Supplement 1: Search Terms for Each Database

Supplement 1: Search Terms for Each Database

1

Supplement 1: Search Terms for Each Database

PUBMED

(ADHD OR adhd OR attention deficit disorder with hyperactivity OR minimal brain disorders OR syndrome hyperkinetic OR hyperkinetic syndrome OR hyperactivity disorder OR hyperactive child syndrome OR childhood hyperkinetic syndrome OR attention deficit hyperactivity disorders OR attention deficit hyperactivity disorder OR adhd attention deficit hyperactivity disorder OR addh OR overactive child syndrome OR attention deficit hyperkinetic disorder OR hyperkinetic disorder OR attention deficit disorder hyperactivity OR attention deficit disorders hyperactivity OR child attention deficit disorder OR hyperkinetic syndromes OR syndromes hyperkinetic OR hyperkinetic syndrome childhood) AND (RCT OR cluster RCT OR clinical trial* OR controlled clinical trial* OR crossover procedure OR cross over stud* OR crossover design OR double blind procedure OR double blind method OR double blind stud* OR single blind procedure OR single blind method OR single blind stud* OR random allocation OR randomization OR random assignment OR randomized controlled trial*) AND (neurofeedback OR “EEG biofeedback” OR neurotherapy OR SCP OR “slow cortical potentials”)

OVID DATABASES: Medline, PsycINFO, EMBASE+EMBASE CLASSIC

(ADHD OR adhd OR attention deficit disorder with hyperactivity OR minimal brain disorders OR syndrome hyperkinetic OR hyperkinetic syndrome OR hyperactivity disorder OR hyperactive child syndrome OR childhood hyperkinetic syndrome OR attention deficit hyperactivity disorders OR attention deficit hyperactivity disorder OR adhd attention deficit hyperactivity disorder OR addh OR overactive child syndrome OR attention deficit hyperkinetic disorder OR hyperkinetic disorder OR attention deficit disorder hyperactivity OR attention deficit disorders hyperactivity OR child attention deficit disorder OR hyperkinetic syndromes OR syndromes hyperkinetic OR hyperkinetic syndrome childhood OR Attention deficit disorder / OR ((atteni$) adj3 (deficit$ OR disorder$ or hyperactiv$ OR hyper?activ$ OR adhd OR addh OR ad??hd)) OR ((hyperkin$ OR hyper?kin$) adj3 (deficit$ OR disorder$ OR hkd))) AND (RCT OR cluster RCT OR clinical trial* OR controlled clinical trial* OR crossover procedure OR cross over stud* OR crossover design OR double blind procedure OR double blind method OR double blind stud* OR single blind procedure OR single blind method OR single blind stud* OR random allocation OR randomization OR random assignment OR randomized controlled trial*) AND (neurofeedback OR EEG biofeedback OR neurotherapy OR SCP OR slow cortical potentials)

ISI WEB of Knowledge (Web of Science [Science Citation Index Expanded], Biological Abstracts, Biosis, Food Science and Technology Abstracts)

(ADHD OR adhd OR attention deficit disorder with hyperactivity OR minimal brain disorders OR syndrome hyperkinetic OR hyperkinetic syndrome OR hyperactivity disorder OR hyperactive child syndrome OR childhood hyperkinetic syndrome OR attention deficit hyperactivity disorders OR attention deficit hyperactivity disorder OR adhd attention deficit hyperactivity disorder OR addh OR overactive child syndrome OR attention deficit hyperkinetic disorder OR hyperkinetic disorder OR attention deficit disorder hyperactivity OR attention deficit disorders hyperactivity OR child attention deficit disorder OR hyperkinetic syndromes OR syndromes hyperkinetic OR hyperkinetic syndrome childhood) AND (RCT OR cluster RCT OR clinical trial OR controlled clinical trial OR crossover procedure OR cross over study OR crossover design OR double blind procedure OR double blind method OR double blind study OR single blind procedure OR single blind method OR single blind study OR random allocation OR randomization OR random assignment OR randomized controlled trial) AND (neurofeedback OR EEG biofeedback OR neurotherapy OR SCP OR slow cortical potentials)

ERIC

(ADHD OR adhd OR attention deficit disorder with hyperactivity OR minimal brain disorders OR syndrome hyperkinetic OR hyperkinetic syndrome OR hyperactivity disorder OR hyperactive child syndrome OR childhood hyperkinetic syndrome OR attention deficit hyperactivity disorders OR attention deficit hyperactivity disorder OR adhd attention deficit hyperactivity disorder OR addh OR overactive child syndrome OR attention deficit hyperkinetic disorder OR hyperkinetic disorder OR attention deficit disorder hyperactivity OR attention deficit disorders hyperactivity OR child attention deficit disorder OR hyperkinetic syndromes OR syndromes hyperkinetic OR hyperkinetic syndrome childhood) AND (RCT OR cluster RCT OR clinical trial OR controlled clinical trial OR crossover procedure OR cross over study OR crossover design OR double blind procedure OR double blind method OR double blind study OR single blind procedure OR single blind method OR single blind study OR random allocation OR randomization OR random assignment OR randomized controlled trial) AND (neurofeedback OR EEG biofeedback OR neurotherapy OR SCP OR slow cortical potentials)

