Advances and Innovations in Aphasia Treatment Trials
Aphasia is a common complication of stroke with a prevalence of ≈1 million in the United States alone.1 Poststroke aphasia (PSA) can be devastating, impacting an individual’s ability to express or comprehend language, often disrupting communication, socialization, and work. Intervention is often necessary to improve language, independence, and quality of life. This article summarizes advances in clinical trials of PSA treatment in the past 5 years. We completed a search of Pubmed to identify clinical trials completed within the past 5 years using the following terms: stroke, aphasia, treatment, speech therapy, speech-language pathology, transcranial direct current stimulation (tDCS), and transcranial magnetic stimulation (TMS). We included the 40 most relevant studies found in our search. Research trends include noninvasive brain stimulation (NIBS), novel Speech-Language Therapy (SLT), pharmacological treatments, and alternative treatments.
Noninvasive Brain Stimulation
NIBS is a promising technique to augment traditional SLT for PSA. tDCS and repetitive TMS (rTMS) are 2 such techniques used in both clinical research and clinical practice. Devido dos Santos et al2 compared a single session each with TMS, tDCS, and sham in randomized order with a naming task and found no statistical significance between before and after stimulation across conditions. Results might reflect the need for greater frequency or intensity of NIBS to improve language. The studies described below delivered NIBS paired with concurrent or subsequent SLT for 2 to 15 sessions. These trials are summarized in Tables 1 and 2.
| Authors | Design | Participants | Type of Stimulation | Location Targeted | No. of Sessions | Results |
|---|---|---|---|---|---|---|
| Campana et al3 | Crossover trial | 20 chronic nonfluent PSA | A-TDCS | Left IFG | 20 (10 anodal and 10 sham) | Damage to specific sites associated with lower responses to A-TDCS |
| Rodriques da Silva et al4 | Double-blind, randomized placebo-controlled trial | 14 subacute-chronic PSA | C-TDCS | Right Broca’s homolog | 5 | Improved response time on the Boston Naming Test, C-TDCS >sham |
| Darkow et al5 | Randomized crossover trial | 16 chronic PSA | A-TDCS | Left primary motor cortex | 2 | Increased activity in language networks with A-TDCS >sham |
| Devido dos Santos et al2 | Double-blind, randomized placebo-controlled trial | 13 chronic PSA | A-TDCS and rTMS 1 Hz | TDCS: Broca’s area; rTMS: right hemisphere Broca’s homolog | 3; 1 A-TDCS, 1 rTMS, 1 sham | No statistically significant difference between conditions |
| Fridriksson et al6,7 | Double-blind, randomized sham-controlled trial | 74 chronic PSA | A-TDCS | Area of the greatest left hemisphere activation | 15 | Improved Naming A-TDCS >sham; especially in participants with val/val BDNF polymorphism |
| Holland et al8 | Pseudorandomized within-subjects crossover trial | 10 healthy subjects with left hemisphere language dominance | A-TDCS | Left inferior frontal cortex | 2; each session consisted of A-TDCS and sham | A-TDCS had significantly better naming response times and blood oxygen level–dependent signal in Broca’s compared with sham |
| Marangolo et al9 | Double-blind, randomized crossover trial | 12 chronic PSA | C-TDCS | Right cerebellum | 20 (10 with TDCS) | Improved verb generation with C-TDCS only |
