Contribution of thalamus-cortex network and cortical habituation mechanisms in multiple sclerosis

OBJECTIVE: Fatigue is one of the most prevalent and debilitating symptoms in individuals with multiple sclerosis (MS). We recorded somatosensory high-frequency oscillatory (HFO) thalamocortical activity in a group of MS patients without history of optic neuritis (ON). Furthermore, we examined if, like what was previously observed in response to visual stimuli, patients exhibit diminished amplitude habituation, and whether this may further exacerbate fatigue in individuals with MS. METHODS: Twenty patients diagnosed with relapsing-remitting MS were prospectively enrolled. The MS cohorts were compared with a cohort of 20 healthy volunteers (HV). Fatigue Severity Scale (FSS) was employed to evaluate the trait levels of reported fatigue. We assessed the N20 somatosensory evoked potentials (SSEPs) parameters and N20-P25 amplitude habituation, and, following the application of a band-pass filter (450-750 Hz), we evaluated electrophysiological parameters of pre- and post-synaptic HFOs. RESULTS: The latency and amplitude of the N20 SSEP and its habituation do not exhibit significant differences between MS patients and HVs. MS patients exhibited delayed latency of negative oscillatory maximum and reduced maximum peak-to-peak amplitude of the pre-synaptic HFOs (all p < 0.01). In patients, post-synaptic HFOs showed a significant delayed latency and a trend towards a reduction in the maximal peak-to-peak amplitude. The pre-synaptic HFO latency of the negative oscillatory maximum, reflecting thalamocortical activity, shows a correlation with the FSS in MS patients (r = 0.522, p = 0.018). No significant ophthalmological anomalies were identified. CONCLUSIONS: Our data revealed a significant reduction and slowing of somatosensory thalamocortical network activity in MS patients without history of ON. Furthermore, our findings showed that fatigue levels may be affected by slowed thalamocortical activity, but not by habituation of cortical responses. SIGNIFICANCE: Our findings suggest a potential role of the thalamo-cortical network on the genesis of MS-related fatigue.