Attention-deficit/hyperactivity disorder (ADHD) is characterised by persisting and impairing symptoms of age-inappropriate inattention and/or hyperactivity/impulsivity (DSM-5). EEG-neurofeedbackIt has been tested for about 45 years, with the latest meta-analyses of randomised controlled trials (RCT) showing small/medium effects compared to non-active controls only. Three small studies piloted neurofeedback of frontal activations in ADHD using functional magnetic resonance imaging or near-infrared spectroscopy, finding no superior effects over control conditions. Brain stimulation has been applied to ADHD using mostly repetitive transcranial magnetic and direct current stimulation (rTMS/tDCS). rTMS has shown mostly negative findings on improving cognition or symptoms. Meta-analyses of tDCS studies targeting mostly the dorsolateral prefrontal cortex show small effects on cognitive improvements with only two out of three studies showing clinical improvements. Trigeminal nerve stimulation has been shown to improve ADHD symptoms with medium effect in one RCT. Modern neurotherapeutics are attractive due to their relative safetyis one of the most common childhood disorders with a worldwide prevalence of around 7%. Problems persist into adulthood in a substantial proportion of cases, and they are associated with comorbidities and potential neuroplastic effects. However, they need to be thoroughly tested for clinical and cognitive efficacy across settings and beyond core symptoms and for their potential for individualised treatmentor academic and social outcomes.
Stimulation Protocol | Outcome Measures (Bold/Underlined = Improvement) | ||||||||
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Study | Design | N | Age | Target | Sessions | Frequency | Duration | Clinical | Cognitive |
Children | |||||||||
Cao et al., 2020 [77][147] |
Single-blind, randomised, parallel (2 active controls: ATX, ATX-rTMS; no sham) | 64 (~20 each) | 6–13 | R DLPFC a | 20 | 18 Hz (100% MT) | 2000 pulses (4 s on, 26 s off) | SNAP-IV | CPT; WISC; IGT |
Gomez et al., 2014 [76][146] |
Open label | 10 | 7–12 | L DLPFC | 5 | 1 Hz (90% MT) | 1500 pulses (on, off n/r) | DSM-IV ADHD symptom checklist (hyperactivity/imp., inattention) | n/t |
Adults | |||||||||
Bloch et al., 2010 [72][142] |
Single-blind, sham-controlled, randomised, crossover | 13 | NR (adults) | R DLPFC a | 1 | 20 Hz (100% MT) | 1680 pulses (2 s on, 30 s off) | PANAS (inattention, total score; mood, anxiety, hyperactivity); VAS (inattention, mood) b | n/t |
Paz et al., 2018 [74][144] |
Double-blind, sham-controlled, randomised, parallel | A: 13 S: 9 | A: 32 S: 30 |
L DLPFC c | 20 | 18 Hz (120% MT) | 1980 pulses (2 s on, 20 s off) | CAARS | TOVA |
Weaver et al., 2012 [73][143] |
Single-blind, sham-controlled, randomised, crossover | 9 | 18 | R DLPFC a | 10 | 10 Hz (100% MT) | 2000 pulses (4 s on, 26 s off) | CGI-I scale; ADHD-IV scale | WAIS/WISC-IV; Connors CPT; DKEFS; Buschke Selective Reminding Test; Symbol Digit Coding test; Finger Oscillation tasks |
Alyagon et al., 2020 [75][145] |
Double-semi-blind, randomised, active and sham-controlled | 52 (15, 14, 14) | 21–46 | R IFC & DLPFC | 15 | 18 Hz (120% MT) | 1440 pulses (2 s on, 20 s off) | CAARS (global ADHD symptoms; hyperactivity/impulsiveness) (BAARS-IV (hyperactivity/impulsiveness), BRIEF-A, BDI) | STROOP; STOP |
Stimulation Protocol | Outcome Measures (Bold/Underlined = Improvement; Cursive = Impairment) |
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Study | Design | n | Mean Age | Anode/Cathode | mA | Sessions | Timing a | Duration (mins) | Clinical | Cognitive |
Children | ||||||||||
† Bandeira et al., 2016 [98][168] |
Open label | 9 | 11 | L DLPFC/R SOA | 2 | 5 | Online | 28 | Patient Global Impression of Improvement | Visual Attention Test (OM); NEPSY-II-inhibition (Switch errors); Digit Span; Corsi Cubes |
Breitling et al., 2016 [99][169] |
Single-blind, sham-controlled, randomised, crossover | 21 | 14 | R IFC/L Cheek | 1 | 1 | Online | 20 | n/t | Flanker (Incongruent trials: COM c,d & RTV c) e |
