research article the mechanisms of movement control and time estimation...

Hindawi Publishing CorporationNeural PlasticityVolume 2013 Article ID 908741 10 pageshttpdxdoiorg1011552013908741

Research ArticleThe Mechanisms of Movement Control and Time Estimation inCervical Dystonia Patients

Pavel Filip12 Ovidiu V Lungu345 Daniel J Shaw1 Tomas Kasparek16 and Martin Bareš12

1 Central European Institute of Technology CEITEC MU Behavioral and Social Neuroscience Research GroupMasaryk University 625 00 Brno Czech Republic

2 First Department of Neurology Faculty of Medicine Masaryk University and St Annersquos Teaching Hospital 656 91 BrnoCzech Republic

3 Department of Psychiatry University of Montreal Montreal QC Canada H3C 3T54 Functional Neuroimaging Unit Research Center of the Geriatric Institute Affiliated with the University of MontrealMontreal QC Canada H3C 3T5

5Department of Research Donald Berman Maimonides Geriatric Center Montreal QC Canada H3C 3T56Department of Psychiatry Faculty of Medicine Masaryk University and St Teaching Hospital 625 00 Brno Czech Republic

Correspondence should be addressed to Pavel Filip pvlfilipgmailcom

Received 6 June 2013 Revised 26 August 2013 Accepted 28 August 2013

Academic Editor Mario U Manto

Copyright copy 2013 Pavel Filip et al This is an open access article distributed under the Creative Commons Attribution Licensewhich permits unrestricted use distribution and reproduction in any medium provided the original work is properly cited

Traditionally the pathophysiology of cervical dystonia has been regarded mainly in relation to neurochemical abnormities in thebasal ganglia Recently however substantial evidence has emerged for cerebellar involvement While the absence of neurologicalldquocerebellar signsrdquo in most dystonia patients may be considered at least provoking there are more subtle indications of cerebellardysfunction in complex demanding tasks Specifically given the role of the cerebellum in the neural representation of time in themillisecond range dysfunction to this structure is considered to be of greater importance than dysfunction of the basal ganglia Inthe current study we investigated the performance of cervical dystonia patients on a computer task known to engage the cerebellumnamely the interception of a moving target with changing parameters (speed acceleration and angle) with a simple response(pushing a button)The cervical dystonia patients achieved significantly worse results than a sample of healthy controls Our resultssuggest that the cervical dystonia patients are impaired at integrating incoming visual information with motor responses duringthe prediction of upcoming actions an impairment we interpret as evidence of cerebellar dysfunction

1 Introduction

Cervical dystonia the most frequent adult focal dystonia is asyndrome characterized by involuntary twisting movementsof the head leading ultimately to temporary or constantabnormal postures interfering with voluntary movement [12] Despite over a century of research since its first descriptionin the literature [3] the pathophysiology of this disease stillremains elusive Aberrant activity in the basal ganglia hasbeen noted repeatedly as the main cause of the sustainedcocontraction of opposing agonist and antagonist muscles[2 4 5] Recently however the cerebellummdashfirst noted indystonia pathophysiology over 25 years ago [6]mdashhas receivedconsiderable attention [7ndash9] Neurophysiological [10] andneuroimaging studies [11] showing increase in gray matter

density in cerebellum [12] abnormal cerebellar activation invarious tasks [13ndash15] and increased glucose metabolism incerebellum [16 17] clearly demonstrate its involvement indystonia Furthermore an elegant review of 25 secondarycervical dystonia cases connects the pathophysiology ofcervical dystonia primarily with cerebellar lesions [18]

For a long time the cerebellum has been associatedexclusively with motor functions Increasingly though thecerebellum is implicated in a wide spectrum of differentprocess controls extending far beyond the typical cerebel-lar domain These include for example attention [19 20]associative learning [21] motivation control [22] and mostrelevant to the present study time assessment [23ndash26] Theprecise role of the cerebellum in the representation of time

2 Neural Plasticity

Table 1 Further information about the cervical dystonia patients

No Demographics Time since onset (years) Tremor Dominant head position distortion TWSTRS Treatment Success rateAge Sex

1 61 F 10 Torticollis 15 Botulotoxin 34882 35 M 7 Yes Torticollis 5 Botulotoxin 42283 65 F 15 Laterocollis 4 Botulotoxin 25624 63 F 9 Torticollis 7 Botulotoxin 13405 73 F 32 Laterocollis 10 Botulotoxin 33646 71 M 27 Laterocollis 8 Botulotoxin 22697 63 M 38 Yes Torticollis 18 Botulotoxin 31338 51 F 4 Yes Torticollis 3 Botulotoxin 43069 54 F 7 Yes Laterocollis 14 Botulotoxin 359610 23 M 6 Torticollis 5 Botulotoxin 359611 38 F 12 Yes Torticollis 13 Botulotoxin 450612 45 M 15 Retrocollis 10 Botulotoxin 435213 60 M 27 Laterocollis 15 Botulotoxin 146114 48 M 22 Torticollis 13 Botulotoxin 211415 49 M 13 Torticollis 8 Botulotoxin 422816 33 M 18 Yes Laterocollis 18 Botulotoxin 243817 59 F 13 Laterocollis 7 Botulotoxin 245418 59 M 16 Torticollis 11 Botulotoxin 466019 62 F 13 Torticollis 7 Botulotoxin 299420 41 F 7 Yes Torticollis 10 Botulotoxin 398121 49 M 11 Yes Laterocollis 15 Botulotoxin 279322 50 M 8 Torticollis 6 Botulotoxin 288623 58 M 6 Laterocollis 11 Botulotoxin 416724 60 F 12 Yes Torticollis 18 Botulotoxin 518525 32 F 12 Yes Torticollis 5 Botulotoxin 290126 66 M 6 Laterocollis 4 Botulotoxin 404327 21 F 3 Yes Torticollis 18 Botulotoxin 492328 68 F 4 Torticollis 10 Botulotoxin 248529 62 F 13 Yes Torticollis 13 Botulotoxin 331830 41 F 4 Laterocollis 5 Botulotoxin 2577

and a delineation of basal ganglia function in this respectare still a matter of continuous research [27ndash29] To datethere is evidence of two dissociable neural timing systemsan ldquoautomaticrdquo system involving the cerebellum and linkedclosely to motor networks is responsible for discrete eventtiming in the range of milliseconds [28 30 31] a ldquocognitivelycontrolledrdquo system comprised of basal ganglia and corticalstructures focused on attention and memory requirementsdeals instead with events in the range of seconds [29 32]

In accordance with this distinction we have shown inprevious studies that subjects with severe cerebellar damage[23] or less severe dysfunction of the cerebellum [25] havepoorer performance on tasks requiring motor timing at thesub-second level Interestingly on the very same task patientswith early stages of Parkinsonrsquos disease (PD) did not differ sig-nificantly from healthy controls [25] Since PD is associatedstronglywith basal ganglia dysfunction this is consistentwiththe above-mentioned distinction and other studies focusingon timing in PD [33 34] The current study builds onthis research by investigating the performance of cervical

dystonia patients on this motor-timing task On the basis ofthe aforementioned evidence we assumed some cerebellardysfunction in our sample of cervical dystonia patients Wehypothesized therefore that these patients would performpoorly at this task relative to a healthy control group due todisrupted time estimation in very short intervals

