It is proposed that people with a greater predisposition to develop AUD have alterations in executive functions, due to maladaptive cellular homeostatic processes and neuronal circuits stimulated by substances, and that these alterations persist even after the withdrawal of the substance (Nestler and Aghajanian, 1997). Also as a multifactorial disorder, it has been considered the implication of family history of consumption (Khemiri et al., 2020; Peterson et al., 1990 \& Tarter et al., 1989) and individual traits, like poor performance on a cognitive test compared to controls, (Shnitko et al., 2018 \& Goudriaan et al., 2011) as a predictor to develop heavy alcohol consumption or AUD. The alteration in executive functions seems to manifest with the perseverance of negative behaviors that prevent new forms of learning and adaptation to situations, and the decrease in the activation of the executive control network, which is correlated with the severity of the AUD (Mayhugh et al., 2014). One executive function that may be related to AUD and treatment success is cognitive flexibility, whose role is to allow thoughts and behaviors to be appropriately adjusted in response to environmental cognitive demands (Uddin., 2021). Studies have shown that the persistence and severity of AUD have been related to impaired cognitive flexibility (Stalnaker et al., 2008), and it is recovered after prolonged alcohol abstinence (Rourke \& Grant, 1999). Therefore, cognitive flexibility may be a treatment biomarker worth exploring. According to a review by McLellan et al. (2000), 40 to 60 % of the patients who are treated for AUD relapse before the first year of follow-up after discharge. At least 60% of those treated for an AUD will relapse within 6 months of treatment (Durazzo and Meyerhoff, 2017; Kirshenbaum et al., 2009; Maisto et al., 2006a; Meyerhoff and Durazzo, 2010). It is for this reason that new treatments are still being sought in addition to standard pharmacological and psychotherapeutic treatments, where non-invasive neuromodulation techniques such as repetitive transcranial magnetic stimulation (rTMS) have shown promising results (Diana et al., 2017).

The Food and Drug Administration (FDA) in 2020 approved the use of rTMS as a therapeutic option for nicotine use disorder, but not for AUD in which positive changes have been found. For example, Addolorato et al., (2017) used high frequency (10 Hz) rTMS in areas of the dorsolateral prefrontal cortex (DLPFC) in humans with AUD and found a reduction in alcohol consumption and an increase in the number of days of drinking abstinence. It has been found that rTMS on the left DLPC increased inhibitory control and selective attention, and reduced depressive and somatization features, in subjects with active alcohol consumption (Del Felice et al., 2016). Since DLPFC is an important region of the executive control network, rTMS in this region in patients with AUD could induce an increase in functional connectivity of this network and consequently increase cognitive flexibility. About the effects of rTMS on cognitive functions, it was found to increase inhibitory control and selective attention (Del Felice et al., 2016, Diana et al., 2017). For all the above, we proposed to conduct a longitudinal study that will assess the cognitive and behavioral characteristics of people with a history of AUD that could play in the first place a crucial part to have developed the disorder. And the effects of TMS on this population, using the non-invasive technique of MRI and the neuropsychological tool to assess the cognitive and behavioral effects.

The aim of this study is to investigate the short- and long-term clinical and cognitive effects of repetitive transcranial magnetic stimulation (rTMS) at a frequency of 10 Hz on the left dorsolateral prefrontal cortex in patients with alcohol use disorder in abstinence and to examine possible changes in brain structure and functional connectivity associated with this intervention. To do this, the investigators will recruit alcohol-dependent patients and stimulate them by rTMS twice daily for 4 weeks. The investigators will follow the patients to determine clinical outcomes at 6 months. The investigators will also measure clinical, cognitive, structural, and functional brain connectivity to assess short- and long-term intervention-related changes (measurements at baseline, 4 weeks, and 6 months).