Cerebellar Development and Clinical Outcome in Attention Deficit Hyperactivity Disorder

Mackie, Susan; Shaw, Philip; Lenroot, Rhoshel; Pierson, Ron K.; Greenstein, Deanna; Nugent, Tom; Sharp, Wendy; Giedd, Jay N.; Rapoport, Judith L.

doi:10.1176/ajp.2007.164.4.647

Cited by 227 publications

(146 citation statements)

References 61 publications

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“…Similarly, slower go signal reaction times in the go/no-go task have been linked to the extent of cerebellar lesions (41). Such human lesion studies implicate the cerebellum in response inhibition, and align with previous reports of subtle cerebellar anatomic anomalies in adults with persistent ADHD(42). Using MEG, we additionally find that ADHD symptoms were associated with cerebellar activity in a time window 500–600 ms after the stop signal.…”

Section: Discussionsupporting

confidence: 86%

Defining the Neural Substrate of the Adult Outcome of Childhood ADHD: A Multimodal Neuroimaging Study of Response Inhibition

Székely

Sudre

Sharp

et al. 2017

AJP

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Background Understanding the neural processes tied to the adult outcome of childhood attention-deficit/hyperactivity disorder (ADHD) could guide novel interventions to improve its clinical course. It has been argued that normalization of prefrontal cortical activity drives remission from ADHD, while anomalies in subcortical processes are ‘fixed’, present even in remission. Using multimodal neuroimaging of inhibitory processes, we test these hypotheses in adults followed since childhood, contrasting remitted against persistent ADHD. Methods Adult participants (35 persistent ADHD; 47 remitted ADHD; 99 never affected) were scanned with fMRI (n=85), magnetoencephalography (n=33) or both (n=63) during a response inhibition task. Results In fMRI analyses, during inhibition, right caudate anomalies both reflected a childhood ADHD history and were present even among those who remitted. By contrast, differences related to adult outcome emerged in cortical (right inferior frontal and inferior parietal/precuneus) and cerebellar regions. Here, the persistent ADHD group showed under-activation, whereas the remitted ADHD group did not differ significantly from the never-affected group. MEG showed that the association between adult symptom severity and prefrontal neuronal activity was confined to the time window covering the act of inhibition (300–350 ms). Group differences in cerebellar and parietal neuronal activity occurred during the time window of performance monitoring processes (500–600 ms). Conclusions By combining fMRI and MEG we pinpoint the location and time window of neuronal activity that underpins the adult outcome of ADHD. We thus separate the cortico-cerebellar processes tied to clinical course of ADHD from the subcortical processes that are not.

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Section: Discussionsupporting

confidence: 86%

Defining the Neural Substrate of the Adult Outcome of Childhood ADHD: A Multimodal Neuroimaging Study of Response Inhibition

Székely

Sudre

Sharp

et al. 2017

AJP

Self Cite

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“…Alterations of this phenomenon have been observed in various psychiatric conditions (Mackie et al , 2007) (Jarvis et al , 2008) (Castellanos et al , 2002) (Pujol et al , 2004) (Hill et al , 2003) and in adolescents with familiar history of severe alcohol abuse (Hill et al , 2007). …”

Section: Discussionmentioning

confidence: 99%

Long-Term Effects of Cannabis on Brain Structure

Battistella

Fornari

Annoni

et al. 2014

Neuropsychopharmacol

289

200

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The dose-dependent toxicity of the main psychoactive component of cannabis in brain regions rich in cannabinoid CB1 receptors is well known in animal studies. However, research in humans does not show common findings across studies regarding the brain regions that are affected after long-term exposure to cannabis. In the present study, we investigate (using Voxel-based Morphometry) gray matter changes in a group of regular cannabis smokers in comparison with a group of occasional smokers matched by the years of cannabis use. We provide evidence that regular cannabis use is associated with gray matter volume reduction in the medial temporal cortex, temporal pole, parahippocampal gyrus, insula, and orbitofrontal cortex; these regions are rich in cannabinoid CB1 receptors and functionally associated with motivational, emotional, and affective processing. Furthermore, these changes correlate with the frequency of cannabis use in the 3 months before inclusion in the study. The age of onset of drug use also influences the magnitude of these changes. Significant gray matter volume reduction could result either from heavy consumption unrelated to the age of onset or instead from recreational cannabis use initiated at an adolescent age. In contrast, the larger gray matter volume detected in the cerebellum of regular smokers without any correlation with the monthly consumption of cannabis may be related to developmental (ontogenic) processes that occur in adolescence.

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“…Several studies, however, have reported significant group differences in conventional volumes of the hippocampus (36), the putamen (45, 46), the globus pallidus (47), the frontal cortex (47, 48), and the cerebellum (47, 49) in youths with ADHD relative to comparison subjects. Thus, examination of both conventional thalamic volumes and morphological features of the thalamic surface is appropriate in the study of ADHD.…”

Section: Discussionmentioning

confidence: 99%

Morphological Abnormalities of the Thalamus in Youths With Attention Deficit Hyperactivity Disorder

Ivanov

Bansal

Hao

et al. 2010

AJP

148

107

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Objective The role of the thalamus in the genesis of attention deficit hyperactivity disorder (ADHD) remains poorly understood. The authors used anatomical MRI to examine the morphology of the thalamus in youths with ADHD and healthy comparison youths. Method The authors examined 46 youths with ADHD and 59 comparison youths 8–18 years of age in a cross-sectional case-control study. Conventional volumes and measures of surface morphology of the thalamus served as the main outcome measures. Results A mixed-effects model comparing whole thalamic volumes revealed no significant differences between groups. Maps of the thalamic surface revealed significantly smaller regional volumes bilaterally in the pulvinar in youths with ADHD relative to comparison subjects. Post hoc analyses showed that ADHD patients who received stimulants (N=31) had larger conventional thalamic volumes than untreated youths with ADHD, and maps of the thalamic surface showed enlargement over the pulvinar in those receiving stimulants. Smaller regional volumes in the right lateral and left posterior thalamic surfaces were associated with more severe hyperactivity symptoms, whereas larger regional volumes in the right medial thalamic surfaces were associated with more severe symptoms of inattention. Conclusion These findings demonstrate reduced pulvinar volumes in youths with ADHD and indicate that this same area is relatively enlarged in patients treated with stimulants compared to those untreated. Associations of hyperactivity scores with smaller regional volumes on the lateral thalamic surface and inattention scores with larger regional volumes on the medial thalamic surface suggest the differential involvement of thalamic subcircuits in the pathogenesis of differing ADHD symptoms.

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Cerebellar Development and Clinical Outcome in Attention Deficit Hyperactivity Disorder

Cited by 227 publications

References 61 publications

Defining the Neural Substrate of the Adult Outcome of Childhood ADHD: A Multimodal Neuroimaging Study of Response Inhibition

Defining the Neural Substrate of the Adult Outcome of Childhood ADHD: A Multimodal Neuroimaging Study of Response Inhibition

Long-Term Effects of Cannabis on Brain Structure

Morphological Abnormalities of the Thalamus in Youths With Attention Deficit Hyperactivity Disorder

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