When decisions of others matter to me: an electrophysiological analysis

Background

Actions of others may have immediate consequences for oneself. We probed the neural responses associated with the observation of another person's action using event-related potentials in a modified gambling task. In this task a "performer" bet either a higher or lower number and could win or lose this amount. Three different groups of "observers" were also studied. The first (neutral) group simply observed the performer's action, which had no consequences for the observers. In the second (parallel) group, wins/losses of the performer were paralleled by similar wins and losses by the observer. In the third (reverse) group, wins of the performer led to a loss of the observer and vice versa.

Results

ERPs of the performers showed a mediofrontal feedback related negativity (FRN) to losses. The neutral and parallel observer groups did similarly show an FRN response to the performer's losses with a topography indistinguishable from that seen in the performers. In the reverse group, however, the FRN occurred for wins of the performer which translated to losses for the observer.

Conclusions

Taking into account previous experiments, we suggest that the FRN response in observers is driven by two evaluative processes (a) related to the benefit/loss for oneself and (b) related to the benefit/loss of another person.     

Functional EEG connectivity during competition

Background

Social behavior and interactions pervasively shape and influence our lives and relationships. Competition, in particular, has become a core topic in social neuroscience since it stresses the relevance and salience of social comparison processes between the inter-agents that are involved in a common task. The majority of studies, however, investigated such kind of social interaction via one-person individual paradigms, thus not taking into account relevant information concerning interdependent participants’ behavioral and neural responses. In the present study, dyads of volunteers participated in a hyperscanning paradigm and competed in a computerized attention task while their electrophysiological (EEG) activity and performance were monitored and recorded. Behavioral data and inter-brain coupling measures based on EEG frequency data were then computed and compared across different experimental conditions: a control condition (individual task, t0), a first competitive condition (pre-feedback condition, t1), and a second competitive condition following a positive reinforcing feedback (post-feedback condition, t2).

Results

Results showed that during competitive tasks participants’ performance was improved with respect to control condition (reduced response times and error rates), with a further specific improvement after receiving a reinforcing feedback. Concurrently, we observed a reduction of inter-brain functional connectivity (primarily involving bilateral prefrontal areas) for slower EEG frequency bands (delta and theta). Finally, correlation analyses highlighted a significant association between cognitive performance and inter-brain connectivity measures.

Conclusions

The present results may help identifying specific patterns of behavioral and inter-brain coupling measures associated to competition and processing of social reinforcements.

     

Pyrid-2-yl and 2-CyanoPhenyl fused heterocyclic compounds as human P2X_{3} inhibitors: a combined approach based on homology modelling,docking and QSAR analysis

P2X receptors are hetero-oligomeric proteins that function as membrane ion channels and are gated by extracellular ATP. The hP2X $_{3}$ subunit is a constituent of the channels on a subset of sensory neurons involved in pain signaling, where ATP released by damaged and inflamed tissue can initiate action potentials. Hence, the inhibition of ATP-activated P2X $_{3}$ receptor is an exciting approach for the treatment of inflammatory and neuropathic pain. Recently, the crystal structures of zebrafish P2X $_{4}$ (zP2X $_{4})$ were obtained in closed, apo state (PDB ID: 3I5D) and ATP-bound, open state (PDB ID: 4DW1). These structures were used to develop a homology model of human P2X $_{3}$ (hP2X $_{3})$ in order to identify through docking studies, the binding modes of known P2X $_{3}$ inhibitors and their key active site interactions, along with a pharmacophore-based 3D-QSAR model for a series of 136 Pyrid-2-yl and 2-CyanoPhenyl fused heterocyclic compounds. These 3D-QSAR models have been developed with different combinations of training and test set divisions obtained by random separation, Jarvis–Patrick clustering, K-means clustering and sphere exclusion methods. The best predictive 3D-QSAR model resulted in training set R $^{2 }$ of 0.75, internal test set Q $^{2}$ of 0.74, Pearson-R value of 0.87 and root mean square error of 0.37. The information generated by the pharmacophore model and docking analyses using the homology model provides valuable clues to design novel potent hP2X $_{3}$ inhibitors.     

