Changes in functional brain networks following sports-related concussion in adolescents.

Sports-related concussion is a major public health issue; however, little is known about the underlying changes in functional brain networks in adolescents following injury. Our aim was to use the tools from graph theory to evaluate the changes in brain network properties following concussion in adolescent athletes. We recorded resting state electroencephalography (EEG) in 33 healthy adolescent athletes and 9 adolescent athletes with a clinical diagnosis of subacute concussion. Graph theory analysis was applied to these data to evaluate changes in brain networks. Global and local metrics of the structural properties of the graph were calculated for each group and correlated with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) scores. Brain networks of both groups showed small-world topology with no statistically significant differences in the global metrics; however, significant differences were found in the local metrics. Specifically, in the concussed group, we noted: 1) increased values of betweenness and degree in frontal electrode sites corresponding to the (R) dorsolateral prefrontal cortex and the (R) inferior frontal gyrus and 2) decreased values of degree in the region corresponding to the (R) frontopolar prefrontal cortex. In addition, there was significant negative correlation between degree and hub value, with total symptom score at the electrode site corresponding to the (R) prefrontal cortex. This preliminary report in adolescent athletes shows for the first time that resting-state EEG combined with graph theoretical analysis may provide an objective method of evaluating changes in brain networks following concussion. This approach may be useful in identifying individuals at risk for future injury.

Neuromuscular defects in a Drosophila survival motor neuron gene mutant.

Autosomal recessive spinal muscular atrophy (SMA) is linked to mutations in the survival motor neuron (SMN) gene. The SMN protein has been implicated at several levels of mRNA biogenesis and is expressed ubiquitously. Studies in various model organisms have shown that the loss of function of the SMN gene leads to embryonic lethality. The human contains two genes encoding for SMN protein and in patients one of these is disrupted. It is thought the remaining low levels of protein produced by the second SMN gene do not suffice and result in the observed specific loss of lower motor neurons and muscle wasting. The early lethality in the animal mutants has made it difficult to understand why primarily these tissues are affected. We have isolated a Drosophila smn mutant. The fly alleles contain point mutations in smn similar to those found in SMA patients. We find that zygotic smn mutant animals show abnormal motor behavior and that smn gene activity is required in both neurons and muscle to alleviate this phenotype. Physiological experiments on the fly smn mutants show that excitatory post-synaptic currents are reduced while synaptic motor neuron boutons are disorganized, indicating defects at the neuromuscular junction. Clustering of a neurotransmitter receptor subunit in the muscle at the neuromuscular junction is severely reduced. This new Drosophila model for SMA thus proposes a functional role for SMN at the neuromuscular junction in the generation of neuromuscular defects.