Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease characterized by progressive motor neuron degeneration in the brain and spinal cord leading to muscle atrophy, paralysis, and death. Mitochondrial dysfunction is a major contributor to motor neuron degeneration associated with ALS progression. Mitochondrial abnormalities have been determined in spinal cords of animal disease models and ALS patients. However, molecular mechanisms leading to mitochondrial dysfunction in sporadic ALS (sALS) patients remain unclear. Also, segmental or regional variation in mitochondrial activity in the spinal cord has not been extensively examined in ALS. In our study, the activity of mitochondrial electron transport chain complex IV was examined in post-mortem gray and white matter of the cervical and lumbar spinal cords from male and female sALS patients and controls. Mitochondrial distribution and density in spinal cord motor neurons, lateral funiculus, and capillaries in gray and white matter were analyzed by immunohistochemistry. Results showed that complex IV activity was significantly decreased only in gray matter in both cervical and lumbar spinal cords from ALS patients. In ALS cervical and lumbar spinal cords, significantly increased mitochondrial density and altered distribution were observed in motor neurons, lateral funiculus, and cervical white matter capillaries. Discrete decreased complex IV activity in addition to changes in mitochondria distribution and density determined in the spinal cord in sALS patients are novel findings. These explicit mitochondrial defects in the spinal cord may contribute to ALS pathogenesis and should be considered in development of therapeutic approaches for this disease.

Language skills increase as the brain matures and language specialization is linked to the left hemisphere. Among distinct language domains, sentence comprehension is particularly vital in language acquisition and, by comparison, requires a much longer time-span before full mastery in children. Although accumulating studies have revealed the neural mechanism underlying sentence comprehension acquisition, the development of the brain’s gray matter and its relation to sentence comprehension had not been fully understood. This thesis employs structural magnetic resonance imaging and diffusion-weighted imaging data to investigate the neural correlates of sentence comprehension in preschoolers both cross-sectionally and longitudinally. The first study examines how cortical thick- ness covariance is relevant for syntax in preschoolers and changes across development. Results suggest that the cortical thickness covariance of brain regions relevant for syntax increases from preschoolers to adults, whilst preschoolers with superior language abilities show a more adult-like covariance pattern. Reconstructing the white matter fiber tract connecting the left inferior frontal and superior temporal cortices using diffusion-weighted imaging data, the second study suggests that the reduced cortical thickness covariance in the left frontotemporal regions is likely due to immature white matter connectivity during preschool. The third study then investigated the cortical thickness asymmetry and its relation to sentence comprehension abilities. Results show that longitudinal cortical thick- ness asymmetry in the inferior frontal cortex was associated with improvements in sentence comprehension, further suggesting the crucial role of the inferior frontal cortex for sentence comprehension acquisition. Taken together, evidence from gray and white matter data provides new insights into the neuroscientific model of language acquisition and the emergence of syntactic processing during language development.

During adolescence, the brain undergoes significant reorganization due to myelination and synaptic pruning. These changes are associated with risk-taking behaviors and the development of social relationships. Recent advancements in adolescent brain development can potentially enhance strategies for preventing and treating mental health disorders. This systematic review focuses on structural changes in the adolescent brain, specifically emphasizing a decrease in gray matter and an increase in white matter changes. Four longitudinal MRI studies were included in this systematic review to identify changes in brain volume among healthy adolescents with an age range of 10 to 19 years. The results revealed observable changes in gray and white matter volume in various brain regions during this period. A decrease in gray matter was observed in the frontal, temporal, and parietal cortex, and several subcortical regions. Contrary to our expectations, the amygdala displayed an increase in gray matter in early adolescence. We expected this findings to occur in late childhood. The results also indicated that males undergo more significant changes in the brain during this period than females. Considering the Social Process Network (SIPN) and triadic model, changes occurring in the frontal cortex and the amygdala could be linked to social behavior. While the changes in the thalamus, hippocampus, and amygdala may be linked to heightened risk-taking and mental health disorders. Further research is necessary to clarify the relationship between mental health disorders, behaviors, and developmental processes during adolescence.