| Marangaolo et al10 | Double-blind, randomized sham-controlled, within-subjects, crossover deign | 9 chronic PSA | A-TDCS and C-TDCS | Bilateral stimulation of left IFG and right IFG | 30 (15 sham and 15 with anodal and cathodal tDCS) | Improved articulation of treated and untreated stimuli and stronger functional connectivity in left hemisphere in TDCS condition |
| Meinzer et al 11 | Double-blind, randomized sham-controlled trial | 26 chronic PSA | A-TDCS | Left primary motor cortex | 8 d (2×1.5 h/d) | Improved trained items and Communicative Effectiveness Index scores A-TDCS >sham, lasting 6 mo |
| Pestalozzi et al12 | Double-blind, sham-controlled, within-subjects design | 14 chronic PSA | A-TDCS | Left dorsolateral prefrontal cortex | 3 (1 with testing, 1 with sham, 1 with A-TDCS) | Improved verbal fluency A-TDCS >sham |
| Sebastian et al13 | Double-blind, within-subject, crossover trial | 1 chronic PSA | A-TDCS | Right cerebellum | 15 | Improved spelling of trained and untrained words A-TDCS >sham |
| Spielmann et al14 | Randomized, crossover trial | 13 chronic PSA | A-TDCS | Left IFG vs left STG | 3 (Sham, TDCS to left IFG, TDCS to left STG) | Unable to determine optimal condition; no improvement on untrained items |
A-TDCS indicates anodal transcranial direct current stimulation; BDNF, brain-derived neurotrophic factor; C-TDCS, cathodal transcranial direct current stimulation; IFG, inferior frontal gyrus; PSA, poststroke aphasia; rTMS, repetitive transcranial magnetic stimulation; STG, superior temporal gyrus; and TDCS, transcranial direct current stimulation.
| Authors | Design | Participants | Type of Stimulation | Location Targeted | No. of Sessions | Results |
|---|---|---|---|---|---|---|
| Haghighi et al15 | Double-blind, randomized, sham-controlled trial | 12 subacute PSA | rTMS, 1 Hz | Right inferior posterior frontal gyrus | 10 | Improved content, fluency, and WAB aphasia quotient rTMS >sham |
| Hara et al16 | Double-blind, sham-controlled, parallel design | 8 chronic PSA | rTMS: 1 Hz LF or 10 Hz HF depending on language activation | Right IFG | 10 | Improvement on Standard Language Test of Aphasia in both groups |
| Hu et al17 | Double-blind, randomized, sham condition trial | 40 subacute-chronic nonfluent PSA | rTMS 10 Hz HF vs 1 Hz LF | Right Broca’s area homolog | 10 | Improved spontaneous speech, auditory comprehension, and WAB aphasia quotient LF >HF and sham |
| Khedr et al18 | Randomized, crossover trial | 30 subacute nonfluent PSA | rTMS; sequential stimulation of each hemisphere | Right Broca’s area homolog (1 Hz) then left Broca’s area (20 Hz) | 10 | Improved word comprehension, naming, repetition, frequency, and aphasia severity in rTMS >sham |
| Rubi-Fessen et al19 | Crossover trial | 30 subacute PSA | rTMS, 1 Hz | Right IFG | 10 | Improved functional communication TMS >sham |
| Tsai et al20 | Randomized, sham-controlled trial | 56 chronic nonfluent PSA | rTMS, 1 Hz | Right pars triangularis | 10 | Improvements in Concise Chinese Aphasia Test, object naming, and naming reaction time rTMS >sham |
| Wang et al21 | Double-blind, randomized trial | 45 nonfluent PSA | rTMS, 1 Hz | Right Broca’s area homolog | 10 | More improved action and object naming in TMS with synchronous SLT vs TMS with subsequent SLT or sham |
HF indicates high frequency; IFG, inferior frontal gyrus; LF, low frequency; PSA, poststroke aphasia; rTMS, repetitive transcranial magnetic stimulation; SLT, Speech-Language Therapy; TMS, transcranial magnetic stimulation; and WAB, Western Aphasia Battery.
