Effects of Transcranial Direct Current Stimulation on Speech and Voice Changes in Parkinson's Disease: a Systematic Review with Meta-Analysis

Pinheiro, Renata Serrano de Andrade; Silva Júnior, Hercílio Barbosa da; Guimarães, Bruno Braga; Lima, Ivonaldo Leidson Barbosa; Bandeira, Rafael Nóbrega; Alves, Nelson Torro

doi:10.1590/2317-1782/e20250002pt

person Renata Serrano de Andrade Pinheiro

conceptualization · data curation · formal data analysis · investigation · methodology · project administration · resources · writing - original manuscript · approval of the final version of the manuscript for publication · visualization · writing - review and editing · responsibility for the accuracy and integrity of all aspects of the research

schoolPrograma de Pós-graduação em Neurociências Cognitiva e Comportamento – PpgNeC, Departamento de Psicologia, Universidade Federal da Paraíba – UFPB - João Pessoa (PB), Brasil.

0000-0002-6089-3934

person Hercílio Barbosa da Silva Júnior

supervision · validation · visualization · writing - review and editing

schoolDepartamento de Pesquisa do Neuronus, Instituto Transdisciplinar de Ensino e Pesquisa sobre o Cérebro - Goiânia (GO), Brasil.

0000-0003-1873-4865

person Bruno Braga Guimarães

supervision · validation · visualization · writing - review and editing

schoolDepartamento de Pesquisa do Neuronus, Instituto Transdisciplinar de Ensino e Pesquisa sobre o Cérebro - Goiânia (GO), Brasil.

0009-0003-7881-6878

person Ivonaldo Leidson Barbosa Lima

supervision · validation · visualization · writing - review and editing

schoolDepartamento de Fonoaudiologia, Universidade Federal do Rio Grande do Norte – UFRN, Natal (RN), Brasil.

0000-0003-1716-1575

person Rafael Nóbrega Bandeira

supervision · validation · visualization · writing - review and editing

schoolDepartamento de Fonoaudiologia, Universidade Federal da Paraíba – UFPB - João Pessoa (PB), Brasil.

0000-0002-5380-5035

person Nelson Torro Alves

conceptualization · data curation · formal data analysis · investigation · methodology · project administration · resources · writing - original manuscript · approval of the final version of the manuscript for publication · visualization · writing - review and editing · responsibility for the accuracy and integrity of all aspects of the research

schoolPrograma de Pós-graduação em Neurociências Cognitiva e Comportamento – PpgNeC, Departamento de Psicologia, Universidade Federal da Paraíba – UFPB - João Pessoa (PB), Brasil.

0000-0003-3678-5762

Conflict of interests:

nothing to declare.

Correspondence address: Renata Serrano de Andrade Pinheiro Programa de Pós-graduação em Neurociências Cognitiva e Comportamento – PPGNeC, Departamento de Psicologia, Universidade Federal da Paraíba – UFPB CCHLA-Center for Humanities, Literature and Arts, Cidade Universitária, Campus I, Castelo Branco I, João Pessoa (PB), Brasil, CEP: 58051-900. E-mail:
reserranoap@gmail.com

Editor:

Larissa Cristina Berti.

	INCLUSION	EXCLUSION
PATIENT	Patients with Parkinson's disease, both sexes, in stages 2 or 3 of the Hoehn-Yahr PD scale.	- Individual health condition: unstable hemodynamics, other neurological disease, or untreated psychiatric illness.
(Population)		- Use of DBS or metal in the brain, or any reason that prevents tDCS.
		- Hearing impairment or use of hearing aids or cochlear implants.
INTERVENTION	Use of Transcranial Direct Current Stimulation (tDCS) to treat voice and speech parameters in patients with Parkinson's disease.	Studies that do not use tDCS in the proposed treatment.
(Intervention)	(a-tDCS, c-tDCS, s-tDCS, or sham)

COMPARISON	Areas of application of the 10-20 System Protocol for tDCS, focusing on voice and speech for individuals with Parkinson's disease.	Studies that do not identify the area stimulated with tDCS.
(Comparison)

OUTCOME	Improvement in voice production and acoustic parameters, speech fluency and intelligibility, and reduction in signs and symptoms of voice and speech disorders.	Studies that do not have voice and speech outcomes.
(Outcomes)

