ADHD Adults Show Lower Interindividual Similarity in Ex-Gaussian Reaction Time Vectors for Congruent Stimuli Compared to Control Peers.

OBJECTIVE: Interindividual similarity refers to how similarly individuals respond when receiving the same stimulus or intervention. In this study, we aimed to examine interindividual similarity in adults with ADHD. METHOD: We used the cosine similarity index of ex-Gaussian reaction time (RT) vectors of mu, sigma, and tau parameters during a Stroop task. RESULTS: Our results demonstrate that the ADHD group exhibits a reduced interindividual similarity index in their ex-Gaussian RT vectors for congruent stimuli compared to the healthy control group. Importantly, we did not find significant differences in the interindividual similarity index to incongruent stimuli between both groups, thus suggesting that this reduced index was selective for congruent stimuli. CONCLUSION: Our findings highlight that ADHD adults exhibit more significant interindividual differences in cognitive functioning when processing congruent stimuli than healthy controls. These results provide new insights into the selective mechanisms underlying ADHD and may contribute to developing new targeted interventions for this disorder.

Pharmacological characterization and differential expression of NMDA receptor subunits in the chicken vestibular system during development.

Previous studies demonstrated that in vitro preparations of the isolated vestibular system of diverse animal species still exhibit stable resting electrical activity and mechanically evoked synaptic transmission between hair cells and primary afferent endings. However, there are no reports related to their neurodevelopment. Therefore, this research aimed to examine whether NMDA receptors mediate these electrical signals in an isolated preparation of the chicken vestibular system at three developmental stages, E15, E18, and E21. We found that the spontaneous and mechanically evoked discharges from primary afferents of the posterior semicircular canal were modulated by agonists NMDA and glycine, but not by the agonist d-serine applied near the synapses. Moreover, the individually applied by bath perfusion of three NMDA receptor antagonists (MK-801, ifenprodil, and 2-naphthoic acid) or high Mg2+ decreased the resting discharge rate, the NMDA response, and the discharge rate of mechanically evoked activity from these primary afferents. Furthermore, we found that the vestibular ganglion shows a stage-dependent increase in the expression of NMDA receptor subunits GluN1, GluN2 (A-C), and GluN3 (A-B), being greater at E21, except for GluN2D, which was inversely related to the developmental stage. However, in the crista ampullaris, the expression pattern remained constant throughout development. This could suggest the possible existence of presynaptic NMDA receptors. Our results highlight that although the NMDA receptors are functionally active at the early embryonic stages of the vestibular system, NMDA and glycine reach their mature functionality to increase NMDA responses close to hatching (E21).

Absence of Neuroplastic Changes in the Bilateral H-Reflex Amplitude following Spinal Manipulation with Activator IV.

Background and Objectives: Chiropractic spinal manipulation is an alternative medical procedure for treating various spinal dysfunctions. Great interest exists in investigating its neuroplastic effects on the central nervous system. Previous studies have found contradictory results in relation to the neuroplastic changes in the H-reflex amplitude as a response to manual spinal manipulation. The discrepancies could be partly due to differences in the unilateral nature of these recordings and/or the variable force exerted in manual techniques applied by distinct chiropractors. Concerning the latter point, the variability in the performance of manual interventions may bias the determination of the significance of changes in H-reflex responses derived from spinal manipulation. To investigate such responses, a chiropractic device can be used to provide more precise and reproducible results. The current contribution aimed to examine whether spinal manipulation with an Activator IV instrument generates neuroplastic effects on the bilateral H-reflex amplitude in dancers and non-dancers. Materials and Methods: A radiograph verified spinal dysfunction in both groups of participants. Since there were significant differences between groups in the mean Hmax values of the H-reflex amplitude before spinal intervention, an assessment was made of the possible dependence of the effects of spinal manipulation with Activator IV on the basal conditions. Results: Ten sessions of spinal manipulation with Activator IV did not cause statistically significant changes in the bilateral H-reflex amplitude (measured as the Hmax/Mmax ratio) in either group. Furthermore, no significant difference was detected in the effects of spinal manipulation between groups, despite their distinct basal H-reflex amplitude. Conclusions: Regarding the therapeutic benefits of a chiropractic adjustment, herein carried out with Activator IV, the present findings suggest that the mechanism of action is not on the monosynaptic H-reflex pathway. Further research is needed to understand the mechanisms involved.

