Early Electrical Activity Research Articles

Development of Prefrontal Circuits and Cognitive Abilities.

The prefrontal cortex is considered as the site of multifaceted higher-order cognitive abilities. These abilities emerge late in life long after full sensorimotor maturation, in line with the protracted development of prefrontal circuits that has been identified on molecular, structural, and functional levels. Only recently, as a result of the impressive methodological progress of the last several decades, the mechanisms and clinical implications of prefrontal development have begun to be elucidated, yet major knowledge gaps still persist. Here, we provide an overview on how prefrontal circuits develop to enable multifaceted cognitive processing at adulthood. First, we review recent insights into the mechanisms of prefrontal circuit assembly, with a focus on the contribution of early electrical activity. Second, we highlight the major reorganization of prefrontal circuits during adolescence. Finally, we link the prefrontal plasticity during specific developmental time windows to mental health disorders and discuss potential approaches for therapeutic interventions.

Human Embryonic Stem Cell-Derived Cardiomyocytes Regenerate the Infarcted Pig Heart but Induce Ventricular Tachyarrhythmias.

SummaryHuman embryonic stem cell-derived cardiomyocytes (hESC-CMs) show considerable promise for regenerating injured hearts, and we therefore tested their capacity to stably engraft in a translationally relevant preclinical model, the infarcted pig heart. Transplantation of immature hESC-CMs resulted in substantial myocardial implants within the infarct scar that matured over time, formed vascular networks with the host, and evoked minimal cellular rejection. While arrhythmias were rare in infarcted pigs receiving vehicle alone, hESC-CM recipients experienced frequent monomorphic ventricular tachycardia before reverting back to normal sinus rhythm by 4 weeks post transplantation. Electroanatomical mapping and pacing studies implicated focal mechanisms, rather than macro-reentry, for these graft-related tachyarrhythmias as evidenced by an abnormal centrifugal pattern with earliest electrical activation in histologically confirmed graft tissue. These findings demonstrate the suitability of the pig model for the preclinical development of a hESC-based cardiac therapy and provide new insights into the mechanistic basis of electrical instability following hESC-CM transplantation.

Modulation of Neocortical Development by Early Neuronal Activity: Physiology and Pathophysiology.

Animal and human studies revealed that patterned neuronal activity is an inherent feature of developing nervous systems. This review summarizes our current knowledge about the mechanisms generating early electrical activity patterns and their impact on structural and functional development of the cerebral cortex. All neocortical areas display distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, intermittent spontaneous activity is synchronized within small neuronal networks, becoming more complex with further development. This transition is accompanied by a gradual shift from electrical to chemical synaptic transmission, with a particular role of non-synaptic tonic currents before the onset of phasic synaptic activity. In this review article we first describe functional impacts of classical neurotransmitters (GABA, glutamate) and modulatory systems (e.g., acetylcholine, ACh) on early neuronal activities in the neocortex with special emphasis on electrical synapses, nonsynaptic and synaptic currents. Early neuronal activity influences probably all developmental processes and is crucial for the proper formation of neuronal circuits. In the second part of our review, we illustrate how specific activity patterns might interfere with distinct neurodevelopmental processes like proliferation, migration, axonal and dendritic sprouting, synapse formation and neurotransmitter specification. Finally, we present evidence that transient alterations in neuronal activity during restricted perinatal periods can lead to persistent changes in functional connectivity and therefore might underlie the manifestation of neurological and neuropsychiatric diseases.

Cajal-Retzius cells: organizers of cortical development

Cajal-Retzius cells (CRc) are a major neuronal population in the marginal zones of the developing neocortex and hippocampus. CRc belong to the earliest born neurons in the cortex and originate from several regions at the pallial-subpallial border. A substantial fraction of CRc disappears during postnatal development. CRc express a variety of neurotransmitter receptors, receive mainly GABAergic synaptic inputs and give rise to glutamatergic synapses. Recent studies identified some modes of how CRc are integrated into immature neuronal circuits, although their exact role for immature information processing remains unknown. As a major source for the extracellular matrix protein reelin, which is critically involved in lamination of the cerebral cortex, CRc are an important factor for the structural development of the neocortex and hippocampus. In addition, CRc contribute to the patterning of cortical areas and shape the development of perforant path connections in the hippocampus. In summary, CRc are a major cellular element in the structural development of the cerebral cortex and may serve as a link between early electrical activity and morphological organization during prenatal und early postnatal development.

