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Background Atypical arousal regulation may explain slower mean reaction time (MRT) in autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder compared with typical development. The locus coeruleus–norepinephrine system (LC-NE) underlies arousal regulation and adapts its activity to the utility of a task. LC-NE tonic and phasic activity are indexed by baseline pupil size (BPS) and stimulus-evoked pupillary response (SEPR). Methods The study assessed pupillometry in ASD (n = 31, 3 female/28 male), attention-deficit/hyperactivity disorder (n = 28, 3 female/25 male), and typically developing control subjects (n = 31, 16 female/15 male) during a visuospatial reaction-time task that manipulates arousal by conditions with low and high task utility. We estimated linear mixed models of BPS, SEPR, and MRT in a per-trial analysis to investigate arousal regulation of task performance. Results Slower MRT occurred in the ASD group compared with the typically developing control group during low-utility conditions while controlling for dimensional ASD and attention-deficit/hyperactivity disorder symptoms. In low-utility conditions, BPS and SEPR were inversely related and both were associated with faster MRT. Increased ASD symptoms across groups were associated with higher BPS during low-utility conditions. Changes in BPS and SEPR between task-utility conditions were smaller in the ASD group. Conclusions Slower visuospatial task performance in ASD is specific to low task utility. Arousal was associated with task performance and showed altered activity in ASD. Increased BPS during low-utility conditions suggested increased LC-NE tonic activity as an ASD symptom marker in children. Smaller changes in BPS and SEPR in ASD indicated attenuated LC-NE activity adaptation in response to high-utility conditions. Slower performance and atypical arousal regulation are probably associated with attenuated LC-NE activity adaptation.

Anxiety disorders are highly prevalent among individuals with a history of prenatal alcohol exposure (PAE), and adolescent rodents demonstrate anxiety-like behavior following moderate PAE on Gestational Day (G) 12. A likely systemic target of PAE is the stress peptide corticotrophin-releasing factor (CRF), as activation of CRF receptor 1 (CRFR1) in the medial nucleus of the central amygdala (CeM) is known to increase anxiety-like behavior in adults. To determine if CRF-CRFR1 interactions underly PAE-induced anxiety, functional changes in CRF system activity were investigated in adolescent male and female Sprague Dawley rats following G12 PAE. Compared to air-exposed controls, PAE increased basal spontaneous (s) inhibitory post-synaptic current (IPSC) frequency in the CeM of males, but not females. Furthermore, PAE blunted CRFR1-regulated miniature (m) IPSCs in a sex- and dose-specific manner, and only PAE males demonstrated tonic CRFR1 activity in the CeM. It was further determined that G12 PAE decreased CRFR1 mRNA in the CeM of males while increasing regional expression in females. Finally, infusion of a CRFR1 agonist into the CeM of adolescents produced a blunted expression of CRFR1-induced anxiety-like behavior exclusively in PAE males, mirroring the blunted physiology demonstrated by PAE males. Cumulatively, these data suggest that CRFR1 function within the CeM is age- and sex-specific, and PAE not only increases the expression of anxiety-like behavior, but may reduce the efficacy of treatment for PAE-induced anxiety through CRFR1-associated mechanisms. Therefore, future research will be necessary to develop targeted treatment of anxiety disorders in individuals with a history of PAE.

BACKGROUND Transcutaneous auricular vagus nerve stimulation (taVNS) may modulate cardiac autonomic function. However, the response rate of the traditional tonic paradigm is low, and the results remain inconsistent. A recent pilot study presented a novel burst paradigm to activate the cardiac parasympathetic system, which might offer a new approach to treat cardiac autonomic function. The present study reassessed the effect of burst taVNS on modulating heart rate variability and explored the difference between burst and traditional tonic paradigms. MATERIALS AND METHODS Forty-two young adults were recruited for this study. Each participant underwent three types of taVNS with sham (30 sec of stimulation), tonic (25 Hz, 500 μsec), and burst (five pulses at 500 Hz every 200 msec) paradigms, respectively, with simultaneous electrocardiogram recording. One-way analysis of variance, multivariate analysis of variance, and linear regression were used for analysis. Multiple testing was performed using Bonferroni correction. RESULTS Both burst and tonic paradigms induced a significant decrease in heart rate, which continued until poststimulation, and increased cardiac parasympathetic activity. Moreover, two parasympathetic system indicators showed significant increase only in burst taVNS. The response rates during burst (35.7%) and tonic (38.1%) stimulations were both higher than that during sham stimulation (11.9%). The response to taVNS showed parameter specificity with few nonresponders to the tonic paradigm responding to the burst paradigm. The overall response rate increased from 38.1% in tonic taVNS to 54.8% in taVNS using both burst and tonic paradigms. For both burst and tonic responders, baseline cardiac parasympathetic activity was found to be significantly negatively correlated with changes during stimulation. CONCLUSION The burst parameter could be used as an alternative strategy for regulating cardiac parasympathetic function by taVNS, which has the potential to be used as a complementary paradigm to traditional tonic taVNS for promoting clinical treatment efficacy.

Right-wing authoritarianism (RWA) and social dominance orientation (SDO) both predict generalized prejudice, dehumanization, intergroup discrimination, oppression, violence, right-wing political party preference, and generally punitive attitudes. Authoritarian attitudes have been theorized to involve maladaptive emotional, cognitive, and social self-regulation. However, there is no study of authoritarianism using the functioning of the parasympathetic nervous system (PNS) as a physiological index of self-regulation, thus leaving it unclear whether regulation is "impaired" with authoritarian attitudes per se. PNS functioning is commonly assessed by examining tonic and phasic heart rate variability (HRV). These two components are recognized to be important in terms of adaptation to stress. Decreased HRV has been associated with hypoactive prefrontal regulation, hyperactive subcortical structures, maladaptive self-regulation, hyper-vigilance, decreased prosocial tendencies, defensiveness, impulsive behaviors, and aggression. Previous research suggests that self-regulatory failure may favor hostile attitudes and prejudicial intergroup behaviors. In a first study, we found that high RWA was associated with lower tonic HRV at rest. In a second study, stress-induced autonomic reactivity and poststress autonomic recovery were examined as potential pathways linking authoritarian attitudes to self-regulation. We found that high RWA and high SDO were associated with (i) lower tonic HRV during stress, (ii) greater autonomic reactivity during stress, and (iii) lower autonomic recovery. Overall, our results suggest that autonomic dysregulation during and following stress is a plausible physiological pathway connecting RWA and SDO to self-regulation. Implications of such results for research on political attitudes are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Abnormal central pain processing is a leading cause of pain in fibromyalgia (FM) and is perceptually characterized with the psychophysical measure of temporal summation of pain (TSP). TSP is the perception of increasingly greater pain in response to repetitive or tonic noxious stimuli. Previous neuroimaging studies have used static (i.e., summary) measures to examine the functional magnetic resonance imaging (fMRI) correlates of TSP in FM. However, functional brain activity rapidly and dynamically reorganizes over time, and, similarly, TSP is a temporally evolving process. This study was undertaken to demonstrate how a complete understanding of the neural circuitry supporting TSP in FM thus requires a dynamic measure that evolves over time.We utilized novel methods for analyzing dynamic functional brain connectivity in patients with FM in order to examine how TSP-associated fluctuations are linked to the dynamic functional reconfiguration of the brain. In 84 FM patients and age- and sex-matched healthy controls, we collected high-temporal-resolution fMRI data during a resting state and during a state in which sustained cuff pressure pain was applied to the leg.FM patients experienced greater TSP than healthy controls (mean ± SD TSP score 17.93 ± 19.24 in FM patients versus 9.47 ± 14.06 in healthy controls; P = 0.028), but TSP scores varied substantially between patients. In the brain, the presence versus absence of TSP in patients with FM was marked by more sustained enmeshment between sensorimotor and salience networks during the pain period. Furthermore, dynamic enmeshment was noted solely in FM patients with high TSP, as interactions with all other brain networks were dampened during the pain period.This study elucidates the dynamic brain processes underlying facilitated central pain processing in FM. Our findings will enable future investigation of dynamic symptoms in FM.

