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Perinatal brain injury is a significant contributor to cerebral palsy, epilepsy, and other neurological disorders, occurring from 20 weeks’ gestation to 28 days postnatally. Approximately 40% of cases are associated with premature birth, whereas 11% result from acute intrapartum hypoxia–ischemia (HI). Despite improvements in neonatal care, the incidence remains stable, underscoring the need for better early detection methods. There is a critical “window of opportunity” for therapeutic intervention postinsult, with therapeutic hypothermia being the only established neuroprotective therapy for term infants. However, its efficacy is limited, as many infants continue to suffer disabilities despite treatment. The development of robust biomarkers is essential to identify infants at risk for significant brain injury and to evaluate the effectiveness of treatments. This chapter explores existing and novel biomarkers for assessing injury, determining treatability, and predicting long-term outcomes after HI, ultimately aiming to enhance management strategies for affected infants and improve prognostic abilities in clinical practice.
The term “prosody” encompasses properties of speech that span several timescales and levels of linguistic units, from the intensity and pitch of phonemes and syllables to the overall timing and intonation of utterances and conversations. Hierarchical temporal structure was introduced as a measure of clustering in sound energy that quantifies the relationship among timescales of prosody and related aspects of speech and music. The present chapter reviews several studies showing that the degree of hierarchical temporal structure in speech signals, as measured by the rate of increase in clustering with timescale, reflects the degree of prosodic composition. Prosodic composition can serve different purposes in communication, including linguistic emphasis and chunking in infant-directed speech, scaffolding of spoken interactions with children whose speech abilities are relatively less developed, and stricter timing in formal interactions. Prosodic composition as expressed by hierarchical temporal structure may serve as a control parameter in speech production and communication.
Brain rhythms at different timescales are observed ubiquitously across cortex. Despite this ubiquitousness, individual brain areas can be characterized by "spectral profiles," which reflect distinct patterns of endogenous brain rhythms. Crucially, endogenous brain rhythms have often been explicitly or implicitly related to perceptual and cognitive functions. Regarding language, a vast amount of research investigates the role of brain rhythms for speech processing. Particularly, lower-level processes, such as speech segmentation and consecutive syllable encoding and the hemispheric lateralization of such processes, have been related to auditory cortex brain rhythms in the theta and gamma range and explained by neural oscillatory models. Other brain rhythms – particularly delta and beta – have been related to prosodic processing (delta) but also higher-level language processing, including phrasal and sentential processing. Delta and beta brain rhythms have also been related to predictions from the motor cortex, emphasizing the tight link between production and perception. More recently, neural oscillatory models were extended to include different levels of language processing.
This book showcases the current state of the art of research on rhythm in speech and language. Decades of study have revealed that bodily rhythms are crucial for producing and understanding speech and language, and for understanding their evolution and variability across populations-not only adults, but also developmental and clinical populations. It is also clear that there is perplexing dimensionality and variability of rhythm within and across languages. This book offers the scientific foundation for harmonizing physiological universality and cultural diversity, fostering collaborative breakthroughs across research domains. Its fifty chapters cover physiology, cognition, and culture, presenting knowledge from neuroscience, cognitive science, psychology, phonetics, and communication research. Ideal for academics, researchers, and professionals seeking interdisciplinary insights into the essence of human communication. This title is also available as open access on Cambridge Core.
This chapter covers all forms of neuronal communication, from neuron-to-neuron signaling to communication with the body and external world. It begins with an overview of electrophysiology, focusing on how action potentials and ion channels drive electrical signaling in neurons. It then explains neurotransmission, detailing how neurotransmitters are synthesized, released, and regulated through processes like reuptake and degradation. The chapter then expands upon the concept of neuronal communication to include how neurons control body functions, such as muscle movement and hormone release, and how they process sensory input like light, sound, and touch through specialized receptors. Finally, the chapter incorporates plasticity, describing how neuronal communication affects synaptic restructuring via processes like long-term potentiation.
Large-scale neural activity during emotional processes can be measured noninvasively and in real time using electroencephalography (EEG) and magnetoencephalography (MEG). Both methods have been applied to the study of human affect, yielding information regarding the time course and cerebral correlates of emotional processes. This chapter aims to provide the reader with an understanding of how EEG and MEG may be used in affective neuroscience, including current trends and new methods in this rapidly expanding field. To this end, we discuss the neurophysiological mechanisms and physical origin of electromagnetic brain signals, highlighting methodological challenges and paradigmatic applications of EEG and MEG in affective neuroscience. We also illustrate methodological approaches used by affective neuroscientists, including experimental designs, data-recording procedures, and analytical methods. The chapter concludes by noting major challenges and future directions for EEG and MEG studies in affective neuroscience research.
