J Neurosci Res. 2021;00:1–17. wileyonlinelibrary.com/journal/jnr | 1 © 2021 Wiley Periodicals LLC 1 | INTRODUCTION Knowledge about the health-promoting and well-being enhanc- ing power of meditative practices has a long history, with great examples in the Buddhist tradition of mindfulness meditation and of Hatha Yoga (Chiesa & Serretti, 2009). Although derived from religious contexts, meditation was includedamong psycho- therapeutic approaches around 30 years ago, as a self-regulation strategy applied in treatment programs for mental health (Kabat-Zinn, 1982). Initially defined as the “Stress Reduction and Relaxation Program” protocol (Kabat-Zinn et al., 1985) and sub- sequently modified and renamed as “Mindfulness-Based Stress Reduction” (MBSR) (Kabat-Zinn et al., 1992), MBSR represents an attempt to integrate mindfulness meditation practices and Hatha Yoga stretching exercises into a standardized training, with poten- tial application in both medical and psychological clinical practice (Chiesa & Serretti, 2009; Kabat-Zinn et al., 1985). MBSR has been shown to be effective in reducing symptoms in various psychiatric Received: 8 December 2020 | Accepted: 15 December 2020 DOI: 10.1002/jnr.24798 RESEARCH ARTICLE Mindfulness-based stress reduction training modulates striatal and cerebellar connectivity Emiliano Santarnecchi 1 | Eutizio Egiziano 2 | Sicilia D’Arista 2 | Concetta Gardi 3 | Sara M. Romanella 4 | Lucia Mencarelli 1,4 | Simone Rossi 2,3,4,5 | Mario Reda 2 | Alessandro Rossi 4 Edited by Sandra Chanraud and Junie Warrington. Reviewed by Majd Abdallah and Nicolas Farrugia. 1 Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA 2 Department of Neurological, Neurosurgical and Behavioral Sciences, University of Siena, Siena, Italy 3 Department of Molecular and Developmental Medicine, University of Siena, Siena, Italy 4 Siena Brain Investigation and Neuromodulation Laboratory (SiBIN-Lab), Department of Medicine, Surgery and Neuroscience, Unit of Neurology and Clinical Neurophysiology, Siena Medical School, Siena, Italy 5 Department of Medicine, Surgery and Neuroscience, Human Physiology Section, Siena Medical School, Siena, Italy Correspondence Emiliano Santarnecchi, Berenson-Allen Center for Noninvasive Brain Stimulation, Division of Cognitive Neurology, Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, KS-450, Boston, MA 02215, USA. Email: esantarn@bidmc.harvard.edu Abstract Mindfulness is a meditation practice frequently associated with changes in subjec- tive evaluation of cognitive and sensorial experience, as well as with modifications of brain activity and morphometry. Aside from the anatomical localization of functional changes induced by mindfulness practice, little is known about changes in functional and effective functional magnetic resonance imaging (fMRI) connectivity. Here we performed a connectivity fMRI analysis in a group of healthy individuals participating in an 8-week mindfulness-based stress reduction (MBSR) training program. Data from both a “mind-wandering” and a “meditation” state were acquired before and after the MBSR course. Results highlighted decreased local connectivity after training in the right anterior putamen and insula during spontaneous mind-wandering and the right cerebellum during the meditative state. A further effective connectivity analysis re- vealed (a) decreased modulation by the anterior cingulate cortex over the anterior portion of the putamen, and (b) a change in left and right posterior putamen excita- tory input and inhibitory output with the cerebellum, respectively. Results suggest a rearrangement of dorsal striatum functional and effective connectivity in response to mindfulness practice, with changes in cortico-subcortical-cerebellar modulatory dynamics. Findings might be relevant for the understanding of widely documented mindfulness behavioral effects, especially those related to pain perception. KEYWORDS brain connectivity, MBSR, meditation, mindfulness, putamen