Hepatic encephalopathy is associated with slowed and delayed stimulus-associated somatosensory alpha activity.

OBJECTIVE: Hepatic encephalopathy (HE) is associated with motor symptoms and attentional deficits, which are related to pathologically slowed oscillatory brain activity. Here, potential alterations of oscillatory activity in the somatosensory system were investigated. METHODS: 21 patients with liver cirrhosis and varying HE severity and 7 control subjects received electrical stimulation of the right median nerve while brain activity was recorded using magnetoencephalography (MEG). Oscillatory activity within the contralateral primary somatosensory cortex (S1) and its stimulus-induced modulation were analyzed as a function of disease severity. RESULTS: Median nerve stimuli evoked an early broadband power increase followed by suppression and then rebound of S1 alpha and beta activity. Increasing HE severity as quantified by the critical flicker frequency (CFF) was associated with a slowing of the alpha peak frequency and a delay of the alpha rebound. CONCLUSION: The present results provide the first evidence for a slowing of oscillatory activity in the somatosensory system in HE in combination with a previously unknown deficit of S1 in adjusting activation levels back to baseline. SIGNIFICANCE: These findings advance the understanding of the manifold symptoms of HE by strengthening the theory that disease related slowing of oscillatory brain activity also affects the somatosensory system.

Pre- and post-stimulus alpha activity shows differential modulation with spatial attention during the processing of pain.

Extensive work using magneto- and electroencephalography (M/EEG) suggests that cortical alpha activity represents a top-down controlled gating mechanism employed by processes like attention across different modalities. However, it is not yet clear to what extent this presumed gating function of alpha activity also applies to the processing of pain. In the current study, a spatial attention paradigm was employed requiring subjects to attend to painful laser stimuli on one hand while ignoring stimuli on the other hand. Simultaneously, brain activity was recorded with MEG. In order to disentangle pre- and post-stimulus effects of attention, alpha activity was analyzed during time windows in anticipation of and in response to painful laser stimulation. Painful laser stimuli led to a suppression of alpha activity over both ipsi- and contralateral primary somatosensory areas irrespective if they were attended or ignored. Spatial attention was associated with a lateralization of anticipatory pre-stimulus alpha activity. Alpha activity was lower over primary somatosensory areas when the contralateral hand was attended compared to when the ipsilateral hand was attended, in line with the notion that oscillatory alpha activity regulates the flow of incoming information by engaging and/or disengaging early sensory areas. On the contrary, post-stimulus alpha activity, for stimuli on either hand, was consistently decreased with attention over contralateral areas. Most likely, this finding reflects an increased cortical activation and enhanced alerting if a painful stimulus is attended. The present results show that spatial attention results in a modulation of both pre- and post-stimulus alpha activity associated with pain. This flexible regulation of alpha activity matches findings from other modalities. We conclude that the assumed functional role of alpha activity as a top-down controlled gating mechanism includes pain processing and most likely represents a unified mechanism used throughout the brain.

Lowered frequency and impaired modulation of gamma band oscillations in a bimodal attention task are associated with reduced critical flicker frequency.

Visual attention is associated with occipital gamma band activity. While gamma band power can be modulated by attention, the frequency of gamma band activity is known to decrease with age. The present study tested the hypothesis that reduced visual attention is associated with a change in induced gamma band activity. To this end, 26 patients with liver cirrhosis and 8 healthy controls were tested. A subset of patients showed symptoms of hepatic encephalopathy (HE), a frequent neuropsychiatric complication in liver disease, which comprises a gradual increase of cognitive dysfunction including attention deficits. All participants completed a behavioral task requiring shifts of attention between simultaneously presented visual and auditory stimuli. Brain activity was recorded using magnetoencephalography (MEG). The individual critical flicker frequency (CFF) was assessed as it is known to reliably reflect the severity of HE. Results showed correlations of behavioral data and HE severity, as indexed by CFF. Individual visual gamma band peak frequencies correlated positively with the CFF (r=0.41). Only participants with normal, but not with pathological CFF values showed a modulation of gamma band power with attention. The present results suggest that CFF and attentional performance are related. Moreover, a tight relation between the CFF and occipital gamma band activity both in frequency and power is shown. Thus, the present study provides evidence that a reduced CFF in HE, a disease associated with attention deficits, is closely linked to a slowing of gamma band activity and impaired modulation of gamma band power in a bimodal attention task.

IgA-coated particles of Hepatitis A virus are translocalized antivectorially from the apical to the basolateral site of polarized epithelial cells via the polymeric immunoglobulin receptor.

Although Hepatitis A virus (HAV) is transmitted by the faecal-oral route, its target for replication is the liver. Little is known of its interactions with cells of the gastrointestinal tract, and it is not known by which mechanisms HAV crosses the intestinal epithelium. In this study, it is shown that HAV associated with IgA is translocated from the apical to the basolateral compartment of polarized epithelial cells via the polymeric immunoglobulin receptor by IgA-mediated reverse transcytosis. The relevance of this mechanism, by which HAV-IgA complexes may overcome the intestinal barrier and contribute to infections of the liver, results from the fact that HAV-IgA complexes are infectious for hepatocytes and that significant amounts of intestinal HAV-IgA are present during acute infections, which are also partly transmitted. Besides supporting the primary infection, this mechanism may play a role in relapsing infections by establishing an enterohepatic cycle for HAV.