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AA EM M IN IM O N O G RA PH 35 A B S TR A C T: S ince 1985, w hen the technique of transcranial m agneticstim ulation (TM S ) w as first developed, a w ide range of applications inhealthy and diseased subjects has been described.C om prehension ofthephysiologicalbasis ofm otorcontroland corticalfunction has been im proved.M odifications ofthe basic technique ofm easuring centralm otor conductiontim e (C M C T)have included m easurem entofthe corticalsilentperiod,pairedstim ulation in a conditioning testparadigm ,repetitive transcranialm agnetic

stim ulation (rTM S ),and peristim ulus tim e histogram s (P S TH ).These m eth-ods allow dissection ofcentralm otor excitatory versus inhibitory interplay onthe corticalm otor neuron and its presynaptic connections atthe spinalcord,and have proven to be pow erful investigational techniques. TM S can beused to assess upper and low er m otor neuron dysfunction, m onitor theeffects ofm any pharm acologicalagents,predictstroke outcom e,docum entthe plasticity ofthe m otorsystem ,and assess its m aturation and the effectsof aging, as w ellas perform intraoperative m onitoring. The recent use ofrTM S in the treatm entofdepression and m ovem entdisorders is novel,andopens the w ay for other potentialtherapeutic applications.

2002 A m erican A ssociation ofE lectrodiagnostic M edicine.M uscle N erve 2 5 : 160175,2002

D O I 10.1002/m us.10038

M A G N E T IC S T IM U L A T IO N O F T H E C E N T R A L

A N D P E R IP H E R A L N E R V O U S S Y S T E M S

M A R K U S W E B E R , M D ,1 a n d A N D R E W A . E IS E N , M D , F R C P (C )2

1 D epartm ent of N eurology,K anton sspital,C H -9007 St.G allen ,Sw itzerland2 N eurom uscular D iseases U nit,V ancouver G eneralH ospital,

V ancouver,B ritish C olum bia,C anada

Early exp erim en ts in hum an s u sed high -voltage,short-duration electrical stim ulation applied to thescalp overlying the m otor cortex, a rather u ncom -fortable proced ure and inappropriate for rou tineclinical use. In 1985, B arker and colleagues5 intro-duced the techniqu e o ftranscranialm agn etic stim u-lation (TM S) w hich led to a n ew era of research inm otor con trolan d corticalfunction.Since thattim e,interest in T M S has steadily increased and a vast lit-erature has already accum ulated.

T hism inim on ograph considers currentconceptsof the anatom ical and physiological basis of T M S,

discusses m ethodological aspects,review s the differ-ent techn iqu es and m easurem en ts in use,and criti-cally an alyzes its utility in clinical practice an d basicneuroscience.

A N A T O M Y A N D P H Y S IO L O G Y O F T H E C O R T IC A L

M O T O R N E U R O N A L S Y S T E M

M otor function in hum an s is subserved by severaldistinctyetintercon nected anatom icalregions.T heyinclude the prim ary m otor cortex, also know n asB rod m ann area 4, the prem otor areas and sup ple-m entary m otor cortex, basal gan glia,thalam us,cer-ebellum , brain stem , and reticular form ation . T heprim ary m otor cortex isdifferentfrom other region s

of the cerebralcortex in that it is thicker but has alow er cell density. T he m ain ou tput cells are thelarge pyram idalcellsin lam ina V and sm aller cells inlam ina III. T heir d en drites show a preferential ori-entation parallel to the m ain axis of the precentralgyrus.

T he spinalm oton eurons (SM N s) of the cord arethe finalcom m on pathw ay of the m o tor system to

w hich the higher centers and pyram idal cells m ake

A b b re v ia tio n s : A H C ,a nterior horn cell;A LS ,am yotrop hic lateralsclero-sis;C M ,corticalm otor neu rona l;C M A P, com po und m uscle action p oten-tial; C M C T, cen tral m otor cond uction tim e; E M G , electrom yog rap hic;

G A B A ,gam m a-am inobutyric acid;ISI,interstim ulus interval;M EP,m otorevoked potential; M S, m ultiple sclerosis; PLS , prim ary lateralsclerosis;PSTH , peristim ulus tim e histog ram s; rTM S, rep etitive transcranial m ag-netic stim ulation;SM N s, spinalm o toneurons; T, tesla; TM S ,transcranialm ag ne tic stim ulationK e y w o rd s : corticalfunction;corticalm o tor neuronalsystem ;m otor con-trol; m otor evoked potential; p eristim ulus tim e histog ram ; transcran ialm ag ne tic stim ulationC o rre s p o n d e n c e to : A A EM ,421 FirstAvenue SW ,Suite 3 00 East,R och-ester,M N 55902;e-m ail:aaem @ aa em .net

2002 A m erican A ssociation of Electrod iag nostic M edicine. Pub lishedby John W iley & Sons,Inc.

1 6 0 M agnetic Stim ulation M U SC LE & N ER VE February 2002

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direct or,m o re com m o nly,indirect con nection s viam ultiple descending tracts.In non-hum an prim atesand other m am m als, these descend ing tracts con-

verge on the spinal m oton euron. In hum ans, thesophistication and com plexity ofm otor con trol,p ar-ticularly in the face an d distal aspects of the lim bs,has largely sacrificed m any of these indirect tracts

w ith the expansion of the cortical m otor neuronal(C M ) system . T his C M system originates from largepyram idal cells in the prim ary m o tor cortex and isthe on ly descend ing m o tor pathw ay th at m akesm on osynaptic connection s w ith the SM N s.(See Por-ter and Lem on ,107 for a com p rehensive review ofcorticospinalfunction in hum ans.) E ach corticalm o-tor neuron synapsesw ith m any SM N s,and each SM Nreceives input from m an y d ifferent C M cells. T hisarrangem entof convergence and divergen ce is m ostabundant for the distalm usclesespecially those ofthe hand and facial m usculature.It is w hat affordshum ans their am azing degree of fraction ated con-

trol and allow s for a large repertoire of differentm ovem en tsserved by the sam e m u scle.C M controlislargely responsible for delicate con trolofforce,pre-cision grip,angulation ,rate o fchange ofm ovem ent,and m uscle ten sion.Itis likely thatthe C M system is

vital to the acqu isition of new m otor skills, w hich,on ce learned,are prob ably transferred to m ore cau-dalparts of the n ervous system ,including the spinalcord. G lutam ate is the prim ary excitatory neuro-transm itter of the C M system .

T he C M system issubjectto excitatoryand inhibi-tory m odulation. T he stellate or basket cells are lo-cated prim arily in lam inae III an d V . Their axonterm inals form predo m inantly inhibitory, gam m a-am inob utyric acid (G A B A ) synapses o n dendriticshafts, som ata,an d/ or proxim alaxonalsegm ent ofthe pyram idal neu ron (cortical m otor neuron )39

and are horizon tally orien tated.T hese interneuronsm od ulate the respo nse of pyram idal neurons to ex-citatory inputs.

