Parkinson's disease treatments: focus on transcranial direct current stimulation (tDCS)

Figures & data

Table 1 Summary of studies exploring the use of tDCS across motor and non-motor complications in Parkinson’s disease

Authors	Year	Motor	Cognitive	Other	Electrode size (cm^2)	Electrode intensity (mA)	Anode	Cathode	Sessions	Duration per session (minutes)	Study type	Adjunct	Disease state (HY)	Sample	Active	Sham	Outcomes	Result
Boggio et al^Citation71	2006		Working memory		35	1	Left DLPFC; M1 (left assumed)	Contralateral right orbit	2	20	Single-blind (assumed); cross-over			9	9	9	Three-back letter working mem paradigm	Nonsignificant
						2	Left DLPFC; M1 (left assumed)	Contralateral right orbit	2	20	Single-blind (assumed); cross-over			9	9	9	Three-back letter working mem paradigm	Significant (DLPFC only)
Fregni et al^Citation25	2006	UL			35	1	Left M1	Right supraorbital	1	20	Double-blind; cross-over		2.4 HY	9	9	9	MEP; UPDRS; sRT; PPT	Significant
					35	1	Right supraorbital	Left M1	1	20	Double-blind; cross-over			8	8	8	MEP; UPDRS; sRT; PPT	Nonsignificant
					35	1	Left DLPFC	Right supraorbital	1	20	Double-blind; cross-over			9	9	9	UPDRS; sRT; PPT	Significant
Benninger et al^Citation26	2010	Gait and UL	Reaction time	Depression	97.5 (anode); 25 (cathode)	2	10 cm anterior to Cz × 4 sessions; prefrontal cortices (forehead above eyebrows) × 4 sessions	Mastoids	8 (2/3 pw)	20	Double-blind		2.4±0.2	25	13	12	10 m walk; UL bradykinesia; UPDRS; sRT; BDI; health survey; SelfAx of mobility	Nonsignificant
Pereira et al^Citation76	2013			Verbal fluency	35	2	Left DLPFC or left TPC	Right supraorbital	1 (left DLPFC)+ 1 (left TPC)	20	Crossover; no blinding (2 montages tested)		1.6±0.5 HY	16	32	0	Verbal fluency (fixation, repetition, semantic, phonemic); fMRI	Significant (DLPFC over TPC)
Verheyden et al^Citation41	2013	Gait and posture			Not stated	1	M1 of dominant hemisphere	Contralateral supraorbital	1 + sham	15	Double-blind; cross-over		1–4 HY	20	20	20	Sit to stand; functional reach; 180° turn; TUG; 10 m walk	Nonsignificant
Doruk et al^Citation28	2014	UL	Exec	Mood/behavior	35	2	Left or right DLPFC	Supraorbital contralateral to anode placement	10 (5 pw)	20	Double-blind; 2 site			18	11 (6+5)	7	TMT A&B; WCST; PCL; WM; Stroop; HPVOT; CPM; MMSE; BDI; HAS; UPDRS III; sRT; 4-CRT; PPT; FT; WT; BU; SP	Significant (cog not motor)
Kaski et al^Citation50	2014	Gait			Anode: 40; cathode: 40	2	Anterior to Cz	Inion	1	15	Double-blind; RCT; cross-over	Physical therapy during stimulation		16	8	8	Gait velocity; TUG	Significant
Manenti et al^Citation54	2014	Gait			35	2	Left then right DLPFC for all patients	Contralateral supraorbital	2	7	Double-blind; 2 montages tested on each patient L&R DLPFC		1.3±1.1	10	20	10	TUG	Significant (right DLPFC)
Valentino et al^Citation56	2014	Gait			Not stated	2	M1 corresponding to leg, patient started walking post freezing	Contralateral orbitofrontal	5	20	Double-blind; cross-over		2–4 HY	10	10	10	Motor UPDRS; stand-walk-sit	Significant
Biundo et al^Citation53	2015		MCI			2	Left DLPFC	Right supraorbital	16 (4 pw)	20	Double-blind	Computer-based cog training		24	12	12	RBANS	Significant
Salimpour et al^Citation31	2015	UL			N/A	N/A	Experiment 1: No stimulation	No stimulation	N/A	N/A	N/A		1–2.5 HY	15 PD + 15 Healthy	N/A	N/A	N/A	N/A
					25	1	Experiment 2: Left M1	Right M1	1	25	Not stated			10	10	0	UPDRS (motor assumed); bimanual UL task; unimanual task; unimanual max force	Nonsignificant
					25 (assumed)	2	Experiment 3: Right M1	Left M1	1	25	Not stated			10	10	0	Motor UPDRS; bimanual UL task; unimanual task; unimanual max force	Significant
					25 (assumed)	Not stated	Experiment 4: Right or left M1	Right or left M1	3 (consecutive days)	Not stated	Double-blind; 3 montages tested (contra M1 anode; contra M1 cathode; sham)			10	10	0	Motor UPDRS; (bimanual UL task; unimanual task; unimanual max force – all assumed)	Significant (cathodal montage only)
					25 (assumed)	2	Experiment 5: Ipsilateral to affected side	Contralateral to affected side	5 (day 1: measures; days 2–3: sham; days 4–8: stim; days 9–10: measures)	Not stated	Not stated – single-blind (assumed)			8	8	8	Motor UPDRS; bimanual UL task; unimanual task; unimanual max force	Significant
Costa-Ribeiro et al^Citation49	2017	Gait			35	2	2 cm anterior to vertex in sagittal midline	Supraorbital area of most affected side	10 (2/3 pw)	13	Double-blind	Gait training	1–3 HY	24	11	11	TUG; UL-MT; MEP; aMT	Significant
Costa-Ribeiro et al^Citation49	2016	Gait			35	2	Cz	Supraorbital contralateral to most affected side	10 (3 pw)	13	Double-blind; RCT	Cued gait training		24	11	11	10 m walk; TUG; cadence; stride	Nonsignificant
Ferrucci et al^Citation33	2016	Dyskinesia			35	2	1–2 cm below inion	Shoulder	5 + sham	20	Double-blind; cross-over		2–3 HY	9	9	4	UPDRS III &IV; PDQ-8; BDI; VAT; sRT	Significant
					35	2	Left and right M1	Right deltoid	5 + sham	20	Double-blind; cross-over		2–3 HY	9	9	5	UPDRS III &IV; PDQ-8; BDI; VAT; sRT	Significant
Manenti et al^Citation52	2016		MCI		35	2	DLPFC – contralateral to most affected side	Ipsilateral supraorbital	10 (5 pw)	25	Double blind	Physical therapy during stimulation	2.2/2.3 HY	20	10	10	PDCRS	Significant
Schabrun et al^Citation30	2016	Gait			35	2	Left M1	Contralateral supraorbital	9 (3 pw)	20	Double-blind; parallel group design	Gait training	2–3 HY	16	8	8	Gait speed, step length, cadence, TUG, bradykinesia, motor speed	Nonsignificant
Swank et al^Citation55	2016	Gait			Not stated	2	Left DLPFC	Right DLPFC	1 active; 1 sham	20	Single-blind (assumed); cross-over		2 HY (median)	10	10	10	TUG (alone); TUG (manual); TUG (cognitive); PDQ-39	Nonsignificant
Forogh et al^Citation82	2017			Fatigue/daytime sleepiness	35	2 (assumed)	Left DLPFC	Right DLPFC	8 (2 weeks)	20	Double-blind	Occupational therapy		23	12	11	FSI; ESS	Significant (fatigue only)
Lattari et al^Citation51	^Citation1 2017	Balance and gait			35	2	Left DLPFC	Right supraorbital cortex	1	20	Double-blind; cross-over		2.3506.±1.06	17	17	17	Berg; DGI; TUG	Significant − all measures