Supplement 2

Criteria for standard neurofeedback protocol as set out in Arns et al., 2014 (Arns M, Heinrich H, Strehl U. Evaluation of neurofeedback in ADHD: the long and winding road. Biol Psychol 2014;95:108-115)

- Well-investigated neurofeedback protocols comprise TBR (theta/beta EEG ratio), SMR (sensorimotor rhythm) and SCP (slow cortical potentials) neurofeedback protocols:

  • Training of the theta/beta EEG ratio (often defined as 4–8 Hz [theta] over 13–21 Hz [beta]): children are taught to decrease the excess theta and increase beta EEG activity at fronto-central locations
  • Training of event-related SCP shifts (starting at DC to 0.1Hz in trials lasting several seconds): children are taught to regulate negativity (related to the contingent negative variation and attentional resources) and positivity in separate trials at central or fronto-central locations

- Non-standard neurofeedback protocols comprise e.g. “QEEG-based” protocols with 2-channel training where the SMR is trained over the frontal cortex instead of over the motor cortex or training of the so-called “engagement index” at Fz (decreasing theta and alpha and increasing SMR and beta)

- It is crucial that the active treatment is in line with principles of learning theory and conditioning principles: e.g., automatic thresholding is clearly not in accordance with principles of learning theory

- The protocol needs to implement techniques to promote “generalization” into daily life, such as transfer trials, which seem to play a role in the correlation between learning and outcome

- Studies should report whether learning actually took place

Table S1. Studies Excluded From the Meta-Analysis, With the Reasons for Exclusion (in Alphabetical Order)