N A T U R E O F T R A N S C R A N I A L

M A G N E T I C S T I M U L A T IO N

Since the introduction of T M S, there has been adebate over w hich structures are activated by the

m agnetic stim u lus. A rapidly chan ging m agneticfield is gen erated that induces electrical curren tsw ithin the cortex.5,43 Sh ort-laten cy contractions areevoked in contralaterallim b m uscles.T he laten cy isin keep ing w ith a m onosynaptic con nection.4,43,61,86

A single low -intensity anodal electrical stim ulusdelivered to the exp osed surface of the cortex inm onkeys preferen tially activates pyram idal tract,neuron s directly in the region of the axon hillock

(Fig. 1, left).70 T his results in a single descendingvolley recordable from the pyram idal tract, w hichhasbeen term ed the D w ave or directwave.42,43,62,105

Increasing the stim ulusinten sity activates inputcells,causing indirect, transsynaptic activation of pyram i-dal tract n eurons. A series of recordable volleys,nam ed I w aves to indicate their indirect origin, fol-

low the initialD w ave.T he I w aves are separated byintervalsofab out1.5 to 2 m s.A nesthesia and coo lingof the m otor cortex h ave a profou nd depressant ef-fecton the Iw avesbutnoto n the D w ave.63 Epidu ralrecordings of m ultiple descending volleys from thespinal cord of consciou s hum an patients have pro-

vided eviden ce that transcranial electrical stim ula-tion activates the m otor cortex in hum an s and ani-m als in the sam e w ay.19,49

T he sam e exp erim ents have also con firm ed thatthreshold transcranial m agn etic stim u li over thehand area ofthe m otor cortex preferentially activatethe pyram idal cells indirectly (transsynap tically)

throu gh excitatory interneuron s (Fig.1,righ t).T heon setlatency of the com pou nd m uscle action poten-tial (C M A P) from sm all hand m u scles is ap proxi-m ately 2 m s later (Fig. 1, bottom righ t, solid line)than the electrically induced response. H ow ever,

w ith higher stim ulus intensitieso r certain lateralcoilpositions,the laten cy m ay shorten ,consisten tw ith D

w ave activation (Fig. 1, bottom right, dotted line).T he d ifferent activation of pyram idal cells probablyis related to the orien tation of the induced curren t.Electricalstim ulation cau ses the curren tto flow in alldirections parallel an d radial to the surface, thuspen etrating the radially orien ted pyram idal cells.T M S, how ever, induces current flow parallel to thesurface of the b rain,preferentially exciting horizon -tally orien ted neurons.T he resultis thatradially ori-ented n euron s w illh ave a higher threshold for m ag-netic stim ulation than electric stim ulation. T his is

w hy coilorientation is im po rtant;even a slight po si-tion alchange o f the m agnetic coilon the scalp canprofoundly affect the size an d latency of the m otorevoked potential (M E P).14,85,96 The response oflow er lim b m uscles has a sim ilar laten cy w ith electri-caland m agn etic stim ulation.T hissuggeststhatb othtechniques have the sam e activation site in the ros-

tral pyram idal axon s as they leave the cortex andreadily produce D w ave activity.115W hether T M S ac-tivates a bi-or polysynaptic pathw ay in healthy sub-

jects is presently u nclear. Stud ies on m on keys havefailed to iden tify disynaptic excitation of m otoneu -ron s from the p yram idaltract.83

T M S also activates the local circuit inhibitory in-terneu ron s.Severalipsi-an d contralateralinhibitoryph enom ena have been revealed w ith dou ble (con di-

M agnetic Stim ulation M U SC LE & N ER VE February 2002 1 6 1

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tion ing) stim ulusparadigm sand rT M S,w hich w illbediscussed below .

F a c ilita tio n . W hen T M S is perform ed w ith the tar-get m uscle steadily con tracting,itshow s differentre-sults than w hen the m uscle is relaxed. M uscle con -traction has three m ain effects72: the threshold forevoking the m otor respon se is reduced, the latencyof the M EP is shortened , and the am p litud e of theM E P ism arked ly increased.46,61,122 T hese facilitatoryeffects can also be induced sim ply b y the subjectsthinking abou t the m aneuver or contraction of an-other m uscle (either on the sam e or op posite side),butthe extentoffacilitation islessthan thatinducedby con traction ofthe targetm uscle.72,121 T he un der-lying m ech an ism sfor facilitation are noten tirely un-

derstood but likely include increased cortical andspinal excitability.122,137 W ith volun tary contraction ,the resting poten tialofthe anterior horn cell(A H C )is closer to threshold, requiring less tem poral sum -m ation of descend ing volleys,w hich m eans thatthedischarge can occur at an earlier I or D w ave, thusshortening the on set latency.Fu rtherm ore,w ith in-creasing force, according to the H en nem an sizeprinciple,larger and faster con ducting spinalm oto-

neuron s w illbe recruited,thus shortening the on setlatency. T he increase of the C M A P am p litude indi-cates recruitm ent of a greater num ber of spinalm o-ton euron s.T his could also be due to increased spi-nal excitability,increased synchron ization of spinalm oton euron firing, or an increasing num ber of I

w aves bringing m ore A H C s to threshold.

M A G N E T IC S T I M U L A T O R A N D C O IL S

T he com pon ents of a m agnetic stim ulator consistofa capacitor an d an inductor (the stim ulating coil).T he en ergy for stim ulation is derived from charginga bank of capacitors up to about 4 kV, w hich w hendischarged indu ces a current of up to 5,000 A thatpasses through the cop per stim ulating coil,creatinga brief butinten se m agn etic field.T issues,sku ll,and

scalp presen t little or no im p edance to a m agneticfield of rapidly changing inten sity.T he direction ofcurren tflow in the coilisopposite to the d irection ofthe induced currentsin the n ervoustissue.H ow ever,the m agn etic field declines rapidly w ith distance.

T he inten sity ofthe m agn etic field isrepresen tedby flux lines around the coilan d ism easured in tesla(T).T he stim ulating curren t,w hich ism axim alin anannulus underneath the coil,m ay be either biphasic

F IG U R E 1 . P referentialexcitation ofpyram idalcells atthe axon hillock by electricalstim ulation (leftside)versus transsynapticalactivation

by m agnetic stim ulation (right side). H igher stim ulus intensities result in a shorter latency of the m agnetically evoked m otor evoked

potential(M E P ) (dotted lines).P referentialD or Iw ave activation (spinalcord volleys) is indicated by solid lines (see also text).


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or m on op hasic.B ecause the direction and phases ofcurrentflow determ ine w hich neuron alelem entsareactivated w ithin the cortex, a b iphasic im pulse m aystim ulate d ifferentpopulationsofcellsthan a m ono-ph asic im p u lse. T h e respo n ses to m o n op h asicstim uli ten d to be unilateral, w hereas responses tom ultiphasic stim uli m ay be bilateral. If the initial

curren t flow in a circular coil positioned over thevertex is clockw ise,the left hem isph ere w ill be acti-vated. R eversing the direction of the initialcurrentw illactivate the righthem isph ere.Large roun d coilsproduce fields that penetrate the deepest, and them agn etic fields are distributed through a larger vol-um e oftissue,resulting in n onfocalstim ulation.C en -tered over the vertex, the circum ference of the coiloverlies the hand area o f the m otor cortex. Sm allercoils, especially butterfly or figure-eight shap ed ,elicit m o re focal stim ulation w ith activation occur-ring beneath the intersection site, bu t prod uce arelatively w eak an d less pen etrating m agn etic field.

