ADHD

Neurocognitive Profile of ADHD

Lecture Outline

  • What is ADHD and its aetiology?

  • What are the cognitive and brain correlates of ADHD?

  • How can neurocognitive findings inform diagnostic and treatment practices?

  • Neurodiversity: a new lens for understanding ADHD

What is ADHD?

  • ADHD is a common neurodevelopmental condition.

    • Prevalence in children: 5-10%.

    • Prevalence in adults: 3-5% worldwide.

  • Characterized by developmentally inappropriate and impairing levels of:

    • Inattention

    • Hyperactivity-Impulsivity

  • Methods of Assessment:

    • Parent-report

    • Teacher-report

    • Self-report

    • References: Polanczyk et al., 2014; Willcutt et al., 2012; Faraone et al., 2005.

Signs of ADHD

Inattentiveness

  • Style of behavior involving disorganisation and lack of persistence:

    • Distractible

    • Forgetful

    • Difficulty following directions

    • Disorganised

Hyperactivity

  • Excess movement:

    • Fidgety behavior

    • Always on the go

    • Talking excessively

Impulsivity

  • Acting without reflection:

    • Interrupting others

    • Blurting out answers

    • References: Polanczyk et al., 2014; Willcutt et al., 2012; Faraone et al., 2005.

Associated Features of ADHD

  • Developmental Traits:

    • Language and speech delays

    • Motor challenges

  • Emotional Symptoms:

    • Low frustration tolerance

    • Irritability

    • Emotional lability

  • Co-occurring Disorders:

    • Autism spectrum disorders (ASD)

    • Mood disorders

    • Anxiety disorders

    • Obsessive-compulsive disorder (OCD)

    • Oppositional defiant disorder (ODD)

    • Conduct disorder (CD)

    • Tourette syndrome

  • Cognitive Challenges:

    • Linked to ADHD's strong association with cognitive difficulties.

    • Reference: DSM-5, 2013; Franke et al., 2018.

ADHD Across Development

  • ADHD often persists into adolescence and adulthood.

    • Persisting cases: 2-4% prevalence in adults.

    • Characterization of individuals by:

    • Persisters: Individuals who continue to exhibit ADHD symptoms.

    • Remitters: Individuals who no longer demonstrate symptoms.

    • References: Faraone et al., 2006; Cheung et al., 2015; Sibley et al., 2016.

ADHD Fluctuation Patterns

  • ADHD can exhibit varied patterns over time.

Case Example: Fluctuating Pattern of Remission

  • Symptom remission threshold: Exceeded within the population showing ADHD.

  • Key Factors:

    • Absence of impairment can lead to symptom recovery.

    • Treatment impacts symptom trajectories.

    • Reference: Sibley et al., 2022. American Journal of Psychiatry

ADHD Persistence and Clinical Outcomes

  • When ADHD persists, it's associated with detrimental outcomes: Academic failures, social challenges, etc.

  • Differences between ADHD in childhood vs. adulthood:

    • Childhood hyperactivity may translate to adulthood as restlessness

    • Example: Physical impulsivity in children may shift to verbal impulsivity in adults.

    • Inattention:

    • Childhood - Problems payable in classrooms

    • Adulthood - Difficulties concentrating at work.

    • References: Asherson et al., 2005 & 2016.

Aetiology of ADHD

  • Multifactorial Disorder: Complex interplay of genetic and environmental risk factors.

  • Genetic Factors:

    • Involvement of genes in dopaminergic, noradrenergic, and serotonergic systems.

    • Numerous common genetic variants that exert a small effect.

  • Environmental Factors:

    • Consider preterm birth, low birth weight, maternal smoking, alcohol consumption during pregnancy, and psychosocial adversities.

    • References: Plomin et al., 2009; Demontis et al., 2022.

Phenotype and Endophenotype

  • The distinction between phenotype and endophenotype illustrated by neurobiological and neuropsychological deviations.

    • Levels of Expression: Vary per individual and associated risk factors.

    • Reference: Rommelse et al., 2008.

Summary of Core Concepts

  • ADHD is a prevalent neurodevelopmental disorder that can persist into adulthood.

  • It has a complex aetiology influenced by genetic and environmental factors, typically involving multiple genes with small effects.

  • Heritable cognitive and brain abnormalities can be associated with ADHD, classified as endophenotypes.

Evaluation of Cognition and Brain Correlates of ADHD

Cognitive Assessments

  • Computerised Tasks:

    • Continuous Performance Test (CPT)

    • Eriksen Flanker Task

    • Oddball Task

    • Go/No-Go Task

  • Neuropsychological Assessments:

    • Intelligence Quotient (IQ) measures

    • Digit Span Backwards (DSB)

    • Digit Span Forwards (DSF)

    • Stroop Test

    • Wisconsin Card Sorting Task (WCST)

Neuroimaging Techniques in ADHD

  • Structural and Functional Imaging:

    • sMRI & fMRI for assessing brain structures and functions.