References / Reasons for Exclusion
Arns M, Kenemans JL. Neurofeedback and ADHD: Vigilance stabilization through sleep spindles and circadian networks: A working mechanism? Clinical EEG and Neuroscience. Conference: Future of Neurofeedback. 2012;44(2). / Abstract meeting
Bink M, I.L LB, Popma A, Van Nieuwenhuizen C. Effectiveness of neurofeedback in adolescents with ADHD features and comorbid disorders: A randomized controlled trial. Clinical EEG and Neuroscience. Conference: Future of Neurofeedback. 2012;44(2). / Abstract meeting
Cardo E, Servera M, Bernad M, Meisel V. Pharmacological treatment versus neurofeedback in typical symptomatology of attention deficit hyperactivity disorder. European Neuropsychopharmacology. Conference: 26th European College of Neuropsychopharmacology, ECNP Congress Barcelona Spain. Conference Start. 2013;23:S584. / Abstract meeting
Doehnert M, Brandeis D, Straub M, Steinhausen H-C, Drechsler R. Slow cortical potential neurofeedback in attention deficit hyperactivity disorder: is there neurophysiological evidence for specific effects? Journal of Neural Transmission. 2008;115:1445-1456. / Only partial randomization
Drechsler R, Brandeis D. Efficacy of neurofeedback training in ADHD: The importance of appropriate control conditions. Behavioural Neurology. Conference: Joint Meeting of the FESN/GNP. 2013;27(3). / Abstract meeting
Drechsler R, Straub M, Doehnert M, Heinrich H, Steinhausen HC, Brandeis D. Controlled evaluation of a neurofeedback training of slow cortical potentials in children with Attention Deficit/Hyperactivity Disorder (ADHD). Behavioral and Brain Functions. 2007;3:35. / Same study as Doehnert
(2008); see above
Gevensleben H, Holl B, Albrecht B, et al. Distinct EEG effects related to neurofeedback training in children with ADHD: A randomized controlled trial. International Journal of Psychophysiology. 2009;74:149-157. / Secondary analysis of
included trial
(Gevensleben
et al. [2009]).
Gevensleben H, Holl B, Albrecht B, et al. Neurofeedback training in children with ADHD: 6-month follow-up of a randomised controlled trial. European Child and Adolescent Psychiatry. 2010;19:715-724. / Secondary analysis of
included trial
(Gevensleben
et al. [2009]).
Gevensleben H, Kleemeyer M, Rothenberger LG, et al. Neurofeedback in ADHD: further pieces of the puzzle. Brain topography. 2014;27:20-32. / No RCT
González-Castro P, Cueli M, Rodríguez C, García T, Álvarez L. Efficacy of
Neurofeedback Versus Pharmacological Support in Subjects with ADHD. Appl
Psychophysiol Biofeedback. 2015 Aug 20. [Epub ahead of print] PubMed PMID: 26290167. / No RCT
Heinrich H. Standard neurofeedback protocols in children with ADHD: Methodical introduction and results from clinical studies. Behavioural Neurology. Conference: Joint Meeting of the FESN/GNP. 2013;27(3). / Abstract meeting
Heywood C, Beale I. EEG biofeedback vs. placebo treatment for attention-deficit/hyperactivity disorder: a pilot study. Journal of Attention Disorders. 2003;7:43-55. / Case series with n=5
analyzed pre vs post.
Lansbergen MM, van Dongen-Boomsma M, Buitelaar JK, Slaats-Willemse D. ADHD and EEG-neurofeedback: a double-blind randomized placebo-controlled feasibility study. J Neural Transm (Vienna) 2011;118:275-284 / Pilot study included in the larger study by Vollebregt et al. (2014; same dataset as van Dongen-Boomsma et al. [2013])
Leins U, Goth G, Hinterberger T, Klinger C, Rumpf N, Strehl U. Neurofeedback for children with ADHD: a comparison of SCP and Theta/Beta protocols. Applied psychophysiology and biofeedback. 2007;32:73-88. / Not randomization vs control
Levesque J, Beauregard M, Mensour B. Effect of neurofeedback training on the neural substrates of selective attention in children with attention-deficit/hyperactivity disorder: a functional magnetic resonance imaging study. Neuroscience Letters. 2006;394:216-221. / Secondary analysis of
included trial (Beauregard
and Levesque [2006]). Neuropsychological data already included from Beauregard
and Levesque (2006)
Li L, Yang L, Zhuo CJ, Wang YF. A randomised controlled trial of combined EEG feedback and methylphenidate therapy for the treatment of ADHD. Swiss medical weekly. 2013;143:w13838. / Control: medication + non-feedback attention training
Liechti MD, Maurizio S, Heinrich H, et al. First clinical trial of tomographic neurofeedback in attention-deficit/hyperactivity disorder: Evaluation of voluntary cortical control. Clinical Neurophysiology. 2012;123:1989-2005. / No RCT
Marx AM, Ehlis AC, Furdea A, et al. Near-infrared spectroscopy (NIRS) neurofeedback as a treatment for children with attention deficit hyperactivity disorder (ADHD)-a pilot study. Frontiers in human neuroscience. 2015;8:1038. / Data based on intermediate outcomes (after 12 sessions; the full study by Holtmann et al. [2014] included 25 sessions). As such, they are preliminary and can be potentially misleading. We therefore excluded these data
Maurizio S, Liechti MD, Brandeis D, Jaencke L, Drechsler R. Differential EMG Biofeedback for Children with ADHD: A Control Method for Neurofeedback Training with a Case Illustration. Applied Psychophysiology and Biofeedback. 2013;38:109-119. / No RCT
Meisel V, Servera M, Garcia-Banda G, Cardo E, Moreno I. Neurofeedback and standard pharmacological intervention in ADHD: a randomized controlled trial with six-month follow-up. Biological psychology. 2013;94:12-21. / Control: medication
Monastra VJ, Monastra DM, George S. The effects of stimulant therapy, EEG biofeedback, and parenting style on the primary symptoms of attention-deficit/hyperactivity disorder. Applied Psychophysiology and Biofeedback. 2002;27:231-49. / Not randomized
Ogrim G, Hestad KA. Effects of neurofeedback versus stimulant medication in attention-deficit/hyperactivity disorder: a randomized pilot study. Journal of child and adolescent psychopharmacology. 2013;23:448-457. / Control: medication
Perreau-Linck E, Lessard N, Lévesque J, Beauregard M. Effects of neurofeedback training on inhibitory capacities in ADHD children: A single-blind, randomized, placebo-controlled study." Journal of Neurotherapy. 2010;14:229-242. / Case series, no group
statistics provided.
Steiner NJ, Frenette EC, Rene KM, Brennan RT, Perrin EC. In-school neurofeedback training for ADHD: sustained improvements from a randomized control trial. Pediatrics. 2014;133:483-492. / Follow-up of Steiner et al. (2014)
Strehl U, Leins U, Danzer N, Hinterberger T, Schlottke PF. EEG-Feedback für Kinder mit einer Aufmerksamkeitsdefizit- und Hyperaktivitaetsstoerung (ADHS). Erste Ergebnisse aus einer randomisierten, kontrollierten Pilotstudie. [EEG feedback for children with attention deficit disorder with hyperactivity. Preliminary results from a randomized, controlled pilot study]. Kindheit und Entwicklung. 2004;13:180-189 / No control group;
compared two different
neurofeedback protocols.
Strehl U, Leins U, Goth G, Klinger C, Hinterberger T, Birbaumer N. Self-regulation of slow cortical potentials: A new treatment for children with attentiondeficit/ hyperactivity disorder. Pediatrics. 2006;118:E1530- E1540. / Same study as Strehl et al.
2004; see above

Note: ADHD = attention-deficit/hyperactivity disorder; RCT = randomized control trial.

