Investigating the Use of Transcranial Magnetic Stimulation (TMS) for Primary Progressive Apraxia of Speech (PPAOS)
Phase: NA
Conditions: Apraxia Speech
Sponsor: University of Miami

 
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TI T L E:  
I n vesti gati n g t he Use of 
Tra nscra nial Ma g netic 
Sti m ulati o n ( T M S) f or 
Pri mar y Pr o gressi ve 
A pra xia of S peec h ( P P A O S) 
 
V E R SI O N  
N U M B E R : 
N/ A  
V E R SI O N D A T E:  J ul y 1 7, 2 0 1 8  
P R O T O C O L  
N U M B E R:  
2 0 1 6 1 1 2 5  
P RI N CI P A L 
I N V E S TI G A T O R: 
J o y ce Ri os G o mes Os man  
N C T N U M B E R:  
N C T 0 3 0 2 8 3 2 4  
 
 
 
 
 
 
 
 
 
  
 
 
   
 
 
 

 
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I N S T R U C TI O N S: 
1)  Pr ot oc ol Title  
I n v esti gati n g t he Use of Tra nscra nial Ma g netic Sti m ulati o n ( T M S) f or Pri mar y 
Pr o gr essi ve A pr a xia of S peec h ( P P A O S) 
 
2)  IR B  Re vie w Hist or y * 
N o ne  
3)  O bjecti ves * 
T he  p ur p ose of t his st u d y is t o e x pl ore t he e xte nt t o w hic h T M S  ca n 
i m pr o ve s peec h i n p atie nts wit h P P A O S. 
We h y p ot hesize t hat t he use of T M S will  i m pr o ve A O S meas ures o n t he 
A O S rati n g s cale. 
4)  B ac k gr o u n d * 
 
A pra xia of s peec h ( A O S) is a m ot or s peec h dis or d er affecti n g t he pr o gra m mi n g of 
m ot or s peec h pr o d u cti o n. It is c h aracterize d b y t he i m paire d a bilit y t o c o or di nate 
t he se q ue ntial, artic ulat or y m o ve me nts necessar y t o pr o d uce s peec h s o u n d. A O S 
ca n res ult fr o m  left he mis p here str o ke; h o w e ver A O S ca n als o occ ur as a pri mar y 
s peec h dis or d er, us uall y ass ociate d wit h ne ur o d e ge nerati ve dis ease. W he n A O S is 
t he o nl y si g n or s y m pt o m of a ne ur o d e ge n erati ve c o n diti o n, it is calle d pri mar y 
pr o gressi ve A O S ( P P A O S).  T he a nat o mical l ocalizati o n of P P A O S  is t h o u g ht t o 
be pri maril y t he  t he left s u peri or m ot or a n d s u p ple me ntar y m ot or c orte x as see n i n 
pri or st u dies b y h y p o met a b olis m i n  Fl u or o de o x y gl uc ose p ositr o n e missi o n 
t o m o gra p h y  ( F D G-P E T) , a n d patter ns of atr o p h y o n M RI (J ose p hs et al. 2 0 0 6, 
J ose p hs et al. 2 0 1 2, W hit well et al. 2 0 1 3). A n ot her st u d y i de ntifie d t he l eft 
pre m ot or a n d m ot or c ortices as c o m m o n areas of i nfarct i n str o ke p atie nts 
prese nti n g wit h A O S wit h o ut ass ociate d a p h asia  ( Graff-Ra df or d et al. 2 0 1 4) 
 
W he n A O S is relate d t o str o ke, li n g uistic re h a bilitati o n has s h o w n t o be be neficial 
t o i m pr o ve la n g u a ge perf or ma nce. H o we ver, t here is li mite d be nefit of li n g uistic 
re ha bilitati o n i n patie nts wit h P P A O S or A O S relate d t o pri mar y pr o gressi ve 
a p hasia ( P P A) .  I n ma n y ne ur ol o gi cal diseas es i ncl u di n g pri mar y pr o gressi ve 
a p hasia, t he acti vit y of certai n brai n areas h as bee n s h o w n t o be altere d. I n t hese 
cases, i n di vi d uals ha ve e x perie nce d i m pr o ve me nts i n m ot or a n d c o g niti ve 
s y m pt o ms w he n n o n-i n v asi ve brai n sti m ulati o n was a p plie d t o rest ore bala nce i n 
t he brai n ( Fi n occ hiar o et al 2 0 0 6, C otelli et al. 2 0 1 2, Tre b bast o ni et al. 2 0 1 3, Wa n g 
et al. 2 0 1 3, Tsa p ki ni et al. 2 0 1 4, Ger vits et al. 2 0 1 6, Teic h ma n et al. 2 0 1 6). 
Tra ncr a nial Ma g n etic Sti m ulati o n ( T M S) is per ha ps t he m ost c o m m o n f or m of  
ne ur osti m ulati o n tec h ni q ue. I n a n o n- i n v asi ve ma n ner, it utilizes ma g netic e ner g y t o 
i n d uce ver y mil d electrical c urre nts i n t he brai n, w hic h ca n be us e d t o e val u ate t he 
acti vit y le vel of a s pecifi c brai n area, or t o alter t h e acti vit y area of a s p ecific brai n 
area tra nsie ntl y.   
 

 
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T o date, t her e is o nl y o ne case re p ort e x a mi ni n g t h e r ole of T M S  i n la n g ua ge 
perf or ma n ce i n P P A O S i n a patie nt wit h a n u n derl yi n g dia g n osis of pr o gressi ve 
s u pra n uclear pals y ( P S P) w h o als o prese nt e d wit h pri mar y pr o gressi ve n o nfl ue nt 
a p hasia (P P N F A) ( S pa g n ol o 2 0 1 3). After 1 4 sessi o ns of T M S tar geti n g t he left 
Br oca/ d ors olater al prefr o ntal c orte x a n d bilateral prefr o ntal c ortices o v er a 4 -wee k 
peri o d, t he patie nt was n ote d t o ha ve i ncrease d m eta b olis m o n F D G- P E T i n t he left 
p osteri or ci n g ulate a n d l eft i nferi or fr o ntal g yr us o ne da y aft er treat me nt al o n g wit h 
i m pr o ve me nt i n se veral c o g niti ve d o mai ns o n ne ur o ps yc h ol o gical testi n g. T here 
ha ve bee n se veral ot her r e p orts i n t he literat ure s u g gesti n g be n efit of T M S i n 
pa tie nts wit h pri mar y pr o gr essi ve a p hasi as ( Fi n o cc hiar o et al 2 0 0 6; C otelli et al. 
2 0 1 2 ;  Tre b bast o ni et al. 2 0 1 3,) Bas e d o n t hese pre vi o us st u dies, we belie v e t here 
ma y b e a r ole f or T M S i n i m pr o vi n g s peec h o ut p ut i n patie nts wit h P P A O S. 
 
