Short-term effects of transcranial direct current stimulation on motor speech in Parkinson's disease: a pilot study

NEUROLOGY AND PRECLINICAL NEUROLOGICAL STUDIES - ORIGINAL ARTICLE Jou nal o Neu al T ansmission (2024) 131:791–797 h ps://doi.o g/10.1007/s00702-024-02771-5 he e idence sugges s ha le odopa has no signi ican sho - e m e ec s on speech (Skodda e al. 2010; Ca allie i e al. 2021). Longi udinal s udies (Rusz e al. 2016; Tykalo a e al. 2015) e ealed ha le odopa adminis a ion in he ea ly s ages o PD may imp o e consonan a icula ion bu also lead o mo e dys luen speech. A ecen s udy (Rusz e al. 2021) ound a iable esponses o long- e m le odopa adminis a ion among ea ly PD pa ien s depending on spe- ci ic HD pheno ypes. Speech indings a e he deep b ain s imula ion (DBS) also a y (Skodda e al. 2014; Baudouin e al. 2023). P e i- ous esea ch showed ha DBS may imp o e oice emo o oice in ensi y (T ipoli i e al. 2011; Tsuboi e al. 2014), bu a he same ime, i may wo sen speech in elligibili y (T ipoli i e al. 2011, 2014; Pin o e al. 2014; Tsuboi e al. 2014). P edic i e ac o s o his de e io a ion include longe disease du a ion and lowe speech in elligibili y be o e su - ge y (T ipoli i e al. 2014; Pin o e al. 2023). Taken oge he , he e ec s o pha macological and su gical in e en ions on HD a e limi ed and a ied. The e o e, he e is a need o In oduc ion App oxima ely 90% o indi iduals wi h PD expe ience hypokine ic dysa h ia (HD) as he disease p og esses (Ramig e al. 2008). HD is de ined by dec eased a iabili y in pi ch and olume, imp ecise a icula ion, impai ed speech p osody, and inapp op ia e silences (B abenec e al. 2017). S udies examining he e ec o dopamine gic medica ion on HD epo mixed esul s (B abenec e al. 2017). Mos o I ena Rek o o a [email p o ec ed] 1 Applied Neu oscience Resea ch G oup, Cen al Eu opean Ins i u e o Technology – CEITEC, Masa yk Uni e si y, B no, Czech Republic 2 Depa men o Telecommunica ions, B no Uni e si y o Technology, B no, Czech Republic 3 Facul y o Medicine and S . Anne’s Uni e si y Hospi al, Fi s Depa men o Neu ology, B no, Czech Republic Abs ac In oduc ion: Hypokine ic dysa h ia (HD) is a common mo o speech symp om o Pa kinson’s disease (PD) which does no espond well o PD ea men s. We in es iga ed sho - e m e ec s o ansc anial di ec cu en s imula ion ( DCS) on HD in PD using acous ic analysis o speech. Based on ou p e ious s udies we ocused on s imula ion o he igh supe io empo al gy us (STG) - an audi o y eedback a ea. Me hods: In 14 PD pa ien s wi h HD, we applied anodal, ca hodal and sham DCS o he igh STG using a c oss-o e design. A p o ocol consis ing o speech asks was pe o med p io o and immedia ely a e each s imula ion session. Linea mixed models we e used o he e alua ion o he e ec s o each s imula ion condi ion on he ela i e change o acous ic pa ame e s. We also pe o med a simula ion o he mean elec ic ield induced by DCS. Resul s: Linea mixed model showed a s a is ically signi ican e ec o he s imula ion condi ion on he ela i e change o median du a ion o silences longe han 50 ms (p = 0.015). The ela i e change a e he anodal s imula ion (mean = -5.9) was signi ican ly lowe as compa ed o he ela i e change a e he sham s imula- ion (mean = 12.8), p = 0.014. We also ound a co ela ion be ween he mean elec ic ield magni ude in he igh STG and imp o emen o a icula ion p ecision a e anodal DCS (R = 0.637; p = 0.019). Conclusions: The explo a o y s udy showed ha anodal DCS applied o e he audi o y eedback a ea may lead o sho e pauses in a speech o PD pa ien