The GABA type A receptor (GABAAR) belongs to the family of pentameric ligand-gated ion channels and plays a key role in inhibition in adult mammalian brains. Dysfunction of this macromolecule may lead to epilepsy, anxiety disorders, autism, depression, and schizophrenia. GABAAR is also a target for multiple physiologically and clinically relevant modulators, such as benzodiazepines (BDZs), general anesthetics, and neurosteroids. The first GABAAR structure appeared in 2014, but the past years have brought a particularly abundant surge in structural data for these receptors with various ligands and modulators. Although the open conformation remains elusive, this novel information has pushed the structure–function studies to an unprecedented level. Electrophysiology, mutagenesis, photolabeling, and in silico simulations, guided by novel structural information, shed new light on the molecular mechanisms of receptor functioning. The main goal of this review is to present the current knowledge of GABAAR functional and structural properties. The review begins with an outline of the functional and structural studies of GABAAR, accompanied by some methodological considerations, especially biophysical methods, enabling the reader to follow how major breakthroughs in characterizing GABAAR features have been achieved. The main section provides a comprehensive analysis of the functional significance of specific structural elements in GABAARs. We additionally summarize the current knowledge on the binding sites for major GABAAR modulators, referring to the molecular underpinnings of their action. The final chapter of the review moves beyond examining GABAAR as an isolated macromolecule and describes the interactions of the receptor with other proteins in a broader context of inhibitory plasticity. In the final section, we propose a general conclusion that agonist binding to the orthosteric binding sites appears to rely on local interactions, whereas conformational transitions of bound macromolecule (gating) and allosteric modulation seem to reflect more global phenomena involving vast portions of the macromolecule.
The ‘Viroporin’ family comprises a number of mostly small-sized, integral membrane proteins encoded by animal and plant viruses. Despite their sequence and structural diversity, viroporins share a common functional trend: their capacity to assemble transmembrane channels during the replication cycle of the virus. Their selectivity spectrum ranges from low-pH-activated, unidirectional proton transporters, to size-limited permeating pores allowing passive diffusion of metabolites. Through mechanisms not fully understood, expression of viroporins facilitates virion assembly/release from infected cells, and subverts the cell physiology, contributing to cytopathogenicity. Compounds that interact with viroporins and interfere with their membrane-permeabilizing activity in vitro, are known to inhibit virus production. Moreover, viroporin-defective viruses comprise a source of live attenuated vaccines that prevent infection by notorious human and livestock pathogens. This review dives into the origin and evolution of the viroporin concept, summarizes some of the methodologies used to characterize the structure–function relationships of these important virulence factors, and attempts to classify them on biophysical grounds attending to their mechanisms of ion/solute transport across membranes.
Multilingual language control is commonly investigated using picture-naming paradigms with explicit instructions when to switch between languages. In daily life, language switching also occurs without external cues. Cued language-switching tasks usually show a switch cost (i.e., slower responses on switch than non-switch trials). Findings of switch costs in response times are mixed for voluntary language switching. This pre-registered study uses a bilingual picture-naming paradigm to compare voluntary and cued language switching in 25 highly proficient Dutch-English bilinguals using EEG. We analysed the N2 ERP component and midfrontal theta oscillations, two common electrophysiological markers of cognitive control in task and language switching. We observed significantly smaller behavioural switch costs in the voluntary task. This suggests that voluntary language switching is less effortful than switching based on external cues. However, we found no electrophysiological switch effects in either task. We discuss factors which may contribute to the inconsistency between behavioural and electrophysiological findings.
Alternate electrocardiogram acquisition with fewer leads lacks systematic evaluation in children. This study aims to determine if electrocardiograms with fewer leads maintain diagnostic accuracy in paediatrics.
Methods:
This is a single-centre review of 200 randomly selected standard 12-lead electrocardiograms from our hospital database (2017–2020) for patients aged 2 weeks to 21 years. An overlay technique generated 8-lead (limb + V1/V6) and 6-lead (limb only) variations of the 12-lead tracings, resulting in a total of 600 electrocardiograms, which were then interpreted by two independent paediatric electrophysiologists.
Results:
In total, 18% (35/200) of the baseline electrocardiograms were abnormal. Intervals were measured in lead II for all electrocardiograms. Comparing 12-lead to 6- and 8-lead electrocardiograms, there was almost perfect agreement for specific rhythm identification (97.5–100%, κ 0.85-1). The 8-lead showed substantial agreement with 12-lead electrocardiograms when identifying specific electrocardiogram patterns (97.5–100%, κ 0.66–1). A similar degree of agreement was not demonstrated with the 6-lead variant. Utilising the 12-lead electrocardiogram as the gold standard, sensitivity and specificity of the 8- and 6-lead electrocardiogram were > 89% for specific rhythm identification. Specificity for specific pattern recognition was > 99% while sensitivity was < 90% for certain variables for both 6- and 8-lead electrocardiogram, likely due to smaller sample size and fewer abnormal electrocardiograms. There was high percent reader agreement (92.5–100%).
