High-Frequency Ipsilesional versus Low-Frequency Contralesional Transcranial Magnetic Stimulation after Stroke: Differential Effects on Ipsilesional Upper Extremity Motor Recovery

Abstract

Background and Objectives: Stroke is a major cause of death and disability worldwide; therefore, transcranial magnetic stimulation (TMS) is being widely studied and clinically applied to improve motor deficits in the affected arm. However, recent studies indicate that the function of both arms can be affected after stroke. It currently remains unknown how various TMS methods affect the function of the ipsilesional upper extremity. Materials and Methods: Thirty-five subacute stroke patients with upper extremity motor deficits were enrolled in this study and randomly allocated into three groups, receiving either (1) low-frequency rTMS over the contralesional hemisphere; (2) high-frequency rTMS over the ipsilesional hemisphere; or (3) no stimulation. Experimental groups received 10 rTMS sessions over two weeks alongside standard rehabilitation, and the control group received the same procedures except for rTMS. Both affected and unaffected upper extremity motor function was evaluated using hand grip strength and Functional Independence Measure (FIM) tests before and after rehabilitation (7 weeks apart). Results: All groups showed significant improvement in both the affected and unaffected hand grip and FIM scores (p < 0.05). HF-rTMS led to a notably higher increase in unaffected hand grip strength than the control group (p = 0.007). There was no difference in the improvement in affected upper extremity motor function between the groups. The FIM score increase was lower in the control group compared to experimental groups, although not statistically significant. Conclusions: This study demonstrates the positive effect of ipsilesional HF-rTMS on the improvement in unaffected arm motor function and reveals the positive effect of both LF- and HF-rTMS on the affected upper extremity motor function recovery.

Full text

Citation: Petruseviciene, L.; Sack,
A.T.; Kubilius, R.; Savickas, R.
High-Frequency Ipsilesional versus
Low-Frequency Contralesional
Transcranial Magnetic Stimulation
after Stroke: Differential Effects on
Ipsilesional Upper Extremity Motor
Recovery. Medicina 2023,59, 1955.
https://doi.org/10.3390/medicina
59111955
Received: 6 October 2023
Revised: 29 October 2023
Accepted: 1 November 2023
Published: 6 November 2023
Copyright: © 2023 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
medicina
Article
High-Frequency Ipsilesional versus Low-Frequency
Contralesional Transcranial Magnetic Stimulation after Stroke:
Differential Effects on Ipsilesional Upper Extremity
Motor Recovery
Laura Petruseviciene 1, 2, *, Alexander T. Sack 3, Raimondas Kubilius 1,2 and Raimondas Savickas 1,2
1Department of Rehabilitation, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania;
raimondas.kubilius@lsmuni.lt (R.K.); raimondas.savickas@lsmuni.lt (R.S.)
2Department of Physical Medicine and Rehabilitation, Hospital of Lithuanian University of Health Sciences
Kaunas Clinics, 50161 Kaunas, Lithuania
3Faculty of Psychology and Neuroscience, Maastricht University, 6229 ER Maastricht, The Netherlands;
a.sack@maastrichtuniversity.nl
*Correspondence: laura.petruseviciene@lsmu.lt; Tel.: +37-037-327-182
Abstract:
Background and Objectives: Stroke is a major cause of death and disability worldwide;
therefore, transcranial magnetic stimulation (TMS) is being widely studied and clinically applied to
improve motor deficits in the affected arm. However, recent studies indicate that the function of both
arms can be affected after stroke. It currently remains unknown how various TMS methods affect
the function of the ipsilesional upper extremity. Materials and Methods: Thirty-five subacute stroke
patients with upper extremity motor deficits were enrolled in this study and randomly allocated into
three groups, receiving either (1) low-frequency rTMS over the contralesional hemisphere; (2) high-
frequency rTMS over the ipsilesional hemisphere; or (3) no stimulation. Experimental groups received
10 rTMS sessions over two weeks alongside standard rehabilitation, and the control group received
the same procedures except for rTMS. Both affected and unaffected upper extremity motor function
was evaluated using hand grip strength and Functional Independence Measure (FIM) tests before
and after rehabilitation (7 weeks apart). Results: All groups showed significant improvement in both
the affected and unaffected hand grip and FIM scores (p< 0.05). HF-rTMS led to a notably higher
increase in unaffected hand grip strength than the control group (p= 0.007). There was no difference
in the improvement in affected upper extremity motor function between the groups. The FIM score
increase was lower in the control group compared to experimental groups, although not statistically
significant. Conclusions: This study demonstrates the positive effect of ipsilesional HF-rTMS on
the improvement in unaffected arm motor function and reveals the positive effect of both LF- and
HF-rTMS on the affected upper extremity motor function recovery.
