Table 5.
Details of EEG studies of candidate monitoring/response biomarkers.
| Authors, year | Country | N ADHD | N Control | Age | % Male | % White | Design | Candidate biomarker(s) | Key findings |
|---|---|---|---|---|---|---|---|---|---|
| Aggensteiner et al. [115] | Germany | 103 (77 at follow-up) | 0 | M = 8.7, SD = 0.9 | 85% | Not reported | 3-month slow cortical potential-NF vs. semi-active control (electromyogram biofeedback) RCT | Cue P3 and contingent negative variation during cued go/no-go task | Attentional (cue P3) and preparatory (contingent negative variation) brain activity and performance non-specifically reduced after treatment. Contingent negative variation in the slow cortical potential-NF group increased with clinical improvement. |
| Aldemir et al. [116] | Turkey | 20 (all medication free) | 20 | M = 9, SD = 3 | Not reported | Not reported | 3-month MPH vs. ATX | Power across frequency bands during rest | Similar effects of MPH and ATX on EEG power across frequency bands in the ADHD group, especially at frontal and temporal regions. |
| Barry et al. [99] | Australia | 50 (all medication naïve) | 50 | M = 10.2, SD = 1.5 | 64% | Not reported | Single dose ATX | Beta power during rest | ATX increased absolute and relative beta power and produced topographic changes in other bands in the ADHD group. |
| Bresnahan et al. [102] | Australia | 50 (DEX responders) | 50 | M = 31, SD = 9 | 50% | Not reported | 4-week DEX, open label | Delta and theta power during rest | Significant reduction in absolute delta, absolute and relative theta, and total power in the ADHD group to levels similar to controls. |
| Chiarenza et al. [44] | Italy | 61 (all medication free for >5 times half-lives) | Not reported (reference database) | M = 10.4, SD = 2.9 | 85% | Not reported | 12-month ATX, open label | Absolute power across frequency bands during rest | Treatment-related reductions of absolute power in all frequencies over frontal, central and temporal regions in responders, becoming similar to controls. Non-significant changes in non-responders. |
| Clarke et al. [104] | Not reported (probably Australia) | 50 (all medication naïve or medication free for >5 times half-lives) | 40 | Range = 8–13 | 100% | Not reported | 6-month MPH or DEX, open label | Theta and beta power, TBR during rest | MPH/DEX increased beta power and reduced theta power and TBR in ADHD group, to levels similar to controls. |
| Clarke et al. [105] | Not reported (probably Australia) | 20 (all inattentive type, medication naïve or medication free for >5 times half-lives) | 10 | Range = 8–13 | 100% | Not reported | 6-month MPH or DEX, open label | Theta, alpha, beta power, theta/alpha ratio during rest | MPH/DEX increased alpha and beta power and reduced theta power and theta/alpha ratio in inattentive ADHD group, to levels similar to controls. |
| Groom et al. [96] | UK | 28 (all combined type, MPH responders) | 28 | M = 12.5, SD = 1.8 | 96% | Not reported | Single dose MPH | N2 and P3 amplitudes during go/no-go task | MPH increased N2 and P3 amplitudes in the ADHD group. |
| Groom et al. [98] | UK | 28 (all combined type, MPH responders) | 28 | M = 12.5, SD = 1.8 | 96% | Not reported | Single dose MPH | ERN and Pe during go/no-go task | MPH increased ERN and Pe amplitudes in the ADHD group. |
| Hermens et al. [107] | Australia | 34 (16 medication naïve, 18 MPH free for >2 weeks) | 34 | M = 13.8, SD = 1.6 | 82% | Not reported | 4-week MPH, open label | Theta power, P3 during oddball task | MPH reduced theta power and increased P3 amplitude in the ADHD group, to levels similar to controls. |
| Isiten et al. [106] | Turkey | 43 (all drug naïve) | 0 | M = 11.9, SD = 2.3 | 77% | Not reported | 1.5-year MPH, open label | Beta power during rest | MPH decreased TBR and increased beta power; no effect on theta power. |
| Janssen et al. [103] | Netherlands | 112 (all medication free for >1 month) | 0 | M = 9.6, SD = 1.6 | 75% | Not reported | 10-week MPH vs. NF vs. physical activity RCT | Theta power during rest and stop signal task | MPH reduced theta power during rest and task more than physical activity. NF reduced theta power during rest more than physical activity. Greater NF-related theta reductions correlated with symptom improvement. |