Conclusions:
8-lead electrocardiograms provide comparable diagnostic accuracy to 12-lead electrocardiograms for children. This information holds potential for future technological advancements in electrocardiogram acquisition tailored specifically for paediatrics. Additional studies are required to further refine conventional electrocardiogram acquisition.
The Automatic Selective Perception (ASP) model posits that listeners make use of selective perceptual routines (SPRs) that are fast and efficient for recovering lexical meaning. These SPRs serve as filters to accentuate relevant cues and minimize irrelevant information. Years of experience with the first language (L1) lead to fairly automatic L1 SPRs; consequently, few attentional resources are needed in processing L1 speech. In contrast, L2 SPRs are less automatic. Under difficult task or stimulus conditions, listeners fall back on more automatic processes, specifically L1 SPRs. And L2 speech perception suffers where there is a mismatch between the L1 and the L2 phonetics because L1 SPRs may not extract the important cues needed for identifying L2 phonemes. This chapter will present behavioral and neurophysiology evidence that supports the ASP model, but which also indicates the need for some modification. We offer suggestions for future directions in extending this model.
Electrocardiograms are frequently obtained in infants and children. Training specific to paediatric electrocardiogram interpretation is necessary given that cardiac physiology and electrocardiogram findings in children are different than adults and change throughout infancy and childhood. Distributed practice may be an effective method to improve paediatric residency electrocardiogram education efforts.
Methods:
A pre-survey was administered to paediatric and internal medicine/paediatrics residents to ascertain baseline comfort with electrocardiogram interpretation. Subsequently, residents were emailed a clinical vignette with an associated electrocardiogram and multiple-choice question 1–2 times monthly. After submitting their answer, residents were taken to a webpage explaining key concepts explored in the clinical vignette. After 6 and 12 months, a survey was administered asking residents to again rate their confidence in the same electrocardiogram interpretation skills.
Results:
The longitudinal email-based curriculum increased exposure to electrocardiogram training. Six months of participation in the curriculum correlated with significant increases in confidence in electrocardiogram interpretation skills. While there was no further increase in confidence seen at 12 months, the improvement seen at 6 months was durable. Participation in the curriculum most significantly correlated with changes in confidence in ability to utilise a stepwise approach for electrocardiogram interpretation.
Conclusions:
The curriculum resulted in durable improvement in confidence in electrocardiogram interpretation skills for paediatric residents at our centre, suggesting that email-based distributive practice can be an effective method for skill and knowledge improvement for complex educational topics.
This study aimed to compare the peripheral-to-central auditory systems of people with coronavirus disease 2019 to a well-matched control group and examine the long-term effects of coronavirus disease 2019 on the auditory system.
Method
Participants who were outpatients of coronavirus disease 2019 (n = 30) were compared with a well-matched control group (n = 30). Behavioural and electrophysiological tests were performed, and tests were repeated at six months in the coronavirus disease 2019 group.
Results
Statistically significant differences were observed in the right ear at 10 kHz (p = 0.007) and 12.5 kHz (p = 0.028), and in the left ear at 10 kHz (p = 0.040) and 12.5 kHz (p = 0.040) between groups. The groups had no difference regarding the other audiological test results (p > 0.05).
Conclusion
Extended high-frequency thresholds were affected in the coronavirus disease 2019 patients. No other findings indicated that the peripheral-to-central auditory system was affected. The effect on extended high-frequency thresholds appeared permanent, but no clinically significant new, late-onset auditory system effects were observed.
This study aimed to determine the precautions that can be taken to increase the reliability of the vestibular evoked myogenic potentials test without being affected by the asymmetry of the sternocleidomastoid muscle and the issues that should be considered in the interpretation of vestibular evoked myogenic potential results if these precautions are not taken.
Method
Individuals with sternocleidomastoid muscle activity of less than 30 μV in cervical vestibular evoked myogenic potential testing and an asymmetry ratio of more than 0.35 were excluded. In our study, individuals were divided into different groups according to sternocleidomastoid muscle asymetry.
Results
A total of 53 individuals were included in the study. Intergroup comparisons were made to determine the effect of electromyogram scaling and filter use on amplitude asymmetry ratio according to sternocleidomastoid muscle asymmetry.
Conclusion
Keeping the sternocleidomastoid muscle asymmetry not exceeding 10 μV maximises the reliability of cervical vestibular evoked myogenic potentials. As a result of our study, it can be concluded that in clinical applications the asymmetry should not exceed 20 μV.
