Ongoing Activity Research Articles

Evidence of Neuroplastic Changes after Transcranial Magnetic, Electric, and Deep Brain Stimulation.

Electric and magnetic stimulation of the human brain can be used to excite or inhibit neurons. Numerous methods have been designed over the years for this purpose with various advantages and disadvantages that are the topic of this review. Deep brain stimulation (DBS) is the most direct and focal application of electric impulses to brain tissue. Electrodes are placed in the brain in order to modulate neural activity and to correct parameters of pathological oscillation in brain circuits such as their amplitude or frequency. Transcranial magnetic stimulation (TMS) is a non-invasive alternative with the stimulator generating a magnetic field in a coil over the scalp that induces an electric field in the brain which, in turn, interacts with ongoing brain activity. Depending upon stimulation parameters, excitation and inhibition can be achieved. Transcranial electric stimulation (tES) applies electric fields to the scalp that spread along the skull in order to reach the brain, thus, limiting current strength to avoid skin sensations and cranial muscle pain. Therefore, tES can only modulate brain activity and is considered subthreshold, i.e., it does not directly elicit neuronal action potentials. In this review, we collect hints for neuroplastic changes such as modulation of behavior, the electric activity of the brain, or the evolution of clinical signs and symptoms in response to stimulation. Possible mechanisms are discussed, and future paradigms are suggested.

The Characteristics of Pediatric Patients with Familial Mediterranean Fever Treated with Anti-Interleukin-1 Treatment.

Objective:Interleukin-1 inhibitors are effective agents used in colchicine resistance or intolerance during the treatment of familial Mediterranean fever. This study aims to review the characteristics of patients treated with interleukin-1 inhibitors and their long-term follow-up in a large pediatric cohort of familial Mediterranean fever patients.Materials and Methods:The study was conducted in a pediatric rheumatology reference center. The patients treated with interleukin-1 inhibitors for at least 6 months were included and compared to other patients with familial Mediterranean fever. Clinical and laboratory characteristics of the cohort were recorded.Results:Among 542 patients with familial Mediterranean fever, 6.1% (n = 33) were treated with interleukin-1 inhibitors. Colchicine resistance was the reason in 82.8% and renal amyloidosis in 17.2% of the patients. Patients with interleukin-1 inhibitors had earlier disease onset and higher frequencies of acute arthritis, chest pain, and erysipelas-like erythema with pathogenic exon 10 mutations of the MEFV gene (all P < .04). All patients diagnosed with renal amyloidosis also received interleukin-1 inhibitors. Six patients were switched from anakinra to canakinumab or vice versa to control ongoing disease activity. Attack frequency was reduced in all patients. Conclusion:Interleukin-1 inhibitors are used in a relatively small number of pediatric patients with familial Mediterranean fever. Patients presenting with earlier disease onset, acute arthritis, chest pain, and erysipelas-like erythema and carrying pathogenic exon 10 mutations of the MEFV gene may show a higher need for interleukin-1 inhibitors. In pediatric familial Mediterranean fever patients who are resistant to colchicine, interleukin-1 inhibitors seem to be highly effective agents.

Eruptions and Social Media: Communication and Public Outreach About Volcanoes and Volcanic Activity in Italy

