Impairment in ADHD: Implications for - Alberta Health Servicesfcrc.albertahealthservices.ca/professional/education/docs/2015-04... · Circuit Impairment in ADHD: Implications for
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
Dorsolateral and Orbital FrontalSubcortical Circuit Impairment in ADHD: Implications forCircuit Impairment in ADHD: Implications for
Differential Diagnosis and TreatmentJames B. Hale, PhD, ABPdNPediatric Neuropsychologist
Professor of Paediatrics, Psychiatry, and EducationProfessor of Paediatrics, Psychiatry, and EducationUniversity of Calgary
“Everyone knows what attention is. It is What is Attention?
ythe taking possession by the mind, in clear and vivid form, of one out of what seem several simultaneously possible objects or trains of thought. Focalization, concentration of consciousness are of itsconcentration, of consciousness are of its essence. It implies withdrawal from some things in order to deal effectively withthings in order to deal effectively with others, and is a condition which has a real opposite in the confused, dazed, William James
Principles ofscatterbrained state.”
Principles of Psychology (1890)
Is this primary attention or executive function?H d t ti l t iHow do we separate cortical tone, primary attention, and executive attention?
Executive FunctionProgramming, Regulating, and Verifying Mental Activityog a g, egu at g, a d Ve fy g e ta ct v ty
Cingulate circuit control of arousal, decision‐making, and performance monitoring
Dorsolateral Circuit in Learning, Language, and Motor Disorders
DorsolateralPrefrontalCortex
CaudateNucleus
GlobusPallidus Thalamus
SubstantiaNigra COOL
EXECUTIVE
Dorsolateral circuit control of planning, organizing, monitoring, evaluating, hifti d dif i b h i i l di COGNITIVE i hibitishifting, and modifying behaviour, including COGNITIVE response inhibition
Dorsolateral circuit control of working memory, memory encoding, and retrieval
Orbital Circuit in Learning, Language, and Motor Disorders
“Cool” ADHD vs. Schizophrenia vs. “Hot” Conduct Disorder vs. Anxiety Disordery
• Attention deficit not diagnostic, since all neuropsychiatric disorders have poor attentionADHD i h d l l h i i l d l• ADHD right dorsolateral hypoactivity leads to external distraction
• Schizophrenia left dorsolateral hypoactivity leads toSchizophrenia left dorsolateral hypoactivity leads to internal distraction
• Conduct disorder orbital hypoactivity leads to poor i l l d i diff hemotional control and indifference to others
• Anxiety disorder orbital hyperactivity leads to emotional overcontrol and excessive concern for othersemotional overcontrol and excessive concern for others
• Externalizing disorders overuse initiation structures and underuse inhibitory ones
Optimal Executive Function Requires Frontal-Subcortical Circuit Balance!
Orbital Prefrontal Circuit and Theory of MindHale & Fitzer, 2015; Applied Neuropsychology: Child
• Theory of Mind – The ability to take the perspective of others or feel empathy
• Does empathy only require perception or does it• Does empathy only require perception, or does it also require action?
• Posterior systems linked to affect perceptionParietal lobe and “mirror” neuronsTemporal lobe and face recognition
• Why is theory of mind linked to the frontal systems?Pars opercularis and imitationM di l bit l t d th f i dMedial orbital cortex and theory of mind
• Balancing orbital function critical, too little or too much is a problem! p
• Balancing perception and action in social relationships
Questions, Questions, QuestionsADHD Pathways, Neurochemistry, and Stimulant Response
• Dorsolateral‐dorsal cingulate (cognitive impulsivity) and orbital‐ventral cingulateimpulsivity) and orbital ventral cingulate (emotional impulsivity) differences?
• Mesocortical (tegmentum‐dorsolateral), ( g ),mesolimbic (orbital‐amygdala‐hippocampus‐nucleus accumbens), andnigrostriatal (substantia nigra‐basal ganglia) dopamine (DA) pathways? What role does Glutamate have? How about GABA?Glutamate have? How about GABA?
• Inverted‐U shape stimulant response in dorsal and ventral systems how do wedorsal and ventral systems, how do we achieve balance?
American Academy of Pediatrics Standard of Care ADHD Medical PracticeStandard of Care ADHD Medical Practice1) Primary care physician should evaluate any child with academic or behaviouralany child with academic or behavioural problems and inattention, hyperactivity, orimpulsivity symptoms
2) ADHD diagnosis: DSMIV criteria, 2 settings, and multisource information for rule outs
3) Coexisting conditions assessment4) Treatment includes medications and/or
evidence‐based behavior therapy, both best5) Titrate maximum medication dose with minimum adverse effects
• ADHD is a neurodevelopmental disorder defined by behavioural criteria, leading to neuropsychological , g p y gheterogeneity and attenuated treatment efficacy
• Are academic deficits the common pathway? Poorer d d t ti i l d ti lik l igrades, grade retention, special education likely in
ADHD (especially if executive deficits)
WHAT CAUSES ADHD ACADEMIC DEFICITS?
OR
P A il bili E i D fi iPoor AvailabilityFor Learning?
Methylphenidate (MPH) Treatment and ADHD• MPH effective in 60 to 90% of children with ADHD, but just what does “response” meanresponse mean
• Dopamine agonists (block DA reuptake to reduce frontal‐striatal hypoactivity)to reduce frontal striatal hypoactivity)
• Improves classroom behaviour and peer interactions, but not long‐term academic achievement
• Few serious side effects, but “zombie effect” noted in some childreneffect noted in some children
Best dose for cognition appears to be lowerthan best dose for behavior in good responders(see Arnsten & Pliszka, 2011; Berridge et al., 2006; Hale et al., 2011; Kubas et al., 2012)
Alberta Children’s Hospital DoubleBlind Placebo Biphentin Protocolp
• Children diagnosed by physician, confirmed by psychologist, consent, and random assignment
• Standard of Care control group = baseline, best dose, 6 months; open trial
• Experimental group = baseline randomized• Experimental group = baseline, randomized placebo, low dose, high dose, best dose, 6 months, blinded trial
• Neuropsychological tests and parent/teacher• Neuropsychological tests and parent/teacher behaviour ratings, academic baseline and 6 months; neuroimaging baseline‐best dose only
• Data rank ordered across conditions with nonparametric randomization tests to determine cognitive and behavioural response separately
• Graphic and statistical response reported to physician/parent for clinical decision‐making
Drug Trial Example: Lisa• 11 year, 7 month‐old friendly and outgoing girl with love for adventure and being outdoorsA d i d i l• Academic and social concerns: Inattentive, easily distracted, fidgetyFrequently off‐taskq yPoor writing skillsNoncompliant behaviourLi i d i l killLimited social skills
• Comprehensive neuropsychological evaluation revealed neuropsychological, academic and p y gbehavioural data consistent with ADHD
• Following consultation with parents, pediatrician referred Lisa to double‐blindpediatrician referred Lisa to double blind placebo controlled methylphenidate trial
Discussion• Are academic achievement deficits due to poor • Are academic achievement deficits due to poor availability for learning or executive deficits?
• Doubleblind placebo medication trials detect pneuropsychological and behavioral response
• Children with executive impairment and ADHDC bi d T h b t di ti Combined Type show robust medication response
• Children with low impairment and ADHDInattentive Type less likely to respondInattentive Type less likely to respond
• Differential dorsal and ventral circuit effects could explain why best dose for cognition lower than best p y gdose for behaviour
• Neuropsychological and behavioral medication tit ti d dj t t t t h ld ti i titration and adjunct treatments should optimize both academic and behaviour outcomes