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www.mghcme.org Neuroimaging and ADHD Stephen V. Faraone, Ph.D. Departments of Psychiatry & of Neuroscience and Physiology SUNY Upstate Medical University @StephenFaraone
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Neuroimaging and ADHD
Stephen V. Faraone, Ph.D.
Departments of Psychiatry & of Neuroscience and PhysiologySUNY Upstate Medical University@StephenFaraone
www.mghcme.org
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Structural and Functional
Brain Anomalies in ADHD
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Meta-analysis of fMRI Inhibition Tasks(Hart et al., JAMA Psychiatry, 2013)
Regions of decreased (red and orange) and increased (blue) activation in ADHD patients compared withcontrols.
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Meta-analysis of fMRI AttentionTasks(Hart et al., JAMA Psychiatry, 2013)
Regions of decreased (red and orange) and increased (blue) activation in ADHD patients compared withcontrols.
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Co
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ize
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children adolescents adults
Note: In children all case-control findings are significant, in adolescents onlythe hippocampus result is. No differences are signficant in adults.
Meta-Analysis of subcortical and cortical brain regions across the lifespan (ENIGMA-ADHD, n>4000)
(Hoogman et al., Lancet Psych, 2018; Hoogman et al., submitted)
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Questions Raised by the ENIGMA-ADHD
Study
• Do the data support any evidence for structural brain
abnormalities in ADHD adults?
• In some cases, can the brain recover from ADHD?
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Machine Learning: Application to
ENIGMA-ADHD Data(Zhang-James et al., submitted)
• Training Phase: Derive complex predictive model using
70% of the data using Random Forests
• Validation Phase: Assess accuracy of model with 15% of
the data
• Iterate between test and validation phase to find the best
model
• Test Phase: Use the last 15% of the data to assess the
accuracy of the model in an independent data set
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ROC Curves(Zhang-James et al., submitted)
Feature Importance(Zhang-James et al., submitted)
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Recovery of Brain
Imaging Anomalies in
Adulthood
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The Age Dependent Decline of ADHD(Faraone et al., Nature Reviews Disease Primers, 2015)
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Developmental Trajectories: the ADHD
Caudate Normalizes with Age(Castellanos et al., JAMA, 2002)
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Developmental Trajectories of Cortical Thickness(Shaw et al., Am J Psychiatry, 2011)
Maturation of the brain indicated by age at which cortex attains peak thickness. Lighter areas are thinner, darker areas thicker.Hypothesis: ADHD is characterized by delay rather than deviance in cortical maturation
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Rate of Prefrontal Cortical Thinning(Shaw et al., Am J Psychiatry, 2011)
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ADHD Symptoms and Total Brain Volume in
Healthy Adults(Hoogman et al., PLOS One, 2012)
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Effects of Stimulants
on Brain Structure and Function
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Meta-analysis: Effects of Stimulants on MRI
PFC Activation from Timing Task(Hart et al., Neuroscience & Biobehav. Rev. , 2012)
Percent of patients on long-term stimulant treatment predicts more normal right dorsolateral PFC activation (p<0.0005)
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Meta-analysis of fMRI AttentionTasks(Hart et al., JAMA Psychiatry, 2013)
Meta-regression analysis for attention shows that thepercentage of patients receiving long-term psychostimulant treatment is associated with more normal right caudate activation relative to healthycontrols.
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Meta-Analysis of sMRI Studies, (Nakao et al., Am J. Psychiat, 2011)
Percentage of patients on stimulant medication was correlated with gray matter volume in the right caudate, controlling for age
Longitudinal Study of Stimulant Treatment and
Cortical Thickness(Shaw et al., AJP, 2009)
Left Middle/Inferior Frontal Gyrus Right Medial PFC
No evidence that psychostimulants were associated with ‘slowing’ of overall growth of the cortical mantle
Blue: On Meds; Red: Off Meds; Green: Controls
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Summary: Functional
Effects of Brain Networks
in ADHD
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• Under-activation of fronto-striatal and fronto-parietal networks consistent with impaired goal-directed executive processes
• Under-activation of frontal control over the limbic system consistent with the emotional dysregulation seen in ADHD
Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20
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• Lower activation of the ventral striatum in ADHD in anticipation of reward leads to poor executive control over reward regulation.
• Under-activation of ventral attention networks leads to poor executive control of attention to behaviourally relevant external stimuli.
Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20
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Coordination of Brain Networks(Kenzie et al. Front. Neurol., 2018)
ADHD patients show small or absent anti-correlations between the default mode network (DMN) and the cognitive control network, lower connectivity within the DMN itself, and lower connectivity within the cognitive and motivational loops of the fronto-striatal circuits.
Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20
Executive Control of attention, cognition, emotion & behavior
DaydreamingInternal distractibility
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The medicines that treat ADHD work in the pathways implicated by neuroimaging studies
Faraone, S. V. et al. (2015) Attention-deficit/hyperactivity disorder Nat. Rev. Dis. Primers doi:10.1038/nrdp.2015.20
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Thanks for Listening!
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