Altered motor cortical plasticity in patients with hepatic encephalopathy: A paired associative stimulation study.

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. CONCLUSIONS: 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.

Altered neuronal response during rapid auditory processing and its relation to phonological processing in prereading children at familial risk for dyslexia.

Developmental dyslexia (DD) is a learning disability affecting 5-17% of children. Although researchers agree that DD is characterized by deficient phonological processing (PP), its cause is debated. It has been suggested that altered rapid auditory processing (RAP) may lead to deficient PP in DD and studies have shown deficient RAP in individuals with DD. Functional neuroimaging (fMRI) studies have implicated hypoactivations in left prefrontal brain regions during RAP in individuals with DD. When and how these neuronal alterations evolve remains unknown. In this article, we investigate functional networks during RAP in 28 children with (n = 14) and without (n = 14) a familial risk for DD before reading onset (mean: 5.6 years). Results reveal functional alterations in left-hemispheric prefrontal regions during RAP in prereading children at risk for DD, similar to findings in individuals with DD. Furthermore, activation during RAP in left prefrontal regions positively correlates with prereading measures of PP and with neuronal activation during PP in posterior dorsal and ventral brain areas. Our results suggest that neuronal differences during RAP predate reading instruction and thus are not due to experience-dependent brain changes resulting from DD itself and that there is a functional relationship between neuronal networks for RAP and PP within the prereading brain.