Maturation of auditory temporal integration and inhibition assessed with event-related potentials (ERPs)

Background

We examined development of auditory temporal integration and inhibition by assessing electrophysiological responses to tone pairs separated by interstimulus intervals (ISIs) of 25, 50, 100, 200, 400, and 800 ms in 28 children aged 7 to 9 years, and 15 adults.

Results

In adults a distinct neural response was elicited to tones presented at ISIs of 25 ms or longer, whereas in children this was only seen in response to tones presented at ISIs above 100 ms. In adults, late N1 amplitude was larger for the second tone of the tone pair when separated by ISIs as short as 100 ms, consistent with the perceptual integration of successive stimuli within the temporal window of integration. In contrast, children showed enhanced negativity only when tone pairs were separated by ISIs of 200 ms. In children, the amplitude of the P1 component was attenuated at ISIs below 200 ms, consistent with a refractory process.

Conclusions

These results indicate that adults integrate sequential auditory information into smaller temporal segments than children. These results suggest that there are marked maturational changes from childhood to adulthood in the perceptual processes underpinning the grouping of incoming auditory sensory information, and that electrophysiological measures provide a sensitive, non-invasive method allowing further examination of these changes.     

Antihydrogen (hydrogen) atom formation

In this paper we show how the ATHENA data samples on the antihydrogen ( ${\bar{\rm H}}$ ) formation in very different conditions provide useful information on the two different possible mechanisms: the 3-body reaction ( $\bar{p}+{e^+}+{e^+}\rightarrow {\bar{\rm H}}+ e^+$ ) and the 2-body reaction ( $\bar{p}+{\rm e^+}\rightarrow {\bar{\rm H}}+{h\nu}$ ).     

Presynaptic action of neurotensin on dopamine release through inhibition of D2 receptor function

Background

Statistical learning is a candidate for one of the basic prerequisites underlying the expeditious acquisition of spoken language. Infants from 8 months of age exhibit this form of learning to segment fluent speech into distinct words. To test the statistical learning skills at birth, we recorded event-related brain responses of sleeping neonates while they were listening to a stream of syllables containing statistical cues to word boundaries.

Results

We found evidence that sleeping neonates are able to automatically extract statistical properties of the speech input and thus detect the word boundaries in a continuous stream of syllables containing no morphological cues. Syllable-specific event-related brain responses found in two separate studies demonstrated that the neonatal brain treated the syllables differently according to their position within pseudowords.

Conclusion

These results demonstrate that neonates can efficiently learn transitional probabilities or frequencies of co-occurrence between different syllables, enabling them to detect word boundaries and in this way isolate single words out of fluent natural speech. The ability to adopt statistical structures from speech may play a fundamental role as one of the earliest prerequisites of language acquisition.     

Formulation of a killed whole cell pneumococcus vaccine - effect of aluminum adjuvants on the antibody and IL-17 response

Background

Streptococcus pneumoniae causes widespread morbidity and mortality. Current vaccines contain free polysaccharides or protein-polysaccharide conjugates, and do not induce protection against serotypes that are not included in the vaccines. An affordable and broadly protective vaccine is very desirable. The goal of this study was to determine the optimal formulation of a killed whole cell pneumococcal vaccine with aluminum-containing adjuvants for intramuscular injection.

Methods

Four aluminium-containing adjuvants were prepared with different levels of surface phosphate groups resulting in different adsorptive capacities and affinities for the vaccine antigens. Mice were immunized three times and the antigen-specific antibody titers and IL-17 responses in blood were analyzed.

Results

Although all adjuvants induced significantly higher antibody titers than antigen without adjuvant, the vaccine containing aluminum phosphate adjuvant (AP) produced the highest antibody response when low doses of antigen were used. Aluminum hydroxide adjuvant (AH) induced an equal or better antibody response at high doses compared with AP. Vaccines formulated with AH, but not with AP, induced an IL-17 response. The vaccine formulated with AH was stable and retained full immunogenicity when stored at 4°C for 4 months.