Italy is the land of iconic volcanoes, whose activity has been witnessed, described and portrayed for centuries. This legacy has greatly contributed to shaping the public perception of volcanoes and their impact, well beyond the national borders. Stories about famous eruptions overlap and nowadays easily mix up with the impressive footage that is readily available from ongoing eruptions worldwide. As a result, the public discourse may flatten the wide spectrum of possible phenomena into an oversimplified sketch of volcanic eruptions and their impact, where all events seem equally probable and look alike. Actual volcanoes differ in size, eruption magnitude, state of activity, eruptive style, geographical position, and each is located within a specific social and cultural context. All these elements combine in defining the consequences of volcanic activity as well as in determining the severity of the damage and the size of the impacted area. How can we convey such a complexity to the general public? Can social media contribute to raise awareness and build a more resilient society? An effective hazard communication should propose a comprehensible yet realistic description of volcanic settings and provide adequate tools to recognize and understand the specific features of each phenomenon and volcanic area. As we write, two Italian volcanoes display persistent eruptive activity, while other two are going through unrest phases that started in 2012, at Campi Flegrei, and in late summer of 2021, at Vulcano Island. Other active volcanoes (Vesuvius, Ischia, Colli Albani, Lipari, and Pantelleria) have been dormant for tens, hundreds, or thousands of years. Communication in these different contexts also require different approaches that take into account the specific needs of local communities. Social media may provide a unique opportunity to quickly share relevant news and information. Yet, this type of communication has its challenges and volcano observatories can rarely rely on expert social media managers. Sharing experiences and lessons learned is a key to ensure the growth of the volcanological community and improve its ability to connect and engage local residents. Here we discuss the online communication strategies implemented by the Istituto Nazionale di Geofisica e Vulcanologia (INGV) since 2018 to inform Internet and social media users about volcanoes, volcanology, and ongoing volcanic activity, both in Italy and abroad. We describe the internal procedures that we developed and practiced and the experience gathered so far, during both quiet periods and a few volcanic crises. Our experience confirms previous indications about the importance of a steady online presence and suggests that public interest is not always easily predictable.

Pragmatist Hope during COVID-19

Pragmatist Hope during COVID-19

Are You Really Muted?: A Privacy Analysis of Mute Buttons in Video Conferencing Apps

Video conferencing apps (VCAs) make it possible for previously private spaces — bedrooms, living rooms, and kitchens — into semi-public extensions of the office. For the most part, users have accepted these apps in their personal space without much thought about the permission models that govern the use of their private data during meetings. While access to a device’s video camera is carefully controlled, little has been done to ensure the same level of privacy for accessing the microphone. In this work, we ask the question: what happens to the microphone data when a user clicks the mute button in a VCA? We first conduct a user study to analyze users’ understanding of the permission model of the mute button. Then, using runtime binary analysis tools, we trace raw audio flow in many popular VCAs as it traverses the app from the audio driver to the network. We find fragmented policies for dealing with microphone data among VCAs — some continuously monitor the microphone input during mute, and others do so periodically. One app transmits statistics of the audio to its telemetry servers while the app is muted. Using network traffic that we intercept en route to the telemetry server, we implement a proof-of-concept background activity classifier and demonstrate the feasibility of inferring the ongoing background activity during a meeting — cooking, cleaning, typing, etc. We achieved 81.9% macro accuracy on identifying six common background activities using intercepted outgoing telemetry packets when a user is muted.

Neuronal activity under transcranial radio-frequency stimulation in metal-free rodent brains in-vivo

As the use of Radio Frequency (RF) technologies increases, the impact of RF radiation on neurological function continues to receive attention. Whether RF radiation can modulate ongoing neuronal activity by non-thermal mechanisms has been debated for decades. However, the interactions between radiated energy and metal-based neural probes during experimentation could impact neural activity, making interpretation of the results difficult. To address this problem, we modified a miniature 1-photon Ca2+ imaging device to record interference-free neural activity and compared the results to those acquired using metal-containing silicon probes. We monitored the neuronal activity of awake rodent-brains under RF energy exposure (at 950 MHz) and in sham control paradigms. Spiking activity was reliably affected by RF energy in metal containing systems. However, we did not observe neuronal responses using metal-free optical recordings at induced local electric field strengths up to 230 V/m. Our results suggest that RF exposure higher than levels that are allowed by regulatory limits in real-life scenarios do not affect neuronal activity.

Adenosine is released during thalamic oscillations to provide negative feedback control