Transcranial Direct Current Stimulation
tDCS utilizes surface electrodes to deliver a constant, weak current to the brain that reduces (or increases) the threshold of activation of neurons, influencing cortical excitability. tDCS is a safe, low-cost adjunct to traditional SLT to maximize language outcomes in individuals with PSA. Anodal and cathodal tDCS (or both) have been utilized in clinical trials. Anodal tDCS is applied to the perilesional area to excite neuronal activity, whereas cathodal tDCS is applied to the healthy hemisphere to inhibit cross-hemisphere inhibition, allowing greater activation of the injured hemisphere. Early, small studies of tDCS to augment aphasia therapy in PSA reported mostly positive effects.22
In all clinical trials we reviewed from the last 5 years, tDCS was administered for 20 minutes with a current ranging from 1 to 2 mA.2–14 The location of electrode placement, SLT treatment methods, and number of sessions were variable. tDCS resulted in better language outcomes (relative to sham) in each of these trials. Pestalozzi et al12 assessed the effects of anodal tDCS to left dorsolateral prefrontal cortex compared with sham, finding immediate improvement in verbal fluency after a single session of tDCS (6.5–5.5 words; P=0.010) and improvement in latency of naming high-frequency pictures (1264.9–1913 ms; P=0.034) but no improvement in naming accuracy. Marangolo et al9 found cathodal tDCS to the right cerebellum significantly improved verb generation when compared with sham (44% versus 15%; P<0.001), with effects persisting at 1 week follow-up. Another study placed cathodal tDCS on the right homolog to Broca’s area, finding the tDCS group had quicker response times with naming therapy when compared with the sham group (1.29–2.57; P=0.050).4 Anodal tDCS placed at the left inferior frontal gyrus (IFG) in conjunction with conversational language therapy resulted in significantly greater improvement compared with sham in picture description (19.5±24.60 versus 10.61±24.50; P=0.033), noun naming (18.30±12.87 versus 9.15±11.34; P=0.024), and verb naming (18.40±17.80 versus 7.30±8.86; P=0.019).3 Several studies have found anodal tDCS delivered at M1 paired with naming treatment stimulates language centers of the brain and improves functional language outcomes as compared with sham.5,11
The largest clinical trial of tDCS to augment naming treatment for PSA targeted the area of greatest activation in the left hemisphere during spoken naming (localized on pretreatment functional magnetic resonance imaging [fMRI]). In this double-blind, sham-controlled study of tDCS, 74 individuals with chronic PSA were randomized to anodal tDCS versus sham, matching for aphasia severity and type.6 Both groups had identical computer-delivered naming therapy for 15 sessions. TDCS was associated with greater change in number of correctly naming pictured objects, the primary outcome measure: 13.9 words (95% CI, 9.0–18.7) for tDCS versus 8.2 words (95% CI, 3.8–12.6) for sham.6 There was a 70% greater improvement in correct naming for anodal tDCS relative to sham. Furthermore, outcome was influenced by an interaction between anodal tDCS and a single-nucleotide polymorphism of the BDNF (brain-derived neurotrophic factor) gene, rs6265.7 Participants with the normal val/val genotype who received tDCS showed greater response to aphasia treatment than val/val participants who received sham, and greater response to aphasia treatment than the Met allele carriers, regardless of tDCS condition.7
Because expensive technology such as fMRI is not readily available across clinical settings, some investigators have explored behavioral methods for identifying ideal electrode placement. Spielmann et al14 compared electrode placement on the left IFG or the left superior temporal gyrus using anodal tDCS versus sham. On average, placement at the left IFG resulted in better posttreatment performance, although there was large variability in individual responses. It was not possible to establish optimal placement in some participants.14 Patients with nonfluent aphasia due to frontal cortex damage benefitted from stimulating the frontal cortex, whereas patients with fluent aphasia did not benefit from single-session stimulation at either site.14 There was no improvement in performance on untrained items with single-session stimulation; therefore, trained items serve as a better outcome measure to establish optimal placement.