Conclusions

Antibodies are important for protection against systemic streptococcal disease and IL-17 is critical in the prevention of nasopharyngeal colonization by S. pneumoniae in the mouse model. The formulation of the whole killed bacterial cells with AH resulted in a stable vaccine that induced both antibodies and an IL-17 response. These experiments underscore the importance of formulation studies with aluminium containing adjuvants for the development of stable and effective vaccines.     

Immunotherapeutic role of Ag85B as an adjunct to antituberculous chemotherapy

Background

Immunotherapy to enhance the efficiency of the immune response in tuberculosis patients and to eliminate the persisters could be an additional valuable strategy to complement anti-mycobacterial chemotherapy. This study was designed to assess the immunotherapeutic potential of Ag85B as an adjunct to chemotherapy and its effect against active and persister bacteria left after therapy in mouse model of tuberculosis.

Methods

6-8 week old female Balb/c mice were infected with Mycobacterium tuberculosis and treated with chemotherapy or immunotherapy. Protective efficacy was measured in terms of bacterial counts in lungs and spleen. Immune correlates of protection in terms of Th1 and Th2 cytokines were measured by ELISA.

Results

Therapeutic effect of Ag85B was found to be comparable to that of short term dosage of antituberculous drugs (ATDs). The therapeutic effect of ATDs was augmented by the simultaneous treatment with rAg85B and moreover therapy with this protein allowed us to reduce ATD dosage. This therapy was found to be effective even in case of drug persisters. The levels of antigen specific IFNγ and IL-12 were significantly increased after immunotherapy as compared to the basal levels; moreover antigen specific IL-4 levels were depressed on immunotherapy with Ag85B.

Conclusion

We demonstrated in this study that the new combination approach using immunotherapy and concurrent chemotherapy should offer several improvements over the existing regimens to treat tuberculosis. The therapeutic effect is associated not only with initiating a Th1 response but also with switching the insufficient Th2 immune status to the more protective Th1 response.     

Modeling of HOT (111) HgCdTe MWIR detector for fast response operation

The paper reports on photoelectrical performance of the mid-wave infrared (MWIR) (111) HgCdTe high operating temperature detector for the fast response conditions. Detector structure was simulated with software APSYS by Crosslight Inc. The detailed analysis of the time response as a function of device architecture and applied voltage was performed pointing out optimal working conditions. The time response of the MWIR HgCdTe detector with 50 % cut-off wavelength of \(\lambda _{c} \approx 5.3\, \upmu \hbox {m}\) at \(T = 200\)  K was estimated at the level of \(\tau _{s} \approx \) 2,500 ps for \(V = 100\)  mV and series resistance \(R_{Series} = 510\,\Omega \) . The series resistance’s reduction enables to reach \(\tau _{s}\approx 60\!-\!500\)  ps.     

Neuroprotective effects of edaravone-administration on 6-OHDA-treated dopaminergic neurons

Background

A recent human clinical trial of an Alzheimer's disease (AD) vaccine using amyloid beta (Aβ) 1–42 plus QS-21 adjuvant produced some positive results, but was halted due to meningoencephalitis in some participants. The development of a vaccine with mutant Aβ peptides that avoids the use of an adjuvant may result in an effective and safer human vaccine.

Results

All peptides tested showed high antibody responses, were long-lasting, and demonstrated good memory response. Epitope mapping indicated that peptide mutation did not lead to epitope switching. Mutant peptides induced different inflammation responses as evidenced by cytokine profiles. Ig isotyping indicated that adjuvant-free vaccination with peptides drove an adequate Th2 response. All anti-sera from vaccinated mice cross-reacted with human Aβ in APP/PS1 transgenic mouse brain tissue.

Conclusion

Our study demonstrated that an adjuvant-free vaccine with different Aβ peptides can be an effective and safe vaccination approach against AD. This study represents the first report of adjuvant-free vaccines utilizing Aβ peptides carrying diverse mutations in the T-cell epitope. These largely positive results provide encouragement for the future of the development of human vaccinations for AD.     