PP14.2 – 2563: Early electrical brain activity in preterm neonates with very low birth weight with prolonged respiratory therapy without clinical and ultrasound features of acute brain damages

There is prevalence of neurodevelopmental impairment in children born extremely premature and in recent years it is observed and considers as a result of acute brains damage occurring during the first postnatal weeks. Development of methods that enable early identification of functional disorders and risk of acute brain injury in preterm infants is obvious necessary in NICU (neonatal intensive care unit). Aim To demonstrate the physiological features of brain activity in the early neonatal period in preterm infants receiving respiratory therapy (prolonger mechanical ventilation), with very low birth weights and gestational age up to 32 weeks, in acute neonatal period without clinical and brains images sings detecting by cranial ultrasound. Subjects: We studied 10 neurologically healthy preterm babies with prolonged mechanically ventilation, they gestation age was between 27–30 weeks (averages M=28.6±3.59 weeks), with averages weight birth (M) 1077±359 grams. Nobody obtained sedation therapy. Methods Scalp EEG was recorded with 8 electrodes on 3–5 days after birth, duration – 1 hour. Repeated cranial ultrasound investigations (cUS) were performed on days1, 3 and 7 and 4 weeks after birth. Results Structural brain changes has not been detected by cUS in all patients. Early EEG activity in all preterm patients consists of patterns discontinue: inter burst interval (IBI) and burst of electrical activity. Maximum duration of IBI was 8–25 sec, (M=15.8±10.45 sec), minimum duration – 4–12 sec (M=8, 2±6.28 s). Averages time of IBI in preterm infants with very low birth weight was 6–18.5 sec (M=11.4±8.97). Conclusion Study demonstrates that the electro-cortical background activity, in the early neonatal period in preterm infants with very low birth weight and receiving respiratory therapy (prolonger mechanical ventilation), without clinical and neuroimigine damage sings is presented by trace discontinue. The average durations of inter burst interval is 11.4±8.97 s.

Developmental mapping of small‐conductance calcium‐activated potassium channel expression in the rat nervous system

Early electrical activity and calcium influx regulate crucial aspects of neuronal development. Small-conductance calcium-activated potassium (SK) channels regulate action potential firing and shape calcium influx through feedback regulation in mature neurons. These functions, observed in the adult nervous system, make them ideal candidates to regulate activity-and calcium-dependent processes in neurodevelopment. However, to date little is known about the onset of expression and regions expressing SK channel subunits in the embryonic and postnatal development of the central nervous system (CNS). To allow studies on the contribution of SK channels to different phases of development of single neurons and networks, we have performed a detailed in situ hybridization mapping study, providing comprehensive distribution profiles of all three SK subunits (SK1, SK2, and SK3) in the rat CNS during embryonic and postnatal development. SK channel transcripts are expressed at early stages of prenatal CNS development. The three SK channel subunits display different developmental expression gradients in distinct CNS regions, with time points of expression and up-or downregulation that can be associated with a range of diverse developmental events. Their early expression in embryonic development suggests an involvement of SK channels in the regulation of developmental processes. Additionally, this study shows how the postnatal ontogenetic patterns lead to the adult expression map for each SK channel subunit and how their coexpression in the same regions or neurons varies throughout development. J. Comp. Neurol. 522:1072–1101, 2014. © 2013 Wiley Periodicals, Inc.

Simultaneous coronary angiography during titration of radiofrequency energy for ablation of left ventricular summit tachycardia in the ‘inaccessible area’

A 45-year-old patient with an implantable cardioverter defibrillator and a decreased left ventricular (LV) ejection fraction (40%) due to non-ischaemic cardiomyopathy was referred for ablation of recurrent LV outflow tract tachycardia. Endocardial and coronary venous mapping revealed earliest electrical activation within the distal great cardiac vein (GCV). Endocardial LV ablation was unsuccessful and …

Electrical activity patterns and the functional maturation of the neocortex

At the earliest developmental stages, sensory neocortical areas in various species reveal distinct patterns of spontaneous neuronal network activity. These activity patterns either propagate over large neocortical areas or synchronize local neuronal ensembles. In vitro and in vivo experiments indicate that these spontaneous activity patterns are generated from neuronal networks in the cerebral cortex, in subcortical structures or in the sensory periphery (retina, cochlea, whiskers). At early stages spontaneous periphery-driven and also sensory evoked activity is relayed to the developing cerebral cortex via the thalamus and the neocortical subplate, which amplifies the afferent sensory input. These early local and large-scale neuronal activity patterns influence a variety of developmental processes during corticogenesis, such as neurogenesis, apoptosis, neuronal migration, differentiation and network formation. The experimental data also indicate that disturbances in early neuronal patterns may have an impact on the development of cortical layers, columns and networks. In this article we review our current knowledge on the origin of early electrical activity patterns in neocortical sensory areas and their functional implications on shaping developing cortical networks.