Fo r sm allhand m uscles,the optim alstim ulation siteis som e 5 cm lateral to the vertex on the interauralline w ith the figu re-eigh t coil orien tated 45 to theparasagittal plane.

M E T H O D S A N D M E A S U R E M E N T S

Fo r rou tine studies,the m agn etic stim ulator is con -n ected w ith standard n eed le electrom yograph ic(EM G ) equipm ent(Fig.2).A synchronization pulseoccurring at the m om ent of the stim u lators dis-charge serves as an external trigger that starts asw eep thatw illdisplay the recorded m o tor respon se

of a target m uscle.M easurem ents include the corti-calthreshold, latency and central con duction tim e,am plitud e,an d M E P/ C M A P ratio.

C O R T I C A L T H R E S H O L D

In a relaxed target m uscle, the cortical thresholdreflects the globalexcitability of the m otor pathw ay,

including large pyram idal cells, cortical excitatoryand inhibitory interneu rons, and spinal m oton eu-rons.Even sligh t voluntary con traction of the targetm u scle reduces the corticalthreshold.T hreshold tom agn etic stim ulation is usually defined as the stim u-lusrequired to elicitreproducible responses of50 to100 V in about50% of 10 to 20 con secutive trials.65

W hen m otor po tentials are recorded from a m od -estly activated target m uscle,the response should bearou nd 200 to 300 V so thatitcan be distinguishedreliably from background activity.T he position of acircular coil cen tered over the vertex is less criticalthan positioning a figu re-eigh tcoil.T he optim alcoil

position and orien tation ofthe figu re-eigh tcoilm ayeven be different for each intrinsic h and m uscle.14

M ills and N ithi88 have recently d evelop ed a m orereliable m easure of threshold. A single stim ulus at20% of m axim um stim ulator ou tput is given andsingle trials at 10% increm ents are then perform eduntil a response is obtained. T he intensity is thendecreased 1% at a tim e until 10 stim uli fail to giveany respon se.T his is referred to as the low er thresh-old.T he stim ulus inten sity is then increased by 1% increm ents untilallof 10 stim uliinduce a respon seof greater than 20 V in am p litude w ith a latency of

F IG U R E 2 . P rinciple of TM S and calculation of centralm otor conduction tim e (C M C T). M E P1 is recorded after transcranial m agnetic

stim ulation (S1

),M E P2

after cervicalstim ulation (S2

).C M C T is estim ated by onsetlatency ofT1

m inus onset latency ofT2

.


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17 to 30 m s.T his is referred to as the upper thresh-old. U sing this app roach, the low er threshold m ea-sured 38 8.6% and the up per threshold 46.6 9.4% . Threshold in adu lts is indep enden t of age,gender, and hem isphere, bu t varies w ith differenttargetm u scles.88,131 Itislow estfor hand m usclesandhigh est for p roxim alarm m uscles,leg m uscles,and

axial m uscles. T his is in keep ing w ith the m ore ex-ten sive cortical represen tation of hand versus m oreproxim alm uscles.

L A T E N C Y A N D C E N T R A L C O N D U C T I O N T IM E

L atency and central condu ction tim e dep end onw hether the M EP w as recorded at rest or w ith acti-vation , w hich shortens the latency by several m illi-seconds. H ow ever, th e latency do es n ot chan gem uch on ce 20% or m ore of m axim um volun tarycon traction is used.T hus,if latency is the on ly con -sideration ,force do es not need to be accurately con -trolled and the subject can be asked to m oderately

contractthe m uscle.T he o nsetof the M E P is usuallyreadily iden tifiable. T he shortest of four to five re-spon ses shou ld be m easured. In som e diseases, theM E P m ay be m arkedly redu ced in am plitud e and ,

w hen facilitation isused,partially bu ried in the back-grou nd EM G . T his often m akes the on set latencydifficult to recognize,and superim posing a num berof potentials m ay then be helpful. T o calculate thecentral m otor condu ction tim e (C M C T ), cond uc-tion in the periph eralsegm ento fthe m otor pathw ay(A H C to m u scle) is estim ated and then subtractedfrom the onset latency of the M E P (Fig.2).

For cervicalrootstim ulation,the m ostactive partof the coil is positioned just rostral to the spinousprocessofC 7 in the m idline or w ithin 2 cm lateraltothis position . B ecause a peripheral nerve is beingstim ulated, it is of n o consequ ence w hich w ay thecoil faces.T he lum bo sacral roo ts can be stim ulatedby position ing the coilw ith the m idpointof its lead-ing inner edge m idline over the particular vertebralbody of interest.T here is no need to obtain a m axi-m al respon se. T he prim ary aim is to elicit severalsuperim posable respon ses from w hich an accurateon setlatency can be m easured.H ow ever,for periph-eral electrical stim ulation of m otor n erves, laten cy

depen ds critically on the axons stim ulated in a sub-m axim alrespon se.A s response am plitude increases,latency alm ostalw ays shortens.T he sam e m ay app lyfor m agn etic root stim ulation , bu t this has n ot yetbeen system atically investigated .N evertheless,stim u-lating the nerve roo ts either m agn etically or electri-cally excites the nerve roo ts in the region of theintervertebral foram en .78,79 T he on set latency d oesnot, therefore, include the con duction tim e from

the A H C to the intervertebral foram en and theC M C T w ill be estim ated as sligh tly too lon g. T his isno t the case w hen using the F-w ave m ethod. T hecon duction tim e from spin al m otor n euron tom uscle is given by the form ula (F + M 1)/2 w here Fis the shortest F-w ave latency, M the on set of thedirectm uscle respon se,and 1 m s is allow ed for the

turnarou nd tim e at the A H C . Latency varies w ithheigh tan d arm length,therefore,centralm otor con -duction is sligh tly faster in w om en than m en .36,54,88

Latency and centralcon duction increase in a linearfashion w ith increasing age, but the correlation is

w eak.50,88

A M P L IT U D E A N D M E P /C M A P R A T I O

T he absolute am plitud e of the M E P depend s oncom p lex interaction s betw een the C M and the A H Cat the m o m en t of stim u lation .It reflects the sum ofup per and low er m o tor n euron activity. T here canbe considerable inter-trial as w ell as intra-individual

variation especially w hen stim ulating w ith thresholdor sligh tly suprathreshold inten sities. W ith increas-ing stim ulus inten sity,the response becom es m orestab le.71 M an y factors acco unt for this variability,m ost of w hich are difficult or im possible to con trolin the clinical setting.C oil position is critical;m ini-m alan gulation of the coileven atthe sam e site m aydrastically ch ange the am plitude of subsequen t re-spon ses. A s discussed above, even m od est m usclecontraction greatly facilitates the response an d it isim perative to state w hether the response w as elicited

w ith the target m uscle relaxed or un der volun tarycontraction.Iffacilitation isused for am plitude m ea-surem ents,force or overallm uscle activity should beestim ated.T his can be accom plished by either usingisom etric strain gauges or rectifying and integratingthe b ackgrou nd needle E M G to provide a m easureasa percentage ofthe m axim um .48 T he am plitude isusually m easured peak-to-peak.

