Improving ideomotor limb apraxia by electricalstimulation of the left posterior parietal cortex

Nadia Bolognini,1,2 Silvia Convento,1 Elisabetta Banco,2,3 Flavia Mattioli,4 Luigi Tesio3,5 andGiuseppe Vallar1,2

Limb apraxia, a deficit of planning voluntary gestures, is most frequently caused by damage to the left hemisphere, where,

according to an influential neurofunctional model, gestures are planned, before being executed through the motor cortex of the

hemisphere contralateral to the acting hand. We used anodal transcranial direct current stimulation delivered to the left posterior

parietal cortex (PPC), the right motor cortex (M1), and a sham stimulation condition, to modulate the ability of six left-brain-

damaged patients with ideomotor apraxia, and six healthy control subjects, to imitate hand gestures, and to perform skilled hand

movements using the left hand. Transcranial direct current stimulation delivered to the left PPC reduced the time required to

perform skilled movements, and planning, but not execution, times in imitating gestures, in both patients and controls. In patients,

the amount of decrease of planning times brought about by left PPC transcranial direct current stimulation was influenced by the

size of the parietal lobe damage, with a larger parietal damage being associated with a smaller improvement. Of interest from a

clinical perspective, left PPC stimulation also ameliorated accuracy in imitating hand gestures in patients. Instead, transcranial

direct current stimulation to the right M1 diminished execution, but not planning, times in both patients and healthy controls. In

conclusion, by using a transcranial stimulation approach, we temporarily improved ideomotor apraxia in the left hand of left-

brain-damaged patients, showing a role of the left PPC in planning gestures. This evidence opens up novel perspectives for the use

of transcranial direct current stimulation in the rehabilitation of limb apraxia.

1 Department of Psychology and NeuroMI-Milan Centre for Neuroscience, University of Milano-Bicocca, Milan, Italy2 Laboratory of Neuropsychology, IRCSS Italian Auxological Institute, Milan, Italy3 Department of Neurorehabilitation Sciences, IRCCS Italian Auxological Institute, Milan, Italy4 SSVD Neuropsychology Unit, Department of Neurological Science and Vision, Spedali Civili, Brescia, Italy5 Department of Biomedical Sciences for Health, University of Milan, Milan, Italy

Correspondence to: Giuseppe Vallar, MD,

Department of Psychology, University of Milano-Bicocca, Piazza dell’Ateneo Nuovo 1,

20126-Milan, MI, Italy

E-mail: giuseppe.vallar@unimib.it

Keywords: apraxia; stroke rehabilitation; motor cortex; parietal lobe

Abbreviations: tDCS = transcranial direct current stimulation; JHFT = Jebsen Hand Function Test; PPC = posterior parietal cortex

IntroductionLimb apraxia is a higher-order motor disorder, whose

hallmark is the inability or difficulty to perform purposeful

limb movements (gestures), typically with the upper limbs

(Geschwind, 1975). Limb apraxia, as many other

neuropsychological disorders (e.g. unilateral spatial neglect;

Vallar, 1998), is conceived as multi-componential. A ‘core’

component includes impairments in the imitation of hand

postures, use of single mechanical tools, and pantomime of

tool use. These impairments are not explained by elemental

deficits of motor and sensory systems, or defects in

doi:10.1093/brain/awu343 BRAIN 2014: Page 1 of 12 | 1

Received July 19, 2014. Revised September 12, 2014. Accepted October 12, 2014.

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language comprehension (Goldenberg, 2013). The neural

underpinnings of limb apraxia are characterized by a hemi-

spheric asymmetry: lesions involve more frequently the left

hemisphere, particularly the left premotor-frontal and pos-

terior-parietal regions, rather than the right hemisphere of

right-handed patients (Haaland et al., 2000; Hanna-Pladdy

et al., 2001; Foundas, 2013).

An early influential anatomo-functional model of limb

apraxia was put forward at the beginning of the 20th cen-

tury by the German physician Hugo Karl Liepmann [for a

biographical profile, see Goldenberg, 2003; Liepmann,

1908, 1925; English translations in Liepmann (1977,

1988)]. On the basis of clinical observations, Liepmann

drew a distinction between a ‘movement formula’, and

the motor execution of the intended gesture. The gener-

ation of the formula is mainly based on neural activity in

the temporo-parieto-occipital cortex of the left hemisphere

of right-handed individuals. This motor plan is conveyed to

the sensorimotor central cortex of the left hemisphere,

which provides motor signals to the right hand. For move-

ments of the left hand, transfer of the formula to the sen-

sorimotor cortex in the right hemisphere, via callosal

connections, is required, as the movement plan is primarily

conveyed to the left sensorimotor cortex. This hemispheric

asymmetry implies that left-brain-damaged patients, who

frequently show right-sided motor deficits that may mask

apraxia in the dominant right hand, exhibit apraxia in the

left hand, which receives planning for skilled action by the

left hemisphere.

Liepmann’s model has received support by neuropsycho-

logical clinical observations (Geschwind, 1965; Leiguarda

and Marsden, 2000; Goldenberg, 2013). Recently, we cor-

roborated this view with a transcranial direct current

stimulation (tDCS) study in healthy right-handed partici-

pants (Convento et al., 2014). Anodal tDCS of the right

primary motor (M1) and of the left posterior parietal cor-

tices (PPC) fastens motor performance of the non-dominant

left hand, as assessed by the Jebsen Hand Function Test

(JHFT; Jebsen et al., 1969); a slowing of motor perform-

ance is induced by the cathodal tDCS of the same areas.

Instead, stimulation of the right PPC and of the left M1 is

ineffective. When execution and planning stages are distin-

guished, the anodal tDCS of the left PPC selectively facili-

tates action planning, while the anodal tDCS of the right

M1 modulates action execution only. Broadly in line with

these findings, anodal tDCS applied to the left inferior par-

ietal lobule of healthy participants facilitates the matching

of visual hand gestures, in a perceptual same/different task

(Weiss et al., 2013).