5)  I ncl usi o n a n d E xcl usi o n Criteri a * 
Patie nts will be recr uite d fr o m t he Ne ur ol o g y cli nic at t he U ni versit y of 
Mia mi.  
I n cl usi o n Criteria 
 A d ults a ges 1 8 a n d a b o v e w h o are a ble t o c o ns e nt or ha ve a pr o x y 
w h o is willi n g t o c o nse nt o n t heir be half 
 Dia g n os is of pri mar y pr o gressi ve a pra xia of s peec h base d o n 
ne ur ol o gi cal e v al uati o n  
E x cl usi o n Criteria  
 A n y u n c o ntr olle d me dical c o n diti o n e x pecte d t o li mit life e x pecta nc y or i nterfer e 
wit h partici pati o n i n t he trial (i.e. u nsta ble ca ncer, se vere d e pressi o n or a n xiet y b y 
D S M -IV criteria)  
 A b n or mal stress t est, as deter mi ne d b y t h e treati n g p h ysici a n  ( u nless car di ol o g y 
clear a nce pr o vi de d)  
 Acti ve s u bsta nce a b use or alc o h ol de pe n d e nce  
 U nc orr ecte d visi o n or heari n g d eficits t hat w o ul d precl u de a d mi nistrati o n of t he 
c o g niti ve meas ur es  
 U n willi n g or  u na ble  t o  pr o vi de  writte n  i nf or me d  c o nse nt  a n d  d o  n ot  ha ve  a n  
a p pr o priate pr o x y w h o is a ble t o pr o vi de c o ns e nt o n t heir be half 
 Hist or y of fai nti n g s pells of u n k n o w n or u n deter mi ne d eti ol o g y t hat mi g ht c o nstit ute 
seiz ures 
 Hist or y of seiz ures, dia g n osis of e pile ps y, hist or y of a b n or mal (e pile ptif or m) E E G or 
fa mil y hist or y of treat me nt resista nt e pile ps y  
 N o me dicati o n is a n a bs ol ute e xcl usi o n fr o m T M S. Me dicati o ns will be re vie we d b y 
t he res p o nsi ble M D a n d  a decisi o n a b o ut  i ncl usi o n will  be ma de base d  o n t he  
f oll o wi n g: 

 
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o  T he s u bject’s past me dical hist or y, dr u g d ose, hist or y of rece nt me dicati o n 
c ha n ges or d urati o n of treat me nt, a n d c o m bi nati o n wit h ot her C N S acti ve 
dr u gs.  
o  T he p u blis he d T M S g ui deli nes re vie w me dicati o ns t o be c o nsi dere d wit h 
T M S  
 A n y metal i n t he brai n, s k ull or else w here u nless a p pr o ve d b y t he res p o nsi ble M D  
 A n y me dical de vices (i.e. Car diac pace ma ker, dee p brai n sti m ulat or, me dicati o n 
i nf usi o n p u m p, c oc hlear i m pla nt, va gal ner ve sti m ulat or) u nless ot her wise a p pr o ve d 
b y t he res p o nsi ble M D  
 S u bsta nce a b use or de pe n de nce wit hi n t he past si x m o nt hs  
 A bse nce of c ortic os pi nal f u ncti o nal i nte grit y 
 I n a bilit y t o pr o vi de i nf or me d c o nse nt or ha v e a n a p pr o priate pr o x y pr o vi de 
c o nse nt o n t heir be h alf 
 A ge y o u n ger t h a n 1 8 years 
 Pre g n a nc y  
 Pris o ners 
 
 
6)  N u m ber  of S u bjects *  
T his is a si n gle ce nter st u d y wit h 1 0  pla n ne d s u bjects. 
7)  St u d y Ti meli nes *  
After ha vi n g a p ote ntial r esearc h partici p a nt  has b ee n i de ntifie d, w e will 
call hi m/ her  t o disc uss t he st u d y a n d deter mi ne b ot h eli gi bilit y a n d i nterest 
i n partici pati n g i n t he st u d y. Partici pa nts will u n der g o T M S safet y 
scree ni n g t o e ns ure t hat t he y are eli gi ble t o p artici pate, f oll o wi n g t h e T M S 
Safet y G ui deli nes (R ossi et al. 2 0 0 9 ). Partici pati o n will i n v ol ve a pre-st u d y 
f M RI s ca n t o i de ntif y a t ar get f or T M S a p plicati o n, a n d pre-st u d y 
ne ur o ps yc h ol o gical testi n g. T he pr o p ose d ti meli ne of T M S will be 1 0 
sessi o ns o ver a 2- w ee k p eri o d, f oll o we d b y a s ec o n d, p ost-T M S 
ne ur o ps yc h ol o gical testi n g sessi o n t o assess f or i m pr o ve me nt. Patie nts 
w h o d o n ot ha ve si g nifica nt be nefit or c ha n ge i n s y m pt o ms after t h e first 
1 0 sessi o ns of r T M S ma y be offere d a n a d diti o nal 1 0 sessi o ns w here t he 
brai n re gi o n bei n g tar get e d will be c ha n ge d base d o n f M RI d ata a n d t he 
i n vesti gat ors' cli nical i m pressi o n. We will t he n pla n t o f oll o w u p wit h 
patie nts at 1 m o nt h t o assess d urati o n of effects of t he treat me nt. T he 
patie nts will be re -sc ore d usi n g t he A pra xia of S peec h Rati n g Scale a n d 
will u n der g o a sec o n d n e ur o ps yc h ol o g i cal testi n g batter y. We will als o 
i de ntif y a n y p ost-treat me nt a d verse effects d uri n g t his visit . 
8)  St u d y E n d p oi nts *  
T he pri mar y st u d y e n d p oi nt will be i m pr o ve me nt o n t he la n g u a ge p erf or m a nce 
meas ure d b y n e ur o ps yc h ol o gical testi n g a n d t he A pra xia of S peec h Rati n g Scal e  
(a t o ol desi g n e d t o meas ure t he prese nce a n d se v erit y of a pra xia of s peec h t hat 
uses a 5 -p oi nt rati n g scal e t o assess 1 6 ite ms (see attac he d material, [Stra n d et al. 

 
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2 0 1 4] ).We will als o l o o k at gl o bal acti vit y le v els of t he brai n utilizi n g si n gle-
p ulses pre - a n d p ost- T M S . 
 
9)  Pr oce d ures I n v ol ve d *  
 
Partici pa nts will u n der g o a pre -t est assess me nt (c o nsisti n g of ne ur o ps yc h ol o gical 
perf or ma n ce  a n d will be sc ore d usi n g t he A pra xia of S peec h Rati n g Scale ). 
F oll o wi n g t his visit, partici pa nts will recei v e 1 0 sessi o ns of re petiti ve T M S i n a 4 
wee k peri o d. After t hat, partici pa nts will u n der g o a p ost- test assess me nt i n w hic h 
t he y will be r esc or e d usi n g t he A pra xia of S peec h Rati n g scal e a n d reassesse d o n 
ne ur o ps yc h ol o gical testi n g. We will c ollect t his  i nf or mati o n, al o n g wit h 
de m o gr a p hic a n d b asic me dical i nf or mati o n (a ge, ge n d er, race, ha n de d n ess, 
e d ucati o n le vel, a n d me dical c o m or bi dities) fr o m t he partici pa nts’ me dical rec or ds. 
T his i nf or mati o n will be i m p orta nt f or re p orti n g res ults ( de m o gra p hic i nf or mati o n), 
sc ori n g t h e ne ur o ps yc h ol o gical testi n g (e d ucati o n le vel), a n d i n deter mi ni n g 
eli gi bilit y t o u n der g o T M S ( me dical c o m or bi dities).  
 