STUDY DESIGN	Intervention studies (cross-sectional or longitudinal), with randomized or non-randomized clinical trials, and other studies addressing Transcranial Direct Current Stimulation (tDCS) in individuals with PD.	Accuracy, Prevalence, Prognosis.
(Study Design)

DATA REPORT	Use data to analyze and estimate the effects of tDCS associated with voice and speech training or assessment in PD.
(Data Report)

TYPE OF PUBLICATIONS	Must have been published in a peer-reviewed journal within the last ten years and in any language.
(Type of Publications)

AUTHORS/YEAR	JOURNAL/ PUBLISHMENT DOI	TYPE OF STUDY/TREATMENT TECHNIQUE	OBJECTIVE	tDCS METHOD/PARAMETERS	MAIN FINDINGS	CONCLUSION
FOX, MD; BUCKNER, RL et al (2014)	PNAS PLUS DOI: 10.1073/pnas.1405003111	A. CONCEPTUAL OR THEORETICAL Invasive and Noninvasive Brain Stimulation in Psychiatric and Neurological Disorders	Identify diseases treated with invasive and non-invasive stimulation, list the stimulation sites considered most effective in each disease using resting-state functional connectivity MRI.	- The literature search revealed 14 different psychiatric or neurological diseases with published reports of efficacy for both invasive brain stimulation and non-invasive brain stimulation. - Correlations between DBS regions and all other brain voxels were computed and related to sites with evidence of efficacy as targets for non-invasive brain stimulation (TMS or tDCS).	- Diseases and stimulation areas: Alzheimer's disease - DBS (fornix), TMS or tDCS (bilateral DLPFC + parietal/temporal), Depression - DBS (subgenual, VC/VS, NA, MFB, habenula), TMS or tDCS (e-DLPFC, d-DLPFC), Epilepsy - DBS (thalamus (AN, CM), MTL), TMS or tDCS (EEG active focus, cerebellum), Pain - DBS (PAG, thalamus (VPL/VPM)), TMS or tDCS (M1), Parkinson's disease - DBS (STN, GPi), TMS or tDCS (M1, SMA), and others.	This work supports a network perspective for understanding and treating neuropsychiatric diseases, highlighting the therapeutic potential of the brain as a target for network modulation.
MITERKO, LN ; BAKER, KB et al (2019)	The Cerebellum DOI: 10.1007/s12311-019-01041-5	Consensus Article: Experimental Neurostimulation of the Cerebellum	Report the most advanced techniques for manipulating cerebellar circuits in humans and animal models and define the main obstacles and issues for moving forward.	-Recent paradigms of animal and human stimulation that utilized the cerebellum were presented, identifying key successes and failures, which are essential for improvements in human therapy. Important obstacles were outlined and possible ways to overcome them were suggested.	- Recently described anatomical connections between the cerebellum and basal ganglia expand the potential applications of cerebellar tDCS in dystonias and other disorders. - Cerebellar tDCS modifies cerebellar cortex excitability with minor side effects. - Cerebellar anodal tDCS improves the kinematics of handwriting and circle-drawing tasks in patients with writing dystonia and promotes the rehabilitation of speech and language deficits.	- Anodal tDCS increased the ability to learn from mistakes, as well as form and retain motor memory. The cerebellum also has a broad influence and contributes significantly to non-motor domains, such as cognition. - Positive results of anodal tDCS on verbal fluency and pain perception in healthy individuals and cognitive symptoms in Parkinson's patients.

