From THE DEPARTMENT OF WOMEN’S AND CHILDREN’S HEALTH Karolinska Institutet, Stockholm, Sweden NEURAL CORRELATES OF HAND FUNCTION IN TYPICALLY DEVELOPING INDIVIDUALS AND CHILDREN WITH UNILATERAL CEREBRAL PALSY

The ability to use our hands is crucial in order to achieve the goals of almost all activities in everyday life. Most of us learn how to handle objects and adjust our hand and finger movements to perform increasingly difficult tasks during childhood and adolescence. This is what is expected, but what happens to our hand motor skills when the motor system is damaged during development and things no longer go according to plan? The motor cortex and corticospinal system are common sites of brain damage in the prenatal and perinatal period and it is well established that the corticospinal system has the capacity of substantial re‐organization. One main focus of this thesis is how the underlying brain lesion and pattern of re‐organization affects hand function in children with unilateral cerebral palsy (CP). A second focus of this thesis is the ability to use a precision grip during dexterous manipulation of unstable objects, both in adults and typically developing children. The main aim of study I was to analyze the internal scale validity of the Strength–Dexterity Test (SD‐test) in a typical pediatric population. This test that was developed to measure dynamic control of fingertip forces during grasping. In study II, items from the SD‐test was used to study the neuroanatomical correlates of fingertip force vector direction and magnitude control in adults using functional magnetic resonance imaging (fMRI). Study III and IV included children with unilateral CP. The aim of these studies was to investigate associations between hand function, brain lesion characteristics, and motor projection patterns using conventional structural magnetic resonance imaging (MRI), transcranial magnetic stimulation (TMS) (Study III) and diffusion tensor imaging study (IV). The results from Study I show that the SD‐test has internal scale validity when administered in a typically developing pediatric population. The SD‐test measures a uniqe unidimensional latent trait that is likely to reflect individual differences in dynamic control of the fingertip force vectors. Study II confirms a recently described bilateral fronto‐parieto‐cerebellar network for manipulation of increasingly unstable objects. Dynamical control of fingertip force direction, was associated with activity in the bilateral precentral gyri, postcentral gyri/sulci at the level of the intraparietal sulci and bilaterally in the cerebellum (lobule VI), while fingertip force magnitude was related to unilateral activation of the (contra lateral) precentral gyrus and bilateral cerebellum. The results from study III showed that motor projection patterns appeared to be influenced by lesion extent and location, but not by lesion type. The results also showed that children with ipsilateral projections can develop fairly good hand function and this has not previously been reported. The overall findings from study IV indicate that diffusion measures correlated with hand function in the non‐dominant hand in children with unilateral CP, and that diffusion MRI provides additional information to visual analysis of conventional structural MRI about structural changes in corticofugal fibers in this group of children. The overall clinical implications and conclusions from this thesis are that combined information from TMS, visual inspection of conventional structural MRI and the use of quantitative measures from diffusion MRI can improve our ability to predict hand function in children with unilateral CP. The SD‐test, although still requiring further development to be a clinical useful tool, offers the possibility to, in a clinical setting, capture an important aspect of dexterous fine motor control. The SD‐test also provides an interesting concept that can be used to study the neural correlates of dynamic control of fingertip forces.