Virtual-Reality Performance-Based Assessment of Cognitive Functions in Adult Patients With Acquired Brain Injury: A Scoping Review.

Individuals with acquired brain injury (ABI) commonly present with impairments in cognitive abilities. As these competencies seem to be predictive of patients' abilities to reintegrate into the everyday settings, it is crucial to assess them properly. However, previous research has indicated that patients may perform relatively well on standard tests of cognitive functioning, but may nonetheless encounter significant difficulties in organizing and executing everyday tasks. In order to overcome this issue, virtual reality (VR) methods have been introduced in clinical practice with the aim of creating assessments that simulate real-world activities and thus, provide a clearer picture of patients' functioning in everyday settings. This review offers an overview of VR assessment tools described in the scientific literature between 2010 and 2019. Overall, 38 relevant records describing 31 different tools were found. Among these tools, 16 assessed executive functions and prospective memory, while the other 15 assessed visuo-spatial abilities. Although promising results have been reported, our analysis indicated that about half of the tools deliver tasks that differ from everyday activities, thus limiting the generalizability of patients' performance to the real-world. Moreover, a variety of methodological shortfalls related to study Internal and External Validity have been highlighted, which hamper the possibility of drawing definite recommendations on tool choice. These limitations suggest the importance of putting considerable efforts into the improvement or development of VR tools for patients with ABI for both research and clinical purposes, considering the great potential of this form of assessment.

Pleiotropic effects of spastin on neurite growth depending on expression levels.

Hereditary spastic paraplegia (HSP) is characterized by weakness and spasticity of the lower limbs, owing to degeneration of corticospinal axons. The most common form is due to heterozygous mutations in the SPG4 gene, encoding spastin, a microtubule (MT)-severing protein. Here, we show that neurite growth in immortalized and primary neurons responds in pleiotropic ways to changes in spastin levels. Spastin depletion alters the development of primary hippocampal neurons leading to abnormal neuron morphology, dystrophic neurites, and axonal growth defects. By live imaging with End-Binding Protein 3-Fluorescent Green Protein (EB3-GFP), a MT plus-end tracking protein, we ascertained that the assembly rate of MTs is reduced when spastin is down-regulated. Spastin over-expression at high levels strongly suppresses neurite maintenance, while slight spastin up-regulation using an endogenous promoter enhances neurite branching and elongation. Spastin severing activity is exerted preferentially on stable acetylated and detyrosinated MTs. We further show that SPG4 nonsense or splice site mutations found in hereditary spastic paraplegia patients result in reduced spastin levels, supporting haploinsufficiency as the molecular cause of the disease. Our study reveals that SPG4 is a dosage-sensitive gene, and broadens the understanding of the role of spastin in neurite growth and MT dynamics.