s. Keywo ds Pa kinson’s disease · Hypokine ic dysa h ia · T ansc anial elec ic s imula ion · Acous ic analysis · Supe io empo al gy us Recei ed: 9 Feb ua y 2024 / Accep ed: 25 Ma ch 2024 / Published online: 9 Ap il 2024 © The Au ho (s) 2024 Sho - e m e ec s o ansc anial di ec cu en s imula ion on mo o speech in Pa kinson’s disease: a pilo s udy LubosB abenec1· DanielKo ac2· Ji iMekyska2· LenkaRehulko a1,3· Ve onikaKab o a1,3· I enaRek o o a1,3 1 3 L. B abenec e al. explo e o he me hods ha a ge di e en aspec s o speech and could po en ially be used also in la e s ages o PD. We ocused ou esea ch on non-in asi e b ain s imula- ion me hods (NIBS). In PD pa ien s wi h HD, epe i i e ansc anial magne ic s imula ion ( TMS) has been mos ly applied o e a p ima y o o acial a ea (OFSM1) wi h incon- sis en esul s (B abenec e al. 2017). Howe e , p e ious esea ch showed ha pa icula ly he igh pos e io supe io empo al gy us (STG), a co ical egion in ol ed in audi- o y speech eedback (Liu e al. 2023), plays an impo an ole in modula ion o mo o aspec s o speech p oduc ion in PD pa ien s (New e al. 2015; Klobusiako a e al. 2021). In ou p e ious s udy (B abenec e al. 2019), we demons a ed ha a single session o 1 HZ TMS o e he igh STG may lead o signi ican imp o emen o a icula ion in PD. The imp o emen s we e signi ican ly highe han imp o emen s a e 10 Hz s imula ion o e he le OFSM1, and mo e p o- nounced han he s imula ion o a con ol s imula ion si e (B abenec e al. 2019). A subsequen s udy also showed ha mul iple sessions o ac i e TMS o e he igh STG, as compa ed o sham s imula ion, had long-las ing posi i e e ec s on HD, pa icula ly on pe cep ual measu es o a ic- ula ion, p osody, and speech in elligibili y. These e ec s we e suppo ed by emo e s imula ion-induced b ain plas- ici y changes wi hin he a icula o y ne wo ks (B abenec e al. 2021). In ou cu en p ojec , we aim o de elop a p og am o emo e ea men o HD. To achie e ou goal, we chose ansc anial di ec cu en s imula ion ( DCS) ha can be used emo ely by pa ien s a home oge he wi h a concu - en Lee Sil e man Voice T ea men (LSVT), i.e., he bes documen ed he apy o symp oms o HD in PD (Yuan e al. 2020). In PD pa ien s, DCS and o he modes o em- po al elec ical s imula ion ( ES) ha e mos ly been used o modula e gai speed, eezing o gai , limb b adykinesia, a en ion and execu i e unc ions, and b ain exci abili y (Ni e al. 2022). S udies also p o ided e idence ha home- based DCS ea men is easible and sa e o PD pa ien s (Dobbs e al. 2018). To ou knowledge, esea ch on he e ec s o DCS/ ES on HD symp oms in PD has no ye been conduc ed. In his pilo s udy, we pa icula ly concen a ed on iden i- ying a sui able elec ode mon age and examined immedia e a e e ec s o a single session o DCS on HD symp oms. These acu e e ec s could las up o an hou (Ni sche e al. 2008; B unoni e al. 2012). S udies ha e also shown ha di e en cu en low di ec ions may esul in di e en a e - e ec s, and he di ec ion o he exci abili y shi migh be di e gen , dependen no only on s imula ion pola i y, bu also on he speci ic elec ode mon age (Ni sche e al. 2008). The e o e, we applied bo h anodal and ca hodal DCS o he igh STG. We also used SimNIBS (Thielsche e al. 2015) so wa e o simula ion o he mean elec ic ield induced by DCS. Rega ding beha io al ou comes, we ocused on he acous ic pa ame e s ha we e esponsi e o non-in asi e b ain s imula ion me hods in ou p e ious s udies (B abenec e al. 2017, 2019). Me hods Pa icipan s The inclusion c i e ia o en olmen in o he s udy we e as ollows: (1) clinically es