MANTO,M, et al (2022)	The Cerebellum DOI: 10.1007/s12311-021-01344-6	New Directions and Next Steps in the Non-Invasive Approach to Cerebellar Brain Stimulation in Health and Disease	To report advances made in the use of cerebellar NIBS and reach consensus on future steps to move forward.	- Use of TMS to explore cerebellar neurophysiology; current knowledge on cerebello- cerebellar tDCS; the role of animal models in cerebellar applications of NIBS; clinical application of cerebellar NIBS (motor learning, stroke recovery, speech and language functions, neuropsychiatric and movement disorders, and pain syndromes).	- Functional neuroimaging has shown a cerebellar role in verbal fluency in neurostimulation research. Anodal cerebellar tDCS (right posterolateral cerebellum) improved phonemic fluency. Lin et al. - Nineteen patients with SCA underwent neuronavigated cTBS (right cerebellum vs. sham stimulation) producing sustained vowels while perceiving the pitch change in their voice. Compared to sham, cerebellar cTBS led to smaller magnitudes of vocal compensations for pitch disturbances, demonstrating that cerebellar NIBS can modulate abnormal auditory-vocal integration in SCA.	Non-invasive cerebellar stimulation represents a promising tool for therapeutic purposes, both in motor, cognitive, and psychiatric pathological conditions. Targeting tDCS to the cerebellum to indirectly affect cortical and subcortical activity may be effective in alleviating symptoms of various pathologies, as well as improving cognitive functions or motor learning in healthy individuals.
MONTEMURRO,NALIAGA,N et al (2022)	International Journal of Environmental Research and Public Health DOI: 10.3390/ijerph19148799	New targets and new technologies in the treatment of Parkinson's disease	The aim of this narrative review is to show new targets in DBS surgery, as well as new technologies that are under study and have shown promising results to date.	Literature review of databases for an overview of new therapeutic targets for PD, as well as their limitations. Review research that will become effective and routine treatments for PD in the near future.	- Non-invasive modulation of spontaneous neuronal activity with electric current (1–2 mA) by two or more electrodes on the scalp for the regulation of neuronal membrane potentials, changes in neurotransmitters, glia and microvessels. - Provides neuronal plasticity by generating long-term synapses (BDNF) - (tDCS) affects the motor symptoms of the disease, with the most prominent results being related to rehabilitation.	Progress in device development is reflected in increasingly personalized treatments and the targeting of new targets. These new devices offer the advantage of being lower cost and minimally invasive or non-invasive.
SALUJA, A; GOYAL,V; DHAMIJA, RK (2022)	Indian Academy of Neurology - Neuro‑Rehabilitation Supplement DOI: 10.4103/aian.aian_164_22	Multimodal rehabilitation therapy in Parkinson's disease and related disorders	To evaluate and summarize current evidence on rehabilitation strategies in PD and atypical parkinsonian syndromes. Highlight evidence and advances in the rehabilitation of patients with parkinsonism.	-A literature search was conducted in MEDLINE (PubMed) and Cochrane. Relevant results from the full text and abstracts of the studies were reviewed. Randomized clinical trials (RCTs), trial protocols, consensus guidelines, cohort studies, systematic reviews, meta-analyses, review articles, pilot studies, case reports, observational studies, and pre-post studies.	- Speech and Language Rehabilitation in PD - 89% of PD patients may develop speech and voice disorders (reduced volume, monotonous voice, and breathy quality), articulation (imprecise consonants and vowel centralization), and frequency (increased, decreased, and variable). Speech-language therapy improved sound pressure levels during sustained phonation, reduced Voice Handicap Index scores, and improved reading of the Rainbow Passage and monologue.	Incorporating rehabilitation strategies, particularly early in the disease course, can improve motor and non-motor symptoms, along with the Quality of Life of patients with PD.
