A diffusion decision model analysis of the cognitive effects of neurofeedback for ADHD.

OBJECTIVE: To examine cognitive effects of neurofeedback (NF) for attention-deficit hyperactivity disorder (ADHD) as a secondary outcome of a randomized clinical trial. METHOD: In a double-blind randomized clinical trial (NCT02251743), 133 7-10-year olds with ADHD received either 38 sessions of NF (n = 78) or control treatment (n = 55) and performed an integrated visual and auditory continuous performance test at baseline, mid- and end-treatment. We used the diffusion decision model to decompose integrated visual and auditory continuous performance test performance at each assessment into cognitive components: efficiency of integrating stimulus information (v), context sensitivity (cv), response cautiousness (a), response bias (z/a), and nondecision time for perceptual encoding and response execution (Ter). Based on prior findings, we tested whether the components known to be deficient improved with NF and explored whether other cognitive components improved using linear mixed modeling. RESULTS: Before NF, children with ADHD showed main deficits in integrating stimulus information (v), which led to less accurate and slower responses than healthy controls (p = .008). The NF group showed significantly more improvement in integrating auditory stimulus information (v) than control treatment (significant group-by-time-by-modality effect: p = .044). CONCLUSIONS: NF seems to improve v, deficient in ADHD. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cognitive markers for efficacy of neurofeedback for attention-deficit hyperactivity disorder - personalized medicine using computational psychiatry in a randomized clinical trial.

BACKGROUND: Exploring whether cognitive components (identified by baseline cognitive testing and computational modeling) moderate clinical outcome of neurofeedback (NF) for attention-deficit hyperactivity disorder (ADHD). METHOD: 142 children (aged 7-10) with ADHD were randomly assigned to either NF (n = 84) or control treatment (n = 58) in a double-blind clinical trial (NCT02251743). The NF group received live, self-controlled downtraining of electroencephalographic theta/beta ratio power. The control group received identical-appearing reinforcement from prerecorded electroencephalograms from other children. 133 (78 NF, 55 control) children had cognitive processing measured at baseline with the Integrated Visual and Auditory Continuous Performance Test (IVA2-CPT) and were included in this analysis. A diffusion decision model applied to the IVA2-CPT data quantified two latent cognitive components deficient in ADHD: drift rate and drift bias, indexing efficiency and context sensitivity of cognitive processes involving information integration. We explored whether these cognitive components moderated the improvement in parent- and teacher-rated inattention symptoms from baseline to treatment end (primary clinical outcome). RESULTS: Baseline cognitive components reflecting information integration (drift rate, drift bias) moderated the improvement in inattention due to NF vs. control treatment (p = 0.006). Specifically, those with either the most or least severe deficits in these components showed more improvement in parent- and teacher-rated inattention when assigned to NF (Cohen's d = 0.59) than when assigned to control (Cohen's d = -0.21). CONCLUSIONS: Pre-treatment cognitive testing with computational modeling identified children who benefitted more from neurofeedback than control treatment for ADHD.

Effects of Trainer Continuity and Experience on Neurofeedback Treatment of ADHD in Children.

OBJECTIVE: To examine whether trainer continuity and experience impacted the significantly improved inattention scores (pre-post d = 1.44-1.53) seen in both the control and active treatment groups of "Double-Blind Placebo-Controlled Randomized Clinical Trial of Neurofeedback for Attention-Deficit/Hyperactivity Disorder" (2021). METHODS: The primary trainer was the one who coached the most treatment sessions with a participant. A trainer was considered experienced after coaching 100 sessions. The percentage of sessions each participant had with their primary trainer and percentage with an experienced trainer were entered as independent variables into linear mixed models in SASv.9.4 with improvement in inattention ratings by parents and teachers (primary outcome) as dependent variable. RESULTS: Effect of trainer continuity on primary outcome was not significant (B = -0.016, SE = 0.153, t(123) = -0.11, p = .916). However, percent of sessions with an experienced trainer correlated with increased improvement (B = 0.238, SE = 0.095, t(123) = 2.51, p = .013). CONCLUSION: Neurofeedback trainer continuity does not appear important, while trainer experience with at least 100 sessions correlates with better outcomes.

