Neural correlates of conscious tactile perception: An analysis of BOLD activation patterns and graph metrics

Theories of human consciousness substantially vary in the proposed spatial extent of brain activity associated with conscious perception as well as in the assumed functional alterations within the involved brain regions. Here, we investigate which local and global changes in brain activity accompany conscious somatosensory perception following electrical finger nerve stimulation, and whether there are whole-brain functional network alterations by means of graph metrics. Thirty-eight healthy participants performed a somatosensory detection task and reported their decision confidence during fMRI. For conscious tactile perception in contrast to undetected near-threshold trials (misses), we observed increased BOLD activity in the precuneus, the intraparietal sulcus, the insula, the nucleus accumbens, the inferior frontal gyrus and the contralateral secondary somatosensory cortex. For misses compared to correct rejections, bilateral secondary somatosensory cortices, supplementary motor cortex and insula showed greater activations. The analysis of whole-brain functional network topology for hits, misses and correct rejections, did not result in any significant differences in modularity, participation, clustering or path length, which was supported by Bayes factor statistics. In conclusion, for conscious somatosensory perception, our results are consistent with an involvement of (probably) domain-general brain areas (precuneus, insula, inferior frontal gyrus) in addition to somatosensory regions; our data do not support the notion of specific changes in graph metrics associated with conscious experience. For the employed somatosensory submodality of fine electrical current stimulation, this speaks for a global broadcasting of sensory content across the brain without substantial reconfiguration of the whole-brain functional network resulting in an integrative conscious experience

Alpha-band brain oscillations shape the processing of perceptible as well as imperceptible somatosensory stimuli during selective attention

Attention filters and weights sensory information according to behavioral demands. Stimulus-related neural responses are increased for the attended stimulus. Does alpha-band activity mediate this effect and is it restricted to conscious sensory events (suprathreshold), or does it also extend to unconscious stimuli (subthreshold)? To address these questions, we recorded EEG in healthy male and female volunteers undergoing subthreshold and suprathreshold somatosensory electrical stimulation to the left or right index finger. The task was to detect stimulation at the randomly alternated cued index finger. Under attention, amplitudes of somatosensory evoked potentials increased 50--60 ms after stimulation (P1) for both suprathreshold and subthreshold events. Pre-stimulus amplitude of peri-Rolandic alpha, that is mu, showed an inverse relationship to P1 amplitude during attention, compared to when the finger was unattended. Interestingly, intermediate and high amplitudes of mu rhythm were associated with the highest P1 amplitudes during attention and smallest P1 during lack of attention, that is, these levels of alpha rhythm seemed to optimally support the behavioral goal (“detect” stimuli at the cued finger while ignoring the other finger). Our results show that attention enhances neural processing for both suprathreshold and subthreshold stimuli and they highlight a rather complex interaction between attention, Rolandic alpha activity, and their effects on stimulus processing

Neural correlates of conscious tactile perception: An analysis of BOLD activation patterns and graph metrics

Theories of human consciousness substantially vary in the proposed spatial extent of brain activity associated with conscious perception as well as in the assumed functional alterations within the involved brain regions. Here, we investigate which local and global changes in brain activity accompany conscious somatosensory perception following electrical finger nerve stimulation, and whether there are whole-brain functional network alterations by means of graph metrics. Thirty-eight healthy participants performed a somatosensory detection task and reported their decision confidence during fMRI. For conscious tactile perception in contrast to undetected near-threshold trials (misses), we observed increased BOLD activity in the precuneus, the intraparietal sulcus, the insula, the nucleus accumbens, the inferior frontal gyrus and the contralateral secondary somatosensory cortex. For misses compared to correct rejections, bilateral secondary somatosensory cortices, supplementary motor cortex and insula showed greater activations. The analysis of whole-brain functional network topology for hits, misses and correct rejections, did not result in any significant differences in modularity, participation, clustering or path length, which was supported by Bayes factor statistics. In conclusion, for conscious somatosensory perception, our results are consistent with an involvement of (probably) domain-general brain areas (precuneus, insula, inferior frontal gyrus) in addition to somatosensory regions; our data do not support the notion of specific changes in graph metrics associated with conscious experience. For the employed somatosensory submodality of fine electrical current stimulation, this speaks for a global broadcasting of sensory content across the brain without substantial reconfiguration of the whole-brain functional network resulting in an integrative conscious experience

Modulation of Somatosensory Alpha Rhythm by Transcranial Alternating Current Stimulation at Mu-Frequency