 
Si n gle P ulse T M S  
 
  Pri or t o a n d f oll o wi n g eac h T M S visit, a pre T M S si de effects q uesti o n naire 
  will be perf or me d.. 
 
We will use t he T M S mac hi ne t o assess t he gl o bal acti vit y le vels of t he brai n 
utilizi n g si n gle - p ulses a n d t o set t he para met ers f or t he re p etiti ve T M S . T M S will 
be deli vere d usi n g a bi p hasic fi g ure of ei g ht c oil. T his sti m ulati o n p hase will c o nsist 
of 3  batc hes of 3 0 T M S p ulses deli vere d e ver y 5 -7 sec o n ds at 1 2 0 % of resti n g m ot or 
t hres h ol d ( R M T). T his is t he sta n dar d wa y of setti n g t he para meters of t he T M S. We 
defi ne t he R M T as t he i nte nsit y at w hic h 5 res p o nses are o btai ne d (a b o ut 5 0 μ V ) 
w he n we gi ve 1 0 sti m ulati o n p ulses.  
 
 
Re petiti ve T M S  
 
Re petiti ve T M S will be deli vere d at 9 0 % of t he resti n g m ot or t hres h ol d at 
2 0 Hz   ( 5 0 trai ns, 4 0 p ulses wit h 2 8 sec o n d i nter-trai n i nter val), w hi c h was  b ase d 
o n para meters use d i n pri or st u dies i ncl u di n g  o ne pri or case re p ort i n w hic h 
r T M S was pre vi o usl y us e d a n d re p orte d   
t o lea d t o i m pr o ve me nts i n s peec h i n  
a n i n di vi d ual wit h P P A O S ( S pa g n ol o et al.   2 0 1 3), a n d t w o st u dies i n w hic h 
r T M S was use d i n pri mar y pr o gressi ve a p h asia, a si milar c o n diti o n i n w hic h t he 
sa me tar get w as sti m ulate d ( C otelli et al. 2 0 1 2, A ntcza k et al. 2 0 1 8). 
 
1 0)  D at a a n d S peci me n B a n ki n g *  
We will n ot pla n t o c ollect or ba n k a n y s p eci me ns wit h t his st u d y.  
1 1)  D at a M a n a ge me nt *  
 
T here is o nl y o ne d oc u m e nt t hat lists t he i n di vi d ual’s na me a n d t h e s u bject n u m ber 
t hat will be assi g ne d t o hi m/ her u p o n gi vi n g i nf or me d c o nse nt t o partici pat e i n t his 

 
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st u d y. T his d oc u me nt will be ke pt at t he Pri nci pal I n v esti gat or’s Office at 5 9 1 5 
P o nce d e Le o n Bl v d, C or al Ga bles, F L, 3 3 1 4 6. Data will be st ore d f or a mi ni m u m 
of 3 years, a n d i n acc or d a nce wit h U ni versit y P olicies t hereafter. We w o ul d li ke t o 
kee p de- i d e ntifie d data, s o t hat ot her st u dies ma y be nefit fr o m t hes e after st u d y 
c o m pleti o n. De-i de ntifie d data will be st ore d at t h e Pr ofessi o nal Arts Ce nter ( 1 1 5 0 
N W 1 4t h Street, S uite 6 0 2- B, Mia mi, F L 3 3 1 3 6) a n d Cli nical Researc h B uil di n g 
( 1 1 2 0 N W 1 4t h Street 1 3t h Fl o or, Mia mi, F L 3 3 1 3 6). It will be ke pt i n a l o c ke d 
ca bi net, a n d t he o nl y p e o ple w h o w ill ha ve access t o t his data are pers o n nel  
a p pr o ve d b y t he I R B t o w or k o n t his st u d y.  
 
1 2)  Pr o visi o ns t o M o nit or t he D at a t o E ns ure t he S afet y of S u bjects *  
Data m o nit ori n g  
O nl y a ut h orize d pers o n n el will ha ve access t o t he data c ollecte d d uri n g t he 
st u d y. Partici pa nts’ i nf or mati o n will n ot be s hare d wit h a n y p art y wit h o ut 
I R B-a p pr o val. Researc h data will n ot be release d t o t he partici pa nts.  
Data c ollecti o n will be halte d if t he partici pa nt re q uests it. If t his occ urs, 
s u bject will be ta ke n off t he st u d y a n d t he reas o n of disc o nti n uati o n will 
be d oc u me nte d. D ata c oll ecte d bef ore will be ke pt b y t he i n vesti gat or. 
M o nit ori n g t he saf et y of partici pa nts wit h res pect t o T M S 
T M S has bee n use d i n a gr o wi n g n u m b er of la b orat ories w orl d wi de si nce 
1 9 8 4. A series of a d vers e e ve nts ha ve b ee n i de ntifi e d si nce t he n, a n d h a ve 
bee n t h or o u g hl y re vi e we d f or t he de v el o p me nt of rec o m me n de d s afet y 
g ui deli nes a n d preca uti o ns f or t he use of T M S, first at a c o nse ns us 
c o nfer e nce at t he NI H i n J u ne, 1 9 9 6 a n d, m ore rece ntl y, i n 2 0 0 8 i n Si e na 
(It al y), i n a meeti n g of a n i nter nati o nal pa nel of T M S e x perts ( T he Safet y 
of T M S C o nse ns us Gr o u p).  
T he pri nci pal i n vesti gat or will e ns ure t hat t hese g ui deli nes are w ell - k n o w n 
b y all st u d y i n vesti gat ors a n d will caref ull y f oll o w t hese u p date d safet y 
g ui deli nes i n t he pr ese nt st u d y. 
1 3)  Wit h dr a w al of S u bjects *  
As t he great est ris k t o s u bjects wit h T M S as d oc u me nte d i n pri or 
literat ure, is seiz ure, t he de vel o p me nt of a s eiz ure d uri n g or i m me diat el y 
f oll o wi n g T M S will be gr o u n ds f or wit h dra wal fr o m t he st u d y. Si milarl y, 
t he de vel o p me nt of a n e w ris k fact or f or seiz ure d uri n g t he st u d y peri o d 
will be gr o u n ds f or wit h dra wal (i n cl u di n g n e w str o ke/str uct ural brai n 
lesi o n, ce ntral ner v o us s yste m i nfecti o n s uc h as m e ni n gitis or e n ce p halitis, 
or tra u matic br ai n i nj ur y).  

 
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1 4)  Ris ks t o S u bjects *  
 
 
Ris ks ass ociate d wit h  T M S:  
 
T M S has bee n use d i n a gr o wi n g n u m b er of la b orat ories w orl d wi de si nce 1 9 8 4. A 
series of a d v erse e ve nts h a ve bee n i de ntifie d si nce t he n, a n d ha ve b ee n t h or o u g hl y 
re vie we d f or t he d e vel o p me nt of rec o m me n d e d safet y g ui d eli nes a n d preca uti o ns 
f or t he use of T M S, first at a c o nse ns us c o nfere nce at t he NI H i n J u ne, 1 9 9 6 a n d, 
m ore rece ntl y, i n 2 0 0 8 i n Sie na (Ital y), i n a meeti n g of a n i nter nati o nal p a nel of 
T M S e x perts ( R ossi et al. 2 0 0 9 ). We will care f ull y f oll o w t hese u p date d safet y 
g ui deli nes i n t he pr ese nt st u d y. 
 