WEISMER, G et al (2023)	Brain Sciences DOI: 10.3390/brainsci13050768	Nonverbal oromotor performance and speech motor control: theory and review of empirical evidence	Outline general issues related to non-speech oromotor tasks and their relationship to speech production	- Twelve studies were found on the relationships between nonverbal oromotor performance and speech production measures in healthy individuals (3 with positive results; 2 with mixed results; 7 with negative results). - 19 studies on the relationships between nonverbal oromotor performance and speech production measures in neurologically based speech disorders (3 with positive results, 5 with mixed results, and 11 with negative results).	Transcranial direct current stimulation (tDCS) was applied to jaw movements associated with speech, maximum syllable repetition, and chewing. The relationship between nonverbal oromotor performance and speech production measures was negative. The results showed that the effects of tDCS are task-dependent.	To advance the research and clinical disciplines of speech motor control, the study of speech production and its goal of providing listeners with linguistically relevant, time-varying acoustic signals is necessary and (I believe) sufficient.
BAIG, FN (2023)	Brain Stimulation DOI:10.1016/j.brs.2023.01.354	B. SYSTEMATIC REVIEW RS: Update on the therapeutic efficacy of non-invasive brain stimulation for dysarthria recovery: a systemic review	To collect evidence of the usefulness of NIBS in the treatment of dysarthria through the systematic evaluation of original research articles.	DATABASES: Google Scholar, Embase, Scopus, PubMed, Cochrane, and Web of Science. KEYWORDS: Dysarthria, tDCS, TMS, neurological disorder	Fourteen of the 9.244 studies were included. Nine used TMS and five evaluated tDCS. Adjunctive speech-language therapy (SLP) to NIBS was offered in six studies. Dysarthria resulted from cerebral palsy, stroke, PD, cerebellar ataxia, traumatic brain injury, and supranuclear palsy. 83% of the studies found positive effects of NIBS. The significant post-treatment difference between the sham and treatment groups was associated only with the sequential movement rate (Hedges' g = 0.79, 95% CI [0.075, 1.50] P = 0.03), favoring tDCS.	Most studies that have identified the benefits of SBNI have not provided evidence for complete recovery from dysarthria. Large-scale clinical investigations are needed to evaluate the effectiveness of SBNI in treating dysarthria.
BALZANA, P et al (2022)	Annals of Physical and Rehabilitation Medicine DOI: 10.1016/j.rehab.2021.101580	RS: Non-invasive brain stimulation for the treatment of neurogenic dysarthria.	To examine the evidence base for non-invasive central and peripheral stimulation to improve speech-related functions in people with dysarthria and determine the effects of an intervention.	DATABASES: MEDLINE PsychINFO EMBASE CINAHL Linguistics and Language Behavioral Abstracts Web of Science The Cochrane Register of Controlled Trials and 2 trial registries were completed. KEYWORDS: Brain and electrical stimulation, Dysarthria, and Research design.	A total of 6,186 studies were identified; 10 studies (6 randomized controlled trials and 4 crossover studies) met the inclusion criteria. The 10 studies (268 adults with Parkinson's disease, stroke, and neurodegenerative cerebellar ataxia) focused on NIBS (6 TMS; 3 tDCS; and 1 tACS). Most trials reported one or more positive effects of stimulation on dysarthria-related features. All 3 studies provided anodal stimulation over the cerebellum or M1, with a current intensity of 2 mA. tDCS was administered for 20 (n=2) or 30 (n=1) min. In all trials, stimulation was administered 5 times per week for a total of 10 sessions.	The evidence for the use of noninvasive brain stimulation in the treatment of dysarthria remains inconclusive. Research trials that provide reliable and replicable results are needed.