Abbreviations: DLPFC, dorsolateral prefrontal cortex; Exec, executive function; M1, primary motor cortex; MCI, mild cognitive impairment; PD, Parkinson’s disease; TPC, temporoparietal cortex; UL, upper limb; sRT, simple reaction time; UPDRS, Unified Parkinson’s Disease Rating Scale; MEP, motor-evoked potential; tDCS, transcranial direct current stimulation; fMRI, functional MRI. N/A, not available; HY, Hoehn & Yahr; RCT, randomized controlled trial; PPT, Purdue Pegboard Test; WCST, Wisconsin Card Sorting Test; CPM, Colored Progressive Matrices; MMSE Mini mental state examination; HPVOT, Hooper Visual Organization Test; HAS, Hamilton Anxiety Scale; 4-CRT, 4-choice reaction time; FT, Finger Tapping; WT, walking time; BU, buttoning up; SP supination-pronation; RBANS, Repeatable battery assessment of neuropsychological status; aMT, active motor threshold; PDQ8 Parkinson’s disease quality of life questionnaire; VAT, visual attention task; PDCRS, parkinson’s disease cognitive rating scale; FSI, fatigue severity index; ESS, Epworth Sleepiness Scale; DGI, dynamic gait index; Berg, Berg Balance Scale; UL-MT, upper limb motor task; stim, stimulation; SelfAx, self-assessment; BDI, Beck Depression Index; TUG, timed up and go; cog, cognition; L&R, left and right; PCL, probabilistic classification learning; TMT A&B, trial making tests A&B; WM, working memory; pw, per week; TPC, temporoparietal cortex; Cz, central electrode in 10–20 electroencephalogram placement.

Boggio PS, Ferrucci R, Rigonatti SP, et al. Effects of transcranial direct current stimulation on working memory in patients with Parkinson’s disease. J Neurol Sci. 2006;249(1):31–38.

