Effect of Transcranial Direct Current Stimulation on Motor Speech in Nonfluent Primary Progressive Aphasia: A Case Report

Abstract

Introduction

Primary progressive aphasia (PPA) is a neurodegenerative disorder that causes a gradual decline in language function. While combining transcranial direct current stimulation (tDCS) with rehabilitation of speech and language disorders (SLD rehab) has shown promise, its effect on motor speech disorders such as dysarthria and apraxia of speech (AOS), common in nonfluent variant PPA (nfvPPA), has been unclear.

Case Presentation

This study used an N-of-1 crossover design to investigate the effects of SLD rehab-tDCS on articulation and vocalization in a 77-year-old male patient with nfvPPA, dysarthria, and AOS. In the intervention phase, intervention A (anodal tDCS over the left inferior frontal gyrus from the precentral regions, combined with SLD rehab) was compared with intervention B (sham stimulation with SLD rehab) across both short-term (single session) and long-term (12 sessions over 6 weeks) phases, with intervention A preceding B. In both the short- and long-term phases, the assessments of articulation and vocalization showed greater improvement following intervention A. The long-term intervention also led to improvements in general aphasia severity. Furthermore, brain perfusion SPECT imaging revealed increased blood flow in the left fronto-subcortical network.

Conclusions

These preliminary findings from a single case suggest that SLD rehab-tDCS may have the potential to improve not only language but also speech motor functions in nfvPPA.

Introduction

Primary progressive aphasia (PPA) is classified into three types, nonfluent/agrammatic variant PPA (nfvPPA), semantic variant PPA, and logopenic variant PPA, based on the characteristics of language impairment [1]. NfvPPA is sometimes accompanied by dysarthria and apraxia of speech (AOS), characterized by effortful and halting speech with inconsistent errors of speech sounds and distortions [1]. Dysarthria is referred to as impairment in motor control and speech execution, whereas AOS is an impairment in planning and programming speech movements. These motor speech deficits, which significantly impact communication, are linked to neurodegeneration in the left inferior frontal gyrus (IFG), premotor cortex, and related subcortical structures [2, 3].

Transcranial direct current stimulation (tDCS) is a type of noninvasive brain stimulation that modulates membrane potentials and firing rates in neurons and can induce neuroplasticity [4]. Regarding tDCS for poststroke aphasia, a previous meta-analysis revealed that tDCS over the left IFG combined with rehabilitation of speech and language disorders (SLD rehab) markedly improved noun naming [5]. Meanwhile, tDCS over the left IFG combined with SLD rehab also exerted positive effects on PPA; the reported trainings included verbal narration of children’s books [6], verb naming and writing therapy [7], which use language stimuli to facilitate semantic/lexical processing. Previous tDCS studies in PPA have shown promise, but have primarily focused on improving lexical/semantic processing through tasks like naming or narrative therapy. As for AOS in patients with nfvPPA, tDCS combined with word repetition reduced segmental intervals compared with sham, and the effects were generalized to untrained words [8]. However, there have been few reports on the effects of tDCS on dysarthria and AOS in patients with PPA, and there is limited evidence regarding the efficacy of tDCS for the motor speech components of nfvPPA.

This represents a critical knowledge gap, as improving articulation and vocalization is essential for these patients. Therefore, this study aimed to address this gap. Using an N-of-1 study design, we assessed whether tDCS combined with SLD rehab could have an effect not only on language function but also on articulation and vocalization, in a patient with nfvPPA.

Case Report

Case Description

The patient was a Japanese 77-year-old right-handed man with a bachelor’s degree in education and a history of hypertension. At age 71, he noticed that he could not articulate his thoughts well. Four years later, he had little spontaneous speech, word-finding difficulty, and AOS but no oral-facial apraxia, dysphagia, or abnormal behavior. Six years after the initial symptoms (at age 77), there was a slight decrease in spontaneity, and neurological findings indicated mild dysarthria and right-hand clumsiness. Brain magnetic resonance imaging revealed a slightly enlarged left ventricle and slight atrophy of the left parietal operculum area (Fig. 1a), and ¹²³ⁱI-IMP single-photon emission computed tomography (SPECT) showed decreased blood flow, particularly in the left thalamus, basal ganglia, and frontal lobes (Fig. 1b). NfvPPA was diagnosed based on the formal criteria of language function [1]. The Western Aphasia Battery (WAB) scores for patient performance before intervention are presented in Table 1.

Fig. 1.

a MRI FLAIR. b¹²³ⁱI-IMP SPECT before (upper) and after (lower) long-term intervention A. MRI, magnetic resonance imaging.

Table 1.

Patient performance before the short-term evaluations

Patient performance
ODK1
Average “Pa” (SD)	3.40 (0.43)
Average “Ta” (SD)	3.47 (0.34)
Average “Ka” (SD)	2.67 (0.19)
Average “PaTaKa” (SD)	0.8 (0.16)
MPT2
Average MPT (SD)	8.00 (0.43)
WAB
AQ	65.6
Spontaneous speech	10
Comprehension	8.45
Repetition	6.8
Naming	7.5
Reading	8.6
Writing	5.05
Construction	7.95

AQ, aphasia quotient.

