Premie DCD Imaging Intervention Study

RATIONALE Developmental coordination disorder (DCD) is one of the most common disorders in children (Wann, 2007), affecting 5-6% of the school-age population; this is > 400,000 children in Canada, or 1-2 children in every classroom (American Psychiatric Association, 2013; Statistics Canada, 2013). Compared with children born at term, preterm children (born 2-4 months early) are 6-8 times more likely to develop DCD (Edwards…Zwicker, 2011). DCD significantly interferes with a child's ability to learn motor skills and to perform everyday activities, such as getting dressed, tying shoelaces, using a knife and fork, printing, playing sports, or riding a bicycle. While it was once believed that children would outgrow this condition, longitudinal research has shown that functional difficulties can persist into adolescence and adulthood (Cantell, Smyth, \& Ahonen, 2003; Cousins \& Smyth, 2003). Furthermore, secondary psychosocial difficulties often develop, including poor self-esteem, depression, anxiety, problems with peers, loneliness, and decreased participation in physical and social activities (Zwicker, Harris, \& Klassen, 2013). Up to half of children with DCD will have co-occurring attention deficit hyperactivity disorder (ADHD) (Kadesjo \& Gillberg, 1998). As a chronic health condition, DCD often interferes with an individual's function and quality of life across their lifespan (Cousins \& Smyth, 2003; Zwicker et al., 2013)

The cause of DCD is not known, and it is under-recognized, under-diagnosed, and under-treated (Blank et al., 2012). In particular, the investigators do not understand the neural basis of DCD, making it difficult to understand why children with DCD struggle to learn motor skills and to determine how to best intervene to optimize function.

To change the negative trajectory of children with DCD, the investigators need a better understanding of the neural basis of DCD, along with further rehabilitation efforts to improve outcomes. Recently, the investigators and others have conducted small neuroimaging studies to begin to understand brain differences in DCD (Querne et al., 2008; Kashiwagi et al., 2009, Zwicker et al., 2010, 2011, 2012b). These studies, while novel and significant in advancing the field of DCD, are limited by small sample sizes. To further define the neural correlates of DCD, the investigators need to perform larger studies and take advantage of new neuroimaging techniques. To date, no studies have examined neural correlates of DCD in the preterm population, a group that is at particularly high risk for the disorder. In addition, brain imaging studies may determine whether improvements in motor function with current "best practice" rehabilitation intervention are associated with changes in brain structure/function. A greater understanding of the neural basis of DCD may result in earlier diagnosis and early rehabilitation to mediate better brain development.

Currently, the investigators have a study underway that assesses whether rehabilitation intervention and improved outcomes in children with DCD are associated with concurrent brain changes (H14-00397). This proposed research extends this study to determine whether preterm children with DCD show similar brain changes.

SPECIFIC OBJECTIVES AND HYPOTHESES

The proposed study (in conjunction with my current DCD-imaging-intervention study: H14-00397) will allow us to compare brain structure and function in full-term children with DCD and in preterm children with the disorder. While the investigators expect similar neural correlates between the two groups, the investigators hypothesize that the preterm DCD may also show unique brain differences, which may affect their response to rehabilitation. The investigators will address two specific objectives as outlined below:

Objective 1: To characterize structural and functional brain differences in full-term and preterm children with DCD.

Hypothesis: In our current study, the investigators hypothesized that, compared to typically-developing children, children with full-term DCD will show smaller cerebellar volume, differences in microstructural development in motor, sensory and cerebellar pathways, and decreased strength of connectivity in resting, default mode, and motor networks. The investigators expect that preterm children will show similar structural and functional brain differences as full-term children with DCD, but that they may also show mild white matter injury.

Approach: The investigators will use magnetic resonance (MR) imaging and advanced MR techniques to characterize brain structure and function; the investigators will use morphometry to measure cerebral and cerebellar volumes, diffusion tensor imaging (DTI) to assess microstructural development, and functional connectivity MRI to measure connectivity in different brain networks. The investigators will also explore fMRI during a mental rotation task and spectroscopy of the basal ganglia.

Objective 2: To determine if current best-practice rehabilitation intervention induces neuroplastic changes in brain structure/function and positive outcomes in preterm children with DCD.

Hypotheses: Compared to their waitlist scan, the investigators expect that post-treatment scans of preterm children will show: (1) strengthened functional connectivity in resting, default mode, and motor networks; (2) increased integrity of the frontal-cerebellar pathway; (3) increased gray matter volume in the dorsolateral prefrontal, motor and cerebellar cortices; and (4) improved performance and satisfaction ratings of child-chosen functional motor goals. The investigators also expect that there will be a positive association between functional improvements and changes in brain structure/function.

Approach: The investigators will measure brain changes at three time points: once before a waiting period as a baseline scan (conducted as part of the Miller-Grunau Trajectories study at age 8-9 years: C05-0579), once immediately before beginning treatment (12 weeks after the first scan), and once after 12 weeks of intervention. As part of treatment, children will identify three functional motor goals as a target for intervention. The investigators will use the Canadian Occupational Performance Measure (COPM; Law et al., 2005) to measure the child's rating of their performance and satisfaction pre- and post-intervention. To supplement the COPM, the investigators will videotape the child performing each of their motor goals before and after intervention, and an independent occupational therapist will use the Performance Quality Rating Scale (PQRS) to objectively measure performance and change in performance (Miller et al., 2001). As a secondary measure, the investigators will evaluate fine and gross motor skills using the Bruininks-Oseretsky Test of Motor Proficiency-2 (BOT-2: Bruininks \& Bruininks, 2005).