The effects of cerebellar transcranial alternating
current stimulation on hand tremor in Parkinson's
disease: a primary study
Soraya Rahimi1, Mahshad Dezhsetan1, Farzad Towhidkhah1*, Bijan Forogh2, seyed Amirhassan Habibi3
1 2
Biomedical Engineering Department Physical Medicine & Rehabilitation Department
Amirkabir University of Technology Iran University of Medical Sciences
Tehran, Iran Tehran, Iran
*
Email: towhidkhah@aut.ac.ir
Abstract— Parkinson's disease (PD) is a neurodegenerative
disorder with motor and cognitive symptoms. Tremor is an
important symptom of this disease. Since the discovery of
dopamine concentrations depletion in the basal ganglia, they are
the clinical and research targets in PD. However, increasing
anatomical, pathophysiological, and clinical evidence suggested
that the cerebellum may contribute substantially to the clinical
symptoms of PD. In this study, to investigate the effect of the
cerebellum on tremor, electric field distribution of two montages
are theoretically compared by using the head model and then
clinically applied tACS for 15 minutes at a frequency equal to the
peak frequency of individual patient. To evaluate tremor pre and
post stimulation, two tasks are defined. This recording has not
been performed on PD. A tri-axial accelerometer is placed to
record tremor over the index finger. In the time domain, the
average total amplitude of the rest tremor has decreased
significantly (p < 0.05). In the frequency domain, the average
median frequency and the average area under the power spectrum
density in Task 1 and Task 2 have increased. This technique
showed cerebellar tACS could be useful in Parkinson’ tremor.
Keywords: Parkinson’s disease; tACS; Cerebellum; Tremor
I. INTRODUCTION
Parkinson’s disease (PD) is a prevalent neurodegenerative
disorder. It includes motor and cognitive dysfunctions. Motor
dysfunctions consist of tremor, bradykinesia, akinesia, rigidity,
gait disturbance, and postural instability. Tremor is an
important feature of PD that reduces the quality of life. Patients
can be divided into two groups: tremor dominant and akinesia
dominant.
Invasive procedures like DBS can be useful in reducing tremor.
But because of its invasiveness and complications, researchers
are seeking other ways. In recent years, transcranial electrical
stimulation (tES) has also been used to treat tremor. There are
very few studies on tES that focus specifically on treating
tremors in Parkinson's disease [1-4].
Since the discovery of markedly decreased dopamine
concentrations in the basal ganglia in the 1960s [5], the basal
ganglia are the primary clinical and research targets in
Parkinson’s disease. More recently, the importance of the
involvement of other structures, such as the cerebellum, has
also been recognized [6]. The findings of Hoshi et al. show that
the cerebellum has a strong disynaptic projection to the striatum
3
Neurology Department
Iran University of Medical Sciences
Tehran, Iran
by the thalamic route [7]. Bostan et al. also found that the
subthalamic nucleus (STN) has a disynaptic projection via the
pathway of the pontine nuclei to the cerebellar cortex [8].
Moreover, Yu et al. reported that the left and right cerebellum
and the contralateral motor cortex were hyperactive in PD
patients [9].
Previously, the cerebellum was only designated as a
coordinator of voluntary movements, gait, posture, and motor
functions. Often its effect on PD was not investigated.
However, increasing anatomical, pathophysiological, and
clinical evidence suggested that the cerebellum may contribute
substantially to the clinical symptoms of PD [6].
The purpose of this study was to investigate the effect of
cerebellar tACS on hand tremor of PD. To achieve this goal, the
first electric field distribution of two montages are theoretically
compared by using the head model and then clinically applied
tACS and hand tremor are recorded before and after
stimulation. This recording has not been performed on
Parkinson's tremor. In section II, the methodology is explained,
and the results are presented in section III. Section IV discusses
and concludes.
II. METHODS
A. Stimulation
Ipsilateral cerebellar stimulation was delivered through rubber
electrodes, encased in saline-soaked sponges. The active
electrode was positioned on the 3 cm lateral of the inion, and
the return electrode was centered on the buccinator muscle
contralateral to the recorded tremor. The applied current is
sinusoidal waveform with a range of 2 mA for 15 minutes, and
the size of the electrodes is 7×5 cm2. tACS delivered at the peak
frequency of tremor [10].
B. Modeling of electrical stimulation
To assess the magnitude of the electric field and current-flow to
cerebellum and ROI in the brain, we generated a computational
model of the head using the finite element method (FEM) via
SIMNIBS v 2.1 pipeline [11]. The protocol of creating head
model via SIMNIBS described in Saturnino et al. [11]. In
summary, we used a high-resolution T1-weighted MR image
scan of a healthy adult male. The image segmented using
SPM12) (www.fil.ion.ucl.ac.uk) Toolbox in the MATLAB TABLE I. . BIOLOGICAL TISSUE CONDUCTIVITIES
environment (www.mathworks.com), into six tissue types: Conductivities
skin, skull, cerebrospinal fluid, gray matter, white matter, and Tissue Electrical conductivity(S/m)
eyes (Fig. 1). Then we finally produce a volumetric mesh with
Scalp 0.465
all of the segmented tissues. At this point, after importing the
mesh into SIMNIBS, electrodes placed on the head and current Skull 0.01
applied. We designed the dimensions of the electrodes similar CSF 1.654
to our experimental procedure and defined their material as
rubber with saline-soaked sponges. GM 0.275

