Purpose: The purpose of this systematic review is to evaluate motor cortex reorganization in amputees as indexed by transcranial magnetic stimulation (TMS) cortical mapping and its relationship with phantom limb pain (PLP). Methods: Pubmed database were systematically searched. Three independent researchers screened the relevant articles, and the data of motor output maps, including the number of effective stimulation sites, center of gravity (CoG) shift, and their clinical correlations were extracted. We calculated a pooled CoG shift for motor cortex TMS mapping. Results: The search yielded 468 articles, 11 were included. Three studies performed correlation between the cortical changes and PLP intensity, and only one study compared cortical mapping changes between amputees with pain and without pain. Results showed (i) enlarged excitable area and a shift of CoG of neighboring areas toward the deafferented limb area; (ii) no correlation between motor cortex reorganization and level of pain and (iii) greater cortical reorganization in patients with PLP compared to amputation without pain. Conclusion: Our review supports the evidence for cortical reorganization in the affected hemisphere following an amputation. The motor cortex reorganization could be a potential clinical target for prevention and treatment response of PLP.

Background. Although recent evidence has shown a new role of fluoxetine in motor rehabilitation, results are mixed. We conducted a randomized clinical trial to evaluate whether combining repetitive transcranial magnetic stimulation (rTMS) with fluoxetine increases upper limb motor function in stroke. Methods. Twenty-seven hemiparetic patients within 2 years of ischemic stroke were randomized into 3 groups: Combined (active rTMS + fluoxetine), Fluoxetine (sham rTMS + fluoxetine), or Placebo (sham rTMS + placebo fluoxetine). Participants received 18 sessions of 1-Hz rTMS in the unaffected primary motor cortex and 90 days of fluoxetine (20 mg/d). Motor function was assessed using Jebsen-Taylor Hand Function (JTHF) and Fugl-Meyer Assessment (FMA) scales. Corticospinal excitability was assessed with TMS. Results. After adjusting for time since stroke, there was significantly greater improvement in JTHF in the combined rTMS + fluoxetine group (mean improvement: -214.33 seconds) than in the placebo (-177.98 seconds, P = 0.005) and fluoxetine (-50.16 seconds, P < 0.001) groups. The fluoxetine group had less improvement than placebo on both scales (respectively, JTHF: -50.16 vs -117.98 seconds, P = 0.038; and FMA: 6.72 vs 15.55 points, P = 0.039), suggesting that fluoxetine possibly had detrimental effects. The unaffected hemisphere showed decreased intracortical inhibition in the combined and fluoxetine groups, and increased intracortical facilitation in the fluoxetine group. This facilitation was negatively correlated with motor function improvement (FMA, r2 = -0.398, P = 0.0395). Conclusion. Combined fluoxetine and rTMS treatment leads to better motor function in stroke than fluoxetine alone and placebo. Moreover, fluoxetine leads to smaller improvements than placebo, and fluoxetine's effects on intracortical facilitation suggest a potential diffuse mechanism that may hinder beneficial plasticity on motor recovery.

Chapter 10 introduces the most commonly used non-parametric tests, as well as the appropriate situations for their use. It also examines concepts of sample size, power, and validity when using these tests. In addition, this chapter discusses the major advantages and disadvantages of non-parametric tests, and how they compare to their optimal parametric alternatives. A brief theoretical explanation is provided for the main non-parametric tests, including Wilcoxon Sign Rank, Mann-Whitney, and Kruskal-Wallis. However, the main goal of this chapter is to provide a summary of how to use them correctly. Additionally, the reader will learn how to perform and interpret the output for these tests in statistical softwares (STATA and SPSS).

Chapter 9 provides an introduction to statistical testing,alongside the most common parametric tests. It reviews the basis of hypothesis testing while highlighting important concepts such as chance, bias, and confounding. Additionally, this chapter discusses fundamental topics in basic statistics, including p-value, type I and type II errors, alpha (α‎), beta (β‎), and statistical significance. The reader is taken throughout the basics of the theoretical explanation of t-test, ANOVA and linear regression, together with the indications of appropriate use for each of them. Additionally, the reader will learn how to perform and interpret the output for these tests in statistical softwares (e.g., STATA and SPSS). This chapter also examines the concept of normality and central limit theorem (CLT), and how it applies to the evaluation of data distribution.

Selective serotonin reuptake inhibitors (SSRIs) are currently widely used in the field of the neuromodulation not only because of their anti-depressive effects but also due to their ability to promote plasticity and enhance motor recovery in patients with stroke. Recent studies showed that fluoxetine promotes motor recovery after stroke through its effects on the serotonergic system enhancing motor outputs and facilitating long term potentiation, key factors in motor neural plasticity. However, little is known in regards of the exact mechanisms underlying these effects and several aspects of it remain poorly understood. In this manuscript, we discuss evidence supporting the hypothesis that SSRIs, and in particular fluoxetine, modulate inhibitory pathways, and that this modulation enhances reorganization and reestablishment of excitatory-inhibitory control; these effects play a key role in learning induced plasticity in neural circuits involved in the promotion of motor recovery after stroke. This discussion aims to provide important insights and rationale for the development of novel strategies for stroke motor rehabilitation.