AUTHORS/ YEAR	JOURNAL /PUBLISHMENT DOI	TYPE OF STUDY / TREATMENT TECHNIQUE	OBJECTIVE	tDCS METHOD / PARAMETERS	MAIN FINDINGS	CONCLUSION
PEREIRA, JB et al (2013)	Brain Stimulation DOI: 10.1016/j.brs.2012.01.006	C. EMPIRICAL Clinical Trial tDCS Modulation of verbal fluency networks by transcranial direct current stimulation (tDCS) in Parkinson's disease.	To evaluate the effects of tDCS on the functional networks of phonemic and semantic fluency in patients with PD.	- 16 patients with idiopathic PD; N=16 - Unified Parkinson's Disease Rating Scale (UPDRS) and Hoehn & Yahr Scale; Mini-Mental and Depression Scale; - Neuropsychological tests. tDCS at 2 mA for 20 min; atDCS over F3 (left DLPFC) or P3-T5 (left TPC); and ctDCS over right FP2.	- Effects of tDCS on verbal fluency (F(1,15) = 14.079, P<0.002), DLPFC stimulation increased the number of words produced. - Effects of tDCS on semantic fluency - F(1,15) = 3.092, P<0.102) DLPFC stimulation increased the number of words produced.	tDCS improved functional connectivity in verbal fluency and deactivation task-related networks more when applied over the DLPFC than did TPC in PD.
PIETROBON et al. (2021)	Audiology Communication Research DOI: 10.1590/2317-6431-2020-2343	Clinical Case tDCS Audiovisual production therapy combined with transcranial current stimulation improves naming in a patient with Broca's aphasia and Parkinson's disease	Stimulating Broca's area with tDCS due to the deficit in naming tasks, in the left inferior prefrontal cortex (Broca's area).	-A 79-year-old patient with PD (stage 4 on the Hoehn and Yahr scale) and chronic nonfluent post-stroke aphasia, with severe naming deficits; N=1 - Combination of audiovisual production therapy and anodal tDCS (2 mA) applied to the left inferior prefrontal cortex (F7), nine 20-minute sessions + naming of images of common objects with the aid of short videos.	Significant increase in naming scores between pre- and post-treatment, both for trained and untrained but phonemically similar images (generalization).	The results presented initial evidence that audiovisual production therapy combined with anodal tDCS over Broca's area may represent a viable alternative for patients with severe naming deficits.
LEYDON,C et al. (2022)	Perspectives - SIG 2 Neurogenic Communication Disorders DOI: 10.1044/2021_PERSP-21-00040	Clinical Trial tDCS Speech Changes After Transcranial Direct Current Stimulation in Individuals Diagnosed with Parkinson's Disease	To examine the impact of tDCS on speech production in individuals diagnosed with PD.	-Six men, aged 65 to 78, diagnosed with PD. N=6 -A double-blind, crossover, controlled study of the immediate effects of tDCS on the premotor cortex for speech production. - - Auditory-perceptual (AVS) and acoustic voice outcomes (fundamental frequency, intensity, NHR, and speech rate) pre- and post-anodal and sham simulation	-Speech rate was below normative levels for all participants before tDCS. Speech rate increased significantly in conversation after stimulation, but not in sham tDCS, exceeding normative values for two participants. NHR increased after stimulation. There were no significant differences in other measures of disturbance; perceptual ratings, fundamental frequency, or intensity were recorded.	All participants completed the protocol without discomfort. The observed increase in speech rate needs to be interpreted in the context of arousal resulting from tDCS neurostimulation.
ROSA, RR, et al. (2023)	Audiology Communication Research DOI: 10.1590/2317-6431-2023-2795pt	Clinical Case tDCS Effects of transcranial direct current stimulation (tDCS) on voice and speech in Parkinson's disease: a case report	To compare the effectiveness of conventional speech therapy combined with tDCS and tDCS alone.	-Two male patients with PD and hypokinetic dysarthria who underwent speech-language pathology evaluation. N=2. S1 - 10 sessions of 20 minutes of tDCS S2 - 10 sessions of 20 minutes of tDCS + speech-language pathology therapy Evaluated pre- and post-operatively with a 30-day follow-up. 10 consecutive days of anodal tDCS in the primary motor cortex (M1), 10-20 system (C3), and cathodal (FP2)	-Improvements in phonation time, velar movement, and other dysarthria measures were most significant in S1. - Acoustic analysis of the glottal source showed improvements in frequency measures and jitter, shimmer, and increased noise in S2. - S1 presented better results in the auditory-perceptual assessment of speech and voice, while S2 obtained better scores in the acoustic analysis.	Conventional speech-language therapy combined with tDCS has a more significant impact on speech and voice than tDCS alone, demonstrating the potential of tDCS as a complementary treatment for patients with PD.
JOHARI K (2024)	Cochrane Library - Cochrane Central Register of Controlled Trials	Clinical Trial tDCS Speech and Voice Outcomes After HD-tDCS on the Left SMA	To investigate the immediate and short-term effects of HD-tDCS in the left supplementary motor area (SMA) on speech and voice deficits.	24 participants with PD and 24 matched controls. N=48 Anodal tDCS on Supplemental Motor Area (SMA) 2 mA / 20 minutes 5 consecutive days Conducting a randomized clinical trial protocol registered with Cochrane regarding the immediate and short-term effects of high-definition transcranial direct current stimulation (HD tDCS) on the left supplementary motor area (SMA) on speech and voice deficits.	Growing evidence supports the use of non-invasive brain stimulation techniques such as tDCS to improve motor and non-motor symptoms in PD. However, there is limited evidence for the use of tDCS in improving speech and voice disorders in PD. Furthermore, there is no established long-term effect of tDCS on speech and voice deficits in PD.	There are no results yet, the study is ongoing.
BRABENEC, L et al (2024)	Journal of Neural Transmission DOI: 10.1007/s00702-024-02771-5	Clinical Trial tDCS Short-Term Effects of Transcranial Direct Current Stimulation on Motor Speech in Parkinson's Disease: A Pilot Study	Develop a program for remote treatment of HD-tDCS combined with LSVT®	-14 right-handed patients with clinically established PD. N=14 - (MoCA) for dementia, MoCA>20; ON medication without dyskinesias; presence of dysarthria symptoms -Three sessions of tDCS stimulation (anodal, cathodal, and sham stimulation) of 2 mA for 20 minutes, separated by one day, with speech tasks lasting up to 10 minutes with 150 words.	Through linear mixed model (LMM) analysis, a significant effect of the stimulation condition was observed on changes in the median duration of silences longer than 50 ms (F(2,21.8)=5.1, p=0.015), inappropriate silences that negatively impact speech rhythm and fluency.	Anodal tDCS targeting the auditory feedback area in the right hemisphere can significantly improve speech motor fluency in patients with PD.

