Cerebellum & stims Ivanov

Published on March 20, 2020
APSARD Blogger

A recent structural magnetic resonance imaging (MRI) study of pre-adolescent and adolescent youth reports findings relevant to clinicians who treat ADHD patients of any age.  It suggests that stimulant medications normalize cerebellar volumes.  See more at


A recent structural magnetic resonance imaging (MRI) study of pre-adolescent and adolescent youth reports findings relevant to clinicians who treat ADHD patients of any age (Ivanov, et al.. (2014). Neuropsychopharmacology 39, 718-26.).   We know from much prior work that ADHD is associated with small volumes in several regions of the brain.   In this new paper, Ivanov and colleagues replicate this finding for the cerebellum. Their work supports the idea that defects in the attentional and cognitive control mechanisms regulated by neural connections among striatum, cerebellum and the frontal lobes.  Several decades of prior MRI studies suggest that these frontal-striatal-cerebellar networks contribute to the risk for ADHD.  These networks have been implicated by multiple studies and confirmed by meta-analyses.  Scientists who study ADHD point to these data as evidence that changes in the brain  underlie the pathophysiology of ADHD.  Yet some in the media and blogosphere have suggested that these brain defects are caused by the medications that treat the disorder.   Ivanov et al.’s study addresses this issue.  They did not conduct a prospective clinical trial, but there was sufficient variability of stimulant therapy in their sample to examine the effects of stimulants on cerebellar volumes.    Here is what they found.  The ADHD patients who had been treated with stimulant medications for longer durations showed larger cerebellar hemispheres.  The implications are clear.  Rather than being toxic to the brain, stimulant medication possibly normalizes cerebellar volumes. I use the term “possibly” because these studies are naturalistic, cross-sectional studies, not prospective randomized clinical trials (RCTs).  Because long term RCTs are not feasible, none exist.   Ivanov’s data raise the intriguing possibility that stimulants lead to increases in brain structure to compensate for ADHD defects.  Is this finding a fluke?   Probably not, because other studies report similar results.  In fact, Frodl and colleagues reviewed eleven structural MRI studies and used meta-analysis to show that ADHD associated brain volume reductions in the right globus pallidus and putamen were greatest for those patients that had not received pharmacotherapy (Frodl, T. & Skokauskas, N. (2012). Acta Psychiatr Scand 125, 114-26.).  Possibly beneficial effects of ADHD medications have also been seen in reviews of functional MRI studies.  These studies suggest that, in addition to normalizing brain structures, pharmacotherapy for ADHD may normalize neural functioning (Paloyelis, Y. et al. (2007). Expert Rev Neurother 7, 1337-56.).  Importantly, administering clinically effective doses of stimulants boosts brain activations in ADHD patients in regions that are typically under-activated in ADHD (i.e., caudate, prefrontal cortex, cingulate and cerebellum).  So, we can see from prior studies, that Ivanov’s finding is not isolated.  Importantly, these results do not mean that stimulants create “super brains” or that they should be used for performance enhancement.  But they offer some relief from the concern that ADHD  medications are toxic to the brain.  And instead suggest that these medications possibly normalize brain structure and functioning as measured by MRI.

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