2 Methods and Materials

21 Participants Thirty healthy individuals (15 males meanage = 555 yrs SD = 126 yrs) and 30 primary cervical dystonia(CD) patients (14 males mean age = 520 yrs SD = 1365 yrs)participated in the study All patients showed only symptomsof pure cervical dystoniamdashthere were no further dystoniasigns (for more information see Table 1) The cervical dysto-nia subjects did not suffer from hand tremor nor abnormalupper-arm posture Only patients with no shoulder elevationor a slightly elevated shoulder (maximallymoderate elevationwith 13ndash23 possible movement range) participated in thestudy All subjects were right-handed None of the subjects

Neural Plasticity 3

had history of color blindness According to theMontgomeryand Asberg Depression Rating Scale (MADRS) no subjectssuffered from clinical depression (mean score = 650 SD =685) [35] Prior to testing the patients were scored on theToronto Western Spasmodic Torticollis Rating Scale (meanscore = 102 SD = 464) [36] The patients were recruitedfrom theMovement Disorders Outpatient Clinic at St AnnersquosUniversity Hospital Brno Czech Republic The study wasapproved by the hospitalrsquos Institutional Review Board

22 The Task The subjects performed the same motor-timing computer task as that employed in our earlier studies[23 25] In this task participants are required to press akey with the dominant hand in order to launch a ldquopro-jectilerdquo that will intercept a circular green ldquotargetrdquo objectmoving from the left side of the screen toward the upper-right corner (Figure 1) This projectile is launched from thelower-right corner of the screen and travels at a constantspeed of 200 cms on an upward and unchanging trajectoryParticipants are instructed to launch the projectile at theoptimal time for it to hit the moving target in a prespecifiedstationary and fixed interception zone positioned in theupper-right corner of the screen (Figure 1(a)) Following asuccessful interception or ldquohitrdquo a small explosion animationis produced as a feedback for the subject (Figure 1(b)) In caseof failure no explosion occurs

On each trial the green target is launched from the leftedge of the screen and travelled towards the fixed interceptionzone at three possible angles (0∘ 15∘ and 30∘) relative to thehorizontal plane of the screen It travels in three differentmanners (ie constant velocity deceleration and accelera-tion) and at three different speeds (slow medium and fast)Ergo with all possible combinations of these variables (typespeed and angle) the target can travel in 27 different waysThe green target diameter is 1 cm the projectile diameteris 03 cm Trials were organized into 12 blocks each with apseudorandomized combination of target movement param-eters (type speed and angle) Each particular movementcombination was presented twice on each block with eachblock formed by 54 trials (27 combinations times 2 instances)Therefore each movement combination occurred 24 times(12 blocks times 2 instances) during the whole procedure Theblocks were separated by breaks of 20-second durations Theentire procedure lasted approximately 35 minutes Before thetask subjects underwent one experimental block as practiceWhen performing the task participants were seated 60 cmin front of the 1410158401015840 computer screen No special amendmentsor mechanical supports for the head and arms were usedSubjects feeling discomfort or pain during the task wereexcluded from the final analysis

In addition to the experimental condition describedabove subjects performed two control conditions The first(control condition 1 [CC1]) involved instantaneous intercep-tion of the moving target comparable to the experimentalcondition Participants were required to press the buttonas soon as the target reached the interception zone whichwas marked by a pink crosshair (Figure 1(c)) In this casesubjects were not required to estimate the travel time of the

projectile in other words this condition tested the ability ofthe subjects to judge the temporal characteristics of the targetunder less demanding circumstances The second controlcondition (CC2) involved the detection of the target colorchange Here the participants were required to press thebutton as quickly as possible when themoving target changedcolor from green to red (Figure 1(d)) The color changeoccurred randomly along its trajectory In this condition wetested simple reaction time that required accurate pursuitof the target along its trajectory but no estimation of targetmovement The subjects were shown explicitly the transitionfrom green and red targets in advance and asked if they wereable to detect accurately the color change

23 Data Analysis The variables of interest were the hit ratio(ie the number of successful hits relative to the total numberof trials) across the different movement combinations (iespeed angle and type) the total number of hits and early andlate errors (ie subjects pressing the button before or afterthe target entered the interception zone) and the responsetime (RT) In order to use parametric statistical techniquesrequiring a normal distribution for the hit ratio (normally abinary variable in each trial) we computed the percentage ofhits for each subject and for each trial type in each blockand we then averaged these values across blocks Whencomparing the number of hits and early and late errors weemployed nonparametric techniques namely we employedthe Chi-square test to compare the distribution of early andlate errors between the control group and the patient groupGiven that the outcome of an individual trial (hit early errorand late error) may be influenced by the outcome obtainedin the previous trial we performed a trial-by-trial analysisto determine the extent to which subjects were able to usetheir very last experience (the previous trial) to improve theirperformance in the current trial In this case we used theChi-square test and the Cramerrsquos 119881 and phi coefficient (acorrection of Chi-square as a function of the number of casesconsidered)

The task was designed to produce varying levels ofdifficulty Specifically the individual combinations of vari-ables lead to different time windows where a successfulinterception was possible (in the range of about 50 to 175ms)the shorter the time interval to press the button the moredifficult the task for example higher target speeds weremoredifficult to intercept Therefore we expected higher hit ratiosfor trials with wider compared with shorter time windowsThe effects of the movement parameter combinations on thehit ratio were assessed using a general linear model analysis(GLM) Finally we compared the hit ratio between blocks 1ndash6 and blocks 7ndash12 to evaluate possible learning effects duringthe course of the experiment

All analyses were performed in SPSS (SPSS Inc ChicagoIL USA)

3 Results

In the following analyses we have excluded the ldquoanglerdquomovement parameter since it had been proven to be of no

4 Neural Plasticity

(a) (b)

(c) (d)

Figure 1 The task and experimental conditions (a) The main interception task The green ball moves from the left side of the screen to theinterception zone in the upper right corner of the screen (as for the position corresponding to the pink cross square in Figure 1(c)) The blueldquogunrdquo in the lower right corner fires a ldquoprojectilerdquo travelling at a constant speed to intercept the green ball (b) Successful hit If the ball isintercepted by the projectile both objects explode In case of miss there is no animation (c) Control condition 1There is no projectile in thiscondition The subject is supposed to press the button at the very moment the green ball reaches the interception zone marked by the crossinside the pink square If the subject is successful the ball explodes (d) Control condition 2 the green ball once again moves from the leftside of the screen to the interception area However there is no gunprojectile or pink interception square The subject is supposed to pressthe button as soon as the ball changes its color from green to red

significant effect on hit ratio or reaction time [23 25] Wedid not notice any fatigue of motor or cognitive nature in thesubjects

31 Reaction Time In the control condition CC2 we founda significant difference in the reaction time to color changebetween the patient group (mean = 34184ms SD = 5740)and the healthy group (mean = 28872ms SD = 3210 [F

158

= 1938 119875 lt 00001]) As shown in Figure 2(a) this revealedthat healthy controls were faster in the task than the patients

Furthermore the GLM analysis to determine the maineffect of target movement type showed significant interac-tions between the independent factors (group type of move-ment and speed [F

