Single-trial neuromagnetic analysis reveals somatosensory dysfunction in chronic Minamata disease

Abstract

Methylmercury pollution is a global problem, and Minamata disease (MD) is a stark reminder that exposure to methylmercury can cause irreversible neurological damage. A "glove and stocking type" sensory disturbance due to injured primary sensory cortex (SI) (central somatosensory disturbance) is the most common neurologic sign in MD. As this sign is also prevalent in those with polyneuropathy, we aimed to develop an objective assessment for detecting central somatosensory disturbances in cases of chronic MD. We selected 289 healthy volunteers and 42 patients with MD. We recorded the sensory nerve action potentials (SNAPs) and somatosensory evoked magnetic fields (SEFs) to median nerve stimulation with magnetoencephalography. Single-trial epochs were classified into three categories (N20m, non-response, and P20m epochs) based on the cross-correlation between averaged sensor SEFs and individual epochs. We assessed SI responses (the appearance rate of P20m [P20m rate] and non-response epochs [non-response rate]) and early somatosensory cortical processing (N20m amplitude, reproducibility of N20m in single-trial responses [cross-correlation value], and induced gamma-band oscillations of the SI [gamma response] of single epochs excluding non-response epochs). Receiver operating characteristic curve analyses were used to examine the diagnostic accuracy of each parameter. We found that SNAPs exerted a marginal effect on the N20m. The N20m amplitude, cross-correlation value, and gamma response were significantly reduced in the MD group on either side (p < 0.0001), suggestive of altered early somatosensory cortical processing. Interestingly, the P20m rate and non-response rate were significantly increased in the MD group on either side (p < 0.0001), thereby suggesting impaired SI responses. Notably, P20m and absent N20m peaks were observed in 6 and 11 patients with MD, respectively, which may be attributed to increased numbers of P20m epochs. The cross-correlation value exhibited the highest correlation with the P20m rate or non-response rate. Thus, reduced reproducibility of N20m may play an important role in chronic MD. The cross-correlation value exhibited the highest correlation with the gamma response for both SI parameters in early somatosensory cortical processing. The area under the curve was > 0.77 (range: 0.77-0.79) for all parameters. Their confidence intervals overlapped with each other; thus, each SEF parameter likely had an approximately equivalent discrimination ability. In conclusion, chronic MD is characterized by impaired SI responses and alterations in early somatosensory cortical processing. Thus, single-trial neuromagnetic analysis of somatosensory function may be useful for detecting central somatosensory disturbance and elucidating the relevant pathophysiological mechanisms even in the context of chronic MD.

Keywords: Central somatosensory disturbance; Magnetoencephalography; Methylmercury poisoning; Minamata disease; Single-trial analysis; Somatosensory function.