¹Average number of 1 s after 3 trials.

²The longest time among the three trials.

Study Design

The N-of-1 trial design was chosen to systematically evaluate the intervention’s efficacy within a single patient. Although nfvPPA is progressive, this patient exhibited a relatively stable, gradual decline in language function over several years before the study began. We implemented washout periods to minimize carryover effects between interventions.

The study consisted of two phases (Fig. 2). This case report was prepared in accordance with the CARE guidelines.

Fig. 2.

Study design of the short-term and long-term interventions.

Short-Term Phase. A single session of intervention A was followed by a single session of intervention B, separated by a 7-day washout period to minimize carryover effects.

Long-Term Phase. This phase began after a 14-day washout period following the short-term phase. It consisted of 12 sessions of intervention B (sham), followed by a 14-day washout period, and then 12 sessions of intervention A (anodal). Interventions were administered twice a week for 6 weeks in each block.

Interventions

Two types of interventions were performed according to an N-of-1 study design.

Intervention A (SLD Rehab-tDCS). Anodal tDCS was delivered at 2 mA. An anodal electrode (5 × 7 cm) was placed on the scalp in the area corresponding to the left IFG from the precentral middle and lower regions determined based on the patient’s brain magnetic resonance imaging. A cathodal electrode was placed on the right anterior forehead.

Intervention B (SLD Rehab-sham). Sham stimulation was delivered using the same electrode placement. A 10-min SLD rehab (lengthened vowel phonation, picture naming, and word fluency) was performed concurrently with 10-min tDCS (2 mA, 10 s of fade-in and fade-out, SLD rehab-tDCS) and sham stimulation (10 s of fade-in and fade-out, 10 s of 2 mA, SLD rehab-sham) (NeuroConn DC, GmbH).

Clinical Measurements

Speech-language functions were evaluated using the oral diadochokinesis (ODK), maximum phonation time (MPT), and the Apraxia of Speech Rating Scale (ASRS-3.5) [9] to assess articulation and vocalization, while WAB was used to assess overall language ability. ASRS-3.5 and WAB were used for long-term evaluations only (Fig. 2).

Short-Term Evaluations

Clinical evaluations were performed before and immediately after the short-term interventions. ODK and MPT were evaluated. In the ODK evaluation, the patient was asked to repeat the monosyllables “pa,” “ta,” “ka” and trisyllable “pataka” each for 5 s as fast as possible. The maximum repeated times of each syllable were evaluated by three trials and averaged. In the MPT, the patient was asked to phonate the vowel “a” as long as possible. The longest time was evaluated among the three trials.

Long-Term Evaluations

Clinical evaluations were performed before and immediately after the long-term interventions. In addition to ODK and MPT, WAB and ASRS-3.5 were also evaluated. Spontaneous speech and repetition tasks of WAB, ODK, and MPT were used as a speech sample for ASRS-3.5. Two blinded speech-language therapists evaluated the ASRS-3.5.

IMP SPECT Evaluations

¹²³ⁱI-IMP SPECT images were taken before and 2 weeks after long-term intervention A. They were not taken before and after long-term intervention B due to the patient’s unavailability.

Results

No adverse or unanticipated events occurred during the interventions. The patient did not experience sensations such as phosphenes, cutaneous irritation, or pain.

Short-Term Effects

The MPT and trisyllable scores of ODK improved after intervention A and worsened after intervention B. Meanwhile, the monosyllable scores worsened after intervention A and improved after intervention B (Fig. 3a).

Fig. 3.

a Results of the short-term evaluations: intervention A (real stimulation) and intervention B (sham stimulation). b Results of the long-term evaluations: intervention A (real stimulation) and intervention B (sham stimulation). c ASRS-3.5 results of the long-term interventions. Intervention A = real stimulation; Intervention B = sham stimulation. Distribution of 0–4 ratings (%) for ASRS items. 0 = not present; 4 = always evident or marked in severity. AMRs, alternating motion rates; SMRs, sequential motion rates; ODK, oral diadochokinesis; MPT, maximum phonation time; WAB, Western Aphasia Battery; AQ, aphasia quotient.

Long-Term Effects

MPT and the monosyllable and trisyllable scores of ODK improved after intervention A compared with intervention B. As for language function, the aphasia quotient and subscores other than “comprehension” and “reading” improved in the WAB after intervention A compared with intervention B (Fig. 3b). In the ASRS-3.5, the scores for “distorted substitutions,” “slow rate,” “alternating motion rates (AMRs),” “sequential motion rates,” “reduced words or AMRs per breath,” and “visible/silent groping” improved after intervention A. Meanwhile, the scores for “distortion,” “slow rate,” and “visible/silent groping” worsened after intervention B (Fig. 3c).

IMP SPECT Evaluations

¹²³ⁱI-IMP SPECT showed improvement of asymmetry in blood flow, particularly an increase in the left thalamus, basal ganglia, and frontal lobe after long-term intervention A (Fig. 1b).