Random noise stimulation in the treatment of patients with neurological disorders.

Random noise stimulation technique involves applying any form of energy (for instance, light, mechanical, electrical, sound) with unpredictable intensities through time to the brain or sensory receptors to enhance sensory, motor, or cognitive functions. Random noise stimulation initially employed mechanical noise in auditory and cutaneous stimuli, but electrical energies applied to the brain or the skin are becoming more frequent, with a series of clinical applications. Indeed, recent evidence shows that transcranial random noise stimulation can increase corticospinal excitability, improve cognitive/motor performance, and produce beneficial aftereffects at the behavioral and psychological levels. Here, we present a narrative review about the potential uses of random noise stimulation to treat neurological disorders, including attention deficit hyperactivity disorder, schizophrenia, amblyopia, myopia, tinnitus, multiple sclerosis, post-stroke, vestibular-postural disorders, and sensitivity loss. Many of the reviewed studies reveal that the optimal way to deliver random noise stimulation-based therapies is with the concomitant use of neurological and neuropsychological assessments to validate the beneficial aftereffects. In addition, we highlight the requirement of more randomized controlled trials and more physiological studies of random noise stimulation to discover another optimal way to perform the random noise stimulation interventions.

Balanced Expression of G Protein-coupled Receptor Subtypes in the Mouse, Macaque, and Human Cerebral Cortex.

G-protein coupled receptors (GPCRs) modulate brain function by signaling through heterotrimeric Gq/11, Gs, and Gi/o protein subtypes. Researchers frequently study neuromodulation via these GPCR-subtypes on a 'cell-by-cell' basis. Although useful to explore a small number of interactions among neuromodulatory systems under controlled settings, this approach fails to account for a global organization of GPCRs in the brain. Furthermore, because multiple receptors and signal transduction pathways are present in single cells, neuromodulation is controlled by groups of GPCRs rather than by individual receptors. Using an integrative approach, the present study examined how large GPCR-subtype communities (ensembles) are expressed in different anatomical regions. Using the Allen Brain Atlas (http://www.brain-map.org/), we analyzed the mRNA expression energy of hundreds of GPCR-subtypes located in mouse, macaque, and human brains. We found that although there was a heterogeneous expression of GPCR-mRNA across all cortical regions, there were strong spatial correlations among congregated Gq/11-, Gs-, and Gi/o-linked systems. Correlation strength increased with age but dropped when randomly removing genes from their corresponding groups. These findings suggest that the expression patterns of GPCR subtypes and receptor families are intricately intertwined. Well-orchestrated interactions by neuromodulatory-GPCR ensembles could be crucial for the brain to function as a highly integrated complex system.

Low-field thoracic magnetic stimulation increases peripheral oxygen saturation levels in coronavirus disease (COVID-19) patients: A single-blind, sham-controlled, crossover study.

