The interplay of heuristics and parsing routines in sentence comprehension: evidence from ERPs and reaction times

Semantic anomalies like "the fox that hunted the poacher" elicit P600 effects. Kolk et al. [Kolk, H.J., Chwilla, D.J., Van Herten, M., Oor, P.J.W., 2003. Structure and limited capacity in verbal working memory: a study with event related potentials. Brain and language, 85(1), 1-36] proposed that this P600 effect is triggered by a conflict between the outcome of a lexical strategy with that of the parsing routine. Specifically, when the lexical strategy indicates that the poacher hunted the fox, the full parse leads to the conclusion that the fox was the one who did the hunting. We tested this hypothesis by replicating the study cited above but manipulating the context by means of instruction. Participants were informed that semantic anomalies were created on purpose and that they should not be misled by these anomalies but instead focus on syntax or sentence structure. This instruction led to a strong reduction in P600 effect. This result supports the view that expectations play an important role in the generation of P600 effects to semantic anomalies, as proposed by Kolk et al. [Kolk, H.J., Chwilla, D.J., Van Herten, M., Oor, P.J.W., 2003. Structure and limited capacity in verbal working memory: a study with event related potentials. Brain and language, 85(1), 1-36].     

The P3b and P600(s): Positive contributions to language comprehension

Since its discovery in the 1960s, the P300 has been contributing both directly and indirectly to language research. Perhaps most notably, it has been suggested that the P600, an ERP component that was first characterized in the context of syntactic processing, could be a variant of the P3b subcomponent of the P300. Here, we review studies on both sides of the debate. We also review the “semantic P600,” a positivity with a similar time course and distribution to the P600 seen for syntactic manipulations but that is obtained in response to some types of semantic anomalies. Because most current theories of the P600 try to account for both the syntactic and the semantic variant, linking the syntactic P600 to the P3b might also imply a similar link for the semantic P600. However, we describe emerging research in our lab that casts doubt on the idea that the syntactic P600 and the semantic P600 are the same effect. We argue that grouping ERP responses primarily by domain (language vs. nonlanguage) is likely to be misleading and suggest alternative ways of determining whether ERP effects reflect similar or different processing mechanisms.     

Age-related changes in the impact of contextual strength on multiple aspects of sentence comprehension

Contextual information influences multiple aspects of language comprehension extended over time. To determine how age-related changes impact normal comprehension, effects of contextual strength were examined with event-related potentials. Increased contextual constraint facilitated semantic processing (reduced N400s). Effects were smaller and delayed for older adults, and sensitivity to contextual information was diminished for weak contexts. Both groups elicited a later left-lateralized frontal negativity associated with reinterpretation of context when multiple interpretations of a sentence were likely. Older adults evidenced the frontal negativity over a wider range of constraint. The change in the use of contextual information across age is attributed to decreased reliance on predictive processing for older adults. Thus, age-related changes in comprehension lead to differential engagement of processing resources over time for older adults.     

Principal component analysis of the P600 waveform: RF and gender effects

The aim of the present study was to examine the patterns of activation of the P600 waveform of the event-related potentials (ERP), applying principal component analysis (PCA) and repeated measures ANOVA, and whether these patterns are RF and gender dependent. The ERPs of thirty-nine healthy subjects (20 male and 19 female) were recorded during an auditory memory task in the presence and absence of RF, similar to that emitted by mobile phones. Both PCA and ANOVA produced congruent results, showing that activation of the P600 component occurs early and more intensely in the region of the posterior electrodes and in a less intense manner in the central electrodes. Conversely, the activation at the anterior electrodes arises later with a considerably reduced intensity. In the absence of RF female subjects exhibited significantly lower amplitudes at anterior electrodes and earlier latencies at central electrodes than male subjects. These differences disappear in the presence of RF. Consequently, the P600 component follows distinct patterns of activation in the anterior, central and posterior brain areas and gender differences are observed simultaneously at several electrodes within these areas. Finally, the gender-related functional architecture with regard the P600 component appears to be RF sensitive. In conclusion, the application of the PCA procedure provides an adequate model of the spatially distributed event-related dynamics that correspond to the P600 waveform.     

