Cerebellar Development and Clinical Outcome in Attention Deficit Hyperactivity Disorder

Columbia University, New York, New York, United States
American Journal of Psychiatry (Impact Factor: 12.3). 04/2007; 164(4):647-55. DOI: 10.1176/appi.ajp.164.4.647
Source: PubMed


Anatomic magnetic resonance imaging (MRI) studies have detected smaller cerebellar volumes in children with attention deficit hyperactivity disorder (ADHD) than in comparison subjects. However, the regional specificity and longitudinal progression of these differences remain to be determined. The authors compared the volumes of each lobe of the cerebellar hemispheres and vermis in children with ADHD and comparison subjects and used a new regional cerebellar volume measurement to characterize the developmental trajectory of these differences.
In a longitudinal case-control study, 36 children with ADHD were divided into a group of 18 with better outcomes and a group of 18 with worse outcomes and were compared with 36 matched healthy comparison subjects. The volumes of six cerebellar hemispheric lobes, the central white matter, and three vermal subdivisions were determined from MR images acquired at baseline and two or more follow-up scans conducted at 2-year intervals. A measure of global clinical outcome and DSM-IV criteria were used to define clinical outcome.
In the ADHD groups, a nonprogressive loss of volume was observed in the superior cerebellar vermis; the volume loss persisted regardless of clinical outcome. ADHD subjects with a worse clinical outcome exhibited a downward trajectory in volumes of the right and left inferior-posterior cerebellar lobes, which became progressively smaller during adolescence relative to both comparison subjects and ADHD subjects with a better outcome.
Decreased volume of the superior cerebellar vermis appears to represent an important substrate of the fixed, nonprogressive anatomical changes that underlie ADHD. The cerebellar hemispheres constitute a more plastic, state-specific marker that may prove to be a target for clinical intervention.