2116= 1424 119875 lt 0001]) As Figure 2(b)

depicts reaction times were slower for constant speed thanduring acceleration or deceleration trials This interestingfinding could point to the fact that changes in color are easierto spot when the target movement is variable relative towhen it is constant Even if this is seemingly counterintuitiveit is consistent with our previous results when comparingthe reaction time to color change in moving and stationarytargets [25] We had found that moving targets are easierand quicker to react to possibly suggesting that following amoving target increases the attention of the subject resultingin faster responses There was no interaction effect however

which indicates that the two groups are affected similarly bythe kinematics of the target

32 Hit Ratios The first control condition (CC1) wasdesigned to eliminate the need of complex estimationdepending on the movement types (CC1 see Figure 1) Weperformed a GLM analysis to compare the patient group withthe control group The dependent variable was the hit ratioand the independent factorswere the group (cervical dystoniapatients and healthy controls) movement type (accelerationdeceleration and constant) and speed (fast medium andslow) We observed a significant difference in the hit ratiobetween the healthy control group (mean = 071 SD = 004)and the patients (mean = 057 SD 018 119875 lt 0001 seeFigure 3) The three-way interaction term was not significant(F4116

= 160 119875 gt 005) however indicating that the successrate was not affected differentially by the movement type orspeed of the target across groups in contrast to themain task

In both groups performance in CC1 was superior toperformance in the main task (F

158= 5436 119875 lt 0001

see Figure 3) This is an expected result since the main taskis associated with far more complex temporal estimation oftargetmovement parameters Indeed even in the control con-dition patients had lower hit ratios than healthy individuals(F158

= 2287 119875 lt 0001)

Neural Plasticity 5

0

50

100

150

200

250

300

350

400

Control group Dystonia group

Mea

n re

actio

n tim

e in

the c

ontro

lco

nditi

on2

(ms95

C

I)

(a)

Control groupDystonia group

240

260

280

300

320

340

360

380

Constant Acceleration Deceleration

Mea

n re

actio

n tim

e in

the c

ontro

lco

nditi

on2

(ms95

S

EM)

(b)

Figure 2 Reaction times (a) Mean reaction time in the control condition 2 the reaction time of the patients was significantly slower thanthe reaction time in the control group (b) Mean reaction times as a function of movement type in two groups These results show that evenif the patient group was generally slower (Figure 2) the reaction time was not affected by other parameters of the moving target (speedacceleration) in a different way This finding excludes the eventuality that the differences between the groups in the other main parametersmay be due to oculomotor difficulties in the cervical dystonia group [37]

0

01

02

03

04

05

06

07

08


Mai

n hi

t rat

io in

the m

ain

task

and

cont

rol c

ondi

tion1

(SEM

)

Performance of the two groups in the controltask 1 and the main task

Control task 1

Main task

Figure 3 Performance in the main task and the control task 1

A comparison of performance in the first and secondhalf of the task revealed a significant difference in hit ratiosin both groups indicating that the participants improvedtheir performance over time (controls F

129= 587 119875 lt

005 patients F129

= 527 119875 lt 005) We observed nosignificant interaction between the two groups (F

158= 019

119875 gt 005) indicating that performance changed similarly inboth patients and healthy controls over time

Regarding the movement parameters there was a sig-nificant effect of both movement type and speed on the hitratio in both groups (Figure 4) Overall the increase in targetspeed led to a decrease of hit ratio both in healthy (F

258=

1558 119875 lt 0001) and in cervical dystonia patients group

(F258

= 1628 119875 lt 0001) Similarly the deceleration andconstant movements of the target lead to higher hit ratiosthan when the target was accelerating in both groups (F

258

= 7796 119875 lt 0001 for controls and F258

= 7729 119875 lt 0001for patients) However there was also a significant interactionbetween the speed and type of movement in each group(F4116


= 2872119875 lt 0001 for patients)This effect indicated that hit ratio wasinversely related to speed when target moved with constantand accelerating speed whereas this effect was reversed fortargets with decelerating speeds (Figure 4)

A detailed analysis of the hit rates revealed that the hitratio distribution in the cervical dystonia group was muchwider than that of the healthy controls (Figure 5) Based onthis distribution we classified the patient group into twosubgroups according to a threshold set at the lower limitof the healthy group performance Group 1 with a hit ratiocomparable to the healthy controls (119899 = 15 patients) andGroup 2 with lower hit ratios (119899 = 15 patients) We analyzedthe individual characteristics in both patient subgroups Theparameters we focused on were age sex disease severity(TWSTRS score) dystonia clinical presentation (head tremoror deviation) length of the disease and age at which the dis-ease manifested None of these factors differed significantlybetween the groups however (119875 gt 02) Taken togetherthese results imply that the presumed cerebellar deficit incervical dystonia patientsmdashregardless of severitymdashleads toworse performance in time estimation in general In somepatients however this ability is impaired only slightly relativeto the healthy population while in others the dysfunctionmanifests as a far greater ldquodisabilityrdquo

33 Early and Late Errors We also examined the distributionof errors to determine the characteristics of unsuccessful

6 Neural Plasticity

0

015

03

045

06


Mea

n hi

t rat

io (9

5

CI)

Type of target movement

Healthy controls

FastMediumSlow

(a)

0

015

03

045

06

Mea

n hi

t rat

io (9

5

CI)

Constant Acceleration DecelerationType of target movement

FastMediumSlow

CD patients

(b)

Figure 4 Mean hit ratio as a function of movement type and speed of the target in the main task

Num

ber o

f sub

ject

s with

resp

ectiv

e hit

ratio

24

22

20

18

16

14

12

10

8

6

4

2


010000 200 300 400 500 600

()

Figure 5 Histogram of hit ratios distributions in the patient groupand the control group showing wider distribution curve for thecervical dystonia patients

reactions that is whether the subjects were too early or toolate in general to intercept the target The two types of errorsseemed approximately equally distributed in the early and latespectrum in both subject groups (see Figure 6(a)) the ratioof earlylate errors was 41735827 in the cervical dystoniagroup and 43845616 in the control group Nonparametrictests indicate that these two groups differed in the distributionof early and late errors however with patients making morelate than early errors (Cramerrsquos 119881 and phi coefficient = 021119875 lt 001)

34 Trial by Trial Adaptation Figure 6(b) illustrates thedistribution of early and late errors according to the per-formance in the previous trial We determined whether thefeedback from the previous trial had a significant impact onthe performance in the current trialWehypothesized that thesubjects could benefit from the outcome of the previous trialby adjusting their motor timing in the current trial Analysesrevealed a significant effect of the preceding trial outcomeon the distribution of early and late errors and hits in boththe healthy control and patient group (Cramerrsquos 119881 and phicoefficient = 007 119875 lt 001 and 008 119875 lt 001 resp) Therewere however slightly different qualitative outcomes whencomparing healthy subjects and cervical dystonia patientsThe residual standardized scores indicate that the success inthe previous trial increased the hit rate on the current trialand reduced the rate of early errors in both the patient andthe control group By the same token patients had more lateerrors and fewer hits in the current trial after a late error inthe preceding trial whereas for the healthy group late errorsdid not lead to a significant change in hit ratio