B ecau se of its variability,the absolute am plitudeis of lim ited clinicalvalue.H ow ever,in the authorsexp erien ce, a side-to-side difference of 50% orgreater can be regarded as abn orm al in patients

w ithou t low er m otor neuron disease. T he M E P/C M A P ratio takes account of the low er m otor n eu-

ron con tribu tion and is a m ore useful indicator ofdisease originating in the cortex.H ow ever,the ratiois very variable, ranging in norm al subjects from 10to 100% . T he recen tly d eveloped triple stim ulationtechnique provides a m ore accurate and lessvariableestim ate of u pper m otor neuron activation . It hasbeen applied in a variety of u pp er m otor neurondisorders,15,81,82,113 but the techn ique can be un -com fortable for patien ts.


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C O R T IC A L M A P P I N G

T he m otor cortex is organized in term s o f m ove-m en ts rather than m u scles.Individualm u scles havem ultiple represen tations (con vergen ce) an d a givenC M m ay p rovide inpu t to several spinal m oton eu-rons of different m uscles (divergen ce). B ecauseT M S preferen tially activates fast-conducting cortico-

spinal fibers, m aps reflect only the ou tput functionand distribution of the m o st direct fast-con ductingcorticalm otor neuron alfibers.For m app ing the to-pographic structure of cortical m otor areas, a bu t-terfly (figu re-eigh t) coilis usually used,becau se them ore focused field gives a m ore accurate m ap. T hesurface of the cortex is m arked o ut in 1 cm squ aresusing C z (internation al10 to 20 system ) asthe zerozero m ark. Points are extended anteriorly and pos-teriorly along the sagittalplane an d over the leftan drigh them ispheres in the coron alp lane.W ith a stan-dard stim ulus m agnitude, the coil is system aticallym oved over the m otor cortex,w hich then produ cesa m ap of different M E P am p litudes at each site.131

T he greatestM E P am p litude is evoked in the centerof the m ap (optim al position ) an d declines as thecoilism oved aw ay from it.W ith the figu re-eigh tcoil,the optim alp osition to elicitresponses in sm allh an dm uscles is 5 to 7 cm lateral to the vertex on theinterau ral line.90,112 O ther m easurem ents includ ethe n um ber of excitable scalp position s and the cen -ter of gravity.44,89,132 A fram eless stereotactic systemallow s m ore p recise coilplacem en t.74

P L A S T I C I T Y O F T H E M O T O R C O R T E X

M otor m app ing experim ents that use the m agneticcoil in consciou s h um ans have now clearly do cu-m ented plasticity ofthe m otor cortex and its ability toreorgan ize in certain circum stances.24,33,34,76,91,100,114

Piano practice for a few days tends to increase thesize of the corticalm otor area for relevant m uscles.In con gen ital atresia of the forearm and hand akinto thatseen in thalidom ide teratogenicity,the proxi-m al arm develop s a larger than norm al representa-tion.

W hen hem isph erectom y is perform ed early inlife,ipsilateralm otor represen tation becom es m u ch

m ore p ron ounced,and corticalstim ulation inducesbilateral responses.38 In adults, learnin g-inducedrepresen tationalplasticity has been dem onstrated inblind B raille readers.102,104 In long-stan ding B raillereaders, the represen tation of the first dorsal inter-osseous m u scle of the reading finger is m u ch largerthan the ho m ologous m uscle on the other side,

w hereas the adductor digiti m inim i of the readinghand is sm aller than that of the non -reading hand

and con trolsubjects.In other w ords,the corticalrep-resentation of the reading finger has becom e en-larged at the expense of other fingers.A lso, the ac-quisition of new fine m otor skills in norm al subjectsisassociated w ith reorganization ofthe m otor cortexoutput m ap.37,99 D ifferent areas of the m otor m apenlarge depending on the new ly acqu ired skill.Spi-

nalcord injury also results in enlargem entof ou tputm aps projecting to m uscles p roxim al to the lesionlevel.38 R eorganization of the m otor cortex ou tpu tm ap has also been show n w ith altered sensory inpu tassociated w ith im m obilization , isch em ic n erveblock, dystonia,stroke,an d facialpalsy.15,27,56,110,111

M app ing of corticalareas other than the m o torcortex is also possible.D epending on the exact coilposition and curren tdirection,T M S ofthe occipitalcortex evokes phosphenes in different areas of the

visual field.5 T M S of the sensorim otor cortex occa-sionally triggerssom atotopically organized paresthe-sias but m ay also block detection of an electrically

evoked sen sory stim ulus.

T H E C O R T I C A L S IL E N T P E R I O D

A s m ention ed earlier,T M S also produ ces inhibitoryph enom ena,the m ostconsistentbeing the presenceof a lon g period of needle E M G silence du ring asustained voluntary con traction (Fig.3).T his is akinto the silen tp eriod obtained by stim ulating a periph-eralm otor nerve d uring contraction of a m uscle.109

T he duration of the silentperiod ,u sually defined asthe tim e from the beginning o f the M E P to the re-turn of voluntary need le E M G activity,is linearly re-lated to stim ulus inten sity but indepen den t of the

levelo f backgrou nd con traction .For clinicalconsis-tency, m easurem en ts shou ld be m ade w ith definedstim ulus inten sities in relation to individual m otorthresholds.Silent period s are longest in sm allhandm uscles(200 to 300 m s) and lessprom inentin proxi-m alarm m uscles and leg m uscles.W eak stim ulicandepress E M G activity w hile eliciting no m o tor re-sponse,indicating that the threshold for this inhibi-toryeffectislessthan for the excitatoryeffect.Spinalinhibitory m echanism s such as R en shaw inhibitionare con sidered to con tribute only to the first 50 m sto 60 m s of the T M S-induced corticalsilent period ,

w hereas m ost of the sup pression is du e to different

cortical inhibitory m ech an ism s.28,53,109 The neuro-nal elem ents respon sible for these effects are top o-graph ically close to the corticospinal neurons an dare m ost likely the local inhibitory interneuron s,

w hich use G A B A as their transm itter.

P A IR E D C O R T I C A L S T I M U L A T I O N

T w o transcranialm agn etic stim ulidelivered in a con -ditioning test paradigm can be used to assess intra-


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corticalinhibitoryand excitatorym ech anism s.94 T heeffects depen d on the type ofstim ulus (electricalorm agn etic),the scalp site atw hich stim uliare applied,th e in ten sity of bo th the con dition ing and teststim uli,the m uscle activity,and the interstim ulus in-terval(ISI).W ith the m uscle at rest,the response ofa suprath reshold stim ulus is inhibited by a sub-threshold conditioning stim ulusatintervals of1 to 5m s and facilitated from about 10 to 20 m s.75 T heinhibitory effect is reduced w ith voluntary contrac-tion. T he inhibition is due to the effects of local-circuitinhibitory interneurons and also the resultof

inhibitory collaterals from excited corticospinal fi-bers.75 T hreshold pairs of stim uli of equ alstrengthresultin inhibition ofthe testresponse at ISI of5 to30 m s, and facilitation at ISI of 40 to 90 m s. A dif-ferent pattern occurs with high er stim ulus inten si-ties:ISI of25 to 50 m scause facilitation,an d ISIof60to 200 m s cause inhibition.U sing p airsof thresholdstim uli(0.9 to 1.1 tim es threshold or a suprathresh-old con ditioning stim ulus) follow ed by a subthresh-

old teststim ulus,short-laten cy excitatory effects(ISI1 to 6 m s) can be dem on strated.T hese effects showperiod icity rem iniscent of the I w aves recorded di-rectly from the p yram idal tract. T he p aradigm canbe used to assess drug effects and pathologicalcon -ditions.29,77,139

