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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.
� The Author (2014). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved.
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Brain Advance Access published December 5, 2014
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.
ReferencesBarbieri C, De Renzi E. The executive and ideational components of
apraxia. Cortex 1988; 24: 535–43.
Berlucchi G, Buchtel HA. Neuronal plasticity: historical roots and
evolution of meaning. Exp Brain Res 2009; 192: 307–19.
Berlucchi G. Brain plasticity and cognitive neurorehabilitation.
Neuropsychol Rehabil 2011; 21: 560–78.Bisiach E, Faglioni P. Recognition of random shapes by patients with
unilateral lesions as a function of complexity, association value and
delay. Cortex 1974; 10: 101–10.
Boggio PS, Castro LO, Savagim EA, Braite R, Cruz VC, Rocha RR,
et al. Enhancement of non-dominant hand motor function by anodal
transcranial direct current stimulation. Neurosci Lett 2006; 404:
232–6.Boggio PS, Nunes A, Rigonatti SP, Nitsche MA, Pascual-Leone A,
Fregni F. Repeated sessions of noninvasive brain DC stimulation is
associated with motor function improvement in stroke patients.
Restor Neurol Neurosci 2007; 25: 123–9.
Bolognini N, Miniussi C, Gallo S, Vallar G. Induction of mirror-touch
synaesthesia by increasing somatosensory cortical excitability. Curr
Biol 2013a; 23: R436–7.
Bolognini N, Olgiati E, Maravita A, Ferraro F, Fregni F. Motor and
parietal cortex stimulation for phantom limb pain and sensations.
Pain 2013b; 154: 1274–80.
Bolognini N, Olgiati E, Xaiz A, Posteraro L, Ferraro F, Maravita A.
Touch to see: neuropsychological evidence of a sensory mirror
system for touch. Cereb Cortex 2012; 22: 2055–64.
Bolognini N, Pascual-Leone A, Fregni F. Using non-invasive brain
stimulation to augment motor training-induced plasticity. J
Neuroeng Rehabil 2009; 6: 8.
Bolognini N, Vallar G, Casati C, Latif LA, El-Nazer R, Williams J,
et al. Neurophysiological and behavioral effects of tDCS combined
with constraint-induced movement therapy in poststroke patients.
Neurorehabil Neural Repair 2011; 25: 819–29.Brunoni AR, Zanao TA, Vanderhasselt M-A, Valiengo L, de
Oliveira JF, Boggio PS, et al. Enhancement of affective processing
induced by bifrontal transcranial direct current stimulation in pa-
tients with major depression. Neuromodulation 2014; 17: 138–42.
Buxbaum LJ, Haaland K, Hallett M, Wheaton L, Heilman KM,
Rodriguez A, et al. Treatment of limb apraxia: moving forward to
improved action. Am J Phys Med Rehabil 2008; 87: 149–61.
Buxbaum LJ, Shapiro AD, Coslett HB. Critical brain regions for tool-
related and imitative actions: a componential analysis. Brain 2014;
137: 1971–85.
Buxbaum LJ. Ideomotor apraxia: a call to action. Neurocase 2001; 7:
445–58.
Caffarra P, Vezzadini G, Dieci F, Zonato F, Venneri A. Rey-Osterrieth
complex figure: normative values in an Italian population sample.
Neurol Sci 2002; 22: 443–7.
Cattaneo Z, Pisoni A, Papagno C. Transcranial direct current stimu-
lation over Broca’s region improves phonemic and semantic fluency
in healthy individuals. Neuroscience 2011; 183: 64–70.
Cohen J. Eta-squared and partial eta-squared in fixed factor anova
designs. Educ Psychol Meas 1973; 33: 107–12.
Convento S, Bolognini N, Fusaro M, Lollo F, Vallar G.
Neuromodulation of parietal and motor activity affects motor plan-
ning and execution. Cortex 2014; 57: 51–9.
Convento S, Vallar G, Galantini C, Bolognini N. Neuromodulation of
early multisensory Interactions in the visual cortex. J Cogn Neurosci
2012; 25: 685–96.
Dovern A, Fink GR, Weiss PH. Diagnosis and treatment of upper limb
apraxia. J Neurol 2012; 259: 1269–83.
Foundas AL. Apraxia: neural mechanisms and functional recovery. In:
Barnes MP, Good DC, editors. Handbook of Clinical Neurology.
