Relationship between Executive Function and the Nature and Function of the Brain Injury in Children with Congenital Hemiplegia.

BROAD AIM: This investigation aims to examine executive functioning (EF) and related constructs (i.e., intelligence, memory, attention, concentration, psychological functioning, adaptive functioning, and functional ability) in children with congenital hemiplegia. It also aims to examine the relationship between EF and the underlying brain structure alterations and abnormalities including location of the lesions, extent of the lesions, and the presumed timing of the lesions, using MRI. In addition the relationship between performance on EF and white matter density as measured by DTI and functional connectivity will be analysed. Finally, it aims to examine the brain structure-function relationship between performance on an EF task (the Flanker task) which focuses on executive attention and brain lesion location and extent and the neurovascular changes based on the Blood Oxygen Level Dependent (BOLD) response, as measured with functional MRI. HYPOTHESES: 1.It is hypothesised that compared to matched controls, children with hemiplegia would show EF impairments in the following specific domains: (a) attentional control; (b) cognitive flexibility; (c) goal setting; (d) information processing; (e) working memory; (f) verbal fluency; and, (e) in everyday life (as measured by parent and teacher report). 2.It is hypothesised that EF will correlate with the lesion site, and in particular, we will test correlations with: (a) side; (b) location; and, (c) extent (as measured by structural MRI). 3.It is hypothesised that poor EF will correlate with the nature, density, and location of white matter damage/connectivity (as measured by DTI). 4. It is hypothesised that poor performance on the Flanker task will correlate with altered activiation patterns which can be mapped based on the changes in the Blood Oxygen Level Dependent (BOLD) response as measured by functional MRI. The changes in blood axygenation resulting from brain activation produce a measurable effect in MR images. SPECIFIC AIMS: 1.To examine executive function (i.e., skills necessary for novel, goal-directed, and complex activity, such as planning and organisation) in children with congenital hemiplegia 2.To examine the relationship between the presence, location, extent, and timing of brain lesions (using structural MRI scans) and executive function in children with hemiplegia. 3.Establish whether children with left and right hemiplegia exhibit the same executive function profile; alternatively, do children with right hemiplegia have different strengths/impairments on executive function compared to children with left hemiplegia, and vice versa. 4.To examine the relationship between white matter connectivity and executive functions using diffusion tension imaging (i.e., a technique that is part of an MRI that evaluates white matter pathways in the brain). 5. to examine the relationship between the performance on a specific executive function task (the Flanker) task and neurovascular changes using the BOLD response as measured by fMRI (i.e., a technique which shows changes in cerebral blood flow in response to behavioural activation). BACKGROUND: Congenital hemiplegia is the most common type of CP among children born full term and the second most common type in children born prematurely. In addition to motor deficits seen in congenital hemiplegia, associated difficulties, such as cognitive impairments, have been identified. In spite of this, there is a paucity of literature on congenital hemiplegia examining neuropsychological consequences, in particular EF. Dysfunction in the executive system can result in numerous cognitive deficits that negatively influence daily functioning, such as impaired planning, monitoring, reasoning, concept formation, mental flexibility, social judgments, and attention. Having a better understanding of potential EF deficits in congenital hemiplegia will aid future rehabilitative interventions aimed at improving functional independence in this population. Further, if we are able to correlation EF with specific lesion sites, we will be able to predict potential EF impairments in children and thus provide earlier rehabilitative interventions. The Flanker task is used to emphasize the stimulus-response inhibitory processing which is an important part of attention. The task activates the executive attention network, including the midline frontal areas (anterior cingulated) and the lateral prefrontal cortex (Bush et al., 2000; MacDonald & Carter, 2000), which is associated with conflict in responses (Fan et al., 2002). The Flanker task challenges the ability to inhibit irrelevant information (Hazeltine et al., 2000). It is found that during tasks which explore inhibitory processes the main focus of increased brain activity is at the right inferior frontal cortex (Collette et al., 2006; Hazeltine et al., 2000). Problems with attention and EF are associated with lesions in the periventricular white matter in anterior (Schatz et al., 2001; White & Christ, 2005) or parietal regions (Pavlova et al., 2008). Furthermore, it is suggested that lesions of the basal ganglia, the thalamic systems, or both affect focused attention (Mirsky, 1989) as well as EF. The changes in cerebral blood flow as measured with fMRI will show activation patterns associated with the Flanker task. Poor performance on the Flanker task in children with congenital hemiplegia may correlate with an altered pattern of cerebral blood flow compared to normal children. RESEARCH PLAN: 40 children with congenital hemiplegia aged 8 – 16 years (20 with right congenital hemiplegia and 20 with left congenital hemiplegia) will be recruited. Twenty further children without congenital hemiplegia will also be recruited and will be matched as closetly as possible for age and gender (N = 60). All 60 children will complete a battery of neuropsychological assessments and parents will be asked to complete self-report measures in approximately a 2 1/2 hour assessment session. School teachers will also be asked to complete one self-report measure. Children with congenital hemiplegia will also either complete an MRI scan or previous MRI scans will be accessed from the Queensland Cerebral Palsy Children’s Health Services Database. In the second phase of this study the children are invited to complete a first or second scan (if they had a previous scan in phase 1) in which the diffusion tensor imaging and functional MRI data will be collected. Before the real scan the children have the chance to practice in a “mock scanner”. During the fMRI scan the Flanker task is performed which can also be practised outside the scanner before the scanning procedure. This phase of the study will approximately take 1 1/2 hour of which 40 to 50 minutes will be spend inside the scanner.