ABSTRACT: Severe acute respiratory syndrome coronavirus-2 may cause low oxygen saturation (SpO2) and respiratory failure in patients with coronavirus disease (COVID-19). Hence, increased SpO2 levels in COVID-19 patients could be crucial for their quality of life and recovery. This study aimed to demonstrate that a 30-minute single session of dorsal low-field thoracic magnetic stimulation (LF-ThMS) can be employed to increase SpO2 levels in COVID-19 patients significantly. Furthermore, we hypothesized that the variables associated with LF-ThMS, such as frequency, magnetic flux density, and temperature in the dorsal thorax, might be correlated to SpO2 levels in these patients.Here we employed an LF-ThMS device to noninvasively deliver a pulsed magnetic field from 100 to 118 Hz and 10.5 to 13.1 milliTesla (i.e., 105 to 131 Gauss) to the dorsal thorax. These values are within the intensity range of several pulsed electromagnetic field devices employed in physical therapy worldwide. We designed a single-blind, sham-controlled, crossover study on 5 COVID-19 patients who underwent 2 sessions of the study (real and sham LF-ThMS) and 12 patients who underwent only the real LF-ThMS.We found a statistically significant positive correlation between magnetic flux density, frequency, or temperature, associated with the real LF-ThMS and SpO2 levels in all COVID-19 patients. However, the 5 patients in the sham-controlled study did not exhibit a significant change in their SpO2 levels during sham stimulation. The employed frequencies and magnetic flux densities were safe for the patients. We did not observe adverse events after the LF-ThMS intervention.This study is a proof-of-concept that a single session of LF-ThMS applied for 30 minutes to the dorsal thorax of 17 COVID-19 patients significantly increased their SpO2 levels. However, future research will be needed to understand the physiological mechanisms behind this finding.The study was registered at ClinicalTrials.gov (Identifier: NCT04895267, registered on May 20, 2021) retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04895267.

Modeling Post-Scratching Locomotion with Two Rhythm Generators and a Shared Pattern Formation.

This study aimed to present a model of post-scratching locomotion with two intermixed central pattern generator (CPG) networks, one for scratching and another for locomotion. We hypothesized that the rhythm generator layers for each CPG are different, with the condition that both CPGs share their supraspinal circuits and their motor outputs at the level of their pattern formation networks. We show that the model reproduces the post-scratching locomotion latency of 6.2 ± 3.5 s, and the mean cycle durations for scratching and post-scratching locomotion of 0.3 ± 0.09 s and 1.7 ± 0.6 s, respectively, which were observed in a previous experimental study. Our findings show how the transition of two rhythmic movements could be mediated by information exchanged between their CPG circuits through routes converging in a common pattern formation layer. This integrated organization may provide flexible and effective connectivity despite the rigidity of the anatomical connections in the spinal cord circuitry.

Noisy Light Augments the Na+ Current in Somatosensory Pyramidal Neurons of Optogenetic Transgenic Mice.

In previous reports, we developed a method to apply Brownian optogenetic noise-photostimulation (BONP, 470 nm) up to 0.67 mW on the barrel cortex of in vivo ChR2 transgenic mice. In such studies, we found that the BONP produces an increase in the evoked field potentials and the neuronal responses of pyramidal neurons induced by somatosensory mechanical stimulation. Here we extended such findings by examining whether the same type of BONP augments the Na+ current amplitude elicited by voltage-clamp ramps of dissociated pyramidal neurons from the somatosensory cortex of ChR2 transgenic and wild type mice. We found that in all neurons from the ChR2 transgenic mice, but none of the wild type mice, the peak amplitude of a TTX-sensitive Na+ current and its inverse of latency exhibited inverted U-like graphs as a function of the BONP level. It means that an intermediate level of BONP increases both the peak amplitude of the Na+ current and its inverse of latency. Our research suggests that the impact of BONP on the Na+ channels of pyramidal neurons could be associated with the observed augmentation-effects in our previous in vivo preparation. Moreover, it provides caution information for the use of an appropriate range of light intensity, <0.67 mW, which could avoid opto non-genetics (also termed "optonongenetic") related responses due to light-induced temperature changes.

Changes in Serotonin Modulation of Glutamate Currents in Pyramidal Offspring Cells of Rats Treated With 5-MT during Gestation.