Sonic hedgehog signaling is decoded by calcium spike activity in the developing spinal cord

Evolutionarily conserved hedgehog proteins orchestrate the patterning of embryonic tissues, and dysfunctions in their signaling can lead to tumorigenesis. In vertebrates, Sonic hedgehog (Shh) is essential for nervous system development, but the mechanisms underlying its action remain unclear. Early electrical activity is another developmental cue important for proliferation, migration, and differentiation of neurons. Here we demonstrate the interplay between Shh signaling and Ca(2+) dynamics in the developing spinal cord. Ca(2+) imaging of embryonic spinal cells shows that Shh acutely increases Ca(2+) spike activity through activation of the Shh coreceptor Smoothened (Smo) in neurons. Smo recruits a heterotrimeric GTP-binding protein-dependent pathway and engages both intracellular Ca(2+) stores and Ca(2+) influx. The dynamics of this signaling are manifested in synchronous Ca(2+) spikes and inositol triphosphate transients apparent at the neuronal primary cilium. Interaction of Shh and electrical activity modulates neurotransmitter phenotype expression in spinal neurons. These results indicate that electrical activity and second-messenger signaling mediate Shh action in embryonic spinal neurons.

Contexts for Dopamine Specification by Calcium Spike Activity in the CNS

Calcium-dependent electrical activity plays a significant role in neurotransmitter specification at early stages of development. To test the hypothesis that activity-dependent differentiation depends on molecular context, we investigated the development of dopaminergic neurons in the CNS of larval Xenopus laevis. We find that different dopaminergic nuclei respond to manipulation of this early electrical activity by ion channel misexpression with different increases and decreases in numbers of dopaminergic neurons. Focusing on the ventral suprachiasmatic nucleus and the spinal cord to gain insight into these differences, we identify distinct subpopulations of neurons that express characteristic combinations of GABA and neuropeptide Y as cotransmitters and Lim1,2 and Nurr1 transcription factors. We demonstrate that the developmental state of neurons identified by their spatial location and expression of these molecular markers is correlated with characteristic spontaneous calcium spike activity. Different subpopulations of dopaminergic neurons respond differently to manipulation of this early electrical activity. Moreover, retinohypothalamic circuit activation of the ventral suprachiasmatic nucleus recruits expression of dopamine selectively in reserve pool neurons that already express GABA and neuropeptide Y. The results are consistent with the hypothesis that spontaneously active neurons expressing GABA are most susceptible to activity-dependent expression of dopamine in both the spinal cord and brain. Because loss of dopaminergic neurons plays a role in neurological disorders such as Parkinson's disease, understanding how subpopulations of neurons become dopaminergic may lead to protocols for differentiation of neurons in vitro to replace those that have been lost in vivo.

Visual sensory processing deficit in the occipital region in children with attention-deficit/hyperactivity disorder as revealed by event-related potentials during cued continuous performance test

Recent studies described several changes of attention-related components of late frontal event-related potentials (ERPs) during Go/NoGo paradigm in children with attention-deficit/hyperactivity disorder (ADHD). We aimed to determine whether ERP components corresponding to earlier encoding of visual incoming information are also modulated by attentional disorders. We recorded high-resolution EEG in 15 children meeting DSM-IV criteria for ADHD, comprising 15 age-matched control groups during an equiprobable Go/NoGo task in a cued continuous performance test (CPT-AX) paradigm. Both P100 and N200 ERP components were measured in response to both Go and NoGo stimuli. We analyzed both components with SwLORETA in order to localize their brain sources. A low rate of Go correct response and high rate of omission errors were observed in ADHD children. When compared to controls, these displayed delayed P100 and N200 latency, and lower P100-NoGo amplitude. In addition, the P100 latency was delayed for NoGo compared to Go condition. The source of P100 was located in occipital area. A sizable decrease in early electrical activity was found in ADHD, especially in the NoGo condition. Our results suggest an early deficit in visual sensory integration within the occipital cortex in children with ADHD.

I heard that coming: event-related potential evidence for stimulus-driven prediction in the auditory system.

The auditory system has been shown to detect predictability in a tone sequence, but does it use the extracted regularities for actually predicting the continuation of the sequence? The present study sought to find evidence for the generation of such predictions. Predictability was manipulated in an isochronous series of tones in which every other tone was a repetition of its predecessor. The existence of predictions was probed by occasionally omitting either the first (unpredictable) or the second (predictable) tone of a same-frequency tone pair. Event-related electrical brain activity elicited by the omission of an unpredictable tone differed from the response to the actual tone right from the tone onset. In contrast, early electrical brain activity elicited by the omission of a predictable tone was quite similar to the response to the actual tone. This suggests that the auditory system preactivates the neural circuits for expected input, using sequential predictions to specifically prepare for future acoustic events.