AUTHOR/YEAR tDCS DEVICE	TYPE OF STIMULATION	MEDICATION STATUS	STIMULATION SITE (ANODE/CATHODE)	ELECTRODE SIZE	INTENSITY (mA)	DURATION IN MINUTES	NUMBER OF SESSIONS
PEREIRA, JB et al (2013) Phoresor, Iomed Inc.(EUA)	Crossover experiment of tDCS combined with fMRI	ON	ANODE F3 (DLPFC) LEFT OR P3-T5 (TPC) LEFT CATHODE FP2 RIGHT	A PAIR OF ELECTRODES SPONGE 35 cm2	2mA	20 MINUTES	1 SESSION (2h break between experiments)
PIETROBON et al. (2021) DC-STIMULATOR, neuroConn (Germany)	Combination of audiovisual verbal production therapy and anodal tDCS	ON	ANODE F7 LEFT HEMISPHERE (DRILL) CATHODE FP2 RIGHT	TWO SPONGE ELECTRODES 35 cm2	2mA	20 MINUTES	9 SESSIONS
LEYDON,C et al. (2022) Neuroelectrics Starstim (Switzerland)	Cross-over study of the immediate effects of tDCS on the premotor cortex of speech production	ON	ANODE F3(DLPFC) LEFT SHAM F3(DLPFC) LEFT	Ag/AgCl Electrodes	2mA	20 MINUTES	2 SESSIONS (crossover - active or sham with a 1-2 week interval)
ROSA, RR, et al. (2023) NKL Microestim Foco tDCS (Brazil)	Effects of tDCS on voice and speech in Parkinson's disease	ON	ANODE C3 (M1 - PRIMARY MOTOR CORTEX) CATHODE FP2 RIGHT.	TWO SPONGE ELECTRODES 7×5cm2	2mA	20 MINUTES	10 SESSIONS
JOHARI K (2024) Soterix HD-tES de 9 MxN. (New York)	Speech and voice outcomes after HD-tDCS over the left SMA	ON	ANODE F3(DLPFC) LEFT CATHODE FP2 RIGHT.	ELECTRODES HD (1.2 cm diameter) with HD-tDCS cap	2mA	20 MINUTES	5 SESSIONS CONSECUTIVE
BRABENEC, L et l (2024) DC-STIMULATOR PLUS (Germany)	Short-term effects of tDCS on motor speech in Parkinson's disease	ON	ANODIC ANODE - STG RIGHT POSTERIOR CATHODE - STG LEFT POSTERIOR CATHODIC CATHODE - STG RIGHT POSTERIOR ANODE - STG LEFT POSTERIOR	TWO SPONGE ELECTRODES 5×5cm2	2mA	20 MINUTES	3 SESSIONS ANODAL CATHODAL SHAM SEPARATED BY ONE DAY WITHOUT STIMULATION

[1] Caption: tDCS - Transcranial direct current stimulation atDCS - Anodal Transcranial Direct Current Stimulation ctDCS - Cathodal Transcranial Direct Current Stimulation sham or stDCS - Simulated Transcranial Direct Current Stimulation DP - Parkinson's Disease DBS - Deep Brain Stimulation AASI - Individual Sound Amplification Device.