  
M ore C o m m o n 
 Hea dac hes a n d/ or Nec k Pai n: U p t o 2 0 %- 4 0 % of s u bjects u n der g oi n g T M S 
e x perie nce hea dac hes or nec k pai n, w hic h are b elie ve d t o be d ue t o m uscle 
te nsi o n. All pri or cases of hea dac hes i n d uce d b y T M S ha ve pr o m ptl y res ol ve d 
wit h a si n gle d ose of acet a mi n o p he n ( T yle n ol ®) or a n o nster oi dal a nti-
i nfla m mat or y dr u g (N S AI D). I n s o me cases T M S ma y ca use faci al disc o mf ort 
o n t he sa me si de of sti m ulati o n.  
 
Rare  
 
 Seiz ures: T M S ca n ca use a se iz ure; h o we ver, t his is a n e xtre mel y rare pr o bl e m. 
Re petiti ve T M S ca n i n d uce a seiz ure e ve n i n t he a bse nce of pre -e xisti n g brai n 
lesi o ns, e pile ps y, or ot h er seiz ure ris k fact ors, b ot h i n patie nts a n d healt h y 
s u bjects. Fr o m t he se v eral t h o usa n ds of st u dies t hat ha ve use d T M S t o date, a 
t otal of 1 6 cases ha v e bee n re p ort e d, of w hic h 9 cases occ urre d after t he 1 9 9 8 
safet y g ui deli nes. Base d o n t he a vaila ble d ata, t he re p orte d ris k of seiz ures is 
less t ha n 1 i n 1 0 0 0 f or re petiti ve T M S. A d diti o nall y, T M S has bee n rarel y 
ass ociate d wit h seiz ure -li ke e ve nts a n d s y n c o pe. N e vert heless, t his is a ver y 
c o ncer ni n g c o m plicati o n a n d t o ma ke t he s u bjects’ ris k as s mall as p ossi ble, 
t he i n vesti gat ors will f oll o w preca uti o ns t hat are rec o m me n de d b y t he 
I nter nati o nal S ociet y f or Tra nscra nial Sti m ulati o n a n d me nti o ne d i n t he 2 0 0 8 
u p date d saf et y g ui d eli nes of T he Safet y of T M S C o nse ns us Gr o u p . Se veral 
i n vesti gat ors are n e ur ol o gists, a n d at least o ne of t he m will be prese nt d uri n g 
t he T M S a n d a ble t o r u n a ra pi d res p o nse a n d treat t he patie nt i n case of 
seiz ure. 
 
 Heari n g Pr o ble ms: T M S pr o d uces a l o u d clic ki n g s o u n d w he n t he c urre nt is 
passe d t hr o u g h t he sti m ulati o n c oil. T his l o u d clic k ca n res ult i n c o n c urre nt 
ri n gi n g i n t he ear a n d s h ort-ter m decrease d heari n g if n o pr otecti o n is use d. I n 
or der t o pre v e nt t his p o te ntial a d verse effect s u bjects will be gi ve n ear pl u gs. 
A ni mal a n d h u ma n st u dies ha ve de m o nstrate d t hat ear pl u gs ca n effecti vel y 
pre ve nt t he ris k of h eari n g dist ur ba n ce d ue t o T M S. I n or d er t o i nf or m a n d 
pr otect t he s u bjects, w e will ta ke t he f oll o wi n g pre ca uti o ns:  
 

 
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o  I nf or m s u bjects of t he ris k of per ma n e nt heari n g l oss, if a n ear pl u g 
s h o ul d l o ose n, bec o me d etac he d, or fall o ut.  
o  I nf or m s u bjects t hat t he y s h o ul d i m me diatel y re p ort t o t he i n vesti gat or 
a n y l o ose ni n g or detac h me nt of a n ear pl u g d uri n g T M S.  
o  I mme diat el y st o p T M S t o re place ear pl u gs if t he s u bject re p orts or if 
a n i n vesti gat or o bser v es t hat a n ear pl u g h as l o ose n e d or has falle n o ut.   
o  As k t he s u bject if t he y are e x perie nci n g a n y h eari n g pr o ble ms 
f oll o wi n g e v er y sessi o n of T M S 
o  Pr o m pt referr al f or a u dit or y assess me nt of all i n di vi d uals w h o 
c o m plai n of heari n g l oss, ti n nit us, or a ural f ull ness f oll o wi n g 
c o m pleti o n of T M S. 
 
T he ris k of heari n g l oss wit h o ur T M S c oil is ver y l o w wit h n o re p orte d 
i nci de nce of tra nsie nt or l asti n g pr o ble ms usi n g t h e met h o ds o utli ne d i n t his 
st u d y.   
 
 S y nc o pe: S y nc o p e ca n o cc ur d ue t o a n xiet y a n d ps yc h o- p h ysical disc o mf ort 
d uri n g testi n g a n d tr eat m e nt wit h T M S. T his is re p orte d less t ha n seiz ure 
acti vit y. S u bjects will be m o nit ore d f or feeli n g a n y si g ns or s y m pt o ms of a 
pe n di n g s y n c o pal e ve nt (i.e. feeli n g dizz y or li g ht hea de d). T M S will 
i m me diatel y be st o p pe d a n d t he s u bject will be assiste d.  
 
 Me m or y: T M S c o ul d i n d uce s h ort-ter m c ha n ges i n me m or y, atte nti o n a n d 
ot her c o g niti ve a n d me nt al f u ncti o ns. T his is a rare ris k, as safet y st u dies 
c o n d ucte d f o u n d t hes e e v e nts t o be rare a n d tra nsie nt.  
 
 M o o d: Ac ute ps yc hiatric effects ha ve b ee n des cri b e d i n patie nts recei vi n g 
r T M S. Alt h o u g h si n gl e cases s u g gest a ca usal relati o ns hi p bet wee n r T M S a n d 
ma nia, t he o ver all rate ( 1 3 cases)  acr oss 5 3 ra n d o mize d c o ntr olle d st u dies 
(c o m bi ne d N = 5 2 0) i n de pressi o n a p pears t o be l o w ( 0. 8 4 % ma nia f or acti ve 
r T M S vs. 0. 7 3 % f or s ha m r T M S) a n d e ve n b el o w nat ural s witc h rates i n 
patie nts wit h bi p olar dis or ders recei vi n g m o o d sta bilizers ( 2. 3 – 3. 4 5 %). 
Si milarl y, cases of r T M S i n d uce d ps yc h otic s y m pt o ms, a n xiet y, a gitati o n, 
s uici dal i deati o n a n d i ns o m nia, ha ve bee n re p orte d, b ut it is u n k n o w n w het her 
t hese occ ur at hi g her rates c o m pare d t o t he n at ural c o urse of disease b ei n g 
treate d or ass ociate d wit h ot her i nter ve nti o n Ps yc h otic s y m pt o ms a n d s uici dal 
i deati o n ha ve ne v er bee n descri be d i n n or mal s u bj ects d uri n g or after r T M S. 
S u bjects wit h ps yc hiatric pr o ble ms will n ot be i ncl u de d i n t his st u d y, s o m o o d 
c ha n ges are n ot a ntici p ate d.  
 
