Previous studies suggest that low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) over contralateral premotor cortex (PMC) might ameliorate Focal Hand Dystonia (FHD) symptoms. In the present study behavioral and muscle activity outcomes were explored in a patient with FHD following a single and multiple sessions of rTMS. The patient's behavior was assessed on handwriting tasks, while surface EMG signals were recorded. In Experiment 1 evaluations were performed before and after one session of active and sham 1Hz rTMS over contralateral PMC. In Experiment 2, evaluations were performed before and after six sessions of the same treatment. In Experiment 1 active rTMS improved the patient's performance, although the EMG amplitude did not change. In Experiment 2, the patient showed an improvement of performance along with a decrease of 20% in the EMG amplitude. These results demonstrated that a single session of rTMS ameliorated the patient's performance, while multiple sessions were necessary to reduce muscles activity

Berti, A.

Boccia, G.

Dardanello, D.

Formicola, D.

Nobili, M.

Salatino, A.

Spadea, G.

English

Salatino, Adriana

Boccia, Gennaro

Dardanello, Davide

Formicola, Donato

Spadea, Giulia

Nobili, Marcello

Berti, Anna

DIAL UCLouvain

Acute and cumulative effects of rTMS on behavioural and EMG parameters in Focal Hand Dystonia.

Institutional Research Information System University of Turin

Heliyon 5 (2019) e02770Contents lists available at ScienceDirectHeliyonjournal homepage: www.heliyon.comAcute and cumulative effects of rTMS on behavioural and EMG parametersin Focal Hand DystoniaAdriana Salatino a,*, Gennaro Boccia b, Davide Dardanello b, Donato Formicola b, Giulia Spadea a,Marcello Nobili c, Anna Berti aa Department of Psychology, University of Turin, Via Po 14, 10123, Italyb NeuroMuscularFunction Research Group, Department of Medical Sciences, University of Turin. 12, piazza Bernini, 10143, Torino, Italyc Unit of Neurology, Koelliker Hospital, Turin, ItalyA R T I C L E I N F OKeywords:NeuroscienceBehavioral neuroscienceMuscleNeurologyNervous systemMovement disordersPremotor cortexrTMSDystoniaEMG* Corresponding author.E-mail address: adriana.salatino@unito.it (A. Sahttps://doi.org/10.1016/j.heliyon.2019.e02770Received 14 November 2018; Received in revised f2405-8440/© 2019 The Author(s). Published by Elsnc-nd/4.0/).A B S T R A C TPrevious studies suggest that low-frequency repetitive Transcranial Magnetic Stimulation (rTMS) over contra-lateral premotor cortex (PMC) might ameliorate Focal Hand Dystonia (FHD) symptoms. In the present studybehavioral and muscle activity outcomes were explored in a patient with FHD following a single and multiplesessions of rTMS. The patient's behavior was assessed on handwriting tasks, while surface EMG signals wererecorded. In Experiment 1 evaluations were performed before and after one session of active and sham 1Hz rTMSover contralateral PMC. In Experiment 2, evaluations were performed before and after six sessions of the sametreatment. In Experiment 1 active rTMS improved the patient's performance, although the EMG amplitude did notchange. In Experiment 2, the patient showed an improvement of performance along with a decrease of 20% in theEMG amplitude. These results demonstrated that a single session of rTMS ameliorated the patient's performance,while multiple sessions were necessary to reduce muscles activity.1. IntroductionFocal hand dystonia (FHD) is a task-specific form of dystonia [1],resulting from abnormal neuroplasticity. An electromyographic (EMG)study [2] has demonstrated higher muscles activity during writing tasksin patients with FHD with respect to healthy subjects while other in-vestigations suggested that low-frequency repetitive Transcranial Mag-netic Stimulation (rTMS) over contralateral premotor cortex (PMC)might ameliorate FHD [3,4]. Although a previous study combining theuse rTMS with the assessment of FHD trough a multi-channel EMGtechnique found that co-contraction and overflow showed by dystonicpatients during handwriting decreased after one rTMS session over thePMC [4], the effects of multiple rTMS sessions on muscle activity havenever been investigated.Here, we explored behavioural and muscle activity outcomes,following single (Experiment 1: Acute Effects-AE) and multiple sessions(Experiment 2: Cumulative Effects-CE) of rTMS in a 41-year-old manwhodeveloped FHD, mainly affecting the right index and middle fingers, sixyears before our evaluations. At the onset of the disorder, his symptomsappeared during mouse manipulation, but over time they appearedlatino).orm 2 July 2019; Accepted 29 Oevier Ltd. This is an open access aduring the execution of actions requiring fine movement control. Despitethe severity of his condition, he was free of medications.2. Material and methodsIn Experiment 1, we administered one rTMS session (1-Hz, 900stimuli, 90% of resting Motor Threshold-rMT) over the left PMC, definedas 2 cm anterior and 1 cm medial to the previously defined M1 hotspot[5], and a sham session after a week. In Experiment 2, we