Edited by
Deepak Cyril D'Souza, Staff Psychiatrist, VA Connecticut Healthcare System; Professor of Psychiatry, Yale University School of Medicine,David Castle, University of Tasmania, Australia,Sir Robin Murray, Honorary Consultant Psychiatrist, Psychosis Service at the South London and Maudsley NHS Trust; Professor of Psychiatric Research at the Institute of Psychiatry
Converging lines of pre-clinical, epidemiological, and experimental evidence support an association between cannabis, cannabinoid agonists, and psychosis (see Chapters 14 and 15). The earliest anecdotal reports on observations between the use of cannabis and subsequent psychosis have been validated by a rich literature of longitudinal studies and more recently experimental studies in humans using a wide array of subjective, cognitive, and electrophysiological outcomes relevant to psychosis. This chapter provides an overview of the subjective psychotic phenomena associated with cannabis and cannabinoids and expands on more objective cognitive and psychophysiological cannabis-related effects pertinent to psychosis.
Cardiac arrhythmias occur at all ages. Cardiac mapping and ablation are established methods for curing arrhythmia substrates; however, complications may occur. We report a patient with transient Wenckebach heart block during radiofrequency ablation in the setting of Wolff Parkinson White syndrome despite the ablation catheter being well away from the atrioventricular node, and we speculate on the potential mechanism.
A major pathophysiological hypothesis of schizophrenia states an increased activity of glutamatergic neurons leading to an imbalance of neural excitation and inhibition (E/I-imbalance). One potential molecular mechanism of E/I-imbalance is a dysfunction of voltage-gated sodium channels, which are crucial for the generation of action potentials, the fundamental event of neuronal excitation. Indeed, patients with schizophrenia exhibit an increased burden of rare exonic variants of sodium channel genes, but the literature describing their electrophysiological effect is scarce.
Objectives
The aim of this project is to assess the functional impact of three mutations of the Sodium Voltage-Gated Channel Alpha Subunit 2 (SCN2A) gene / NaV1.2 channel which were identified in four patients with schizophrenia, using a heterologous expression system.
Methods
Three variants of the human SCN2A gene (R850P, V1282F and S1656P) were created using site-directed mutagenesis. HEK293T cells transfected with either the mutant or wild type constructs are being investigated by voltage-clamp technique, applying activation, steady-state fast inactivation, use dependency and ramp protocols.
Results
All three mutated constructs were successfully created. Preliminary recordings from the V1282F mutant indicate a shift of both the activation and steady-state fast inactivation to the hyperpolarized direction.
Conclusions
In a subgroup of patients, E/I imbalance may be a consequence of Nav1.2 mutations leading to increased excitability of glutamatergic neurons. By integrating insights from different mutations we aim to identify traits of a potentially shared disease pathway which may provide a basis for the development of novel therapeutics.
Precision medicine in psychiatry is based on the identification of homogeneous subgroups of patients with the help of biosignatures—sets of biomarkers—in order to enhance diagnosis, stratification of patients, prognosis, evaluation, and prediction of treatment response. Within the broad domain of biomarker discovery, we propose retinal electrophysiology as a tool for identification of biosignatures. The retina is a window to the brain and provides an indirect access to brain functioning in psychiatric disorders. The retina is organized in layers of specialized neurons which share similar functional properties with brain neurons. The functioning of these neurons can be evaluated by electrophysiological techniques named electroretinogram (ERG). Since the study of retinal functioning gives a unique opportunity to have an indirect access to brain neurons, retinal dysfunctions observed in psychiatric disorders inform on brain abnormalities. Up to now, retinal dysfunctions observed in psychiatric disorders provide indicators for diagnosis, identification of subgroups of patients, prognosis, evaluation, and prediction of treatment response. The use of signal processing and machine learning applied on ERG data enhances retinal markers extraction, thus providing robust, reproducible, and reliable retinal electrophysiological markers to identify biosignatures in precision psychiatry. We propose that retinal electrophysiology may be considered as a new approach in the domain of electrophysiology and could now be added to the routine evaluations in psychiatric disorders. Retinal electrophysiology may provide, in combination with other approaches and techniques, sets of biomarkers to produce biosignatures in mental health.
The objective was to use bibliometric analysis to create an infographic of motor unit number estimation methods over the past 50 years. The original method was published in 1971, but secondary and tertiary waves of research using alternative methods occurred in the early 2000s and a decade later. A metric of influence was used to determine if different methods had clear peaks of use over the past 50 years. While the original method continues to register influence, the MUNIX method introduced in 2004 stands out as the most influential method to estimate the innervation status of skeletal muscles.