 De ntal Pai n: T he p ossi bilit y of de ntal p ai n d uri n g r T M S has bee n re p orte d. 
T his p ote ntial a d verse effect of T M S w o ul d occ ur d uri n g t he sti m ul us. We 
will e nc o ura ge t h e partici pa nt t o alert t he st u d y i n vesti gat or s h o ul d s uc h 
disc o mf ort occ ur. I n t hat case, t he sti m ulati o n sessi o n will be ter mi nate d 
i m me diatel y, a n d t he p artici pa nt will be e nc o ura ge d t o see k a de ntal 
e val uati o n. T his is a ver y rare o cc urre n ce, b ut it ma y p oi nt t o t he prese nce of a 

 
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ca vit y t h at ma y re q uir e care. T his a d v erse effect s h o ul d n ot lea d t o a n y l as ti n g 
pr o ble ms or c o m plicati o ns. 
 
 Fi nall y, e ve n t h o u g h T M S has bee n use d i n se v eral la b orat ories w orl d wi d e 
si nce 1 9 8 4, t here c o ul d b e s o me u nf ores ee n c o m plicati o ns, a n d t he patie nts 
will be i nf or me d a b o ut t his p ossi bilit y.  
 
            Electr o m y o gra p h y ( E M G ): 
T he stic k y p a ds use d f or t he test ma y ca use s ki n irritati o n or re d ness.  T a ki n g t he 
stic k y pa ds off ca uses dis c o mf ort si milar t o w he n t a ki n g off a b a n d-ai d.  
 
Breac h of C o nfi de ntialit y 
T here is als o a ris k of breac h of c o nfi de ntialit y if p ers o nal healt h i nf or mati o n 
gat h ere d  d uri n g t h e st u d y is accesse d b y pers o ns n ot i n v ol ve d i n t he st u d y. T o 
g uar d a gai nst t his, i nf or mati o n a b o ut st u d y patie nts will be ke pt c o nfi de ntial a n d 
ma na ge d acc or di n g t o HI P A A re q uire me nts. O nl y pers o ns i n v ol ve d i n t he st u d y 
will be gr a nte d access t o t he i nf or mati o n. 
 
1 5)  P ote nti al Be nefits t o S u bjects *  
Base d o n pri or case r e p orts d oc u me nti n g i m pr o ve me nt of la n g u a ge 
f u ncti o n wit h T M S i n P P A O S pri mar y pr o gressi ve a p hasias a n d p ost-
str o ke la n g ua ge dis or d ers, we belie ve t h at t here is a p o te ntial f or T M S t o 
i m pr o ve s peec h f u ncti o n (as meas ure d b y ne ur o ps yc h ol o gical testi n g a n d 
t he A pra xia of S peec h R ati n g Scal e) i n st u d y p a rtici pa nts wit h pri mar y 
pr o gressi ve a pra xia of s p eec h . T his be n efit is p ote ntiall y better t ha n 
be nefits t hat t he y c o ul d e x pect t o ac hie ve wit h s peec h t hera p y al o ne (t he 
c urre nt sta n d ar d of car e a n d o nl y ot her a vaila ble treat me nt  a vaila ble 
o utsi de of a res ear c h pr ot oc ol). H o we v er, gi ve n t h at t his is a researc h 
st u d y, we ca n n ot g uara nt ee a n y direct be n efit.  
1 6)  V ul ne r a ble P o p ul ati o ns * 
C o g niti vel y- i m p aire d a d ults will be a ble t o partici pate  i n t his st u d y, 
pr o vi de d t hat t he partici p a nt has a n a p pr o priate pr o x y w h o is a bl e t o si g n a 
c o nse nt f or m o n his or her be half. We will p ut i n place s pecific pla ns t o 
cl osel y m o nit or t hese p artici pa nts ( o utli ne d i n detail u n der secti o n 2 3). 
1 7)  M ulti -Site Rese arc h * 
We are n ot pla n ni n g t o i ncl u de a n y a d diti o nal sites i n t his st u d y. 
1 8)  C o m m u nit y -B ase d P artici p at or y Rese arc h * 
We  d o n ot ha ve pla ns f or c o m m u nit y i n v ol ve me nt i n t he desi g n of t his 
st u d y, at t his ti me. 

 
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1 9)  S h ari n g of Res ults wit h S u bjects * 
We will s hare t he res ults of t he f M RI st u d y, n e ur o ps yc h ol o gical testi n g, 
m ot or c orte x e x cita bilit y fi n di n gs, a n d A pra xia of S peec h Rati n g Scale 
sc ores wit h t he patie nts at all f oll o w u p visits. 
2 0)  Setti n g 
Descri be t he sites or l oc ati o ns w here y o ur rese arc h te a m will c o n d uct t he 
rese arc h. 
I d e ntificati o n a n d r ecr uit me nt of s u bjects, as well as all f oll o w u p visits 
will ta ke place at t he U ni versit y of Mia mi Ne ur ol o g y Cli nic i n t he 
Pr ofessi o nal Arts Ce nter b uil di n g. T he a d dress is 1 1 5 0 N W 1 4 t h St reet, 
Mia mi, F l ori da 3 3 1 3 6. T M S will be perf or me d at t he Ne ur o m ot or 
Plasticit y La b orat or y a n d ne ur o ps yc h ol o gical testi n g will ta ke place i n t he 
ne ur o ps y c h ol o gical testi n g s uite  at t he s a me a d dres s. 
At t his ti me, t here are n o pla ns f or a c o m m u nit y a d vis or y b oar d or 
researc h perf or m e d at a n y a d diti o nal sites. 
2 1)  Res o urces A v ail a ble  
Dr. J o yce G o m es -Os ma n  P h D, P T is a researc h ne ur oscie ntist wit h 
e xte nsi ve e x perie nce i n cli nical researc h a n d n o n -i n vasi ve brai n 
sti m ulati o n a p pr oac hes, w hic h i ncl u de tra ns cra ni al ma g n etic sti m ulati o n 
( T M S) a n d electr oe nce p h al o gra p h y ( E E G). Dr. G o mes-Os ma n is t he 
Direct or of t h e Ne ur o m ot or Plasticit y La b orat or y, at t he U ni versit y of 
Mia mi Miller Sc h o ol of Me dici ne a n d has a p u blicati o n rec or d t hat 
i ncl u de ma n y st u dies utilizi n g n o n-i n vasi ve brai n sti m ulati o n b y mea ns of 
tra nscra ni al ma g netic sti m ulati o n a n d tra nscra ni al direct c urre nt 
sti m ulati o n t o c haracterize t he ne ur o p h ysi ol o g y a n d i n d uce 
ne ur osti m ulati o n (as a p ote ntial t hera pe utic a p pr oac h) i n i n di vi d uals wit h 
ne ur ol o gi c i m pair me nts a n d healt h y i n di vi d uals. Dr. G o mes- Os ma n  h as 
e x pa n de d her k n o wle d ge i n Ne ur ol o g y a n d n o n- i n vasi ve brai n sti m ulati o n 
tec h ni q ues d uri n g her p ost d oct oral fell o ws hi p wit h Dr. Al var o Pas c ual-
Le o n e, a n i nter nati o nall y rec o g nize d lea d er i n t his fiel d, at t he Bere ns o n -
Alle n Ce nter f or N o n- I n v asi ve Sti m ulati o n at Bet h Israel D eac o n ess 
Me dical Ce nter at Har v ar d Me dical Sc h o ol. S he re mai ns affiliate d as a 
researc h sc h ol ar, a n d is c urre ntl y c o n d ucti n g st u dies t o i n vesti gate t h e 
effects of aer o bic e x er cise o n ne ur o plasticit y a n d c o g niti ve f u n cti o n i n 
healt h y  i n di vi d uals. I n a d diti o n, s he is a lect urer at t he “I nte nsi ve C o urse 
i n Tra nscr a nial Ma g netic Sti m ulati o n”, or ga nize d b y t his Ce nter. 
 