    • EEG: Used to analyze electrical activity in the brain.

    • Event-Related Potentials (ERPs): Measured for evaluating brain responses to stimuli.

Executive Functions (EF) in ADHD

Components of Executive Functions

  • EF processes include:

    • Self-monitoring

    • Inhibition

    • Initiation

    • Working memory

    • Emotional control

    • Task monitoring

    • Shifting attention

    • Sustained attention

    • Flexibility

    • Planning

    • Organizing

    • Reference: Willcutt et al., 2005.

Neuroanatomy of Executive Functions

  • Involves:

    • Inhibition of inappropriate responses

    • Decision making and motivation

    • Related regions: Frontal lobes, including prefrontal cortex.

EF Challenges in Children with ADHD

  • Common Issues with EF include:

    • Planning difficulties

    • Working Memory deficits

    • Inhibition problems

  • Research indicates varied responses among children with ADHD regarding their EF profiles.

    • Reference: Willcutt et al., 2005.

Meta-analysis of EF Challenges in ADHD

  • Consistent group differences noted:

    • Response inhibition (commission errors)

    • Vigilance (omission errors)

    • Working memory (DSB particularly highlighted)

    • Planning abilities measured via tools like Tower of Hanoi

  • Impacted not explained by differences in intelligence or academic achievement.

    • Reference: Willcutt et al., 2005.

Low-level Cognitive Processes in ADHD

  • Challenges identifying with:

    • Temporal information processing

    • Intra-individual variability (reaction time variability)

    • Reward processing tendencies

  • References: Franke et al., 2018; Kuntsi & Klein, 2012.

Theoretical Models of ADHD

  • Multiple models have proposed to explain the neurocognitive mechanisms behind ADHD:

    • Executive Dysfunction Models:

      • Barkley (1997): Response inhibition central to understanding ADHD.

      • Diamond (2005): Interplay between working memory and response inhibition provides insight into inattention and hyperactivity.

      • Castellanos (2006): Differentiates between “cold” and “hot” executive function concerning attention and activity levels.

    • Delay Aversion Model:

      • Sonuga-Barke (2005): Explains impulsiveness in ADHD as a motivational drive to avoid the feelings from delay.

    • Multiple Deficit Models:

      • Acknowledges that ADHD behaviors arise from distinct cognitive deficits, acknowledging clinical and cognitive diversity.

Cognitive Training in ADHD Treatment

  • Cognitive training is being examined as a potential intervention for ADHD, focusing on improvements in:

    • Attention control

    • Impulse control

    • Working memory

    • Executive function skills.

  • Activities typically include attention training, working memory games, and focused executive function tasks.

Neuroanatomical Findings in ADHD

  • Findings indicate differences in brain structures and functions between children/adolescents and adults with ADHD versus controls:

    • Lower grey matter density and abnormalities in white matter.

    • Reduced total brain volume as well as size of certain structures like the amygdala, caudate, hippocampus, and putamen.

    • Evidence of delayed cortical maturation particularly significant in children/adolescents.

    • References: Poral et al., 2011; Nakao et al., 2011; Shaw et al., 2007, 2015; Hoogman et al., 2017.

Delayed Cortical Maturation in ADHD

  • Data demonstrates a consistent delay in cortical maturation, illustrated through a study depicting the proportion of cortical points reaching peak thickness across different ages for ADHD versus typically developing controls.

    • Reference: Shaw et al., 2007.

Functional Brain Activity in ADHD

  • Studies indicate reductions in brain activity for individuals with ADHD in various regions compared to controls:

    • Frontal areas engaged during inhibitory and motor function tasks.

    • Temporal and parietal regions linked to attentional tasks.

    • Reference variability across studies regarding findings on functional activity and participant characteristics.

Neurology and Cognitive Function

  • Neurophysiological findings indicated through EEG demonstrate:

    • Reduced amplitude in critical brain responses indicating attention allocation and execution, including smaller Cue-P3 waves and CNV amplitudes for response preparation.

    • References: Kaiser et al., Neuroscience and Biobehavioral Reviews, 2020.

Behavior-Cognition-Brain Relationships

  • The interaction of behavior, cognitive processing, and brain activity makes up the symptomatology of ADHD with a focus on decision-making, attention, reward processing, and relevant neural circuits involved in executive functions.

    • References: Durston et al., 2011; Marek et al., 2022.

Evaluation of Neurobiology Studies

  • ADHD displays heterogeneous symptoms and variability in neural responses, complicating consistent identification of neurological biomarkers.