Physiological oscillations in the cortico-thalamo-cortical loop occur during processes such as sleep, but these can become dysfunctional in pathological conditions such as absence epilepsy. The purine neuromodulator adenosine can act as an endogenous anticonvulsant: it is released into the extracellular space during convulsive seizures to activate A1 receptors suppressing on-going activity and delaying the occurrence of the next seizure. However, the role of adenosine in thalamic physiological and epileptiform oscillations is less clear. Here we have combined immunohistochemistry, electrophysiology, and fixed potential amperometry (FPA) biosensor measurements to characterise the release and actions of adenosine in thalamic oscillations measured in rodent slices. In the thalamus, A1 receptors are highly expressed particularly in the ventral basal (VB) thalamus and reticular thalamic nucleus (nRT) supporting a role for adenosine signalling in controlling oscillations. In agreement with previous studies, both adenosine and adenosine A1 receptor agonists inhibited thalamic oscillations in control (spindle-like) and in epileptic conditions. Here we have shown for the first time that both control and epileptiform oscillations are enhanced (i.e., increased number of oscillatory cycles) by blocking A1 receptors consistent with adenosine release occurring during oscillations. Although increases in extracellular adenosine could not be directly detected during control oscillations, clear increases in adenosine concentration could be detected with a biosensor during epileptiform oscillation activity. Thus, adenosine is released during thalamic oscillations and acts via A1 receptors to feedback and reduce thalamic oscillatory activity.

Research activity, facilitators and barriers amongst trainee and early-career family physicians in sub-Saharan Africa: A cross-sectional survey.

BackgroundPrimary health care systems in sub-Saharan Africa (SSA) need context-specific evidence to address current challenges. Increased family physician (FP) research activity could help fill this gap.AimTo describe the research activity, facilitators and barriers amongst AfriWon Renaissance members.SettingAn online programme was designed to improve research activity amongst members of AfriWon Renaissance, an organisation of early-career and trainee FPs in SSA. This article provides a baseline description of their research activity.MethodsAll AfriWon Renaissance members were invited to participate in an online survey. A content-validated study tool assessed research activity, including participation in research meetings, engagement in research mentorship, number of projects and published articles. Facilitators and barriers were assessed via Likert scales and two open-ended questions. The researchers conducted descriptive statistics using Epi Info 7, a content analysis of open-ended responses and triangulation.ResultsAmongst the 77 respondents, 49 (63.6%) were still in training. Over two-thirds (71.4%) had participated in a research discussion in the past month. Whilst more than half (63.5%) reported having a manuscript under development, only 26 (33.8%) reported a recent publication. Nearly all (94.8%) intend to continue research in their FP careers. The most common facilitators were the institutional requirement to conduct research and having supportive peers and mentors. The most predominant barriers were time constraints and a lack of training on analysis.ConclusionThere is a cohort of committed young FP researchers who would benefit from efforts to address identified barriers and support for their ongoing research activity, in order to increase primary care research outputs in SSA.

Making of the Arctic dream – affective resources in the strategies of Arctic coastal states

ABSTRACT Fossil fuel resources continue to play a significant role in the strategies and policies of Arctic states, despite the accelerating global climate crisis. This is especially the case in the context of the Arctic coastal states of Russia, Norway, Denmark, Canada, and the United States, whose waters are expected to hide a significant share of the world’s remaining oil and gas reserves. In contrast with existing literature on political strategy documents, we approach the Arctic strategies of these five states with an interest in their understudied affective dimension. Relying on conceptually informed thematic content analysis, we demonstrate how resource affects—mainly desire, hope, pride, and denial—are created, circulated and utilized in the establishment of the states’ Arctic resource policies. Furthermore, our analysis draws attention to the central role that affects play in legitimizing ongoing and future hydrocarbon activity in the rapidly warming circumpolar North.

Rhythmic interactions between the mediodorsal thalamus and prefrontal cortex precede human visual perception

The thalamus is much more than a simple sensory relay. High-order thalamic nuclei, such as the mediodorsal thalamus, exert a profound influence over animal cognition. However, given the difficulty of directly recording from the thalamus in humans, next-to-nothing is known about thalamic and thalamocortical contributions to human cognition. To address this, we analysed simultaneously-recorded thalamic iEEG and whole-head MEG in six patients (plus MEG recordings from twelve healthy controls) as they completed a visual detection task. We observed that the phase of both ongoing mediodorsal thalamic and prefrontal low-frequency activity was predictive of perceptual performance. Critically however, mediodorsal thalamic activity mediated prefrontal contributions to perceptual performance. These results suggest that it is thalamocortical interactions, rather than cortical activity alone, that is predictive of upcoming perceptual performance and, more generally, highlights the importance of accounting for the thalamus when theorising about cortical contributions to human cognition.