Although we know sensation is continuous, research on long-lasting and continuously changing stimuli is scarce and the dynamic nature of ongoing cortical processing is largely neglected. In a longitudinal study, 38 participants across four sessions were asked to continuously rate the intensity of an applied tonic heat pain for 20 min. Using group-independent component analysis and dual regression, we extracted the subjects’ time courses of intrinsic network activity. The relationship between the dynamic fluctuation of network activity with the varying time courses of three pain processing entities was computed: pain intensity, the direction of pain intensity changes, and temperature. We were able to dissociate the spatio-temporal patterns of objective (temperature) and subjective (pain intensity/changes of pain intensity) aspects of pain processing in the human brain. We found two somatosensory networks with distinct functions: one network that encodes the small fluctuations in temperature and consists mainly of bilateral primary somatosensory cortex (SI), and a second right-lateralized network that encodes the intensity of the subjective experience of pain consisting of SI, secondary somatosensory cortex, the posterior cingulate cortex, and the thalamus. We revealed the somatosensory dynamics that build up toward a current subjective percept of pain. The timing suggests a cascade of subsequent processing steps toward the current pain percept.

ORAI1 and stromal interaction molecule 1 (STIM1) are the critical mediators of store-operated Ca2+ entry by acting as the pore subunit and an endoplasmic reticulum–resident signaling molecule, respectively. In addition to Ca2+ signaling, STIM1 is also involved in regulation of the type I IFN (IFN-I) response. To examine their potential role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, we generated ORAI1 and STIM1 knockout human HEK293–angiotensin-converting enzyme 2 cells and checked their responses. STIM1 knockout cells showed strong resistance to SARS-CoV-2 infection as a result of enhanced IFN-I response. On the contrary, ORAI1 deletion induced high susceptibility to SARS-CoV-2 infection. Mechanistically, ORAI1 knockout cells showed reduced homeostatic cytoplasmic Ca2+ concentration and severe impairment in tonic IFN-I signaling. Transcriptome analysis showed downregulation of multiple antiviral signaling pathways in ORAI1 knockout cells, likely because of reduced expression of the Ca2+-dependent transcription factors of the AP-1 family and MEF2C. Accordingly, modulation of homeostatic Ca2+ concentration by pretreatment with ORAI1 blocker or agonist could influence baseline IFNB expression and resistance to SARS-CoV-2 infection in a human lung epithelial cell line. Our results identify a novel role of ORAI1-mediated Ca2+ signaling in regulating the tonic IFN-I levels, which determine host resistance to SARS-CoV-2 infection.

Veterinarians often need to sedate or anesthetize fish to perform physical examinations or other diagnostic procedures. Sedation may also be required to transport fish. Painful procedures require complete anesthesia with appropriate antinociceptive agents. Regulations and withdrawal times apply to food animal species in many countries. Specific protocols are therefore warranted in commercial fish versus ornamentals. Tonic immobility of elasmobranchs and electric anesthesia should never be used to perform painful procedures. Anesthetic monitoring in fish remains challenging. This review summarizes ornamental fish anesthesia and discusses techniques used in the commercial fish industry and in field conditions.

OBJECTIVE: A substantial number of sexual assault victims report experiencing some form of peritraumatic tonic immobility (TI). A self-report questionnaire that is widely used to assess TI retrospectively is the Tonic Immobility Scale (TIS). This study explored the factor structure of the TIS in a clinical sample of adolescent and young adults.METHOD: The sample comprised 131 female rape victims, aged 13-25, who were referred for specialized trauma-focused treatment. An exploratory factor analysis (EFA) was performed.RESULTS: The EFA showed support for a three-factor model, with factors TI, Fear, and Detachment. Item correlations ranged from .32 to .57 for TI, from .14 to .35 for Fear, and .29 for the two Detachment items.CONCLUSIONS: We found support for a three-factor solution distinguishing TI, fear, and detachment, suggesting the need to further develop the TIS with different subscales in varying age groups and clinical samples. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

ObjectivesSensory methods use human senses to evaluate product attributes. This review provides an overview of the types of sensory methods used to evaluate the perception of flavour in tobacco and other nicotine-containing (ToNic) products and to discuss how sensory data could inform flavoured ToNic product policy.Data sourcesPubMed, Embase and Web of Science.Study selectionAll peer-reviewed studies evaluating ToNic products using a sensory method published before 23 May 2020.Data extractionTwo independent coders completed title/abstract and full-text screening to choose articles for inclusion (Cohen’s kappa=0.85, strong agreement). Each coder completed data extraction on half the articles, recording relevant information (eg, sensory methods used, results). The coders categorised sensory methods and generated overarching themes.Data synthesisOf 110 articles identified, we included 29 articles containing 35 studies that used sensory methods to investigate ToNic products. The sensory methods included analytic methods such as discrimination and descriptive tests and hedonic methods such as liking tests. Six themes emerged regarding how sensory methods can be used to understand consumer perception and liking of ToNic products and to inform ToNic product policy.ConclusionsThe identified studies highlight that sensory data can inform ToNic product policy. Analytic and sensory hedonic ratings can be used to assess a ToNic product’s ability to promote addiction in the user (ie, abuse liability). Lastly, hedonic ratings can provide information to assess potential use behaviours.

Diverse physiological phenotypes in a neuronal population can broaden the range of computational capabilities within a brain region. The avian cochlear nucleus angularis (NA) contains a heterogeneous population of neurons whose variation in intrinsic properties results in electrophysiological phenotypes with a range of sensitivities to temporally modulated input. The low-threshold potassium conductance (GKLT) is a key feature of neurons involved in fine temporal structure coding for sound localization but a role for these channels in intensity or spectrotemporal coding has not been established. To determine whether GKLT affects the phenotypical variation and temporal properties of NA neurons, we applied dendrotoxin (DTX), a potent antagonist of Kv1-type potassium channels, to chick brain stem slices in vitro during whole-cell patch clamp recordings. We found a cell-type specific subset of NA neurons were sensitive to DTX: single-spiking NA neurons were most profoundly affected, as well as a subset of tonic firing neurons. Both tonic I (phasic onset bursting) and tonic II (delayed firing) neurons showed DTX sensitivity in their firing rate and phenotypical firing pattern. Tonic III neurons were unaffected. Spike time reliability and fluctuation sensitivity measured in DTX-sensitive NA neurons was also reduced with DTX. Finally, DTX reduced spike threshold adaptation in these neurons, suggesting that GKLT contributes to the temporal properties that allow coding of rapid changes in the inputs to NA neurons. These results suggest that variation in Kv1 channel expression may be a key factor in functional diversity in the avian cochlear nucleus.New and noteworthyThe dendrotoxin-sensitive voltage-gated potassium conductance typically associated with neuronal coincidence detection the timing pathway for sound localization is demonstrated to affect spiking patterns and temporal input sensitivity in the intensity pathway in the avian auditory brain stem. The Kv1-family channels appear to be present in a subset of cochlear nucleus angularis neurons, regulate spike threshold dynamics underlying high-pass membrane filtering, and contribute to intrinsic firing diversity.

Objective: This study aimed to investigate the relationship between acute-phase reactants and oxidative stress and epilepsy.Methods: The patient group consisted of 67 patients who applied to the Pediatric Neurology outpatient clinic and were diagnosed with generalized type epilepsy according to ILAE classification, 33 were receiving monotherapy and 34 were receiving antiepileptic medication in the form of polytherapy. The control group included 30 healthy volunteer participants with similar sociodemographic characteristics in the same age range, without epilepsy or any known chronic disease. Total anti-Oxidant Status (TAS) and total Oxidant Status (TOS) were measured according to the method developed by Erel, and the oxidative stress index (OSI) was calculated. Sensitive C-reactive protein (Hs-CRP) levels were measured.Results: Both TOS and OSI levels of the patients who received antiepileptic monotherapy and polytherapy were statistically significantly higher than the control group (p = 0.004, the TOS levels of the patients who received antiepileptic monotherapy and polytherapy were 19.29 ± 1.27, 19.22 ± 1.26, respectively, control group 14.49 ± 1.75, OSI levels of patients receiving antiepileptic monotherapy and polytherapy 1.66 ± 0.12, 1.72 ± 0.11, control group 1.27 ± 0.11), respectively. The Hs-CRP level (0.59 ± 0.06 mg / L, 1.09 ± 0.06 mg / L, respectively) of the patients who received monotherapy and polytherapy was statistically significant compared to the control group (0.42 ± 0.02 mg / L) significantly higher.Conclusion: In this study, the findings suggest that epileptic seizures increase oxidative stress parameters and antioxidant mechanisms are insufficient to reduce oxidative damage. In addition, considering the high serum Hs-CRP levels, it is extremely important to develop treatment strategies that can control the inflammatory process in treating resistant epilepsy., Amaç: Bu çalışmada akut faz reaktanları ile oksidatif stres ve epilepsi arasındaki ilişkinin araştırılması amaçlanmıştır.Gereç ve Yöntem: Hasta grubu, Çocuk Nörolojisi polikliniğine başvuran ve ILAE sınıflamasına göre jeneralize tip epilepsi tanısı alan, 33’ü monoterapi, 34’ü ise politerapi şeklinde antiepileptik ilaç tedavisi almakta olan 67 hastadan oluşmaktaydı. Kontrol grubu, epilepsi veya bilinen herhangi bir kronik hastalığı olmayan, aynı yaş aralığında benzer sosyodemografik özelliklere sahip özelliklere sahip 30 sağlıklı gönüllü katılımcıyı içeriyordu. Toplam anti-oksidan durumu (TAS) ve toplam oksidan durumu (TOS) Erel tarafından geliştirilen yönteme göre ölçülmüş ve oksidatif stres indeksi (OSI) hesaplanmıştır. Hassas C-reaktif protein (Hs-CRP) seviyeleri ölçüldü.Bulgular: Antiepileptik monoterapi ve politerapi alan hastaların hem TOS hem OSI düzeyleri kontrol grubuna göre istatistiksel olarak anlamlı derecede yüksek bulundu(p=0.004), antiepileptik monoterapi ve politerapi alan hastaların TOS düzeyleri sırasıyla 19.29±1.27, 19.22±1.26, kontrol grubu 14.49±1.75, antiepileptik monoterapi ve politerapi alan hastaların OSI düzeyleri sırasıyla 1.66±0.12, 1.72±0.11, kontrol grubu 1.27±0.11). Monoterapi ve politerapi alan hastaların Hs-CRP düzeyi (sırasıyla 0.59±0.06 mg/L, 1.09±0.06 mg/L), kontrol grubuna göre (0.42±0.02 mg/L) istatistiksel olarak anlamlı derecede yüksek bulundu.Sonuç: Bu çalışmada, epileptik nöbetin oksidatif stres parametrelerini arttırdığı ve antioksidan mekanizmaların oksidatif hasarı azaltmada yetersiz kaldığı sonucuna varılmıştır. Ayrıca yüksek serum Hs-CRP seviyeleri göz önüne alındığında, dirençli epilepsinin tedavisinde inflamatuar süreci kontrol edebilen tedavi stratejilerinin geliştirilmesi son derece önemlidir.