Discussion

In this N-of-1 study, a short-term intervention of SLD rehab-tDCS appeared to improve trisyllable ODK and MPT, and a long-term intervention of 12 sessions was associated with broader improvements across motor speech and language measures, which were not observed after SLD rehab with sham stimulation alone.

Effects of SLD Rehab-tDCS on the Left Fronto-Subcortical Network

In the present study, an anodal electrode was placed on the left IFG from the precentral middle and lower regions, a key site where neurodegeneration is observed in nfvPPA [2]. These brain regions could be the neurological factors explaining the improvement of dysarthria and AOS in this case. The tDCS over the left inferior primary motor cortex of patients with chronic stroke with dysarthria improved the MPT and ODK scores [10]. Several foci of responsibility for AOS have been proposed; the left anterior insula [11], left precentral gyrus [12, 13], and studies of anodal tDCS over the left IFG reported improved AOS in patients with cerebrovascular diseases [14] and PPA [8]. The IFG over which the anode was placed in this study is a key region for language comprehension and production. A meta-analytic connectivity modeling proposed that the opercular part of the left IFG stands out as a major hub in the language network with connections to multiple regions, such as the cortices (precentral gyrus, inferior and superior parietal lobules, insula, anterior/posterior middle temporal gyrus, etc.), subcortical nuclei (claustrum, thalamus, etc.), and cerebellum [15]. Anodal tDCS over the language network, including the left IFG, in combination with SLD rehab may be important to improve speech-language function. Furthermore, SPECT imaging suggested enhanced brain perfusion in the left fronto-subcortical network after the long active intervention, but in this study, we were unable to evaluate ¹²³¹I-IMP SPECT after the long-term sham intervention due to the patient’s unavailability.

Effects of SLD Rehab-tDCS: Short Term

The ODK (trisyllable), which is defined as “excellent” for AOS detection in the ASRS interjudge reliability [9], and short-term intervention A could have induced the recovery of AOS and dysarthria, each involving the planning and execution of a series of speech-related movements. One possible factor for the decrease in the monosyllable scores of ODK was that it was the first item in the pre- and postintervention A evaluation and showed strong effortfulness, partly due to the influence of tension. This increased effort may have influenced the speech produced in this study.

Effects of SLD Rehab-tDCS: Long Term

The long-term interventions in this study improved the scores of the ODK (monosyllables and trisyllables), MPT, and WAB aphasia quotients in the assessment of postintervention A compared with intervention B. Of these, ODK (monosyllables and trisyllables) and MPT were related to the ASRS-3.5 assessment items “AMRs,” “sequential motion rates,” and “reduced words or AMRs per breath,” respectively, and WAB (free speech and repetition) was associated with the ASRS-3.5 assessment items “distorted substitutions,” “slow rate,” and “visible/silent groping.” These results of the quantified evaluation of speech features indicate that SLD rehab-tDCS was effective for both semantic/lexical processing and voluntary control elements of articulation and vocalization.

Limitation of This Study

Although the patient demonstrated a relatively stable and gradual decline in language function over several years prior to enrollment, we cannot fully exclude the possibility that disease progression occurred during the study period. This issue is particularly relevant given our crossover design in which the active stimulation condition preceded the sham condition. Despite the inclusion of washout periods intended to minimize carryover effects, any ongoing neurodegenerative process could have disproportionately influenced performance during the sham phase and thereby biased the comparison between conditions. The potential impact of disease-related decline on within-subject contrasts remains a limitation of this single-case study. Further investigations are warranted to more rigorously evaluate intervention effects, employing larger sample sizes and adequately powered randomized controlled trials with counterbalanced intervention orders.

It is also necessary to determine whether improvement of blood flow asymmetry is an effect of SLD rehab-tDCS or training alone. In addition, SLD rehab-tDCS could have strengthened the extrapyramidal tract system connected with the left IFG, which is involved in the coordination of oro-laryngo-pharyngeal muscle tones and movements during speech and articulatory movements. Further studies are warranted to evaluate activities of the whole brain, including the basal ganglia systems.

Acknowledgments

The authors would like to thank M.K. and Y.I. for their assistance with data collection and analysis.

Statement of Ethics

In accordance with local and national guidelines, ethical approval was not required for this study. The patient provided written informed consent for participation in the study and for the publication of this case report. The CARE Checklist for this case report is available as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000549960).

Conflict of Interest Statement

All authors declare that they have no conflicts of interest.

Funding Sources

This study was supported by the Grants-in-Aid for Scientific Research (23K21593) from the Japan Society for the Promotion of Science, by JST-CREST under Grant No. JPMJCR23P3 and by AMED under Grant No. JP24zf0127010 for S.K. The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Author Contributions

Y.O., S.K., and F.O. designed the study and collected and interpreted the data. S.K. contributed to the initial draft of the manuscript. All authors approved the final version of the manuscript.

Funding Statement

This study was supported by the Grants-in-Aid for Scientific Research (23K21593) from the Japan Society for the Promotion of Science, by JST-CREST under Grant No. JPMJCR23P3 and by AMED under Grant No. JP24zf0127010 for S.K. The funding agencies had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Data Availability Statement

All data generated or analyzed during this study are included in this article and its supplementary material files. Further inquiries can be directed to the corresponding author.