Introduction: Transcranial alternating current stimulation (tACS) is emerging as an interventional tool to modulate different functions of the brain, potentially by interacting with intrinsic ongoing neuronal oscillations. Functionally different intrinsic alpha oscillations are found throughout the cortex. Yet it remains unclear whether tACS is capable of specifically modulating the somatosensory mu-rhythm in amplitude. Objectives: We used tACS to modulate mu-alpha oscillations in amplitude. When compared to sham stimulation we expected a modulation of mu-alpha oscillations but not visual alpha oscillations by tACS. Methods: Individual mu-alpha frequencies were determined in 25 participants. Subsequently, blocks of tACS with individual mu-alpha frequency and sham stimulation were applied over primary somatosensory cortex (SI). Electroencephalogram (EEG) was recorded before and after either stimulation or sham. Modulations of mu-alpha and, for control, visual alpha amplitudes were then compared between tACS and sham. Results: Somatosensory mu-alpha oscillations decreased in amplitude after tACS was applied at participants’ individual mu-alpha frequency. No changes in amplitude were observed for sham stimulation. Furthermore, visual alpha oscillations were not affected by tACS or sham, respectively. Conclusion: Our results demonstrate the capability of tACS to specifically modulate the targeted somatosensory mu-rhythm when the tACS frequency is tuned to the individual endogenous rhythm and applied over somatosensory areas. Our results are in contrast to previously reported amplitude increases of visual alpha oscillations induced by tACS applied over visual cortex. Our results may point to a specific interaction between our stimulation protocol and the functional architecture of the somatosensory system

Best-practice IgM- and IgA-enriched immunoglobulin use in patients with sepsis

Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Despite treatment being in line with current guidelines, mortality remains high in those with septic shock. Intravenous immunoglobulins represent a promising therapy to modulate both the pro- and anti-inflammatory processes and can contribute to the elimination of pathogens. In this context, there is evidence of the benefits of immunoglobulin M (IgM)- and immunoglobulin A (IgA)-enriched immunoglobulin therapy for sepsis. This manuscript aims to summarize current relevant data to provide expert opinions on best practice for the use of an IgM- and IgA-enriched immunoglobulin (Pentaglobin) in adult patients with sepsis. Main text: Sepsis patients with hyperinflammation and patients with immunosuppression may benefit most from treatment with IgM- and IgA-enriched immunoglobulin (Pentaglobin). Patients with hyperinflammation present with phenotypes that manifest throughout the body, whilst the clinical characteristics of immunosuppression are less clear. Potential biomarkers for hyperinflammation include elevated procalcitonin, interleukin-6, endotoxin activity and C-reactive protein, although thresholds for these are not well-defined. Convenient biomarkers for identifying patients in a stage of immune-paralysis are still matter of debate, though human leukocyte antigen–antigen D related expression on monocytes, lymphocyte count and viral reactivation have been proposed. The timing of treatment is potentially more critical for treatment efficacy in patients with hyperinflammation compared with patients who are in an immunosuppressed stage. Due to the lack of evidence, definitive dosage recommendations for either population cannot be made, though we suggest that patients with hyperinflammation should receive an initial bolus at a rate of up to 0.6 mL (30 mg)/kg/h for 6 h followed by a continuous maintenance rate of 0.2 mL (10 mg)/kg/hour for ≥ 72 h (total dose ≥ 0.9 g/kg). For immunosuppressed patients, dosage is more conservative (0.2 mL [10 mg]/kg/h) for ≥ 72 h, without an initial bolus (total dose ≥ 0.72 g/kg). Conclusions: Two distinct populations that may benefit most from Pentaglobin therapy are described in this review. However, further clinical evidence is required to strengthen support for the recommendations given here regarding timing, duration and dosage of treatment

Reduction of somatosensory functional connectivity by transcranial alternating current stimulation at endogenous mu-frequency

Alpha, the most prominent human brain rhythm, might reflect a mechanism of functional inhibition for gating neural processing. This concept has been derived predominantly from local measures of inhibition, while large-scale network mechanisms to guide information flow are largely unknown. Here, we investigated functional connectivity changes on a whole-brain level by concurrent transcranial alternating current stimulation (tACS) and resting-state functional MRI in humans. We specifically focused on somatosensory alpha-band oscillations by adjusting the tACS frequency to each individual´s somatosensory (mu-) alpha peak frequency (mu-tACS). Potential differences of Eigenvector Centrality of primary somatosensory cortex (S1) as well as on a whole brain level between mu-tACS and sham were analyzed. Our results demonstrate that mu-tACS induces a locally-specific decrease in whole-brain functional connectivity of left S1. An additional exploratory analysis revealed that this effect primarily depends on a decrease in functional connectivity between S1 and a network of regions that are crucially involved in somatosensory processing. Furthermore, the decrease in functional centrality was specific to mu-tACS and was not observed when tACS was applied in the gamma-range in an independent study. Our findings provide evidence that modulated somatosensory (mu-) alpha-activity may affect whole-brain network level activity by decoupling primary sensory areas from other hubs involved in sensory processing