ablished PD (c i e ia by Pos- uma e al. 2016), (2) igh -handedness, (3) p esence o HD symp oms based on he assessmen o a speech he a- pis and he esul s o a 3F Tes Dysa h ic p o ile o al sco e (Kos alo a 2013), (4) Czech as hei i s language. Exclusion c i e ia we e (1) alcohol o d ug abuse, (2) hal- lucina ions, (3) any diagnosed psychia ic diso de (4) demen ia, based on he Mon eal Cogni i e Assessmen (MoCA) es o demen ia, MoCA > 20 (Biundo e al. 2014), and on a clinician’s in e iew wi h a ca egi e (5) ca dio pacemake o any MRI-incompa ible me al in he body, (6) epilepsy. The disease se e i y was assessed using he Uni ied Pa - kinson’s Disease Ra ing Scale (UPDRS), pa III (Mo o Examina ion) scale. All pa icipan s we e on a s able dopa- mine gic medica ion a leas 4 weeks p io o baseline assessmen and du ing he whole s udy. The pa ien s we e es ed in he ON medica ion s a e wi hou dyskinesias since we wan ed o modula e HD symp oms in a eal-li e scena io in pa ien s on dopamine gic medica ion. All pa ien s signed an in o med consen o m ha was app o ed by he local e hics commi ee. S udy design Pa icipan s unde wen DCS o e he igh pos e io STG. A he baseline isi , each pa icipan unde wen a speech assessmen using he 3F Tes Dysa h ic p o ile (Kos alo a 2013) ( o de ails see Table S1 in Supple- men a y ma e ials). S uc u al MRI scans (T1 MPRAGE) we e pe o med o ameless s e eo ac ic na iga ion o he elec ode placemen . A e he baseline isi , each pa icipan unde wen h ee s imula ion sessions (anodal, ca hodal, and sham s imula ion), sepa a ed by one day wi hou s imula ion. A c osso e double-blind design was used, and s imula ion p o ocols we e andomized ac oss subjec s and sessions. A p o ocol consis ing o speech asks las ed up o 10 min and was pe o med p io o and immedia ely a e each s imula ion session. 1 3 792 Sho - e m e ec s o ansc anial di ec cu en s imula ion on mo o speech in Pa kinson’s disease: a pilo … Acous ic analysis o speech The speech p o ocol con ained a special eading ask ( ead- ing a phone ically balanced pa ag aph con aining 150 wo ds; pa ien s we e allowed ead he ex in ad ance). HD symp oms we e assessed using speech pa ame e s o in e - es based on ou p e ious esea ch.(B abenec e al. 2019) Mo e speci ically, we quan i ied ongue and jaw igidi y ( elF1SD and elF2SD), monopi ch ( elF0SD), du a ion o silences (Du MED), and i egula speech hy hms (SPIR) (see Table 1 o de ailed desc ip ion o he pa ame e s). TDCS p o ocol S imula ion was applied h ough a ba e y-d i en de ice (DC-S imula o Plus, neu oConn GmbH, Ge many). Bo h elec odes we e posi ioned o e he igh and le pos e io supe io empo al gy us (STG) (MNI coo dina es: X = 40, Y = − 38, Z = 14; X = − 40, Y = − 38, Z = 14; based on ou p e ious esea ch) (B abenec e al. 2021). We used he T1 MRI scan-based ameless s e eo ac ic neu ona iga ion o speci y he exac loca ion o he elec ode cen e in each indi idual. Fo anodal s imula ion, he anode was placed o e he igh STG and he ca hode o e he le STG. Fo ca hodal s imula ion, he ca hode was placed o e he igh STG and he anode o e he le STG. A cu en o 2 mA was deli e ed using wo ubbe elec- odes (5 × 5 cm) o 20 min. The elec ode was held in place by a conduc i e gel. The sham s imula ion was applied wi h he same se ings, bu he s imula o was u ned o a e 30 s. S a is ical analysis We used linea mixed models (LMM) o e alua e he e ec s o each s imula ion condi ion on he ela i e changes in acous ic pa ame e s. The s imula ion condi ion was a ixed ac o in LMM. Pos -hoc pai wise compa isons o es ima ed ma