35 Hit Ratio and the Time Window As previously men-tioned the temporal window within which a successfuloutcome is possible is an indication of the task difficultythe longer this time interval the greater the likelihood thatsubjects could execute the movement successfully We com-puted the correlation between windowwidth and hit ratio forboth the healthy control and patient group and then com-pared these correlation coefficients between them Figure 7illustrates the relationship between hit ratio (percentage)and window width (in milliseconds) for both groups Whilewe obtained a significantly positive correlation coefficientfor both groups (a higher hit ratio corresponded to widerwindow width) we did not find any significant differencebetween them In fact the hit ratios of two groups were

Neural Plasticity 7

2725 2510

34704271

38053218

000

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000

Dystonia group Control group

All

tria

ls (

)

Late errorsHitsEarly errors

Axis title

(a)

2359

1960

2464

4207

4490

3897

3434

3550

3639

Early error

Hits

Late error

Current trial

Prev

ious

tria

l

Control group

Early errorHitsLate error


2792

2153

2436

3370

3923

2823

3838

3923

4741

Current trial

Dystonia group

Early error

Hits

Late error

Prev

ious

tria

l

(b)

Figure 6 Error distribution (a) Distribution of early and late errors in healthy subjects and cervical dystonia patients (b) Trial-by-trialdistribution of hits and errors The effect of feedback and the impact of the success rate in the previous trial on the hit ratio and earlylateerrors distribution In the graph the error type distribution is presented as a function of the previous trial result

affected similarly by the window width indicating that theslopes were similar (F

1536= 0411 119875 gt 005 sim20 change

in hit ratio for 100ms window width in each group) Alsothere was greater variability among patients while windowwidth explained 317 of the variability in hit ratio amonghealthy individuals this factor explained only 193 of thevariability among patients This finding may be related to theheterogeneity of the disease manifestation among patients

4 Discussion

This current study investigatedwhether patients with cervicaldystonia exhibit impaired performance on a motor-timingtask known to require cerebellar input Using a motor-timingcomputer task we reveal the following pattern of resultsthe principal finding is a lower hit ratio of the patients incomparison to the control group in a specific motor-timing

task in association with significantly slower reaction timeto a simple color change in the dystonia group On theother hand the ability to take advantage of the wider timewindow was comparable in cervical dystonia patients andthe control group Likewise there was a significant effect ofboth movement type and speed on the success rate in thecontrol group and cervical dystonia patients not showinga prominent difference between those two groups Visual-motor integration at the millisecond range which is believedto be a substantial constituent of cerebellum responsibilities[28 30 31] is of crucial importance for success on this taskAlthough the cerebellum is not noted traditionally as one ofthe major sources of dystonia development interest towardsthis neuronal structure has increased recently [8 9 38] withits role in the pathophysiology of the dystonia suggestedby animal models [7 39 40] imaging studies [11 41 42]neurophysiological studies [10] and even secondary cervicaldystonia analyses [18 43] Our findings demonstrate that the

8 Neural Plasticity

20

40

60

80

25 50 75 100 125 150 175

Hit

ratio

Time window

Dystonia groupControl group


0

Figure 7 The effect of response window width and hit ratioThe relationship between hit ratio (percentage) and window width(milliseconds) for the two groups

temporal estimation of target parameters and requirementsfor a quick motor response posed a fundamental problemfor the cervical dystonia patients This is consistent withthe notion that the cerebellum may also be affected by thisdisease

It remains to be determined whether the cerebellumstands at the very pathophysiology origin of cervical dystoniaor it forms only a component of a complex network compen-sating for dysfunction of other parts of the brain Neverthe-less our data indicate that cervical dystonia subjects showdecreased performance on a task in which the cerebellumhas been shown previously to play an essential role [23ndash25]Our results are also consistent with the current theories ofa discrete event timing network responsible for time inter-pretation and assessment in the millisecond range located incerebellum [28 30 31]The cerebellum is hypothesized to be amajor node in timing tasks with noncontinuous movements[44 45] a function fitting undeniably with the spirit of ourtask The cerebellum hosts a vast convergence of mossy fiberinputs [46] and it is known to be involved in the synthesisof information from virtually all brain areas As such thecerebellar structure is well situated for complex predictionsof an integrative character providing crucial data for furtherprocessing by the cerebral cortex [47 48]

Of course the nature of our study makes it impossible toassess complexly the extent of eventual cerebellar dysfunc-tion this network node is associated with a wide spectrum offunctions of whichwewere interested specifically in only onethat is movement timing Performance on other tasks involv-ing cerebellum function such as attention [19 20] associativelearning [21] and motivation control [22] remains to beinvestigated This leaves a window for further research intothe association between the cerebellum and dystonia open Inparticular imaging studies of cerebellum connectivity and its

eventual functional abnormities in cervical dystoniawill be ofgreat importance Nevertheless our observation of decreasedperformance in a timing task in patients with no clearneurological cerebellar signs (eg ataxia and dysmetria) couldbe attributed to abnormal cerebellar activity in dystoniamdashspecifically a gain of cerebellar function similar to epilepsyin the cerebral cortex [39 49] This very abnormity mightbe related closely to cortical excitability disorder in cervicaldystonia patients [50] leading possibly to typical cervicaldystonia symptoms

Of course it would be inappropriate to dismiss com-pletely the contribution from the basal ganglia which is bothan important pathophysiological nodewith direct connectionto dystonia in general and an essential contributor to motortiming In our previous study however dysfunction of thebasal ganglia a structure noted particularly in attention andmemory tasks in the range of seconds [29 32 51] did not leadto lower performance in our motor-timing task [25] Patientswith Parkinsonrsquos disease despite their hypokinesia per-formed at levels comparable to healthy subjects In contrastpatients with essential tremor and spinocerebellar ataxiadisorders connected with cerebellum dysfunctions showedcomparable problems in time estimation and movementanalysis Moreover the late error ratio in spinocerebellarataxia patients was increased in comparison with healthycontrolsmdasha trend observed also in cervical dystonia patientsAnother important observation in our study is that thecervical dystonia patients and the spinocerebellar ataxiapatients in addition to poor performance had abnormaltiming adjustment

Furthermore we should not overlook the possibility thatthe impaired performance in cervical dystonia patients wascaused by oculomotor problems Should this be true thedistribution of errors should shift in favor of late errors inthe cervical dystonia patientsThis was not the case howeverMoreover the increasing speed and accelerationdecelerationposing higher demands for the visuomotor abilities of thesubject that is the shorter time window influenced cervicaldystonia patients to the same extent as healthy controls Wealso observed that the reaction time was not affected by theparameters of the moving target (ie speed or acceleration)differently between the two groups This rejects further thepossibility that differences between the groups arise fromoculomotor difficulties in the cervical dystonia group

Lastly the slight abnormal shoulder posture of somecervical dystonia subjects might be considered to contributeto our pattern of findings We find this unlikely howeveras the task is designed specifically to minimize the aspectof unnatural posture Subjects did not use the whole limbor bigger limb segments to intercept the target they wererequiredmerely to push the response buttonwith their finger

Our results contribute to our understanding of boththe role of the cerebellum dystonia pathophysiology andits function in general A growing body of research in thisformer area implicates an increasing number of defectiveneural network nodes in this disease [52 53] thus challengingthe traditional view of dystonia Indeed although it is clearthat basal ganglia play a significant role in dystonia patho-physiology our findings pointing to cerebellum dysfunction

