• psychopathological symptoms
• neuropsychological profile
• neuroplasticity
• neurofunctional correlates
• cognitive development
• cerebral palsy
• working memory training

Neurodevelopmental disabilities are a group of disorders with onset in the developmental period characterized by alterations of the central nervous system due to early brain damage, genetic/chromosomal abnormalities, epilepsy or environmental conditions which can give rise to intellectual disability, neuropsychological deficits, specific learning deficits, movement and posture disorders, such as Cerebral Palsy, and psychiatric disturbances. Other neurodevelopmental disorders frequently co-occur and determine impairments in personal, social, academic, and vocational functioning (Diagnostic and Statistical Manual of Mental disorders, Fifth edition, 2013).
Neurodevelopmental disabilities are currently being studied based on different levels of description-behavioral, cognitive, neural-within a cognitive neuroscience framework, far distant from the adult domain-specific modularization approach. The modern cognitive neuroscience framework (Marechal et al., 2007; Johnson and de Haan, 2011) fuelled by recent breakthroughs in the fields of brain connectivity and genetics, posits that brain-behaviour relationships in childhood are best understood as being subsumed by progressive specialization and localization of function within the complex two-way interaction between genes and various environments.
Traditionally, neurodevelopmental disorders have been often investigated through the lens of single levels of description rarely correlating, in the same patient, neuropsychological, neurofunctional and psychiatric evidence.
The aim of this PhD thesis is to study Cerebral Palsy as a model of neurodevelopmental disability by integrating different levels of description for understanding such a complex and multifaceted neurodevelopmental disorder. According to the modern classification, Cerebral Palsy is described as “a group of permanent disorders of movement and posture causing activity limitation that are attributed to non-progressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication and behaviour, by epilepsy and by secondary musculoskeletal problems” (Rosenbaum et al., 2007). Current literature is underlining the crucial role of such associated deficits in determining outcome both in terms of neuropsychological and academic functioning as well as on a social, emotional and participation levels, and thus the limits of plasticity in the face of early damage to the central nervous system.
Five studies have been conducted to investigate, in children with cerebral palsy with bilateral white matter lesions, the neuropsychological profile and neuroanatomical correlates, the impact of the neuropsychological profile on psychopathological and academic problems, and the effect of an intensive cognitive training on neuropsychological functioning and on the neurofunctional mechanisms underlying plasticity. The aims were pursued by means of new clinicaland instrumental approaches: on a behavioural level of description, the Developmental Neuropsychological Battery-NEPSY-II (Korkman M, Kirk U, Kemp SL, 2007; Italian standardization Urgesi C, Campanella F, Fabbro F, 2011), a comprehensive neuropsychological investigation, and CogMed Working Memory Training (RoboMemo®, CogMed Cognitive Medical Systems AB, Stockholm, Sweden), an evidence-based computerized program; on a neurofunctional level of description, a novel semi-quantitative scale for classification of brain MRI lesion severity (Fiori et al., 2014) and high density sleep EEG to measure changes in slow waves activity (electroencephalographic power between 0.5-4.5 Hz), crucial for regulating synaptic plasticity and cortical reorganization (Huber et al., 2004). Finally on a psychiatric level of description, psychopathological symptoms were investigated with a parent-report measure (CBCL, Achenbach et al., 1991).
In the first study the aim was to analyze the profile of neuropsychological strengths and weaknesses, by NEPSY-II, and their relationship with neuroanatomical findings on brain MRI in children with bilateral cerebral palsy due to periventricular leukomalacia and normal verbal intelligence (Study 1). The results showed a neuropsychological impairment profile characterized by a multi-level structure: visuo-spatial and sensorimotor skills were severely impaired in almost all of the children, while difficulties in attention and executive functions were an additional weakness specifically associated with the involvement to anterior/medial corpus callosum and thalamus. Language and verbal memory were confirmed to be a specific strengths in this clinical population.
The second study focused on the academic abilities in children with bilateral cerebral palsy to verify if there was a pattern of learning deficits specifically characterizing bilateral white matter lesions and not unilateral lesions. For this purpose, children with bilateral lesions were compared to age and intelligence matched children with unilateral lesions (Study 2). A high percentage (55%) of children with cerebral palsy showed reading or text comprehension difficulties and no significant differences across clinical forms of cerebral palsy were found, suggesting the different neurofunctional alterations leading to unilateral or bilateral brain lesion do not differently impact the compensative strategies for reading and text comprehension.
The impact of the neuropsychological profile on paychopthological problems was investigated studying the behavioural and emotional characteristics and their correlations with the clinical and neuropsychological profiles (Study 3). The findings showed that the internalizing problems, that is social withdrawal and somatic problems, characterized a high percentage of children (35%) and resulted strongly correlated with the degree of impairment in non-verbal intelligence level, visuo-spatial and manual motor abilities as well as social competences. In the last year of the PhD project, an evidence-based training program has been administered to a sample of children with bilateral cerebral palsy due to periventricular leukomalacia in order to improve the neuropsychological impairments, attention and executive functions, found impaired in Study 1 (Study 4). A significant, directly trained effect on working memory abilities was found independently of clinical characteristics. An additional not-directly trained effect on impaired neuropsychological functions, such as visuo-spatial, inhibition and verbal updating, was found to be correlated to the degree of impairment in gross-motor function and verbal intelligence level. In a subgroup of children with bilateral cerebral palsy due to periventricular leukomalacia, the slow waves activity results at high density sleep EEG before and after training, have suggested new hypotheses on the neurofunctional mechanisms underlying plasticity such as sustained compensation or functional restitution (Study 5). Positive correlations between the improvement of impaired neuropsychological functions, such as visuo-spatial memory and manual planning, and the frequency-specific increase of the slow waves activities in fronto-occipital regions were found, suggesting a cortical reorganization process functionally connected with the trained neuropsychological domains. The introduction of this PhD thesis is oriented to briefly describe the neurodevelopmental disorder, cerebral palsy, and to illustrate the new instrumental and rehabilitative approaches used to study this clinical disorder.