Imaging studies have explored the neural mechanisms of tDCS effects on language in PSA. One voxel-based lesion symptom mapping study showed that individuals with damage to the left basal ganglia, insula, and superior and inferior longitudinal fasciculi had lower response to tDCS.3 The authors concluded that integrity of left subcortical structures and white matter language pathways influences the benefits of tDCS.3 Darkow et al5 investigated in the effects of tDCS on functional brain activity to determine effects of tDCS in individuals with PSA compared with healthy controls. Participants were hooked up to an intrascanner tDCS device with anode placed at M1 and underwent an fMRI while naming pictures they could consistently name, as established in baseline testing.5 Relative to sham, tDCS resulted in enhanced activity in language regions and reduced activity in domain-general brain regions associated with working memory and response selection including anterior cingulate cortex, left insula, and right lingual gyrus.5 The investigators indicated tDCS may improve efficiency at the neural level, by increasing activity in the language areas such that language success can be achieved with lesser demands on cognitive processes of working memory and response selection.5 Interestingly, activity was enhanced in only the language networks and not the motor or visual networks, even though stimulation was placed on M1. These and other results indicate that placement of the electrodes may not matter as much as activating the language network with language treatment during the tDCS.5,8 One study of aphasia after bilateral middle cerebral artery stroke showed that right cerebellar tDCS resulted in both (1) greater improvements in spelling, compared with sham paired with the same therapy (39/40 versus 21/40, P<0.0001 for trained words and 33/40 versus 11/40, P<0.0001 for untrained words), and (2) enhanced connectivity between right cerebellum and frontal and temporal cortex, evaluated with resting-state fMRI.13 Other studies have also reported increased resting-state connectivity between specific brain regions resulting from tDCS paired with language therapy.10
Transcranial Magnetic Stimulation
rTMS is another form of NIBS that has been used to supplement SLT in PSA. rTMS can be delivered at both high frequency (excitatory) and low frequency (inhibitory). Low-frequency rTMS is often applied to the contralesional right hemisphere to inhibit right hemisphere activation during language-related tasks and to encourage perilesional left hemisphere activation16 in both the subacute and chronic PSA.
Subacute
Both low-frequency and high-frequency rTMS have been beneficial in improving language outcomes when paired with SLT in subacute PSA. Khedr et al18 applied bihemispheric rTMS using high frequency to the injured left IFG and low frequency to the right sided, homologous IFG for a total of 10 sessions followed by 30 minutes of SLT, compared with sham. Patients who received rTMS showed significantly greater improvements compared with sham in accuracy of word comprehension (P=0.04), naming (P=0.01), repetition (P=0.002), and in aphasia severity (1.8±1.2 versus 0.9±0.3; P=0.018).18 This significant improvement was present immediately after treatment and at 2-month follow-up. Haghighi et al15 found that low-frequency rTMS applied to the right IFG at 1 Hz for 30 minutes paired with SLT for 45 minutes, 5× per week over 2 weeks, compared with sham with the same SLT, resulted in improved scores on the Farsi Western Aphasia Battery (aphasia quotient, 50.27±28.37 versus 39.50±18.14). Large effect sizes were observed for speech content and fluency scores and aphasia quotient.15 Rubi-Fessen et al19 applied rTMS at 1 Hz to the right IFG compared with sham, each with subsequent 45-minute SLT. They found that rTMS led to greater improvement compared with sham in all language measures, including functional communication (34.20±12.09 versus 32.93±14.84 on the Amsterdam-Nijimegen Everyday Language Test A scale; P=0.050).19
Chronic
Both low- and high-frequency rTMS are effective in improving language outcomes in chronic PSA as well. Hara et al16 used functional near-infrared spectroscopy to determine the hemisphere of language activation to determine rTMS delivery method. They implemented 1 Hz (inhibitory) rTMS to contralesional right IFG in those with left sided language activation and implemented 10 Hz (excitatory) rTMS to right IFG in those with right hemisphere activation during language tasks.16 Both groups received intensive SLT following rTMS. The groups showed equally significant improvements in language functions,16 indicating that right hemisphere activation during language may not always be maladaptive. Authors suggest that lesion site and size may determine whether perilesional areas can take on language functions or the right hemisphere is needed to compensate.16 Likewise, Tsai et al20 found that applying low-frequency rTMS in the area contralateral to the lesion followed by 1 hour of SLT also resulted in greater improvements compared with sham in object naming (47.4±28.3 versus 35.3±30.1; P<0.05), object naming reaction time (12.1±4.9 vs 13.9±5.1; P<0.01), action naming (34.8±24.6 versus 25.9±20.4; P<0.01), and action naming reaction time (15.4±5.2 versus 15.4±5.7; P<0.01) immediately after treatment and lasting ≤3 months.20 Hu et al17 also found that both high- and low-frequency rTMS to the contralesional hemisphere resulted in significant mean improvement compared with sham and controls, although low-frequency rTMS yielded greater improvements, perhaps because fewer participants had right hemisphere dominance for language after stroke.