2 2)  Pri or A p pr o v als  
We will n ot nee d t o o btai n pri or a p pr o v als pri or t o starti n g t his st u d y. 

 
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2 3)  Recr uit me nt Met h o ds  
S u bjects will be recr uite d fr o m t he U ni versit y of Mia mi Ne ur ol o g y cli nic 
after h a vi n g b ee n i de ntifi e d b y a ne ur ol o gist i n t hat practice as ha vi n g t he 
dia g n osis of pri mar y pr o gr essi ve a pra xia of s peec h d uri n g re g ularl y 
sc he d ule d cli nic a p p oi nt me nts t o recei ve care. W he n a p ote ntial patie nt is 
i de ntifie d, t he ne ur ol o gist will disc uss t he st u d y briefl y wit h t he p atie nt 
a n d assess his/ her i nter est i n partici pati n g d uri n g t he re g ularl y s c he d ule d 
cli nic visit. If t he p atie nt is i ntereste d i n lear ni n g m ore, t he ne ur ol o gist will 
f or war d t he patie nt’s na me a n d c o ntact i nf or mati o n t o t he st u d y 
i n vesti gat ors, w h o will c o ntact t he patie nt b y p h o ne t o e x plai n t he st u d y i n 
m ore detail a n d det er mi ne if t he patie nt is eli gi ble t o partici pate. T here 
will n ot be a n y s u p ple me ntal materials use d t o recr uit s u bjects.  
T here are n o pla ns f or pa y m e nts t o s u bjects i n e x c ha n ge f or p artici pati o n 
i n t his st u d y. 
Recr uit me nt of C o g niti vel y I m paire d A d ults : 
We  will  all o w certai n c o g niti vel y i m paire d s u bjects t o partici pate i n t he 
st u d y. If a p ote ntial  s u bject is i ntereste d i n partici p ati n g, he/s he m ust ha v e 
a n a p pr o pri ate pr o x y w h o is willi n g a n d a ble t o  si g n a pr o x y c o nse nt f or m 
o n his/ her be half. S u bjects will be e val uate d f or ca pacit y  t o pr o vi d e 
c o nse nt at t he scr ee ni n g visit, w hic h will be c o n d ucte d b y a b oar d- certifie d 
ne ur ol o gist. Asse nt will be o btai ne d fr o m all s u bjects. If he/s h e is ca pa bl e, 
t he s u bject will pers o nall y si g n t he writte n i nf or me d c o nse nt, d oc u me nti n g 
his/ her asse nt. Base d o n t he nat ural hist or y of t he u n derl yi n g c o n diti o ns 
ass ociate d wit h pri mar y pr o gressi ve a pra xia of s p eec h, w e d o n ot e x pect 
t hat t he a bilit y of t he p atie nt t o pr o vi de c o nse nt will c ha n ge d uri n g t he 
c o urse of t he st u d y. T h e details of t he st u d y will b e disc usse d at t he 
scree ni n g visit at a le v el c o m pati ble wit h t he parti ci pa nt’s u n dersta n di n g. 
Partici pa nts dee me d t o lac k ca p acit y t o gi v e c o nse nt f or partici pati o n  will 
be cl osel y m o nit ore d at eac h visit f or de vel o p me nt of si de effects  or 
c ha n ge i n a bili t y t o pr o vi de c o nse nt, i ncl u di n g q uesti o ni n g of t he pr o x y, if 
necessar y , t o pr o vi de a d diti o nal i nf or mati o n. Partici pa nts will be 
wit h dra w n fr o m t he st u d y if t he y a p pear t o be u n d ul y distresse d b y 
partici pati o n.  
2 4)  L oc al N u m ber of S u bjects  
We w ill pla n t o recr uit a t otal of 1 0 patie nts t o partici pate i n t he st u d y at 
t he U ni versit y of Mia mi. 
2 5)  C o nfi de nti alit y  
 
  
T here is o nl y o ne d oc u m e nt t hat lists t he i n di vi d ual’s na me a n d t h e s u bject 
  
n u m ber t hat will be assi g ne d t o hi m/ her u p o n gi vi n g i nf or m e d c o nse nt t o 
  
partici pate i n t his st u d y. T his d oc u me nt will be ke pt at t he Pri nci pal I n vesti gat or’s 
  
Office at 5 9 1 5 P o nce de Le o n Bl v d, C oral G a bles, F L, 3 3 1 4 6. Dat a will be st ore d 
 
f or a mi ni m u m of 6 years f oll o wi n g st u d y cl os ure, a n d i n acc or da nce wit h  

 
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U ni versit y P olicies t her eafter. It will be k e pt i n a l oc ke d ca bi net, a n d t he o nl y 
pe o ple w h o will ha ve access t o t his data are p ers o n nel  a p pr o ve d b y t he I R B t o 
w or k o n t his st u d y.  
  
 
2 6)  Pr o visi o ns t o Pr otect t he Pri v ac y I nterests of S u bjects  
 
 
I nf or mati o n a b o ut st u d y patie nts will be ke pt c o nfi de ntial a n d ma n a ge d acc or di n g 
 
t o HI P A A re q uire m e nts. Re g ulati o ns re q uire a si g ne d patie nt HI P A A A ut h orizati o n 
 
i nf or mi n g t he p artici pa nt of t he f oll o wi n g:  
 
 W hat pr otecte d healt h i nf or mati o n ( P HI) will be c ollecte d  
 W h o will ha ve access t o t hat i nf or mati o n a n d w h y 
 W h o will use or discl ose t hat i nf or mati o n  
 
 
If a partici p a nt wit h dra ws c o nse nt or re v o kes a ut h orizati o n t o c ollect or use P HI, 
 
f oll o wi n g r e g ulati o ns, t he i n vesti gat or retai ns t h e a bilit y t o use all i nf or mati on 
  
c ollecte d pri or t o r e v ocati o n of patie nt a ut h orizati o n. 
 
2 7)  C o m pe ns ati o n f or Rese arc h -Rel ate d I nj ur y  
B y f oll o wi n g t he rec o m me n de d safet y g ui deli nes a n d preca uti o ns f or t he use of T M S 
de vel o pe d b y a n  i nter nati o nal pa nel of T M S e x perts (T he Safet y of T M S C o nse ns us 
Gr o u p ), we will caref ull y m o nit or a n y a d verse effects t hat ma y arise a n d n o n ot e x pect 
researc h-relate d i nj ur y t o occ ur.. I n di vi d uals will be i nstr ucte d t o   f oll o w- u p wit h t heir 
me dical i ns ura nce i n t he e ve nt of a n i nj ur y.  
 