The basolateral nucleus of the amygdala (BLA) is responsible for memory retrieval after stress. It regulates hippocampal long-term potentiation (LTP) during stress. Although β-adrenoceptors of the BLA have a critical role in memory, few studies have addressed this question in the BLA, and the results still have been contradictory. The present study was designed to investigate the involvement of β-adrenoceptors of the BLA on hippocampus memory, anxiety, and plasticity in intact and stressed rats. Male Wistar rats were submitted to the electrical foot-shock stress for four consecutive days. Over four consecutive days, animals received bilateral micro-injections of either vehicle or propranolol (4 µg in 1 µl/side) into the BLA (5 min before foot-shock stress). Behavioral (memory, as well as anxiety-like behaviors), electrophysiological, and histological (neural arborization in the hippocampal CA1 pyramidal neurons) studies were performed. Results showed that inhibition of β-adrenoceptors of BLA by propranolol significantly further impaired fear and spatial memory in stressed rats. Similarly, propranolol effectively impaired both memories in the intact animals. Propranolol significantly amplified the slope and amplitude of fEPSP in the CA1 area of the hippocampus only in stressed rats. Foot-shock stress significantly increased the number of dendritic branches in the hippocampus, and propranolol suppressed this effect of stress. It is suggested that β-adrenoceptors in the BLA promote memory and reduce anxiety-like behaviors under tonic and stress conditions. Propranolol dysregulated LTP parameters and reduced dendritic branches, resulting in memory impairment. Probably β-adrenoceptors of BLA regulate evoked responses of CA1 neurons only in stress- and not the tonic condition.

An interoception model for the acute exercise-cognition interaction is presented. During exercise following the norepinephrine threshold, interoceptive feedback induces increased tonic release of extracellular catecholamines, facilitating phasic release hence better cognitive performance of executive functions. When exercise intensity increases to maximum, the nature of task-induced norepinephrine release from the locus coeruleus is dependent on interaction between motivation, perceived effort costs and perceived availability of resources. This is controlled by interaction between the rostral and dorsolateral prefrontal cortices, orbitofrontal cortex, anterior cingulate cortex and anterior insula cortex. If perceived available resources are sufficient to meet predicted effort costs and reward value is high, tonic release from the locus coeruleus is attenuated thus facilitating phasic release, therefore cognition is not inhibited. However, if perceived available resources are insufficient to meet predicted effort costs or reward value is low, tonic release from the locus coeruleus is induced, attenuating phasic release. As a result, cognition is inhibited, although long-term memory and tasks that require switching to new stimuli-response couplings are probably facilitated.

Mature CD4(+) and CD8(+) T cells constitutively experience weak T cell receptor (TCR) stimulation in response to self-antigens, termed tonic (or basal) signaling. How tonic TCR signal strength impacts T cell responses to foreign antigens is an active area of investigation. Such studies rely on surrogate markers of tonic signal strength, including CD5, Ly6C, and transgenic reporters of Nr4a genes. Recent research indicates that strong tonic TCR signal strength influences basal T cell metabolism, effector differentiation, and TCR signal transduction. T cells that experience the strongest tonic TCR signaling exhibit features of T cell activation and negative regulation. These data suggest a model whereby adaptation to tonic signaling has lasting effects that alter T cell activation and differentiation.

Introduction: In assessing patients with a stroke sequel, tonic and postural changes are generally evaluated, but other important information, such as functional capacity, risk of falls, and gait, should also be taken into account. Objective: To correlate the impairment level determined by Brunnstrom's scale, the results of functional tests and analyze the characteristics of the sample as being affected by comorbidities, time and number of strokes occurred. Methods: Cross-sectional evaluation of 50 patients (convenience) at a center of public rehabilitation, using Brunnstrom's scale (1-6, better limb ability closer to 6), Time Up and Go (TUG) (significant mobility deficit and in risk of falls above 20 seconds), Upright Motor Control Test (UMCT) (1-3, bellow 3 are household walkers), Step Test (ST) (disparity between member refers to slower individuals), registration of comorbidity and the time since the stroke happened and the number of episodes. Results: Grade "4" rated for upper and lower limbs by Brunnstrom's Scale, achieving over 20 seconds in TUG, level 2 in UMCT, and commitment of paretic member related to non-paretic on the ST (p

The use of chimeric antigen receptor (CAR)-engineered regulatory T cells (Tregs) has emerged as a promising strategy to promote immune tolerance. However, in conventional T cells (Tconvs), CAR expression is often associated with tonic signaling, which can induce CAR-T cell dysfunction. The extent and effects of CAR tonic signaling vary greatly according to the expression intensity and intrinsic properties of the CAR. Here, we show that the 4-1BB CSD-associated tonic signal yields a more dramatic effect in CAR-Tregs than in CAR-Tconvs with respect to activation and proliferation. Compared to CD28 CAR-Tregs, 4-1BB CAR-Tregs exhibit decreased lineage stability and reduced in vivo suppressive capacities. Transient exposure of 4-1BB CAR-Tregs to a Treg stabilizing cocktail, including an mTOR inhibitor and vitamin C, during ex vivo expansion sharply improves their in vivo function and expansion after adoptive transfer. This study demonstrates that the negative effects of 4-1BB tonic signaling in Tregs can be mitigated by transient mTOR inhibition., Chimeric antigen receptor engineering in T cells has been shown to be of great potential therapeutic benefit in a range of immune pathologies, although the functionality of such cell therapies can be limited due to tonic signalling and the induction of dysfunction. Here the authors show transient inhibition of mTOR can rescue their 41-BB-CAR-Tregs from tonic signalling-induced dysfunction.

The fast reaction of the autonomic nervous system (ANS) to an emotional challenge (EC) is the result of a functional coupling between parasympathetic (PNS) and sympathetic (SNS) branches. This coupling can be characterized by measures of cross-correlations between electrodermal activity (EDA) (under the influence of the SNS) and the RR interval (the interval between R peaks) (under the influence of the PNS and the SNS). Significant interindividual variability has previously been reported in SNS-PNS coupling in emotional situations, and the present study aimed to identify interindividual cross-correlation variability in ANS reactivity. We therefore studied EDA and the RR interval in 62 healthy subjects, recorded during a 24-minute EC. A Gaussian Mixture Model was used to cluster tonic EDA-RR cross-correlations during the EC. This identified two clusters that were characterized by significant or non-significant cross-correlations (SCC and NCC clusters, respectively). The SCC cluster reported higher negative emotion after the EC, while the NCC cluster reported higher scores on the Center for Epidemiologic Studies–Depression scale. The latter finding suggests that NCC is a pathological mood pattern with altered negative perception. Furthermore, a machine learning model that included three parameters indexing the functionality of both branches of the ANS, measured at baseline, predicted cluster membership. Our results are a first step in detecting dysfunctional ANS reactivity in general population.