Thinking ahead: the role and roots of prediction in language comprehension

Reviewed are studies using event-related potentials to examine when and how sentence context information is used during language comprehension. Results suggest that, when it can, the brain uses context to predict features of likely upcoming items. However, although prediction seems important for comprehension, it also appears susceptible to age-related deterioration and can be associated with processing costs. The brain may address this trade-off by employing multiple processing strategies, distributed across the two cerebral hemispheres. In particular, left hemisphere language processing seems to be oriented toward prediction and the use of top-down cues, whereas right hemisphere comprehension is more bottom-up, biased toward the veridical maintenance of information. Such asymmetries may arise, in turn, because language comprehension mechanisms are integrated with language production mechanisms only in the left hemisphere (the PARLO framework).     

Early components of event-related potentials related to semantic and syntactic processes in the Japanese language

Brain activities were compared between semantic and syntactic processing in the Japanese language using event-related potentials with a 58-ch EEG system. We previously found that semantic violations elicited N400 and syntactic violations elicited P600 but not early left anterior negativity (ELAN) or left anterior negativity (LAN) using a relatively long stimulus presentation time (1 s). In the present study, we adopted a shorter stimulus presentation time (0.5 s), which might impose a heavier burden on the working memory system, to test the possible relevance of load on the working memory system to ELAN/LAN. A global field power analysis showed an increased potential field strength at the latency of 320 ms in either type, as well as those at the later latencies reflecting N400 (556 ms) and P600 (712 ms). Statistical analyses revealed a significant negative deflection in the right frontal region for the semantic type, whereas no significant deflection in either specified region was obtained for the syntactic type at the latency of 320 ms. The lack of ELAN/LAN suggested that it was not due to the deactivation of the working memory system. Moreover, scalp current density topographies implied that the processing of the verbal stimuli was mediated by distinct areas within the left temporal region, according to its semantic congruency with the preceding context at a latency as early as 320 ms. These findings are in line with the dual-route hypothesis of reading, which suggests that the reading of verbal stimuli semantically incongruent with the preceding context is dominated by phonological processes rather than lexico-semantic.     

PRORP proteins support RNase P activity in both organelles and the nucleus in Arabidopsis

RNase P is an essential enzyme that cleaves the 5' leader sequence of tRNA precursors. RNase Ps were believed until now to occur universally as ribonucleoproteins in organisms performing RNase P activity. Here we find that protein-only RNase P enzymes called PRORP (for proteinaceous RNase P) support RNase P activity in vivo in both organelles and the nucleus in Arabidopsis. Beyond tRNA, PRORP proteins are involved in the maturation of small nucleolar RNA (snoRNA) and mRNA. Finally, ribonucleoprotein RNase MRP is not involved in tRNA maturation in plants. Altogether, our results indicate that ribonucleoprotein enzymes have been entirely replaced by proteins for RNase P activity in plants.     

Substance P and the regulation of inflammation in infections and inflammatory bowel disease

Substance P (SP) and its natural analogue hemokinin‐1 (HK1) are produced by lymphocytes and macrophages, and at times B cells. These peptides are an important component of the immune response during several infections and in inflammatory bowel disease (IBD). The synthesis of SP and HK1 in leucocytes is subject to immune regulation. IL12 and IL23 stimulate T cells and macrophages to make SP respectively. The cytokines driving HK1 production are not presently defined. These peptides act through a shared receptor called neurokinin‐1. T cells, macrophages and probably other immune cell types can express this receptor. Several cytokines IL12, IL18 and TNFα as well as T‐cell antigen receptor activation induce neurokinin‐1 receptor expression on T cells, while IL10 blocks receptor display. TGFβ delays internalization of the SP/neurokine‐1R complex on T cells resulting in stronger receptor signalling. One of the functions of SP and neurokinin‐1 receptor is to enhance T cell IFNγ and IL17 production, amplifying the proinflammatory response. Thus, SP and HK1 have overlapping functions and are part of a sophisticated immune regulatory circuit aimed at amplifying inflammation at mucosal surfaces and in other regions of the body as shown in animal models of infection and IBD.     

