Impaired Tactile Temporal Discrimination in Patients With Hepatic Encephalopathy

The sensory system constantly receives stimuli from the external world. To discriminate two stimuli correctly as two temporally distinct events, the temporal distance or stimulus onset asynchrony (SOA) between the two stimuli has to exceed a specific threshold. If the SOA between two stimuli is shorter than this specific threshold, the two stimuli will be perceptually fused and perceived as one single stimulus. Patients with hepatic encephalopathy (HE) are known to show manifold perceptual impairments, including slowed visual temporal discrimination abilities as measured by the critical flicker frequency (CFF). Here, we hypothesized that HE patients are also impaired in their tactile temporal discrimination abilities and, thus, require a longer SOA between two tactile stimuli to perceive the stimuli as two temporally distinct events. To test this hypothesis, patients with varying grades of HE and age-matched healthy individuals performed a tactile temporal discrimination task. All participants received two tactile stimuli with varying SOA applied to their left index finger and reported how many distinct stimuli they perceived (“1” vs. “2”). HE patients needed a significantly longer SOA (138.0 ± 11.3 ms) between two tactile stimuli to perceive the stimuli as two temporally distinct events than healthy controls (78.6 ± 13.1 ms; p < 0.01). In addition, we found that the temporal discrimination ability in the tactile modality correlated positively with the temporal discrimination ability in the visual domain across all participants (i.e., negative correlation between tactile SOA and visual CFF: r = −0.37, p = 0.033). Our findings provide evidence that temporal tactile perception is substantially impaired in HE patients. In addition, the results suggest that tactile and visual discrimination abilities are affected in HE in parallel. This finding might argue for a common underlying pathophysiological mechanism. We argue that the known global slowing of neuronal oscillations in HE might represent such a common mechanism

Significant reductions in human visual gamma frequency by the GABA reuptake inhibitor tiagabine revealed by robust peak frequency estimation

The frequency of visual gamma oscillations is determined by both the neuronal excitation–inhibition balance and the time constants of GABAergic processes. The gamma peak frequency has been linked to sensory processing, cognitive function, cortical structure, and may have a genetic contribution. To disentangle the intricate relationship among these factors, accurate and reliable estimates of peak frequency are required. Here, a bootstrapping approach that provides estimates of peak frequency reliability, thereby increasing the robustness of the inferences made on this parameter was developed. The method using both simulated data and real data from two previous pharmacological MEG studies of visual gamma with alcohol and tiagabine was validated. In particular, the study by Muthukumaraswamy et al. [2013a] (Neuropsychopharmacology 38(6):1105–1112), in which GABAergic enhancement by tiagabine had previously demonstrated a null effect on visual gamma oscillations, contrasting with strong evidence from both animal models and very recent human studies was re-evaluated. After improved peak frequency estimation and additional exclusion of unreliably measured data, it was found that the GABA reuptake inhibitor tiagabine did produce, as predicted, a marked decrease in visual gamma oscillation frequency. This result demonstrates the potential impact of objective approaches to data quality control, and provides additional translational evidence for the mechanisms of GABAergic transmission generating gamma oscillations in humans

Critical Flicker Fusion Frequency: A Marker of Cerebral Arousal During Modified Gravitational Conditions Related to Parabolic Flights

In situ evaluation of human brain performance and arousal remains challenging during operational circumstances, hence the need for a rapid, reliable and reproducible tool. Here we hypothesized that the Critical flicker fusion frequency (CFFF) reflecting/requiring visual integration, visuo-motor skills and decision-taking process might be a powerful, fast and simple tool in modified gravity environments. Therefore 11 male healthy volunteers were assessed for higher cognitive functions with CFFF during parabolic flights. They were assessed at different time points: upon arrival to the base, 30 min after subcutaneous scopolamine administration, before parabolas, during hypergravity and microgravity at break time (between the 16th and the 17th parabola), on the return flight and on the ground after landing. First, a stable, and consistent measurement of CFFF could be obtained within 12 s. Second, under modified gravitational conditions, the perceptual ability of participants is significantly modified. Compared to the baseline, evolution is characterized by a significant increase of CFFF when in microgravity (0g: 106.9 ± 5.5%), and a significant decrease of CFFF while in hypergravity (2g: 94.5 ± 3.8%). Other time-points were not statistically different from the baseline value. Although the underlying mechanism is still debated, we suggest that the CFFF test is a global marker of cerebral arousal as the result of visuo-motor and decision taking testing based on a simple visual stimulus with an uncomplicated set up that could be used under various environmental conditions. The authors express an opinion that it would be advisable to introduce CFFF measurement during spaceflights as it allows individual longitudinal assessment of individual ability even under conditions of incomplete physiological compensation, as shown here during parabolic flights