administeredsix sessions of the same treatment, every other day, for two weeks. Theevaluations were performed before (Pre-Acute: Pre-A) and after (Post-A)the single and the sham rTMS sessions (Pre-Sham: Pre-S/Post-S) inExperiment 1, and before rTMS (Pre-Cumulative: Pre-C), one day afterthe end of the rTMS sessions (Post-C). Furthermore, an additional eval-uation was performed two weeks after the intervention (Follow-up: FU)in Experiment 2. For each evaluation, the signature and the word copyingwere performed two times (one pre and one post the rTMS application),except for the FU, where the evaluation was performed only once.In addition, the patient's dystonia was evaluated by the neurologistpre and post the single and the six rTMS sessions. A healthy man (32-ctober 2019rticle under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-A. Salatino et al. Heliyon 5 (2019) e02770year-old) was evaluated using the same tasks and EMG recording.Handwriting was assessed on two tasks (producing the own signature andcopying two words), while surface EMG signals were registered from theeight upper limb muscles reported in the figure caption. A verbal com-mand to start the task was given to the patient and the time spent for theexecution of each task (Execution Time-ET) was calculated with the helpof the videotape recordings. The estimation of the muscle activity wascomputed as the EMG signal amplitude averaged among the wholetask(s). The patient, as well as the healthy volunteer, were screened forinclusion/exclusion criteria for TMS, and they signed a written informedconsent to participate to the study, which was approved by the LocalEthical Committee.3. ResultsIn Experiment 1 active rTMS considerably improved the patient'sperformance, reducing the ET by 73% in signature (rTMS: Pre-A ¼ 26.16s, Post-A¼ 7.16 s; Sham: Pre-S¼ 24.00 s, Post-S¼ 21.00 s) and by 37% inwords coping (rTMS: Pre-A ¼ 19.00 s, Post-A ¼ 12.00 s; Sham: Pre-S ¼24.00 s, Post-S ¼ 21.00 s) although the overall EMG amplitude did notchange after both sessions (See Supplementary Video 1, 2 and 3). InExperiment 2, reduction in ET by 22% was found in signature (Pre-C ¼19.84 s, Post-C ¼ 15.48 s) and by 23% in words coping (Pre-C ¼ 22.00 s,Post-C¼ 17.00 s) in the Post-C ET. Ameliorations were maintained at theFU evaluation with a reduction of 17% in ET for the signature and of 36%in words coping with respect to the Pre-C rTMS evaluation (See Sup-plementary Video 1, 4 and 5).Importantly, in the Post-C assessment the overall EMG amplitudedecreased by 20% (the reduction of muscles contraction was more pro-nounced for the signature, Fig. 1 and Table 1 for more details), althoughthe reduction was not maintained at the FU. The healthy control showedshorter ET and lower muscles activity than patient for both handwritingtasks (6 s for each task). However, the dystonic symptoms evaluationdid not reveal significant improvement associated with these ameliora-tions. In relation to the rMT, in Experiment 1, it did not change in the pre-and post evaluation for both active and sham sessions (i.e. 37% of themachine output). In Experiment 2 the rMT decreased of 3% (i.e. 34% ofFig. 1. Representative examples of the EMG signals during signature for the patientEMG signals during signature for the patient (A/B) and for the healthy participant (Clength (patient's name and surname: 14 characters; healthy participant's name and suexecution are pointed out by the dashed lines and the actual duration of each trial i(FDI), extensor carpi radialis (ECR), extensor carpi ulnaris (ECU), flexor carpi radiaanterior deltoid (AD), upper trapezius (UT). The EMG signals were registered using biamplified (gain ¼ 2000, amplifier EMG-USB, OT Bioelettronica, Torino) and sample2the machine output), although the decrease of rMTwas not maintained atthe FU evaluation (i.e. 37% of the machine output).4. DiscussionThe feature unique to this study is the assessment of both acute andcumulative rTMS effects on FHD symptoms with the analysis of behav-ioural performances and EMG signals recorded from as many as eightupper limb muscles. Previous studies [3,5] have investigated the effectsof low-frequency rTMS in FHD. Overall, our results are in line withprevious evidences, suggesting that inhibitory low-frequency rTMS overcontralateral PMC may ameliorate handwriting performance. However,with respect previous evidences [3–5], here we investigate the changes inmuscles co-contraction and overflow showed by dystonic patient duringhandwriting from as many as eight upper limb muscles following singleand multiple sessions of rTMS. Results have shown a global reduction ofmore than 20% in the observed muscles after six rTMS sessions,demonstrating that multiple rTMS interventions could reduce theabnormal muscle activity in FHD. Since the co-contraction of muscles isone of the characteristics of FHD, which lead to abnormal posturing andreduced fine motor control [1], future rTMS studies should take intoaccount their potential changes after application of rTMS treatment.5. ConclusionsThese results suggest that rTMS represents a useful tool