WM 0.126

Eyes 0.5

Electrode 29.4

frontal regions of the head in M1 stimulation and the posterior

Figure 1. Segmentation of brain to six tissues [skin, skull, cerebral spinal
fluid (CSF), gray matter and white matter,eye].
Furthermore, we assigned all of the conductivities as isotropic
according to Table I Simulation problems solved in SIMNIBS
using the FEM with a linear function. The electric field
distribution in the head model was computed by solving the
quasi-static Laplace equation:
𝐸 = −∇𝜑 (1)
Where E and φ represent the electric field and electric potential
of the tissue, respectively [12]. Overall segmentation and
simulation take about 145 minutes by a corei5 system with 16
GB memory.
The maximum electric field and current-flow for our electrode
montage in the ROI presented in Fig. 2. For the M1-SO
montage, we also performed the above simulations. The results
of these simulations can be seen in Fig. 3. The peak electric
field was calculated on the gray matter in both montages, and
this value was 0.3 (v/m) for cerebellar stimulation and 0.45
(v/m) for stimulation of motor areas. The involvement of the
regions in the cerebellar stimulation were also visible. As
presented in Fig. 2 and Fig. 3 with the same injection, the
intensity of the electric field in the gray matter of the brain is
less in cerebellar stimulation. One of the reasons for this may
be the greater skull thickness in the mentioned area. According
to the equation:
𝐽 = 𝜎𝐸 (2)
Where E and J represent the electric field and current density,
the electric field and the current density are directly related [13].
Since the skull conductivity is lower than other regions (shown
in Table I), less current reaches the gray matter. So, because of
this decrease in the current density, the field is also less at this
point.
C. Participants
The protocol was supported by the ethics committee of the Iran
University of Medical Science. Six Parkinson's patients (3
males, mean age 60.83 yr.) in drug-off condition participated in
the experiments. All participants provided informed written
consent.
D. Material
The used tri-axial accelerometer consists of the LIS3DH
accelerometer sensor and the Arduino Uno board. In
recordings, the accelerometer was placed over the index finger,

Figure 2. Resulting electric field [row (a)] and current distribution [row(b)] simulated with mentioned montage. In the first row we can see the extent
of field distribution and cerebellar involvement. In the second row we can see the distribution of current in the gray matter of the brain and its Gyrus.
 Figure 3. First picture from left shows the montage of M1_SO. The anode located on the M1 and the cathode is on the supraorbital area. However, in the
tACS there is not any different between anode and cathode.

while the person is performing the task. Then three consecutive

recordings were recorded for 15 seconds (Each task takes 45
seconds to record).
E. Experiments
Two recordings were made while subjects sat in a chair
comfortably with their eyes open. Experiment 1 under no
stimulation, and Experiment 2 was when tACS was applied
over the cerebellum. Two tasks were defined to record rest and
action tremor.
Task 1: To record the rest tremor, the participant placed his /
her hands on his / her feet. Task 2: The spiral lines were shown
to the participant, and the person was asked to draw the spiral
tracks. This task measures the action tremor.
F. Statistical Analysis
Due to the limited number of participants and the uncertainty of
the statistical distribution, the Wilcoxon signed-rank test was Figure 4. The after-effects of tACS on average total amplitude in Task 1
used.

