This retrospective study aimed to predict the clinical efficacy of rTMS in PD based on the ALFF and fALFF values in WM. The results showed that the change in UPDRSIII score was correlated with various WM regions, including the ALFF values of the upper right corticospinal tract, the upper left corticospinal tract, the right superior longitudinal fasciculus, the lower right corticospinal tract, the lower left corticospinal tract, and the left superior longitudinal fasciculus and the fALFF values of the left anterior thalamic radiations and the right anterior thalamic radiations. Moreover, a classification framework combining ALFF and fALFF values in WM can effectively distinguish the efficacy of rTMS in PD patients. The functional differences in WM can provide valuable insights into the respondence of rTMS in PD and contribute to our understanding of the underlying mechanisms of the disease.
Our findings suggested that the respondence of TMS in PD patients may be influenced by abnormal WM function. Multimodal MRI studies on PD mice showed that WM damage in mice was manifested by decreased anisotropy fractions in the corpus callosum and substantia nigra [27]. MRI studies have found a significant association between rigidity and myelin degeneration in PD patients [28]. A meta-analysis has demonstrated that disease severity (UPDRSIII score) had a positive effect on the left superior frontal gyrus and a negative effect on the right anterior central gyrus, corpus callosum, right middle temporal gyrus, right striatum, and left upper longitudinal tract [29]. The respondences of TMS on subcortical activity depends on the structural integrity of the brain [30]. In conclusion, WM can be used as a predictor of rTMS efficacy.
While rTMS does not directly target the WM fiber bundles, its respondences can indirectly impact these connectivity pathways. By modulating neural activity in specific cortical regions, TMS can influence the functional connectivity between different brain areas, including those connected by WM pathways. The corticospinal tract begins in the cerebral cortex and terminates in the GM of the spinal cord, governing the voluntary movement of skeletal muscles. Studies of regional and network characteristics of WM function showed that the structure-function coupling of the left corticospinal tract was reduced in PD patients compared with the control group. Previous studies have demonstrated that the FA of the corticospinal tract in PD patients was higher [8]. It has been reported that the FA of the corticospinal tract in the responsive group was lower than in the non-responsive group in levodopa challenge test [31]. Our results showed that the ALFF value of the upper right corticospinal tract in the R group was higher than that in the NR group, and the ALFF value of the lower right corticospinal tract was lower than that in the R group, which may be the result of compensatory activation of the upper corticospinal tract [32]. The superior longitudinal tract is the connecting fiber bundle of the brain hemisphere, connecting the frontal, occipital, and temporal lobes of the brain hemisphere. Damage to this tract can result in impaired motor preparation, which could affect the ability to initiate movement, as well as visuospatial processing [33]. The forceps major is a sickle-shaped fold of the dura that splits from the median line of the cranial roof between the two hemispheres of the brain. The anterior thalamic radiation is the main outflow tract of the thalamus, connecting the dorsomedial thalamic nucleus with the frontal cortex and the anterior thalamic nucleus with the anterior cingulate cortex. Previous studies have found that compared with healthy controls, PD patients with postural instability gait disorder had changes in the upper longitudinal tract, lower longitudinal tract, anterior thalamic radiation, the knee of the corpus callosum, and the corpus callosum [34]. Therefore, the corticospinal tract, upper longitudinal tract, and thalamic radiation tract are important WM tracts in PD patients.
The respondence of TMS in PD patients is likely to be related to WM. Studies have shown that PD patients already have motor cortex and WM tract abnormalities before diagnosis [8]. PD patients with medicine show a change in the responsiveness of the corticocortical circuit [35]. Previous studies have found that after TMS intervention, the pallidum of PD patients becomes larger [2]. Thalamotomy can leave the WM structure intact in PD [36]. Based on our study, the combination of the ALFF values of the upper right corticospinal tract and the lower right corticospinal tract and the fALFF values of the left anterior thalamic radiations and the right anterior thalamic radiations can predict the respondence of TMS on UPDRSIII improvement.
Certainly, it is important to acknowledge some limitations of this study. First, the comparison of WM in PD patients before and after rTMS intervention was not conducted, which could provide valuable insights into the respondences of TMS on WM. Further analyses and investigations are needed to explore these potential changes. Second, cognitive changes were not assessed throughout the study. Previous research has established a connection between WM and cognition, so it would be beneficial to examine any cognitive changes following treatment with TMS [37]. This could contribute to a more comprehensive understanding of the respondences of TMS on PD patients. Last, the sample size in this study was relatively small, which may limit the generalizability of the findings. Increasing the sample size in future studies would help to obtain more reliable and unbiased results. Overall, while this study provided valuable insights into the relationship between ALFF and fALFF values in WM and the treatment response in PD patients, it is crucial to consider these limitations and conduct further research to validate the findings and address the unanswered questions.
In conclusion, we observed significant differences between the R group and the NR group in terms of ALFF and fALFF values in various WM tracts. These ALFF and fALFF values in specific WM tracts were associated with changes in the UPDRSIII score. Furthermore, we developed a classification framework using ALFF and fALFF values in WM, which effectively distinguished between high and low efficacy of rTMS in patients with PD. This suggested that ALFF and fALFF values in WM can potentially be used as predictors of the efficacy of TMS in patients with PD.