Amsterdam: Elsevier; 2013. p. 335–35.
Fregni F, Boggio PS, Mansur CG, Wagner T, Ferreira MJL, Lima MC,
et al. Transcranial direct current stimulation of the unaffected hemi-
sphere in stroke patients. Neuroreport 2005; 16: 1551–5.
Gandiga PC, Hummel FC, Cohen LG. Transcranial DC stimulation
(tDCS): a tool for double-blind sham-controlled clinical studies in
brain stimulation. Clin Neurophysiol 2006; 117: 845–50.Geschwind N. Disconnexion syndromes in animals and man. Part II.
Brain 1965; 88: 585–644.
Geschwind N. The apraxias: neural mechanisms of disorders of
learned movement. Am Sci 1975; 63: 188–95.
Goldenberg G. Apraxia and beyond: life and work of Hugo Liepmann.
Cortex 2003; 39: 509–24.
Goldenberg G. Apraxia and the parietal lobes. Neuropsychologia
2009; 47: 1449–59.
Goldenberg G. Apraxia. The cognitive side of motor control. Oxford,
England: Oxford University Press; 2013.
Haaland KY, Harrington DL, Knight RT. Neural representations of
skilled movement. Brain 2000; 123: 2306–13.
Hanna-Pladdy B, Heilman KM, Foundas AL. Cortical and subcortical
contributions to ideomotor apraxia: analysis of task demands and
error types. Brain 2001; 124: 2513–27.
Left parietal stimulation improves apraxia BRAIN 2014: Page 11 of 12 | 11
Hummel F, Celnik P, Giraux P, Floel A, Wu WH, Gerloff C, et al.Effects of non-invasive cortical stimulation on skilled motor function
in chronic stroke. Brain 2005; 128: 490–9.
Jebsen RH, Taylor N, Trieschmann RB, Trotter MJ, Howard LA. An
objective and standardized test of hand function. Arch Phys MedRehabil 1969; 50: 311–19.
Ladeira A, Fregni F, Campanha C, Valasek CA, De Ridder D,
Brunoni AR, et al. Polarity-dependent transcranial direct current
stimulation effects on central auditory processing. PLoS One 2011;6: e25399.
Leiguarda RC, Marsden CD. Limb apraxias: higher-order disorders of
sensorimotor integration. Brain 2000; 123: 860–79.Liepmann H. Drei Aufsatze aus dem Apraxie-Gebiet. Berlin: S. Karger;
1908.
Liepmann H. Apraktische storungen. In: Curschmann H, Kramer F,
editors. Lehrbuch der nervenkrankheiten. Berlin: Springer; 1925.p. 408–16.
Liepmann H. The syndrome of apraxia (motor asymboly) based on a
case of unilateral apraxia. In: Rottenberg DA, Hochberg FH, edi-
tors. Neurological classics in modern translation. New York: HafnerPress; 1977. p. 155–81.
Liepmann H. Apraxia. In: Brown JW, editor. Agnosia and apraxia:
Selected papers of Liepmann.. Lange, and Potzl. Hillsdale, NJ:
Lawrence Erlbaum Associates, Publishers; 1988. p. 3–39.Marangolo P, Fiori V, Cipollari S, Campana S, Razzano C, Di
Paola M, et al. Bihemispheric stimulation over left and right inferior
frontal region enhances recovery from apraxia of speech in chronicaphasia. Eur J Neurosci 2013; 38: 3370–7.
Marangolo P, Marinelli CV, Bonifazi S, Fiori V, Ceravolo MG,
Provinciali L, et al. Electrical stimulation over the left inferior frontal
gyrus (IFG) determines long-term effects in the recovery of speechapraxia in three chronic aphasics. Behav Brain Res 2011; 225:
498–504.
Molenberghs P, Cunnington R, Mattingley JB. Brain regions with
mirror properties: a meta-analysis of 125 human fMRI studies.Neurosci Biobehav Rev 2012; 36: 341–9.
Monte-Silva K, Kuo M-F, Hessenthaler S, Fresnoza S, Liebetanz D,
Paulus W, et al. Induction of late LTP-like plasticity in the humanmotor cortex by repeated non-invasive brain stimulation. Brain
Stimul 2013; 6: 424–32.
Monte-Silva K, Kuo M-F, Liebetanz D, Paulus W, Nitsche MA.
Shaping the optimal repetition interval for cathodal transcranialdirect current stimulation (tDCS). J Neurophysiol 2010; 103:
1735–40.