For Which Children with ADHD is TBR Neurofeedback Effective? Comorbidity as a Moderator.

We examined psychiatric comorbidities moderation of a 2-site double-blind randomized clinical trial of theta/beta-ratio (TBR) neurofeedback (NF) for attention deficit hyperactivity disorder (ADHD). Seven-to-ten-year-olds with ADHD received either NF (n = 84) or Control (n = 58) for 38 treatments. Outcome was change in parent-/teacher-rated inattention from baseline to end-of-treatment (acute effect), and 13-month-follow-up. Seventy percent had at least one comorbidity: oppositional defiant disorder (ODD) (50%), specific phobias (27%), generalized anxiety (23%), separation anxiety (16%). Comorbidities were grouped into anxiety alone (20%), ODD alone (23%), neither (30%), or both (27%). Comorbidity (p = 0.043) moderated acute effect; those with anxiety-alone responded better to Control than to TBR NF (d = - 0.79, CI - 1.55- - 0.04), and the other groups showed a slightly better response to TBR NF than to Control (d = 0.22 ~ 0.31, CI - 0.3-0.98). At 13-months, ODD-alone group responded better to NF than Control (d = 0.74, CI 0.05-1.43). TBR NF is not indicated for ADHD with comorbid anxiety but may benefit ADHD with ODD.Clinical Trials Identifier: NCT02251743, date of registration: 09/17/2014.

EEG Connectivity in ADHD Compared to a Normative Database: A Cohort Analysis of 120 Subjects from the ICAN Study.

This study explores how EEG connectivity measures in children with ADHD ages 7-10 (n = 140) differ from an age-matched nonclinical database. We differentiated connectivity in networks, Brodmann area pairs, and frequencies. Subjects were in the International Collaborative ADHD Neurofeedback study, which explored neurofeedback for ADHD. Inclusion criteria were mainly rigorously diagnosed ADHD and a theta/beta power ratio (TBR) ≤ 4.5. Using statistical and machine learning algorithms, connectivity values were extracted in coherence, phase, and lag coherence at all Brodmann, subcortical, and cerebellar areas within the main networks in all EEG frequencies and then compared with a normative database. There is a higher rate of dysregulation (more than ± 1.97SD), in some cases as much as 75%, of the Brodmann pairs observed in coherence and phase between BAs 7, 10, and 11 with secondary connections from these areas to BAs 21, 30, 35, 37, 39, and 40 in the ADHD children as compared to the normative database. Left and right Brodmann areas 10 and 11 are highly disconnected to each other. The most dysregulated Brodmann Areas in ADHD are 7, 10, and 11, relevant to ADHD executive-function deficits and provide important considerations when developing interventions for ADHD children.

Brainmarker-I Differentially Predicts Remission to Various Attention-Deficit/Hyperactivity Disorder Treatments: A Discovery, Transfer, and Blinded Validation Study.

BACKGROUND: Attention-deficit/hyperactivity disorder is characterized by neurobiological heterogeneity, possibly explaining why not all patients benefit from a given treatment. As a means to select the right treatment (stratification), biomarkers may aid in personalizing treatment prescription, thereby increasing remission rates. METHODS: The biomarker in this study was developed in a heterogeneous clinical sample (N = 4249) and first applied to two large transfer datasets, a priori stratifying young males (<18 years) with a higher individual alpha peak frequency (iAPF) to methylphenidate (N = 336) and those with a lower iAPF to multimodal neurofeedback complemented with sleep coaching (N = 136). Blinded, out-of-sample validations were conducted in two independent samples. In addition, the association between iAPF and response to guanfacine and atomoxetine was explored. RESULTS: Retrospective stratification in the transfer datasets resulted in a predicted gain in normalized remission of 17% to 30%. Blinded out-of-sample validations for methylphenidate (n = 41) and multimodal neurofeedback (n = 71) corroborated these findings, yielding a predicted gain in stratified normalized remission of 36% and 29%, respectively. CONCLUSIONS: This study introduces a clinically interpretable and actionable biomarker based on the iAPF assessed during resting-state electroencephalography. Our findings suggest that acknowledging neurobiological heterogeneity can inform stratification of patients to their individual best treatment and enhance remission rates.