We report the impact of a Gentle Touch Stimulation (GTS) program. Forty-three mothers provided daily 10-min GTS with C-tactile (CT) afferent optimal stroking touch, for 4 weeks to their 3-12 weeks old infants. CT-afferents are cutaneous unmyelinated, low-threshold mechanosensitive nerves hypothesized to underly the regulatory impact of affective touch. We compared physiological and behavioral responses during a no-touch-baseline (BL), static-touch-baseline (BL-T), intervention/control (GTS/CTRL), Still Face (SF) and Reunion (RU) condition for GTS-infants versus a control-group (CTRL) at the start (T1) and end of (T2) of the program. We collected mother-infant ECG, respiration, cortisol, video-recordings, and diary-reports. At T1, physiological arousal significantly increased during SF in both groups, that is, decreased respiratory sinus arrhythmia (RSA) and R-R interval (RRI). At T2, GTS-infants showed significantly increased RSA, RRI, decreased respiration during GTS, buffering SF-arousal and allowing complete recovery during RU; CTRL-infants showed higher SF-arousal and small recovery, under initial BL-levels. Maternal cardio-respiratory showed a metabolic investment during RU. Cortisol and behavioral analyses showed higher arousal in CTRL-infants than GTS-infants at T2. We suggest that the combination of phasic short-term and tonic long-term responses to CT-optimal stroking touch, delivered in a structured daily manner, contribute to the building of infant stress regulation and resilience.Reportamos el impacto del programa de Estimulación Táctil Suave (GTS). Cuarenta y tres madres les dieron a sus infantes de 3-12 semanas 10 minutos de GTS con un toque táctil-C (CT) aferente óptimo de caricias por 4 semanas. Los aferentes CT son nervios cutáneos amielínicos mecano-sensibles de bajo impacto que según hipótesis rigen el impacto regulatorio del toque afectivo. Comparamos las respuestas fisiológicas y de comportamiento durante un momento de referencia no táctil (BL), un momento de referencia táctil estático (BL-T), intervención/control (GTS-CTRL), la Cara Seria (SF) y la condición de Reunión (RU) para infantes GTS versus un grupo de control (CTRL) al principio (T1) y al final (T2) del programa. Recogimos información ECG de madre-infante, respiración, cortisol, grabaciones en vídeo, y reportes de un diario. Al T1, la estimulación fisiológica significativamente aumentó durante SF en ambos grupos, v.g., una baja en la arritmia respiratoria paranasal (RSA) y el intervalo R-R (RRI). Al T2, los infantes GTS significativamente mostraron un aumento de RSA, RRI, una baja en la respiración durante GTS, amortiguando la estimulación SF y permitiendo un completo recobro durante RU; los infantes de CTRL mostraron una más alta estimulación SF y un pequeño recobro, bajo los niveles BL iniciales. El aspecto cardio-respiratorio materno mostró inversión metabólica durante RU. Los análisis de cortisol y de comportamiento mostraron más altas estimulaciones de infantes de CTRL que en infantes GTS al T2. Proponemos que la combinación de las respuestas fásicas a corto plazo y tónicas a largo plazo a las caricias táctiles óptimas CT, ofrecidas de una manera estructural diaria, contribuyen a moldear la regulación del estrés y capacidad de resistencia del infante.Cet article fait état de l'impact du programme Stimulation Toucher en Douceur (an anglais Gentle Touch Stimulation, que nous abrégeons ici GTS). Quarante-trois mères ont procédé chaque jour à un GTS de 10 minutes avec un toucher par caresse optimale C-tactile (CT) afférent, pendant 4 semaines à leurs nourrissons de 3-12 semaines. Les afférents CD sont des nerfs cutanés amyéliniques, à faible seuil et mécano-sensibles, dont on pense qu'ils sous-tendent l'impact régulatoire du toucher affectif. Nous comparons les réponses physiologiques et les réponses comportementales durant la condition à un niveau de référence NR sans toucher, un niveau de référence toucher statique (NR-T), un contrôle/intervention (GTS/CTRL), Visage Impassible (Still Face, soit SF) et la Réunion (RU) pour les bébés GTS par rapport aux bébés du groupe de contrôle (CTRL) au commencement (T1) et à la fin (T2) du programme. Nous avons recueilli l’électrocardiogramme mère-bébé, la respiration, le niveau de cortisol et les rapports-journaux. Au T1 la stimulation physiologique a augmenté de façon importante durant le SF pour les deux groupes, c'est-à-dire une arythmie des sinus respiratoires (RSA) décrue et un intervalle R-R décru (RRI). Au T2 les bébés GTS ont fait preuve d'une RSA et d'un RRI bien plus élevés, une respiration décrue durant le GTS, un éveil SF tampon et ont fait preuve d'un rétablissement complet durant la RU. Les bébés contrôle ont fait preuve de plus d’éveil SF et d'un petit rétablissement, moins élevés que les niveaux BL initiaux. La cardio-respiration maternelle a fait preuve un investissement métabolique durant la RU. Les analyses de cortisol et les analyses comportementales ont montré un éveil plus élevé chez les bébés-CTRL que chez les bébés GTS au T2. Nous suggérons que la combinaison de réactions phasiques à court terme et de réponses toniques à long terme au toucher caresse CT-optimal, donné chaque jour de manière structurée, contribue à la construction de la régulation du stress du bébé et de sa résilience.Warum sehnen wir uns nach Berührung? Die Auswirkungen täglicher sanfter Berührungsstimulation auf die physiologische und verhaltensbezogene Regulation sowie Resilienz von Mutter und Kind Wir berichten über die Auswirkungen eines Programms zur sanften Berührungsstimulation (Gentle Touch Stimulation; GTS). Dreiundvierzig Mütter wendeten bei ihren 3-12 Wochen alten Säuglingen 4 Wochen lang täglich 10 Minuten GTS an, d.h. eine C-taktile (CT) afferente optimale streichelnde Berührung. Bei den CT-Afferenzen handelt es sich um kutane, nicht-myelinisierte, niedrigschwellig mechanosensorische Nerven, von denen angenommen wird, dass sie den regulierenden Auswirkungen affektiver Berührungen zugrunde liegen. Wir verglichen die physiologischen und verhaltensbezogenen Reaktionen von GTS-Säuglingen im Vergleich zu einer Kontrollgruppe (CTRL) zu Beginn (T1) und am Ende (T2) des Programms während einer berührungsfreien Baseline (BL), einer statischen Berührungsbaseline (BL-T), einer Interventions-/Kontrollbedingung (GTS/CTRL), einer „Still Face“ Bedingung (SF) und einer Wiedervereinigung (RU). Erhoben wurden Mutter-Kind EKG, Atmung, Cortisol, Videoaufzeichnungen und Tagebucheinträge. Zu T1 nahm die physiologische Erregung während der SF in beiden Gruppen signifikant zu, d. h. die respiratorische Sinusarrhythmie (RSA) und das R-R-Intervall (RRI) nahmen ab. Zu T2 zeigten die GTS-Säuglinge signifikant erhöhte RSA, RRI und verringerte Atmung während der GTS, was die SF-Erregung abpufferte und eine vollständige Erholung während der RU ermöglichte. Die CTRL-Säuglinge zeigten eine höhere SF-Erregung und eine geringe Erholung unter den ursprünglichen BL-Werten. Die mütterliche kardio-respiratorische Aktivität zeigte eine metabolische Investition während der RU. Cortisol- und Verhaltensanalysen zeigten eine höhere Erregung bei CTRL-Säuglingen als bei GTS-Säuglingen zu T2. Die Ergebnisse weisen darauf hin, dass die Kombination von phasischen Kurzzeit- und tonischen Langzeitreaktionen auf CT-optimale streichelnde Berührungen, die täglich strukturiert durchgeführt werden, zum Aufbau der Stressregulation und Resilienz von Säuglingen beitragen.なぜ私たちはタッチングを希求するか−毎日の優しいタッチングの刺激が、母Ȁ子の身体生理および行動の調節と レジリエンス(復元力)に及ぼす影響 ジェントルタッチスティミュレーション(GTS)プログラムの効果について報告する。 43人の母親が、生後3〜12週の母親の乳児に、C-tactile(CT)求心性の最適ななでるタッチングを含む10分間のGTSを4週間毎日行った。CT求心性神経は、情緒的なタッチングの調整的な影響を過小評価していると仮定される皮膚の無髄鞘の低閾値のメカノセンシチブ神経である。GTSの非タッチベースライン(BL)、静的タッチベースライン(BL-T)、介入/制御(GTS / CTRL)、スティルフェイス(SF)、および再会(RU)状態での身体生理および行動の反応を、GTS-乳児と対照群(CTRL-乳児)で、プログラムの開始時(T1)と終了時(T2)に比較した。母と子の心電図、呼吸の状態、コルチゾール、ビデオ録画、および日記を記録した。T1では、両グループとも、SF中において身体生理的に有意に覚醒した。つまり、呼吸性洞性不整脈(RSA)とR-R間隔(RRI)が減少した。T2では、GTS-乳児は、RSA、RRIが有意に増加し、GTS中に呼吸数が減少し、SF覚醒は緩まり、RU中に完全に回復を示した。一方、CTRL-乳児は、初期のBLレベル下で、より高いSF覚醒とわずかな回復を示した。母親の心肺系は、RU中に代謝投資を示した。コルチゾールと行動分析では、T2ではGTS-乳児よりもCTRL-乳児でより高い覚醒を示した。構造化され毎日提供されるCT最適なストロークタッチングに対する相性の短期的および強壮性の長期的反応の組み合わせが、乳児のストレス調節と回復の構築に寄与するとした。.我们报告了一项“温和触摸刺激” (GTS) 项目的影响。43位母亲利用“C组触觉 (CT) 传入神经”的最佳轻抚触摸方式每天为其3-12周大的婴儿提供10分钟的GTS, 为期4周。C组触觉传入神经是皮肤无髓鞘、低阈值的机械敏感性神经, 被认为是情感触摸调节影响的基础。我们在项目开始 (T1) 和结束 (T2) 阶段比较了GTS-婴儿与对照组在无接触基线 (BL)、静态接触基线 (BL-T)、干预/对照 (GTS/CTRL)、静止面孔 (SF) 以及重聚 (RU) 条件下的生理和行为反应。我们收集了母婴心电图、呼吸、皮质醇、录像和日记报告。在T1阶段, 两组婴儿在SF期间的生理唤醒显著增加, 即呼吸性窦性心律不齐 (RSA) 和R-R间期 (RRI) 减少。在T2阶段, GTS-婴儿的RSA、RRI显著增加, GTS期间呼吸减少, SF-唤醒减缓, 并在RU期间呈现完全恢复;在初始BL水平下, CTRL-婴儿表现出更高的SF-唤醒和微小恢复程度。在RU期间, 母亲的心肺功能显示出代谢消耗。皮质醇和行为分析显示, 在T2阶段, CTRL-婴儿的唤醒程度高于GTS-婴儿。我们建议, 对CT的最佳轻抚触摸方式应结合阶段性短期反应和强直长期反应, 以结构化的日常方式开展, 这有助于建立婴儿压力调节和复原力。.لماذا نتوق إلى اللمس؟ تأثير تحفيز اللمسة اللطيفة اليومية على التنظيم الفسيولوجي والسلوكي للأم والطفل والمرونة نعرض في هذه الدراسة تأثير برنامج تحفيز اللمسة اللطيفة (GTS). اشتركت مجموعة من 43 أمًا في الدراسة حيث طلب منهم تقديم 10 دقائق يومياً من اللمسة المثالية مع التمسيد لمدة 4 أسابيع لأطفالهن الذين تتراوح أعمارهم بين 3-12 أسبوعًا. المستقبلات العصبية منخفضة العتبة في الحساسية الميكانيكية و يُفترض أنها تتحكم في التأثير التنظيمي لللمس العاطفي. قمنا بمقارنة الاستجابات الفسيولوجية والسلوكية خلال حالة عدم وجود اللمس (BL) ، واللمس الثابت (T-BL) ، ومجموعة التدخل / المجموعة الضابطة (GTS / CTRL) ، والوجه الثابت (SF) ، ومجموعة Reunion (RU) للأطفال في برنامج اللمسة اللطيفة (GTS) مقارنة بالمجموعة الضابطة (CTRL) في نقطة البداية (T1) ونقطة النهاية (T2) من البرنامج. قمنا بجمع بيانات رسم القلب ، والتنفس ، والكورتيزول ، وتسجيلات الفيديو ، وتقارير اليوميات. في نقطة البداية (T1) ، زادت الاستثارة الفسيولوجية بشكل ملحوظ خلال حالة الوجه الثابت (SF) في كلا المجموعتين ، أي انخفاض عدم انتظام ضربات القلب التنفسي (RSA) و (RRI). وفي نقطة النهاية (T2) ، أظهر الرضع في برنامج (GTS) زيادة ملحوظة في RSA ، RRI ، وانخفاض التنفس أثناء GTS ؛ بينما أظهر الرضع في المجموعة الضابطة استثارة أعلى للوجه الثابت (SF) وفترة انتعاش قصيرة ، تحت مستويات BL الأولية. وأظهرت تحليلات الكورتيزول والسلوكية إثارة أعلى عند الرضع في المجموعة الضابطة عن الرضع في مجموعة التدخل عند نقطة النهاية (T2). تقترح الدراسة أن الجمع بين الاستجابات المرحلية قصيرة المدى وطويلة المدى للمس التمسيدي الأمثل الذي يقدم بشكل يومي ونظامي ، يمكن أن يساهم في بناء المرونة وتنظيم الإجهاد لدى الرضع.