R E P E T IT IV E T R A N S C R A N I A L M A G N E T I C S T I M U L A T IO N

R ep etitive transcranialm agnetic stim ulation (rT M S)is only possible w ith special stim ulators that h avetech nical features allow ing the generation of fastrates of stim ulation .T he techniqu e perm its m odula-tion ofcorticospinal excitability.26 T he effects,rang-ing from inhibition to facilitation, depen d on thestim ulation param eters (stim ulus inten sity, inter-stim ulus interval,n um ber ofstim uli,an d intervalbe-tw een successive trains) and m ay lastbeyond the du-ration ofthe rT M S itself.26,103 L asting effectsofhigh -frequency rT M S (greater than 1 H Z) on clinical

sym ptom shave been seen in Parkinsonsdisease an ddepressed patients,w hereaslow -frequency rT M S cantransien tly im prove sym ptom s in patien ts w ith task-specific dystonia.55,101,119 Further clinical applica-tionsinclude treatm en toffocalepilepsy,corticalm y-o clo n u s, sp asticity, an d ob sessive-co m p u lsivedisorders.O ther effects outside the m otor areas in-clude in terferen ce w ith langu age, cogn itive pro-cesses, and m em o ry.98 T he different therapeuticben efits of rT M S are not easy to explain bu t m ayinclude n eurom od ulatory effects from released neu-rotransm itters and changes in cerebralbloo d flow .

H igh frequ ency and intensity rT M S m ay causeepilep tic seizures. Secondarily generalized seizuresfollow ing rT M S have b een reported in healthy sub-

jects and patients w ith epilepsy and dep ression ,bu tthere isno evidence for the develop m entofepilepsyafter an rT M S-provoked seizure.129 Spread ofexcita-tion in the cortex,aseviden ced by C M A Ps app earingin m uscles rem ote from th e target m u scle andneed le E M G activity that persists after the stim ulusends,iscon sidered an indicator ofinduced epilepticactivity.8,103 T hese observation s w ere used as the ba-sis on w hich the m axim um safe com bination s ofstim u lus inten sity,frequen cy,an d d uration of single

trains of rT M S w ere defined.

130

D I R E C T S T I M U L A T I O N O F C O R T I C O S P I N A L

T R A C T A X O N S

It is usually n ot possible to stim ulate the pyram idaltractaxo nsdirectly (postsynaptically) w ith a m agnet.H ow ever, U gawa et al.128 dem onstrated that this isfeasible w ith a dou ble con e type of coil that is ca-pable of delivering stim uli to deep structures. T he

F IG U R E 3 . S ilentperiod in a norm alsubjectand an A LS patient.

R ecordings w ere m ade from a m odestly contracting abductor

digitim inim im uscle.


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coilisplaced over the inion stim ulating ipsilateraltothe side ofrecording.L atency to the h and m usclesisabou t 16.5 m s, com pared to abou t 20 m s after cor-tical an d 12.5 m s after cervical root stim ulation,

w hich suggests that th e corticospin al p athw ay isstim ulated at the levelofthe pyram idaldecussation.Indicatorsthatthe response indeed originates in the

tractand not pyram idalcells include con sistency oflatency and shape of the respon se an d a latency thatisiden ticalto thatevoked by electricalstim ulation atthe sam e site.

T his m ethod is useful to confirm thatprolon gedlaten cy of a M E P elicited by cortical stim ulation isdue to slow ed con duction w ithin the spinal tractsand not the result of increased tem poralor spatialdispersion resulting from im paired intracortical ini-tiation of the descending volley at the level of thepyram idal cell.127

P E R IS T I M U L U S T IM E H I S T O G R A M S

T he corticalm otor neuron alsystem (the C M and itstarget spinalm otoneuron ) can be investigated usingperistim ulus tim e histogram s (PST H s) (Fig.4).T hefiring probability of a voluntarily activated m otorunit is m o dulated w hen it is subjected to a series oftranscranial m agnetic stim uli.18,42 The PSTH re-corded from forearm and hand m uscles typicallyshow s a m arked increase in the firing probabilityoccurring at about 20 to 25 m s after the stim ulus,

w hich is referred to as the prim ary peak.T he on setlatency of the prim ary peak is in keep ing w ith a vol-ley d escending throu gh the fast-con ducting m ono-synaptic (corticospinal) pathw ay.T he configu rationof the prim ary p eak (am plitude, du ration , and dis-persion) reflects the rising phase of the com positeexcitatory postsynap tic poten tialatthe A H C inducedby the descending corticalvolley.T histechniqu e hasbeen app lied to severaldiseases bu thasbeen of par-ticu lar valu e in am yo trop h ic lateral sclero sis(A LS).134

U S E O F T H E M A G N E T IC C O IL F O R P E R I P H E R A L

N E R V E S T I M U L A T IO N

U se of the m agnetic coilfor study of the p eripheralnervous system is presen tly lim ited by its inability to

deliver a controlled focalstim ulus.For exam ple,itisdifficult to stim ulate the m edian and ulnar nerveindependently w hen the coilisplaced o verthe w rist.It is also difficult to elicit m axim um am plitudeC M A Ps in a reproducible m ann er as is po ssible w ithcon ventional electrical stim ulation. H o w ever, m oreadvances in coil design show prom ise in im p rovingthe p recision and thusthe utility ofm agn etic periph-eralnerve stim ulation.11

Peripheralnerves are m ost readily stim ulated bythe m agnetic coil at sites where there is an abrup tchange in the volum e con du ctor or atsites of nerveben ding.78,79 T his m ay explain the p aradoxicalease

w ith w hich proxim al rather than distal nerves arestim ulated. T his can be helpful for stim ulating thedeep ly placed p hrenic nerve in the n eck.T he d irec-tion of curren t flow is critical in cortex stim ulationbu t not in peripheral nerve stim ulation . H ow ever,the C M A P latency m ay change by a fraction of am illisecond w hen the curren t direction is reversed,possibly as a result of the cathodal-anodalreversaleffect an d/or shallow er rise-tim e in the strength of

the m agn etic field w ith reversed flow .

S A F E T Y C O N S ID E R A T I O N S A N D S ID E E F F E C T S

Since B arkers develop m ent of the first com m ercialm agn etic stim ulator, m any thou sands of p atien tsand norm al individuals throu ghou t the w orld haveundergone m agn etic stim ulation w ithout ill effect.

A dverse effects of single pu lse m agnetic stim ulation

F IG U R E 4 . P eristim ulus tim e histog ram s (P S TH s). W ell-

synchronized prim ary peak of shortduration in a controlsubject

(top) and K ennedys disease (m iddle). D ispersed prim ary peak

consisting of a double peak in A LS (bottom ).


