Improved Naming After Transcranial Direct Current Stimulation in Aphasia Alessia Monti*, Filippo Cogiamanian*, Sara Marceglia, Roberta Ferrucci, Simona MrakicSposta, Maurizio Vergari, Stefano Zago, and Alberto Priori
Neurostimulation Unit, Department of Neurological Sciences, University of Milan, Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena, Milan, Italy
*the first two authors equally contributed to the work
Corresponding author: Prof Alberto Priori Dipartimento di Scienze Neurologiche Università degli Studi di Milano Ospedale Maggiore Policlinico Padiglione Ponti V. F. Sforza 35 Milano, 20122 Italy phone ++39-02-50320438 e-mail:
[email protected]
Keywords: Broca’s area, aphasia, aphasia treatment, stroke, tDCS Number of words: 1354
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ABSTRACT Transcranial direct current stimulation (tDCS) has been proposed as an adjuvant technique to improve functional recovery after ischemic stroke. In this study we evaluate the effect of tDCS over left fronto-temporal (F-T) areas in eight chronic non-fluent post-stroke aphasic patients. The protocol consisted in the assessment of picture naming (accuracy and response time) before and immediately after anodal or cathodal tDCS (2 mA, 10 min) and sham stimulation. Whereas anodal tDCS and sham tDCS failed to induce any changes, cathodal tDCS significantly improved the accuracy of the picture naming task by 33.6±13.8% ([mean±SEM] p=0.033).
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Transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) induce excitability changes in the normal brain.[1-3] These non-invasive brain stimulation techniques can be also adjuvant strategies to improve functional recovery after ischemic stroke.[4] Aphasia is a dramatic and frequent consequence of stroke. Nonetheless, although the ability to generate lists of words increases after tDCS in normals,[5] the effects of tDCS in patients with aphasia are unknown. This study aimed to assess the effect of tDCS over the damaged left fronto-temporal (F-T) areas in patients with chronic, non-fluent, post-stroke aphasia. To do so we used a computer-controlled picture naming task before and after anodal tDCS (AtDCS), cathodal tDCS (CtDCS) or sham (i.e. placebo stimulation) tDCS (StDCS). To assess the specificity of our findings, in additional control experiments patients were evaluated before and after CtDCS over the occipital cortex. METHODS Subjects Eight right-handed chronic non-fluent aphasic patients (4 males and 4 females, age 60.38±11.99) were studied after ethical committee approval and informed consent. All the patients underwent a complete neuropsychological evaluation, including a shorter version of Token Test [6] and a standard language examination currently in use at the “Language Rehabilitation Unit” of the Neurological Department of Milan University.[7] Patients with severely impaired auditory verbal comprehension (Token Test < 8), severe apraxia of speech, seizures in the last 12 months, psychiatric disease and dementia were excluded. Table 1 summarizes patient demographics and stroke characteristics. 3
Table 1. Clinical characteristics of patients and effect of tDCS on accuracy of naming before and after stimulation Patients Age, Education tDCS Sex No. years , years
Stroke etiology
Lesion Time after site stroke, yrs
Aphasia type
Accuracy of naming (range 0-20) before
after
A
16/20
16/20
C
16/20
18/20
S
18/20
19/20
A
13/20
12/20
C
12/20
16/20
S
11/20
11/20
A
16/20
16/20
S
17/20
17/20
A
17/20
17/20
S
15/20
16/20
C
5/20
10/20
A
6/20
6/20
S
6/20
7/20
C
13/20
15/20
S
10/20
10/20
C
7/20
9/20
A
4/20
4/20
S
7/20
6/20
C
17/20
19/20
S
18/20
17/20
Co/S 1
A, C
43
F
8
Thrombosis L MCA
8
B
(F)
2
3
A, C
A
68
48
M
F
13
8
Thrombosis L MCA
Thrombosis L MCA
Co/S (F,P)
Co/S (F,T,P)
4
3
G
B
S 4
A
74
M
5
Thrombosis L MCA
5
G
(F,P) Co/S 5
C,A
62
M
12
Thrombosis L MCA
4
G
(F, T, P)
6
C
51
F
17
SAH of R anterior communicating a. + vasospasm L MCA
Co/S 3
B
(F) Co/S
7
C, A
75
F
5
Thrombosis L ICA
2
G
(F)
8
Mean (SD)
C
62
60.37 (11.98)
M
17
Thrombosis L ICA
Co/S (F,P)
2,5
10.62
3.93
(4.86)
(1.89)
B
F indicates female; M, male; B, Broca’s aphasia; G, global aphasia; C, cathodal tDCS; A, anodal tDCS; S, sham stimulation; ICA, internal carotid artery; MCA, middle cerebral artery; SAH, subarachnoid hemorrhage; Co, cortical; S, subcotical; F, frontal; T, temporal; P, parietal; L, left; R, right.
