The purpose of this study was to clarify whether SLF damage was associated with working memory impairments, and whether occupational experience, considered as a component of CR, predicted working memory after tumor resection in patients with frontal lobe lesions. Working memory was estimated using the digit span backward, tapping span backward, verbal 2-back, and spatial 2-back tasks, and the level of cognitive activity in the patients' main occupation was assessed using the occupational complexity index. In this study, we showed that a larger disconnection ratio of SLFs was significantly associated with lower working memory performance, and that occupational complexity scores significantly predicted working memory after tumor resection. Furthermore, we found that the occupational complexity “data” domain predicts verbal working memory scores. In recent years, the effects of CR have been investigated not only in dementia or aging, but also in a broader range of disorders, such as traumatic brain injury and stroke,,; however, no study had focused on occupational complexity as a CR in patients with frontal lobe tumors. To our knowledge, this is the first study to demonstrate that occupational complexity, as a CR, predicts working memory after tumor resection in patients with frontal lobe tumors.
To investigate the relationship between damage to the fronto-parietal networks and working memory after brain tumor resection, we analyzed the relationships between the disconnection ratio of the SLFs I, II, and III and working memory scores. The results of correlation analysis showed that SLFs’ disconnection ratio was significantly associated with working memory. Although spatial 2-back task scores were not significantly associated with SLFs’ disconnection ratio, an overall negative association was observed. In particular, a higher disconnection ratio of the right SLF I was associated with lower rates of correct responses in the spatial 2-back task (Supplementary Table 1). On the other hand, the significant negative associations between tapping span backward scores and the disconnection ratio of the left SLF II were unexpected, since visuospatial information processing has been considered to localize mainly in the right hemisphere. However, previous studies indicated that visuospatial working memory tasks recruited activation within broader areas, including the bilateral white matter networks,. Therefore, our finding of negative associations between tapping span backward scores and the left SLF disconnection ratio is consistent with these reports.
We showed that higher occupational complexity is associated with higher verbal working memory after tumor resection. Previous studies in patients with brain lesions have shown that CR proxies, such as premorbid IQ and education, were associated with neuropsychological outcomes, including working memory,. Furthermore, among the three domains of occupational complexity, scores of the “data” domain predicted verbal working memory scores. These results are consistent with previous studies showing that higher levels of occupational complexity, especially in the “data” domain, were associated with higher cognitive function, including working memory, in healthy participants,.
Our findings that “people” and “things” occupational complexity were not significantly associated with working memory were unexpected. One possible explanation is that since the included patients belonged to a wide range of ages, we did not consider the tie that participants engaged in their primary occupation. In a previous study, for individuals whose principal occupation duration was > 23 years, “people” or “things” were associated with a lower risk of dementia. Occupation duration may also be an important factor affecting CR. Further studies considering occupation duration are needed to investigate the effects of CR on occupational complexity.
The present study showed no significant association between occupational complexity and spatial working memory, including the tapping span backward and spatial 2-back tasks. This result can be explained by the feature of functional compensation, considered as one of the mechanisms governing the protective effect of CR. Functional compensation refers to recruiting alternative neural networks in order to cope with brain pathology. This compensation is related to brain anatomy, which leads to dynamic, redistributable, and reorganizable neural networks. A study focusing on compensation in CR found that individuals with high white matter hyperintensities and high education levels (i.e. individuals with larger brain damage and higher CR) compensatively recruited broader areas, including the putamen and thalamus, in addition to the fronto-parietal network, during working memory tasks. In the study of gliomas, the functional compensatory capacity has been shown to differ between cortical and subcortical regions, wherein white matter tracts experienced lower functional compensation than cortical areas. In addition, a previous study reported that right SLF I and II damage led to chronic impairments in spatial working memory. In our study, the disconnectome maps showed that the right SLF I and II were particularly damaged. Considering these findings, CR may not play a protective role by compensation if white matter tracts, such as SLFs, are damaged. With respect to verbal working memory, in addition to the DLPFC, the superior temporal gyrus and middle temporal gyrus, are highly compensatory regions, are also involved verbal working memory,,,. Therefore, regarding the verbal working memory of patients with frontal lobe tumors, patients with higher CR can better cope with the decline in verbal working memory by using these highly compensatory networks, even if fronto-parietal networks are damaged. To elucidate the mechanism of CR in brain tumor patients, further studies are needed to clarify which neural networks are actually used as compensatory mechanisms.
The present study has several limitations. First, we did not include patients with severe brain lesions in this study. Thus, it is unclear whether occupational complexity as CR index affects working memory after tumor resection in patients with more severe lesions and cognitive impairment. Second, the sample size was relatively small, and the statistical power low. Overall, our results were consistent with previous studies; however, further investigation with an increased sample size is needed. Third, since this study is a cross-sectional study using data after tumor resection, we were not able to investigate changes in working memory before and after surgery. Therefore, further studies focusing on changes of working memory from preoperative to postoperative conditions are needed to clarify the protective effects of occupational complexity. Lastly, the present study has shown that patients engaged in occupations with higher complexity suffer less working memory impairments after tumor resection; however, the neural mechanisms underlying the protective effects of occupational complexity have not been elucidated. In patients with high levels of occupational complexity, it is unclear which compensatory brain areas are utilized to cope with working memory decline. To clinically apply CR in the future, further research elucidating the neural mechanisms of CR in patients with brain tumors is essential.