## 4 Discussion  
Here, we investigated the effects of clinical rTMS treatments applied to different psychiatric conditions, both on clinical symptomatology and cognitive domains. Our results suggest that these specific brain stimulations produced amelioration of clinical symptomatology but did not induce any appreciable enhancement of cognitive functioning as a simple effect or in interaction with the diagnosis. Notably, the use of a custom data-driven approach for the statistical analysis allowed us to produce a dimensional characterization of the subjects' profile and to parallelly test the effect of TMS protocols on clinical outcomes and cognitive functioning. Thus, our results do not support the \"global\" hypothesis that TMS protocols lead to symptomatic improvements only through cognitive domain enhancements. This does not necessarily imply that TMS of the areas we stimulated does not produce effects on cognitive domains (as reported by several studies, e.g., [34; 35]),  
Figure 4: **Effect of TMS on DD. ** (**a**) The boxplot shows the values of the subjects’ devaluation coefficient k of DD when the reward is EUR 500 before (PRE) and after (POST) TMS treatment (Chi-sq\({}_{1}\): 1.1765, \(p\) = 0.278). (**b**) The boxplot shows the values of the subjects’ devaluation coefficient k of DD when the reward is EUR 10,000 before and after TMS treatment (Chi-sq\({}_{1}\): 0.1639, \(p\) = 0.685). (Red dots are SUD subjects, blue dots are MDD subjects, green dots are OCD subjects; ns \(p>0.05\)). but rather that these effects do not remain stable over time in the clinical subjects we considered. Important limitations of our study relate to the absence of a sham group, the fact that some subjects were concurrently undergoing psychotherapy and pharmacological treatments, and a possible learning effect due to the repeated administration of tests. However, given that no general cognitive enhancement effect was found, we can affirm that these TMS protocols did not impact the cognitive domain in a broad sense. Regarding MDD, most studies investigating the effect of TMS stimulation on cognitive performance in subjects with major depression did not find cognitive improvements [36], supporting our analysis results. As for TMS clinical pathways in subjects with OCD and SUD, we found no literature references to cognitive enhancement. One hypothesis could be that, by facilitating TMS-induced plasticity phenomena, cognitive remediation interventions should be incorporated into the clinical pathway. For Alzheimer's disease, it has been observed that cognitive enhancement is greater when compared to TMS [35]. In the future, combining TMS and cognitive training could \"boost\" the therapeutic effect of TMS more effectively. It remains uncertain which factors TMS acted on in our protocols to improve clinical symptomatology in a general and nonspecific manner. Considering less \"cold\" psychological domains [15], such as DD, a transdiagnostic factor was impaired in all three pathologies and can be modulated by non-invasive brain stimulation [37]. Other limitations concern the sample size. However, it is possible to find articles in the literature with a similar or even smaller sample size [38; 39; 40; 41; 42]. Furthermore, the statistical analyses are still capable of detecting effects, as in the case of the treatment effect on PC1 and the diagnosis effect on PC2. We can conclude by hypothesizing that cognitive improvement may not be strictly necessary for symptom improvement. It is important to emphasize that our results do not exclude the possibility that cognitive enhancement could be a valid therapeutic strategy for the conditions we treated, but this was not observed in the clinical pathway we analyzed. To create more personalized and effective therapeutic pathways, it is useful to identify the factors and psychological domains on which different stimulation protocols act.