Abnormal spatiotemporal processing of emotional facial expressions in childhood autism: dipole source analysis of event‐related potentials

Previous studies of face processing in autism suggest abnormalities in anatomical development, functioning and connectivity/coordination of distributed brain systems involved in social cognition, but the spatial sequence and time course of rapid (sub-second) neural responses to emotional facial expressions have not been examined in detail. Source analysis of high-density event-related potentials (ERPs) is an optimal means to examine both the precise temporal profile and spatial location of early electrical brain activity in response to emotionally salient stimuli. Therefore, we recorded 128-channel ERPs from high-functioning males with autism (aged 6-10 years), and age-, sex- and IQ-matched typically developing controls during explicit and implicit processing of emotion from pictures showing happy, angry, fearful, sad and neutral facial expressions. Children with autism showed normal patterns of behavioural and ERP (P1, N170 and P2) responses. However, dipole source analysis revealed that ERP responses relating to face detection (visual cortex) and configural processing of faces (fusiform gyrus), as well as mental state decoding (medial prefrontal lobe), were significantly weaker and/or slower in autism compared with controls during both explicit and implicit emotion-processing tasks. Slower- and larger-amplitude ERP source activity in the parietal somatosensory cortices possibly reflected more effortful compensatory analytical strategies used by the autism group to process facial gender and emotion. Such aberrant neurophysiological processing of facial emotion observed in children with autism within the first 300 ms of stimulus presentation suggests abnormal cortical specialization within social brain networks, which would likely disrupt the development of normal social-cognitive skills.

Glycine Receptors Mediate Excitation of Subplate Neurons in Neonatal Rat Cerebral Cortex

The development of the cerebral cortex depends on genetic factors and early electrical activity patterns that form immature neuronal networks. Subplate neurons (SPn) are involved in the construction of thalamocortical innervation, generation of oscillatory network activity, and in the proper formation of the cortical columnar architecture. Because glycine receptors play an important role during early corticogenesis, we analyzed the functional consequences of glycine receptor activation in visually identified SPn in neocortical slices from postnatal day 0 (P0) to P4 rats using whole cell and perforated patch-clamp recordings. In all SPn the glycinergic agonists glycine, beta-alanine, and taurine induced dose-dependent inward currents with the affinity for glycine being higher than that for beta-alanine and taurine. Glycine-induced responses were blocked by the glycinergic antagonist strychnine, but were unaffected by either the GABAergic antagonist gabazine, the N-methyl-d-aspartate-receptor antagonist d-2-amino-5-phosphonopentanoic acid, or picrotoxin and cyanotriphenylborate, antagonists of alpha-homomeric and alpha1-subunit-containing glycine receptors, respectively. Under perforated-patch conditions, glycine induced membrane depolarizations that were sufficient to trigger action potentials (APs) in most cells. Furthermore, glycine and taurine decreased the injection currents as well as the synaptic stimulation strength required to elicit APs, indicating that glycine receptors have a consistent excitatory effect on SPn. Inhibition of taurine transport and application of hypoosmolar solutions induced strychnine-sensitive inward currents, suggesting that taurine can act as a possible endogenous agonist on SPn. In summary, these results demonstrate that SPn express glycine receptors that mediate robust excitatory membrane responses during early postnatal development.

Surgical treatment of ventricular tachycardias: Complete versus partial encircling endocardial ventriculotomy

Forty consecutive patients underwent electrophysiologically guided encircling endocardial ventriculotomy as treatment for recurrent sustained ventricular tachycardia resulting from coronary artery disease and previous myocardial infarction. Twelve patients (30%, Group I) had a complete encircling endocardial ventriculotomy and 28 (70%, Group II) had a partial encircling endocardial ventriculotomy (54.4% +/- 2.2% of the left ventricular endocardial circumference) at the earliest electrical activation during ventricular tachycardia. There were no significant differences between the two groups in age, sex ratio, New York Heart Association class, coronary disease, aneurysm location, concomitant bypass grafting, and left ventricular function. One patient of Group I and two patients of Group II did not survive the perioperative period (8% versus 7%, not significant). The survivors were restudied electrophysiologically about 3 weeks after the operation. Eight patients of Group I and 19 patients of Group II were free of ventricular tachycardia (no spontaneous or inducible ventricular tachycardia) without antiarrhythmic drugs (73% versus 73%, not significant). The mean follow-up period in Group I is 22.6 months and in Group II, 15.2 months. Five patients of Group I and of Group II developed severe left ventricular dysfunction (46% versus 8%; p = 0.025). Also, congestive heart failure was a significant cause of death in Group I patients (p = 0.036). In conclusion, electrophysiologically guided partial encircling endocardial ventriculotomy is highly efficient as a surgical treatment of recurrent sustained ventricular tachycardia. Complete encircling endocardial ventriculotomy offers no better ablation of arrhythmias and should be avoided because of its apparent hazards to left ventricular performance.