III. RESULTS
All processing is done in MATLAB 2018b software.
Acceleration is recorded in three directions by a tri-axial
accelerometer. In the time domain, the mean acceleration
amplitude, and in the frequency domain, the median frequency
and power spectrum density (PSD) are extracted as features. In
all instances, post-stimulation changes are compared to pre-
stimulation.
A. Time-domain
In Task 1 and Task 2, the average amplitude of acceleration
decreased in all three directions (Task 1: Percent of Changes
Ratio of X=34.17%, Y=57.61%, Z=68.26%. Task2: X=22.9%,
Y=17.28%, Z=12.57%). Overall, the average total amplitude
signal in rest tremor (Task 1) decreased by about 54.77% (p =
0.0313) and in action tremor (Task 2) by about 15.63% (p = Figure 5. The after-effects of tACS on average total amplitude in Task 2
0.218) compared to pre-stimulation (Fig. 4 and Fig. 5).
Fig. 6. displays tremor signal in pre and post stimulation for
case 5.

Figure 7. The after-effect of tACS on average mdian frequency in Task1

Figure 6. Tremor signal in pre and post stimulation for case 5 in Task 1

B. Frequency domain
The average median frequency is increased by 17.74% in Task
1(p = 0.0938) and 12.49% in Task 2 (p = 0.337). The results for
median frequency are displayed in Fig. 7 and Fig. 8.
To evaluate the frequency domain, we divided the frequency
into three intervals of 2-7, 7-12, and 12–17 Hz.
The average area under the PSD in Task 1(p = 0.0313) and Task
2 increased. The measure of changes reported in Table II and
III.