Changes in stimuli and feeding in pregnant mothers alter the behavior of offspring. Since behavior is mediated by brain activity, it is expected that postnatal changes occur at the level of currents, receptors or soma and dendrites structure and modulation. In this work, we explore at the mechanism level the effects on Sprague-Dawley rat offspring following the administration of serotonin (5-HT) agonist 5-methoxytryptamine (5-MT). We analyzed whether 5-HT affects the glutamate-activated (IGlut) and N-methyl-D-aspartate (NMDA)-activated currents (IGlut, INMDA) in dissociated pyramidal neurons from the prefrontal cortex (PFC). For this purpose, we performed voltage-clamp experiments on pyramidal neurons from layers V-VI of the PFC of 40-day-old offspring born from 5-MT-treated mothers at the gestational days (GD) 11 to 21. We found that the pyramidal-neurons from the PFC of offspring of mothers treated with 5-MT exhibit a significant increased reduction in both the IGlut and INMDA when 5-HT was administered. Our results suggest that the concentration increase of a neuromodulator during the gestation induces changes in its modulatory action over the offspring ionic currents during the adulthood thus contributing to possible psychiatric disorders.

The Hemodynamic Mass Action of a Central Pattern Generator.

The hemodynamic response is a neurovascular and metabolic process in which there is rapid delivery of blood flow to a neuronal tissue in response to neuronal activation. The functional magnetic resonance imaging (fMRI) and the functional near-infrared spectroscopy (fNIRS), for instance, are based on the physiological principles of such hemodynamic responses. Both techniques allow the mapping of active neuronal regions in which the neurovascular and metabolic events are occurring. However, although both techniques have revolutionized the neurosciences, they are mostly employed for neuroimaging of the human brain but not for the spinal cord during functional tasks. Moreover, little is known about other techniques measuring the hemodynamic response in the spinal cord. The purpose of the present study was to show for the first time that a simple optical system termed direct current photoplethysmography (DC-PPG) can be employed to detect hemodynamic responses of the spinal cord and the brainstem during the functional activation of the spinal central pattern generator (CPG). In particular, we positioned two DC-PPG systems directly on the brainstem and spinal cord during fictive scratching in the cat. The optical DC-PPG systems allowed the trial-by-trial recording of massive hemodynamic signals. We found that the "strength" of the flexor-plus-extensor motoneuron activities during motor episodes of fictive scratching was significantly correlated to the "strengths" of the brainstem and spinal DC-PPG signals. Because the DC-PPG was robustly detected in real-time, we claim that such a functional signal reflects the hemodynamic mass action of the brainstem and spinal cord associated with the CPG motor action. Our findings shed light on an unexplored hemodynamic observable of the spinal CPGs, providing a proof of concept that the DC-PPG can be used for the assessment of the integrity of the human CPGs.

Resetting the Respiratory Rhythm with a Spinal Central Pattern Generator.

There is evidence that a variety of central and afferent stimuli, including swallowing, can produce phase resetting in the respiratory rhythmicity. Also, there are reports about the intrinsic linkage between locomotion and respiration. However, little is known about the interaction between the central pattern generators (CPGs) for scratching and respiration. The present study aims to examine whether the activation of scratching CPG produces phase resetting of the respiratory rhythm. We employed decerebrate cats to apply brief tactile stimuli to the pinna during the inspiratory-expiratory transition. We observed that those stimuli to the pinna not eliciting fictive scratching did not reset the respiratory rhythm. However, when the pinna stimuli elicited fictive scratching, then the respiratory rhythm exhibited a significant phase resetting. We also found interneurons in the medulla oblongata exhibiting phase resetting related to scratching-CPG episodes. This second finding suggests that this type of resetting involves brainstem components of the respiratory CPG. These results shed new light on the resetting action from a spinal CPG on the respiratory rhythm.

Effects of Short-Term Random Noise Electrical Stimulation on Dissociated Pyramidal Neurons from the Cerebral Cortex.

