*Article* **Abnormal Dorsal Caudate Activation Mediated Impaired Cognitive Flexibility in Mild Traumatic Brain Injury**

**Hui Xu 1,2,\*, Xiuping Zhang <sup>3</sup> and Guanghui Bai 1,4,\***


**Abstract:** Background: Mild traumatic brain injury (mTBI) is an important but less recognized public health concern. Previous studies have demonstrated that patients with mTBI have impaired executive function, which disrupts the performance of daily activities. Few studies have investigated neural mechanisms of cognitive flexibility in mTBI patients using objective tools such as the psychological experiment paradigm. Here, we aimed to examine neural correlates of cognitive flexibility in mTBI. Methods: Sixteen mTBI patients and seventeen matched healthy controls (HCs) underwent functional MRI during a rule-based task-switching experimental paradigm. Linear models were used to obtain within-group activation maps and areas of differential activation between the groups. In addition, we conducted mediation analyses to evaluate the indirect effect of abnormal dorsal caudate activation on the association between information processing speed and cognitive flexibility in mTBI. Results: mTBI patients exhibited significantly longer reaction time in the task switching (TS) condition compared to HCs, reflecting impaired cognitive flexibility. In addition, the patients showed reduced activation in the dorsal caudate (dCau), anterior cingulate cortex, and other frontal regions during the TS condition. Mediation analysis revealed that the reduced dCau activation had a significant effect on the relationship between information processing speed and cognitive flexibility in mTBI. Conclusions: Abnormal dorsal caudate activation in mTBI mediates impaired cognitive flexibility, which indicated dorsal caudate might be playing a vital role in the cognitive flexibility of mTBI patients. These findings highlight an alternative target for clinical interventions for the improvement of cognitive functions in mTBI.

**Keywords:** mild traumatic brain injury; functional MRI; cognitive flexibility; task switching; dorsal caudate