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of the m otor cortex are extrem ely rare.Induction ofepileptic seizuresand kindling h ave caused the m ostconcern bu t there have on ly been a few reports ofseizuresoccurring ator shortly after the tim e ofm ag-netic stim ulation.35,64,66 Form al stud ies on know nep ilep tics h ave failed to induce either clinical sei-zuresor electroen cephalographic epileptiform activ-

ity.139

H o w ever,it has becom e clear that rT M S,de-pen ding on the stim ulation param eters(see above),can evoke seizures in norm al subjects and patients

w ith neurological disease.130 O ther concerns haveincluded possible brain cell dam age w ith cognitiveand other dysfunction and com plications from dis-lodging neu rosurgically inserted m etal clips. It ispossible that m agn etically induced curren ts cou lddam age the internal electron ics of biom edical de-

vices such as cardiac pacem akers. T he coils shou ldtherefore not be placed in the vicinity of cardiacpacem akers.C ardiac m uscle can only be stim ulated

w ith the m agnetic coilifitis placed directly overthe

open heart;ap plying a m agn etic coilo ver the lateralchest w allin the process of stim ulating the intercos-talnerves has not caused cardiac irregularities.N ev-ertheless,it is ad visable to avoid stim ulating directlyover the p recordium .

Fo rm al psychom etric testing before and aftersingle pulse m agnetic stim ulation has indicated noassociated cogn itive im p airm en t. E ndocrine assess-m en t of the pituitary-hypothalam ic axis after T M Shas show n no con sistent changes.67,84

M agn etic stim ulation can activate the auricularm u scles, especially in young children . T he noiselevelofolder stim u latorsraised the concern of tem -porary hearing im pairm ent b ut n o lasting effects

w ere fou nd w ith the sm allnum ber ofstim uliapp liedto m ostsubjects.97 Fo r routine clinicalp ractice,10 to15 stim uliare usually m ore than sufficien tto achievethe desired inform ation.Severalh undred subthresh-old stim uli,as required for PST H s,are equally safe.

A s a general guide, previou s cranial neurosurgery,the w earing of an electrically sen sitive biom edicaldevice such as a cardiac pacem aker or intrathecalpum p, and a history of seizures are relative contra-indications.

M A T U R A T IO N O F T H E C O R T IC A L M O T O R

N E U R O N A L S Y S T E M A N D A G E -R E L A T E D C H A N G E S

M agn etic stim ulation is ideal for the study of them aturation of m otor pathw ays.A dult values for cen-tral m o tor con duction velocity are attained a few

years after central sensory con du ction . In both in-stances, adult values for peripheral con duction arereached earlier than central con duction , im plyingthat peripheral m yelination precedes central m y-

elination. In children, C M C T linearly declines w ithage.A dult values for centralm otor con duction canusually be attained by 4 years of age.H ow ever,cor-ticalthreshold rem ainshigh untilthe en d ofthe firstdecade.92 T he disparity betw een attainm entof adult

values of centralm otor cond uction velocity and cor-ticalthreshold is consisten tw ith the notion thatcen -

tralm yelination is com pleted before synaptogenesis.O n the other end of the age spectrum ,M EP am p li-tude declines an d central m otor conduction tim egradually increases w ith increasing age.Injury to them o tor cortex in young children can be follow ed byexcellen tfunctionalrecovery ofthe affected lim b(s).In such situations,m agn etic stim ulation ofthe unaf-fected cortex inducesnotonly the usualcontralater-al respon se bu t also a large ipsilateral one. T his isprobably the resultofcorticospinalsprouting w ithinthe pyram idal tract leading to an elabo ration of ip-silateral projections.18 It has been m orph ologicallycon firm ed thatsprouting ofcentralfiberscan occur,

using labeling of corticospinal cells.

M A G N E T I C S T I M U L A T I O N I N D IS E A S E

M any abnorm alities revealed by m agn etic stim ula-tion are not disease specific and, like m o st otherneurophysiologicaltests,the results m ust be con sid-ered in the ligh tofclinicaldata.Frequen tly the cor-relation betw een clinicaldeficit and degree o f M E Pabnorm alities is rather poor.In gen eral, dem yelin-ation of cen tral m otor pathw ays is associated w ithm o re m arked con duction slow ing an d prolon gationof centralconduction tim es.O n the other han d,inneuron al disease, the M E P, if recordable, is of re-duced am plitude bu t usually is only m odestly pro-longed in laten cy.

A m y o tro p h ic L a te ra l S c le ro s is . E arlier studies inA L S usin g electrical stim ulation of th e cortexshow ed m odest prolon gation of centralm otor con-duction tim e, frequently m arked M E P attenuation ,and ,in som e cases,absence of the M EP.68 TM S re-

veals sim ilar abnorm alities. T he prom inent abnor-m ality is an absent or sm all M EP that is frequentlydispersed (Fig. 5). T his correlates w ith the occur-rence of dispersed prim ary peaks in the P ST H (Fig.

4, b ottom ), w hich m ay reflect hyperexcitability ofC M con nection s.In general,the correlation of cen-tralm otor conduction prolon gation w ith other M E Pabn orm alities and w ith clinicalupper m otor neuronsign s (hyperreflexia, finger flexion, im paired finefinger m ovem ent) is po or.117

V ariou s neuroph ysiological m ethod s em ployingT M S h ave also indicated hyperexcitability ofthe m o-tor cortex in A LS.47,58,73,87,93 T he threshold requ ired


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to stim ulate the m otor cortex w ith a m agn etic coilisreduced early in the disease, especially in patien ts

w ith preserved m uscle bu lk and prom inent fascicu-lations.89 O ther T M S studies suggestthatcorticalin-hibitory m echanism sare also im paired in A L S.95 Forexam ple,the corticalsilen tperiod,a m easure ofcor-ticospinalinhibition,is shorten ed com pared to nor-m al subjects (Fig. 3, bo ttom ), and a sub thresholdconditioning stim ulus delivered shortly before a su-prathreshold teststim ulus fails to inhibit the testre-spo nse in A L S.60

PST H s in patients with A LS show a diversity ofabn orm alities ranging from the prim ary peak beingsm all (or absent) to being large and increased in

tem porald ispersion.

133

O ver tim e,the dispersion in-creases and dou ble prim ary peaks occur,suggestingactivation of slow -con ducting indirect pathw ays. In-directeviden ce suggests thatthese abnorm alities aresupraspinalin origin and are n ot the result of A H Cdisease.In K ennedys disease (bu lbar-spinal m uscu-lar atrop hy),the p rim ary peak of the P ST H is nor-m al(Fig.4,m iddle),w hich confirm s thatthe abn or-m al PST H in A L S is du e to sup raspinald isease.133

Patien ts w ith prim ary lateralsclerosis (PLS) showsign ificantly elevated thresholds to T M S and longercentral cond uction tim e to both up per and low erlim bs. H ow ever, using PST H s, it can be dem on -strated thatthe onset latency ofthe prim ary peak in

A L S and PL S do es not significantly d iffer,im plyingthat T M S activates the sam e po pu lation of C M con-

nection s in A L S and P LS.