Compulsive checking behavior of quinpirole-sensitized rats as an animal model of Obsessive-Compulsive Disorder(OCD): form and control

Background

A previous report showed that the open field behavior of rats sensitized to the dopamine agonist quinpirole satisfies 5 performance criteria for compulsive checking behavior. In an effort to extend the parallel between the drug-induced phenomenon and human obsessive-compulsive disorder (OCD), the present study investigated whether the checking behavior of quinpirole rats is subject to interruption, which is an attribute characteristic of OCD compulsions. For this purpose, the rat's home-cage was placed into the open field at the beginning or the middle of a 2-hr test.

Results

Introduction of the home-cage reduced checking behavior, as rats stayed inside the cage. After 40 min, checking resurfaced, as quinpirole rats exited the home-cage often. An unfamiliar cage had no such effects on quinpirole rats or saline controls.

Conclusions

Checking behavior induced by quinpirole is not irrepressible but can be suspended. Results strengthen the quinpirole preparation as an animal model of OCD compulsive checking.     

Differential expression of Cathepsin S and X in the spinal cord of a rat neuropathic pain model

Background

Proteoglycan (PG) in the extracellular matrix (ECM) of the central nervous system (CNS) may act as a barrier for neurite elongation in a growth tract, and regulate other characteristics collectively defined as structural neural plasticity. Proteolytic cleavage of PGs appears to alter the environment to one favoring plasticity and growth. Brevican belongs to the lectican family of aggregating, chondroitin sulfate (CS)-bearing PGs, and it modulates neurite outgrowth and synaptogenesis. Several ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) are glutamyl-endopeptidases that proteolytically cleave brevican. The purpose of this study was to localize regions of adult CNS that contain a proteolytic-derived fragment of brevican which bears the ADAMTS-cleaved neoepitope sequence. These regions were compared to areas of Wisteria floribunda agglutin (WFA) reactivity, a common reagent used to detect "perineuronal nets" (PNNs) of intact matrix and a marker which is thought to label regions of relative neural stability.

Results

WFA reactivity was found primarily as PNNs, whereas brevican and the ADAMTS-cleaved fragment of brevican were more broadly distributed in neuropil, and in particular regions localized to PNNs. One example is hippocampus where the ADAMTS-cleaved brevican fragment is found surrounding pyramidal neurons, in neuropil of stratum oriens/radiatum and the lacunosum moleculare. The fragment was less abundant in the molecular layer of the dentate gyrus. Mostly PNNs of scattered interneurons along the pyramidal layer were identified by WFA. In lateral thalamus, the reticular thalamic nucleus stained abundantly with WFA whereas ventral posterior nuclei were markedly immunopositive for ADAMTS-cleaved brevican. Using Western blotting techniques, no common species were reactive for brevican and WFA.

Conclusion

In general, a marked discordance was observed in the regional localization between WFA and brevican or the ADAMTS-derived N-terminal fragment of brevican. Functionally, this difference may correspond to regions with varied prevalence for neural stability/plasticity.     

A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion

Background

Our goal was to examine the spatiotemporal integration of tactile information in the hand representation of human primary somatosensory cortex (anterior parietal somatosensory areas 3b and 1), secondary somatosensory cortex (S2), and the parietal ventral area (PV), using high-resolution whole-head magnetoencephalography (MEG). To examine representational overlap and adaptation in bilateral somatosensory cortices, we used an oddball paradigm to characterize the representation of the index finger (D2; deviant stimulus) as a function of the location of the standard stimulus in both right- and left-handed subjects.

Results

We found that responses to deviant stimuli presented in the context of standard stimuli with an interstimulus interval (ISI) of 0.33s were significantly and bilaterally attenuated compared to deviant stimulation alone in S2/PV, but not in anterior parietal cortex. This attenuation was dependent upon the distance between the deviant and standard stimuli: greater attenuation was found when the standard was immediately adjacent to the deviant (D3 and D2 respectively), with attenuation decreasing for non-adjacent fingers (D4 and opposite D2). We also found that cutaneous mechanical stimulation consistently elicited not only a strong early contralateral cortical response but also a weak ipsilateral response in anterior parietal cortex. This ipsilateral response appeared an average of 10.7 ± 6.1 ms later than the early contralateral response. In addition, no hemispheric differences either in response amplitude, response latencies or oddball responses were found, independent of handedness.