L Cheek/R IFC | 1 | 1 | Online | 20 | n/t | Flanker | ||||
Munz et al., 2015 [97][167] |
Double-blind, sham-controlled, randomised, crossover | 14 | 12 | L DLPFC/R Cheek; R DLPFC/L Cheek |
0.25 | 1 | Offline | 25 (5 on, 1 off) | n/t | Go/No-Go (Go RT & RTV); Motor memory; Alertness |
Nejati et al., 2020, Exp 1 [101][171] |
Double-blind, sham-controlled, randomised, crossover | 15 | 10 | L DLPFC/R DLPFC | 1 | 1 | Offline | 15 | n/t | Go/No-Go; N-back (Acc, RT); Stroop (Incongruent trials: COM & RT); WCST (Completion time) |
Nejati et al., 2020, Exp 2 [101][171] |
Double-blind, sham-controlled, randomised, crossover | 10 | 9 | L DLPFC/R SOA | 1 | 1 | Offline | 15 | n/t | Go/No-Go; N-back (Acc c, RT) d; WCST (Total categories completed, total & pers errors) d |
R SOA/L DLPFC | 1 | 1 | Offline | 15 | n/t | Go/No-Go (No--Go acc) d; N-back; WCST (Total categories completed, total & pers errors c) d | ||||
Prehn-Kristensen et al., 2014 [96][166] |
Double-blind, sham-controlled, randomised, parallel | 12 | 12 | L DLPFC/R Cheek; R DLPFC/L Cheek | 0.25 | 1 | Offline | 25 (5 on, 1 off) | n/t | Declarative Memory (Acc); Alertness; Digit Span |
Soff et al., 2017 [94][164] |
Double-blind, sham-controlled, randomised, crossover | 15 | 14 | L DLPFC/Vertex | 1 | 5 | Online | 20 | FBB-ADHD(Inattention f) g,h | QbTest (Inattention f; hyperactivity i) g,h |
Soltaninejad et al., 2019 [91][161] | Single-blind, sham-controlled, randomised, crossover | 20 | 16 | L DLPFC/R SOA | 1.5 | 1 | Online | 15 | n/t | Go/No-Go (Go Acc) c,d; Stroop |
R SOA/L DLPFC | 1.5 | 1 | Online | 15 | n/t | Go/No-Go (NoGo Acc) c,j; Stroop | ||||
‡ Soltaninejad et al., 2015 [91][161] |
Single-blind, sham-controlled, randomised, crossover | 20 | 16 | rIFC/L SOA | 1 | 1 | Online | 15 | n/t | Go/No-Go (Go Acc); Stroop |
Sotnikova et al., 2017 [95][165] |
Double-blind, sham-controlled, randomised, crossover | 13 | 14 | L DLPFC/Vertex | 1 | 1 | Online | 20 | n/t | QbTest (RT, RTV k, OMs, Acc) l |
Breitling et al., 2020 [99][169] |
Double-blind, sham- and HD-tDCS controlled, randomised, crossover | ADHD: 15HC: 15 | 13 (10–16) |
R IFC/L SOA | 1 | 3 with CT | Online | 20 | n/t | WM task; ERPs N200; P300 |
Salehinejad et al., 2020 [100][170] |
Single-blind, sham-controlled, randomised, cross-over | 19 | 9 (8–12) |
1 | 2 | Online | 23 | n/t | ANT (orienting); GNG; SAT; Stroop | |
† Westwood et al., 2021 [92][162] |
Double-blind, sham-controlled, randomised, parallel | 50 | 14 | R IFC/L SOA | 1 | 15 | Online | 20 | ADHD-RS; Conners 3P | GNG; Stop; Simon; WCST; CPT; MCT; time estimation; NIH WM; Verbal Fluency |
Nejati et al., 2020 [101][171] |
Double-blind, sham-controlled, randomised, cross-over | 20 | 9 | L DLPFC/R vmPFC R DLPFC/L vmPFC Sham |
1 | 1 | Online | 20 | n/t | BART; CDDT (k20, k10) |
† Berger et al., 2021 [104][174] |
Double-blind, active controlled, randomised, cross-over | 19 | 7–12 | L DLPFC (tDCS)/R SOA L DLPFC/R IFC (tRNS) |
0.75 | 5 | Online | 5 | n/t | ADHD-RS; Working & short-term memory, Moxo-CPT (all improved with tRNS vs. tDCS) |
Adults | ||||||||||
† Allenby et al., 2018 [107][177] |
Double-blind, sham-controlled, randomised, crossover | 37 | 32 | L DLPFC/R SOA | 2 | 3 | Online | 20 | n/t | Conners CPT (COM m); Stop Task |
Cachoeira et al., 2017 [108][178] |
Double-blind, sham-controlled, randomised, parallel | A: 9 S: 8 |
A: 31 S: 34 |
R DLPFC/L DLPFC | 2 | 5 | Offline | 20 | ADHD Checklist (Inattention, Total) n; SDS (after tDCS); ADHD total score 2 weeks | None |
Cosmo et al., 2015 [105][175] |
Double-blind, sham-controlled, randomised, parallel | A: 30 S: 30 |
A: 32 S: 33 |
LDLPFC/R DLPFC | 1 | 1 | Offline | 20 | n/t | Go/No-Go |
Jacoby et al., 2018 [106][176] |
Single-blind, sham-controlled, randomised, crossover | 20 | 23 | L&R DLPFC/Cerebellum | 1.8 | 1 | Offline | 20 | n/t | CPT (multi-button presses) |
Dubreuil-Vall et al., 2020 [109][179] |
Double-blind, sham-controlled, randomised, crossover | 37 | 18–67 | L DLPFC/R SOA R DLPFC/R SOA |
2 | 1 | Offline | 30 | n/t | Flanker (incongruent RT) n = 18; L P300; L N200. Stop (go RTs); L P200. n = 19 Flanker; Stop |