Transcranial random noise electrical stimulation (tRNS) of the human brain is a non-invasive technique that can be employed to increase the excitability of the cerebral cortex; however, the physiological mechanisms remain unclear. Here we report for the first time the effects of short-term (250 ms) random noise electrical stimulation (RNS) on in-vitro acutely-isolated brain pyramidal neurons from the somatosensory and auditory cerebral cortex. We analyzed the correlation between the peak amplitude of the Na+ current and its latency for different levels of RNS. We found three groups of neurons. The first group exhibited a positive correlation, the second, a negative correlation, and the third group of neurons did not exhibit correlation. In the first group, both the peak amplitude of a TTX-sensitive Na+ current and its inverse of latency followed similar inverted U-like functions relative to the electrical RNS level. In this group, the RNS levels in which the maximal values of the inverted U-like functions occurred were the same. In the second group, the maximal values of the inverted U-like functions occurred at different levels. In the third group, only the peak amplitude of the Na+ current exhibited a clear inverted U-like function, but the inverse of the latency versus the electrical RNS, did not exhibit a clear inverted U-like function. A Hodgkin-Huxley neuron model reproduces our experimental results and shows that the observed behavior in the Na+ current could be due to the impact of RNS on the kinetics of activation and inactivation of the Na+ channels.

Afterdischarges of Spinal Interneurons Following a Brief High-Frequency Stimulation of Ia Afferents in the Cat.

Spinal motoneurons exhibit sustained afterdischarges and plateau potentials following a brief high-frequency stimulation of Ia afferents. Also, there is evidence that spinal cord interneurons exhibit plateau potentials. However, to our knowledge, there are no reports about the possible afterdischarge behavior of lumbar spinal interneurons activated by Ia afferents. Given that there are spinal interneurons receiving monosynaptic inputs from Ia afferents, these cells could then be activated in parallel to motoneurons after repetitive muscle stretch. We explored this possibility in cats with a precollicular-postmammillary decerebration. We found that a brief high-frequency stimulation of Ia afferents produces afterdischarges that are highly correlated to a DC slow potential recorded at the cord dorsum. We conclude that in the cat spinal cord, not only the motoneurons but also the interneurons from the superficial and deep dorsal horn produce sustained afterdischarges, thus highlighting the importance of interneurons in the spinal neuronal circuitry. The significance of our finding is that it opens the possibility that the spinal cord interneurons activated by Ia afferents could also exhibit bistability, a relevant phenomenon well-characterized in the motoneurons.

Augmenting EEG-global-coherence with auditory and visual noise: Multisensory internal stochastic resonance.

The present investigation documents the electrophysiological occurrence of multisensory internal stochastic resonance (MISR) in the human electroencephalographic (EEG) coherence elicited by auditory and visual noise.We define MISR of EEG coherence as the phenomenon for which an intermediate level of input noise of a sensory modality enhances EEG coherence in response to another noisy sensory modality. Here, EEG coherence is computed by the global weighted coherence (GWC), modulated by quasi-Brownian noise. Specifically, we examined whether a particular level of auditory noise together with constant visual noise (experimental condition 1) and a specified level of visual noise together with constant auditory noise (experimental condition 2), improves EEG's GWC. We compared GWC between ongoing EEG basal activity (BA), zero noise (ZN), optimal noise (ON), and high noise (HN).The data disclosed an intermediate level of input noise that enhances the GWC for the majority of the subjects, thus demonstrating for the first time the occurrence of multisensory internal stochastic resonance (SR) in visuoauditory processing within the central nervous system.

The Spinal Neurons Exhibit an ON-OFF and OFF-ON Firing Activity Around the Onset of Fictive Scratching Episodes in the Cat.

In a previous report, we found neurons with ON-OFF and OFF-ON firing activity in the obex reticular formation during scratching. The aim of the present study was to examine whether the spinal neurons also exhibit this type of activity in relation to the "postural stage" of fictive scratching in the cat. We found that the extensor and intermediate scratching neurons exhibit an ON-OFF firing rate; conversely, the flexor neurons show an OFF-ON activity, relative to every scratching episode. These patterns of spiking activity are similar to those found in neurons from the obex reticular formation during scratching. Our findings provide support to the following hypotheses. First, there is a possible functional link between supraspinal and spinal, ON-OFF and OFF-ON neuronal groups. Second, the fictive goal-directed motor action to maintain the fictive "postural stage" of the hindlimb during fictive scratching is associated with the neuronal tonic activity of the OFF-ON spinal neurons, whereas the ON-OFF spinal neurons are associated with an extensor tone that occurred prior the postural stage.