Keywords:
transcranial magnetic stimulation; stroke rehabilitation; affected upper extremity; unaf-
fected upper extremity; neurorehabilitation
1. Introduction
Stroke remains the second leading cause of death [
1
] and one of the leading causes of
severe long-term adult disability worldwide [
2
,
3
]. The incidence rate of stroke increased
almost twice during the past three decades, affecting 12.2 million people annually world-
wide [
1
]. Moreover, due to an increase in conventional stroke risk factors across the entire
age range, such as hypertension, hyperlipidemia, smoking, and obesity, there has been
an increase in stroke incidence in the young [
3
]. Approximately 80% of stroke survivors
suffer from impaired upper extremity motor function [
4
,
5
]. Only 30% to 50% of these stroke
survivors regain functional hand movements within six months after stroke [
5
,
6
] and the
majority are left with disabling neurological deficits [
7
]. This emphasized the need for
Medicina 2023,59, 1955. https://doi.org/10.3390/medicina59111955 https://www.mdpi.com/journal/medicina

Medicina 2023,59, 1955 2 of 9
new, improved treatment options to better support the rehabilitation of these patients. To
address this need, scientists have increasingly focused on non-invasive brain stimulation
technologies capable of modulating brain excitability in order to improve motor deficits in
subacute and chronic stroke patients. One such method is repetitive transcranial magnetic
stimulation (rTMS), an established brain technique using electromagnetic stimulation to
assess and alter cortical excitability and network connectivity in the healthy and diseased
brain [5,6,8].
In a healthy brain, unilateral activation of the primary motor cortex (M1) induces in-
hibitory effects on contralateral M1 through transcallosal pathways [
9
]. The balance of this
interhemispheric inhibition (IHI) has been shown to be impaired after unilateral stroke [
10
].
As a consequence of damaged intracortical connections, contralesional M1 can be disin-
hibited due to reduced inter-hemispheric suppression from the damaged ipsilesional M1,
resulting in pathological overexcitability of the unaffected motor cortex. This disinhibition
of the unaffected hemisphere may directly affect motor function recovery [
9
,
11
,
12
]. De-
pending on the frequency with which rTMS is applied, cortical excitability can be either
suppressed or facilitated [
13
]. Low frequency (
≤
1 Hz, low-frequency (LF)-rTMS) has been
shown to reduce and high frequency (>1 Hz, high-frequency (HF)-rTMS) has been shown
to increase the excitability of the targeted brain region [
13
,
14
]. Following this rationale, it
has previously been shown that both LF-rTMS applied to the contralesional hemisphere as
well as HF-rTMS applied to the ipsilesional hemisphere can have a positive effect on the
affected contralesional upper extremity motor function recovery after ischemic stroke. It,
however, remains largely unclear which of these two different protocols (LF versus HF)
applied to which hemisphere (ipsilesional or contralesional) is the most effective [
13
,
15
–
18
].
Interestingly and also following the logic of inter-hemispheric suppression, effects of either
rTMS protocol should not exclusively be monitored for the affected limb contralateral to
the site of the lesion, but should also include assessing possible effects on the ipsilesional
arm function.
