Transcranial direct current stimulation (tDCS) has been proposed as an adjuvant technique to improve functional recovery after ischaemic stroke. This study evaluated the effect of tDCS over the left frontotemporal areas in eight chronic non-fluent post-stroke aphasic patients. The protocol consisted of the assessment of picture naming (accuracy and response time) before and immediately after anodal or cathodal tDCS (2 mA, 10 minutes) 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 a mean of 33.6% (SEM 13.8%).
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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 also be adjuvant strategies to improve functional recovery after ischaemic stroke.4 Aphasia is a dramatic and frequent consequence of stroke. Nonetheless, although the ability to generate lists of words increases after tDCS in normal individuals,5 the effects of tDCS in patients with aphasia are unknown.
This study aimed to assess the effect of tDCS over the damaged left frontotemporal 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, cathodal tDCS or sham (ie, placebo stimulation) tDCS. To assess the specificity of our findings in additional control experiments patients were evaluated before and after cathodal tDCS over the occipital cortex.
Eight right-handed chronic non-fluent aphasic patients (four men and four women, aged 60.38 years, SEM 11.99) were studied after ethical committee approval and informed consent. All the patients underwent a complete neuropsychological evaluation, including a shorter version of the token test6 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 past 12 months, psychiatric disease and dementia were excluded. In table 1 are reported patient demographics and stroke characteristics.
Picture naming task
For each picture naming session subjects were asked to name pictures presented on a personal computer screen from one out of four lists (A–D). The accuracy of naming (the number of pictures correctly named in a 20-item list; we scored “1” for correct responses and “0” for errors) and the mean response times (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 two items from a variety of semantic categories (living and non-living). Italian standardized norms for the name agreement and synonyms of the target word were accepted.8
Transcranial direct current stimulation
tDCS (2 mA, 10 minutes) 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 the left frontotemporal areas (Broca’s region, defined as the crossing point between T3-Fz and F7-Cz according to the 10–20 system)9 and the other above the right shoulder (reference electrode).10 Experiment 2: the stimulating electrode was placed over the occipital areas (2 cm over the inion) and the reference over the right shoulder. For sham tDCS (ie, placebo), electrodes were placed as for real stimulation but the stimulator was turned off after 10 seconds. Apart from occasional, transient and short-lasting tingling and burning sensations below the electrodes, tDCS remained below the conscious cutaneous sensory threshold throughout the experimental session. Therefore, the patients could not discriminate the polarity of the stimulation (anodal or cathodal) or the real tDCS from the sham tDCS.
Patients were assigned to an “anodal tDCS” group (four subjects) and a “cathodal tDCS” group (four subjects). The first group underwent anodal tDCS and sham tDCS over the left frontotemporal areas, whereas the second underwent cathodal tDCS and sham tDCS. Active (anodal tDCS or cathodal tDCS) and sham tDCS were tested in random order and at least one week elapsed between sessions. As two subjects of the first group and two of the second group were stimulated with inverted polarity, in total, six patients underwent anodal tDCS/sham tDCS in two separate sessions and six patients underwent cathodal tDCS/sham tDCS in two separate sessions. The subjects and the examiner were blinded to 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. Individual patients did not receive the same list twice (fig 1A).
Picture naming was assessed as in experiment 1 in all eight subjects before and after occipital lobe cathodal tDCS and sham tDCS. Two months elapsed between experiments 1 and 2.
Statistical analysis on each group was performed using two-way analysis of variance (ANOVA) (within factors: stimulation (anodal tDCS/cathodal tDCS versus sham tDCS); time (before versus after)) and paired Student’s t test. We used Bonferroni correction for multiple ANOVA testing, therefore we used the threshold of p<0.012. Values in the text are means ± SEM.
tDCS over the left frontotemporal areas (experiment 1)
Baseline values in the two groups did not differ (anodal tDCS 12.17 (SEM 1.48), cathodal tDCS 11.67 (SEM 1.48), t test p = 0.81). The two-way ANOVA failed to show a significant difference in the anodal tDCS group (stimulation × time, p = 0.20) but disclosed a significant difference in the cathodal tDCS group (stimulation × time p = 0.002). Whereas anodal tDCS and sham tDCS failed to induce a significant naming improvement (anodal tDCS: before 12.0 (SEM 2.29), after 11.83 (SEM 2.29); sham tDCS before 12.33 (SEM 2.09), after 12.66 (SEM 2.23)), cathodal tDCS increased naming accuracy (cathodal tDCS: before 11.67 (SEM 1.96), after 14.50 (SEM 1.69), Tukey’s post-hoc test p = 0.002; sham tDCS: before 11.67 (SEM 2.14), after 11.67 (SEM 2.16), Tukey’s post-hoc test p = 0.99). The significant improvement in picture naming after cathodal tDCS was confirmed by the analysis of the percentage change in baseline values after treatment (cathodal tDCS: 33.6 (SEM 13.8%) versus sham tDCS: 0.4 (SEM 4.3%), paired t test p = 0.033; fig 1B).
No differences regarding the qualitative features of errors (anomia and more rarely semantic errors) were found between baseline and poststimulation evaluations.
Two-way ANOVA showed no significant differences in the anodal tDCS group (stimulation × time, p = 0.29) and in the cathodal tDCS group (stimulation × time, p = 0.22). The analysis of RT percentage changes confirmed the absence of significant effects after tDCS (paired t test: anodal tDCS p = 0.099, cathodal tDCS p = 0.31).
tDCS over the occipital area (experiment 2)
The two-way ANOVA did not show any significant effect either for the accuracy (stimulation × time, p = 0.60) or for the RT (stimulation × time, p = 0.74).
After cathodal tDCS over the left frontotemporal areas in patients with non-fluent aphasia the accuracy of picture naming significantly improved by some 34%. Because anodal tDCS and sham tDCS of the same areas did not induce any effect and cathodal tDCS over the occipital cortex failed to induce any change, the improvement in naming after cathodal tDCS over the left frontotemporal areas is polarity and site specific. Also, the lack of changes in the RT argues against the hypothesis that the improvement in naming arises from non-specific changes in arousal or attention. Our results after 10 minutes of cathodal tDCS are in line with those obtained after 10 days low frequency repetitive TMS over the right Broca’s in four chronic aphasic patients.11 Notably, tDCS is more simple than repetitive TMS and in our experiments cathodal tDCS improved patients after a single, 10-minute application.
After a stroke, abnormally increased cortical inhibition contributes to motor dysfunction. TMS studies revealed that cortical inhibition is abnormally increased in the affected hemisphere and that motor recovery after a stroke parallels the reduction in cortical inhibition, thus suggesting that “motor dysfunction may be caused by hyperactivity of cortical inhibitory interneurons”.12 Also, interhemispheric inhibition from the intact to the affected hemisphere is abnormally increased in patients with stroke.13 Because cathodal tDCS 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,15 we used an extracephalic reference electrode, avoiding confusion regarding the source of the observed effect. As in our previous studies with this electrode's setup,10 15 none of our subjects complained of side effects or showed clinical signs attributable to current spread to the brainstem.
In conclusion, whatever the mechanism, cathodal tDCS over the damaged left frontotemporal areas improves naming in chronic non-fluent aphasic patients. tDCS is simple, safe and inexpensive and thus it might possibly be useful in the management of post-stroke aphasia.
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 Professor Anna Basso, Dr Alessandra Caporali and Mrs Elena Fenu for their help in the selection of patients.
Competing interests: None.
Ethics approval: Ethics approval was obtained.
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