ginal means we e made wi h he Bon e oni co ec ion. Age, gende , and le odopa equi alen dose (LED) we e used as co a ia es in all LMMs. Wilcoxon signed- ank es s we e used o compa e he alues o hese pa ame e s p io o and a e each s imula ion condi ion. A Spea man co - ela ion analysis was used o assess associa ions be ween he DCS-induced changes and he simula ion o he elec ic ield in igh STG. These s a is ical p ocedu es we e pe - o med wi h IBM SPSS Ve sion 25.0 (IBM Co p., A monk, NY, USA). Table 1 Analyzed acous ic ea u es in eading ask HD dimension and speci ic diso de Acous ic ea u e Fea u e de ini ion Fea u e in e p e a ion Rigidi y o ongue and jaw elF1SD, elF2SD S anda d de ia ion o i s (F1) and second (F2) o man ela i e o i s mean. Highe alue means be e pe o mance Monopi ch elF0SD Pi ch a ia ion, de ined as a s anda d de ia ion o F0 con ou ela i e o i s mean. Highe alue means be e pe o mance I egula hy hm o speech SPIR Numbe o pauses ela i e o o al speech ime a e emo ing pe iods o silence las ing less han 50 ms. Highe alue means be e pe o mance Longe du a ion o silences Du MED Median du a ion o silences longe han 50 ms. Lowe alue means be e pe o mance 1 3 793 L. B abenec e al. Resul s We en olled 14 igh -handed pa ien s wi h clinically es ab- lished PD. All had mild o mode a e HD based on he assessmen o a speech he apis and he esul s o a 3F Tes Dysa h ic o al sco e (Kos alo a 2013). The maximum o al sco e is 90 (no mal speech), and he minimum sco e is 0. See Table 2 o demog aphic and clinical da a. Using linea mixed model analysis (LMM) (see Table 3), we obse ed a signi ican e ec o he s imula ion condi- ion on changes in he median du a ion o silences longe han 50 ms (F(2,21.8) = 5.1, p = 0.015), i.e. inapp op ia e silences ha nega i ely impac speech hy hm and speech luency (B abenec e al. 2017). The ela i e dec eases in long pauses a e anodal s imula ion (mean = -5.9) we e signi ican ly highe han he changes a e he sham s imula- ion (mean = 12.8), p = 0.014, and non-signi ican ly highe han he changes induced by he ca hodal s imula ion (mean = -0.5), p = 0.111 (see Fig. 1). Resul s o Pos -hoc Wilcoxon es showed ha anodal s imula ion induced a signi ican dec ease o his pa ame e (p = 0.047) (see Table 4). Elec ic ield simula ion, as assessed by SimNIBS, (Thiel- sche e al. 2015) indica ed a signi ican co ela ion be ween he mean elec ic ield in he igh STG and ela i e changes in he s anda d de ia ion o he second o man a e anodal DCS (R = 0.637; p = 0.019) (see Table 5 and Fig. 2). This pa ame e desc ibes he ongue and jaw mo emen s, and i is used o e alua ing a icula ion p ecision (B abenec e al. 2017). Howe e , his pa ame e did no signi ican ly change due o he s imula ion. Elec ic ield simula ion in SimNIBS SimNIBS so wa e ( e sion 4.0.1) was used o calcula e he elec ic ield induced by DCS, based on he ini e elemen me hod and indi idualized e ahed al head meshes gene - a ed om he s uc u al T1 images o he pa icipan . Elec- ic ield simula ions we e compu ed o bo h ca hodal and anodal mon ages. Bo h elec odes we e posi ioned based on he MNI coo dina es men ioned p e iously. The mean elec ic ield in he igh STG (sphe e adius = 10 mm) was calcula ed using a MATLAB sc ip . Table 2 Demog aphic and clinical a iables Gende Female/Male 7/7 Age (yea s) Mean 70.78 (SD 7.84) Du a ion o PD (yea s) Mean 5.03 (SD 4.18) LED (mg/day) Mean 1014.04 (SD 343.16) UPDRS III Mean 11.21 (SD 4.24) 3F Tes To al sco e Mean 74.42 (SD 7.41) MOCA Mean 25.43 (SD 2.14) M - Mean; SD - S anda d de ia ion; PD - Pa kinson’s