Neural Plasticity 9

together with the results of clinical and animal studies [3954 55] associate dystonia with defective interactions amongdifferent components of the motor network rather than thedysfunction of any one node Standing on the doorstep of thefirst real complex insight and understanding of cerebellumand the central nervous system itself backed up by ever-advancing technological possibilities we cannot afford tooverlook this slowly crystallizing role of the cerebellum in thepathophysiology of cervical dystonia

Conflict of Interests

There are no potential conflict of interests regarding thispaper and no financial or personal relationships that mightbias this work

Acknowledgments

This work was supported by the ldquoCEITEC-Central EuropeanInstitute of Technologyrdquo Project (CZ1051100020068)from the European Regional Development Fund and byMinistry of Health of the Czech RepublicMinistry ofHealthrsquos Departmental Research and Development ProgramIII (2010ndash2015) NT13437 Ovidiu Lungu is supported byMaimonides Medical FoundationThe authors wish to thankIvica Husarova MD Eduard Minks MD and Hana Stre-itova MD for their contribution in referring the patientsand useful comments on the paper

References

[1] S Fahn S B Bressman and C D Marsden ldquoClassification ofdystoniardquo Advances in Neurology vol 78 pp 1ndash10 1998

[2] A Albanese K Bhatia S B Bressman et al ldquoPhenomenologyand classification of dystonia a consensus updaterdquo MovementDisorders vol 28 no 7 pp 863ndash873 2013

[3] H Oppenheim ldquoUber eine eigenartige kramotkrankheit deskindlichen und jugendlichen alters (dysbasia lordotica progres-siva dystonia musculorum deformans)rdquo Neurologie Central-blatt vol 30 pp 1090ndash1107 1911

[4] J L Vitek ldquoPathophysiology of dystonia a neuronal modelrdquoMovement Disorders vol 17 no 3 pp S49ndashS62 2002

[5] M R DeLong andTWichmann ldquoCircuits and circuit disordersof the basal gangliardquoArchives of Neurology vol 64 no 1 pp 20ndash24 2007

[6] N A Fletcher R Stell A E Harding and C D MarsdenldquoDegenerative cerebellar ataxia and focal dystoniardquo MovementDisorders vol 3 no 4 pp 336ndash342 1988

[7] M Vidailhet D Grabli and E Roze ldquoPathophysiology ofdystoniardquo Current Opinion in Neurology vol 22 no 4 pp 406ndash413 2009

[8] A Sadnicka B S Hoffland K P Bhatia B P van de Warren-burg and M J Edwards ldquoThe cerebellum in dystoniamdashhelp orhindrancerdquo Clinical Neurophysiology vol 123 no 1 pp 65ndash702012

[9] P Filip O V Lungu and M Bares ldquoDystonia and the cerebel-lum a new field of interest in movement disordersrdquo ClinicalNeurophysiology vol 124 no 7 pp 1269ndash1276 2013

[10] J Liepert T Kucinski O Tuscher F Pawlas T Baumer andCWeiller ldquoMotor cortex excitability after cerebellar infarctionrdquoStroke vol 35 no 11 pp 2484ndash2488 2004

[11] M Obermann C Vollrath A de Greiff et al ldquoSensory disin-hibition on passive movement in cervical dystoniardquoMovementDisorders vol 25 no 15 pp 2627ndash2633 2010

[12] B Draganski C Thun-Hohenstein U Bogdahn J Winklerand A May ldquolsquoMotor circuitrsquo gray matter changes in idiopathiccervical dystoniardquoNeurology vol 61 no 9 pp 1228ndash1231 2003

[13] H Kadota Y Nakajima M Miyazaki et al ldquoAn fMRI study ofmusicians with focal dystonia during tapping tasksrdquo Journal ofNeurology vol 257 no 7 pp 1092ndash1098 2010

[14] X-Y Hu L Wang H Liu and S-Z Zhang ldquoFunctionalmagnetic resonance imaging study of writerrsquos cramprdquo ChineseMedical Journal vol 119 no 15 pp 1263ndash1271 2006

[15] R S Baker A H Andersen R J Morecraft and C DSmith ldquoA functional magnetic resonance imaging study inpatients with benign essential blepharospasmrdquo Journal ofNeuro-Ophthalmology vol 23 no 1 pp 11ndash15 2003

[16] M Niethammer M Carbon M Argyelan and D EidelbergldquoHereditary dystonia as a neurodevelopmental circuit disorderevidence from neuroimagingrdquo Neurobiology of Disease vol 42no 2 pp 202ndash209 2011

[17] D Alvarez-Fischer M Grundmann L Lu et al ldquoProlongedgeneralized dystonia after chronic cerebellar application ofkainic acidrdquo Brain Research vol 1464 pp 82ndash88 2012

[18] M S LeDoux and K A Brand ldquoSecondary cervical dystoniaassociatedwith structural lesions of the central nervous systemrdquoMovement Disorders vol 18 no 1 pp 60ndash69 2003

[19] E Perlov L Tebarzt van Elst M Buechert et al ldquoH1-MR-spectroscopy of cerebellum in adult attention deficithyper-activity disorderrdquo Journal of Psychiatric Research vol 44 no 14pp 938ndash943 2010

[20] J C Bledsoe M Semrud-Clikeman and S R Pliszka ldquoNeu-roanatomical and neuropsychological correlates of the cerebel-lum in children with attention-deficithyperactivity disorder-combined typerdquo Journal of the American Academy of Child andAdolescent Psychiatry vol 50 no 6 pp 593ndash601 2011

[21] D Timmann J Drepper M Frings et al ldquoThe human cerebel-lum contributes to motor emotional and cognitive associativelearning A reviewrdquo Cortex vol 46 no 7 pp 845ndash857 2010

[22] D J Bauer A L Kerr and R A Swain ldquoCerebellar dentatenuclei lesions reduce motivation in appetitive operant condi-tioning and open field explorationrdquo Neurobiology of Learningand Memory vol 95 no 2 pp 166ndash175 2011

[23] M Bares O Lungu T Liu T Waechter C M Gomez andJ Ashe ldquoImpaired predictive motor timing in patients withcerebellar disordersrdquo Experimental Brain Research vol 180 no2 pp 355ndash365 2007

[24] M Bares O V Lungu T Liu T Waechter C M Gomez andJ Ashe ldquoThe neural substrate of predictive motor timing inspinocerebellar ataxiardquo The Cerebellum vol 10 no 2 pp 233ndash244 2011

[25] M Bares O V Lungu I Husarova and T Gescheidt ldquoPre-dictive motor timing performance dissociates between earlydiseases of the cerebellum and parkinsonrsquos diseaserdquo Cerebellumvol 9 no 1 pp 124ndash135 2010

[26] I Husarova O V Lungu RMarecek et al ldquoFunctional imagingof the cerebellum and basal ganglia during predictive motortiming in early parkinsonrsquos diseaserdquo Journal of Neuroimaging2011

10 Neural Plasticity

[27] D L Harrington R R Lee L A Boyd S Z Rapcsak andR T Knight ldquoDoes the representation of time depend on thecerebellum Effect of cerebellar strokerdquo Brain vol 127 no 3 pp561ndash574 2004

