Transcranial direct current stimulation (tDCS) effects on traumatic brain injury (TBI) recovery: A systematic review

Zaninotto, Ana Luiza; El-Hagrassy, Mirret M.; Green, Jordan R.; Babo, Maíra; Paglioni, Vanessa Maria; Benute, Glaucia Guerra; Paiva, Wellingson Silva

doi:10.1590/1980-57642018dn13-020005

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Original Article • Dement. neuropsychol. 13 (2) • Apr-Jun 2019 • https://doi.org/10.1590/1980-57642018dn13-020005 linkcopy

Transcranial direct current stimulation (tDCS) effects on traumatic brain injury (TBI) recovery: A systematic review

Efeitos da estimulação transcraniana por corrente contínua (ETCC) na recuperação do traumatismo cranioencefálico (TCE): uma revisão sistemática

Authorship SCIMAGO INSTITUTIONS RANKINGS

ABSTRACT.

Traumatic brain injury (TBI) is a major cause of chronic disability. Less than a quarter of moderate and severe TBI patients improved in their cognition within 5 years. Non-invasive brain stimulation, including transcranial direct current stimulation (tDCS), may help neurorehabilitation by boosting adaptive neuroplasticity and reducing pathological sequelae following TBI.

Methods: we searched MEDLINE/PubMed and Web of Science databases. We used Jadad scale to assess methodological assumptions.

Results: the 14 papers included reported different study designs; 2 studies were open-label, 9 were crossover randomized clinical trials (RCTs), and 3 were parallel group RCTs. Most studies used anodal tDCS of the left dorsolateral prefrontal cortex, but montages and stimulation parameters varied. Multiple studies showed improved coma recovery scales in disorders of consciousness, and improved cognition on neuropsychological assessments. Some studies showed changes in neurophysiologic measures (electroencephalography (EEG) and transcranial magnetic stimulation (TMS), correlating with clinical findings. The main methodological biases were lack of blinding and randomization reports.

Conclusion: tDCS is a safe, non-invasive neuromodulatory technique that can be given as monotherapy but may be best combined with other therapeutic strategies (such as cognitive rehabilitation and physical therapy) to further improve clinical cognitive and motor outcomes. EEG and TMS may help guide research due to their roles as biomarkers for neuroplasticity.

Key words: traumatic brain injury; neuronal plasticity; rehabilitation; non-invasive brain stimulation; transcranial direct current stimulation

