Targeted Engagement of the Action Selection Network during Task-Oriented Arm Training after Stroke.

Action selection (AS), or selection of an action from a set of alternatives, is an important movement preparation process that engages a frontal-parietal network. The addition of AS demands to arm training after stroke could be used to engage this motor planning process and the neural network that supports it. The purpose of this case series is to describe the feasibility and outcomes associated with task-oriented arm training aimed at engaging the AS behavioral process and the related neural network in three individuals with chronic stroke. Three participants with mild to moderate motor deficits completed 13 to 15 sessions of task-oriented arm training that included AS cues for each movement repetition; cues dictated movement direction, height, or distance. Before and after training, individuals completed an AS brain-behavior probe during functional MRI. AS behavioral performance improved after training (increased accuracy, decreased reaction time) in all participants while brain activation in the AS network (dorsal premotor, parietal, dorsolateral prefrontal cortices) decreased in two participants. Gains in motor function were also found in all three participants, especially on patient-reported measures of perceived difficulty and confidence to complete upper extremity functional tasks. It was feasible to target the AS behavioral process and the related neural network through the addition of AS demands to functional, task-oriented arm training in three individuals with mild to moderate motor dysfunction poststroke.

Select 3',5'-cyclic nucleotide phosphodiesterases exhibit altered expression in the aged rodent brain.

3',5'-cyclic nucleotide phosphodiesterases (PDEs) are the only known enzymes to compartmentalize cAMP and cGMP, yet little is known about how PDEs are dynamically regulated across the lifespan. We mapped mRNA expression of all 21 PDE isoforms in the adult rat and mouse central nervous system (CNS) using quantitative polymerase chain reaction (qPCR) and in situ hybridization to assess conservation across species. We also compared PDE mRNA and protein in the brains of old (26 months) versus young (5 months) Sprague-Dawley rats, with select experiments replicated in old (9 months) versus young (2 months) BALB/cJ mice. We show that each PDE isoform exhibits a unique expression pattern across the brain that is highly conserved between rats, mice, and humans. PDE1B, PDE1C, PDE2A, PDE4A, PDE4D, PDE5A, PDE7A, PDE8A, PDE8B, PDE10A, and PDE11A showed an age-related increase or decrease in mRNA expression in at least 1 of the 4 brain regions examined (hippocampus, cortex, striatum, and cerebellum). In contrast, mRNA expression of PDE1A, PDE3A, PDE3B, PDE4B, PDE7A, PDE7B, and PDE9A did not change with age. Age-related increases in PDE11A4, PDE8A3, PDE8A4/5, and PDE1C1 protein expression were confirmed in hippocampus of old versus young rodents, as were age-related increases in PDE8A3 protein expression in the striatum. Age-related changes in PDE expression appear to have functional consequences as, relative to young rats, the hippocampi of old rats demonstrated strikingly decreased phosphorylation of GluR1, CaMKIIα, and CaMKIIß, decreased expression of the transmembrane AMPA regulatory proteins γ2 (a.k.a. stargazin) and γ8, and increased trimethylation of H3K27. Interestingly, expression of PDE11A4, PDE8A4/5, PDE8A3, and PDE1C1 correlate with these functional endpoints in young but not old rats, suggesting that aging is not only associated with a change in PDE expression but also a change in PDE compartmentalization.