The Cognitive Neuroplasticity of Reading Recovery following Chronic Stroke: A Representational Similarity Analysis Approach.

Damage to certain left hemisphere regions leads to reading impairments, at least acutely, though some individuals eventually recover reading. Previous neuroimaging studies have shown a relationship between reading recovery and increases in contralesional and perilesional activation during word reading tasks, relative to controls. Questions remain about how to interpret these changes in activation. Do these changes reflect functional take-over, a reorganization of functions in the damaged brain? Or do they reveal compensatory masquerade or the use of alternative neural pathways to reading that are available in both patients and controls? We address these questions by studying a single individual, CH, who has made a partial recovery of reading familiar words following stroke. We use an fMRI analysis technique, representational similarity analysis (RSA), which allows us to decode cognitive function from distributed patterns of neural activity. Relative to controls, we find that CH shows a shift from visual to orthographic processing in contralesional regions, with a marginally significant result in perilesional regions as well. This pattern supports a contralesional reorganization of orthographic processing following stroke. More generally, these analyses demonstrate how powerful RSA can be for mapping the neural plasticity of language function.

Neuronal overexpression of human VAPB slows motor impairment and neuromuscular denervation in a mouse model of ALS.

Four mutations in the VAMP/synaptobrevin-associated protein B (VAPB) gene have been linked to amyotrophic lateral sclerosis (ALS) type 8. The mechanism by which VAPB mutations cause motor neuron disease is unclear, but studies of the most common P56S variant suggest both loss of function and dominant-negative sequestration of wild-type protein. Diminished levels of VAPB and its proteolytic cleavage fragment have also been reported in sporadic ALS cases, suggesting that VAPB loss of function may be a common mechanism of disease. Here, we tested whether neuronal overexpression of wild-type human VAPB would attenuate disease in a mouse model of familial ALS1. We used neonatal intraventricular viral injections to express VAPB or YFP throughout the brain and spinal cord of superoxide dismutase (SOD1) G93A transgenic mice. Lifelong elevation of neuronal VAPB slowed the decline of neurological impairment, delayed denervation of hindlimb muscles, and prolonged survival of spinal motor neurons. Collectively, these changes produced a slight but significant extension in lifespan, even in this highly aggressive model of disease. Our findings lend support for a protective role of VAPB in neuromuscular health.