Sensory
Trick in a Patient with Cervical
Dystonia:
Insights
from Magnetoencephalography
Abhimanyu
Mahajan, Andrew Zillgitt,
Susan M. Bowyer, Christos Sidiropoulos
Abstract:
Background: The proposed mechanisms for the
sensory trick include peripheral sensory
feedback to aid in correcting abnormal posture
or movement. Case report: A 53-year-old woman
with cervical dystonia underwent
magnetoencephalography pre- and post-botulinum
toxin injection and sensory trick, which was
described as yawning. Study revealed
connectivity between the left frontal and
inferior frontal gyrus before yawning, which
changed to the visual cortex and right middle
frontal gyrus with yawning. Beta frequencies
reduced and gamma frequencies increased after
yawning. Discussion: The increase in gamma
frequency bands may indicate increased GABAergic
activity. Increase in connectivity in the right
cerebellar region underscores the importance of
cerebellum in pathogenesis of dystonia.
1. Introduction
Sensory tricks or 'alleviating maneuvers'
are voluntary maneuvers that lessen the severity
of abnormal movement or posture in people with
dystonia. Up to 83% of cervical dystonia
patients note partial to complete improvement
with a sensory trick [1]. Sensory tricks
may involve complex sensorimotor tasks such as
singing or even yawning [2]. Although
the exact mechanism by which a sensory trick is
beneficial is not well known, proposed
mechanisms have suggested peripheral sensory
feedback to aid in correcting the abnormal
posture or movement [3] and modulation
of parietal lobe activity.
Deficits in visuospatial and executive
pathways in people with dystonia have previously
been described [3,4,5]. In addition,
attenuation of abnormal muscle activity with a
sensory trick has been associated with reduced
activation of supplementary motor area and
primary sensorimotor cortex [3].
Patients with adult-onset primary cervical
dystonia with effective sensory tricks have been
reported to have better visuotactile
discrimination and shorter disease duration
[4].
Magnetoencephalography (MEG) is a useful
tool for analyzing brain connectivity in
epilepsy, but has rarely been used in focal
dystonias [6]. In this case study, we
attempted to explore the mechanism of action of
a sensory trick, using MEG for the first time,
by comparing cerebral oscillations at the
network level in a patient with cervical
dystonia pre- and post-sensory trick, as well as
pre- and post-administration of botulinum
toxin.
2. Case Description
A previously healthy 53-year-old woman
presented with an 8-month history of right
torticollis and left laterocollis responsive to
treatment with botulinum toxin injections. Her
sensory trick consisted of alleviation of her
symptoms upon yawning. MEG data were acquired in
10 min scans with eyes open, using a 148-channel
whole-head magnetometer system (4D Neuroimaging,
San Diego, CA, USA) inside a magnetically
shielded room. A total of 4 resting-state MEG
scans were collected, two right before the
injection of botulinum toxin and another two 2
weeks after the injection of botulinum toxin.
Pre-botulinum toxin injection scans were taken
before and after yawning, and similarly after
the injection of botulinum toxin.
The data were sampled at a rate of 508.6 Hz
(DC to 100 Hz) and were then forward and
backward bandpass filtered 3-50 Hz. An artifact
filter, utilizing ICA, was used to remove heart
signals observed in the MEG recordings. Then MEG
Coherence Source Imaging (CSI) was performed to
assess neuronal synchrony within different brain
regions [6]. A Standard MRI was
segmented, and the brain surface was represented
by a cortical model of approximately 4000
dipoles, each having an x, y, and z orientation
at each site. Sites were distributed to
represent the same volume of cortical gray
matter. This model was then morphed to fit the
digitized head shape collected during the MEG
acquisition.
Post-acquisition data processing was
performed using MEG Tools, an open-source Matlab
(The Mathworks Inc., Natick, MA, USA)-based
software module for MEG brain imaging. MEG-CSI
was quantified by applying a time frequency
decomposition technique, the short-time Fourier
transformation (sFFT). After transformation to a
time frequency representation, the strengths of
network interactions were estimated by
calculation of coherence, a measure of synchrony
between signals from different brain regions for
each FFT frequency component. The 10 min of
rest-state MEG data were prepared for source
imaging by division into 80 segments, each
containing 7.5 s of data of relatively uniform
brain behavior [6]. For each of these
data segments, signals from neuronal sources
were isolated using an independent component
analysis (ICA) spatiotemporal decomposition
technique designed to extract signals from
distinct compact sources that exhibit burst
behavior and minimal temporal overlap with other
active sources.
These ICA signal components have MEG spatial
magnetic field patterns corresponding to one or
a few spatially distinct compact sources that
are much easier to image accurately using a
current-distribution source imaging technique
(MR-FOCUSS) [7]. MR-FOCUSS only images
amplitudes above 20% of the maximum amplituded
threshold. Separate from the imaging algorithm,
the cross-spectrum between ICA signals was
calculated. In these cross-spectrum
calculations, a sequence of FFT spectra were
calculated using 0.5 s windows and 25% overlap
with FFT amplitudes for 24 frequency bins 2 Hz
in width between 3 and 50 Hz. The imaging
results and the signal cross-spectrum were used
to calculate the coherence between all pairings
(~1400 locations in the brain) of active
cortical locations within each of the 24
frequency bins. Finally, for each active source,
the average coherence across frequencies and
sources was calculated. In these MEG-CSI
results, the localization of imaged brain
activity is strongly dependent on the frequency
bands with greatest power. Coherence analysis
results were encoded as a color spectrum for
values between 1 (entirely coherent) and 0 (no
coherence) and overlaid on the patient's MRI
with the solutions restricted to to the gray
matter.