for thetreatment of FHD symptoms, since it decreased muscle over-excitationand improved the patient's performance. They also show that a singlesession of rTMS may ameliorate patient's performance, but multiplesessions are necessary to reduce the muscle activity of the upper affectedlimb, although after two weeks the initial changes were not maintained.These findings indicate also that surface EMG represents a non-invasiveand useful method to evaluate neuromuscular modulations after rTMStreatment. Finally, due to the differences we found in the behaviouraloutcomes between the Post-A and the Post-C evaluation, we stronglysupport the utility to assess both acute and cumulative effects of a singlerTMS session in case of multiple sessions for the treatment of the FHD.and for the healthy participant. The figure shows representative examples of the). The patient and the healthy participant had approximately the same full namername: 13 characters). For each trial the beginning and the end of the actual tasks reported (in seconds). EMG signals are reported from: first dorsal interosseouslis (FCR), long head of biceps brachii (BB), long head of triceps brachii (TB),polar Ag/AgCl surface electrodes (Spes Medica, Battipaglia, Italy) and they wered at 2048Hz and bandpass filtered (20–450 Hz).Table 1Values of the EMG amplitude, i.e. the average rectified value (ARV) of the EMG signals expressed in microVolt.Muscles Pre-ACUTE Post-ACUTE % of Change Pre-CUMULATIVE Post-CUMULATIVE % of ChangeFDI 48.4 41.3 -14.7 49.8 33.5 -32.7ECR 44.9 46.8 4.2 88.9 69.3 -22.0ECU 29.2 33 13.0 39.7 29.2 -26.4FCR 20.4 21 2.9 30.3 14.1 -53.5BB 7.3 9.2 26.0 46.2 35.7 -22.7TB 24 20 -16.7 24.5 5.2 -78.8AD 4.5 4.4 -2.2 3.6 2.9 -19.4UT 27.3 17.9 -34.4 37 22 -40.5The values of the EMG ARV for the eight muscles observed, in both the Experiments (Acute and Cumulative). In the column “% of Change” is reported the change,expressed in percentage between the pre and the post evaluation for both the Experiments.A. Salatino et al. Heliyon 5 (2019) e02770However, given that the present data were collected on a single FHDpatient, no clear conclusions can be drawn from this finding. Therefore,the ability to draw generalizable conclusion is severely hindered by thislimitation. Future studies on large number of patients, also targetingdifferent brain areas [6], are necessary to further investigate the physi-ologic and behavioral effects of multiple sessions of rTMS in FHD.DeclarationsAuthor contribution statementAdriana Salatino: Conceived and designed the experiments; Per-formed the experiments; Analyzed and interpreted the data; Wrote thepaper.Gennaro Boccia: Performed the experiments; Analyzed and inter-preted the data; Wrote the paper.Davide Dardanello, Donato Formicola, Giulia Spadea: Performed theexperiments; Analyzed and interpreted the data.Marcello Nobili: Conceived and designed the experiments; Analyzedand interpreted the data.Annamaria Berti: Conceived and designed the experiments; Analyzedand interpreted the data; Wrote the paper.Funding statementThis work was supported by San Paolo Foundation grants to Anna-maria Berti.Competing interest statementThe authors declare no conflict of interest.3Additional informationSupplementary content related to this article has been publishedonline at https://doi.org/10.1016/j.heliyon.2019.e02770.AcknowledgementsThe study has been funded San Paolo Foundation grants to AB. Theauthors report no other financial disclosure. The authors wish to thankMario Del Piano for his valuable suggestions about videos preparation.References[1] M.P. Sheehy, C.D. Marsden, Writers' cramp-a focal dystonia, Brain 105 (Pt 3) (1982)461–480.[2] A. Sivadasan, M. Sanjay, M. Alexander, S.R. Devasahayam, B.K. Srinivasa, Utility ofmulti-channel surface electromyography in assessment of focal hand dystonia,Muscle Nerve 48 (3) (2013) 415–422, 2013 Sep.[3] M. Borich, S. Arora, T.J. Kimberley, Lasting effects of repeated rTMS application infocal hand dystonia, Restor. Neurol. Neurosci. 27 (1) (2009) 55–65.[4] N. Murase, J.C. Rothwell, R. Kaji, R. Urushihara, K. Nakamura, N. Murayama,T. Igasaki, M. Sakata-Igasaki, T. Mima, A. Ikeda, H. Shibasaki, Subthreshold low-frequency repetitive transcranial magnetic stimulation over the premotor cortexmodulates writer's cramp, Brain. Jan 128 (Pt 1) (2005) 104–115. Epub 2004 Oct 13.[5] T.J. Kimberley, M.R. Borich, S. Arora, H.R. Siebner, Multiple sessions of low-frequency repetitive transcranial magnetic stimulation in focal hand dystonia:clinical and physiological effects, Restor. Neurol. Neurosci. 31 (5) (2013) 533–542.[6] R. Ricci, A. Salatino, H.R. Siebner, G. Mazzeo, M. Nobili, Normalizing biased spatialattention with parietal rTMS in a patient with focal hand dystonia, 2014, BrainStimul 7 (6) (2014) 912–914. Epub 2014 Aug 4.

Acute and cumulative effects of rTMS on behavioural and EMG parameters in Focal Hand Dystonia

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Acute and cumulative effects of rTMS on behavioural and EMG parameters in Focal Hand Dystonia

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