An increasing number of studies indicate that the function of the ipsilesional arm is
also affected after unilateral stroke likely because 10% to 15% of corticospinal pathways run
uncrossed through the spinal cord to the end muscles [
19
,
20
]. Yet, in stroke rehabilitation,
little focus has been targeted toward the ipsilesional arm function and the impact of its
deficit on functional independence [
19
,
21
], nor did the previous rTMS studies systematically
report effects on both affected and unaffected arm function.
This present study aimed to evaluate the relative effect of different rTMS treatment
approaches (LF versus HF) on both ipsilesional and contralesional extremity motor func-
tion recovery in subacute stroke patients in the context of a treatment such as a usual
rehabilitation program.
2. Materials and Methods
2.1. Participants
Thirty-five subacute stroke patients with upper extremity motor deficits were enrolled
in this study according to the following criteria: (1) ischemic stroke of the middle cerebral
artery (MCA) or ischemic vertebrobasilar (VB) stroke, confirmed through instrumental
tests (CT, MRI); (2) acute hemiplegia/hemiparesis, hand motor deficit, muscle
strength ≤4
points (as assessed by the Lovett scale); (3) time after the stroke before inclusion in this
study is no more than 1 month; (4) no severe deficit in cognitive functional (a Mini-Mental
State Examination (MMSE)
≥
18 points); (5) no contraindications of rTMS; and (6) 18 years
and older. Exclusion criteria were as follows: (1) patients with implanted ferromagnetic
or other metal devices sensitive to a magnetic field in the head or neck area; cochlear
implants; implanted neurostimulators, pacemakers, or drug delivery pumps; (2) complete
aphasia or severe cognitive impairment (a Mini-Mental State Examination (MMSE) < 18
points); (3) taking tricyclic antidepressants, neuroleptics, or benzodiazepines; (4) previous
skull fractures or other head injuries with loss of consciousness; (5) history of epilepsy or

Medicina 2023,59, 1955 3 of 9
seizures; (6) spasticity of the upper limb (Ashworth scale > 2); and (7) pregnancy. This
study was conducted in accordance with the Declaration of Helsinki [22].
This study was approved by Kaunas Regional Biomedical Research Ethics Committee
(No: BE-2-86). All participants gave informed consent before the experiment.
In this study, we present findings derived from an ongoing clinical trial registered on
clinicaltrials.gov, ID: NCT05646134.
2.2. Study Design
Based on a randomized, single-blind controlled trial, all patients who were admitted
to the Neurorehabilitation department between December 2021 and December 2022 and
met the inclusion criteria were enrolled in this study and were randomly allocated into
three groups, receiving either (1) low-frequency rTMS over contralesional hemisphere;
(2) high-frequency rTMS over ipsilesional hemisphere; or (3) no stimulation. As none
of the patients had undergone TMS treatment before, individuals in the experimental
groups were blinded to their group allocation. All participants in the experimental groups
received 10 sessions of rTMS over two weeks along with routine rehabilitation procedures:
physiotherapy and occupational therapy for both affected and less affected arms, massage
of the affected extremities, electrostimulation, and psychological consultations. Participants
in the control group received the same procedures except for rTMS treatment. Both affected
and unaffected upper extremity motor function was evaluated through the hand grip
strength [
23
] test performed using a digital hand-held dynamometer at the beginning and
the end of rehabilitation (7 weeks apart). In addition, the Functional Independence Measure
(FIM) test [
24
] was performed before and after the rehabilitation to evaluate the functional
independence of participants.
2.3. Intervention
Repetitive transcranial magnetic stimulation procedures were performed using a
Magstim
®
Rapid2 stimulator (Software number: 3473, Version: V13.0), equipped with an
eight-figure coil. At the beginning of the procedure, the primary motor cortex (M1) and
resting motor threshold (RMT) were established. A resting motor threshold (RMT) was
defined as the lowest intensity that could elicit any time-locked movement caudal to the
wrist in five out of ten trials [
14
]. In the LF-RTMS group, stimulation was performed at 1 Hz,
80% of RMT, over the M1 of the contralesional hemisphere, applying a total of 1200 pulses
(10 trains, 120 pulses per train, intertrain interval 20 s). In the HF-RTMS group, stimulation
was performed at 10 Hz, 80% of RMT, over the M1 of the ipsilesional hemisphere in a
total of 1200 pulses (30 trains, 40 pulses per train, intertrain interval 20 s). Subjects in the
control group did not receive rTMS intervention. All participants received the same routine
rehabilitation procedures: physiotherapy, occupational therapy, massage of the affected
extremities, electrostimulation, and psychological consultations.