Characterizing Underlying Cognitive Components of ADHD Presentations and Co-morbid Diagnoses: A Diffusion Decision Model Analysis.

OBJECTIVE: To Explore whether subtypes and comorbidities of attention-deficit hyperactivity disorder (ADHD) induce distinct biases in cognitive components involved in information processing. METHOD: Performance on the Integrated Visual and Auditory Continuous Performance Test (IVA-CPT) was compared between 150 children (aged 7 to 10) with ADHD, grouped by DSM-5 presentation (ADHD-C, ADHD-I) or co-morbid diagnoses (anxiety, oppositional defiant disorder [ODD], both, neither), and 60 children without ADHD. Diffusion decision modeling decomposed performance into cognitive components. RESULTS: Children with ADHD had poorer information integration than controls. Children with ADHD-C were more sensitive to changes in presentation modality (auditory/visual) than those with ADHD-I and controls. Above and beyond these results, children with ADHD+anxiety+ODD had larger increases in response biases when targets became frequent than children with ADHD-only or with ADHD and one comorbidity. CONCLUSION: ADHD presentations and comorbidities have distinct cognitive characteristics quantifiable using DDM and IVA-CPT. We discuss implications for tailored cognitive-behavioral therapy.

Vitamin D levels in children with attention deficit hyperactivity disorder: Association with seasonal and geographical variation, supplementation, inattention severity, and theta:beta ratio.

We examined seasonal and geographic effects on vitamin D [25(OH)D] levels, association with attention-deficit/hyperactivity disorder (ADHD) symptom severity, and effects of supplementation in 222 children age 7-10 with rigorously diagnosed ADHD. 25(OH)D insufficiency rates were 47.2 % in Ohio and 28.5 % 400 miles south in North Carolina. Nadir of 25(OH)D levels was reached by November in Ohio, not until January in NC. Thirty-eight children with insufficiency/deficiency took vitamin D (1000-2000 IU/day for a month); levels rose 52 %. Although inattention did not correlate with 25(OH)D at screen nor improve significantly with supplementation, inattention improvement after supplementation correlated with 25(OH)D increase (rho = 0.41, p = 0.012). A clinically significant proportion of children with ADHD have insufficient 25(OH)D even at summer's end, more so in the winter and north of the 37th parallel. The significant correlation of inattention improvement with 25(OH)D increase suggests further research on 25(OH)D as ADHD treatment.

Different Spectral Analysis Methods for the Theta/Beta Ratio Calculate Different Ratios But Do Not Distinguish ADHD from Controls.

There has been ongoing research on the ratio of theta to beta power (Theta/Beta Ratio, TBR) as an EEG-based test in the diagnosis of ADHD. Earlier studies reported significant TBR differences between patients with ADHD and controls. However, a recent meta-analysis revealed a marked decline of effect size for the difference in TBR between ADHD and controls for studies published in the past decade. Here, we test if differences in EEG processing explain the heterogeneity of findings. We analyzed EEG data from two multi-center clinical studies. Five different EEG signal processing algorithms were applied to calculate the TBR. Differences between resulting TBRs were subsequently assessed for clinical usability in the iSPOT-A dataset. Although there were significant differences in the resulting TBRs, none distinguished between children with and without ADHD, and no consistent associations with ADHD symptoms arose. Different methods for EEG signal processing result in significantly different TBRs. However, none of the methods significantly distinguished between ADHD and healthy controls in our sample. The secular effect size decline for the TBR is most likely explained by factors other than differences in EEG signal processing, e.g. fewer hours of sleep in participants and differences in inclusion criteria for healthy controls.

Neurofeedback and Attention-Deficit/Hyperactivity-Disorder (ADHD) in Children: Rating the Evidence and Proposed Guidelines.