In the light of this evidence, we investigated whether

tDCS applied over the left PPC, ipsilateral to the side of

the lesion (ipsilesional), and over the right M1, contralat-

eral to the side of the lesion (contralesional), can improve

ideomotor apraxia in stroke patients. Ideomotor apraxia is

characterized by errors in the ‘proper temporo-spatial or-

ganization of the sequence of movements that must imple-

ment the representation of the action’ (Barbieri and De

Renzi, 1988), when patients are required to imitate in-

transitive (not involving objects or tools), symbolic (such

as the sign for ‘crazy’), and non-symbolic gestures

(Buxbaum, 2001; Buxbaum et al., 2008; Foundas, 2013;

Goldenberg, 2013). Damage to the left inferior parietal

lobule is a correlate of ideomotor apraxia (Goldenberg,

2009; Buxbaum et al., 2014); this region is activated by

tasks requiring the imitation of gestures (Muhlau et al.,

2005; Molenberghs et al., 2012).

Based on our study in healthy participants (Convento

et al., 2014), we attempted to verify the hypothesis that

anodal tDCS of the left PPC ameliorates ideomotor

apraxia, improving the imitation of intransitive gestures,

assessed with a standard clinical test (De Renzi et al.,

1980). Then, apraxic patients were presented with the

JHFT to verify whether tDCS could improve their perform-

ance in motor tasks mimicking activities of daily living.

Materials and methods

Participants

Participants were recruited in the Department ofNeurorehabilitation Sciences of the IRCCS IstitutoAuxologico Italiano (Milan, Italy), and in the Hospital‘Spedali Civili’ (Brescia, Italy); they were fully right-handed,as assessed through the Edinburgh Handedness Inventory(Oldfield, 1971), and had no contraindication to tDCS(Poreisz et al., 2007; Rossi et al., 2009). Accepted recommen-dations for the safe use of non-invasive brain stimulation wereapplied (Rossi et al., 2009). The protocol was read and ex-plained to patients and their caregivers. Participants gave theirinformed consent to the protocol, which had been approved bythe Ethical Committee of each research centre, and was carriedout in accordance with the ethical standards of the Declarationof Helsinki. Three patients (Patients P1, P2 and P4; Table 1)signed the written informed consent; for the other three pa-tients (Patients P3, P5 and P6), the caregiver signed it, becauseof the patients’ inability to produce a signature, even using theunaffected left hand.

Two groups of participants entered the study: (i) six neuro-logical healthy controls (one male, mean age = 66.7 years,standard deviation � 6.68, range = 57–76; mean years ofschooling = 11.5 � 3.73, range 8–14), with no history or evi-dence of neurological disease; and (ii) six left-hemisphere-damaged patients (four males, mean age = 72.16 � 7.2 years;mean years of schooling = 11.16 � 9.2; duration of dis-ease = 12.50 � 21.53 months).

Patients had no history or evidence of previous neurologicalor psychiatric disorders, or dementia. The patients’ demo-graphic and clinical data are summarized in Table 1. Thetwo groups of participants did not differ with respect totheir age [unpaired t-test, t(10) = �1.36, P = 0.2], and yearsof schooling [t(10) = �0.13, P = 0.9].

Baseline evaluation

The baseline assessment, performed 1 week before the firstexperimental session, included: (i) a standard neurological

2 | BRAIN 2014: Page 2 of 12 N. Bolognini et al.

exam (Bisiach and Faglioni, 1974); (ii) the Token Test, assess-ing auditory comprehension of verbal commands (De Renziand Faglioni, 1978); (iii) a controlled association task on se-mantic and phonemic cues (Novelli et al., 1986); (iv) visuo-spatial and auditory-verbal short-term memory spans (Orsiniet al., 1987); (v) constructional apraxia (Spinnler and Tognoni,1987; Caffarra et al., 2002); (vi) ideomotor apraxia (De Renziet al., 1980); (vii) oral apraxia (De Renzi and Faglioni, 1996);and (viii) ideational apraxia (De Renzi and Lucchelli, 1988).

The patients’ individual scores are shown in Table 1.

Lesion data

Figure 1 shows the lesion mapping of the six left-brain-damaged patients (Rorden and Brett, 2000). CT scans hadbeen taken between 2 and 10 weeks before the assessment infive of six patients, 24 weeks with respect to the testing in onepatient (Patient P5). Regions of interest, defining the locationand size of the lesion for each patient, were reconstructed by atemplate technique, manually drawing the lesion on the stand-ard template from the Montreal Neurological Institute (MNI;Rorden and Brett, 2000).

Experimental tasks

Ideomotor Apraxia Test

The test comprised 24 intransitive gestures, divided in 12

‘symbolic’ (e.g. the sign of ‘OK’), and 12 ‘non-symbolic’

(e.g. ‘hand under the chin’) gestures. The examiner demon-

strated each gesture, one at a time, with the right hand.

Participants had received instructions to reproduce the

demonstrated gesture with their left hand. If an item was

not correctly reproduced at the first demonstration, a

second one was given, up to three demonstrations.

Accuracy scores at each gesture ranged from 0 to 3

(3 = correct reproduction at the first demonstration;

2 = correct reproduction at the second demonstration;

1 = correct reproduction at third demonstration; 0 = incor-

rect reproduction at the third demonstration). The total

score ranged from 0 to 72 points. A score 553 was de-

fective, and taken as an indication of the presence of

ideomotor apraxia (De Renzi et al., 1980). During baseline

evaluation, all 24 gestures were shown. In the experimental

sessions, to ensure that participants performed the gestures

within the temporal window of the after-effects of tDCS, 12

of 24 gestures were given, which showed a static posture or

a motor sequence: thumb and index finger making a circle

(sign of ‘OK’); index and medium finger abducted (sign of

‘V’, victory); index finger and little finger extended, with

the others flexed (‘sign of the horns’); index finger lifted up,

with the other fingers flexed; mimicking a man walking,

with the index and medium fingers alternately moving for-

ward on the table; opening and closing the index on the

medium finger (sign of ‘scissors’); prone hand on the table,

middle finger arched over the index finger, with the other

fingers flexed; thumb constricted between the index and

middle fingers; snapping fingers (the thumb and another

finger) for three times; give a slap, extending the middle

finger from the distal phalanx of the thumb for three

times; tapping the four lateral fingers on the table three

times, always starting from the index finger; supine hand

on the table, flexing the index and then the middle finger

on the thumb, while the other finger was kept extended.