[28] J T Coull R-K Cheng and W H Meck ldquoNeuroanatomicaland neurochemical substrates of timingrdquo Neuropsychopharma-cology vol 36 no 1 pp 3ndash25 2011

[29] D L Harrington J L Zimbelman S C Hinton and S M RaoldquoNeural modulation of temporal encoding maintenance anddecision processesrdquo Cerebral Cortex vol 20 no 6 pp 1274ndash1285 2010

[30] G Koch M Oliveri S Torriero S Salerno E L Gerfo andC Caltagirone ldquoRepetitive TMS of cerebellum interferes withmillisecond time processingrdquo Experimental Brain Research vol179 no 2 pp 291ndash299 2007

[31] E DrsquoAngelo and C I de Zeeuw ldquoTiming and plasticity inthe cerebellum focus on the granular layerrdquo Trends in Neuro-sciences vol 32 no 1 pp 30ndash40 2009

[32] P A Lewis and R C Miall ldquoDistinct systems for automaticand cognitively controlled time measurement evidence fromneuroimagingrdquo Current Opinion in Neurobiology vol 13 no 2pp 250ndash255 2003

[33] Q J Almeida J S Frank E A Roy A E Patla and M S JogldquoDopaminergic modulation of timing control and variability inthe gait of Parkinsonrsquos diseaserdquoMovement Disorders vol 22 no12 pp 1735ndash1742 2007

[34] M Jahanshahi C R G Jones J Zijlmans et al ldquoDopaminergicmodulation of striato-frontal connectivity duringmotor timingin Parkinsonrsquos diseaserdquo Brain vol 133 no 3 pp 727ndash745 2010

[35] S A Montgomery and M Asberg ldquoA new depression scaledesigned to be sensitive to changerdquo The British Journal ofPsychiatry vol 134 no 4 pp 382ndash389 1979

[36] E S Consky and A E Lang ldquoClinical assessments of patientswith cervical dystoniardquo Neurological Disease and Therapy vol25 p 211 1994

[37] M P Grant R J Leigh S H Seidman D E Riley andJ P Hanna ldquoComparison of predictable smooth ocular andcombined eye-head tracking behaviour in patients with lesionsaffecting the brainstem and cerebellumrdquo Brain vol 115 no 5pp 1323ndash1342 1992

[38] L Avanzino and G Abbruzzese ldquoHow does the cerebellumcontribute to the pathophysiology of dystoniardquo Basal Gangliavol 2 no 4 pp 231ndash235 2012

[39] R S Raike H A Jinnah and E J Hess ldquoAnimal models ofgeneralized dystoniardquo NeuroRx vol 2 no 3 pp 504ndash512 2005

[40] H A Jinnah E J Hess M S LeDoux N SharmaM G Baxterand M R DeLong ldquoRodent models for dystonia researchcharacteristics evaluation and utilityrdquo Movement Disordersvol 20 no 3 pp 283ndash292 2005

[41] M Carbon M F Ghilardi M Argyelan V Dhawan S BBressman and D Eidelberg ldquoIncreased cerebellar activationduring sequence learning inDYT1 carriers an equiperformancestudyrdquo Brain vol 131 no 1 pp 146ndash154 2008

[42] R Opavsky P Hlustık P Otruba and P Kanovsky ldquoSensori-motor network in cervical dystonia and the effect ofbotulinumtoxin treatment a functional MRI studyrdquo Journal of the Neuro-logical Sciences vol 306 no 1 pp 71ndash75 2008

[43] V C Extremera J Alvarez-Coca G A Rodrıguez J MPerez J L R de Villanueva and C P Dıaz ldquoTorticollis is ausual symptom in posterior fossa tumorsrdquo European Journal ofPediatrics vol 167 no 2 pp 249ndash250 2008

[44] RMC Spencer T VerstynenM Brett andR Ivry ldquoCerebellaractivation during discrete and not continuous timed move-ments an fMRI studyrdquo NeuroImage vol 36 no 2 pp 378ndash3872007

[45] H Loras H Sigmundsson J B Talcott F Ohberg and A KStensdotter ldquoTiming continuous or discontinuous movementsacross effectors specified by different pacing modalities andintervalsrdquo Experimental Brain Research vol 220 no 3-4 pp335ndash347 2012

[46] J R de Gruijl P Bazzigaluppi M T G de Jeu and C I deZeeuw ldquoClimbing fiber burst size and olivary sub-thresholdoscillations in a network settingrdquo PLoS Computational Biologyvol 8 no 12 Article ID e1002814 2012

[47] M-U Manto ldquoOn the cerebello-cerebral interactionsrdquo Cerebel-lum vol 5 no 4 pp 286ndash288 2006

[48] M Molinari M G Leggio and M H Thaut ldquoThe cerebellumand neural networks for rhythmic sensorimotor synchroniza-tion in the human brainrdquo Cerebellum vol 6 no 1 pp 18ndash232007

[49] D Eidelberg J R Moeller A Antonini et al ldquoFunctional brainnetworks in DYT1 dystoniardquo Annals of Neurology vol 44 no 3pp 303ndash312 1998

[50] P Kanovsky M Bares H Streitova H Klajblova P Danieland I Rektor ldquoAbnormalities of cortical excitability and corticalinhibition in cervical dystonia evidence from somatosensoryevoked potentials and paired transcranial magnetic stimulationrecordingsrdquo Journal of Neurology vol 250 no 1 pp 42ndash502003

[51] J-C Dreher and J Grafman ldquoThe roles of the cerebellum andbasal ganglia in timing and error predictionrdquo European Journalof Neuroscience vol 16 no 8 pp 1609ndash1619 2002

[52] M Hallett ldquoPathophysiology of dystoniardquo Journal of NeuralTransmission Supplement no 70 pp 485ndash488 2006

[53] N Murase J C Rothwell R Kaji et al ldquoSubthreshold low-frequency repetitive transcranial magnetic stimulation over thepremotor cortex modulates writerrsquos cramprdquo Brain vol 128 no1 pp 104ndash115 2005

[54] V K Neychev X Fan V I Mitev E J Hess and H A JinnahldquoThe basal ganglia and cerebellum interact in the expression ofdystonic movementrdquo Brain vol 131 no 9 pp 2499ndash2509 2008

[55] V K Neychev R E Gross S Lehericy E J Hess and H A Jin-nah ldquoThe functional neuroanatomy of dystoniardquo Neurobiologyof Disease vol 42 no 2 pp 185ndash201 2011

Submit your manuscripts athttpwwwhindawicom

Neurology Research International

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Alzheimerrsquos DiseaseHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

International Journal of

ScientificaHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


BioMed Research International


Research and TreatmentSchizophrenia

The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014


Neural Plasticity


Parkinsonrsquos Disease


Research and TreatmentAutism

Sleep DisordersHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Neuroscience Journal

Epilepsy Research and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Psychiatry Journal


Computational and Mathematical Methods in Medicine

Depression Research and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014


Brain ScienceInternational Journal of

StrokeResearch and TreatmentHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Neurodegenerative Diseases


Journal of

Cardiovascular Psychiatry and NeurologyHindawi Publishing Corporationhttpwwwhindawicom Volume 2014