The above studies delivered SLT immediately following delivery of rTMS. Wang et al21 compared SLT delivery immediately following rTMS to synchronous delivery of SLT with rTMS. They found that 1 Hz of rTMS to right IFG with synchronous SLT was more effective than either sham (SLT alone) or rTMS with subsequent SLT. Improvements in verbal expression included description, object naming, and action naming and lasted ≤3 months.21 Although synchronous SLT may be more beneficial, rTMS produces a loud clicking noise during administration, which can prove distracting to the patient during SLT.
Advances in SLT
Recent research in SLT has focused largely on interventions to improve expressive language, specifically in chronic PSA.23–31 Constraint Induced Aphasia Therapy (CIAT) and Intensive Language Action Treatment are group therapy methods. CIAT requires patients to communicate verbally with each other while playing a card game, while prohibiting use of any nonverbal communication methods.27 In intensive Language Action Treatment, patients interact by requesting picture cards from each other and naming pictures using carrier phrases.24
In one-on-one treatment, a number of therapies utilize multiple modalities to stimulate language recovery. Power-Afa23 is an Italian software program consisting of phonological, semantic, orthographic, morphological, and syntactic tasks of varying levels of complexity that are adjusted over time. Phonomotor treatment is an intensive protocol that trains individual sounds and progresses to training of 1 to 3 syllable words and nonwords using articulatory-motor, acoustic, tactile kinesthetic, and orthographic modalities.25 In Verb Network Strengthening Treatment, the therapist provides a verb and asks the patient to generate related agents and receivers of the action; additionally, participants answer wh- questions about each generated schema.26 Other treatments focus specifically on verbal expression. Melodic Intonation Therapy focuses only on verbal expression with an established protocol involving the therapist singing short utterances and tapping to the rhythm alongside the patient.28,29 As the patient progresses, utterances become increasingly complex and the therapist cueing decreases.28,29 Harnish et al31 utilized an intensive naming treatment presenting 50 pictures 8× across a session for a total of 400 repetitions a session. A phonological treatment Earobics uses software to target sound to picture matching, letter-to-sound mapping, auditory segmentation, rhyme detection, word-to-picture matching, and auditory discrimination.30 The study design, participant number, and results of each study are summarized in Table 3.