The demonstration of each gesture by the experimenter

began and finished at the same position on the table. The

experimenter had been trained to demonstrate each gesture

as much as possible in the same way, keeping the same

velocity. Participants were required to look at each demon-

stration, and to reproduce the shown gesture, starting im-

mediately after the demonstration was over, as soon as the

examiner’s hand had touched the table, which represented

the ‘go’ signal for the patient’s reproduction of the gesture.

Participants had received instruction to lay their left hand

back on the table, after the completion of each trial. The

participants’ performance was video-recorded for off-line

analysis; the registration started when the examiner’s

hand was lifted up from the table.

Jebsen Hand Function Test

This standardized 7-item test was designed as a broad

measure of daily, skilled hand function, to provide a

Table 1 Demographic and neurological data and baseline neuropsychological assessment of six left-brain-damaged

patients

Patients Age/

sex

Education

(years of

schooling)

Duration

of disease

(months)

Cerebrovascular

attack

Neurological

deficit

Token

Test

0–36

Verbal

fluency

Immediate

memories

Apraxia

Digit Spatial IMA IA OA CA

M V SS Ph Se (0–72) (0–120) (0–24) (0–14 a/0–36 b)

P1 77/F 18 1 I + - - 23 c 10 c 29 3 c 2 c 43/72 c 116/120c 13c 14a/14

P2 79/F 10 2 I + - - 28.5 10c 15c 3c 2c 47/72c 120/120 23 14a/14

P3 70/M 18 1 I + - - 17c 0c 0c 4c 4c 43/72c 107/120c 1c 12a/14

P4 59/M 8 15 I + - - 34 0c 0c 2c 3c 52/72c 120/120 4c 6b/36c

P5 76/M 5 55 H + + - 22.5c 0c 0c 5 3c 24/72c 76/120c 14c 7b/36c

P6 72/M 8 4 I + - - 3c 0c 0c 3c 4c 13/72c 24/120c 0c 8a/14

Ph/Se = phonemic/semantic verbal fluency; H = haemorrhagic; I = ischaemic; IMA = ideomotor apraxia; IA = ideational apraxia; OA = oral apraxia; CA = constructional apraxia; Right

M/V/SS = motor/visual field/somatosensory deficit.aDrawing Copy; bRey Complex Figure; cDefective score according to available norms.

Left parietal stimulation improves apraxia BRAIN 2014: Page 3 of 12 | 3

quantitative evaluation of unilateral hand performance, by

assessing speed of execution, rather than movement quality.

The JHFT has been used for evaluating hand motor func-

tion in stroke patients, and for measuring the effects of

neuromodulation on hand motor performance in both

healthy participants, and stroke brain-damaged patients

(Hummel et al., 2005; Boggio et al., 2006, 2007;

Convento et al., 2014). Six of the seven tasks of the

JHFT were used: turning cards, picking up small objects

and placing them in a can, lifting small objects with a

spoon, stacking checkers, lifting light and heavy cans.

The handwriting task was excluded, as in previous tDCS

studies (Hummel et al., 2005; Boggio et al., 2006, 2007),

including the one on which this study was based (Convento

Figure 1 Left-hemispheric lesions of six patients with ideomotor apraxia.

4 | BRAIN 2014: Page 4 of 12 N. Bolognini et al.

et al., 2014). Participants performed the tasks with their

non-dominant left hand, unaffected by motor deficits in

left-brain-damaged patients. They had received instructions,

both verbally and through demonstration by the examiner,

to perform each task as accurately, and as rapidly as pos-

sible (Jebsen et al., 1969). Total time of execution, calcu-

lated as the sum of the execution times of the six JHFT

tasks, was the primary outcome for analyses. During the

task, the participants’ performance was video-recorded for

off-line analysis; the registration started at the beginning of

the patient’s hand movement.

Lexical search and production

Participants received instructions to produce as many

words as possible, in a limited time interval. In the baseline

assessment, verbal fluency was assessed on three semantic

and three phonemic cues. In the experimental session only

phonemic cues were used, namely the letters ‘F’, ‘P’ and ‘L’.

A time limit of 60 s was given for each letter, with a score

416 being defective (Novelli et al., 1986).

Transcranial direct currentstimulation

tDCS was delivered by a battery-driven, constant current

stimulator (BrainStim, EMS, http://brainstim.it), through a

pair of saline-sponge electrodes (25 cm2, 5 � 5 cm). In

every experimental session, tDCS was applied for a total

10 min (fade-in/fade-out phases = 10 s), with an intensity of

2 mA, in accordance with current safety data (Poreisz et al.,

2007).

For stimulation of the right M1, the anode was placed

over C4, according to the 10:20 EEG system. When the left

PPC was targeted, the anodal electrode was placed over P3.

In both cases, the cathodal reference electrode was placed

over the contralateral supraorbital area (Rosenkranz et al.,

2000; Fregni et al., 2005; Hummel et al., 2005; Boggio

et al., 2006, 2007; Nitsche et al., 2008; Bolognini et al.,

2011). For sham tDCS, the same electrode montage was

used, placing the anode over one of the target areas,

which was randomized across participants. The same par-

ameters of the active stimulation were used, but the stimu-

lator was turned off after 30 s; this ensured that

participants felt the initial itching sensation at the beginning

of tDCS, but preventing any effective modulation of cor-

tical excitability by tDCS (Gandiga et al., 2006). Current

intensity was gradually increased (at the beginning of the

session) and decreased (at the end), to diminish its percep-

tion (i.e. fade-in/fade-out phases). The sham and real modes

of tDCS were activated through codes set by the BrainStim

software, which controlled the tDCS device. By such codes,

the device was activated by the experimenter, and it always

showed on the display ‘on’, and the parameters of stimu-

lation during the procedure, but independently of the type

of stimulation (‘real’ versus ‘sham’). This method has been

shown to be reliable for keeping both the experimenter and

the participant blind to sham and real tDCS (Gandiga

et al., 2006), and it is commonly used in tDCS investiga-

tions, both in neurological patients (Fregni et al., 2005;

Bolognini et al., 2013b; Brunoni et al., 2014), and in

healthy participants (Ladeira et al., 2011; Convento et al.,

2012; Bolognini et al., 2013a).