Comparison of three reference methods for the measurement of intracellular pH using 31P MRS in healthy volunteers and patients with lymphoma

³¹P magnetic resonance spectroscopy (³¹P MRS) can measure intracellular pH (pH_i) using the chemical shift difference between pH‐dependent inorganic phosphate (P_i) and a pH‐independent reference peak. This study compared three different frequency reference peaks [phosphocreatine (PCr), α resonance of adenosine triphosphate (αATP) and water (using ¹H MRS)] in a cohort of 10 volunteers and eight patients with non‐Hodgkin's lymphoma (NHL). Well‐resolved chemical shift imaging (CSI) spectra were acquired on a 1.5T scanner for muscle, liver and tumour. The pH was calculated for all volunteers and patients using the available methods. The consistency of the resulting pH was evaluated. The direct P_i–PCr method was best for those spectra with a very well‐defined PCr, such as muscle (pH=7.05 ± 0.02). In liver, the P_i–αATP method gave more consistent results (pH=7.30 ± 0.06) than the calibrated water‐based method (pH=7.27 ± 0.11). In NHL nodes, the measured pH using the P_i–αATP method was 7.25 ± 0.12. Given that the measured range includes some biological variation in individual patients, treatment‐related changes of the order of 0.1 pH units should be detectable. © 2013 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.     

Masking of a first target in the attentional blink attenuates the P3 to the first target and delays the P3 to the second target

The attentional blink (AB) refers to the decline in report accuracy of a second target (T2) when presented shortly after a first target (T1) in a rapid serial visual presentation (RSVP) of distractors. It is known that masking T1 increases the magnitude of the AB, and masking a single target (equivalent to T1) in a RSVP stream attenuates the P3 to the target in correct trials. The major purpose of the present study was to clarify how these two effects may be integrated. An intervening distractor was presented at lag 1 (T1+1), at lag 2 (T1+2), or at neither of these two lags (no distractor). T2 was always presented at lag 3, as the last item in the stream. The P3 to T1 was attenuated and the P3 to T2 delayed in the T1+1 condition compared to the two other distractor conditions. These results clearly show that masking T1 attenuates the P3 to T1 and delays the P3 to T2 in the AB. Implications for extant theories of the AB are discussed.     

Substance P in Dorsal Root Ganglion Neurons in Young and Adult Rats,after Nociceptive Stimulation during the Neonatal Period

The nervous system is highly plastic during the neonatal period, being sensitive to noxious stimuli, which may cause short‐ and long‐term pain responsivity changes. Understanding plasticity in peripheral pain pathways is crucial, particularly when the nervous system is still under development and remodeling process. Substance P (SP) is widely used as a marker for peripheral neurons with unmyelinated and small myelinated fibers. We investigated the number of SP immunoreactive neurons in the dorsal root ganglion (DRG) of male and female Wistar rats, 15 and 180 days after nociceptive stimulation during the neonatal period. Right and left 5th lumbar (L5) DRG were incubated in rabbit polyclonal anti‐substance P primary followed by biotinylated donkey anti‐rabbit secondary antibodies. Reaction was revealed with a nickel‐diaminobenzidine solution. Labeled neurons were counted and compared between ages, genders and groups. Gender differences were present in both ages, with the number of SP‐positive DRG neurons being larger in 15‐days‐old males on both sides. After 180 days, males showed a larger number of SP‐positive neurons than females only on the nociceptive stimulated side. An increased number of SP‐positive neurons in the DRG on the stimulated side was present in females, immediately after nociceptive stimulation, but not after 180 days. In conclusion, neonatal noxious stimulation caused a permanent increase in SP‐positive DRG neurons in males that was not observed in females, suggesting that differences in pain processing/responsivity between genders could be related to morphological alterations of the nervous system. Anat Rec, 301:849–861, 2018. © 2017 Wiley Periodicals, Inc.     