| Authors | Design | Participants | Treatment | Dosage | Results |
|---|---|---|---|---|---|
| Barbancho et al32 | Double-blind, randomized placebo-controlled trial | 27 chronic PSA | CIAT with memantine or CIAT with placebo | 3 h/d for 2 wk; total: 30 h | Western Aphasia Battery scores improved with memantine; improved even more with memantine+CIAT |
| Breitenstein et al33 | Multicenter, open-label, blinded end point, randomized controlled trial | 156 chronic PSA | Evidence-based SLT vs deferral of same SLT for 3 wk | 10 h/wk of individual and group therapy (30+ h) | Significant improvement lasting at least 6 mo |
| Breitenstein et al34 | Double-blind, randomized placebo-controlled trial | 10 chronic PSA | Levadopa with SLT; placebo with SLT | 4 h/d for 10 d ; total: 40 h | Improved naming and verbal communication in both groups |
| De Luca et al23 | Randomized controlled trial | 32 chronic PSA | Power-Afa computer-based intervention vs traditional therapy | 45 min/d; 3 d/wk for 8 wk; (18 h) | Improved repetition, selective attention, denomination, and reading; Power-Afa >traditional |
| Dignam et al35 | Nonrandomized, parallel-group, prepost test design | 34 chronic PSA | Intensive therapy vs distributed therapy | 48 h in 3 wk or 48 h in 8 wk | Distributed delivery had greater impact on Boston Naming Test scores |
| Edmonds et al26 | Multiple baseline design | 11 chronic PSA | VNeST | 35 h | Improved trained and untrained sentence probes, object and action naming |
| Harnish et al31 | Feasibility study | 8 chronic PSA | Computer-based naming treatment | 1 h/d; 4 d/wk for 2 wk | Improvements after 1 treatment session maintained at 2 mo |
| Kendall et al25 | Nonrandomized trial | 26 chronic PSA | Phonomotor therapy vs delayed phonomotor therapy | Two 1-h sessions/d, 5 d/wk for 6 wk; total: 60 h | Improved naming of untrained items lasting ≤3 mo post |
| Stahl et al24 | Randomized, crossover, controlled trial | 18 chronic PSA | ILAT vs naming therapy | 3.5 h/d for 6 d (21 h) | Greater language improvements in ILAT >naming therapy |
| van der Meulen et al28 | Multicenter, randomized controlled trial | 27 subacute PSA | MIT vs control intervention (comprehension oral and written) | 5 h/wk for 6 wk ; total: 30 h | Significant improvement with MIT |
| Wan et al29 | Prepost design | 11 chronic PSA | MIT vs untreated | 1.5 h/d, 5 d/wk for 15 wk; total: 110 h | Improvements in speech lead to structural changes in the right hemisphere |
| Woldag et al27 | Single-blind, randomized controlled trial with 3 arms | 60 acute PSA | CIAT group therapy 3 h/d for 10 d (30 h) vs conventional group 2 h/d for 10 d vs two 30-min individual therapy sessions/d and 1 h of group therapy for 10 d (14 h) | 3 h/d for 10 d (30 h) or 2 h/d for 10 d (20 h) or two 30-min individual therapy sessions/d and 1 h of group therapy/d for 10 d (14 h) | All groups showed significant improvement |
| Woodhead et al30 | Double-blind, placebo-controlled, crossover, within-subjects design | 20 chronic PSA | Earobics vs earobics with donepezil | 10 h/wk for 5 wk (50 h) | Donepezil had a negative effect |
| Woodhead et al36 | Baseline-controlled, repeated measures, crossover design | 21 chronic PSA | EG1: iReadMore with anodal tDCS; EG2: iReadMore with Sham | Two 4-wk blocks; 34 h of training; 11 stimulation sessions | Improved reading of trained words with iReadMore, small facilitation with anodal stimulation |
CIAT indicates Constraint Induced Aphasia Therapy; ILAT, Intensive Language Action Treatment; MIT, Melodic Intonation Therapy; PSA, poststroke aphasia; SLT, Speech-Language Therapy; tDCS, transcranial direct current stimulation; and VNeST, Verb Network Strengthening Treatment.