Experimental procedure

Each participant underwent three sessions: (i) anodal tDCS

to left PPC; (ii) anodal tDCS to right M1; and (iii) sham

tDCS. The order of the three sessions, separated by at least

24 h to minimize carry-over effects (Bolognini et al., 2013a;

Monte-Silva et al., 2013), was counterbalanced, and ran-

domized across participants. Both the experimenter and

each participant were blinded with respect to the experi-

mental conditions (active versus sham tDCS).

The day before the first session, patients and control par-

ticipants practiced the JHFT six times to familiarize with

the tasks, and to achieve a stable performance level. A pre-

vious recent study has shown that this training enabled

healthy participants to reach a stable performance level

(Convento et al., 2014). To verify the effectiveness of the

training in stabilizing JHFT performance, the total times of

execution at each training trial and at the baseline of the

first experimental session were submitted to one-way re-

peated-measures ANOVAs, one for each experimental

group, with Repetition (1 to 6) as the within-subject

factor. A significant effect of Time emerged for both pa-

tients [F(5,25) = 6.61, P5 0.001, ph2 = 0.57], and healthy

controls [F(5,25) = 9.10, P5 0.0001, ph2 = 0.64], revealing

a speed-up of performance between the first three training

sessions (patients: first = 48.14 � 7.61 s, second = 45.69 �

7.90 s, third = 39.84 � 7.49 s; controls: first = 38.00 �

5.87 s, second = 33.95 � 4.27 s, third = 32.46 � 4.97 s;

Bonferroni-corrected pairwise multiple comparisons:

P5 0.05). Instead, no significant differences were found

in the total times of execution of the JHFT between the

last three training sessions, in both patients (fourth = mean

39.84 � 9.49 s, fifth = 39.55 � 10.23 s, sixth = 39.32 �

9.97 s), and control participants (fourth = 32.71 � 4.84 s,

fifth = 32.89 � 5.49 s, sixth = 31.83 � 5.24 s). Performance

speed did not change between the last training session

and the first experimental session (i.e. baseline) in both

patients [sixth training session = 39.32 � 9.97 s, first experi-

mental session = 39.32 � 8.63 s; paired t-test, t(5) = �1.17,

P = 0.20], and controls [sixth training session =

31.83 � 5.24 s, first experimental session = 30.29 � 4.73 s;

t(5) = �0.45, P = 0.60].

During each tDCS session, participants performed the

three tasks (ideomotor apraxia, JHFT, and phonemic flu-

ency), given in a fixed order, immediately before (pre-tDCS)

and after (post-tDCS) having received tDCS. This multiple-

baseline design was used for controlling carry-over effects

across tDCS sessions (Monte-Silva et al., 2010, 2013;

Bolognini et al., 2013a). To obtain a reliable measure of

motor performance, the JHFT was repeated three times

Left parietal stimulation improves apraxia BRAIN 2014: Page 5 of 12 | 5

before (baseline: JHFT 1–3), and three times after stimula-

tion (post-tDCS: JHFT 4–6).

Each experimental session for ideomotor apraxia, includ-

ing training, was video recorded with a digital camera

(Panasonic Lumix DMC-TZ4). Two independent operators

made the subsequent off-line evaluation of performance

speed based on video recordings, in order to minimize

any error. Such evaluation was carried out through the

use of a digital chronometer with millisecond precision,

and displayed during the video playing. The total time

for each gesture was calculated by starting the chronometer

at the same moment of the beginning of the experimenter’s

gesture production (lifting up the arm from the table), and

stopping it when participants had completed their perform-

ance, and laid their hand back on the table. Execution time

was calculated starting the chronometer when participants

initiated the reproduction of the gesture, and stopping it at

the same end point of the total time (the patient’s hand laid

back on the table). In this way, by subtracting the execu-

tion time from the total time, a measure of the time

required for gesture planning (the planning time) was com-

puted (Convento et al., 2014).

For the JHFT, following the procedure of Convento

et al.’s (2014) Experiment 1, the total times of performance

for each of the six tasks were measured, starting the chron-

ometer when the participant initiated the movement (fol-

lowing the starting signal by the experimenter), and

stopping it when each activity was completed; the total

times of each of the six tasks were then summed, and

averaged for the three JHFT assessments. Before the ana-

lyses, the normal distribution of the data was evaluated by

the Kolmogorov–Smirnov Test, and their homogeneity by

Levene’s Test. Given the positive skewness of response

times at the ideomotor apraxia and JHFT tests, these

data were log-transformed to minimize the impact of

outliers, and normalize distributions (Sokal and Rohlf,

1995). The accuracy scores at the phonemic fluency and

at the ideomotor apraxia tests met the assumptions of

a normal distribution, and no transformations were

applied.

Statistical analyses

The Statistica Software (Statsoft, Version 6.0) was used for

analyses. The execution and planning times in the

Ideomotor Apraxia Test, the total times in the JHFT (pri-

mary outcome measures), and the phonemic fluency scores,

were used to evaluate the effects of tDCS in patients and

controls. These data were submitted to repeated-measures

ANOVAs with Group (left-brain-damaged patients, con-

trols subjects) as the between-subject factor, Session (right

M1; left PPC; sham), and Time (pre-tDCS; post-tDCS) as

the within-subject factors. For patients, a repeated-measures

ANOVA with Session and Time as within-subject main

factors was performed on the ideomotor apraxia accuracy

scores, since healthy participants made no errors in this test

in any session. The partial Eta squared (ph2), which

measures the proportion of total variance that is attribut-

able to a main factor or to an interaction (Cohen, 1973),

was also calculated for each repeated-measures ANOVA.

Significant main effects and interactions were analysed by

Bonferroni-corrected pairwise comparisons.

Results

Ideomotor Apraxia Test

In both patients and control participants a reduction of

planning times was found after anodal tDCS of the left

PPC, with sham stimulation being ineffective (Fig. 2A).

Conversely, execution times diminished after anodal tDCS

of right M1 (Fig. 2B), with sham stimulation again being

ineffective.