disease; LED - Le odopa equi alen dose; UPDRS III - Uni ied Pa kinson’s disease a ing scale; MOCA - Mon eal Cogni i e Assessmen Table 3 Acous ic analysis - Resul s o linea mixed models Acous ic pa ame e Fp alue elF1SD 5.136 0.211 elF2SD 2.528 0.104 elF0SD 1.657 0.214 SPIR 0.759 0.481 Du MED 5.135 0.015 Fig. 1 Rela i e changes in he median du a ion o silences longe han 50 ms a e dis inc ac i e and sham DCS 1 3 794 Sho - e m e ec s o ansc anial di ec cu en s imula ion on mo o speech in Pa kinson’s disease: a pilo … Discussion This explo a o y c oss-o e andomized s udy ound ha anodal DCS a ge ing he audi o y eedback a ea in he igh hemisphe e can signi ican ly imp o e mo o speech luency in PD pa ien s. Mo eo e , he elec ic ield in his egion was posi i ely co ela ed wi h anodal DCS-induced changes in a icula ion p ecision. These esul s a e in pa ial acco d wi h he esul s o ou TMS s udy in which low- equency s imula ion was used. No ably, TMS-induced BOLD signal inc eases o he igh STG we e associa ed wi h changes o he same a icula ion pa ame e as in he cu en s udy (B abenec e al. 2019). The e o e, i seems plausible ha bo h s imula ion p o o- cols may lead o simila neu al changes, bu unlike in ou TMS s udy he e ec o anodal DCS alone was p obably oo weak o ansla e in o signi ican beha io al imp o e- men s in a icula ion. Imp o ed mo o speech luency was no iden i ied in ou single session TMS s udy; howe e , Table 4 Resul s o Wilcoxon es ; p alues Acous ic pa ame e Median be o e s imula ion Median a e s imula ion p alue Anodal DCS elF1SD 0.560 0.586 0.463 elF2SD 0.249 0.249 0.650 elF0SD 0.162 0.160 0.087 SPIR 2.011 1.913 0.861 Du MED 0.110 0.110 0.047 Ca hodal DCS elF1SD 0.589 0.559 0.064 elF2SD 0.249 0.237 0.039 elF0SD 0.156 0.158 0.311 SPIR 2.031 1.834 0.087 Du MED 0.105 0.100 0.670 Sham DCS elF1SD 0.579 0.557 0.136 elF2SD 0.249 0.256 0.695 elF0SD 0.170 0.166 0.272 SPIR 1.991 1.971 0.638 Du MED 0.110 0.110 0.127 Table 5 Co ela ions be ween s imula ed elec ic ields in he igh STG and ela i e changes in acous ic pa ame e s a e s imula ion elF1SD elF2SD elF0SD SPIR Du MED Anodal DCS Spea man R 0.231 0.637 -0.192 -0.159 -0.450 P alue 0.448 0.019 0.529 0.603 0.123 Ca hodal DCS Spea man R 0.165 0.033 0.099 -0.407 0.093 P alue 0.590 0.915 0.748 0.168 0.762 Fig. 2 Co ela ion be ween he mean elec ic ield in he igh STG and ela i e changes in he s anda d de ia ion o he second o man a e anodal DCS 1 3 795 L. B abenec e al. Open Access This a icle is licensed unde a C ea i e Commons A ibu ion 4.0 In e na ional License, which pe mi s use, sha ing, adap a ion, dis ibu ion and ep oduc ion in any medium o o ma , as long as you gi e app op ia e c edi o he o iginal au ho (s) and he sou ce, p o ide a link o he C ea i e Commons licence, and indica e i changes we e made. The images o o he hi d pa y ma e ial in his a icle a e included in he a icle’s C ea i e Commons licence, unless indica ed o he wise in a c edi line o he ma e ial. I ma e ial is no included in he a icle’s C ea i e Commons licence and you in ended use is no pe mi ed by s a u o y egula ion o exceeds he pe mi ed use, you will need o ob ain pe mission di ec ly om he copy igh holde . To iew a copy o his licence, isi h p://c ea i ecommons. o g/licenses/by/4.0/. Re e ences Baudouin R, Lechien JR, Ca pen ie L e al (2023) Deep b ain s imula- ion impac on Voice and Speech Quali y in Pa kinson’s Disease: a sys ema ic e iew. 