2 Neural Plasticity

Table 1 Further information about the cervical dystonia patients

No Demographics Time since onset (years) Tremor Dominant head position distortion TWSTRS Treatment Success rateAge Sex

1 61 F 10 Torticollis 15 Botulotoxin 34882 35 M 7 Yes Torticollis 5 Botulotoxin 42283 65 F 15 Laterocollis 4 Botulotoxin 25624 63 F 9 Torticollis 7 Botulotoxin 13405 73 F 32 Laterocollis 10 Botulotoxin 33646 71 M 27 Laterocollis 8 Botulotoxin 22697 63 M 38 Yes Torticollis 18 Botulotoxin 31338 51 F 4 Yes Torticollis 3 Botulotoxin 43069 54 F 7 Yes Laterocollis 14 Botulotoxin 359610 23 M 6 Torticollis 5 Botulotoxin 359611 38 F 12 Yes Torticollis 13 Botulotoxin 450612 45 M 15 Retrocollis 10 Botulotoxin 435213 60 M 27 Laterocollis 15 Botulotoxin 146114 48 M 22 Torticollis 13 Botulotoxin 211415 49 M 13 Torticollis 8 Botulotoxin 422816 33 M 18 Yes Laterocollis 18 Botulotoxin 243817 59 F 13 Laterocollis 7 Botulotoxin 245418 59 M 16 Torticollis 11 Botulotoxin 466019 62 F 13 Torticollis 7 Botulotoxin 299420 41 F 7 Yes Torticollis 10 Botulotoxin 398121 49 M 11 Yes Laterocollis 15 Botulotoxin 279322 50 M 8 Torticollis 6 Botulotoxin 288623 58 M 6 Laterocollis 11 Botulotoxin 416724 60 F 12 Yes Torticollis 18 Botulotoxin 518525 32 F 12 Yes Torticollis 5 Botulotoxin 290126 66 M 6 Laterocollis 4 Botulotoxin 404327 21 F 3 Yes Torticollis 18 Botulotoxin 492328 68 F 4 Torticollis 10 Botulotoxin 248529 62 F 13 Yes Torticollis 13 Botulotoxin 331830 41 F 4 Laterocollis 5 Botulotoxin 2577

and a delineation of basal ganglia function in this respectare still a matter of continuous research [27ndash29] To datethere is evidence of two dissociable neural timing systemsan ldquoautomaticrdquo system involving the cerebellum and linkedclosely to motor networks is responsible for discrete eventtiming in the range of milliseconds [28 30 31] a ldquocognitivelycontrolledrdquo system comprised of basal ganglia and corticalstructures focused on attention and memory requirementsdeals instead with events in the range of seconds [29 32]

In accordance with this distinction we have shown inprevious studies that subjects with severe cerebellar damage[23] or less severe dysfunction of the cerebellum [25] havepoorer performance on tasks requiring motor timing at thesub-second level Interestingly on the very same task patientswith early stages of Parkinsonrsquos disease (PD) did not differ sig-nificantly from healthy controls [25] Since PD is associatedstronglywith basal ganglia dysfunction this is consistentwiththe above-mentioned distinction and other studies focusingon timing in PD [33 34] The current study builds onthis research by investigating the performance of cervical

dystonia patients on this motor-timing task On the basis ofthe aforementioned evidence we assumed some cerebellardysfunction in our sample of cervical dystonia patients Wehypothesized therefore that these patients would performpoorly at this task relative to a healthy control group due todisrupted time estimation in very short intervals

2 Methods and Materials

21 Participants Thirty healthy individuals (15 males meanage = 555 yrs SD = 126 yrs) and 30 primary cervical dystonia(CD) patients (14 males mean age = 520 yrs SD = 1365 yrs)participated in the study All patients showed only symptomsof pure cervical dystoniamdashthere were no further dystoniasigns (for more information see Table 1) The cervical dysto-nia subjects did not suffer from hand tremor nor abnormalupper-arm posture Only patients with no shoulder elevationor a slightly elevated shoulder (maximallymoderate elevationwith 13ndash23 possible movement range) participated in thestudy All subjects were right-handed None of the subjects

Neural Plasticity 3









3 Results


4 Neural Plasticity

(a) (b)

(c) (d)




158



2116= 1424 119875 lt 0001]) As Figure 2(b)






158= 5436 119875 lt 0001


= 2287 119875 lt 0001)

Neural Plasticity 5

0

50

100

150

200

250

300

350

400


Mea

n re

actio

n tim

e in

the c

ontro

lco

nditi

on2

(ms95

C

I)

(a)


240

260

280

300

320

340

360

380


Mea

n re

actio

n tim

e in

the c

ontro

lco

nditi

on2

(ms95

S

EM)

(b)


0

01

02

03

04

05

06

07

08


Mai

n hi

t rat

io in

the m

ain

task

and

cont

rol c

ondi

tion1

(SEM

)


Control task 1

Main task



129= 587 119875 lt

005 patients F129


158= 019



258=


(F258


258







6 Neural Plasticity

0

015

03

045

06


Mea

n hi

t rat

io (9

5

CI)


Healthy controls

FastMediumSlow

(a)

0

015

03

045

06

Mea

n hi

t rat

io (9

5

CI)


FastMediumSlow

CD patients

(b)


Num

ber o

f sub

ject

s with

resp

ectiv

e hit

ratio

24

22

20

18

16

14

12

10

8

6

4

2


010000 200 300 400 500 600

()





Neural Plasticity 7

2725 2510

34704271

38053218

000

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000


All

tria

ls (

)


Axis title

(a)

2359

1960

2464

4207

4490

3897

3434

3550

3639

Early error

Hits

Late error

Current trial

Prev

ious

tria

l

Control group



2792

2153

2436

3370

3923

2823

3838

3923

4741

Current trial

Dystonia group

Early error

Hits

Late error

Prev

ious

tria

l

(b)



1536= 0411 119875 gt 005 sim20 change


4 Discussion



8 Neural Plasticity

20

40

60

80

25 50 75 100 125 150 175

Hit

ratio

Time window



0










Neural Plasticity 9




Acknowledgments


References





































































Neural Plasticity










Psychiatry Journal









Journal of


Neural Plasticity 3









3 Results


4 Neural Plasticity

(a) (b)

(c) (d)




158



2116= 1424 119875 lt 0001]) As Figure 2(b)






158= 5436 119875 lt 0001


= 2287 119875 lt 0001)

Neural Plasticity 5

0

50

100

150

200

250

300

350

400


Mea

n re

actio

n tim

e in

the c

ontro

lco

nditi

on2

(ms95

C

I)

(a)


240

260

280

300

320

340

360

380


Mea

n re

actio

n tim

e in

the c

ontro

lco

nditi

on2

(ms95

S

EM)

(b)


0

01

02

03

04

05

06

07

08


Mai

n hi

t rat

io in

the m

ain

task

and

cont

rol c

ondi

tion1

(SEM

)


Control task 1

Main task



129= 587 119875 lt

005 patients F129


158= 019



258=


(F258


258







6 Neural Plasticity

0

015

03

045

06


Mea

n hi

t rat

io (9

5

CI)


Healthy controls

FastMediumSlow

(a)

0

015

03

045

06

Mea

n hi

t rat

io (9

5

CI)


FastMediumSlow

CD patients

(b)