OBJECTIVES Swift extubation is important to prevent detrimental effects of invasive mechanical ventilation but carries the risk of extubation failure. Accurate tools to assess extubation readiness are lacking. This study aimed to describe the effect of extubation on diaphragm activity in ventilated infants and children. Our secondary aim was to compare diaphragm activity between failed and successfully extubated patients. DESIGN Prospective, observational study. SETTING Single-center tertiary neonatal ICU and PICU. PATIENTS Infants and children receiving invasive mechanical ventilation longer than 24 hours. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Diaphragm activity was measured with transcutaneous electromyography, from 15 minutes before extubation till 180 minutes thereafter. Peak and tonic activity, inspiratory amplitude, inspiratory area under the curve, and respiratory rate were calculated from the diaphragm activity waveform. One hundred forty-seven infants and children were included (median postnatal age, 1.9; interquartile range, 0.9-6.7 wk). Twenty patients (13.6%) failed extubation within 72 hours. Diaphragm activity increased rapidly after extubation and remained higher throughout the measurement period. Pre extubation, peak (end-inspiratory) diaphragm activity and tonic (end-inspiratory) diaphragm activity were significantly higher in failure, compared with success cases (5.6 vs 7.0 μV; p = 0.04 and 2.8 vs 4.1 μV; p = 0.04, respectively). Receiver operator curve analysis showed the highest area under the curve for tonic (end-inspiratory) diaphragm activity (0.65), with a tonic (end-inspiratory) diaphragm activity greater than 3.4 μV having a combined sensitivity and specificity of 55% and 77%, respectively, to predict extubation outcome. After extubation, diaphragm activity remained higher in patients failing extubation. CONCLUSIONS Diaphragm activity rapidly increased after extubation. Patients failing extubation had a higher level of diaphragm activity, both pre and post extubation. The predictive value of the diaphragm activity variables alone was limited. Future studies are warranted to assess the additional value of electromyography of the diaphragm in combined extubation readiness assessment.

Tonic or phasic electrical epidural stimulation of the lumbosacral region of the spinal cord facilitates locomotion and standing in a variety of preclinical models with severe spinal cord injury. However, the mechanisms of epidural electrical stimulation that facilitate sensorimotor functions remain largely unknown. This review aims to address how epidural electrical stimulation interacts with spinal sensorimotor circuits and discusses the limitations that currently restrict the clinical implementation of this promising therapeutic approach.