2.4. Statistical Analysis
Statistical analysis of the data was performed using the statistical software package
IBM SPSS 22.0. When analyzing the data, descriptive numerical characteristics were
calculated: the number of cases, median, and 25th–75th percentiles (Q1–Q3). Qualitative
non-parametric criteria were assessed using the chi-square (
χ2
) test, and quantitative non-
parametric criteria were assessed using the Kruskal–Wallis test. The significance was set at
p< 0.05.
3. Results
Forty-eight patients with a history of first-ever unilateral ischemic stroke, admitted
at the Neurorehabilitation department of the Hospital of Lithuanian University of Health
Sciences Kaunas Clinics for standard stroke rehabilitation from December 2021 to December
2022, were screened for inclusion in this study. Thirty-five patients that met the criteria and
gave written informed consent were enrolled in this study and randomly allocated into

Medicina 2023,59, 1955 4 of 9
three groups: (1) contralesional LF-rTMS (n= 11), (2) ipsilesional HF-rTMS (n= 13), and
a control group (n= 11). A flow chart showing inclusion into this study is presented in
Figure 1.
Medicina 2023, 59, x FOR PEER REVIEW 4 of 9
3. Results
Forty-eight patients with a history of first-ever unilateral ischemic stroke, admied
at the Neurorehabilitation department of the Hospital of Lithuanian University of Health
Sciences Kaunas Clinics for standard stroke rehabilitation from December 2021 to
December 2022, were screened for inclusion in this study. Thirty-five patients that met the
criteria and gave wrien informed consent were enrolled in this study and randomly
allocated into three groups: (1) contralesional LF-rTMS (n = 11), (2) ipsilesional HF-rTMS
(n = 13), and a control group (n = 11). A flow chart showing inclusion into this study is
presented in Figure 1.
Figure 1. Study flow chart.
Demographic characteristics and baseline values between the groups are
summarized in Table 1. There were no significant differences among the groups.
Table 1. Demographic characteristics of subjects among the groups.
Variables LF-rTMS (n = 11) HF-rTMS (n = 13) Control (n = 11) p Value
Age, years,
median (Q1–Q3) 64.00 (54.00–76.00) 66.00 (60.00–71.00) 76.00 (71.00–82.00) 0.07
Gender,
Male/Female 7/4 9/4 5/6 0.47
Stroke location,
MCA/vertebrobasilar 10/1 11/2 9/2 0.82
Affected side,
Right/left 7/4 5/8 7/4 0.35
RMT,
median (Q1–Q3) 55.00 (50.00–60.00) 51.00 (39.00–59.00) - 0.39
Unaffected upper
extremity hand grip
strength, kg,
median (Q1–Q3)
32.00 (29.00–40.00) 36.00 (23.00–44.00) 22.00 (17.00–36.00) 0.11
Figure 1. Study flow chart.
Demographic characteristics and baseline values between the groups are summarized
in Table 1. There were no significant differences among the groups.
Table 1. Demographic characteristics of subjects among the groups.