Muhlau M, Hermsdorfer J, Goldenberg G, Wohlschlager AM,
Castrop F, Stahl R, et al. Left inferior parietal dominance in gestureimitation: an fMRI study. Neuropsychologia 2005; 43: 1086–98.
Nitsche MA, Cohen LG, Wassermann EM, Priori A, Lang N, Antal A,
et al. Transcranial direct current stimulation: state of the art 2008.Brain Stimul 2008; 1: 206–23.
Novelli G, Papagno C, Capitani E, Laiacona M, Vallar G, Cappa SF.
Tre test clinici di ricerca e produzione lessicale. Taratura su soggetti
normali. Arch Psicol Neurol Psichiatr 1986; 47: 477–506.
Oldfield RC. The assessment and analysis of handedness: theEdinburgh inventory. Neuropsychologia 1971; 9: 97–113.
Orsini A, Grossi D, Capitani E, Laiacona M, Papagno C, Vallar G.
Verbal and spatial immediate memory span. Normative data from
1355 adults and 1112 children. Ital J Neurol Sci 1987; 8: 539–48.Poreisz C, Boros K, Antal A, Paulus W. Safety aspects of transcranial
direct current stimulation concerning healthy subjects and patients.
Brain Res Bull 2007; 72: 208–14.
De Renzi E, Faglioni P. Normative data and screening power of ashortened version of the Token Test. Cortex 1978; 14: 41–9.
De Renzi E, Faglioni P. L’aprassia. In: Denes G, Pizzamiglio L,
editors. Manuale di neuropsicologia. Bologna: Zanichelli; 1996. p.557–93.
De Renzi E, Lucchelli F. Ideational apraxia. Brain 1988; 111:
1173–85.
De Renzi E, Motti F, Nichelli P. Imitating gestures. A quantitativeapproach to ideomotor apraxia. Arch Neurol 1980; 37: 6–10.
Rorden C, Brett M. Stereotaxic display of brain lesions. Behav Neurol
2000; 12: 191–200.
Rosenkranz K, Nitsche MA, Tergau F, Paulus W. Diminution of train-ing-induced transient motor cortex plasticity by weak transcranial
direct current stimulation in the human. Neurosci Lett 2000; 296:
61–3.
Rossi S, Hallett M, Rossini PM, Pascual-Leone A. Safety, ethical con-siderations, and application guidelines for the use of transcranial
magnetic stimulation in clinical practice and research. Clin
Neurophysiol 2009; 120: 2008–39.Sokal RR, Rohlf FJ. Biometry. New York, NY: Freeman; 1995.
Sparing R, Thimm M, Hesse MD, Kust J, Karbe H, Fink GR.
Bidirectional alterations of interhemispheric parietal balance by
non-invasive cortical stimulation. Brain 2009; 132: 3011–20.Spinnler H, Tognoni G. Standardizzazione e taratura Italiana di test
neuropsicologici. Ital J Neurol Sci 1987; 6 (Suppl. 8): S1–120.
Teuber H-L. Physiological psychology. Annu Rev Psychol 1955; 9:
267–96.Vallar G. Spatial hemineglect in humans. Trends Cogn Sci 1998; 2:
87–97.
Vallar G. The methodological foundations of human neuropsychology:studies in brain-damaged patients. In: Boller F, Grafman J,
Rizzolatti G, editors. Handbook of Neuropsychology. Amsterdam,
The Netherlands: Elsevier; 2000. p. 305–44.
Weiss PH, Achilles EIS, Moos K, Hesse MD, Sparing R, Fink GR.Transcranial direct current stimulation (tDCS) of left parietal cortex
facilitates gesture processing in healthy subjects. J Neurosci 2013;
33: 19205–11.
West C, Bowen A, Hesketh A, Vail A. Interventions for motorapraxia following stroke. Cochrane Database Syst Rev 2008; 1:
CD004132.
Will B, Dalrymple-Alford J, Wolff M, Cassel J-C. Reflections on theuse of the concept of plasticity in neurobiology. Translation and
adaptation by Bruno Will, John Dalrymple-Alford, Mathieu Wolff
and Jean-Christophe Cassel from J. Paillard. J Psychol 1976; 1:
33–47. Behav Brain Res 2008; 192: 7–11.
12 | BRAIN 2014: Page 12 of 12 N. Bolognini et al.