Stimulant medication and behaviour therapy are the most often applied and accepted treatments for Attention-Deficit/Hyperactivity-Disorder (ADHD). Here we explore where the non-pharmacological clinical intervention known as neurofeedback (NFB), fits on the continuum of empirically supported treatments, using standard protocols. In this quantitative review we utilized an updated and stricter version of the APA guidelines for rating 'well-established' treatments and focused on efficacy and effectiveness using effect-sizes (ES) and remission, with a focus on long-term effects. Efficacy and effectiveness are compared to medication and behaviour therapy using benchmark studies. Only recent systematic reviews and meta-analyses as well as multi-centre randomized controlled trials (RCT's) will be included. Two meta-analyses confirmed significant efficacy of standard neurofeedback protocols for parent and teacher rated symptoms with a medium effect size, and sustained effects after 6-12 months. Four multicenter RCT's demonstrated significant superiority to semi-active control groups, with medium-large effect sizes end of treatment or follow-up and remission rates of 32-47%. Effectiveness in open-label studies was confirmed, no signs of publication bias were found and no significant neurofeedback-specific side effects have been reported. Standard neurofeedback protocols in the treatment of ADHD can be concluded to be a well-established treatment with medium to large effect sizes and 32-47% remission rates and sustained effects as assessed after 6-12 months.

EEG Theta/Beta Ratio Calculations Differ Between Various EEG Neurofeedback and Assessment Software Packages: Clinical Interpretation.

The quantitative electroencephalographic (QEEG) theta/beta power ratio (TBR) has been shown to have an association with attention-deficit hyperactivity disorder (ADHD), with a previous tacit assumption of equivalence across hardware and software systems. Therefore, the International Collaborative ADHD Neurofeedback (ICAN) randomized clinical trial used a fixed TBR ≥ 4.5 cutoff as measured by the Thought Technology Monastra-Lubar Assessment Suite as an inclusion criterion, 1.5 SD above norms collected with that system. However, a difference was noted between the TBR calculated by that assessment suite and the TBR computed by EEGer, the neurofeedback software used for treatment, leading us to investigate the discrepancy. The difference may arise from different calculation methods. This article explains and compares various computational methods used to calculate and display EEG values, including TBR, elucidating why the values are not equivalent across equipment and software programs. Two major sources of variance are (1) how "spectral leakage" at the ends of bands is handled and (2) whether voltages of bins within a band are first averaged and then squared to get bandwidth power or are first squared to get power (turning negative voltages into positive power) and then averaged to get the bandwidth power; the latter method results in higher band power. This article compares methods of computing the TBR. Biofeedback practitioners and investigators should be aware of the algorithms their systems use when interpreting TBRs and require normative comparison data collected with the same system.

A review of neurofeedback treatment for pediatric ADHD.

OBJECTIVE: The aim of this paper was to review all randomized published trials and unpublished conference presentations on the neurofeedback (NF) treatment of pediatric ADHD, and their relevance, strengths, and limitations. METHOD: Via PsychInfo and Medline searches and contacts with NF researchers 14 studies were identified and reviewed. RESULTS: The majority were conducted from 1994 to 2010, with 5- to 15-year-olds, usually male and White with the combined type of ADHD. Most studies used theta/beta NF with a unipolar-electrode placement at Cz and demonstrated, where reported, an overall ADHD mean effect size of d = 0.69, a medium effect. Main study strengths, within some studies, include use of randomization, treatment control conditions, Diagnostic and Statistical Manual of Mental Disorders criteria, evidence-based assessment of ADHD, standard treatment outcome measures, multidomain assessment, and, for some studies, moderate sample size, some type of blind and the identification of medication as a concomitant treatment. Main study limitations (and directions for future research) include the lack of adequate blinding of participants, raters and NF trainers, a sham-NF/blinded control treatment condition, posttreatment follow-up, generalizability, specific details about delivery of NF, identification and control of comorbidity, and the identification, measurement, and control of concomitant treatments and potential side effects. CONCLUSION: Based on the results and methodologies of published studies, this review concludes that NF for pediatric ADHD can be currently considered as "probably efficacious."