Planning time

The repeated-measures ANOVA on planning times showed

significant main effects of Group [F(1,10) = 84.51, P50.0001, ph2 = 0.89], Session [F(2,20) = 6.85, P = 0.005,

ph2 = 0.40], and Time [F(1,10) = 29.58, P5 0.001, ph2 =

0.74]. The Time � Session [F(2,20) = 27.30, P5 0.0001,

ph2 = 0.73], and the Group � Time [F(1,10) = 14.42,

P5 0.001, ph2 = 0.59] interactions were significant. The

Group � Session [F(2,20) = 0.21, P = 0.80, ph2 = 0.02],

and the Group � Session � Time [F(2,20) = 0.56, P = 0.50,

ph2 = 0.05] interactions were not significant. For the

Session � Time interaction, Bonferroni-corrected pairwise

comparisons showed a significant difference between the

pre- and the post-tDCS planning times only after left PPC

tDCS (pre-tDCS = 33.67 � 8.67 s, post-tDCS = 28.79 �

8.15 s, P5 0.0001). tDCS to the right M1 did not modulate

performance. Planning times after stimulation of the left PPC

differed (P5 0.0001) from those of all the other post-tDCS

sessions (Fig. 2A). No differences in planning times in the three

pre-tDCS sessions were found.

To assess the effect of tDCS in the two groups, separate

repeated-measures ANOVAs were performed, with Session

(right M1, left PPC, sham) and Time (pre-tDCS, post-

tDCS) as the within-subjects main factors. In healthy con-

trols, the main effect of Time [F(1,5) = 26.03, P = 0.004,

ph2 = 0.84] was significant, whereas that of Session

did not attain the significance level [F(2,10) = 2.84,

P = 0.09, ph2 = 0.37]. The Time � Session interaction

[F(2,10) = 13.88, P5 0.001, ph2 = 0.74] was significant:

the differences between pre- and post-tDCS planning

times were significant for left PPC tDCS (pre-tDCS =

26.17 � 1.05 s; post-tDCS = 21.73 � 1.97 s, P5 0.01), but

not for right M1 or sham tDCS. In patients, the ANOVA

showed a significant main effect of Session [F(2,10) = 4.24,

P5 0.05, ph2 = 0.46], while the main effect of Time was

not significant [F(1,5) = 3.73, P = 0.10, ph2 = 0.40].

The Time � Session interaction was significant

[F(2,10) = 13.96, P = 0.002, ph2 = 0.74]: similar to healthy

6 | BRAIN 2014: Page 6 of 12 N. Bolognini et al.

controls, for left PPC tDCS the difference between planning

times pre-tDCS (41.19 � 5.40 s) and post-tDCS

(35.86 � 4.74 s, P50.05) was significant; instead, no dif-

ferences were found after right M1 or sham tDCS.

Execution time

The repeated-measures ANOVA on execution times

showed significant main effects of Group [F(1,10) = 32.49,

P50.0001, ph2 = 0.76], and of Time [F(1,10) = 8.61,

P = 0.02, ph2 = 0.46], whereas the main effect of Session

[F(2,20) = 0.53, P = 0.60, ph2 = 0.05] was not significant.

The Time � Session interaction [F(2,20) = 19.73, P50.0001, ph2 = 0.66] was significant. The Group � Time

[F(1,10) = 3.41, P = 0.09, ph2 = 0.25], Group � Session

[F(2,20) = 0.48, P = 0.60, ph2 = 0.04], and Group �

Session � Time [F(2,20) = 0.83, P = 0.40, ph2 = 0.07] inter-

actions were not significant. Execution times after right

M1 tDCS differed from execution times before stimulation

(pre-tDCS = 44.50 � 15.65 s, post-tDCS = 39.87 � 15.58 s,

P50.01); no such differences were found for left PPC

tDCS and for sham tDCS. The three pre-tDCS conditions

did not differ from each other in each group (Fig. 2B).

In healthy control subjects, the repeated-measures

ANOVA showed a significant main effect of Time

[F(1,5) = 12.93, P5 0.02, ph2 = 0.72], whereas the main

effect of Session was not significant [F(2,10) = 0.54,

P = 0.06, ph2 = 0.1]. The Session � Time interaction

[F(2,10) = 14.20, P5 0.001, ph2 = 0.74] was significant:

the difference between execution times before and after

right M1 tDCS (pre-tDCS =31.60 � 5.57 s, post-

tDCS = 27.21 � 5.19 s, P50.001) was significant; no sig-

nificant differences were found for PPC and sham tDCS. In

patients, the main effects of Session [F(2,10) = 0.42,

P = 0.60, ph2 =0.08], and of Time [F(1,5) = 0.54,

P = 0.50, ph2 = 0.1] were not significant, whereas

the Session � Time interaction was significant

([F(2,10) = 7.19, P5 0.01, ph2 =0.59]. The difference be-

tween execution times before and after right M1 tDCS

(pre-tDCS =57.41 � 10.43 s, post-tDCS = 52.53 � 11.08 s,

P5 0.05) was significant; no significant differences were

found for left PPC and sham tDCS.

As shown in Fig. 3, the patients’ accuracy scores in the

Ideomotor Apraxia Test increased after anodal tDCS of left

PPC. The repeated-measures ANOVA showed a significant

main effect of Time [F(1,5) = 25.56, P5 0.004,

ph2 = 0.97], whereas the main effect of Session was not

significant [F(2,10) = 0.90, P = 0.43, ph2 = 0.16]. The

Time � Session interaction [F(2,10) = 5.28, P5 0.03,

ph2 = 0.70] was significant. The difference between accur-

acy scores before and after left PPC-tDCS was significant

(24.50 versus 28.67, P5 0.05), with an increase of correct

responses. No significant differences between pre- and post-

tDCS for the right M1, and the sham stimulation condi-

tions were found.