Одно из перспективных направлений в создании спортивных напитков заключается во включении в их состав биологически активных компонентов растений, произрастающих в экстремальных условиях вегетации. В настоящей работе на их основе была разработана рецептура спортивного напитка, характеризующегося высокими тонизирующими свойствами («Inka Jungle»). В качестве одного из функциональных компонентов напитка использовали экстракт корнеплодов маки перуанской, произрастающей на высокогорных плато Боливии, Перу и северо-запада Аргентины на высоте 3500-4500 м над уровнем моря в условиях резких перепадов температур, интенсивной солнечной радиации и сильных ветров. Совокупность этих условий наделяет данное растение уникальными биологическими свойствами. При потреблении маки перуанской усиливаются и стабилизуются процессы возбуждения в центральной нервной системе, и как результат - «просыпается» жизненная активность человека, улучшается настроение, повышаются работоспособность, а также физическая и умственная выносливость. В качестве другого функционального компонента в состав напитка «Inka Jungle» включен экстракт кустарника Тёрнеры раскидистой или дамианы, зона произрастания которого - Южная и Центральная Америка и страны Карибского бассейна. Установлено, что прием экстракта листьев дамианы снимает нервозность, дает энергию при наступлении физической усталости, возникающей, например, после интенсивных тренировок и соревнований, повышает общий тонус организма. В состав напитка «Inka Jungle» в качестве функциональных компонентов включены также аминокислоты группы BCAA - лейцин, изолейцин, валин и L-карнитин, а также вспомогательные компоненты, формирующие его необходимые потребительские характеристики - загуститель (камедь ксантановая), регулятор кислотности (лимонная кислота), пищевой ароматизатор («гранат-клубника»), пищевой краситель («кармин») и консервант (сорбиновая кислота). Наличие в составе напитка «Inka Jungle» ряда жизненно важных компонентов позволяет при его приеме существенно увеличить интенсивность тренировок спортсменов, повысить их эффективность, обеспечить психоэмоциональную устойчивость атлетов, достичь эффективной защиты их организма от свободных радикалов и ускорить процесс восстановления после перенесенных интенсивных физических и психологических нагрузок. A promising direction in the development of sports drinks is the inclusion in their composition of biologically active components of plants growing in extreme vegetation conditions. The aim of this work was to create on their basis a sports drink characterized by high tonic properties («Inka Jungle»). As one of the functional components of the drink, was used an extract of the root vegetables of Peruvian maca, which grows on the high plateaus of Bolivia, Peru and northwestern Argentina at an altitude of 3500-4500 meters above sea level in conditions of sharp temperature changes, intense solar radiation and strong winds. The combination of these conditions endows this plant with unique biological properties. Consuming Peruvian maka intensifies and stabilizes the processes of excitation in the central nervous system, and as a result, a person's vital activity «wakes up», his mood improves, his working capacity rises, and his physical and mental endurance increases. As another functional component of the «Inka Jungle» drink, it contains an extract of Turner shrub or damiana, which grows in South and Central America and the Caribbean. It was found that damiana leaf extract relieves nervousness, gives energy when physical fatigue occurs, for example, after intense training and competition, and increases the overall potential of the body. The composition of the «Inka Jungle» drink as functional components also includes amino acids of the BCAA group - leucine, isoleucine, valine and L-carnitine, as well as auxiliary components that form its necessary consumer characteristics - a thickener (xanthan gum), an acidity regulator (citric acid), food flavoring («pomegranate-strawberry») and food coloring («carmine») and preservative (sorbic acid). The presence in the composition of the drink «Inka Jungle» of a number of vital components allows, when taken, to significantly increase the intensity of training of athletes, to increase their efficiency, to ensure their psycho-emotional stability, to achieve effective protection of their body from free radicals and to accelerate the recovery process after suffering intense physical and psychological stress.

Objective: Electrodermal activity (EDA) has been widely used to assess human response to stressful stimuli, including pain. Recently, spectral analysis of EDA has been found to be more sensitive and reproducible for assessment of sympathetic arousal than traditional indices (e.g., tonic and phasic components). However, none of the aforementioned analyses incorporate the differential characteristics of EDA, which could be more sensitive to capturing fast-changing dynamics associated with pain responses. Methods: We have tested the feasibility of using the derivative of phasic EDA and the modified time-varying spectral analysis of EDA. Sixteen subjects underwent four levels of pain stimulation using electric stimulation. Five-second segments of EDA were used for each level of stimulation, and pre-stimulation segments were considered stimulation level 0. We used support vector machines with the radial basis function kernel and multi-layer perceptron for three different scenarios of stimulation-level classification tasks: five stimulation levels (four levels of stimulation plus no stimulation); low, medium, and high pain stimulation (stimulation levels 0-1, 2, and 3-4, respectively); and high stimulation levels (stimulation levels 3-4) vs. no stimulation. Results: The maximum balanced accuracies were 44% (five stimulation levels), 63% (for low, medium, and high pain stimulation), and 87% (sensitivity 83% and specificity 89%, for high stimulation vs. no stimulation). Conclusion: The differential characteristics of EDA contributed highly to the accuracy of pain stimulation level detection of the classifiers. The external validity dataset was not considered in the study. Significance: Our approach has the potential for accurate pain quantification using EDA.

Lombroso and Fejerman, in 1977, described non-epileptic movements in normal infants and named them "benign myoclonus of early infancy", which were recently relabelled by Fernandez-Alvarez as "benign polymorphous movement disorder of infancy" (BPMDI). The focus of our study was to describe, categorize and point out the peculiar clinical representations of these heterogeneous phenomena through our video footage, particularly to those less experienced in paediatric neurology. We included all infants with a video-EEG performed at our unit or a home video recording of "Fejerman-Lombroso", "benign myoclonus of early infancy", "shuddering attacks" or "paroxysmal non-epileptic movements". Twenty-one children were selected. Age at onset ranged between two and 13 months, age at disappearance ranged between seven and 16 months, age at recording ranged between four and 16 months, and duration of the phenomena ranged between two weeks and 19 months. In total, 85% infants had normal neurodevelopment at onset and follow-up (mean follow-up: 31.47 months) and 15% presented with neuropsychological or neurosensory deficits. We distinguished four different patterns of movements: movement of the head in 50%, shuddering attacks in 30%, tonic brief contractions of the trunk and limbs in 10%, and elevation of the shoulders in 10%. These motor phenomena do not affect neurological status and are not associated with developmental delay. Considering that clinical interpretation may be challenging, especially relative to epileptic seizures, we present an explanatory video of these characteristic events. We also propose a new definition that is simple to remember: "transient infant movements" (TIM).

Purpose In recent years, neuromodulation has experienced a renaissance. Novel waveforms and anatomic targets show potential improvements in therapy that may signify substantial benefits. New innovations in peripheral nerve stimulation and dorsal root ganglion stimulation have shown prospective evidence and sustainability of results. Sub-perception physiologic bursting, high-frequency stimulation and feedback loop mechanisms provide significant benefits over traditional tonic spinal cords stimulation (SCS) in peer reviewed investigations. We reviewed the themes associated with novel technology in the context of historical stalwart publications. Findings New innovations have led to better nerve targeting, improvements in disease-based treatment, and opioid alternatives for those in chronic pain. In addition, new neural targets from both structural and cellular perspectives have changed the field of Neurostimulation. Summary For many years, tonic SCS was representative of neuromodulation, but as this review examines, the progression of the field in the past decade has reshaped patient options.

Peripheral chemoreceptors’ (PCh) hyperactivity increases sympathetic tone. An augmented acute ventilatory response to hypoxia, being a marker of PCh oversensitivity, was also identified as a marker of poor prognosis in HF. However, not much is known about the tonic (chronic) influence of PCh on cardio-respiratory parameters. In our study 30 HF patients and 30 healthy individuals were exposed to 100% oxygen for 1 min during which minute ventilation and hemodynamic parameters were non-invasively recorded. Systemic vascular resistance (SVR) and mean arterial pressure (MAP) responses to acute hyperoxia differed substantially between HF and control. In HF hyperoxia caused a significant drop in SVR in early stages with subsequent normalization, while increase in SVR was observed in controls. MAP increased in controls, but remained unchanged in HF. Bilateral carotid bodies excision performed in two HF subjects changed the response to hyperoxia towards the course seen in healthy individuals. These differences may be explained by the domination of early vascular reaction to hyperoxia in HF by vasodilation due to the inhibition of augmented tonic activity of PCh. Otherwise, in healthy subjects the vasoconstrictive action of oxygen remains unopposed. The magnitude of SVR change during acute hyperoxia may be used as a novel method for tonic PCh activity assessment.

Objective: to evaluate the role of seizure severity and epileptiform activity index (IEA) assessment in newly-diagnosed idiopathic generalized epilepsy with generalized tonic-clonic awakening seizures (GTCS).Material and methods. The study included 31 patients with newly-diagnosed generalized epilepsy with GTCS aged 14–52 years (mean age 25.06±9.3 years), which were divided into two groups depending on seizure severity: Group 1 (n=9, 29%) with 50% (responders), seizure rate decrease by Results. Total EAI at baseline was significantly higher in patients from Group 2 (p=0.019). Despite markedly reduced EAI level in both groups, in Group 1 (less than 18 points by NHS3) EAI was significantly lower compared to Group 2 (≥18 points) at all subsequent visits: visit 2 (p=0.038), visit 3 (p=0.035), visit 4 (p=0.047), and visit 5 (p=0.022).Conclusions. Assessing seizure severity may become an additional objective criterion while evaluating treatment efficacy.