Figure S1. Cochran risk of bias tool: graphic output.

Figure S2. Cochran risk of bias tool: characteristic of included studies. Note: Detailed ratings of each paper are available upon request.

Figure S3. Funnel plots and Egger’s tests for meta-analyses of effects of neurofeedback on attention-deficit/hyperactivity disorder (ADHD) core symptoms (most proximal and probably blinded measures): most proximal measures (MPROX). Note: SE = standard error; SMD = standard mean difference.

Egger's test for small-study effects: Regress standard normal deviate of intervention effect estimate against its standard error.

Number of studies = 13 Root MSE = 1.221

------

Std_Eff | Coef. Std. Err. t p>|t| [95% Conf. Interval]

------+------

slope | .1181913 .2792311 0.42 .680 -.4963922 .7327748

bias | -1.463625 .9022906 -1.62 .133 -3.449554 .5223028

------

Test of H0: no small-study effects p = .133

Note: Coef. = coefficients; MSE = mean standard error; Std_Eff = standard effects.

Figure S4. Funnel plots and Egger’s tests for meta-analyses of effects of neurofeedback on attention-deficit/hyperactivity disorder (ADHD) core symptoms (most proximal and probably blinded measures): probably blinded measures (PBLIND). Note: SE = standard error; SMD = standard mean difference.

Egger's test for small-study effects: Regress standard normal deviate of intervention effect estimate against its standard error.

Number of studies = 8 Root MSE = .5877

------

Std_Eff | Coef. SE t p>|t| [95% Conf. Interval]

------

slope | -.8903656 .2957594 -3.01 .024 -1.614063 -.1666684

bias | 2.305329 .8942946 2.58 .042 .117069 4.493589

------

Test of H0: no small-study effects p = .042

Note: Coef. = coefficients; MSE = mean standard error; Std_Eff: standard effects.

Egger’s test for small study effects suggests a bias may be acting for PBLIND (p= .042), but this needs to be interpreted carefully. Those studies with the larger standard errors (i.e. smaller n’s) are producing larger positive SMDs. Since a beneficial effect of intervention is indicated by more negative SMDs, the results suggest that the significant Egger’s test is not indicating publication bias in terms of under-reporting of null results from smaller studies but rather that small studies are of less good design and therefore fail to detect the expected benefit of intervention.

Figure S5. Results of the meta-regression analysis to assess the relationship between number of neurofeedback sessions and standardized mean difference (SMD) for most proximal and probably blinded assessment of attention-deficit/hyperactivity disorder (ADHD) core symptoms: most proximal measures (MPROX).

Meta-regression Number of obs = 13

REML estimate of between-study variance tau2 = .07733

% residual variation due to heterogeneity I-squared_res = 45.22%

Proportion of between-study variance explained Adj R-squared = -31.94%

With Knapp-Hartung modification

------

var2 | Coef. Std. Err. t p>|t| [95% Conf. Interval]

------+------

var1 | .0080086 .0213991 0.37 .715 -.0390905 .0551076

_cons | -.6149715 .7164024 -0.86 .409 -2.191763 .9618196

------

Note: Adj = adjusted; Coef. = coefficients; Cons = constant; MSE = mean standard error; n of obs = number of observations; n of sess = number of sessions; REML = restricted maximum likelihood; res = results; Std_Eff = standard effects; Std Err = standard error; Var = variance.

Figure S6. Results of the meta-regression analysis to assess the relationship between number of neurofeedback sessions and standardized mean difference (SMD) for most proximal and probably blinded assessment of attention-deficit/hyperactivity disorder (ADHD) core symptoms: probably blinded measures (PBLIND).

Meta-regression Number of obs = 8

REML estimate of between-study variance tau2 = 0

% residual variation due to heterogeneity I-squared_res = 0.00%

Proportion of between-study variance explained Adj R-squared = .%

With Knapp-Hartung modification

------

var2 | Coef. Std. Err. t p>|t| [95% Conf. Interval]

------

var1 | -.0157701 .0245817 -0.64 .545 -.0759194 .0443793

_cons | .3818454 .835393 0.46 .664 -1.662288 2.425978

------

NOTE: Adj = adjusted; Coef. = coefficients; Cons = constant; MSE = mean standard error; n of obs = number of observations; n of sess = number of sessions; REML = restricted maximum likelihood; res = results; Std_Eff = standard effects; Std Err = standard error; Var = variance