Jebsen Hand Function Test

Figure 4 shows that in both patients, who were overall

slower, and control participants total times decreased

after tDCS of both right M1 and left PPC, as compared

to pre-tDCS, while sham stimulation was ineffective. The

repeated-measures ANOVA showed significant main effects

of Time [F(1,10) = 31.75, P5 0.0001, ph2 = 0.76], and of

Group [F(1,10) = 8.38, P5 0.02, ph2 = 0.45], while the

main effect of Session [F(2,20) = 1.90, P = 0.17,

ph2 = 0.16] was not significant. The Time � Session inter-

action was significant [F(2,20) =24.73, P5 0.0001,

ph2 = 0.71]. The Group � Time [F(1,10) = 0.12, P = 0.70,

ph2 = 0.01], Group � Session [F(2,20) = 0.96, P = 0.40,

ph2 = 0.08], and Group �Time � Session [F(2,20) = 1.30,

P = 0.30, ph2 = 0.11] interactions did not attain the signifi-

cance level. For the Time �Session interaction, the differ-

ences between total times at the baseline and after anodal

tDCS of both right M1 (pre-tDCS = 35.05 � 8.66 s, post-

tDCS = 32.61 � 7.85 s, P5 0.001), and left PPC

Figure 2 Ideomotor Apraxia Test: planning and execution

times. Mean (� standard error) planning (A) and execution (B)

times (s) of six left-brain-damaged patients with ideomotor apraxia,

and six control participants (Controls), by tDCS session (sham, left

PPC, right M1), and time (pre- and post-tDCS). *Significant

difference.

Left parietal stimulation improves apraxia BRAIN 2014: Page 7 of 12 | 7

(pre-tDCS = 33.88 � 7.03 s, post-tDCS = 31.62 � 6.05 s,

P50.0001) were significant, showing a speed up of per-

formance (Fig. 4).

In healthy controls the repeated-measures ANOVA

showed a significant main effect of Time [F(1,5) = 11.73,

P50.02, ph2 = 0.68], whereas the main effect of Session

[F(2,10) = 0.22, P = 0.81, ph2 = 0.04] did not attain the sig-

nificance level. The Session � Time interaction [F(2,10) =

12.08, P5 0.002, ph2 = 0.71] was significant. Total times

before and after right M1 tDCS (pre-tDCS = 29.86 � 5.08 s,

post-tDCS =27.72 � 4.81 s, P5 0.001), and left PPC tDCS

(pre-tDCS = 29.37 � 4.24 s, post-tDCS = 27.73 � 3.80 s,

P50.01) were significantly different; no differences were

found for sham tDCS. For patients, the repeated-measures

ANOVA showed a significant main effect of Time

[F(1,5) = 29.58, P5 0.003, ph2 = 0.86], whereas the main

effect of Session [F(2,10) = 3.07, P = 0.09, ph2 = 0.38] did

not reach significance. The Session � Time interaction

[F(2,10) = 13.55, P5 0.001, ph2 = 0.73] was significant.

Total times before and after right M1 tDCS (pre-

tDCS = 40.26 � 8.64 s, post-tDCS = 37.52 �7.41 s, P50.05), and left PPC tDCS (pre-tDCS = 38.39 � 6.48 s,

post-tDCS =35.51 � 85.45 s, P5 0.01) were significantly

different; no differences were found for sham tDCS.

Phonemic fluency

Control participants scored higher (38 � 12.9) than left-

brain-damaged patients (3.5 � 3.4). As shown in Fig. 5,

no significant modulation of verbal performance was

induced by tDCS. The ANOVA showed a significant

main effect of Group [F(1,10) = 37.04, P5 0.0001,

ph2 = 1], while the main effects of Session [F(2,20) = 0.75,

P = 0.50, ph2 = 0.15], and Time [F(1,10) = 1.47, P = 0.20,

ph2 = 0.19], as well as the Group � Session [F(2,20) =0.39,

P = 0.60, ph2 = 0.10], Group � Time [F(1,10) = 1.72,

P = 0.20, ph2 = 0.22], Session � Time [F(2,20) = 0.08, P =

0.90, ph2 = 0.06], and Group � Session � Time [F(2,20) =

0.44, P = 0.60, ph2 = 0.11] interactions were not significant.

Effects of time since stroke and oflesion size and location

To control for time since stroke, lesion volume, and size of

the parietal and frontal damage, which could have influ-

enced the effects of tDCS in apraxic patients, one-way re-

peated-measures ANCOVAs were performed. Time (pre-

and post-tDCS) was the within-subject factor; the linear

and interactive covariates were length of illness (time

since stroke in months, Table 1), total lesion volume

(mean lesion volume = 63.13 cm3� 55.42 range = 5.8–

156 cm3), and the sizes of the parietal and frontal damages,

Figure 4 JHFT: total time. Mean (� standard error) total time

(s) of six left-brain-damaged patients with ideomotor apraxia and

Controls, by tDCS session (sham, left PPC, right M1), and time (pre-

and post-tDCS). *Significant difference.

Figure 3 Ideomotor Apraxia Test. Mean (� standard error)

accuracy score of six patients with ideomotor apraxia, by tDCS

session (sham, left PPC, right M1), and time (pre- and post-tDCS).

*Significant difference.

Figure 5 Phonemic Fluency Test: scores. Mean (� standard

error) accuracy score of six patients with ideomotor apraxia and

Controls, by tDCS session (sham, left PPC, right M1), and time (pre-

and post-tDCS).

8 | BRAIN 2014: Page 8 of 12 N. Bolognini et al.

measured in each patient by estimating the number of

voxels of damage of these regions (Rorden and Brett,

2000; Bolognini et al., 2012). The dependent variables

were the scores in the sessions where a significant tDCS

effect had been detected by the previous ANOVAs,

namely: planning times and accuracy scores at the

Ideomotor Apraxia Test, and total times at the JHFT,

before and after left PPC tDCS; execution times at the

Ideomotor Apraxia Test and total times at the JHFT,

before and after right M1 tDCS. Table 2 shows that in

the majority of the repeated-measures ANCOVAs, the

main effect of Time was significant, confirming the reliabil-

ity of the effects by PPC and M1 tDCS. Importantly, the

interaction between Time and the covariates was significant

only for the parietal lesion covariate, in the analysis of the

parietal tDCS effect on the planning times at the Ideomotor

Apraxia Test (P5 0.03).

