ABSTRACT
OBJECTIVE: Although neuronal activity drives all aspects of cortical development, how human brain rhythms spontaneously mature remains an active area of research. We sought to systematically evaluate the emergence of human brain rhythms and functional cortical networks over early development. METHODS: We examined cortical rhythms and coupling patterns from birth through adolescence in a large cohort of healthy children (n=384) using scalp electroencephalogram (EEG) in the sleep state. RESULTS: We found that the emergence of brain rhythms follows a stereotyped sequence over early development. In general, higher frequencies increase in prominence with striking regional specificity throughout development. The coordination of these rhythmic activities across brain regions follows a general pattern of maturation in which broadly distributed networks of low-frequency oscillations increase in density while networks of high frequency oscillations become sparser and more highly clustered. CONCLUSION: Our results indicate that a predictable program directs the development of key rhythmic components and physiological brain networks over early development. SIGNIFICANCE: This work expands our knowledge of normal cortical development. The stereotyped neurophysiological processes observed at the level of rhythms and networks may provide a scaffolding to support critical periods of cognitive growth. Furthermore, these conserved patterns could provide a sensitive biomarker for cortical health across development.
Subject(s)
Cerebral Cortex/growth & development , Electroencephalography , Nerve Net/growth & development , Sleep/physiology , Adolescent , Analysis of Variance , Brain Mapping/methods , Child , Child, Preschool , Circadian Rhythm/physiology , Electrooculography , Female , Humans , Infant , Infant, Newborn , Male , Neural Networks, Computer , Reference ValuesABSTRACT
The production of an antibody single chain fragment (scFv) in insect cells was accompanied by the formation of an insoluble intracellular precursor even with the inclusion of the bee melittin signal peptide. The presence of the precursor polypeptide suggests a limitation in the processing of the signal peptide so a baculovirus containing a signal peptidase from Bacillus subtilis (SipS) was constructed for expression studies. When the wild type SipS was coexpressed with scFv, preprocessed scFv fragments were no longer detected in insect cell lysates. Conversely, coexpression of scFv alone or with an inactive mutant SipS resulted in at least 30% of the intracellular polypeptide in an unprocessed form at 3 days post infection. Production of scFv in the medium was also enhanced in the presence of SipS; however, low secretion levels indicate the presence of a post-processing bottleneck.
