Carl Anderson, Ph'D'

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Functional MRI Measures of the Cerebellar Vermis
in Childhood ADHD

• Carl Anderson, Ph.D.
• Instructor in Psychiatry
• Harvard Medical School
• and McLean Hospital

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Vermis a midline region of the cerebellum.
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Anterior Vermis

• Involved in posture, attention,
• emotion.
• Coordination of head and eye movement.

Posterior Vermis
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Clinical Signs in ADHD

• Clumsiness
• Impulsiveness
• Slow reaction times
• Inattentive
• Hyperactive

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The Vermis and ADHD?

• Cerebellar lesions (including the vermis) in
  young rats are associated a period of behavioral
  hyperactivity during adolescence which declines
  in adulthood (Altman, 1987).
• MRI-based morphometric analysis of the cerebellum
  indicate that the "inferior posterior lobe" of
  the vermis is smaller in 47 ADHD boys (Berquin et
  al., 1998)

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Objective Measures of Hyperactivity
(Teicher et al., 1996)
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(from Teicher et al., 1996)
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Objective Measures of Hyperactivity
Measures of movement Micro events (number of
movements). Temporal scaling (distribution of
micro events). Standard deviation (SD) of
reaction times during the CPT.
(Teicher et al., 1996)
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Functional MRI of methylphenidate effects
Triple blind (parent, child, rater), randomized,
placebo-controlled study of effects of
methylphenidate (0, 0.5, 0.8, 1.5 mg/kg ) on
activity, attention and fMRI.
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Subjects Eight boys with ADHD (9.3 1.6 yr.)
served as subjects in this study, which was
approved by the McLean Hospital Institutional
Review Board. Met criteria for ADHD on
DSM-IV(at least 6 of 9 symptoms of inattention or
hyperactivity-impulsively). Children were treated
continuously for one week with placebo or
specific dose of methylphenidate and then tested
for drug efficacy using objective measures of
attention and activity (Teicher et al., 1996),
and fMRI within 1 - 3 hours of their afternoon
dose. Time between dose and testing was held
constant for each subject throughout the four
treatment conditions.
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BOLD (Blood Oxygen Level Dependence) fMRI
Stimulation (S) Background (BG) Activation
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T2 relaxometry Exponential fit to ROI pixels
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T2 relaxometry vs. BOLD fMRI
Background changes in blood flow with chronic
drug treatment are not subtracted.
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T2 Relaxometry
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ROIs (regions of interest)
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Dose-Dependent Changes in T2
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Behavior vs. Vermial T2
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Behavior vs. Vermial T2
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Behavior vs. Vermial T2
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OtherROIs (regions of interest)
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Dose-Dependent Changes in T2
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RESULTS A significant dose-dependent resting
blood flow decrease was observed only in the
vermis F 3,21 5.123, plt .01. Trend
analysis supported a dose-dependent linear
decline of blood flow (reflected in elevated T2
values) in the vermis F 1,27 13.676, plt
.001.
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RESULTS Objective measures of attention and
activity collected within 1 - 3 hours of
methylphenidate adminstration exhibited
significant dose-dependent effects that paralled
vermal blood flow alterations.
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RESULTS -Movements or "micro events" during
the CPT were dose-dependently inhibited. -The
complexity of temporal patterns of movement
were dose-dependently increased during the CPT,
indicative of lower activity.
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RESULTS -The SD of CPT performance was
significantly lowered in a dose-dependent
fashion, indicating an association between
attention and vermal blood flow.
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The Vermis and Behavior(un-medicated)
Vermal blood flow
Basal Ganglia/Putamen (blood flow /Dopamine
turnover)
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The Vermis and Behavior (medicated)
Basal Ganglia / Putamen ( blood flow -
Dopamine turnover)
Vermal blood flow
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The Vermis and Behavior
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Cortical projections to the cerebellum
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CONCLUSIONS AND SPECULATIONS Lower blood
flow in the cerebellar vermis is associated with
reductions in inattention, hyperactivity and
impulsivity in objectively hyperactive
children. Psychopharmacological theories of
stimulant action in ADHD may need to be
reevaluated in light of the emerging role of the
cerebellum in the developmental pathophysiology
of this disorder.
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CONCLUSIONS AND SPECULATIONS Abnormal vermal
blood flow or metabolism is associated with
psychiatric symptoms in ADHD, Early Child Abuse,
Bipolar Disorder, PTSD, and schizophrenia.
The vermis may function in motor and emotional
coordination through bihemispheric influences on
dopamine release in the basal ganglia, amygdala
and accumbens (Snider and Maiti 1976 Supple and
Kapp 1994) via fastigial nucleus projections
(Heath and Harper 1974) to pontine and
mesencephalic and hypothalamic nuclear groups .
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Developmental Biopsychiatry Program at McLean
HospitalSteve B. Lowen Ann Polcari Cindy E.
McGreeneryLuis C. Maas Perry F. RenshawMartin
H. Teicher