Parents of children with ADHD typically report higher levels of parenting stress than parents of typically developing children. Children with ADHD display developmentally inappropriate levels of hyperactivity, impulsivity, and inattention. Some children with ADHD are also prone to particularly high levels of tonic irritability that may explain some of the impairments typically found in ADHD. The present study sought to determine the unique impact of ADHD and tonic irritability on child-related parenting stress domains (e.g., difficult child, parent–child dysfunctional interactions). 145 mothers of children with and without ADHD aged 7–12 years participated in the current study. Mothers completed self-report measures of parenting stress as well as a diagnostic structured interview. Ecological momentary assessment (EMA) was used to assess tonic irritability in an ecological environment. Indirect effects models were specified using PROCESS Model 4. For the parent–child dysfunctional interaction domain, the data were best fit by a model specifying a significant total effect of ADHD that was fully accounted for by an indirect effect through irritability. For the difficult child domain, model testing indicated a significant total effect of ADHD that was partially accounted for by an indirect effect through irritability. The current study adds support to the growing body of literature acknowledging the role of tonic irritability in children with ADHD. Furthermore, the results provide novel insight in the complex relation of irritability, child ADHD, and domains of parenting stress.

Background Perioperative neurocognitive disorder (PND) is a long-term postoperative complication in elderly surgical patients. The underlying mechanism of PND is unclear, and no effective therapies are currently available. It is believed that neuroinflammation plays an important role in triggering PND. The secreted glycoprotein myeloid differentiation factor 2 (MD2) functions as an activator of the Toll-like receptor 4 (TLR4) inflammatory pathway, and α5GABAA receptors (α5GABAARs) are known to play a key role in regulating inflammation-induced cognitive deficits. Thus, in this study, we aimed to investigate the role of MD2 in PND and determine whether α5GABAARs are involved in the function of MD2. Methods Eighteen-month-old C57BL/6J mice were subjected to laparotomy under isoflurane anesthesia to induce PND. The Barnes maze was used to assess spatial reference learning and memory, and the expression of hippocampal MD2 was assayed by western blotting. MD2 expression was downregulated by bilateral injection of AAV-shMD2 into the hippocampus or tail vein injection of the synthetic MD2 degrading peptide Tat-CIRP-CMA (TCM) to evaluate the effect of MD2. Primary cultured neurons from brain tissue block containing cortices and hippocampus were treated with Tat-CIRP-CMA to investigate whether downregulating MD2 expression affected the expression of α5GABAARs. Electrophysiology was employed to measure tonic currents. For α5GABAARs intervention experiments, L-655,708 and L-838,417 were used to inhibit or activate α5GABAARs, respectively. Results Surgery under inhaled isoflurane anesthesia induced cognitive impairments and elevated the expression of MD2 in the hippocampus. Downregulation of MD2 expression by AAV-shMD2 or Tat-CIRP-CMA improved the spatial reference learning and memory in animals subjected to anesthesia and surgery. Furthermore, Tat-CIRP-CMA treatment decreased the expression of membrane α5GABAARs and tonic currents in CA1 pyramidal neurons in the hippocampus. Inhibition of α5GABAARs by L-655,708 alleviated cognitive impairments after anesthesia and surgery. More importantly, activation of α5GABAARs by L-838,417 abrogated the protective effects of Tat-CIRP-CMA against anesthesia and surgery-induced spatial reference learning and memory deficits. Conclusions MD2 contributes to the occurrence of PND by regulating α5GABAARs in aged mice, and Tat-CIRP-CMA is a promising neuroprotectant against PND.

The functioning of the somatosensory system was studied in WAG/Rij rats genetically predisposed to absence epilepsy (AE) and demonstrating depression-like behavior, during the periods when AE had not yet been formed (2–3 months of age) and when this pathology was already well pronounced (6–7 months of age). Healthy Wistar rats, in which the responses of single somatosensory cortical neurons to single-pulse electrical stimulation of the vibrissal area (whiskers) were recorded extracellularly, served as a control. The evoked unit activity of somatosensory cortical neurons in response to afferent stimulation, regardless of age and rat strain identity, was found to include four components: primary (short-latency) excitation and inhibition and secondary (long-latency) excitation and inhibition. In 2–3-month-old WAG/Rij rats, in contrast to Wistar rats, the number of short-latency inhibitory responses was significantly smaller, while the number of long-latency inhibitory responses was significantly larger. It was postulated that the imbalance of varied inhibitory mechanisms in WAG/Rij rats may underlie the development of both AE and depression. In 6–7-month-old WAG/Rij rats (when epileptic activity is well-formed), the secondary excitatory response to afferent stimulation was mainly represented by a multicomponent high-frequency phasic reaction (alternation of short-term discharges with inhibitory periods). In Wistar rats of the same age, the secondary excitation was represented by a tonic reaction. The frequency of phasic discharges is compatible with that of spike-wave activity, which is an electroencephalographic sign of AE. It is assumed that the phasic response may be considered as a neuronal equivalent of epileptic activity, while the spike-wave activity in WAG/Rij rats may be provoked by vibrissal afferentation.

This study examined the effect of temporal changes in corticospinal excitability in motor imagery (MI) and the effect of real-time guides for MI on excitability changes. The MI task involved wrist flexion and motor evoked potentials using transcranial magnetic stimulation were recorded and examined from the flexor carpi radialis. Ballistic (momentary MI) and tonic (continuous MI) conditions were used, and the duration of each MI was different. In Experiment 1, each MI task was performed using an acoustic trigger. In Experiment 2, a real-time guide was presented on a computer screen, which provided a visual indication of the onset and duration of the MI task through via moving dots on the screen. The results indicate that the corticospinal excitability changed differently, depending on the duration of MI. Additionally, with real-time guides, the change in corticospinal excitability became clearer. Thus, corticospinal excitability changes due to the temporal specificities of MI, as well as with actual motor output. Moreover, if MI is actively performed without a guide, it is likely to show an unintended change in corticospinal excitability. It is suggested that when MI is performed with visual guide, the excitatory changes of the corticospinal tract might be different from the actual motor output. Therefore, when using MI for mental practices, it is possible to improve the effect of a guide for MI, such as a visual indicator for motor output. Additionally, when examining neural activities in MI, it may be necessary to consider the characteristics of motion performed by MI.

Aim: To investigate the antiepileptic activity of vortioxetine. Materials and method: Vortioxetine was screened for its antiepileptic activity in Sprague-Dawley rats using maximal electroshock model. 4 groups of rats (each 6 rats) were used. First group was administered distilled water, second group diazepam and the third and fourth groups were given vortioxetine 10mg/kg and 20mg/kg respectively. These drug were given 30 minutes before the animal was subjected to electroshock (150mA, 50Hz for 0.2 seconds). Results: Vortioxetine effectively reduced tonic hind limb extension (THLE) in the rats and the effect was statistically significant compared to the control group. The seizure duration was also significantly lower compared to the control. There was no substantial difference in the duration of seizures and THLE between the diazepam and vortioxetine group. However, the total seizure score of the vortioxetine group was not statistically significant compared to the control group. Conclusion: Vortioxetine has the potential to be clinically useful in treating epilepsy. Further detailed studies using other animal models and in humans are required to prove its efficacy in epilepsy.

Background Sleep disturbances are features of Parkinson's disease (PD), that can already occur before PD diagnosis. The most investigated prodromal PD sleep disorder is REM sleep behavior disorder (RBD). The relation between other polysomnographic (PSG) alterations and the prediagnostic stages of PD, however, is less clear. Methods We performed a retrospective case–control study to characterize polysomnographic alterations in PD and prediagnostic PD. We included 63 PD subjects (33 subjects that underwent a video-PSG before PD diagnosis [13 with and 20 without RBD] and 30 subjects that underwent a PSG after PD diagnosis) and 30 controls. PSGs were analyzed for sleep stages, different RSWA variables, body position, arousals, periodic limb movements, and REM density. Results Higher subscores of all RSWA variables were observed in subjects with PD and prediagnostic PD (with and without RBD). Total RSWA, tonic RSWA and chin RSWA severity were significant predictors for all PD and prediagnostic PD groups. Our study also shows a higher percentage of nocturnal supine body position in all PD and prediagnostic PD groups. Supine body position percentage is the highest in the PD group and has a positive correlation with time since diagnosis. Conclusions These findings suggest that increased total, tonic and chin RSWA as well as nocturnal supine body position are already present in prediagnostic PD, independently of RBD status. Prospective longitudinal studies are necessary to confirm the additional value of these PSG abnormalities as prodromal PD biomarkers.

