*Article* **Neurological Music Therapy Rebuilds Structural Connectome after Traumatic Brain Injury: Secondary Analysis from a Randomized Controlled Trial**

**Aleksi J. Sihvonen 1,2,3,\*, Sini-Tuuli Siponkoski 1,2, Noelia Martínez-Molina 1,2, Sari Laitinen 2,4, Milla Holma 5, Mirja Ahlfors 6, Linda Kuusela 7,8, Johanna Pekkola 8, Sanna Koskinen <sup>9</sup> and Teppo Särkämö 1,2**


**Abstract:** Background: Traumatic brain injury (TBI) is a common and devastating neurological condition, associated often with poor functional outcome and deficits in executive function. Due to the neuropathology of TBI, neuroimaging plays a crucial role in its assessment, and while diffusion MRI has been proposed as a sensitive biomarker, longitudinal studies evaluating treatment-related diffusion MRI changes are scarce. Recent evidence suggests that neurological music therapy can improve executive functions in patients with TBI and that these effects are underpinned by neuroplasticity changes in the brain. However, studies evaluating music therapy induced structural connectome changes in patients with TBI are lacking. Design: Single-blind crossover (AB/BA) randomized controlled trial (NCT01956136). Objective: Here, we report secondary outcomes of the trial and set out to assess the effect of neurological music therapy on structural white matter connectome changes and their association with improved execute function in patients with TBI. Methods: Using an AB/BA design, 25 patients with moderate or severe TBI were randomized to receive a 3-month neurological music therapy intervention either during the first (AB, *n* = 16) or second (BA, *n* = 9) half of a 6-month follow-up period. Neuropsychological testing and diffusion MRI scans were performed at baseline and at the 3-month and 6-month stage. Findings: Compared to the control group, the music therapy group increased quantitative anisotropy (QA) in the right dorsal pathways (arcuate fasciculus, superior longitudinal fasciculus) and in the corpus callosum and the right frontal aslant tract, thalamic radiation and corticostriatal tracts. The mean increased QA in this network of results correlated with improved executive function. Conclusions: This study shows that music therapy can induce structural white matter neuroplasticity in the post-TBI brain that underpins improved executive function.

**Keywords:** music therapy; traumatic brain injury; TBI; executive function; rehabilitation; structural connectivity; connectometry; DTI