Conclusion

Our findings are consistent with the large receptive fields and long neuronal recovery cycles that have been described in S2/PV, and suggest that this expression of spatiotemporal integration underlies the complex functions associated with this region. The early ipsilateral response suggests that anterior parietal fields also receive tactile input from the ipsilateral hand. The lack of a hemispheric difference in responses to digit stimulation supports a lack of any functional asymmetry in human somatosensory cortex.     

Rejection of randomly coinciding events in ZnMoO_4 scintillating bolometers

Random coincidence of events (particularly from two neutrino double beta decay) could be one of the main sources of background in the search for neutrinoless double beta decay with cryogenic bolometers due to their poor time resolution. Pulse-shape discrimination by using front edge analysis, mean-time and \(\chi ^2\) methods were applied to discriminate randomly coinciding events in ZnMoO \(_4\) cryogenic scintillating bolometers. These events can be effectively rejected at the level of 99 % by the analysis of the heat signals with rise-time of about 14 ms and signal-to-noise ratio of 900, and at the level of 92 % by the analysis of the light signals with rise-time of about 3 ms and signal-to-noise ratio of 30, under the requirement to detect 95 % of single events. These rejection efficiencies are compatible with extremely low background levels in the region of interest of neutrinoless double beta decay of \(^{100}\) Mo for enriched ZnMoO \(_4\) detectors, of the order of \(10^{-4}\)  counts/(y keV kg). Pulse-shape parameters have been chosen on the basis of the performance of a real massive ZnMoO \(_4\) scintillating bolometer. Importance of the signal-to-noise ratio, correct finding of the signal start and choice of an appropriate sampling frequency are discussed.     

Microcanonical Analysis of the Curie–Weiss Anisotropic Quantum Heisenberg Model in a Magnetic Field

The anisotropic quantum Heisenberg model with Curie-Weiss-type interactions is studied analytically in several variants of the microcanonical ensemble. (Non)equivalence of microcanonical and canonical ensembles is investigated by studying the concavity properties of entropies. The microcanonical entropy \(s(e,\varvec{m})\) is obtained as a function of the energy \(e\) and the magnetization vector \({\varvec{m}}\) in the thermodynamic limit. Since, for this model, \(e\) is uniquely determined by \({\varvec{m}}\) , the same information can be encoded either in \(s(\varvec{m})\) or \(s(e,m_1,m_2)\) . Although these two entropies correspond to the same physical setting of fixed \(e\) and \({\varvec{m}}\) , their concavity properties differ. The entropy \(s_{{\varvec{h}}}(u)\) , describing the model at fixed total energy \(u\) and in a homogeneous external magnetic field \({\varvec{h}}\) of arbitrary direction, is obtained by reduction from the nonconcave entropy \(s(e,m_1,m_2)\) . In doing so, concavity, and therefore equivalence of ensembles, is restored. \(s_{{\varvec{h}}}(u)\) has nonanalyticities on surfaces of co-dimension 1 in the \((u,\varvec{h})\) -space. Projecting these surfaces into lower-dimensional phase diagrams, we observe that the resulting phase transition lines are situated in the positive-temperature region for some parameter values, and in the negative-temperature region for others. In the canonical setting of a system coupled to a heat bath of positive temperatures, the nonanalyticities in the microcanonical negative-temperature region cannot be observed, and this leads to a situation of effective nonequivalence even when formal equivalence holds.     

Transcranial Magnetic Stimulation for the treatment of tinnitus: Effects on cortical excitability

Background

Low frequency repetitive transcranial magnetic stimulation (rTMS) has been proposed as an innovative treatment for chronic tinnitus. The aim of the present study was to elucidate the underlying mechanism and to evaluate the relationship between clinical outcome and changes in cortical excitability. We investigated ten patients with chronic tinnitus who participated in a sham-controlled crossover treatment trial. Magnetic-resonance-imaging and positron-emission-tomography guided 1 Hz rTMS were performed over the auditory cortex on 5 consecutive days. Active and sham treatments were separated by one week. Parameters of cortical excitability (motor thresholds, intracortical inhibition, intracortical facilitation, cortical silent period) were measured serially before and after rTMS treatment by using single- and paired-pulse transcranial magnetic stimulation. Clinical improvement was assessed with a standardized tinnitus-questionnaire.