Variables LF-rTMS (n= 11) HF-rTMS (n= 13) Control (n= 11) pValue
Age, years,
median (Q1–Q3) 64.00 (54.00–76.00) 66.00 (60.00–71.00) 76.00 (71.00–82.00) 0.07
Gender,
Male/Female 7/4 9/4 5/6 0.47
Stroke location,
MCA/vertebrobasilar 10/1 11/2 9/2 0.82
Affected side,
Right/left 7/4 5/8 7/4 0.35
RMT,
median (Q1–Q3) 55.00 (50.00–60.00) 51.00 (39.00–59.00) - 0.39
Unaffected upper
extremity hand grip
strength, kg,
median (Q1–Q3)
32.00 (29.00–40.00) 36.00 (23.00–44.00) 22.00 (17.00–36.00) 0.11
Affected upper extremity
hand grip strength, kg,
median (Q1–Q3)
0.00 (0.00–2.00) 3.00 (0.00–12.00) 4.00 (0.00–18.00) 0.21
FIM, score,
median (Q1–Q3) 38.00 (34.00–47.00) 44.00 (35.00–55.00) 32.00 (22.00–47.00) 0.15

Medicina 2023,59, 1955 5 of 9
There were no differences among groups before treatment with regard to unaffected
upper extremity hand grip strength (p= 0.11), affected upper extremity hand grip strength
(p= 0.12), and FIM score (p= 0.15). After the treatment, both affected and unaffected upper
extremity hand grip and FIM scores were significantly improved in all groups (p< 0.05).
The exact numbers and pvalues are presented in Table 2.
Table 2.
Motor tests and functional independence test variables of subjects among the groups before
and after the rehabilitation.
Test Group Before After pValue
Unaffected upper extremity hand grip
strength, kg,
median (Q1–Q3)
LF-rTMS (n= 11) 32.00 (29.00–40.00) 41.00 (30.00–48.00) 0.003
HF-rTMS (n= 13) 36.00 (23.00–44.00) 49.00 (30.00–54.00) 0.001
Control (n= 11) 22.00 (17.00–36.00) 24.00 (19.00–38.00) 0.010
Affected upper extremity hand grip
strength, kg,
median (Q1–Q3)
LF-rTMS (n= 11) 0.00 (0.00–2.00) 9.00 (0.00–19.00) 0.018
HF-rTMS (n= 13) 3.00 (0.00–12.00) 9.00 (3.00–21.00) 0.005
Control (n= 11) 4.00 (0.00–18.00) 15.00 (3.00–30.00) 0.011
FIM, score,
median (Q1–Q3)
LF-rTMS (n= 11) 38.00 (34.00–47.00) 78.00 (59.00–88.00) 0.003
HF-rTMS (n= 13) 44.00 (35.00–55.00) 80.00 (72.00–101.00) 0.001
Control (n= 11) 32.00 (22.00–47.00) 62.00 (45.00–72.00) 0.003
Unaffected upper extremity hand grip strength significantly increased more in the
HF-rTMS group compared to the control group (p= 0.007). There was no difference in the
improvement in affected upper extremity motor function between the groups. The FIM
score increased the least in the control group compared to both LF- and HF-rTMS groups,
although the differences were not statistically significant. The exact numbers and pvalues
are presented in Table 3.
Table 3.
Motor tests and functional independence test changes among the groups before and after
the rehabilitation.
Variables LF-rTMS (n= 11) HF-rTMS (n= 13) Control (n= 11) pValue
Unaffected upper extremity hand
grip strength, kg,
median (Q1–Q3)
4.00 (2.00–11.00) 8.00 (5.00–12.00) * 2.00 (0.00–2.00) * 0.007
Affected upper extremity hand
grip strength, kg,
median (Q1–Q3)
9.00 (0.00–10.00) 4.00 (1.00–7.00) 4.00 (0.00–12.00) 0.95
FIM, score,
median (Q1–Q3) 35.00 (22.00–49.00) 38.00 (29.00–48.00) 25.00 (15.00–40.00) 0.11
*—statistical significance.
4. Discussion
In this study, we aimed to evaluate which of the currently applied brain stimulation
approaches for motor stroke rehabilitation is more effective, using high-frequency rTMS
to increase the excitability of the affected ipsilesional hemisphere, or using low-frequency
rTMS to reduce the disinhibited hyperactivity within the unaffected contralesional hemi-
sphere. To this end, we directly compared those two approaches with a control group not
receiving brain stimulation in the rehabilitation program for subacute stroke. Also, we
systematically assessed effects of rTMS on both the ipsilesional and contralesional upper
extremities motor function.
A significantly improved motor function of both affected and unaffected upper extrem-
ities and functional independence were observed in all groups after 7 weeks of rehabilitation.