Author, year	Study design	Total sample size (N)	Electrode placement/polarity	Sponge size	Additional therapies	Stimulation parameters	Total number of tDCS sessions	Primary outcome(s)	Results	Jadad score
Kang etal. 2012	Double-blind, randomized, crossover	N=9	F3 anodal; right supraorbital (Fp2) cathodal	5x5 cm	None	20 min of anodal tDCS, 2 mA; or sham tDCS; 48-hour washout	2	Attention by computerized contrast reaction time task	No significative improvement on RT after tDCS	3
Lesniak et al. 2013	Double-blind, parallel group, pilot study	N=26	F3 anodal; right supraorbital (Fp2) cathodal	5x7 cm	Offline cognitive training	10 min of anodal tDCS, 1 mA; or sham tDCS	15	Episodic memory, working memory and attention	Larger effect size after the intervention compared to sham, but no significant difference between groups	4
Angelakis et al. 2014	Open-label, case series, blinded dose scalation	N=10 (DOC due to TBI n=5)	C3 or F3 anodal; right supraorbital (Fp2) cathodal	5x5 cm	None	Week 1 - 20 min of sham tDCS; Week 2-20 min of anodal tDCS, 1 mA; Weeks 3 and 4 - 20 min of anodal tDCS, 2 mA	20	CRS-R	Conflicting results. Some patients improved up to 2 weeks after stimulation. One patient received 10 extra sessions of tDCS after 3 months and showed improvement. Better improvement on patients with MCS compared to PVS	2
Middleton etal. 2014	Open-label, case series pilot study	N= 5 (n=2 TBI)	Ipsilesional anodal at C3 or C4; and contralesional cathodal	5x5 cm	24 sessions of online physical therapy (3 times per week)	15 min of anodal tDCS, 1.5 mA	24	Fugl-Meyer, Purdue Pegboard, Box and Block, Stroke Impact Scale-16	Positive effects on motor performance up to 6 months after intervention	2
Thibaut etal. 2014	Double-blind, randomized, crossover	N=55 (n=32 DOC due to TBI)	F3 anodal; Fp2 cathodal	5x7 cm	None	20 min of anodal tDCS, 2 mA; or sham tDCS; 48-hour washout	2	CRS-R, GOSe	Improvements for MCS patients on CRS-R total scores. No effect of tDCS on any of the CRS-R subscales on VS/ UWS groups	5
Ulam etal. 2015	Double blind, randomized, parallel group	N=26 (subacute TBI)	F3 anodal; Fp2 cathodal	5x5.6 cm	None	20 min of anodal tDCS, 1 mA; or sham tDCS	10	EEG, neuropsychological assessments	Decreased theta with first session; decreased delta and increased alpha after active tDCS. No changes in sham group. Correlation between decreased delta and improved cognitive tasks in active group	3
Naro etal. 2015	Cross-sectional open-label study	N=45 (n= 20 healthy and n=25 DOC due to TBI or anoxia)	SO anodal (between Fp1 and Fp2); Cz cathodal	5x5 cm anode; 5x7 cm reference electrode	None	10 min of anodal tDCS, 1 mA; or sham tDCS	1	CRS-R, MEP, ICF, ICI, and SICI	Significant effects in all physiological measurements in healthy controls after the tDCS, and on ICI and ICF in DOC patients	2
Sacco etal. 2016	Double-blind, randomized, parallel groups	N=32	F3 or F4 anodal (anode on the lesioned hemisphere and cathode on the other hemisphere); bi-montage F3/ F4 anodal in case of equal hemispheric lesion distribution	5x7 cm	Offline cognitive training	20 min of anodal tDCS, 2 mA; or sham tDCS	10 (twice a day)	TEA, BDI-II, RBANS, AES, fMRI	Shorter reaction times and fewer errors compared to baseline; decreased apathy	2
O'Neil- Pirozzi etal. 2017	Double-blind, crossover pilot study	N=8 (n=4 with chronic severe TBI)	F3 (anodal, cathodal or sham); right supraorbital (Fp2) reference electrode	5x7 cm	None	20 min of anodal or cathodal tDCS, 2 mA; or sham tDCS. 48-hours washout	3	EEG alpha power, P300 amplitude and latency, working memory test	Positive effects on working memory after anodal compared to cathodal tDCS in TBI and control group. No EEG changes	2
Wilke etal. 2017	Double-blind, semi-randomized, crossover study	N=39 (n=17 chronic mild TBI)	C3 anodal; right supraorbital (Fp2) cathodal	5x7 cm anode, 10x10cm cathode	None	20 min of anodal tDCS, 1 mA; or sham tDCS. 7-day washout	2	MRS (GABA concentration), TMS, PCS, cognitive assessment	No changes in any outcome	3
Martens etal. 2018	Double-blind, crossover study	N=27 (n=12 DOC due to TBI)	F3 anodal, right supraorbital (Fp2) cathodal	5x7 cm	None	20 min of anodal tDCS, 2 mA; or sham tDCS; 8-week washout	40 (2-4 weeks stimulation and 8 weeks washout)	Adverse events adherence, CRS-R	Safety, feasibility and behavioral effects - increase in CRS-R scores	5
Estraneo etal. 2017	Double-blind, crossover study	N=23 (n=1 VS due to TBI)	F3 anodal, right supraorbital (Fp2) cathodal	5x7 cm	None	20 min of anodal tDCS, 2 mA; or sham tDCS. One-week washout	10 sessions (5 active and 5 sham stimulation)	CRS-R and EEG	No changes on EEG or CRS-R	4
Thibaut etal. 2017	Double-blind, crossover study	N=21 (n=11 out of 16 DOC due to TBI)	F3 anodal, right supraorbital (Fp2) cathodal	5x7 cm	None	20 min of anodal tDCS, 2 mA; or sham tDCS. One-week washout	10 sessions (5 active and 5 sham stimulation)	CRS-R	Positive treatment effect (CRS-R scores) after one week of anodal tDCS compared to sham	5
Bai etal. 2017	Double-blind, crossover study	N=16 (n=4 VS or MSC due to TBI)	F3 anodal, right supraorbital (Fp2) cathodal	5x5 cm	None	20 min of anodal tDCS, 2 mA; or sham tDCS. 3-day washout	2	TMS (MEP) and EEG	Global cerebral excitability increased in early time windows (0-100 and 100-200 ms) for patients with MCS after anodal tDCS	4

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Academia Brasileira de Neurologia, Departamento de Neurologia Cognitiva e Envelhecimento R. Vergueiro, 1353 sl.1404 - Ed. Top Towers Offices, Torre Norte, São Paulo, SP, Brazil, CEP 04101-000, Tel.: +55 11 5084-9463 | +55 11 5083-3876 - São Paulo - SP - Brazil
E-mail: revistadementia@abneuro.org.br | demneuropsy@uol.com.br

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[TFN01] AES: Apathy Evolution Scale; BDI-II: Beck Depression Inventory (2nd edition); CRS-R: Coma Recovery Scale-Revised; DLPFC: dorsolateral prefrontal cortex (F3 on left, F4 on right); DOC: disorder of consciousness; EEG: electroencephalography; GABA: gamma-aminobutyric acid; GOSe: Glasgow Outcome Scale extended; ICF: intracortical facilitation; ICI: intracortical facilitation; M1: Primary Motor Cortex (C3 on left, C4 on right); MEP: motor evoked potential; MRS: magnetic resonance spectroscopy; MSC: Minimal State of Consciousness; PCS: post-concussion syndrome; PVS: persistent vegetative state; RBANS: Repeatable Battery for the Assessment of Neuropsychological Status; SICI: short-interval intracortical inhibition; SO: Supraorbital (orbitofrontal; FP1 on left, FP2 on right); PCS: post concussion syndrome; TEA: Test of Everyday Attention; tDCS: transcraniai direct current stimulation; TMS: transcranial magnetic stimulation; UWS: unresponsive wakefulness syndrome; VS: vegetative State.