MEG-CSI is currently used in our hospital to
identify hyperactive epileptogenic brain areas
prior to surgery [8,9]. The variance
between coherence from the patients pre- and
post-sensory trick (yawn) and pre- and
post-botulinum injections was assessed for
statistical significance.
3. Discussion
To the best of our knowledge, this is the
first attempt to directly assess changes in
functional connectivity with an effective
sensory trick in a patient with cervical
dystonia using MEG. In this study, we
illustrated changes in coherence, connectivity,
and frequency bands pre- and post-sensory trick
and botulinum toxin treatment. The changes in
coherence pre- and post-sensory trick and pre-
and post-treatment with botulinum toxin
underscore dynamic network changes that may
share similar pathways, specifically within the
visual cortex and frontal lobe. These results
were corroborated with connectivity analysis,
again illustrating changes within pathways
involving the visual and frontal cortices.
Furthermore, there were changes in frequency
bands following both pre- and post-sensory trick
and pre- and post-treatment with botulinum
toxin. Specifically, the sensory trick resulted
in reduced Alpha-band frequencies and an
increase in Gamma-band frequency. Increased
Gamma-band fluctuations in MEG have been shown
to be positively correlated with GABA
concentration in the same cortical region. Using
a combination of MRI spectroscopy, MEG and
visual psychophysics, Edden et al. showed that
Gamma oscillation frequency positively
correlated with GABA concentration in the
primary visual cortex [10].
Using MEG, MRI spectroscopy and fMRI,
Muthukumaraswamy et al. proved that gamma
oscillation frequency is positively correlated
with resting GABA concentration [11].
Similarly, our findings could support
alterations within GABAergic pathways and a
final common pathway in the sensory trick.
Deficiency of intracortical inhibition is the
keystone of pathophysiology in dystonia. These
findings appear concordant with previous
functional imaging studies in people with
dystonia. Previous hypotheses have suggested
that a sensory trick acts by enhancing pathways
between the occipital and parietal lobes through
proprioception [12]. Delnooz et al.
demonstrated improved connectivity in people
with primary cervical dystonia using functional
MRI (fMRI) following treatment with botulinum
toxin. In this study, there was improved
connectivity between the sensorimotor and
primary visual network after treatment with
botulinum toxin [13].
It is well known that dystonia is a network
disorder with clear involvement of the basal
ganglia and cerebellum and their interaction
[14]. The role of the cerebellum in
dystonia is increasingly being studied, although
it is not yet completely understood
[15]. Our study implicates the
cerebellum, temporal and parietal cortex,
thereby adding to the literature on the
cerebellum and sensorimotor control
[16].
Our case study has some definite strengths.
MEG measures the magnetic flux from electrical
currents within the brain, and is therefore a
direct measurement of neuronal activity.
Furthermore, MEG has good spatial resolution
(2-5 mm) and excellent temporal resolution (1
ms) [17,18]. These unique features make
MEG an attractive tool for studying functional
connectivity in a variety of neurological
disorders [6,8,9].
MEG-CSI, using source-space localization,
demonstrates excellent spatial resolution for
cortical imaging [14]. Performing
source-space coherence after
current-distribution imaging negates current
spread, thereby avoiding the relatively poor
spatial resolution of sensor-space coherence.
Our MEG lab sensor, a magnetometer-type system,
was found to have better resolution for deeper
structures.
We decided on a 3-50 Hz filter based on our
experience with epilepsy pre-surgical mapping.
While a 3Hz high-pass filter removes any
breathing artifacts, a 50 Hz low-pass filter
provides all the power that is in the data
without any impact from the 60 Hz power
lines.
Overall, this case report utilized an
underutilized approach, MEG-CSI, to study the
effects of a sensory trick and botulinum toxin
in a patient with cervical dystonia.
Specifically, there were changes in coherence
and connectivity within the visual and frontal
cortices as well as reduced beta frequency bands
and increased Gamma frequency bands pre- and
post-trick and treatment. These findings support
a dystonia network involving the visual and
frontal cortices and potentially suggest a
sensory trick and botulinum toxin similarly
alter GABAergic pathways to create clinical
improvement [10,11].
The case study nature of our report limits
the ability to draw firm statistical
conclusions, yet the widespread changes seen in
connectivity and brain dynamics in the different
conditions clearly indicate that this approach
is suitable for further studies where
quantitative statistics can better support new
insight into the pathogenesis of dystonia at a
network level.
To summarize, an effective sensory trick is
associated with hyper-excitability in the
parietal cortex and perhaps increased gamma
frequency in this region. The parietal cortex, a
center of sensorimotor integration, may play an
integral role in reducing dystonia via
amplification of Gamma frequencies. Botulinum
toxin may have similar effects within the cortex
and cerebellum, and these findings may indicate
a common sensory pathway. Although these
findings are intriguing and promising,
replication in a larger patient cohort is
necessary to verify their validity.
