Treatment effects of N-acetyl cysteine on resting-state functional MRI and cognitive performance in patients with chronic mild traumatic brain injury: a longitudinal study

Mild traumatic brain injury (mTBI) is a significant public health concern, specially characterized by a complex pattern of abnormal neural activity and functional connectivity. It is often associated with a broad spectrum of short-term and long-term cognitive and behavioral symptoms including memory dysfunction, headache, and balance difficulties. Furthermore, there is evidence that oxidative stress significantly contributes to these symptoms and neurophysiological changes. The purpose of this study was to assess the effect of N-acetylcysteine (NAC) on brain function and chronic symptoms in mTBI patients. Fifty patients diagnosed with chronic mTBI participated in this study. They were categorized into two groups including controls (CN, n = 25), and patients receiving treatment with N-acetyl cysteine (NAC, n = 25). NAC group received 50 mg/kg intravenous (IV) medication once a day per week. In the rest of the week, they took one 500 mg NAC tablet twice per day. Each patient underwent rs-fMRI scanning at two timepoints including the baseline and 3 months later at follow-up, while the NAC group received a combination of oral and IV NAC over that time. Three rs-fMRI metrics were measured including fractional amplitude of low frequency fluctuations (fALFF), degree centrality (DC), and functional connectivity strength (FCS). Neuropsychological tests were also assessed at the same day of scanning for each patient. The alteration of rs-fMRI metrics and cognitive scores were measured over 3 months treatment with NAC. Then, the correlation analysis was executed to estimate the association of rs-fMRI measurements and cognitive performance over 3 months (p < 0.05). Two significant group-by-time effects demonstrated the changes of rs-fMRI metrics particularly in the regions located in the default mode network (DMN), sensorimotor network, and emotional circuits that were significantly correlated with cognitive function recovery over 3 months treatment with NAC (p < 0.05). NAC appears to modulate neural activity and functional connectivity in specific brain networks, and these changes could account for clinical improvement. This study confirmed the short-term therapeutic efficacy of NAC in chronic mTBI patients that may contribute to understanding of neurophysiological effects of NAC in mTBI. These findings encourage further research on long-term neurobehavioral assessment of NAC assisting development of therapeutic plans in mTBI.