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Picture naming task For each picture naming session subjects were asked to name pictures presented on a personal computer screen from one out the four lists (A-D). The accuracy of naming (the number of picture correctly named in a 20-items list, we score “1” for the correct responses and “0” for errors”) and the mean response time (RT) were recorded. The lists were homogeneous for difficulties and were controlled for frequency of use, familiarity, visual complexity, grammatical class (nouns) and length in syllables, each list contained 2 items from a variety of semantic categories (living and non-living). Italian standardized norms for the name agreement and synonymous of the target word were accepted. [8] tDCS tDCS (2 mA, 10 min) was delivered by a constant current electrical stimulator (Eldith, Ilmenau, Germany) connected to a pair of electrodes (35 cm2). Experiment 1: one electrode was placed over left F-T areas (Broca’s region, defined as the crossing point between T3-Fz and F7-Cz according to 10-20 system) [9] and the other above the right shoulder (reference electrode).[10] Experiment 2: the stimulating electrode was over occipital areas (2 cm over the inion) and the reference over the right shoulder. For StDCS (i.e. placebo), electrodes were placed as for real stimulation but the stimulator was turned off after 10 s. The subjects therefore felt the initial itching sensation when stimulation began but thereafter received no current. Experiment 1 Patients were assigned to an “AtDCS” group (4 subjects) and a “CtDCS” group (4 subjects). The first group underwent AtDCS and StDCS over the left F-T areas whereas the second underwent CtDCS and StDCS. Active (AtDCS or CtDCS) and StDCS were tested in random order and at least 1 week elapsed between sessions. As two subjects of the first group and two of the second
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group have been submitted to inverted polarity, in total, six patients underwent AtDCS/StDCS in two separate sessions and six patients underwent CtDCS/StDCS in two separate sessions. The subjects and the examiner were blinded about the type of stimulation. For each naming session the accuracy and RT in naming 20 pictures from one list, randomly selected out of four homogeneous lists, before and immediately after tDCS offset were measured. Each patient did not receive the same list twice. Experiment 2 Picture naming was assessed as in experiment 1 in all the 8 subjects before and after occipital lobe CtDCS and StDCS. Two months elapsed between experiment 1 and 2. Data analysis Statistical analysis on each group was performed using two-way ANOVA (within factors: stimulation [AtDCS/CtDCS vs StDCS]; time [before vs after]) and paired Student t-test with Bonferroni correction. Values in the text are means±SEM. RESULTS tDCS over the left F-T areas (Experiment 1) Accuracy: baseline values in the two groups did not differ (AtDCS 12.17±1.48, CtDCS 11.67±1.48 t-test p=0.81). two-way ANOVA failed to show a significant difference in the AtDCS group (stimulation x time, p=0.20) but disclosed a significant difference in the CtDCS group (stimulation x time p=0.002). Whereas AtDCS and StDCS failed to induce significant naming improvement (AtDCS: before 12.0 ± 2.29, after 11.83 ± 2.29; before 12.33 ± 2.09, after 12.66 ± 2.23, figure 1B), CtDCS increased naming accuracy (CtDCS: before 11.67 ± 1.96, after
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14.50 ± 1.69, Tukey’s post-hoc test p = 0.002; S tDCS: before 11.67 ± 2.14, after 11.67 ± 2.16, Tukey’s post-hoc test p = 0.99, Figure 1A). The significant improvement of picture naming by about 33.6% after CtDCS was confirmed by the analysis of percentage change of baseline values after treatment (CtDCS: 33.6 ± 13.8%vs StDCS: 0.4 ± 4.3%, paired t-test p=0.033, Figure 1C). No differences regarding the qualitative features of errors (anomia and more rarely semantic errors) were found between baseline and post-stimulation evaluations. RTs: two-way ANOVA showed no significant differences in the AtDCS group (stimulation x time, p=0.29) and in the CtDCS group (stimulation x time, p=0.22). The analysis of RT percentage changes confirmed no significant differences (paired t-test AtDCS p=0.099, CtDCS p=0.31) tDCS over the occipital area (Experiment 2) The