Studies that utilize a mixed treatment approach, delivering treatment in both individual and group settings, have also been effective in improving language outcomes (Table 3).27,34,35 Some studies have also incorporated computer-delivered or tablet-based therapies, such as iReadMore—an app designed to improve word recognition in people with reading deficits in PSA. Use of iReadMore resulted in significant improvement in reading trained words (8.7%; 95% CI, 6–11.4) but not untrained words.36 However, when combined with tDCS, there was a significant improvement in untrained and trained words.36
Although some studies have identified new treatment methods, much of the recent research explores the ideal intensity of therapy. Breitenstein et al34 found that intensive SLT administered for ≥10 hours a week with a therapist and ≥5 hours per week of self-practice, for 3 weeks including both individual and group settings, resulted in significantly greater improvements in verbal communication when compared with control group who deferred therapy for 3 weeks. Dignam et al35 compared an intensive (16 hours a week for 3 weeks) versus distributed therapy (6 hours a week for 8 weeks) delivery, finding that distributed therapy resulted in greater change in scores on the Boston Naming Test. Similarly, Woldag et al27 found no significant difference in language outcomes with CIAT delivered 3 hours a day for 10 days (30 hours of CIAT), conventional group therapy delivered 3 hours a day for 10 days (30 hours of group therapy), or a combination of individual and group therapy delivered twice a day for a total of 14 hours over 2 weeks. Therefore, the mixed therapy seemed to be the most time-effective or efficient for facilitating language recovery.
Pharmacological and Medical Interventions
Other clinical trials have evaluated the efficacy of medications in improving PSA. However, like previous medication trials for PSA,37 the recent trials have been small (n=10–156) and some have had weak study designs (eg, open labeled; Table 3). Woodhead et al30 found that donepezil was not beneficial in improving PSA and actually had a negative effect on speech comprehension outcomes. Although some studies have indicated that levadopa may augment moderate-intensity language therapy, Breitenstein et al34 found it did not improve outcomes of high-intensity language therapy (63.8% for levadopa versus 66.5% for placebo). On the contrary, memantine had a small positive impact on language functioning, resulting in greater improvement in Western Aphasia Battery Aphasia Quotient, compared with placebo (67.1±5.5 versus 65.8±3.0; P<0.002).32 The effect was smaller than effects reported previously for memantine plus CIAT.32
Other
Raglio et al38 reported that 10 patients randomized to music therapy in addition to 30 sessions of SLT showed significant improvement compared with 10 patients who received 30 sessions of SLT alone (Aachener Aphasia spontaneous speech subtest: P=0.020; Cohen d, 0.35).
In a study of 60 patients with acute to chronic PSA randomized to heart-gallbladder acupuncture versus traditional acupuncture, both groups improved on the Aphasia Battery for Chinese, but the experimental group showed significantly greater improvement in fluency, repetition, naming, and reading scores (P<0.05).39 However, results were not corrected for multiple comparisons.
Another modality currently being explored is a more invasive form of brain stimulation, epidural cortical stimulation (CS). Epidural CS requires surgical implantation of a device, which can then be turned on and off. Cherney40 evaluated epidural CS paired with language therapy compared with language therapy alone. Language therapy included 3 hours a day, 5 days a week for 6 weeks including apraxia drills, confrontational naming, computer practice, and conversational practice. Overall, the CS group showed greater improvements than controls on the Western Aphasia Battery aphasia quotient: 7.98±4.94 (95% CI, −0.83 to 2) versus 4.59±5.17 (95% CI, −1.27 to 1.73).40
Discussion and Limitations
It should be noted that methodological weaknesses in many of the aphasia treatment studies compromise strong conclusions about efficacy. Most trials have been small (Tables 1 through 3); only 3 of the recent trials have included >50 participants,6,7,20,33 and only 1 has included >100 participants.33 Many have not reported that evaluators of outcome have been masked to the treatment group. Although most of the tDCS studies have reported improvement in untrained and trained items13 or on untrained standardized aphasia batteries,11,15–18 some have shown no improvement on untrained items14 or have not reported on generalization.6 Likewise, many behavioral35 and medication32 trials have reported gains on standardized tests, and others report gains on untrained stimuli26; but many others failed to report generalization.
