Cerebellum development during childhood and adolescence: A longitudinal morphometric MRI study
Introduction
The cerebellum has traditionally been associated with balance, motor control, and the ability to learn complex motor sequences. However, a growing body of literature indicates that the cerebellum also plays a prominent role in higher cognitive functions. For instance, cognition but also emotion regulation are affected in patients with vascular and degenerative cerebellar disease (Schmahmann, 2004, Riva and Giorgi, 2000). Electrophysiologic studies indicate that the activity of neurons in selected regions of the cerebellum is related more to cognitive aspects of performance than to motor function (Middleton and Strick, 1997), and functional MRI studies show cerebellar activation in tasks involving language, visuo-spatial analyses, learning and working memory (Stoodley and Schmahmannm, 2009, Desmond et al., 1998). Finally, there have been several histological studies demonstrating cerebellar connections to dorsolateral prefrontal cortex, the medial frontal cortex, the parietal and superior temporal areas (Ramnani, 2006, Middleton and Strick, 1998, Middleton and Strick, 2001).
These cerebellar-subserved higher cognitive functions continue to improve during childhood and adolescence, suggesting that the cerebellum may be undergoing substantial development during this period. Little is known, however, regarding normal development of the cerebellum during childhood or adolescence (Diamond, 2000), including whether developmental trajectories are different between females and males as previous studies, to the best of our knowledge, did not include repeated measurements of the same individuals. Also, little is known regarding differences in the development of cerebellar compartments, despite their having distinct characteristics regarding function, anatomical connections with the cortex, embryological sources and phylogenetic histories, and an important role in neurodevelopmental disorders (Ramnani, 2006). The cerebellum has been implicated in several neurodevelopmental disorders such as attention deficit/hyperactivity disorder, autism, and schizophrenia (Bishop, 2002, Seidman et al., 2005) (Courchesne et al., 1994), and it may be particularly vulnerable to environmental insults (Lesnik et al., 1998).
The relative paucity of previous neuroimaging studies reporting quantitative morphology of the cerebellum and its subdivisions compared to cerebral structures reflects methodologic challenges specific to the cerebellum, including its thinner striations of gray and white matter, its foliated shape, and less obvious anatomic demarcations of functionally distinct subdivisions. We therefore collaborated with the University of Iowa to implement a novel expert-guided cerebellar quantification method on longitudinally acquired MRI scans from a pediatric cohort. We hypothesized that cerebellar regions would show distinct growth curves, and that these trajectories would differ between males and females, similar to what we and others have observed in cerebral development (Lenroot et al., 2007), and that ontologically diverse cerebellar compartments would have different developmental trajectories.
Section snippets
Participant selection
Subjects are healthy participants from an ongoing longitudinal study at the Child Psychiatry Branch of the National Institute of Mental Health. Subjects are recruited from the local community. When multiple siblings were available only one child per family was included; the sibling with 3 or more scans were chosen to maximize the number of available longitudinal scans and otherwise at random. We included only right-handed children in this sample. The healthy participants were screened via
Demographic characteristics
All participants were right-handed, singletons and self-described as being of Caucasian origin. There was no significant difference between the male and female groups in terms of average age at time of scan (females 13.7 years, males 13.9 years). Females came from families with a higher socio-economic status than males (parental Hollingshead Index of Social Status Score was 30 in females versus 21 in males, Mann–Whitney U = 202, df = 48, p = 0.02). There was a trend for group difference in IQ with a
Discussion
This is the first longitudinal study of normal cerebellar development during childhood and adolescence. Total cerebellar volume was larger in males, both with and without adjustment for total brain volume, this difference gradually increased during adolescence. The cerebellum as a whole reached its peak volume later than the cerebrum, suggesting a prolonged developmental course. Different cerebellar compartments had distinct growth patterns with varying degrees of sexual dimorphism. Growth
Acknowledgments
Dr. H. Tiemeier's work on this project was supported by a research fellowship of the Sophia Stichting (2004-025/SWO). This study was funded by the Intramural Program of the National Institute of Mental Health.
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