Num

ber o

f sub

ject

s with

resp

ectiv

e hit

ratio

24

22

20

18

16

14

12

10

8

6

4

2


010000 200 300 400 500 600

()





Neural Plasticity 7

2725 2510

34704271

38053218

000

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000


All

tria

ls (

)


Axis title

(a)

2359

1960

2464

4207

4490

3897

3434

3550

3639

Early error

Hits

Late error

Current trial

Prev

ious

tria

l

Control group



2792

2153

2436

3370

3923

2823

3838

3923

4741

Current trial

Dystonia group

Early error

Hits

Late error

Prev

ious

tria

l

(b)



1536= 0411 119875 gt 005 sim20 change


4 Discussion



8 Neural Plasticity

20

40

60

80

25 50 75 100 125 150 175

Hit

ratio

Time window



0










Neural Plasticity 9




Acknowledgments


References





































































Neural Plasticity










Psychiatry Journal









Journal of


4 Neural Plasticity

(a) (b)

(c) (d)




158



2116= 1424 119875 lt 0001]) As Figure 2(b)






158= 5436 119875 lt 0001


= 2287 119875 lt 0001)

Neural Plasticity 5

0

50

100

150

200

250

300

350

400


Mea

n re

actio

n tim

e in

the c

ontro

lco

nditi

on2

(ms95

C

I)

(a)


240

260

280

300

320

340

360

380


Mea

n re

actio

n tim

e in

the c

ontro

lco

nditi

on2

(ms95

S

EM)

(b)


0

01

02

03

04

05

06

07

08


Mai

n hi

t rat

io in

the m

ain

task

and

cont

rol c

ondi

tion1

(SEM

)


Control task 1

Main task



129= 587 119875 lt

005 patients F129


158= 019



258=


(F258


258







6 Neural Plasticity

0

015

03

045

06


Mea

n hi

t rat

io (9

5

CI)


Healthy controls

FastMediumSlow

(a)

0

015

03

045

06

Mea

n hi

t rat

io (9

5

CI)


FastMediumSlow

CD patients

(b)


Num

ber o

f sub

ject

s with

resp

ectiv

e hit

ratio

24

22

20

18

16

14

12

10

8

6

4

2


010000 200 300 400 500 600

()





Neural Plasticity 7

2725 2510

34704271

38053218

000

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000


All

tria

ls (

)


Axis title

(a)

2359

1960

2464

4207

4490

3897

3434

3550

3639

Early error

Hits

Late error

Current trial

Prev

ious

tria

l

Control group



2792

2153

2436

3370

3923

2823

3838

3923

4741

Current trial

Dystonia group

Early error

Hits

Late error

Prev

ious

tria

l

(b)



1536= 0411 119875 gt 005 sim20 change


4 Discussion



8 Neural Plasticity

20

40

60

80

25 50 75 100 125 150 175

Hit

ratio

Time window



0










Neural Plasticity 9




Acknowledgments


References





































































Neural Plasticity










Psychiatry Journal









Journal of


Neural Plasticity 5

0

50

100

150

200

250

300

350

400


Mea

n re

actio

n tim

e in

the c

ontro

lco

nditi

on2

(ms95

C

I)

(a)


240

260

280

300

320

340

360

380


Mea

n re

actio

n tim

e in

the c

ontro

lco

nditi

on2

(ms95

S

EM)

(b)


0

01

02

03

04

05

06

07

08


Mai

n hi

t rat

io in

the m

ain

task

and

cont

rol c

ondi

tion1

(SEM

)


Control task 1

Main task



129= 587 119875 lt

005 patients F129


158= 019



258=


(F258


258







6 Neural Plasticity

0

015

03

045

06


Mea

n hi

t rat

io (9

5

CI)


Healthy controls

FastMediumSlow

(a)

0

015

03

045

06

Mea

n hi

t rat

io (9

5

CI)


FastMediumSlow

CD patients

(b)


Num

ber o

f sub

ject

s with

resp

ectiv

e hit

ratio

24

22

20

18

16

14

12

10

8

6

4

2


010000 200 300 400 500 600

()





Neural Plasticity 7

2725 2510

34704271

38053218

000

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000


All

tria

ls (

)


Axis title

(a)

2359

1960

2464

4207

4490

3897

3434

3550

3639

Early error

Hits

Late error

Current trial

Prev

ious

tria

l

Control group



2792

2153

2436

3370

3923

2823

3838

3923

4741

Current trial

Dystonia group

Early error

Hits

Late error

Prev

ious

tria

l

(b)



1536= 0411 119875 gt 005 sim20 change


4 Discussion



8 Neural Plasticity

20

40

60

80

25 50 75 100 125 150 175

Hit

ratio

Time window



0










Neural Plasticity 9




Acknowledgments


References





































































Neural Plasticity










Psychiatry Journal









Journal of


6 Neural Plasticity

0

015

03

045

06


Mea

n hi

t rat

io (9

5

CI)


Healthy controls

FastMediumSlow

(a)

0

015

03

045

06

Mea

n hi

t rat

io (9

5

CI)


FastMediumSlow

CD patients

(b)


Num

ber o

f sub

ject

s with

resp

ectiv

e hit

ratio

24

22

20

18

16

14

12

10

8

6

4

2


010000 200 300 400 500 600

()





Neural Plasticity 7

2725 2510

34704271

38053218

000

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000


All

tria

ls (

)


Axis title

(a)

2359

1960

2464

4207

4490

3897

3434

3550

3639

Early error

Hits

Late error

Current trial

Prev

ious

tria

l

Control group



2792

2153

2436

3370

3923

2823

3838

3923

4741

Current trial

Dystonia group

Early error

Hits

Late error

Prev

ious

tria

l

(b)



1536= 0411 119875 gt 005 sim20 change


4 Discussion



8 Neural Plasticity

20

40

60

80

25 50 75 100 125 150 175

Hit

ratio

Time window



0










Neural Plasticity 9




Acknowledgments


References





































































Neural Plasticity










Psychiatry Journal









Journal of


Neural Plasticity 7

2725 2510

34704271

38053218

000

1000

2000

3000

4000

5000

6000

7000

8000

9000

10000


All

tria

ls (

)


Axis title

(a)

2359

1960

2464

4207

4490

3897

3434

3550

3639

Early error

Hits

Late error

Current trial

Prev

ious

tria

l

Control group



2792

2153

2436

3370

3923

2823

3838

3923

4741

Current trial

Dystonia group

Early error

Hits

Late error

Prev

ious

tria

l

(b)



1536= 0411 119875 gt 005 sim20 change


4 Discussion



8 Neural Plasticity

20

40

60

80

25 50 75 100 125 150 175

Hit

ratio

Time window



0










Neural Plasticity 9




Acknowledgments


References





































































Neural Plasticity










Psychiatry Journal









Journal of


8 Neural Plasticity

20

40

60

80

25 50 75 100 125 150 175

Hit

ratio

Time window



0










Neural Plasticity 9




Acknowledgments


References





































































Neural Plasticity










Psychiatry Journal









Journal of


Neural Plasticity 9




Acknowledgments


References





































































Neural Plasticity










Psychiatry Journal









Journal of












































Neural Plasticity










Psychiatry Journal









Journal of


research article the mechanisms of movement control and time estimation...

Documents