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    • "In addition, the absence of a deficit in non-cortical resting state connectivity does not imply the absence of any cerebellar or subcortical deficits, as other neural properties can be affected. For example, volumetric differences in cerebellar and subcortical regions have been related to ADHD pathology (Mackie et al., 2007; Seidman, Valera, & Makris, 2005; Valera et al., 2007). Furthermore, an increasing number of studies does not point to one core brain deficit in ADHD, but instead describes widespread neural abnormalities associated with the disorder (Bush, 2010; Coghill, Hayward, Rhodes, Grimmer, & Matthews, 2014; Durston, 2003; Fair, Bathula, Nikolas, & Nigg, 2012; Sonuga- Barke, 2005). "
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    ABSTRACT: Background: One neurodevelopmental theory hypothesizes remission of attention-deficit/hyperactivity disorder (ADHD) to result from improved prefrontal top-down control, while ADHD, independent of the current diagnosis, is characterized by stable non-cortical deficits (Halperin & Schulz, 2006). We tested this theory using resting state functional MRI (fMRI) data in a large sample of adolescents with remitting ADHD, persistent ADHD, and healthy controls. Methods: Participants in this follow-up study were 100 healthy controls and 129 adolescents with ADHD combined type at baseline (mean age at baseline 11.8 years; at follow-up 17.5 years). Diagnostic information was collected twice and augmented with magnetic resonance imaging (MRI) scanning at follow-up. We used resting state functional connectivity (RSFC) of the executive control network to investigate whether improved prefrontal top-down control was related to a developmental decrease in ADHD symptoms. In addition, we tested whether non-cortical RSFC, i.e., cerebellar and striatal RSFC, was aberrant in persistent and/or remittent ADHD compared to controls. Results: Higher connectivity within frontal regions (anterior cingulate cortex) of the executive control network was related to decreases in ADHD symptoms. This association was driven by change in hyperactive/impulsive symptoms and not by change in inattention. Participants with remitting ADHD showed stronger RSFC than controls within this network, while persistent ADHD cases exhibited RSFC strengths intermediate to remittent ADHD cases and controls. Cerebellar and subcortical RSFC did not differ between participants with ADHD and controls. Conclusions: In line with the neurodevelopmental theory, symptom recovery in ADHD was related to stronger integration of prefrontal regions in the executive control network. The pattern of RSFC strength across remittent ADHD, persistent ADHD, and healthy controls potentially reflects the presence of compensatory neural mechanisms that aid symptomatic remission.
    Cortex 09/2015; 73:62-72. DOI:10.1016/j.cortex.2015.08.012 · 5.13 Impact Factor
    • "Although the link between ADHD and DCD in terms of motor, attentional, hyperactive and impulsive problems has been discussed in various reviews [22] [23] and studies [24] [25] [26] [27] [28] [29], the neurological basis and its association with cognitive and motor problems has rarely been addressed. Numerous morphometric and neuroimaging studies have been conducted in individuals with ADHD, and have identified brain regions with abnormalities which may explain their cognitive and motor deficits [30] [31] [32] [33]. Contrary to ADHD, there are few studies, with small sample sizes and divergent findings, investigating the neurobiology of DCD [34] [35] [36]. "
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    ABSTRACT: Attention deficit hyperactivity disorder (ADHD) has been described as the most prevalent behavioral disorder in children. Developmental coordination disorder (DCD) is one of the most prevalent childhood movement disorders. The overlap between the two conditions is estimated to be around 50%, with both substantially interfering with functioning and development, and leading to poorer psychosocial outcomes. This review provides an overview of the relationship between ADHD and DCD, discussing the common presenting features, etiology, neural basis, as well as associated deficits in motor functioning, attention and executive functioning. It is currently unclear which specific motor and cognitive difficulties are intrinsic to each disorder as many studies of ADHD have not been screened for DCD and vice-versa. The evidence supporting common brain underpinnings is still very limited, but studies using well defined samples have pointed to non-shared underpinnings for ADHD and DCD. The current paper suggests that ADHD and DCD are separate disorders that may require different treatment approaches. Copyright © 2015. Published by Elsevier B.V.
    Behavioural brain research 07/2015; 292. DOI:10.1016/j.bbr.2015.07.009 · 3.03 Impact Factor
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    • "The cerebellum is structurally connected with prefrontal and striatal circuits implicated in ADHD [Bostan et al., 2013]. Structural neuroimaging studies have revealed reduced volumes of the cerebellum or its subregions in ADHD that have been shown to correlate with attentional problems and clinical outcomes [Castellanos et al., 2002; Mackie et al., 2007; Makris et al., in press; Stoodley, 2014]. Additionally , fMRI studies have revealed decreased cerebellar activation in ADHD during performance of a number of cognitive tasks [Suskauer et al., 2008; Valera et al., 2005, 2010b]. "
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    ABSTRACT: Attention-deficit/hyperactivity disorder (ADHD) is increasingly understood as a disorder of spontaneous brain-network interactions. The default mode network (DMN), implicated in ADHD-linked behaviors including mind-wandering and attentional fluctuations, has been shown to exhibit abnormal spontaneous functional connectivity (FC) within-network and with other networks (salience, dorsal attention and frontoparietal) in ADHD. Although the cerebellum has been implicated in the pathophysiology of ADHD, it remains unknown whether cerebellar areas of the DMN (CerDMN) exhibit altered FC with cortical networks in ADHD. Here, 23 adults with ADHD and 23 age-, IQ-, and sex-matched controls underwent resting state fMRI. The mean time series of CerDMN areas was extracted, and FC with the whole brain was calculated. Whole-brain between-group differences in FC were assessed. Additionally, relationships between inattention and individual differences in FC were assessed for between-group interactions. In ADHD, CerDMN areas showed positive FC (in contrast to average FC in the negative direction in controls) with widespread regions of salience, dorsal attention and sensorimotor networks. ADHD individuals also exhibited higher FC (more positive correlation) of CerDMN areas with frontoparietal and visual network regions. Within the control group, but not in ADHD, participants with higher inattention had higher FC between CerDMN and regions in the visual and dorsal attention networks. This work provides novel evidence of impaired CerDMN coupling with cortical networks in ADHD and highlights a role of cerebro-cerebellar interactions in cognitive function. These data provide support for the potential targeting of CerDMN areas for therapeutic interventions in ADHD. Hum Brain Mapp, 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Human Brain Mapping 06/2015; 36(9). DOI:10.1002/hbm.22850 · 5.97 Impact Factor
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