Cortical and subcortical microstructure integrity changes after repetitive transcranial magnetic stimulation therapy in cocaine use disorder and relates to clinical outcomes.

Cocaine use disorder (CUD) is a worldwide public health condition that is suggested to induce pathological changes in macrostructure and microstructure. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as a potential treatment for CUD symptoms. Here, we sought to elucidate whether rTMS induces changes in white matter (WM) microstructure in frontostriatal circuits after 2 weeks of therapy in patients with CUD and to test whether baseline WM microstructure of the same circuits affects clinical improvement. This study consisted of a 2-week, parallel-group, double-blind, randomized controlled clinical trial (acute phase) (sham [n = 23] and active [n = 27]), in which patients received two daily sessions of rTMS on the left dorsolateral prefrontal cortex (lDLPFC) as an add-on treatment. T1-weighted and high angular resolution diffusion-weighted imaging (DWI-HARDI) at baseline and 2 weeks after served to evaluate WM microstructure. After active rTMS, results showed a significant increase in neurite density compared with sham rTMS in WM tracts connecting lDLPFC with left and right ventromedial prefrontal cortex (vmPFC). Similarly, rTMS showed a reduction in orientation dispersion in WM tracts connecting lDLPFC with the left caudate nucleus, left thalamus, and left vmPFC. Results also showed a greater reduction in craving Visual Analogue Scale (VAS) after rTMS when baseline intra-cellular volume fraction (ICVF) was low in WM tracts connecting left caudate nucleus with substantia nigra and left pallidum, as well as left thalamus with substantia nigra and left pallidum. Our results evidence rTMS-induced WM microstructural changes in fronto-striato-thalamic circuits and support its efficacy as a therapeutic tool in treating CUD. Further, individual clinical improvement may rely on the patient's individual structural connectivity integrity.

Sunlight exposure exerts immunomodulatory effects to reduce multiple sclerosis severity.

Multiple sclerosis (MS) disease risk is associated with reduced sun-exposure. This study assessed the relationship between measures of sun exposure (vitamin D [vitD], latitude) and MS severity in the setting of two multicenter cohort studies (nNationMS = 946, nBIONAT = 990). Additionally, effect-modification by medication and photosensitivity-associated MC1R variants was assessed. High serum vitD was associated with a reduced MS severity score (MSSS), reduced risk for relapses, and lower disability accumulation over time. Low latitude was associated with higher vitD, lower MSSS, fewer gadolinium-enhancing lesions, and lower disability accumulation. The association of latitude with disability was lacking in IFN-ß-treated patients. In carriers of MC1R:rs1805008(T), who reported increased sensitivity toward sunlight, lower latitude was associated with higher MRI activity, whereas for noncarriers there was less MRI activity at lower latitudes. In a further exploratory approach, the effect of ultraviolet (UV)-phototherapy on the transcriptome of immune cells of MS patients was assessed using samples from an earlier study. Phototherapy induced a vitD and type I IFN signature that was most apparent in monocytes but that could also be detected in B and T cells. In summary, our study suggests beneficial effects of sun exposure on established MS, as demonstrated by a correlative network between the three factors: Latitude, vitD, and disease severity. However, sun exposure might be detrimental for photosensitive patients. Furthermore, a direct induction of type I IFNs through sun exposure could be another mechanism of UV-mediated immune-modulation in MS.