Longitudinal stability and predictive utility of the visual P3 response in adults with externalizing psychopathology

We determined whether time‐domain P3 amplitude and time‐frequency principal component (TF‐PC) reductions could serve as stable and predictive developmental endophenotypes of externalizing psychopathology. Participants from the Minnesota Twin Family Study were assessed at age 17 and again at age 29 for lifetime externalizing (EXT) disorders. Comparisons of P3 amplitude and TF‐PCs at delta and theta frequencies were made between EXT and unaffected comparison subjects. P3 amplitude and all five extracted TF‐PCs were significantly reduced in those presenting lifetime EXT disorders at both ages 17 and 29 and showed substantial 12‐year rank‐order stability. P3 amplitude and delta TF‐PCs measured at age 17 also predicted subsequent development of EXT by age 29, with every 1‐microvolt decrease in age 17 amplitude associated with an approximately 5% increase in risk for an EXT diagnosis by age 29. Overall, results from this study further confirm that these P3‐derived brain measures maintain their potential as putative EXT endophenotypes through the third decade of life.     

脊髓电刺激对大鼠心肌缺血SP和TRPV1表达的影响

目的探讨脊髓电刺激(SCS)缓解心肌缺血所致心绞痛的作用机制。方法健康雄性SD大鼠24只,随机分为4组:正常对照组,SCS组,心肌缺血组(CAO),SCS+CAO组;应用RT-PCR检测P物质(SP)和瞬时感受器辣椒素门控离子通道蛋白(TRPV1) mRNA在中枢神经系统的表达。结果心肌缺血时SPmRNA在脑干和胸4脊髓的表达明显增加,TRPV1 mRNA的表达无明显变化;SCS可降低SP和TRPV1 mRNA在脑干和胸4脊髓的表达水平。结论痛觉神经递质SP参与了心肌缺血所致心绞痛的神经信号传导,SCS缓解心绞痛可能是通过SP和TRPV1的介导而发挥作用。     

Changes in the P100 latency of the visual evoked potential and the saccadic reaction time during isometric contraction of the shoulder girdle elevators

We investigated changes in the P100 latency of the visual evoked potential (VEP) and the saccadic reaction time (SRT) in relation to the degree of activity of the shoulder girdle elevators. Muscle force was set in 10% increments from 0% to 50% of the maximal voluntary contraction (MVC). The VEP was derived from a midline occipital electrode with reference electrodes on the ears when the right retina was stimulated through the eyelid by light emitting diodes while the eyes were closed. The P100 latency of the VEP was defined as the time from the stimulus onset to the main positive peak. The SRT was defined as the latency until the beginning of eye movement toward the lateral target, which was moved at random time-intervals. P100 latency was shortened until 30% of the MVC, and which it lengthened. The SRT changed in a pattern similar to that observed for the P100 latency. The ratio of the shortening in P100 latency relative to that of the SRT was approximately 20%. All data is presented as the mean value, plus the standard deviation. We believe that the information processing time in the neural pathway from the retina to the visual cortex was shortened up to a certain muscle force of the shoulder girdle elevators, and then this processing time lengthened. These findings indicate that shortening of information processing time in the neural pathway beyond the visual cortex is included in the shortening of the SRT.     

Biphasic effects of substance P on respiratory activity and respiration‐related neurones in ventrolateral medulla in the neonatal rat brainstem in vitro

The effects of substance P (SP) on respiratory activity in the brainstem–spinal cord preparation from neonatal rats (0–4 days old) were investigated. The respiratory activity was recorded from C4 ventral roots and intracellularly from three types of respiration‐related neurones, i.e. pre‐inspiratory (or biphasic E), three subtypes of inspiratory; expiratory and tonic neurones in the ventrolateral medulla (VLM). After the onset of SP bath application (10 nM ^–1 μM ) a dose‐dependent decline of burst rate (by 48%) occurred, followed by a weaker dose‐dependent increase (by 17.5%) in burst rate. The biphasic effect of SP on inspiratory burst rate was associated with sustained membrane depolarization (in a range of 0.5–13 mV) of respiration‐related and tonic neurones. There were no significant changes in membrane resistance in any type of neurones when SP was applied alone or when synaptic transmission was blocked with tetrodotoxin (TTX). The initial depolarization was associated with an increase in inspiratory drive potential (by 25%) as well as in bursting time (by 65%) and membrane excitability in inspiratory and pre‐inspiratory neurones, which corresponded to the decrease in burst rate (C4 activity). The spiking frequency of expiratory and tonic neurones was also increased (by 36 and 48%). This activation was followed by restoration of the synaptic drive potential and bursting time in inspiratory and to a less extent in pre‐inspiratory neurones, which corresponded to the increase in burst rate. The discharge frequency of expiratory and tonic neurones also decreased to control values. This phase followed the peak membrane depolarization. At the peak depolarization, SP reduced the amplitude of the action potential by 4–8% in all types of neurones. Our results suggest that SP exerts a general excitatory effect on respiration‐related neurones and synaptic coupling within the respiratory network in the VLM. The transient changes in neuronal activity in the VLM may underlie the biphasic effect of SP in the brainstem respiration activity recorded in C4 roots. However, the biphasic effect of SP on inspiratory burst rate seems to be also defined by the balance in activity of other SP‐sensitive systems and neurones in the respiratory network in the brainstem and spinal cord, which can modify the activity of medullary respiratory rhythm generator.     

