and reduced activation in control portions of CSTC
circuit [18-19].
However, most studies have mainly examined task-specific
neural anomalies in TS. It is likely that the core neural causes of
TS are task-independent. Several previous studies have also
investigated resting-state functional magnetic resonance
Normalization of Intrinsic Neural Circuits
Governing Tourette’s Syndrome Using Cranial
Electrotherapy Stimulation
Jianping Qiao, Shenhong Weng, Pengwei Wang, Jun Long, and Zhishun Wang
*
, Senior Member, IEEE
T