 PubMed Web of Science ®Google Scholar

Fregni F, Boggio PS, Santos MC, et al. Noninvasive cortical stimulation with transcranial direct current stimulation in Parkinson’s disease. Mov Disord. 2006;21(10):1693–1702.

 PubMed Web of Science ®Google Scholar

Benninger DH, Lomarev M, Lopez G, et al. Transcranial direct current stimulation for the treatment of Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2010;81(10):1105–1111.

 PubMed Web of Science ®Google Scholar

Pereira JB, Junqué C, Bartrés-Faz D, et al. Modulation of verbal fluency networks by transcranial direct current stimulation (tDCS) in Parkinson’s disease. Brain Stimul. 2013;6(1):16–24.

 PubMed Web of Science ®Google Scholar

Verheyden G, Purdey J, Burnett M, Cole J, Ashburn A. Immediate effect of transcranial direct current stimulation on postural stability and functional mobility in Parkinson’s disease. Mov Disord. 2013;28(14):2040–2041.

 PubMed Web of Science ®Google Scholar

Doruk D, Gray Z, Bravo GL, Pascual-Leone A, Fregni F. Effects of tDCS on executive function in Parkinson’s disease. Neurosci Lett. 2014;582:27–31.

 PubMed Web of Science ®Google Scholar

Kaski D, Dominguez RO, Allum JH, Islam AF, Bronstein AM. Combining physical training with transcranial direct current stimulation to improve gait in Parkinson’s disease: a pilot randomized controlled study. Clin Rehabil. 2014;28(11):1115–1124.

 PubMed Web of Science ®Google Scholar

Manenti R, Brambilla M, Rosini S, et al. Time up and go task performance improves after transcranial direct current stimulation in patient affected by Parkinson’s disease. Neurosci Lett. 2014;580:74–77.

 PubMed Web of Science ®Google Scholar

Valentino F, Cosentino G, Brighina F, et al. Transcranial direct current stimulation for treatment of freezing of gait: a cross-over study. Mov Disord. 2014;29(8):1064–1069.

 PubMed Web of Science ®Google Scholar

Biundo R, Weis L, Fiorenzato E, et al. Double-blind randomized trial of t-DCS versus sham in Parkinson patients with mild cognitive impairment receiving cognitive training. Brain Stimul. 2015;8(6):1223–1225.

 PubMed Web of Science ®Google Scholar

Salimpour Y, Mari ZK, Shadmehr R. Altering effort costs in Parkinson’s disease with noninvasive cortical stimulation. J Neurosci. 2015;35(35):12287–12302.

 PubMed Web of Science ®Google Scholar

Costa-Ribeiro A, Maux A, Bosford T, et al. Dopamine-independent effects of combining transcranial direct current stimulation with cued gait training on cortical excitability and functional mobility in Parkinson’s disease. J Rehabil Med. 2016;48(9):819–823.

 PubMed Web of Science ®Google Scholar

Ferrucci R, Cortese F, Bianchi M, et al. Cerebellar and motor cortical transcranial stimulation decrease levodopa-induced dyskinesias in Parkinson’s disease. Cerebellum. 2016;15(1):43–47.

 PubMed Web of Science ®Google Scholar

Manenti R, Brambilla M, Benussi A, et al. Mild cognitive impairment in Parkinson’s disease is improved by transcranial direct current stimulation combined with physical therapy. Mov Disord. 2016;31(5):715–724.

 PubMed Web of Science ®Google Scholar

Schabrun SM, Lamont RM, Brauer SG. Transcranial direct current stimulation to enhance dual-task gait training in Parkinson’s disease: a pilot RCT. PLoS One. 2016;11(6):e0158497.

 PubMed Web of Science ®Google Scholar

Swank C, Mehta J, Criminger C. Transcranial direct current stimulation lessens dual task cost in people with Parkinson’s disease. Neurosci Lett. 2016;626:1–5.

 PubMed Web of Science ®Google Scholar

Forogh B, Rafiei M, Arbabi A, Motamed MR, Madani SP, Sajadi S. Repeated sessions of transcranial direct current stimulation evaluation on fatigue and daytime sleepiness in Parkinson’s disease. Neurol Sci. 2017;38(2):249–254.

 PubMed Web of Science ®Google Scholar

Lattari E, Costa SS, Campos C, de Oliveira AJ, Machado S, Neto GA. Can transcranial direct current stimulation on the dorsolateral prefrontal cortex improves balance and functional mobility in Parkinson’s disease? Neurosci Lett. 2017;636:165–169.

 PubMed Web of Science ®Google Scholar

Parrao-Diaz T, Chana-Cuevas P, Juri-Claverias C, Kunstmann C, Tapia-Nunez J. Evaluation of cognitive impairment in a population of patients with Parkinson’s disease by means of the mini mental Parkinson test. Rev Neurol. 2004;40(6):339–344.

 Web of Science ®Google Scholar