Structural and functional complexity of the humoral response against the Trypanosoma cruzi ribosomal P2 beta protein in patients with chronic Chagas' heart disease

High levels of antibodies against the C-terminus of the Trypanosoma cruzi TcP2 beta ribosomal protein, defined by the peptide EEEDDDMGFGLFD, named R13, have been measured in sera from patients with chronic Chagas' Heart Disease (cChHD). These antibodies also recognize an epitope on the second extracellular loop of the beta 1-adrenergic receptor, inducing a functional response on cardiomyocytes. The aim of this study was to gain novel insights into the structural basis of this cross-reactivity as well as to evaluate the origin of anti-M2- cholinergic receptor antibodies, which are also commonly found in cChHD patients. To address these questions we immunopurified anti-R13 antibodies and studied the structural requirements of epitope recognition. Results showed that the immunopurified antibodies recognized a conformation of R13 in which the third Glu residue was essential for binding, explaining their low affinity for the mammalian homologue (peptide H13: EESDDDMGFGLFD). Alanine mutation scanning showed individual variations in epitope recognition in each of the studied patients. The importance of a negatively charged residue at position 3 for the recognition of anti-R13 antibodies was further confirmed by competition experiments using a Ser3-phosphorylated H13 analogue, which had 10 times more affinity for the anti-R13 antibody than the native H13 peptide. Moreover, anti-R13 antibodies stimulated either the beta 1-adrenergic or the M2-cholinergic receptor, in strict agreement with the functional properties of the IgG fractions from which they derived, demonstrating that the same parasite antigen may generate antibody specificities with different functional properties. This may be a clue to explain the high variability of electrophysiological disturbances found in cChHD.     

31P nuclear magnetic resonance study on changes in phosphocreatine and the intracellular pH in rat skeletal muscle during exercise at various inspired oxygen contents

We measured ATP, phosphocreatine (PCr), inorganic phosphate (P_i), and the intracellular pH in rat hindlimb muscles during submaximal isometric exercise with various O₂ deliveries using³¹P nuclear magnetic resonance spectroscopy (³¹P NMR) to evaluate changes in energy metabolism in relation to O₂ availability. Delivery of O₂ to muscles was altered by controlling the fractional concentration of inspired oxygen (F _IO₂) at 0.50, 0.28, 0.21, 0.11 and 0.08 with monitoring partial pressure of oxygen and carbon dioxide, and bicarbonate at the femoral artery. The steady-state ratio of PCr : (PCr + P_i) during exercise decreased as a function ofF _IO₂ even at 0.21. Significant acidification of the intracellular pH during exercise occurred at 0.08F _IO₂. Change in the PCr : (PCr + P_i) ratio demonstrated that the oxidative capacity, i.e. the maximal rate of the oxidative phosphorylation reaction, in muscle was not limited by O₂ delivery at 0.50F _IO₂, but was significantly limited at 0.21F _IO₂ or below. Change in the intracellular pH at 0.08F _IO₂ could be interpreted as an increase in lactate, suggesting activation of glycolysis. Correlation between the PCr : (PCr + P_i) ratio and the intracellular pH revealed the existence of a critical PCr : (PCr + P_i) ratio and pH for glycolysis activation at around 0.4 and 6.7, respectively.