However, opposite from what was expected, none of the two rTMS approaches signifi-
cantly added an additional improvement in upper extremity motor function or functional
independence when applied as an add-on therapy to the standard rehabilitation program

Medicina 2023,59, 1955 6 of 9
(control group). Yet, we analyzed the rTMS effect on top of an already effective stroke
rehabilitation program; hence, it is more difficult to obtain significant findings. Importantly,
we found that HF-rTMS (10 Hz) applied to the ipsilesional hemisphere significantly im-
proved the unaffected upper extremity hand grip strength compared to the control group.
This is intriguing and potentially relevant as we were unable to identify other studies
that found motor function improvements of the unaffected upper extremity after a course
of rTMS treatment, as we report here. Most previous rTMS studies either evaluated the
motor function of only the affected arm [
15
,
16
,
25
–
28
] or did not observe any significant
differences in unaffected upper extremity motor recovery [
16
,
29
]. Despite the fact that
rTMS has been poorly investigated on ipsilesional arm motor recovery after stroke, our
findings suggest that it might be an effective treatment of both affected and unaffected
upper extremities. This nicely aligns with the increasing number of studies indicating
ipsilesional upper extremity impairments after stroke [
19
], and the recent suggestion that
the grip strength of the unaffected arm might be a predictor for short-term motor recovery
after stroke with motor training of the unaffected arm having a significant correlation with
the functional outcome [30].
After unilateral stroke, the affected side of the brain can cause dysfunction in both
contralesional and ipsilesional arms. It is believed to occur because approximately 10% to
15% of corticospinal pathways travel uncrossed directly from the brain to the end muscles
of the body. The other reason is a phenomenon known as diaschisis, in which a weakened
connection between two areas of the brain caused by damage to one area can lead to
reduced function in the other area [
19
]. While not as obvious as contralesional deficits,
ipsilesional deficits can have a major impact on post-stroke functional recovery since during
many activities of daily living, both limbs are required, and the presence of ipsilesional
impairments can further hinder an individual’s ability to complete these tasks [
19
,
31
].
Additionally, it is acknowledged that ipsilesional arm dysfunction is closely related to the
severity of the stroke, as the higher the damage to the brain, the more likely decreased
ipsilesional function is caused [
21
], as well as with lateralization of the stroke, as a subject
with a stroke in the right hemisphere more often suffers from reduced motor function of
both contra- and ipsilesional arms [
21
,
32
]. However, impaired function of the ipsilesional
arm after a unilateral stroke is often overlooked and consequently left untreated [
31
,
33
,
34
].
Our study shows that ipsilesional HF-rTMS has a significantly better effect on un-
affected upper extremity motor recovery than both LF-rTMS and sham stimulation. We
believe that the primary cause of this outcome is likely diaschisis, which occurs because of
damaged nerve fibers. This damage leads to a reduction in secondary blood flow in the
hemisphere on the same side as the injury [
35
]. Regarding this phenomenon, excitatory
stimulation might increase blood flow, oxygen metabolic rate, cerebral glucose metabolic
rate, and other parameters in both hemispheres via neural connections, resulting in an
improved function of both upper extremities. Naturally, this raises the question if excitatory
rTMS over the intact cortex had even better results for motor recovery. We managed to
find only one study addressing this hypothesis [
36
]. The results of that study suggest
that the modulation of abnormal interhemispheric inhibition might be useful for patients
with mild motor dysfunction but may be less effective for those with severe deficits due to
extensive damage of transcallosal pathways. Therefore, the treatment that can stimulate
the compensatory effects might be superior to the treatment that modulates the excitability
of the brain cortex in severe stroke. However, if HF-rTMS has excitatory effects on both
hemispheres, does LF-rTMS have the opposite suppressor effect? Because LF decreases
the excitability of the intact cortex, some researchers anticipated that it could produce a
reverse effect on the unaffected upper extremity; however, a meta-analysis performed in
2014 ruled out this possible adverse effect, and to our knowledge, this question was not
discussed in future studies [
37
]. We also believe that LF-rTMS is safe for both affected and
unaffected upper extremity motor recovery. However, based on our current findings, it
might not have an impact on compensatory effects in the intact cortex and might thus not
improve ipsilesional arm function.