2 8)  Ec o n o mic B ur de n t o  Su bject s 
T he s u bjects will be res p o nsi ble f or t heir o w n tra ns p ortati o n t o a n d fr o m 
t he st u d y-relate d visits, a n d f or par ki n g c osts relat e d t o t he visits. 
2 9)  C o nse nt Pr ocess  
 Patie nts will re vie w a c o nse nt f or m wit h o ne of t h e pri mar y i n vesti gat ors  at t he 
first visit, t o e ns ure all q uesti o ns are a ns w ers   wit h re gar ds t o t heir  partici pati o n 
i n t he st u d y, a n d a n y p ot e ntial   ris ks. T he y will ha ve t he o p p ort u nit y   
t o as k 
a d diti o nal q uesti o ns   
at a n y of t he visits, a n d ca n re v o ke c o nse nt t o 
 partici pate i n t he  st u d y at a n y ti me. We will pla n t o f oll o w S O P: I nf or me d 
  C o nse nt Pr oc ess f or Researc h ( H R P - 0 9 0). 
N o n -E n glis h S pe a ki n g S u bjects  
All patie nts m ust be fl ue nt i n E n glis h t o partici pat e i n t his st u d y.  
C hil dre n u n der t he a ge of 1 8 will be e x cl u de d fr o m t his st u d y. 

 
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3 0)  Pr ocess t o D oc u me nt C o nse nt i n Writi n g  
We will pla n t o o btai n writte n c o nse nts of all pati e nts partici pati n g i n t his 
st u d y acc or di n g t o t he S O P: Writte n D oc u me ntati o n of C o nse nt ( H R P-
0 9 1). 
3 1)  Dr u gs or De vices  
De vice: Ma g pr o X 1 0 0, Ma g Ve nt ure C or p orati o n, Far u m, De n mar k  
 
 T he Tra ns cra nial M a g netic Sti m ulat or is t he ori gi nal de vice d e vel o pe d b y t h e 
M a gsti m C or p or ati o n  f or t he p ur p ose of electr o ma g netic n e ural tiss ue 
sti m ulati o n i n 1 9 8 4.  T he de vices c o nsist of a b a n k of ca pacit ors t hat ca n b e 
c har ge d u p t o a pre d eter mi ne d a m o u nt of e ner g y a n d t he n q uic kl y disc har ge 
via s oli d state s witc hes i nt o a c oil of c o p per wire.  T his c oil of c o p per wire is 
e ncase d i n plastic.  As t he c urre nt passes t hr o u g h t he c oil, a ma g netic fiel d is 
ge n erat e d f oll o wi n g Fara da y La ws.  T his ma g neti c fiel d will i n t ur n i n d uce a 
sec o n dar y c urr e nt i n a n y tiss ue wit h ca pa bilities t o c o n d uct electricit y t h at is 
place d i n t he pr o xi mit y of t he i n d uce d ma g n etic fi el d.  F or t he p ur p ose of 
brai n sti m ulati o n, t he c oil is hel d o ver t he s u bject’s hea d a n d as t h e c urre nt 
passes t hr o u g h it, i.e., a ma g n etic fiel d is ge nerat e d t hat pe netrates t he scal p 
a n d s k ull wit h o ut bei n g atte n uate d.  T his ma g netic fiel d i n d uces a fl u x of 
c urre nt i n t he br ai n.  T his sec o n dar y c urre nt i n d uce d i n t he brai n i nfl ue n ces 
ne ur o nal acti vit y b y virt u e of m ostl y tra nss y n a ptic effects.  T he effects 
i n d uce d b y t he sti m ulati o n of t he brai n de p e n d o n t he site of sti m ulati o n, si nce 
differe nt areas of t he br ai n c o ntr ol differe nt f u ncti o ns.  I n a d diti o n, sti m ulati o n 
para meters s uc h as f ocalit y of t he ma g n etic fiel d, sti m ul us i nte nsit y a n d 
sti m ul us fre q ue nc y als o c o n diti o n t he i n d uce d effects i n t he brai n.  T he 
Tra nscr a nial Ma g netic Sti m ulat or has n o electric c o ntact wit h t he patie nt or 
s u bject.  T here is n o f ail ure m o de of t he d e vice t h at c o ul d res ult i n t he 
deli ver y of a n e x cessi ve a m o u nt of sti m ulati o n i nte nsit y or n u m ber of sti m uli 
gi ve n a circ uit br ea ki n g s afet y de vice.  T heref ore, t he de vice all o ws 
n o ni n vasi ve sti m ulati o n of t he h u ma n brai n wit h o ut t he use of direct electri cal 
c o ntact bet w ee n t he de vice a n d t he s u bject.  I n pri nci ple, t his de vice pr o vi d es 
t he mea ns of a n electr o d eless, n o ni n vasi ve, a n d pai nless sti m ulati o n of t he 
h u ma n brai n.  It is use d i n c o g niti ve researc h a n d treat me nt of s o me 
ne ur ol o gi c a n d ps yc hi atric c o n diti o ns. 
 
S u p p ort f or n o n -si g nific a nt ris k de vice  
T he n o n- i n vasi ve br ai n sti m ulati o n de vice ( T M S) utilize d i n t he prese nt st u d y 
has bee n cl ear e d b y t he F D A f or t he treat me nt of d e pressi o n. T here ha v e bee n 
nearl y 2, 0 0 0 r esearc h st u dies p u blis he d utilizi n g t his tec h ni q ue, a n d t he safet y 
of t his de vice has bee n esta blis he d. T he First I nter nati o nal Safet y C o nfere nce 
o n Tra ns cra nial Ma g netic Sti m ulati o n t o o k place at t he Nati o nal I nstit utes of 
Healt h i n Bet hes da, M D, i n J u ne 1 9 9 6.  
 
Re prese ntati ves of t he F o o d a n d Dr u g A d mi nistrati o n ( F D A) were prese nt at t hat 
meeti n g a n d t he y s hare d t he c o nse ns us t hat t he e vi de nce acc u m ulate d o ver t he 

 
Pa ge 1 5 of 1 6  
Re vise d : 0 7/ 1 7/ 2 0 1 8 
pre vi o us 1 0 years s u p p orts t he safet y of T M S.  M ore rece ntl y i n 2 0 0 8, a n 
i nter nati o nal pa nel of T M S e x perts ( T he Safet y of T M S C o nse ns us Gr o u p) met 
f or a c o nse ns us c o nfere nce t o re vie w a n d u p date safet y g ui deli nes i n T M S base d 
u p o n re vie w of p u blis he d data ( R ossi et al., 2 0 0 9).  T he e vi de nce re vie we d b y 
t his gr o u p of e x perts i n t he fiel d c o nti n ues t o s u pp ort t he safet y of T M S wit h t he 
a p plicati o n of rec o m me n de d g ui deli nes.   I n t he prese nt st u d y, we are a p pl yi n g it 
f or a differe nt p ur p ose a n d we will strictl y f oll o w t he Safet y G ui deli nes t o T M S.  
 
  
St ora ge a n d usa ge of de vice 
 T he Ma g pr o X 1 0 0 will be st or e d at t he D e part me nt of Ne ur ol o g y Cli nic 
l ocate d at 1 1 5 0 N W 1 4t h Street, S uite 6 0 9, Mia mi, F L 3 3 1 3 6. T he d e vice will 
be use d b y t he pri nci p al i n vesti gat or, a n d o nl y be use d b y ot h er st u d y 
i n vesti gat ors f oll o wi n g a de q uate trai ni n g.  
 