two-way ANOVA did not show any significant effect neither for the accuracy (stimulation x time, p=0.60), nor for the RTs (stimulation x time, p=0.74). DISCUSSION After CtDCS over the left F-T areas in patients with non-fluent aphasia the accuracy of picture naming significantly improved by some 34%. Because AtDCS and StDCS of the same areas did not induce any effect and CtDCS over the occipital cortex failed to induce any change, the improvement in naming after CtDCS over the left F-T areas is polarity and site specific. Also, the lack of changes in the RTs argues against the hypothesis that the improvement in naming arises from non specific changes in arousal or attention. Our results after ten-minutes CtDCS are in line with those obtained after ten-days low frequency rTMS over right Broca’s in four chronic
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aphasic patients.[11] Notably, tDCS is more simple than rTMS, and in our experiments CtDCS improved patients after a single, ten-minutes application. After a stroke, abnormally increased cortical inhibition contributes to motor dysfunction. Yet, TMS studies revealed that cortical inhibition is abnormally increased in the affected hemisphere and that motor recovery after a stroke parallels the reduction of cortical inhibition, thus suggesting that ”motor dysfunction may be caused by hyperactivity of cortical inhibitory interneurons”.[12] Also, interhemispheric inhibition from intact to the affected hemisphere is abnormally increased in patients with stroke.[13] Because CtDCS decreases the excitability of cortical inhibitory circuits,[14] the improvement we observed in patients with aphasia can arise from a tDCS-induced depression of cortical inhibitory interneurones, ultimately leading to a disinhibition and, consequently, to the improved function of the damaged language areas of the cerebral cortex. As fully discussed elsewhere, we used an extracephalic reference electrode, avoiding confusion regarding the source of the observed effect. [15] As well as in our previous studies, none of our subjects showed any change in the heart rate and body temperature or signs and symptoms attributable to the modulation of brainstem activity. In conclusion, whatever the mechanism, CtDCS over the damaged left F-T areas improves naming in chronic non-fluent aphasic patients. tDCS is simple, safe, and inexpensive and, hence, it might be possibly useful in the management of post-stroke aphasia.
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Acknowledgments: the authors are grateful to the patients as well as to their families for their willing participation in many hours of testing. The authors thank Prof. Anna Basso, Dr Alessandra Caporali and Mrs Elena Fenu for their aid to the patients’ selection. Competing interests: the authors report no conflicts of interest
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10. Priori A, Mameli F, Cogiamanian F et al. Lie-specific involvement of dorsolateral prefrontal cortex in deception. Cereb Cortex. 2007;doi: 10.1093/cercor/bhm088 11. Naeser MA, Martin PI, Nicholas M et al. Improved picture naming in chronic aphasia after tms to part of right broca's area: An open-protocol study. Brain Lang. 2005;93:95105 12. Classen J, Schnitzler A, Binkofski F et al. The motor syndrome associated with exaggerated inhibition within the primary motor cortex of patients with hemiparetic. Brain. 1997;120:605-19 13. Murase N, Duque J, Mazzocchio R et al. Influence of interhemispheric interactions on motor function in chronic stroke. Ann Neurol. 2004;55:400-9 14. Lang N, Nitsche MA, Paulus W et al. Effects of transcranial direct current stimulation over the human motor cortex on corticospinal and transcallosal excitability. Exp Brain Res. 2004;156:439-43 15. Cogiamanian F, Marceglia S, Ardolino G et al. Improved isometric force endurance after transcranial direct current stimulation over the human motor cortical areas. Eur J Neurosci. 2007;26:242-9.
FIGURE LEGENDS Figure 1. Panel A. Experimental design. Panel B. Whereas CtDCS significantly (* p=0.0017) improved accuracy of the picture naming task (left), AtDCS did not, in comparison to StDCS (middle). The effect of CtDCS was confirmed by the analysis of naming accuracy as % variation of baseline (right). Error bars are SEM.
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