M u ltip le S c le ro s is . D em yelination inducescon duc-tion block,slow ed conduction,and inability to faith-fully sustain rapid trains of im pulses.T hese charac-teristic p h ysiological d istu rban ces in m u ltip lesclerosis (M S), individually or in com bination, ac-coun t for prolongation of C M C T , reduced M EP /C M A P ratio,increased variability of onset laten cy ofthe M EP (laten cy jitter),and dispersed m orph ology(Fig.6).12,16,62 Slow ing o fcen tralm otor conduction ,the m ost com m on ly seen abn orm ality, can be verym arked and correlates to som e d egree w ith the p res-

ence of up per m otor neuron signs and clinicald efi-cit.69 A com m on site of dem yelination in M S is thecorpus callosum , and interhem ispheric con ductionthrou gh the corpu s callosum is sign ificantly slow edin th is disease.13 Ipsilateral co rtical stim ulationcauses transcallosalinhibition ofa contracting targetm uscle, and this fact can be used to m easure con -duction throu gh the corpuscallosum .A sign ifican tlyincreased excitability threshold in resting or preac-tivated m uscles is frequ en t.T his is usually associated

w ith prolon ged centralcon du ction but m ay also oc-cur as an isolated abn orm ality.M E P studies m ay de-tect sub clinicalinvolvem ent of m otor pathw ays andthe overallsen sitivity is com parable to visualevokedpotentials.57

F IG U R E 5 . S m allcom plex M E P recorded from the abductordigiti

m inim iin A LS at45% stim ulatoroutput.Threshold 35% .N ote the

late com ponent w ith a latency of 45.6 m s w hich corresponds to

the second com ponent of the double prim ary peak (see Fig. 4)

and m ay reflectactivation ofslow conducting corticalm otor neu-

ronalconnections.

F IG U R E 6 . D elayed (upper lim it 25 m s) and sm all M E P w ith

variability of onset latency and dispersed m orphology from the

abductor pollicis brevis in m ultiple sclerosis at 90% stim ulator

output.Threshold 80% .


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Stud ies with PST H s in M S have show n delayedand dispersed prim ary peaks consisting of m ultiplesubpeaks.12 A sim ilar abnorm ality is seen in A LS bu tthe underlying m echanism is different.In M S,con -du ction throu gh the descending m otor tracts is de-layed,w hereas in A L S,conduction slow ing and tem -poraldispersion is caused by selective loss of large,

fast-con ducting pyram idalneurons.135

M o v e m e n t D i s o r d e r s . C on duction tim e throu ghthe descend ing m otor pathw ays is norm alin Parkin-sons disease, H u ntingtons disease, prim ary dysto-nia,essential trem or,and m yoclon us.7,23 D eterm in-ing the corticalthreshold in Parkinsons disease hasproduced inconsisten t results: decreased, norm al,and elevated thresholds have all been reported.23

T he cortical silent period is shortened or norm aland , w hen short, the abn orm ality can be reversedafter levodop a therapy.108 C orticocorticalinhibition,tested at sho rt con ditioning test intervals an d w ith

the m uscle at rest,is reduced in Parkinsons disease.O n the other hand, interstim ulus intervals of be-tw een 40 to 75 m s show greater than norm alinhibi-tion of the test respon se.9 T he physiologicalabnor-m alities in Parkinsons d isease revealed by T M Sprob ably result from a com bination of increased in-hibition and redu ced excitation occurring at bothcorticalan d subcorticallevels.7 In dyston ia and H u n-tingtonsdisease,double stim ulation paradigm shaveprod uced conflicting findings,m ostlikely due to dif-feren tstim ulation param eters.2,59,118 N evertheless,itis likely that future studies w ill reveal useful insigh tinto the pathop hysiologicalm echan ism s and m od eof drug action .

S tro k e . In stroke patien ts,the response after corti-cal stim ulation is often absen t.106 In patien ts in

w hom a respo nse is obtained,the M EP isqu ite oftenof sm all am plitud e and dispersed. C M C T is usuallyonly sligh tly prolonged . T he cortical threshold iscom m o nly fou nd to be raised.25 In a form al study,th e duration of th e silen t period w as m arkedlylon ger on the affected side w hen com p ared w ith acontrol grou p.T his param eter also seem s to detectm ild,subclinicaldisturbances.1 T M S appears to be a

goo d predictor o f stroke ou tcom e.

3,33,60,123,125,126

Arecordable M E P in early stages correlates w ith a fa-vorable ou tcom e, w hereas an absent response pre-dicts p oo r recovery. Patients w ith delayed bu t pres-en t M E Ps recover m o re slow ly th an th ose w ithnorm al M E Ps, but are sim ilar at 12 m on ths. T heC M C T correlates w ell w ith the grade of w eakness.T he finding of an increased threshold correlates

w ith the presence of brisk tend on jerks.

H e re d ita ry S p a s tic P a ra p le g ia a n d S p in o c e re b e lla r

A ta x ia s . In patien tsw ith hereditaryspastic paraple-gia, low er lim b respon ses are alm ost alw ays abnor-m al: absent, reduced, or delayed. U p per lim b re-spon ses, how ever, are usually norm al even in thepresence of clinical upper m otor neuron sign s. Asim ilar pattern can be seen in patien ts w ith heredi-

tary m otor and sensory neuropathy w ith pyram idalsigns.The C M C T to sm allhand m usclesin Friedreichsataxia ism ostoften prolon ged .41 M oreover,the M EPis frequently of sm allam plitude and dispersed.T hesen sitivity iseven greater w hen recording from low erlim b m uscles.In other cerebellar ataxias,ab norm ali-ties are lesssevere and lessfrequen t,w ith the h igh estrate of im pairm ent being seen in spinocerebellarataxias.P rolongation o fcentralm otor con duction isalso a com m on finding in patien tsw ith hum an T -celllym photrop hic virus type Iassociated trop ical spas-tic paraparesis.R esponses in the low er lim bstypicallyshow m arked prolon gation . U pper lim b respo nses

m ay be no rm al or sho w slow ing of centralcon du c-tion less p rom in en t th an recordin gs from legm uscles.138

E p ile p s y a n d D ru g s . A ttem p ts have been m ade touse T M S for localization of epileptic foci,but it ap-pears that the epileptic focus can not be localized

with sufficient resolution using this approach.22,32,136

O ne w ou ld exp ectthatcorticalexcitability m igh tbeincreased in patien ts w ith epilep sy but thresholdm easurem en ts have revealed conflicting results. In-tracorticalinhibition in epilep sy is reduced,but thisis a n on specific finding w hich can be seen in m an yother disorders.Itisunclear w hether changes in cor-ticalexcitability are due to m ed ication or to ep ilep syitself.A ntiepileptic drugsw hich acto n sodium chan-nels (carbam azepine, p hen ytoin, lam otrigine) in-crease m otor threshold bu tdo not have a sign ificanteffect on intracorticalinhibition.In contrast,antiep -ileptic drugs o r m edication m odulating activity ofG A B A receptors(e.g.,benzodiazepines) have n o sig-nificant effect on m otor threshold bu t enhance in-tracortical inhibition an d suppress intracortical fa-cilitation .139 In patien ts evaluated for ep ilep sysurgery,rT M S app lied to the dom inant hem isph ere

can produce speech arrest but does no t alw ays cor-respond directly w ith W ada testresults.10,51

R a d ic u lo p a th y a n d S p o n d y lo tic M y e lo p a th y . M ag-netic stim ulation over the spinal en largem en ts ex-cites the nerve roots a few centim eters distal to the

A H C in the vicinity of the intervertebralforam en.30

T he respon se latency is reprod ucible but the stim u-lus is usually subm axim al. T his precludes standard-


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ization based on the am plitude o f the respon se an ddetection of a m ore distal con duction block. T he

value of m agnetic root stim ulation to evaluate ra-diculop athies is thus lim ited.A s w ith other con duc-tion techniques used to evaluate radiculopathies (F

w aves,som atosensory evoked po tentials,H reflexes,and m agn etic stim ulation),con duction block is dif-

ficultto interpretgiven the variability ofM E P am pli-tude and uncertainty in obtaining a m axim u m am -plitude poten tial.