Refere n ces : 
 
A ntcza k J,  K o wals ka K, LI m o k o qicz-Mr o wiec A, Wac h B, Kas prz y k M B, Rzez nic ka -
Brze g o w y K, K u bi ca J, Sl o wi k A. Re petiti ve tra nscra nial ma g n etic sti m ulati o n f or t he 
treat me nt of c o g niti ve i m pair me nt i n fr o nt ote m p oral de me ntia: a n o pe n-la b el pil ot st u d y. 
Ne ur o ps yc hiatr Dis Treat.  2 0 1 8 Mar 1 3; 1 4: 7 4 9- 7 5 5. 
 
C otelli M , Ma ne nti R , Al berici A , Bra m billa M , C osse d d u M , Za netti O , Mi ozz o A , 
Pa d o va ni A , Mi ni ussi C , B orr o ni B . Prefr o ntal c orte x r T M S e n ha nces acti o n na mi n g i n 
pr o gressi ve n o n- fl ue nt a p hasia. E ur J Ne ur ol.  2 0 1 2 N o v; 1 9( 1 1): 1 4 0 4- 1 2. 
 
Fi n occ hiar o C 1, Mai m o ne M , Bri g hi na F , Picc oli T , Gi glia G , Fierr o B . A case st u d y of 
Pri mar y Pr o gr essi ve A p h asia:  i m pr o ve me nt o n ver bs after r T M S treat me nt. Ne ur ocase.  
2 0 0 6 Dec; 1 2( 6): 3 1 7- 2 1. 
 
Ger vits  F, As h S , C oslett H B , Rasc o vs k y K , Gr oss ma n M , Ha milt o n R . Tra nscra ni al 
direct c urre nt sti m ulati o n f or t he treat me nt of pri m ar y pr o gressi ve a p h asia: A n o pe n -la bel 
pil ot st u d y. Brai n La n g.  2 0 1 6 N o v; 1 6 2: 3 5- 4 1. 
 
Graff -Ra df or d J , J o nes D T, Stra n d E A , Ra bi nstei n A A , D uff y J R , J ose p hs K A. T he 
ne ur oa nat o m y of p ure  a pra xia of s peec h i n str o ke. Brai n La n g.  2 0 1 4 Fe b; 1 2 9: 4 3- 6.  
 
Jose p hs K A , D uff y J R , Stra n d E A , Mac h ul da M M , Se nje m M L , Master A V , L o w e VJ , 
J ac k C R Jr, W hit well J L . C haracterizi n g  a ne ur o d e ge nerati ve s y n dr o me: pri mar y 
pr o gressi ve a pra xia of s p eec h. Br ai n.  2 0 1 2 Ma y; 1 3 5( Pt 5): 1 5 2 2- 3 6. 
 
J ose p hs K A, D uff y J R , Stra n d E A , W hit well J L , La yt o n K F , Parisi J E , Ha user M F , Witte 
RJ , B oe ve B F , K n o p ma n D S , Dic ks o n D W , J ac k C R Jr, Peterse n R C . Cli nic o pat h ol o gical  
a n d i ma gi n g c orr elates  of pr o gressi ve a p h asia a n d a pra xia of s peec h. Brai n.  2 0 0 6 
J u n; 1 2 9( Pt 6): 1 3 8 5- 9 8. 
 

 
Pa ge 1 6 of 1 6  
Re vise d : 0 7/ 1 7/ 2 0 1 8 
R ossi S , Hallett M , R ossi ni P M , Pasc ual -Le o ne A ; Safet y  of T M S C o nse ns us Gr o u p. 
Safet y , et hical c o nsi d erati o ns, a n d a p plicati o n g ui deli nes f or t he use of tra nscra nial 
ma g n etic sti m ulati o n  i n cli nical practice a n d res earc h. Cli n Ne ur o p h ysi ol.  2 0 0 9 
Dec; 1 2 0( 1 2): 2 0 0 8- 3 9. 
 
S pa g n ol o F , C o p pi E , D ella R osa P A , Fic hera M , Bar bi eri A , Ma g n a ni G , Fala uta n o M , 
Za n ge n A , C o mi G , Pera ni D , V ol o ntè M A , Le oca ni L . D ee p  ma g n etic  sti m ulati o n i n a 
pr o gressi ve s u pr a n uclear pals y  patie nt  wit h s peec h i n v ol ve me nt. J Ne ur ol. 2 0 1 3 
Fe b; 2 6 0( 2): 6 7 0- 3. 
 
Stra n d E A , D uff y J R , Clar k H M , J ose p hs K. T he A pra xia of S peec h  Rati n g  Scal e: a t o ol 
f or dia g n osis a n d des cri pti o n  of a pra xia of s peec h . J C o m m u n Dis or d. 2 0 1 4 Se p-
Oct; 5 1: 4 3- 5 0. 
 
Teic h ma n n M , Les oil C , G o dar d J , Ver net M , Bertra n d A , Le v y R , D u b ois B 1, Le m oi ne 
L , Tr u o n g D Q , Bi ks o n M , Kas A , Val er o -Ca bré A . D irect c urre nt  sti m ulati o n o ver t he 
a nteri or te m p or al areas b o osts se ma ntic pr ocessi n g  i n pri mar y pr o gressi ve a p hasia . A n n 
Ne ur ol.  2 0 1 6 N o v; 8 0( 5): 6 9 3- 7 0 7.  
 
Tre b bast o ni A , Racca h R , de Le na C , Za n ge n A , I n g hilleri M. Re petiti ve  d ee p  
tra nscra ni al  ma g netic  sti m ulati o n i m pr o ves ver bal fl ue nc y a n d writte n  la n g ua ge i n a 
patie nt wit h pri mar y pr o gr essi ve a p hasi a-l o g o pe nic varia nt ( L P P A). Brai n Sti m ul.  2 0 1 3 
J ul; 6( 4): 5 4 5- 5 3. 
 
Tsa p ki ni K , Fr a n ga kis C , G o mez Y , Da vis C , Hillis A E . A u g m e ntati o n of s pelli n g 
t hera p y wit h tra nscra nial direct c urre nt sti m ulati o n i n pri mar y pr o gressi ve a p hasia: 
Preli mi nar y r es ults a n d c halle n ges. A p hasi ol o g y.  2 0 1 4; 2 8( 8- 9): 1 1 1 2- 1 1 3 0. 
 
Wa n g J , W u D , C he n Y , Y ua n Y , Z ha n g M . Effects  of tra nscra ni al direct c urre nt 
sti m ulati o n o n la n g ua ge i m pr o ve me nt a n d c ortical  acti vati o n i n n o nfl ue nt varia nt pri mar y 
pr o gressi ve a p h asia. N e ur osci Lett.  2 0 1 3 A u g 9; 5 4 9: 2 9- 3 3. 
 
W hit well J L , D uff y J R , Stra n d E A , Xia R , Ma n dre kar J , Mac h ul da M M , Se nje m M L , 
L o w e VJ , J ac k C R Jr, J ose p hs K A. Disti nct  re gi o nal a nat o mic a n d f u n cti o nal c orrelates  
of ne ur o de ge ner ati ve a pr a xia of s peec h a n d a p hasi a: a n M RI a n d F D G - P E T st u d y. Brai n 
La n g.  2 0 1 3 J u n; 1 2 5( 3): 2 4 5- 5 2.