AI Assisted Data Labeling with Interactive Auto Label

We demonstrate an AI assisted data labeling system which applies unsupervised and semi-supervised machine learning to facilitate accurate and efficient labeling of large data sets. Our system (1) applies representative data sampling and active learning in order to seed and maintain a semi-supervised learner that assists the human labeler (2) provides visual labeling assistance and optimizes labeling mechanics using predicted labels (3) seamlessly updates and learns from ongoing human labeling activity (4) captures and presents metrics that indicate the quality of labeling assistance, and (5) provides an interactive auto labeling interface to group, review and apply predicted labels in a scalable manner.

Memory: Synaptic or Cellular, That Is the Question

According to the commonly accepted opinion, memory engrams are formed and stored at the level of neural networks due to a change in the strength of synaptic connections between neurons. This hypothesis of synaptic plasticity (HSP), formulated by Donald Hebb in the 1940s, continues to dominate the directions of experimental studies and the interpretations of experimental results in the field. The universal acceptance of the HSP has transformed it from a hypothesis into an incontrovertible theory. In this article, I show that the entire body of experimental and clinical data obtained in studies of long-term memory in mammals and humans is inconsistent with the HSP. Instead, these data suggest that long-term memory is formed and stored at the intracellular level where it is reliably protected from ongoing synaptic activity, including pathological epileptic activity. It seems that the generally accepted HSP became a serious obstacle to understanding the mechanisms of memory and that progress in this field requires rethinking this doctrine and shifting experimental efforts toward exploring the intracellular mechanisms.

Gonadal hormone-dependent nociceptor sensitization maintains nociplastic pain state in female mice.

Nociplastic pain conditions develop predominantly in women. We recently established a murine nociplastic pain model by applying postinjury thermal (40°C) stimulation to an injured (capsaicin-injected) area, triggering a transition to a nociplastic pain state manifesting as persistent mechanical hypersensitivity outside of the previously injured area. The nociplastic pain state was centrally maintained by spinal microglia in males but peripherally by ongoing afferent activity at the previously injured area in females. Here, we investigated whether gonadal hormones are critical for the development of this peripherally maintained nociplastic pain state in females. Although the transition to a nociplastic pain state still occurred in ovariectomized females, the pain state was maintained neither by ongoing afferent activity at the previously injured area nor by spinal microglia. Estradiol reconstitution a week before the injury plus postinjury stimulation, but not after the transition had already occurred, restored the development of peripherally maintained nociplastic mechanical hypersensitivity in ovariectomized females. G protein-coupled estrogen receptor antagonism during the transition phase mimicked ovariectomy in gonad-intact females, whereas the receptor antagonism after the transition gradually alleviated the nociplastic mechanical hypersensitivity. At the previously injured area, afferents responsive to allyl isothiocyanate (AITC), a TRPA1 agonist, contributed to the maintenance of nociplastic mechanical hypersensitivity in gonad-intact females. In ex vivo skin-nerve preparations, only AITC-responsive afferents from the nociplastic pain model in gonad-intact females showed ongoing activities greater than control. These results suggest that gonadal hormones are critical for peripherally maintained nociplastic pain state in females by sensitizing AITC-responsive afferents to be persistently active.

Suspected benzodiazepine withdrawal-associated seizures in 3 young dogs undergoing mechanical ventilation.

To describe new onset of generalized seizures in 3 young dogs following cessation of a benzodiazepine-containing sedation protocol to facilitate mechanical ventilation (MV) for hypoxemia. Three dogs under 5 months of age underwent MV due to severe hypoxemia. All 3 dogs were sedated with a constant rate infusion of benzodiazepines as part of their sedation protocol to facilitate MV. All 3 dogs had an acute onset of generalized seizures within 36hours of sedation cessation and weaning from MV. All 3 dogs' seizures were successfully managed with a slow, tapering course of benzodiazepines. One dog was additionally treated with levetiracetam at the time of initial seizure activity, which was discontinued 1year following discharge and absence of ongoing seizure activity. All 3 dogs were discharged successfully with no reports of ongoing seizures or neurologic deficits after discharge. Young dogs managed with benzodiazepines to facilitate MV may have acute onset of generalized seizures following cessation, which can be successfully managed with short-term benzodiazepine therapy. The 3 cases in this series demonstrated a positive outcome and were successfully managed following acute onset of generalized seizure activity post-MV.