A high percentage of abnorm alities in the M E Phas been described in spon dylotic m yelop athy.45

T he C M C T is frequently p rolon ged, the thresholdraised,and the respon se dispersed and of sm allam -plitude. A bn orm alities of central conduction m ayprecede clinical evidence of m yelop athy. Slow edcentralconduction m ay be an early m anifestation ofcord com pression before it is evident on m agneticreson ance im aging.124

P le x o p a th y . A lthough m agn etic stim ulation can beused in plexop athies, the techn iqu e has not beenable to substitute for electrical stim ulation. W ithm agn etic stim ulation at the p lexus level,supram axi-m alrespon sesare notalw ayspossible and the precisesite of stim ulation is uncertain.40,52,112,116 H owever,m agn etic stim ulation provides certain advantages insom e typ es of p lexu s lesion s. Fo r exam p le, aneurapraxic lesion of the upper trunk of the bra-chial plexu s cann ot be detected by electricalstim u-lation of E rbs point, w hich is usually below the le-sion. Accurate localization w ould requ ire directelectrical stim ulation of the spinal roots through am on op olar needle. T his can be achieved non inva-sively b y m agnetic stim ulation. E liciting a responsefrom the deltoid o r biceps is clear evidence of nervecontinuity,an d sign ificantslow ing ofonset laten cies

w ou ld indicate focal dem yelination .95 M E P am pli-tudes after m agnetic plexus stim ulation are variableand on e cann ot com m ent as to the presence o r ab-sence of conduction block.O nce there h asbeen sig-nificant axon alloss,n eedle E M G is the b estm ethodof determ ining axonalcontinuity and reinnervation .Stim ulation of the lum bo sacral plexus and caudaequina is also possible w ith m agn etic stim u lation,

but,like stim ulation of the brachialplexu s,it som e-tim es fails to elicit rep rod u cible, m axim al re-sponses.17,31,80 T his again lim its its value in the as-sessm en t o f lu m b o sacral radiculo p ath ies an dplexopathies.31

P e rip h e ra l N e u ro p a t h ie s . A spreviou sly m ention ed,m agnetic stim ulation ispresen tly lim ited w ith regardto the peripheralnervou s system because of lack of

focality an d inability to elicita poten tialofconsisten tm axim al am plitude. T his precludes, am on gst otherth in gs, accurate detection of con duction block.H ow ever, there are at least tw o situations in w hichuse of the coil is advantageou s.In children w ho donottolerate electricalstim ulation,m agnetic stim ula-tion often allow s m easurem ent of con duction veloc-

ities sufficien tto differen tiate betw een a dem yelinat-in g and an axon al n europath y. Secon dly, indem yelinatin g n eu rop ath ies, cortical stim ulationcan reveal m arked conduction slow ing in the m o stproxim alnerve segm en ts.T he F w ave can often dothe sam e, but w hen the neurop athy is severe it m aybe absent.

C R A N I A L N E R V E S

T he intracranialportion softhe m otorcranialnervesV ,V II,X I,and X IIare readily stim ulated w ith a m ag-netic coil.6,21,129 T o elicit respon ses from m usclesinnervated through the cranialnervesattheir intra-

cran ial-extram edullary portion, the m agn etic coilshould be positioned over the occiput ipsilateraltothe recording site.E vidence indicatesthatthe nervesare excited close o r justdistalto their exitforam ina.B ecause proxim ity of the stim ulus to the surface re-cording electrod es can be a prob lem , a concentricneed le electrode isoften preferred for recording theelicited m uscle respo nse.A n intra-oralperm ucosalrecording device is also helpfulto reduce artifact.

T he central, crossed, corticop on tine portion ofthe m otor cranialnerve conduction is m ore d ifficultto assess.T he coilis optim ally placed 4 cm lateraltothe vertex on a line joining the vertex (C z) and theexternal auditory m eatus. A ctivation of the targetm uscle is usually requ ired to obtain a response.

D IA P H R A G M A T I C C O N D U C T IO N

D iaphragm atic recording is used routinely to diag-nose an d m onitor patien ts w ith im paired respiratoryfun ction . A lth ough electrical stim ulation of th ephrenic nerve is w ell established, cervical m agn eticstim u lation of the phrenic nerves is less painfulandachieves a m ore con stant degree of d iaphragm aticrecruitm en t.120,140 A n un explained ph eno m eno n isthe greater transdiaphragm atic tw itch pressure that

occurs w ith m agnetic rather than electrical stim ula-tion . T his m ay b e due to coactivation of extradia-phragm atic m u scles.N orm alvaluesforthe latency tothe diaphragm using electrical stim u lation in theneck are b etw een 7 and 8 m s,but data are less ho-m ogeneous for m agnetic stim ulation .

T he diagn osis of im paired central respiratorydrive can often be accom p lished by transcorticalm agn etic stim ulation of the m otor cortex w ith re-


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cording of the diaphragm and ph renic nerve re-sponses.T hese studies are ofparticular value in criti-cally ill patients in w hom bo th central and periph-erallesions m ay im p air respiration.140 Phrenic nervepacing is becom ing a m ore frequent substitute forpositive pressure ventilation via tracheotom y in pa-tien ts w ith high cervical cord lesions or cen tral hy-

poventilation. A lthough its in dications are infre-qu ent, T M S m ay help to determ ine w hich patientsm ay ben efit from this treatm ent.120

I N T R A O P E R A T I V E M O N I T O R IN G O F M O T O R

E V O K E D P O T E N T IA L S

T he ability to evoke M EPs during surgery hasbeen ausefuladdition to the battery of neurophysiologicaltests that can be used to m on itor and prevent thedevelopm en t of clinical deficits d uring surgery.5,20

M E P m onitoring is particularly relevant in surgerythatm ay dam age the m otor pathw aysindep end entlyof the sensory pathw ays. Exam ples of this include

resection of spinal cord tum ors, cross-clam ping ofcerebralbloo d vessels,and resection of tum ors andarterioven ous m alform ations involving the m otorcortex and subcortical m otor pathw ays. H ow ever,intraop erative m onitoring is expen sive, requiringdedicated team s and equipm en t, and its cost-effec-tiveness needs to be considered.

E lectrical stim ulation of the cortex w ith record-ing over the spine (preferably using intraduralelec-trodes) is the m ost reliable m ethod because it is in-dependent of the anesthetic used. H ow ever, it ispossible to use m agn etic stim ulation w ith som e an-esthetics such as ketam ine or fentanyl and ob tainreason ably reliable results. If trains of stim uli areused rather than a single stim ulus, the facilitationprodu ced helps overcom e the effects of som e anes-thetics.

R E F E R E N C E S

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