Figure 8. The after-effect of tACS on average mdian frequency in Task 2

TABLE II. AVERAGE AREA UNDER THE PSD IN TASK 1
Average Area Under the PSD
Frequency range (Hz) Pre-stimulation Post-stimulation P-value
IV. DISCUSSION
2-7 0.005 0.0021 0.0313
There are very few studies on transcranial direct current
7 - 12 0.0127 0.2492 0.0313
stimulation (tDCS) that focus specifically on tremors in PD.
12- 17 0.0664 0.6046 0.1563 Benninger et al. used anodal stimulation in the premotor and
motor cortex and reported no progress in improving the
amplitude of the tremor [1]. Fregni et al. reported a 10%
improvement in UPDRS tremor with anodal tDCS on M1
TABLE III. AVERAGE AREA UNDER THE PSD IN TASK 2 [2].Brittain et al. applied tACS over the motor cortex at specified
phase alignments. Five of Parkinson’s patient participated in this
Average Area Under the PSD study. They achieved almost 50% average reduction in
Frequency range (Hz) Pre-stimulation Post-stimulation P-value amplitude of rest tremor and showed online effects of tACS [3].
2-7 0.016 0.0023 0.156
In this study, the amplitude of resting tremor decreased by
7 - 12 0.1209 0.1401 0.312 about 54% and of action tremor by about 11% compared to pre-
stimulation (Fig. 4 and Fig. 5). This changes can show after-
12- 17 0.2071 0.4034 0.218
effects of tACS on the cerebellum. Peripheral tremor is
representative of the cortical oscillatory activity. Tremor can
also be considered sinusoidal [14]. According to the
assumptions, the tremor frequency will be equal to the frequency
of the applied electrical current and the amplitude changes when
there is a phase difference between the two signals.
Since that sinusoidal electric fields produce alternative states
of depolarization and hyperpolarization comparative to the
resting membrane potential of single neurons; it produces higher
and lower firing probability of neurons and consequently
expands the entire neuronal population, these changes have a
little effect on each neuron but have a strong effect on network
dynamics. During continuous tACS, spontaneous activity of an
increasing number of individual neurons set out to synchronize
with the external oscillation, which in turn results in a power
increase of the whole network. In this study, the average area
under PSD can be considered for evaluating the power of the
network in the cerebellum. As observed in results, it increased
in both tasks [15] (Table II and III).
The results showed that the effect on action tremor was less
than rest tremor. It can be related that the stimulation frequency
was equal to the peak of the rest tremor frequency. Studies have
also shown the involvement of the cerebellum in rest tremor [6,
16, 17].
In conclusion, the features extracted from the tasks of this
study showed the effect of cerebellar tACS on tremor. This study
was a primary study with a limited number of participants that
showed off-line effects of tACS on tremor could be examined.
So, by increasing the number of participants and continuing the
process, significant and generalizable changes can be achieved.
REFERENCES
[1]. D.H. Benninger, M. Lomarev, G. Lopez, E.M. Wassermann, X. Li1, E.
Considine, and M. Hallett, “Transcranial direct current stimulation for
the treatment of Parkinson's disease”, Journal of Neurology,
Neurosurgery & Psychiatry, 2010. 81(10): p. 1105-1111.
[2]. F. Fregni, P.S. Boggio, M.C. Santos, M. Lima, A. Vieira, P. Rigonatti,
T.A. Silva, E.R. Barbosa, M.A. Nitsche, and A. Pascual-Leone,
“Noninvasive cortical stimulation with transcranial direct current
stimulation in Parkinson's disease”. Movement disorders, 2006.
21(10): p. 1693-1702.
[3]. J-S. Brittain, P. Probert, T.Z. Aziz, “Tremor suppression by rhythmic
transcranial current stimulation”. Current Biology, 2013. 23(5): p. 436-
440.
[4]. S. Marzban, T. Seifi Ala, F. Towhidkhah, B. Forogh, and S.A Habibi,
“ on the effects of transcranial direct current stimulation on hand
movement in parkinson’s disease: a primary study”, IEEE, ICBME
2017.
[5]. O. Hornykiewicz, “The discovery of dopamine deficiency in the
parkinsonian brain”, in Parkinson’s Disease and Related Disorders.
2006, Springer. p. 9-15.
[6]. T . Wu, and M. Hallett, “The cerebellum in Parkinson’s disease”.
Brain, 2013. 136(3): p. 696-709.
[7]. E. Hoshi, L. Tremblay, J. Feger, and P.L. Carras, “The cerebellum
communicates with the basal ganglia”, Nature neuroscience, 2005.
8(11): p. 1491.
[8]. A.C. Bostan, R.P. Dum, and P.L. Strick, “The basal ganglia
communicate with the cerebellum”, Proceedings of the national
academy of sciences, 2010. 107(18): p. 8452-8456.
[9]. H. Yu, D. Sternad, D.M. Corcos, and D.E. Vaillancour, “Role of
hyperactive cerebellum and motor cortex in Parkinson's disease”,
Neuroimage, 2007. 35(1): p. 222-233.
[10]. J-S. Brittain, H. Cagnan, A.R. Mehta, T.A. Saifee, M.J. Edwards, and
P. Brown, “Distinguishing the central drive to tremor in Parkinson's
disease and essential tremor”, Journal of Neuroscience, 2015. 35(2): p.
795-806.
[11]. G. Saturnino, O. Puonti, J.D. Nielsen, D. Antonenko, K.H. Madsen,
and Axel Thielsche “SimNIBS 2.1: a comprehensive pipeline for
individualized electric field modelling for transcranial brain
stimulation”, bioRxiv. Preprint, 2018. 10: p. 500314.
[12]. A. Thielscher, A. Antunes, and G.B. Saturnino, “Field modeling for
transcranial magnetic stimulation: a useful tool to understand the
physiological effects of TMS?”, in 2015 37th annual international
conference of the IEEE engineering in medicine and biology society
(EMBC). 2015. IEEE.
[13]. Darrigol, o., “Electrodynamics from Ampere to Einstein”, 2002,
oxford university press.
[14]. M. Haeri, Y. Sarbaz, and S. Gharibzadeh, “Modeling the Parkinson's
tremor and its treatments”, Journal of theoretical biology, 2005. 236(3):
p. 311-322.
[15]. T. Neuling, S. Rach, and C.S. Herrmann, “Orchestrating neuronal
networks: sustained after-effects of transcranial alternating current
stimulation depend upon brain states”, Frontiers in human
neuroscience, 2013. 7: p. 161.
[16]. C. Duval, J-F. Daneault, W. Hutchison, A.F. Sadikot, “A brain
network model explaining tremor in Parkinson's disease”,
Neurobiology of disease, 2016. 85: p. 49-59.
[17]. R.C. Helmich, M. Hallett, G. Deushl, I. Toni, and B.R. Bloem, “
Cerebral causes and consequences of parkinsonian resting tremor: a
tale of two circuits Brain”, 2012. 135(11): p. 3206-3226.