Hepatic encephalopathy

Hepatic encephalopathy (HE) is a prognostically relevant neuropsychiatric syndrome that occurs in the course of acute or chronic liver disease. Besides ascites and variceal bleeding, it is the most serious complication of decompensated liver cirrhosis. Ammonia and inflammation are major triggers for the appearance of HE, which in patients with liver cirrhosis involves pathophysiologically low-grade cerebral oedema with oxidative/nitrosative stress, inflammation and disturbances of oscillatory networks in the brain. Severity classification and diagnostic approaches regarding mild forms of HE are still a matter of debate. Current medical treatment predominantly involves lactulose and rifaximin following rigorous treatment of so-called known HE precipitating factors. New treatments based on an improved pathophysiological understanding are emerging

Assessment of Alertness and Cognitive Performance of Closed Circuit Rebreather Divers With the Critical Flicker Fusion Frequency Test in Arctic Diving Conditions

Introduction: Cold water imposes many risks to the diver. These risks include decompression illness, physical and cognitive impairment, and hypothermia. Cognitive impairment can be estimated using a critical flicker fusion frequency (CFFF) test, but this method has only been used in a few studies conducted in an open water environment. We studied the effect of the cold and a helium-containing mixed breathing gas on the cognition of closed circuit rebreather (CCR) divers. Materials and Methods: Twenty-three divers performed an identical dive with controlled trimix gas with a CCR device in an ice-covered quarry. They assessed their thermal comfort at four time points during the dive. In addition, their skin temperature was measured at 5-min intervals throughout the dive. The divers performed the CFFF test before the dive, at target depth, and after the dive. Results: A statistically significant increase of 111.7% in CFFF values was recorded during the dive compared to the pre-dive values (p < 0.0001). The values returned to the baseline after surfacing. There was a significant drop in the divers' skin temperature of 0.48 degrees C every 10 min during the dive (p < 0.001). The divers' subjectively assessed thermal comfort also decreased during the dive (p = 0.01). Conclusion: Our findings showed that neither extreme cold water nor helium-containing mixed breathing gas had any influence on the general CFFF profile described in the previous studies from warmer water and where divers used other breathing gases. We hypothesize that cold-water diving and helium-containing breathing gases do not in these diving conditions cause clinically relevant cerebral impairment. Therefore, we conclude that CCR diving in these conditions is safe from the perspective of alertness and cognitive performance.Peer reviewe

Assessment of Alertness and Cognitive Performance of Closed Circuit Rebreather Divers with the Critical Flicker Fusion Frequency Test in Arctic Diving Conditions

The aim of our study was to research the effect of cold water on the cognition of Finnish technical diving population using the Critical Flicker Fusion Frequency (CFFF) -test. We also studied the effect of breathing gases containing helium on cognition, subjective feeling of cold and on measured temperature of skin. There have not been any CFFF-studies in arctic conditions with a study-setup comparable to ours. Most of the CFFF-studies pertaining to hyperbaric medicine have been conducted in pressure chambers and there are only a handful of studies in open water. 23 subjects performed an identical dive with a controlled trimix gas in an ice- covered water filled quarry. The subjects assessed their thermal comfort at four time points during the dive. In addition, their skin temperature was measured at 5-min intervals throughout the dive. The divers performed the CFFF test before the dive, at target depth, and after the dive. The CFFF-values showed a statistically significant increase to 111.7% during the dive compared to the pre-dive values (p<0.0001). The values returned to pre- dive values after the dive. In previous studies, a similar profile of CFFF-values has been noted. The divers’ skin temperatures showed a statistically significant decrease during the dive (p<0.001). The subjective temperature also decreased during the dive (p=0.01). The results of our study seem to indicate that cold water environment, or breathing gases containing helium have no effect on the profile of the CFFF-values