How Do I Find Clues About Where Myoclonus Is Originating?

Myoclonus is defined as a brief and jerky shock‐like involuntary movement caused by abrupt muscle contraction or sudden cessation of ongoing muscular activity. Myoclonus can be generated by abnormal activity in different parts of the nervous system, both peripheral and central, including cortical and subcortical structures. According to the presumed neural generator, myoclonus is classified as cortical, subcortical (including myoclonus‐dystonia and brainstem/reticular myoclonus), spinal (including segmental spinal and propriospinal myoclonus), and peripheral. The identification of myoclonus subtypes, and therefore its potential source, is clinically important because it can guide diagnosis and treatment. In this video lecture (Video), we reviewed how to determine myoclonus origin. We first reviewed the clinical features typical of each myoclonus subtype. We, then, explored the electrophysiological techniques that can aid in the differential diagnosis of myoclonus, based on its origin. In conclusion, we provided a clinical and electrophysiological overview on how to find clues about neural generators of myoclonus.

The natural frequencies of the resting human brain: An MEG-based atlas

Brain oscillations are considered to play a pivotal role in neural communication. However, detailed information regarding the typical oscillatory patterns of individual brain regions is surprisingly scarce. In this study we applied a multivariate data-driven approach to create an atlas of the natural frequencies of the resting human brain on a voxel-by-voxel basis. We analysed resting-state magnetoencephalography (MEG) data from 128 healthy adult volunteers obtained from the Open MEG Archive (OMEGA). Spectral power was computed in source space in 500 ms steps for 82 frequency bins logarithmically spaced from 1.7 to 99.5 Hz. We then applied k-means clustering to detect characteristic spectral profiles and to eventually identify the natural frequency of each voxel. Our results provided empirical confirmation of the canonical frequency bands and revealed a region-specific organisation of intrinsic oscillatory activity, following both a medial-to-lateral and a posterior-to-anterior gradient of increasing frequency. In particular, medial fronto-temporal regions were characterised by slow rhythms (delta/theta). Posterior regions presented natural frequencies in the alpha band, although with differentiated generators in the precuneus and in sensory-specific cortices (i.e., visual and auditory). Somatomotor regions were distinguished by the mu rhythm, while the lateral prefrontal cortex was characterised by oscillations in the high beta range (>20 Hz). Importantly, the brain map of natural frequencies was highly replicable in two independent subsamples of individuals. To the best of our knowledge, this is the most comprehensive atlas of ongoing oscillatory activity performed to date. Critically, the identification of natural frequencies is a fundamental step towards a better understanding of the functional architecture of the human brain.

Angiotensin II inhibition increases diuresis during acute sympathetic activation in intact and denervated kidneys in rats with chronic myocardial infarction.

We examined urine excretion during primary acute sympathetic activation (PASA) in Wistar-Kyoto rats with myocardial infarction (MI). The rats underwent unilateral renal denervation (RDN) 7weeks after coronary artery ligation. 4-10days later, an acute experiment was performed under anesthetized conditions (n = 8 rats). Isolated carotid sinus pressure was changed stepwise from 60 to 180mmHg, and the relationship between the arterial pressure (AP) and the normalized urine flow (nUF, urine flow normalized by the body weight) was examined. After obtaining the control data, an angiotensin II type 1 receptor blocker telmisartan (2.5mg/kg) was intravenously administered. The effects of RDN, telmisartan, and heart weight (biventricular weight) on the relationship between AP and nUF were examined using multiple regression analyses. Regarding the slope of nUF versus AP (nUFslope), the constant term of the regression was positive (0.315 ± 0.069 μL·min-1·kg-1·mmHg-1), indicating that nUF increased with AP. The heart weight had a negative effect on nUFslope (P < 0.05), suggesting that the severity of MI was associated with the impairment of urine excretion. Telmisartan increased nUFslope by 0.358 ± 0.080 μL·min-1·kg-1·mmHg-1 (P < 0.001), whereas RDN had no significant effect on this parameter. The results indicate that unilateral RDN was unable to abolish the effect of the renin-angiotensin system on urine excretion during PASA. Circulating or locally produced angiotensin II, rather than ongoing renal sympathetic nerve activity, played a dominant role in the impairment of urine excretion during PASA in rats with chronic MI.

