Clinical improvements have been achieved by applying inhibitory

rTMS patterns to either the unaffected hemisphere (Oliveri et al., 2001; Brighina et al., 2003; Mansur et al., 2005; Fregni et al., 2005; Shindo et al., 2006; Takeuchi et al., 2005, 2008) or excitatory rTMS patterns to the injured hemisphere (Khedr et al., 2005; Kim et al., 2006; Yozbatiran et al., 2009). Transcranial DCS has also provided evidence of recovery in several neurological conditions using similar principles (Boggio et al., 2007; Hesse et al., 2007; Reis et al., 2009; Sparing et al., 2009). The insights provided by rTMS and tDCS studies have unequivocally elevated the scientific and clinical drive to alleviate functional impairments in the brain-injured population. However, despite promising results obtained in small-scale studies, limitations in clinical RO4929097 mouse outcomes remain, and neurostimulation has often been considered inconsistent in delivering significant and long-lasting ameliorations when applied to larger populations of

patients. Factors such as lesion size, degree of spontaneous recovery, lesion chronicity, and influence of tissue characteristics are among the variables thought to contribute to behavioral discrepancies in large patient populations receiving neurostimulation treatment (Wagner et al., 2007; Plow RG7204 cost et al., 2009). Furthermore, in order to preserve patient safety, the number of consecutive TMS sessions are restricted, yet research performed in healthy subjects has demonstrated that the accumulation of sessions might be key to enhancing rTMS efficacy (Maeda et al., 2002; Bäumer et al., 2003; Valero-Cabré et al.,

2008). Suppressive rTMS sessions not exceeding ten applications on the intact hemisphere have yielded enhancements in function which are Rapamycin purchase probably still present weeks after the end of the treatment (Avenanti et al., 2012; Koch et al., 2012). However, the therapeutic potential of high-frequency perilesional rTMS in repeated sessions has yet to be consistently assessed in detail. We hereby hypothesized that a very high number of consecutive rTMS sessions applied to lesion-adjacent cortex could maximize functional recovery well beyond spontaneous recovery levels in the chronic phase following focal brain damage. To freely address our hypothesis, we turned to a well-established animal model of visuospatial disorders. We induced focal unilateral lesions in a subregion of the feline posterior parietal cortex, specifically known as the posterior middle suprasylvian area (pMS), leading to enduring visuospatial deficits in the contralesional hemispace (Huxlin & Pasternak, 2004; Rushmore et al., 2010; Das et al., 2012). Subjects were followed for ~2.5 months post-lesion, which was the time required to consistently reach plateau levels of spontaneous recovery. Animals were then treated for 3.