Respiration, heartbeat, and conscious tactile perception

Previous studies have shown that timing of sensory stimulation during the cardiac cycle interacts with perception. Given the natural coupling of respiration and cardiac activity, we investigated here their joint effects on tactile perception. Forty-one healthy female and male human participants reported conscious perception of finger near-threshold electrical pulses (33% null trials) and decision confidence while electrocardiography, respiratory activity, and finger photoplethysmography were recorded. Participants adapted their respiratory cycle to expected stimulus onsets to preferentially occur during late inspiration / early expiration. This closely matched heart rate variation (sinus arrhythmia) across the respiratory cycle such that most frequent stimulation onsets occurred during the period of highest heart rate probably indicating highest alertness and cortical excitability. Tactile detection rate was highest during the first quadrant after expiration onset. Inter-individually, stronger respiratory phase-locking to the task was associated with higher detection rates. Regarding the cardiac cycle, we confirmed previous findings that tactile detection rate was higher during diastole than systole and newly specified its minimum at 250 - 300 ms after the R-peak corresponding to the pulse wave arrival in the finger. Expectation of stimulation induced a transient heart deceleration which was more pronounced for unconfident decision ratings. Inter-individually, stronger post-stimulus modulations of heart rate were linked to higher detection rates. In summary, we demonstrate how tuning to the respiratory cycle and integration of respiratory-cardiac signals are used to optimize performance of a tactile detection task

Respiration, heartbeat, and conscious tactile perception

Previous studies have shown that timing of sensory stimulation during the cardiac cycle interacts with perception. Given the natural coupling of respiration and cardiac activity, we investigated here their joint effects on tactile perception. Forty-one healthy female and male human participants reported conscious perception of finger near-threshold electrical pulses (33% null trials) and decision confidence while electrocardiography, respiratory activity, and finger photoplethysmography were recorded. Participants adapted their respiratory cycle to expected stimulus onsets to preferentially occur during late inspiration / early expiration. This closely matched heart rate variation (sinus arrhythmia) across the respiratory cycle such that most frequent stimulation onsets occurred during the period of highest heart rate probably indicating highest alertness and cortical excitability. Tactile detection rate was highest during the first quadrant after expiration onset. Inter-individually, stronger respiratory phase-locking to the task was associated with higher detection rates. Regarding the cardiac cycle, we confirmed previous findings that tactile detection rate was higher during diastole than systole and newly specified its minimum at 250 - 300 ms after the R-peak corresponding to the pulse wave arrival in the finger. Expectation of stimulation induced a transient heart deceleration which was more pronounced for unconfident decision ratings. Inter-individually, stronger post-stimulus modulations of heart rate were linked to higher detection rates. In summary, we demonstrate how tuning to the respiratory cycle and integration of respiratory-cardiac signals are used to optimize performance of a tactile detection task

Content Representation of Tactile Mental Imagery in Primary Somatosensory Cortex

The imagination of tactile stimulation has been shown to activate primary somatosensory cortex (S1) with a somatotopic specificity akin to that seen during the perception of tactile stimuli. Using fMRI and multivariate pattern analysis, we investigate whether this recruitment of sensory regions also reflects content-specific activation (i.e., whether the activation in S1 is specific to the mental content participants imagined). To this end, healthy volunteers (n = 21) either perceived or imagined three types of vibrotactile stimuli (mental content) while fMRI data were acquired. Independent of the content, during tactile mental imagery we found activation of frontoparietal regions, supplemented with activation in the contralateral BA2 subregion of S1, replicating previous reports. While the imagery of the three different stimuli did not reveal univariate activation differences, using multivariate pattern classification, we were able to decode the imagined stimulus type from BA2. Moreover, cross-classification revealed that tactile imagery elicits activation patterns similar to those evoked by the perception of the respective stimuli. These findings promote the idea that mental tactile imagery involves the recruitment of content-specific activation patterns in sensory cortices, namely in S1

Proc Natl Acad Sci U S A.

During translation, usually only one in approximately 400 misincorporations affects the function of a nascent protein, because only chemically similar near-cognate amino acids are misincorporated in place of the cognate one. The deleterious misincorporation of a chemically dissimilar noncognate amino acid during the selection process is precluded by the presence of a tRNA at the ribosomal E-site. However, the selection of first aminoacyl-tRNA, directly after initiation, occurs without an occupied E-site, i.e., when only the P-site is filled with the initiator tRNA and thus should be highly error-prone. Here, we show how bacterial ribosomes have solved this accuracy problem: In the absence of a Shine-Dalgarno (SD) sequence, the first decoding step at the A-site after initiation is extremely error-prone, even resulting in the significant incorporation of noncognate amino acids. In contrast, when a SD sequence is present, the incorporation of noncognate amino acids is not observed. This is precisely the effect that the presence of a cognate tRNA at the E-site has during the elongation phase. These findings suggest that during the initiation phase, the SD interaction functionally compensates for the lack of codon-anticodon interaction at the E-site by reducing the misincorporation of near-cognate amino acids and prevents noncognate misincorporation