This result indicates that the slowing down of planning

times by left PPC tDCS was influenced by the extent of the

damage affecting the stimulated area (i.e. left PPC). The

three patients (Patients P1, P5 and P6) with parietal

damage (number of voxels = 1730, 4761, 1373, respect-

ively) showed an average smaller reduction of planning

times (�4.44) at the Ideomotor Apraxia Test (Patient

P1 = �4.83 s, Patient P5 = �5.38 s, Patient P6 = �3.11 s),

whereas the three patients with a spared parietal cortex

Table 2 One-way ANCOVAs (F, P and ph2 values) with the within-subjects factor Time, and Lesion volume, Length

of illness, Parietal lesion and Frontal lesion as linear and interactive covariates

Test Covariate Time Time by covariate

Ideomotor

apraxia test

Planning time � left PPC Length of illness F = 26.8, P_ 0.01, ph2 = 0.87 F = 4.6, P = 0.1, ph2 = 0.53

F = 0.6, P = 0.5, ph2 = 0.1

Lesion volume F = 7.6, P_ 0.05, ph2 = 0.65 F = 1.3, P = 0.3, ph2 = 0.24

F = 0.02, P = 0.9, ph2 = 0.01

Frontal lesion F = 18.9, P_ 0.01, ph2 = 0.82 F = 0.4, P = 0.6, ph2 = 0.85

F = 4.7, P = 0.1, ph2 = 0.5

Parietal lesion F = 33.8, P_ 0.01, ph2 = 0.89 F = 11.6, P_ 0.03, ph2 = 0.74

F = 0.6, P = 0.8, ph2 = 0.0

Execution time � right M1 Length of illness F = 15.2, P_ 0.01, ph2 = 0.79 F = 6.2, P = 0.07, ph2 = 0.60

F = 0.5, P = 0.5, ph2 = 0.1

Lesion volume F = 3.4, P = 0.1, ph2 = 0.45 F = 2.4, P = 0.2, ph2 = 0.37

F = 0.02, P = 0.9, ph2 = 0.1

Frontal lesion F = 21.9, P_ 0.01, ph2 = 0.84 F = 2.4, P = 0.2, ph2 = 0.37

F = 0.7, P = 0.8, ph2 = 0.02

Parietal lesion F = 7.7, P_ 0.05, ph2 = 0.66 F = 0.9, P = 0.4, ph2 = 0.17

F = 1.1, P = 0.4, ph2 = 0.2

Accuracy � left PPC Length of illness F = 9.4, P_ 0.04, ph2 = 0.70 F = 0.2, P = 0.7, ph2 = 0.45

F = 0.1, P = 0.9, ph2 = 0.01

Lesion volume F = 5.4, P = 0.08, ph2 = 0.57 F = 0.1, P = 0.8, ph2 = 0.02

F = 0.2, P = 0.7, ph2 = 0.4

Frontal lesion F = 7.8, P_ 0.05, ph2 = 0.66 F = 0.2, P = 0.7, ph2 = 0.04

F = 0.5, P = 0.51, ph2 = 0.1

Parietal lesion F = 18.3, P_ 0.01, ph2 = 0.82 F = 2.5, P = 0.2, ph2 = 0.38

F = 0.4, P = 0.5, ph2 = 0.09

JHFT Total time � left PPC Length of illness F = 37.9, P_ 0.01, ph2 = 0.90 F = 0.2, P = 0.67, ph2 = 0.05

F = 0.4, P = 0.5 ph2 = 0.09

Lesion volume F = 40.1, P_ 0.01, ph2 = 0.90 F = 2.1, P = 0.2, ph2 = 0.33

F = 0.6, P = 0.5, ph2 = 0.1

Frontal lesion F = 35.2, P_ 0.01, ph2 = 0.89 F = 0.6, P = 0.5, ph2 = 0.12

F = 0.1, P = 0.8, ph2 = 0.02

Parietal lesion F = 33.1, P_ 0.01, ph2 = 0.89 F = 0.2, P = 0.7, ph2 = 0.04

F = 0.1, P = 0.8, ph2 = 0.02

Total time � right M1 Length of illness F = 10.7, P_ 0.03, ph2 = 0-72 F = 0.7, P = 0.4, ph2 = 0.14

F = 1.5, P = 0.3, ph2 = 0.3

Lesion volume F = 9.1, P_ 0.04, ph2 = 0.69 F = 1.1, P = 0.3, ph2 = 0.22

F = 1.5, P = 0.3, ph2 = 0.2

Frontal lesion F = 8.5, P_ 0.04, ph2 = 0.68 F = 0.5, P = 0.5, ph2 = 0.11

F = 0.01, P = 0.9, ph2 = 0.01

Parietal lesion F = 13.76, P_ 0.02, ph2 = 0.77 F = 1.7, P = 0.3, ph2 = 0.29

F = 0.5, P = 0.5 ph2 = 0.10

Significant effects in bold.

Degrees of freedom = 1,4.

Left parietal stimulation improves apraxia BRAIN 2014: Page 9 of 12 | 9

(0 voxels) exhibited an average (�6.2) larger benefit

(Patient P2 = �5.52, Patient P3 = �9.93, Patient

P4 = �3.21). It is also worth noting that the average im-

provement of the accuracy score at the Ideomotor Apraxia

Test was smaller (2.3 points) in the three patients showing

an extensive damage to the left parietal cortex (Patient

P1 = + 1, Patient P5= + 2, Patient P6 = + 4), than that

( + 6) of the three patients with spared left parietal cortex

(Patient P2 = + 7, Patient P3 = + 3, Patient P4 = + 8).

The interaction of Time with the other covariates never

reached significance in the ANCOVAs, indicating that

length of illness, lesion volume, and size of the frontal

lesion did not influence the different effects by left PPC

tDCS, and by right M1 tDCS.