  • Findings from studies are often inconsistent regarding brain abnormalities due to differences in methodologies used, sample sizes, or cognitive tasks administered.

Summary of Neuropsychological Profiles

  • ADHD encompasses a variety of cognitive challenges spanning both low-level and high-level functions, with significant structural-functional-neurophysiological brain correlates.

  • Establishing reliable brain-behavior associations remains a complex challenge.

Biomarker Categories in ADHD

  • Susceptibility/Risk Biomarkers: Indicate potential for developing ADHD

  • Diagnostic Biomarkers: Identify presence of ADHD or subtypes

  • Predictive Biomarkers: Identify candidates likely to benefit from specific treatments

  • Monitoring/Response Biomarkers: Detect treatment effects or biological response changes.

    • References: Michelini et al., 2022.

Markers of ADHD Remission

  • Exploration of whether neurocognitive profiles persist or remit when ADHD symptoms improve with age shows inconsistent findings.

  • Most studies indicate challenges in executive function do not distinguish between ADHD remitting vs persisting cases.

    • References: Cheung et al., 2016; Michelini et al., 2016; James et al., 2017; Vainieri et al., 2020.

Distinguishing ADHD from Other Conditions

  • Examples of differentiating ADHD from conditions such as Bipolar Disorder and Autism Spectrum Disorder (ASD) through cognitive tasks such as the Eriksen Flanker Task indicate differences in cognitive demand levels.

    • Reference: Vainieri et al., 2020.

Treatment for ADHD

  • A study randomized children with ADHD to receive treatment with Methylphenidate (MPH) only, Guanfacine (a non-stimulant) only, and a combination of both.

  • EEG activity in midfrontal regions predicted greater improvements in symptoms, suggesting distinct treatment needs based on individual brain profiles. - References: Michelini et al., 2023a; JAACAP.

Acute Medication Effects on Brain

  • After a single dose of a psychostimulant:

    • Increased activity in the right inferior prefrontal cortex, ventral anterior cingulate cortex, and putamen suggests acute effects on neuronal circuits responsible for attention and impulse control.

    • Reference: Rubia et al., 2013.

Monitoring Treatment Effects

  • Combined medication (Methylphenidate + Guanfacine) showed improvement in midoccipital brain activity related to visuo-attentional difficulties, while individual treatments had limited impacts.

    • Reference: Michelini et al., 2023b.

Targeted Interventions for ADHD

  • Trials on the safety and efficacy of Transcranial Magnetic Stimulation (TMS) in ADHD had inconclusive findings regarding efficacy but were deemed safe in young participants.

    • References: Weaver et al., 2012.

Conclusion on Neuropsychological Profiles of ADHD

  • Investigation into ADHD's neuropsychological profile offers insights into underlying processes associated with the disorder.

  • A need for further research into the clinical utility and cost-benefit of cognitive and brain-based technologies is evident.

Neurodiversity Perspective on ADHD

Definitions and Importance

  • Neurodiversity: Describes the diversity of human brain function, encapsulating different ways of interacting with the world, including conditions like ADHD and Autism.

    • References: Chapman 2021; Fletcher-Watson 2022; Sonuga-Barke et al., 2022.

New Paradigms in Understanding ADHD

  • Core Principles:

    • Transition from “core deficits” to recognizing both strengths and challenges.

    • Emphasizes a person-centered approach reflecting the diversity found within individuals with ADHD.

    • Recognizes the high likelihood of co-occurrence with other neurodevelopmental disorders (NDDs).

  • References: Chapman 2021; Fletcher-Watson 2022; Sonuga-Barke et al., 2022.

Evidence Supporting Neurodiversity

  • Cognitive profiles indicate behavioral markers of executive functions shared across neurodevelopmental difficulties, suggesting a commonality between ADHD, ASD, and others.

    • References: Astle et al., 2022; Romer et al., 2021.

Brain Structure and Function Evidence

  • Observed overlaps in executive functions between diagnoses of ADHD and ASD demonstrate structural differences in frontal, temporal, parietal, and striato-thalamic regions involved in cognitive control.

    • References: Carlisi et al., 2017; Rubia, 2018.

Positive Aspects of ADHD

  • Emerging research focuses on the positive characteristics seen in successful adults with ADHD, emphasizing strengths alongside challenges.

    • References: Sedgwick et al.; Schippers et al.; Mind the gap blog.

Final Summary

  • ADHD is increasingly being viewed through a lens of neurodiversity, correlating with the clustering of neurodevelopmental disorders.

  • Emphasis on cognitive profiles supports this perspective.

  • The exploration of positive aspects of ADHD could reform clinical assessment practices.