Investigating human visual processing using MEG and psychophysics

Our visual system organises sensory inputs into coherent object percepts. Knowledge and expectations about objects facilitate perceptual organisation via top-down processing. My PhD set out to investigate the neural mechanisms underpinning this process via frequency-tagging. Frequency-tagging studies embed flickers of different frequencies in a stimulus to drive narrow-band neural responses, which provide indices of spatial integration across the stimulus. My pilot experiments failed to robustly evoke this neural signature of perceptual organisation. Consequently, I conducted the following two lines of research. In a series of MEG studies, I systematically investigated the power of flicker-evoked neural responses as a function of stimulation frequency (Chapter 2). The resulting temporal response tuning profile showed substantial individual variability, which I assessed in relation to two other intrinsic properties of the individual’s visual system (Chapter 3). Spectral features of the temporal tuning profile were found to be associated with an individual’s perceptual temporal resolution but not with the peak frequency of visually-induced gamma oscillations. Moreover, the temporal resolution was found to be unrelated to visual gamma oscillations and the computationally modelled synaptic properties underlying visual gamma (Chapter 4). These MEG studies provide insights into dynamical properties of the visual system and form the methodological basis for future frequency-tagging studies. Besides the MEG research, I conducted a psychophysical study to investigate the top-down modulation of the perception of low-level features in an organised percept (Chapter 5). I found that whether the perceptual sensitivity to a low-level feature is enhanced by top-down processing depends on whether this feature contributes to the object percept. Future studies can investigate this effect further via frequency-tagging, by implementing flickers in the stimuli of the psychophysical task and choosing tagging frequencies informed by my MEG studies, to advance our understanding of the neural mechanisms underlying top-down processing in perceptual organisation

CORTICAL DYNAMICS OF AUDITORY-VISUAL SPEECH: A FORWARD MODEL OF MULTISENSORY INTEGRATION.

In noisy settings, seeing the interlocutor's face helps to disambiguate what is being said. For this to happen, the brain must integrate auditory and visual information. Three major problems are (1) bringing together separate sensory streams of information, (2) extracting auditory and visual speech information, and (3) identifying this information as a unified auditory-visual percept. In this dissertation, a new representational framework for auditory visual (AV) speech integration is offered. The experimental work (psychophysics and electrophysiology (EEG)) suggests specific neural mechanisms for solving problems (1), (2), and (3) that are consistent with a (forward) 'analysis-by-synthesis' view of AV speech integration. In Chapter I, multisensory perception and integration are reviewed. A unified conceptual framework serves as background for the study of AV speech integration. In Chapter II, psychophysics testing the perception of desynchronized AV speech inputs show the existence of a ~250ms temporal window of integration in AV speech integration. In Chapter III, an EEG study shows that visual speech modulates early on the neural processing of auditory speech. Two functionally independent modulations are (i) a ~250ms amplitude reduction of auditory evoked potentials (AEPs) and (ii) a systematic temporal facilitation of the same AEPs as a function of the saliency of visual speech. In Chapter IV, an EEG study of desynchronized AV speech inputs shows that (i) fine-grained (gamma, ~25ms) and (ii) coarse-grained (theta, ~250ms) neural mechanisms simultaneously mediate the processing of AV speech. In Chapter V, a new illusory effect is proposed, where non-speech visual signals modify the perceptual quality of auditory objects. EEG results show very different patterns of activation as compared to those observed in AV speech integration. An MEG experiment is subsequently proposed to test hypotheses on the origins of these differences. In Chapter VI, the 'analysis-by-synthesis' model of AV speech integration is contrasted with major speech theories. From a Cognitive Neuroscience perspective, the 'analysis-by-synthesis' model is argued to offer the most sensible representational system for AV speech integration. This thesis shows that AV speech integration results from both the statistical nature of stimulation and the inherent predictive capabilities of the nervous system

Change blindness: eradication of gestalt strategies

Arrays of eight, texture-defined rectangles were used as stimuli in a one-shot change blindness (CB) task where there was a 50% chance that one rectangle would change orientation between two successive presentations separated by an interval. CB was eliminated by cueing the target rectangle in the first stimulus, reduced by cueing in the interval and unaffected by cueing in the second presentation. This supports the idea that a representation was formed that persisted through the interval before being 'overwritten' by the second presentation (Landman et al, 2003 Vision Research 43149–164]. Another possibility is that participants used some kind of grouping or Gestalt strategy. To test this we changed the spatial position of the rectangles in the second presentation by shifting them along imaginary spokes (by ±1 degree) emanating from the central fixation point. There was no significant difference seen in performance between this and the standard task [F(1,4)=2.565, p=0.185]. This may suggest two things: (i) Gestalt grouping is not used as a strategy in these tasks, and (ii) it gives further weight to the argument that objects may be stored and retrieved from a pre-attentional store during this task