| Janssen et al., 2016b [110] | Netherlands | 112 (all medication free for >1 month) | 0 | M = 9.6, SD = 1.6 | 75% | Not reported | 10-week MPH vs, NF vs. physical activity RCT | P3 amplitude during stop signal task | MPH increased P3 amplitude more than NF and physical activity. Stimulant-related P3 effects were localized in the thalamus and striatum. |
| Kratz et al. [117] | Germany | 23 (all medication naïve) | 0 | M = 9.0, SD = 1.1 | 79% | Not reported | 8-week MPH vs. ATX, cross-over | Contingent negative variation amplitude during attention network test | MPH but not ATX increased contingent negative variation amplitudes. |
| Loo et al. [91] | USA | 10 (all MPH free for 48 hours) | 0 | M = 10.5, SD = 1.3 | 80% | Not reported | Single dose MPH vs. placebo, cross-over | Power across frequency bands during rest and CPT | MPH reduced theta and alpha power and increased beta power in responders, with opposite effects in non-responders. |
| Loo et al. 2004 [92] | USA | 36 | 0 | M = 10.2, SD = 1.3 | 72% | Not reported | Single dose MPH vs. placebo, cross-over | Power across frequency bands during rest and CPT | MPH increased beta power in responders, with opposite effects in non-responders. |
| Loo et al. [109] | USA | 207 (all medication naïve or medication free for >5 times half-lives) | 0 | M = 10.1, SD = 2.1 | 68% | 83% | 8-week MPH, GUAN, MPH + GUAN, RCT | Power across frequency bands during rest | GUAN decreased global alpha power, MPH and MPH + GUAN increased centro-parietal beta power, and MPH + GUAN decreased theta power. Medication-related changes in theta power correlated with behavioral and cognitive improvements. |
| Lubar et al. [93] | USA | 23 (all MPH free for 48 hours) | Not reported (reference database) | Range = 9–11 | 100% | Not reported | Single dose MPH vs. placebo, cross-over | Coherence, phase and asymmetry during rest | MPH ameliorated atypical EEG coherence, phase and asymmetry patterns in the ADHD group, to levels similar to the reference group. |
| Luo et al. [56] | China | 121 | 0 | M = 8.94, range 7.1–12.3 | 83% | Not reported | 3-month remote computerized cognitive, NF, and combined training, RCT | Alpha power during rest | All 3 treatments increased relative alpha power. Pre-training inattention scores corelated negatively with change in relative alpha. |
| McGough et al. [114] | USA | 62 (medication free for >1 month) | 0 | M = 10.4, SD = 1.4 | 65% | 65% | 4-week active vs. sham TNS, RCT | Power in delta, theta, beta, gamma frequency bands during rest | TNS increased right-frontal (delta, theta, beta, and gamma) and mid-frontal (gamma) power. |
| Michelini et al. [118] | USA | 207 (all medication naïve or medication free for >5 times half-lives) | 0 | M = 10.1, SD = 2.1 | 68% | 83% | 8-week MPH, GUAN, MPH + GUAN, RCT | Event-related mid-occipital power during a Sternberg spatial working memory task with encoding, maintenance and retrieval phases | MPH + GUAN decreased midoccipital theta, alpha and beta across task phases, with significantly greater changes than monotherapies. MPH increased midoccipital theta during retrieval. GUAN produced trend-level reductions in midoccipital alpha during maintenance and retrieval. Treatment-related changes in midoccipital power correlated with ADHD improvements. |
| Skirrow et al. [108] | UK | 41 (all medication free for >1 month [stimulants]) or 6 months [other medication]) | 48 | M = 28.5, SD = 9.5 | 100% | Not reported | 3.5-month MPH, open label | Theta power during rest, CPT and sustained attention to response task | MPH normalized in the ADHD group the increase in theta power between rest and task conditions displayed by controls. |
| Song et al. [94] | South Korea | 24 | 0 | M = 8.6, SD = 1.4 | 100% | Not reported | Single dose MPH | Power across frequency bands and TBR during CPT | MPH increased alpha and beta power, decreased theta and delta power, and increased TBR during CPT. No effects during rest. |
| Verbaten et al. [97] | Netherlands | 12 | 0 | M = 11.2, SD = 2.1 | 83% | Not reported | Single dose MPH vs. placebo, RCT | P3 and N2 amplitudes during CPT | MPH increased parietal P3 and frontal N2 amplitudes to targets and non-targets. |
ADHD attention deficit hyperactivity disorder, ATX atomoxetine, CPT continuous performance test, EEG electroencephalography, DEX dexamphetamine, ERP event relate potential, GUAN guanfacine, MPH methylphenidate, iAPF individual alpha peak frequency; M mean age, NF neurofeedback, RCT randomized controlled trial; SD standard deviation, TBR theta/beta ratio, TNS trigeminal nerve stimulation.