Rituximab abrogates aquaporin-4–specific germinal center activity in patients with neuromyelitis optica spectrum disorders

Neuromyelitis optica spectrum disorders (NMOSDs) are caused by immunoglobulin G (IgG) autoantibodies directed against the water channel aquaporin-4 (AQP4). In NMOSDs, discrete clinical relapses lead to disability and are robustly prevented by the anti-CD20 therapeutic rituximab; however, its mechanism of action in autoantibody-mediated disorders remains poorly understood. We hypothesized that AQP4-IgG production in germinal centers (GCs) was a core feature of NMOSDs and could be terminated by rituximab. To investigate this directly, deep cervical lymph node (dCLN) aspirates (n = 36) and blood (n = 406) were studied in a total of 63 NMOSD patients. Clinical relapses were associated with AQP4-IgM generation or shifts in AQP4-IgG subclasses (odds ratio = 6.0; range of 3.3 to 10.8; P < 0.0001), features consistent with GC activity. From seven dCLN aspirates of patients not administered rituximab, AQP4-IgGs were detected alongside specific intranodal synthesis of AQP4-IgG. AQP4-reactive B cells were isolated from unmutated naive and mutated memory populations in both blood and dCLNs. After rituximab administration, fewer clinical relapses (annual relapse rate of 0.79 to 0; P < 0.001) were accompanied by marked reductions in both AQP4-IgG (fourfold; P = 0.004) and intranodal B cells (430-fold; P < 0.0001) from 11 dCLNs. Our findings implicate ongoing GC activity as a rituximab-sensitive driver of AQP4 antibody production. They may explain rituximab’s clinical efficacy in several autoantibody-mediated diseases and highlight the potential value of direct GC measurements across autoimmune conditions.

The frequency-dependent stimulation effects of rTMS on the performance of problem-solving tasks and ongoing oscillations

IntroductionRecent studies suggest that online repetitive transcranial magnetic stimulation (rTMS) can induce local entrainment of ongoing endogenous oscillatory activity that impacts cognitive performance, and the effect may depend on the function of the oscillation. However, little is known about the effects of task-specific frequencies, especially when using an online rTMS paradigm. Our previous electroencephalogram (EEG) study showed that the frontal theta rhythm is associated with the cognitive giving-up processes during problem-solving tasks.ObjectivesIn this study, we combined online rTMS and EEG to examine the frequency-dependent stimulation effects of rTMS on the performance of problem-solving tasks and ongoing oscillations. We hypothesized that rTMS at the theta frequency would induce ongoing theta activity and accelerate the giving-up behaviour.MethodsrTMS was applied during problem-solving tasks with the following conditions: individual theta (4-6Hz)- and alpha (9-13Hz)-TMS, no-TMS, and sham-TMS; the order of conditions was counterbalanced across participants.ResultsOur results showed that theta-frequency rTMS application induced an increase in theta amplitudes and shortened the giving-up response, while a control alpha-frequency rTMS application induced an increase in alpha amplitudes, but did not change giving-up responses.ConclusionsThis study demonstrated the effectiveness of using specific task-relevant stimulation frequency and target location for the modulation of cognitive and behavioral performance. Furthermore, considering the close resemblance between giving-up behaviour and rumination in depression, neuromodulation of cognitive giving-up processes may lead to a new intervention to treat depression by rTMS.DisclosureNo significant relationships.

Metabolic Activity of Neurogenic Heterotopic Ossification on 18F-FDG PET/CT Matching with Ongoing Osteoblastic Activity on Bone Scan.

A 54-year-old man, with previous history of neurogenic heterotopic ossification (HO) in muscles around the left hip following a spinal cord injury ten months earlier, was referred to our nuclear medicine center for an 18fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) to rule out a spondylodiscitis. No sign of spondylodiscitis was found on 18F-FDG PET/CT, but images revealed an increased 18F-FDG uptake in HO areas, matching with ongoing osteoblastic activity on a following bone scan.