Most studies have been performed in participants with chronic PSA (>6 months, often many years, poststroke), in which it is assumed that language performance is relatively stable with no intervention. Studies in subacute28 and acute27 stroke have mostly used randomized designs with evaluators masked to treatment group to try to control for variability in spontaneous recovery that takes place during the early months after stroke. However, the effect size of treatment must be large (or the groups large) to show an effect of treatment over and above the spontaneous improvement, as illustrated in the study by Woldag et al,27 which showed no significant effect of treatment with CIAT group therapy 3 hours/day for 10 days (30 hours) compared with conventional group therapy 2 hours/day for 10 days (20 hours) or individual therapy twice a day and group therapy (14 hours), with 20 participants in each group. One study of tDCS19 used a crossover design and randomized order of treatment with 30 individuals with subacute PSA to partially control for variability of spontaneous recovery (as each participant is compared with themselves, across conditions). This study showed significant improvement in functional communication with tDCS compared with sham, along with language therapy.
Finally, most studies have included participants with a variety of aphasia subtypes or have included individuals with various nonfluent aphasia subtypes (Global, Transcortical Motor, and Broca’s aphasia). The distribution of aphasia subtypes might influence efficacy. That is, it is possible that individuals with Broca’s aphasia respond more to certain types of treatment, while those with Wernicke’s aphasia respond more to other types. However, none of the studies have been adequately powered to identify differential efficacy across subtypes. Therefore, it is not possible to predict for whom the therapy will be effective, even for studies that report statistically significant results for their population.
One caveat about tDCS is that the current is much more disperse than in TMS, making it difficult to identify the optimal stimulation site. On the contrary, there is evidence from fMRI that stimulation over any area of the network being activated by the concurrent language task will facilitate activation throughout the network.8
Conclusions and Future Directions
This review of clinical trials for PSA in the past 5 years reveals that a multitude of interventions can be beneficial in improving language and functional outcomes for patients with PSA, with the majority of research focusing on the chronic phase of aphasia. The most effective or efficient interventions combine SLT with NIBS or medications. It is hypothesized that both NIBS and certain medications that influence neurotransmitters increase long-term potentiation or depression required for neuroplasticity. Thus, these interventions can augment SLT in recruiting nondamaged areas of the left or right hemisphere to assume the functions of the damaged parts.
In regard to NIBS, both TMS and TDCS are generally effective interventions when paired with SLT.2,4,9,12,22 Additionally, epidural CS is another form of brain stimulation that may augment SLT in PSA.40 However, further studies are needed to identify the most effective electrode placement, the optimal dose, and the mechanisms by which NIBS and CS facilitate improvement.
A number of SLT interventions are beneficial when administered at a moderate-to-high intensity in both subacute and chronic aphasia.23–29
With regard to pharmacological interventions, preliminary studies indicate that donepezil has negative effects on speech comprehension, while memantine may have a positive impact on language, but additional studies are needed to confirm these results.30,32 Levadopa has had inconsistent effects on language recovery.34 Music therapy and acupuncture may be effective adjuncts to SLT, although further research is needed to confirm preliminary findings.38,39
Future studies should focus on identifying the most cost-effective combination of interventions. Combining medications with NIBS and SLT, for example, might result in improvement with fewer number of sessions. Randomized trials are also needed to evaluate the effect of computer-delivered or app-delivered interventions, with or without clinician-delivered therapy in both the clinic setting and remotely (telerehabilitation). Furthermore, more trials are needed in the early stage of recovery. These studies are more difficult because they must show an effect of the intervention over and above spontaneous recovery. Thus, only interventions with large effect sizes will yield significant results.
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© 2019 American Heart Association, Inc.
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Received: 13 May 2019
Revision received: 25 July 2019
Accepted: 6 August 2019
Published online: 12 September 2019
Published in print: October 2019
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This study was supported by R01 DC05375 and P50 DC 014664.
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- Effects of repetitive transcranial magnetic stimulation combined with music therapy in non‐fluent aphasia after stroke: A randomised controlled study, International Journal of Language & Communication Disorders, 59, 3, (1211-1222), (2023).https://doi.org/10.1111/1460-6984.12991
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