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Cavanaugh, M.

Publications and source records attributed to Cavanaugh, M..

2 recordsLinked to original sources

Generalisation of training-induced recovery in occipital stroke: neurochemical and fMRI correlates

BACKGROUNDDamage to the early visual cortex after an occipital stroke typically results in the loss of conscious vision in the contralateral hemifield. Nonetheless, extensive perceptual training can restore visual motion discrimination in the blind-field. Here, we assessed, in a cohort study, whether improvements transferred to an untrained Gabor detection task and whether awareness within the blind field increased. We then explored the neural underpinnings of these changes. METHODSEighteen participants (6 female; aged 24-74 years; >6 months post-stroke) completed at least six months of visual rehabilitation in their blind field. Rehabilitation consisted of participants practicing a two-alternative, forced-choice, motion discrimination task using random dot stimuli, five days/week, at home, at one or two non-overlapping, locations in their blind-field. Each participant also completed two in-lab visits: one pre- and one post-training. A subset returned to the lab for a follow-up visit three months later to assess persistence of recovery. In addition to the trained task, an untrained, drifting-Gabor detection task was used to measure transfer of learning and changes in visual awareness at the trained locations. To investigate neural mechanisms underlying generalisation of improvements, participants completed MRI scanning at each lab visit. Magnetic resonance spectroscopy (MRS) was used to quantify GABA and glutamate concentrations in the ipsilesional motion sensitive area, hMT+, and a control voxel in the sensorimotor cortex. Functional MRI was conducted to assess BOLD signal changes in hMT+ and across the rest of the brain during passive viewing of high contrast Gabor stimuli in the blind field. RESULTSParticipants showed significant improvements in motion direction discrimination (trained task) between pre- and post-training in-lab visits, which generalised to improvements in Gabor detection and awareness (untrained task). Reduced GABA and glutamate in ipsilesional hMT+ was linked to improved Gabor detection, but not awareness. Increased BOLD signals in hMT+ and dorsolateral prefrontal cortex also correlated with improved Gabor detection, while awareness changes were linked to higher-level areas associated with visual attention in the contralesional prefrontal cortex (area 46) and inferior parietal lobule. CONCLUSIONSLong-term visual rehabilitation using a global motion discrimination task generalised to enhance both detection and awareness of moving Gabors within the blind field of occipital stroke survivors. Improvements were supported by selective changes in brain regions known to be involved in motion perception and attention respectively, suggesting that a broad network supports recovery, which could be targeted to enhance outcomes.

neuroscience↗

Ribose lowers RpoS translation through RbsD mRNA

The Escherichia coli sigma factor RpoS accumulates during starvation, activates transcription of the general stress response, and then rapidly returns to low levels upon nutrient replenishment. Sugar levels modulate RpoS levels by signaling though central metabolism, ATP and the phosphoenolpyruvate-carbohydrate phosphotransferase system (PTS) transport system, which favors glucose. However, there have been few examples of dedicated control pathways for specific sugars regulating RpoS. We screened an overexpression library with a RpoS- LacZ reporter and found that overexpressing the ribose metabolism rbsD gene reduced RpoS levels. A functional RbsD ribose pyranase protein was not necessary for the effect, suggesting that the RbsD mRNA was responsible for the effect. We used a series of LacZ fusions and RT-qPCR to determine how RbsD mRNA affects RpoS and found that regulation of RpoS occurred at the level of translation. Furthermore, the effect of rbsD overexpression was diminished in strain that did not have the RpoS untranslated hairpin loop or the small RNA chaperone Hfq. RbsD mRNA has previously been shown to bind to the sRNA DsrA. We demonstrated that the effect of RbsD on RpoS was dependent on the sRNAs DsrA and ArcZ and Hfq. Finally, we showed that the sugar ribose lowers RpoS levels in a manner that requires RbsD. In summary, our results demonstrate that RpoS levels respond specifically to ribose though a component of the ribose metabolism pathway and the main player, RbsD, acts as dual function mRNA that has a regulatory role by interacting with the sRNAs that control RpoS.

genetics↗