Paired associative stimulation demonstrates alterations in motor cortical synaptic plasticity in patients with hepatic encephalopathy

TL;DR

This study used paired associative stimulation to demonstrate that patients with hepatic encephalopathy exhibit impaired motor cortex synaptic plasticity, linking molecular disturbances to clinical symptoms.

Contribution

It is the first to show reduced synaptic plasticity in the motor cortex of HE patients using PAS25 TMS protocol.

Findings

Healthy controls showed increased MEP amplitudes after PAS25.

HE patients did not show MEP amplitude increase, indicating impaired plasticity.

Reduced plasticity may be linked to glutamatergic disturbances in HE.

Abstract

Objective: Hepatic encephalopathy (HE) is a potentially reversible brain dysfunction caused by liver failure. Altered synaptic plasticity is supposed to play a major role in the pathophysiology of HE. Here, we used paired associative stimulation with an inter-stimulus interval of 25 ms (PAS25), a transcranial magnetic stimulation (TMS) protocol, to test synaptic plasticity of the motor cortex in patients with manifest HE. Methods: 23 HE-patients and 23 healthy controls were enrolled in the study. Motor evoked potential (MEP) amplitudes were assessed as measure for cortical excitability. Time courses of MEP amplitude changes after the PAS25 intervention were compared between both groups. Results: MEP-amplitudes increased after PAS25 in the control group, indicating PAS25-induced synaptic plasticity in healthy controls, as expected. In contrast, MEP-amplitudes within the HE group did not change and were lower than in the control group, indicating no induction of plasticity. Conclusion: Our study revealed reduced synaptic plasticity of the primary motor cortex in HE. Significance: Reduced synaptic plasticity in HE provides a link between pathological changes on the molecular level and early clinical symptoms of the disease. This decrease may be caused by disturbances in the glutamatergic neurotransmission due to the known hyperammonemia in HE patients.