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J Neu oeng Rehabil 15. h ps://doi.o g/10.1186/S12984-018-0457-9 Klobusiako a P, Mekyska J, B abenec L e al (2021) A icula o y ne - wo k eo ganiza ion in Pa kinson’s disease as assessed by mul i- modal MRI and acous ic measu es. Pa kinsonism Rela Diso d 84:122–128. h ps://doi.o g/10.1016/j.pa k eldis.2021.02.012 Kos alo a M (2013) Tes 3F Dysa ický p o il – no ma i ní hodno y řeči češ ině. Cesk Slo Neu ol N 614–618 Liu D, Chang Y, Dai G e al (2023) Righ , bu no le , pos e io supe io empo al gy us is causally in ol ed in ocal eedback con ol. Neu oImage 278:120282. h ps://doi.o g/10.1016/J. NEUROIMAGE.2023.120282 New AB, Robin Da, Pa kinson AL e al (2015) The in insic es ing s a e oice ne wo k in Pa kinson’s disease. Hum B ain Mapp 36:1951–1962. h ps://doi.o g/10.1002/hbm.22748 he e was a end o imp o ed speech hy hmici y; in o he wo ds, bo h s imula ion p o ocols posi i ely modu- la ed empo al aspec s o mo o speech ou pu . I has o be poin ed ou ha di e en asks we e used in he wo s udies: eading o simple sen ences in he TMS s udy and eading o he whole pa ag aph in he cu en s udy. This s udy has se e al limi a ions. We used he same MNI coo dina es o all pa icipan s and did no implemen indi idualized s imula ion. Howe e , i is impo an o no e ha DCS s imula ion is inhe en ly less ocal, and his pilo s udy se ed as a p epa a ion o home-based s imula ion, whe e achie ing p ecise indi idualiza ion is no p ac ically easible. Ou sample size was de e mined based on he immedia e medium a e e ec s obse ed in a single ses- sion o TMS (B abenec e al. 2019), bu he e ec s o DCS could be much weake . Ne e heless, we obse ed signi i- can e ec o DCS on speech. The main di e ence be ween he e ec s o TMS and DCS is ha TMS can igge an ac ion po en ial and DCS can only modula e es ing memb ane po en ial and change he p obabili y o he ac ion po en ial occu ence (Ni sche e al. 2008). Thus, DCS a ec s ac i e neu ons and is usually combined wi h beha io al aining o mo e p onounced and long- e m e ec s (Ni e al. 2022). In clinical p ac ice, he gold s anda d o ea men o HD is cu en ly he LSVT (Yuan e al. 2020). This high-e o speech he apy is p i- ma ily ocused on imp o ing speech loudness; p e ious s udies showed ha LSVT also inc eased he ac i a ion o he igh STG and hese changes co ela ed wi h imp o ed speech in elligibili y (Baumann e al. 2018). The e o e, in a u u e s udy, we will in es iga e long- e m beha io al e ec s and b ain plas ici y changes due o he home-based long- e m DCS as an add-on ea men o emo e LSVT, deli e ed ia elep ac ice. Acknowledgemen s This p ojec ecei ed unding om he Czech Minis y o Heal h, g an NU22J-04-00074 and om p ojec n .LX22NPO5107(MEYS): Funded by Eu opean Union – Nex Gen- e a ion EU. We also acknowledge he co e acili y MAFIL suppo ed by MEYS CR (LM2023050 Czech-BioImaging), pa o he Eu o-Bio- Imaging (h ps://www.eu obioimaging.eu/) ALM and Medical Imag- ing Node (B no, CZ). Funding Open access publishing suppo ed by he Na ional Tech- nical Lib a y in P ague. This p ojec ecei ed unding om he Czech Minis y o Heal h, g an NU22J-04-00074 and om p ojec n .LX22NPO5107(MEYS): Funded by Eu opean Union – Nex Gen- e a ion EU. Da a a ailabili y The da a ha suppo he indings o his s udy a e a ailable om he co esponding au ho upon easonable eques . Decla a ions Con lic s o in e es None. 1 3 796 Sho - e m e ec s o ansc anial di ec cu en s imula ion on mo o speech in Pa kinson’s disease: a pilo … Skodda S, G önhei W, Schlegel U e al (2014) E ec o sub halamic s imula ion on oice and speech in Pa kinson’s disease: o he be e o wo se? 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