Results

We noted a significant interaction between treatment response and changes in motor cortex excitability during active rTMS. Specifically, clinical improvement was associated with an increase in intracortical inhibition, intracortical facilitation and a prolongation of the cortical silent period. These results indicate that intraindividual changes in cortical excitability may serve as a correlate of response to rTMS treatment.

Conclusion

The observed alterations of cortical excitability suggest that low frequency rTMS may evoke long-term-depression like effects resulting in an improvement of subcortical inhibitory function.     

Precision and accuracy of the subjective haptic vertical in the roll plane

Background

Autophagy, an intracellular response to stress, is characterized by double membrane cytosolic vesicles called autophagosomes. Prolonged autophagy is known to result in autophagic (Type II) cell death. This study examined the potential role of an autophagic response in cultured cerebellar granule neurons challenged with excitotoxin N-methyl-D-aspartate (NMDA).

Results

NMDA exposure induced light chain-3 (LC-3)-immunopositive and monodansylcadaverine (MDC) fluorescent dye-labeled autophagosome formation in both cell bodies and neurites as early as 3 hours post-treatment. Elevated levels of Beclin-1 and the autophagosome-targeting LC3-II were also observed following NMDA exposure. Prolonged exposure of the cultures to NMDA (8-24 h) generated MDC-, LC3-positive autophagosomal bodies, concomitant with the neurodegenerative phase of NMDA challenge. Lysosomal inhibition studies also suggest that NMDA-treatment diverted the autophagosome-associated LC3-II from the normal lysosomal degradation pathway. Autophagy inhibitor 3-methyladenine significantly reduced NMDA-induced LC3-II/LC3-I ratio increase, accumulation of autophagosomes, and suppressed NMDA-mediated neuronal death. ATG7 siRNA studies also showed neuroprotective effects following NMDA treatment.

Conclusions

Collectively, this study shows that autophagy machinery is robustly induced in cultured neurons subjected to prolonged exposure to excitotoxin, while autophagosome clearance by lysosomal pathway might be impaired. Our data further show that prolonged autophagy contributes to cell death in NMDA-mediated excitotoxicity.     

Serum anticholinergic activity and cerebral cholinergic dysfunction: An EEG study in frail elderly with and without delirium

Background

Delirium increases morbidity, mortality and healthcare costs especially in the elderly. Serum anticholinergic activity (SAA) is a suggested biomarker for anticholinergic burden and delirium risk, but the association with cerebral cholinergic function remains unclear. To clarify this relationship, we prospectively assessed the correlation of SAA with quantitative electroencephalography (qEEG) power, delirium occurrence, functional and cognitive measures in a cross-sectional sample of acutely hospitalized elderly (> 80 y) with high dementia and delirium prevalence.

Methods

61 consecutively admitted patients over 80 years underwent an extensive clinical and neuropsychological evaluation. SAA was determined by using radio receptor assay as developed by Tune, and standard as well as quantitative EEGs were obtained.

Results

15 patients had dementia with additional delirium (DD) according to expert consensus using DSM-IV criteria, 31 suffered from dementia without delirium (D), 15 were cognitively unimpaired (CU). SAA was clearly detectable in all patients but one (mean 10.9 ± 7.1 pmol/ml), but was not associated with expert-panel approved delirium diagnosis or cognitive functions. Delirium-associated EEG abnormalities included occipital slowing, peak power and alpha decrease, delta and theta power increase and slow wave ratio increase during active delirious states. EEG measures correlated significantly with cognitive performance and delirium severity, but not with SAA levels.

Conclusion

In elderly with acute disease, EEG parameters reliable indicate delirium, but SAA does not seem to reflect cerebral cholinergic function as measured by EEG and is not related to delirium diagnosis.