DiscussionAnodal tDCS of the left PPC improves skilled motor per-

formance of the left hand of both left-brain-damaged pa-

tients with ideomotor apraxia, and healthy controls. These

findings do not reflect a non-specific pattern of hemispheric

activation by tDCS. The improvement, indexed by the re-

duction of time to perform the JHFT, is brought about not

only by stimulation of the right M1, contralateral to the left

hand, unaffected by primary motor deficits, but also of the

left PPC, namely of the hemisphere ipsilateral to the as-

sessed hand. When in the Ideomotor Apraxia Test a dis-

tinction is drawn between planning and execution times, it

is left PPC tDCS to reduce planning times, and right M1

stimulation to reduce execution times. This pattern matches

the effects of anodal tDCS in young healthy participants

(Convento et al., 2014), and in the controls of the present

study.

These results corroborate the brain-based model pro-

posed by Liepmann (1925). We found a double dissoci-

ation (Teuber, 1955; Vallar, 2000) between the effects of

stimulation of M1 of the right hemisphere (reduction of

execution time, but not of planning time), and those of

stimulation of the PPC of the left hemisphere (reduction

of planning time, but not of execution time). In

Liepmann’s model, planning and motor execution neural

systems are anatomo-functionally organized serially; this

architecture, in the lesion-based neuropsychological ap-

proach, is unable to reveal a functional double dissociation

(Teuber, 1955; Vallar, 2000). Damage to the left motor

cortex brings about a motor deficit, masking apraxia,

which is then assessed in the left hand of left-brain-

damaged patients, with a posterior parietal damage.

However, motor execution systems are symmetrically

located in the two hemispheres: the left (for the right

hand), and the right (for the left hand). The two execution

systems receive signals from the posterior regions of the left

hemisphere (mainly involved in movement planning, with a

hemispheric asymmetry), through left intrahemispheric con-

nections to the left sensorimotor cortex, and a callosal pro-

jection to the right sensorimotor cortex. Accordingly, in

left-brain-damaged patients, the functional independence

of the two systems is suggested by the presence of limb

apraxia in the left hand, unaffected by motor deficits, con-

trasted with the frequently present motor deficits in their

right hand. The occurrence of left-sided motor deficits in

right-brain-damaged patients without apraxia in the right

hand completes the double dissociation. In unimpaired par-

ticipants, the effects of anodal tDCS to the left PPC, with a

decrease of planning, but not of execution, times by the left

hand, and to the right M1, with a decrease of motor exe-

cution, but not of planning, times, represents a double dis-

sociation, not of deficits, but of the tDCS enhancing effects,

coherent with the present neuropsychological data in left-

brain-damaged patients with ideomotor apraxia.

Importantly, in apraxic patients the effects of tDCS to the

left PPC are not confined to latencies, but they also result in

an increase of accuracy scores in the Ideomotor Apraxia

Test, suggesting a possible clinical relevance of the present

findings for rehabilitation. These findings converge in indi-

cating that the neural network modulated by tDCS is func-

tionally spared, at least in part. Whether this functional

sparing reflects post-lesion changes involving neural plasti-

city in structurally spared regions taking over the damaged

function, enhanced residual function of hypo-functioning

regions, or both mechanisms, is unclear (Will et al.,

2008; Berlucchi and Buchtel, 2009; Berlucchi, 2011).

However, as the effects found in left-brain-damaged pa-

tients are qualitatively similar to those found in neurologic-

ally unimpaired participants by means of tDCS (Convento

et al., 2014), one mechanism may involve a partly pre-

served function with similar neural underpinnings. In line

with this view, the amount of the lesion affecting the left

parietal cortex influences the patients’ reduction of plan-

ning times. The neural regions involved in the function of

interest (the programming of action by the upper limbs)

under physiological conditions, when spared by the brain

damage, may still play a role in the temporary functional

recovery driven by anodal tDCS. Patients with left parietal

damage appear to show a minor improvement at the test

for ideomotor apraxia, than patients without parietal in-

volvement. Similar findings were obtained in right-brain-

damaged patients with left neglect, namely: the greater is

the estimated lesion volume, the smaller is the tDCS-

induced reduction of the rightward bias in the line bisection

task (Sparing et al., 2009).

Although the duration of the tDCS effects was not dir-

ectly assessed, our multiple-baseline design allows the con-

trol of carry-over effects across sessions, separated by at

least 24 h: the absence of significant differences between

the baseline performances across tDCS sessions suggests

that the enhancements by tDCS vanished after 24 h.

Future studies will be of importance for determining

whether multiple, consecutive applications of tDCS to the

left parietal cortex may induce a long-lasting, and maybe

larger, improvement of ideomotor apraxia.

In line with the present findings, unilateral (anodal stimu-

lation of the left inferior frontal gyrus of the damaged

10 | BRAIN 2014: Page 10 of 12 N. Bolognini et al.

hemisphere, or cathodal stimulation of the homologous

region of the right hemisphere, Marangolo et al., 2011),

and bilateral tDCS (Marangolo et al., 2013) improve

apraxia of speech, and other aspects of aphasia. In this

study, no effects were found on phonemic fluency, in line

with repeated observations that fluency is modulated by

tDCS delivered to the left premotor cortex (Broca’s area)

of right-handed healthy participants (Cattaneo et al., 2011).

In this study, the frontal stimulation was delivered to M1

of the right hemisphere. The absence of effects on phon-

emic fluency, together with the positive effects on motor

and apraxic functions, provide further evidence against in-

terpretations in terms of non-specific tDCS effects.

The present evidence opens perspectives for delivering

anodal tDCS to the damaged left hemisphere, as an adju-

vant to behavioural treatment (Bolognini et al., 2009) in

the rehabilitation of apraxia. The present effects seem

robust, in the face of patients’ sample size (n = 6), differ-

ences in length of illness, lesion size and location. These

variables did not influence the effects of tDCS, which

have neural specificity, as indicated by the role of the

spared left PPC. This evidence is encouraging for a clinical

rehabilitation trial. Limb apraxia has an adverse influence

on the functional abilities, and on patients’ responsiveness

during physical and language therapies (West et al., 2008).

To date, limb apraxia is a not adequately treated disorder

(Dovern et al., 2012), with a need to develop new thera-

peutic strategies; the present study suggests that tDCS may

be a therapeutic option for limb apraxia.

FundingThis work has been supported in part by F.A.R. from the

University of Milano-Bicocca to G.V., and by Ricerca

Corrente Grants from the Italian Ministry of Health to

the IRCCS Istituto Auxologico Italiano.

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