Medicina 2023,59, 1955 7 of 9
Similar to the results of other authors [
38
,
39
], in our study, the tendency of both LF-
and HF-rTMS treatment to increase the functional independence of patients was observed,
even though, in our case, there was no significant difference compared to the control group.
Our study was not free of limitations. We believe the absence of significantly better
results of both hand grip strength and Functional Independence Measure tests in experi-
mental groups was due to the small sample. Despite the small sample, we also performed
a small number of tests for upper extremity motor function evaluation. Even though grip
strength is considered to be a good indicator of hand function after stroke [
30
], more tests
should be performed since upper extremity function depends not only on muscle strength
but also on dexterity, spasticity, range of motion, and proprioception. Many scientists per-
form a Fugl Meyer Assessment for Upper Extremity (FMA-UE) and Wolf Motor Function
Test (WMFT) in stroke rehabilitation since both of these tests are stroke-specific. Still, FMA-
UE is believed to be more sensitive to changes during the rehabilitation process [
40
]. A
variety of other measures, like the Nine-Hole Peg Test, Box and Block test, Action Research
Arm Test, finger tapping, pinch strength, modified Rankin scale, and Barthel index, are
being used for evaluation of upper extremity motor function rehabilitation [
25
–
29
]. Every
test has its own benefits; therefore, using more outcome measures might be helpful for a
more accurate assessment of stroke rehabilitation. Moreover, rTMS is known to have a
great placebo effect for stroke patients [
41
], and we did not have an opportunity to control
this effect, since we did not apply sham stimulation for the control group. Furthermore, in
this study, we did not assess the impact of education, manual dominance, comorbidities,
and other baselines values that could have an impact on stroke rehabilitation effectiveness.
Assessing baseline values reduces variability, enables comparative analyses, monitors indi-
vidual responses, and upholds scientific rigor, all of which contribute to a comprehensive
and robust assessment of the intervention’s impact [42].
It is crucial to emphasize that although this study presents statistical trends and signif-
icance, understanding the clinical and practical implications of these findings necessitates
additional investigation. Further research is needed to assess this aspect.
5. Conclusions
In conclusion, this study demonstrated the possible effect of both LF- and HF-rTMS
on affected upper extremity motor function recovery in stroke patients. However, due
to the small sample and limited outcome measures, the results were insignificant. It also
showed the differential positive effect of HF-rTMS on the improvement in unaffected arm
motor function. This finding requires a better understanding of how rTMS may affect
the ipsilesional arm motor function after stroke, an area largely under-investigated in the
literature today. Further studies with larger, randomized, controlled samples are needed
for a better assessment of the efficacy and safety of rTMS for the recovery of both affected
and unaffected upper extremity motor function after a stroke.
Author Contributions:
Conceptualization, L.P., A.T.S., R.K. and R.S.; methodology, L.P., A.T.S., R.K.
and R.S.; validation, L.P., A.T.S. and R.S.; formal analysis, L.P.; investigation, L.P. and R.S.; resources,
L.P. and R.S.; data curation, L.P.; writing—original draft preparation, L.P.; writing—review and
editing, L.P., A.T.S., R.K. and R.S.; visualization, L.P.; supervision, A.T.S., R.K. and R.S.; project
administration, R.S. All authors have read and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement:
The study was conducted in accordance with the Declaration
of Helsinki and approved by Kaunas Regional Biomedical Research Ethics Committee of Lithuanian
University of Health Sciences (protocol code BE-2-86; date of approval 14 October 2021).
Informed Consent Statement:
Informed consent was obtained from all subjects involved in the study.
Data Availability Statement:
The data presented in this study are available on request from the
corresponding author. The data are not publicly available due to privacy reasons.
Conflicts of Interest: The authors declare no conflict of interest.

Medicina 2023,59, 1955 8 of 9
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