Multi-modal Neuroimaging Can Identify Brain And Trigeminal Abnormalities In Classical Trigeminal Neuralgia

Classical trigeminal neuralgia(TN)is a severe neuropathic facial pain disorder.As the disorder progresses,pain may become frequent and sustained,thereby increasing the risk of anxiety and depression and substantially diminishing the quality of life.TN is commonly associated with pathological factors of axonopathy and demyelination resulting from neurovascular compression at the trigeminal root entry zone(REZ).Chronic pain,including TN,is maladaptive for the brain structure and function.The close relationship between chronic pain and mental disorders indicates that brain dysfunction plays a central role in the development and maintenance of chronic pain including TN.Using multimodal MRI,we intend to explore the trigeminal microarchitecture changes and structural and functional deficits of the brain in TN patients,which may provide novel insights into the pathophysiology of TN.Diffusion tensor imaging of trigeminal microarchitecture in TN patients.TN is commonly resulted from neurovascular compression at the trigeminal REZ.We used diffusion tensor imaging(DTI)to capture the full extent of trigeminal microarchitecture changes in vivo in TN patients.We have found that the DTI-derived metrics can detect the trigeminal axonal and myelin abnormalities as well as time-dependent reversal following effective decompression surgery in TN patients.Structural and functional alterations of brain in TN patients.TN patients is often associated with an increased tendency toward depression and anxiety.The pathophysiologic mechanism underpinning the comorbidity of chronic pain and mental disorders remains unclear.In this study,we used multimodal MRI to explore the structural and functional brain deficits in TN patients.Reduced gray matter volumes in the bilateral amygdala,periaqueductal gray and right insula were found in TN patients compared with healthy control subjects.The functional connectivity of amygdala with medial prefrontal cortex,dorsolateral prefrontal cortex and thalamus/putamen was also significantly altered in TN patients.Further longitudinal analysis found that the functional abnormalities in amygdala-related circuits were resolved after pain relief.Together,structural and functional deficits in pain-related and emotion-related networks were associated with TN patients,as demonstrated by our multimodal results.Pain relief had protective effects on brain functional connectivity within amygdala-related circuits.How TN disturbs the cortical rhythms and associated brain functional connectivity are unknown.We studied the frequency-specific alterations in intrinsic brain oscillations in TN patients,and found TN patients were accompanied by abnormal oscillation dynamics of intrinsic brain activity exclusively in the frequency of the slow-5 band(0.01-0.027 Hz).In turn,the change in the oscillatory properties is coupled with altered functional circuits with nodes including key components of the default mode network.Taken together,these results provide insights into how classic TN disrupts the cortical rhythms and cross-network interactions of the brain.Abnormalities in infra-slow fluctuations and their connectivity mirror abnormal slow wave propagation of neuronal activity and related learning processes that contribute to abnormal routing of cerebral information flow in chronic pain.These insights may have implications for the understanding and treatment of brain dysfunction in chronic pain patients,including TN patients.Finally,we used connectome-based methods and graph-based network analysis to systematically investigate the alterations in the topological organization of whole-brain functional networks in TN patients.Both TN patients and controls exhibited efficient small-world properties in their functional networks.Compared with controls,TN patients showed decreased function of local specialization.We also found altered node and connectivity attributes of the brain connectome,mainly in the default mode network,somatomotor network,salience network and limbic network.The topological aberrations correlated with the sensory and negative emotional valence in chronic pain patients including TN.