Moreover, both local (Figures 1C and 1D) and distributed circuit modifications are Vorinostat associated with the recovery process. Local changes in the peri-infarct region include changes in dendritic morphology, axon sprouting, neurogenesis, and neural connectivity (Cramer, 2008 and Taub et al., 2002). Functional imaging studies in stroke patients also suggest that plasticity of interhemispheric

as well as intrahemispheric functional connectivity are linked to improvements in function (Cramer, 2008, Grefkes and Ward, 2013 and Taub et al., 2002). A great challenge is to specifically identify which of the local and distributed changes are essential for recovery. These are likely to offer the most robust and potentially HA-1077 clinical trial synergistic therapeutic targets. A hallmark of many neurodegenerative diseases (e.g., Alzheimer’s disease and Parkinson’s disease) is a prolonged

prodromal period during which there is little evidence for global functional deficits despite ongoing degeneration at the cellular level (Cramer et al., 2011). There is great interest in this prodromal period as it offers a window for intervention (Schapira and Tolosa, 2010). A reasonable hypothesis is that during the prodromal period the neural network may undergo adaptive plasticity or homeostatic regulation in response to ongoing degeneration. In the case of Alzheimer’s disease, a growing body of research indicates that amyloid-induced memory deficits may at least in part be due to impaired NMDA-R function those and loss of normal synaptic plasticity (Parihar and Brewer, 2010). Modulation of neural plasticity could be an important therapeutic avenue in both

the prodromal and the symptomatic phase (Cissé et al., 2011). Excessive plasticity can be associated with the development of some disease symptoms. Two examples include focal dystonia (Sheehy and Marsden, 1982) and chronic pain (Saab, 2012). Focal dystonia is a neurological disorder often seen in those who perform repetitive fine motor tasks such as playing music or typing. These patients experience abnormal coactivation of agonist and antagonist muscles during task performance. Maladaptive plasticity triggered by excessive repetitive finger movements in a task requiring high attention contributes in part to the onset of symptoms (Elbert et al., 1998 and Lin and Hallett, 2009). Monkeys required to perform a repetitive fine motor task also appeared to develop dystonic symptoms (Byl et al., 1996). Interestingly, cortical mapping studies in these animals showed that sensory receptive fields were abnormally increased with breakdown of normal topographic boundaries (Figure 1E). Persistent coincident sensory stimulation and excessive plasticity could account for both the change in receptive fields and dystonic symptoms (Byl et al., 1996, Lin and Hallett, 2009 and Wang et al., 1995) (Figure 1F). Chronic pain syndromes are also associated with excessive plasticity in cortical and subcortical networks (Saab, 2012).