In Quest of Pathognomonic/Endophenotypic Markers of Attention Deficit Hyperactivity Disorder (ADHD): Potential of EEG-Based Frequency Analysis and ERPs to Better Detect, Prevent and Manage ADHD

Figures & data

Figure 1 EEG-based frequency analysis using (A) NeuralScan by Medeia showing demo results of: (B) Resting EEG (Eyes Open and Eyes Closed) and Theta/Beta ratio, (C) Visual and Auditory processing, Working Memory and Attention and (D) Theta/Beta ratio, Visual and Auditory processing, Working Memory, Attention Reaction Time (RT) and Reaction Time Variability (RTV).

Figure 2 (A) ADHD and its cross-border co-morbidities: Illustration of symptom sharingandsymptoms unique.^6,7 Percentage of Individuals with ADHD and selected symptom sharing (cross-border) psychiatric comorbidities (³²).

Figure 3 Correlation illustrating the shared genetics of adhd with selected psychiatric co-morbidities and behavioral-cognitive phenotypes.

Table 1 Analytic Approach Followed to Review EEG-Based Cognitive Studies on ADHD from 2000 to 2017

Analytical Approach		Prominent Components & Proposed Functional Significance
ERP’s	Sensory processing	P50:sensory gating, N1 (N100): Sensory processing of unexpected (auditory) stimulus, P1 (P100): Sensory processing of stimulus in the contralateral visual field, N170: Structural encoding of faces, Early posterior negativity (EPN): Selective visual attention toward emotional stimuli, Mismatch negativity (MMN): Detection of infrequent and odd deviant stimulus in a repetitive sequence of auditory or visual stimuli
	Stimulus evaluation	N2: Detection of mismatch and/or inhibition of competing response, N250: Storage of face representation in long-term memory, P2: Sensitivity to various stimulus features, P3a (novelty P3): Novelty processing and involuntary orienting of attention, P3b (classic P3): Attentional engagement and stimulus evaluation/decision-making, N3 (slow wave or late posterior negativity (LPN)), Enhanced attention to stimulus, particularly the nonautomatic, controlled part of the stimulus processing, Negative-going wave over centropariental electrodes peaking at 250–500 ms poststimulus
	Response preparation	CNV Negative-going wave rising around 260–470 ms after a warning stimulus: Response and motor preparation to upcoming stimulus, Lateralised readiness potential (LRP) Negative-going wave over motor cortices contralateral to the responding hands: Motor preparation before action execution, Late positive potential (LPP): Salience of emotional stimuli
	Error detection	Error-related negativity (ERN) Negative-going wave rising 50–100 ms following erroneous response execution over frontocentral electrodes: Unconscious error processing Error-related positivity (PE) Positive-going wave over centro-parietal electrodes peaking around 200–500 ms post-error, after the occurrence of ERN: Conscious error processing
Quantitative EEG (qEEG)		Very-low frequency (VLF, 0.02–0.2 Hz): Default-mode network, Delta: Attention and inhibition, Theta: Cognitive control, learning and memory, Alpha (8–12 Hz, over occipital cortex): Alertness, attention and inhibition, Mu rhythms (8–13 Hz, over sensorimotor cortex): Action execution and observation of others’ actions, Beta: Sensorimotor processing and sensory gating, Gamma:Sensory binding
Time-frequency analyses		Evoked power & Induced power: Dynamic changes in power of a given frequency band over time, Event-related phase-locking OR inter-trial coherence (ITC), Consistency of timing of ERPs across trials (eg, neural variability), Coherence & Cross-frequency coupling: Brain’s regional connectivity and interregional interaction

Table 2 Neurocognitive Domains and the ERP Components Elicited via Appropriate Paradigms in EEG-Based Cognitive Studies on ADHD from 2000–2017

Neurocognitive Domain	Subprocesses Investigated	EEG/ERP Components	Paradigms Used to Elicit ERPs	ADHD
Attention Processing	Cue processing	P50, P1, N1, P2, N2, P3a, P3b, TF-PCA of P3b, LRP, CNV, VLF, delta, theta, alpha, beta, gamma	Visual oddball, Auditory oddball & go/no-go, Fast task,Cued CPT Eriksen flanker task, Two choice reaction
	Response preparation	CNV	Auditory oddball & go/no-go
	Novelty processing
	Sustained attention	VLF	Cued CPT
	Perceptual binding
Inhibition Control		P1, N1, P2, N2, P3b, LRP	Stop-signal Go/no-go
Performance Monitoring	Conflict monitoring	N2, ERN, Pe, CNV, LPP, ITC, theta, early positivity,	Flankers task, Go/no-go, Incentive delay task
	Error processing	ERN, Pe	Go/no-go	*
	Predictions
Face Processing	Structural encoding	N170, P1	Visual oddball with faces
Sensory Processing	Visual processing	P1, theta, alpha	cVEP, Light flash paradigm Tone processing during film. Brightness detection task	*
	Auditory processing	N1, theta, alpha	Tone processing during film	*
	Context modulation
Memory and Language	Working memory	Alpha; P3b	Delayed match-to-sample task Modified 1-back task
	Semantic processing
	Speech processing

Note: EEG and ERP components where ADHD-autism spectrum disorder (ASD) shows an overlap. Boxes shaded grey indicates studies where the ERPs reflective of cogitative status in ADHD were elicited using appropriate paradigms. Blank cells indicate areas on EEG aspects of ADHD not yet studied. Note: Adapted from Lau-Zhu A, Fritz A, McLoughlin G. Overlaps and distinctions between attention deficit/hyperactivity disorder and autism spectrum disorder in young adulthood: Systematic review and guiding framework for EEG-imaging research. Neurosci Biobehav Rev. 2019;96:93–115. Creative Commons license and disclaimer.⁷⁸ Available from: http://creativecommons.org/licenses/by/4.0/legalcode”http://creativecommons.org/licenses/by/4.0/legalcode

Figure 4 Attention among controls and individuals with self-reported ADHD captured via P3 following Go/NoGo Task Note: Adapted from Rodriguez PD, Baylis GC. Activation of brain attention systems in individuals with symptoms of ADHD. Behav Neurol. 2007;18(²):115–30. Creative Commons license and disclaimer available from: http://creativecommons.org/licenses/by/4.0/legalcode”http://creativecommons.org/licenses/by/4.0/legalcode.¹⁴¹

Figure 5 Diagrammatic illustration of the contributing factors to clinical phenotypic presentation of ADHD.

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