Synaptic and extrasynaptic GABA(A) receptor (GABA(A)R)-mediated neurotransmission is a critical component of the suprachiasmatic nucleus (SCN) neuronal network. However, the properties of the GABA(A) tonic current (I(tonic)) and its origin remain unexplored. Spontaneous GABA(A) postsynaptic currents (sGPSCs) and I(tonic) were recorded from SCN neurons with the whole cell voltage-clamp technique at different times of the day. GABA(A)R antagonists (bicuculline, gabazine, and picrotoxin) inhibited sGPSC and induced an outward shift of the holding current, which defined the I(tonic) amplitude. The sGPSC frequency, synaptic charge transfer, and I(tonic) amplitude all demonstrated significant diurnal rhythms, with peaks in the middle of the day [zeitgeber time (ZT)7–8] and nadirs at night (ZT19–20). The I(tonic) amplitude increased proportionally with the sGPSC frequency and synaptic charge transfer during the day and required action potential-mediated GABA release, which was confirmed by TTX application. The activation of presynaptic GABA(B) receptors by baclofen did not significantly alter the I(tonic) of neurons with low-frequency sGPSC. The equilibrium potential (Eq) for I(tonic) was similar to the Eq for chloride and GABA(A) receptor-activated currents. I(tonic) showed outward rectification at membrane potentials over the range of −70 to −10 mV and then was linear at voltages greater than −10 mV. GABA(A)R containing α4-, α5-, and δ-subunits were expressed in SCN, and their contribution to I(tonic) was confirmed by application of the GABA(A)R agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and the GABA(A)R inverse agonist 11,12,13,13a-tetrahydro-7-methoxy-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylic acid ethyl ester (L655,708). Thus, the I(tonic) was mediated by extrasynaptic GABA(A)Rs activated predominantly by GABA diffusing out of GABAergic synapses. NEW & NOTEWORTHY A tonic current (I(tonic)) mediated by GABA(A) receptors (GABA(A)Rs) containing α4-, α5- and δ-subunits was observed in the suprachiasmatic nucleus. The I(tonic) amplitude strongly depended on the action potential-mediated synaptic release of GABA. The equilibrium potential for I(tonic) corresponds to that for GABA(A) currents. The frequency of GABA(A) postsynaptic currents and I(tonic) amplitude increased during the day, with peak in the middle of the day, and then gradually declined with a nadir at night, thus showing a diurnal rhythm.

AIM: This study aimed to investigate the effect of metabotropic glutamate (mGlu) receptor antagonists on the development of seizure caused by maximum electric shock (MES) and the content of lipid peroxidation (LPO) products in the brain of rats. MATERIALS AND METHODS: Experiments were carried out on male Wistar rats (n = 87) with a mass of 180210 g. In this work, MES was administered. Selective antagonists of I and V subtype mGlu receptors were administered 1 h before MES was administered. Control rats were injected an equivalent amount of saline. The intensity of LPO processes was assessed in terms of the level of secondary products reacting with thiobarbituric acid via a spectrophotometric method. RESULTS: MES led to the development of pronounced clonictonic seizures and increased the level of LPO products in the cerebral cortex of rats by more than threefold. A selective antagonist of subtype V mGlu receptors almost completely stopped the tonic phase of rat seizures and largely prevented the intensification of LPO processes caused by MES. Tonic convulsions were observed in 44% of the experimental animals after the administration of a selective subtype I mGlu receptor antagonist. This antagonist also partially reduced the content of LPO products caused by the effect of MES. CONCLUSION: Thus, mGlu receptors are involved in the development of MES-induced seizures in rats. The most pronounced weakening of convulsive manifestations and the prevention of an increase in the level of LPO products caused by MES were observed in the block of subtype V mGlu receptors. The obtained data confirmed the possibility of using subtype V metabotropic receptor antagonists as anticonvulsants for the treatment of epilepsy with generalized convulsive seizures.

Background and Objective This prospective, sham-controlled, randomized, cross-over study (NCT03637075), was designed to test the hypothesis that spinal cord stimulation (SCS) for the treatment of pain can also improve glucose metabolism and insulin sensitivity when compared to sham stimulation. Methods Ten non-diabetic participants (5 females, mean age 48.8 years) who had an SCS system implanted for the treatment of chronic neuropathic pain were studied. Whilst applying a hyperinsulinemic-euglycemic clamp, sham-stimulation and tonic stimulation were performed for 45 min (n=4) or 60 min (n=6) in each case randomly. The insulin sensitivity index and pain levels were determined. A second investigation, BurstDR stimulation was also conducted and the result was compared to that of sham stimulation (cross-over design). Results The insulin sensitivity improved significantly under the tonic stimulation when compared to the sham stimulation (p=0.037). BurstDR stimulation independently did not lead to a significantly improved insulin sensitivity compared to that after sham stimulation (p=0.16). We also examined the pain during the test and found no significant difference between sham and tonic stimulation (p=0.687). Conclusion The results of this study show that tonic stimulation used for the treatment of pain could also improve glucose metabolism and insulin sensitivity. Further investigations are required to investigate the clinical relevance of the role of glucose metabolism in diabetic chronic pain participants and its underlying mechanisms.

The prefrontal cortex (PFC) governs top-down control of attention and is known to be vulnerable in aging. Cortical reorganization with increased PFC recruitment is suggested to account for functional compensation. Here, we hypothesized that reduced PFC output would exert differential effects on attentional capacities in young and aged rats, with the latter exhibiting a more robust decline in performance. A chemogenetic approach involving designer receptors exclusively activated by designer drugs was utilized to determine the impact of silencing PFC projection neurons in rats performing an operant attention task. Visual distractors were presented in all behavioral testing sessions to tax attentional resources. Under control conditions, aged rats exhibited impairments in discriminating signals with the shortest duration from non-signal events. Surprisingly, chemogenetic inhibition of PFC output neurons did not worsen performance amongst aged animals. Conversely, significant impairments in attentional capacities were observed in young subjects following such manipulation. Given the involvement of PFC-projecting basal forebrain cholinergic neurons in top-down regulation of attention, amperometric recordings were conducted to measure alterations in prefrontal cholinergic transmission in a separate cohort of young and aged rats. While PFC silencing resulted in a robust attenuation of tonic cholinergic signaling across age groups, the capacity to generate phasic cholinergic transients was impaired only amongst young animals. Collectively, our findings suggest a reduced efficiency of PFC-mediated top-down control of attention and cholinergic system in aging, and that activity of PFC output neurons does not reflect compensation in aged rats, at least in the attention domain.

Previous data suggest that renal afferent nerve activity is increased in hypertension exerting sympathoexcitatory effects. Hence, we wanted to test the hypothesis that in renovascular hypertension, the activity of dorsal root ganglion (DRG) neurons with afferent projections from the kidneys is augmented depending on the degree of intrarenal inflammation. For comparison, a nonhypertensive model of mesangioproliferative nephritis was investigated. Renovascular hypertension (2-kidney, 1-clip [2K1C]) was induced by unilateral clipping of the left renal artery and mesangioproliferative glomerulonephritis (anti-Thy1.1) by IV injection of a 1.75-mg/kg BW OX-7 antibody. Neuronal labeling (dicarbocyanine dye [DiI]) in all rats allowed identification of renal afferent dorsal root ganglion (DRG) neurons. A current clamp was used to characterize neurons as tonic (sustained action potential [AP] firing) or phasic (1–4 AP) upon stimulation by current injection. All kidneys were investigated using standard morphological techniques. DRG neurons exhibited less often tonic response if in vivo axonal input from clipped kidneys was received (30.4% vs. 61.2% control, p p

Increased use of epidural Spinal Cord Stimulation (eSCS) for the rehabilitation of spinal cord injury (SCI) has highlighted the need for a greater understanding of the properties of reflex circuits in the isolated spinal cord, particularly in response to repetitive stimulation. Here, we investigate the frequency-dependence of modulation of short- and long-latency EMG responses of lower limb muscles in patients with SCI at rest. Single stimuli could evoke short-latency responses as well as long-latency (likely polysynaptic) responses. The short-latency component was enhanced at low frequencies and declined at higher rates. In all muscles, the effects of eSCS were more complex if polysynaptic activity was elicited, making the motor output become an active process expressed either as suppression, tonic or rhythmical activity. The polysynaptic activity threshold is not constant and might vary with different stimulation frequencies, which speaks for its temporal dependency. Polysynaptic components can be observed as direct responses, neuromodulation of monosynaptic responses or driving the muscle activity by themselves, depending on the frequency level. We suggest that the presence of polysynaptic activity could be a potential predictor for appropriate stimulation conditions. This work studies the complex behaviour of spinal circuits deprived of voluntary motor control from the brain and in the absence of any other inputs. This is done by describing the monosynaptic responses, polysynaptic activity, and its interaction through its input–output interaction with sustain stimulation that, unlike single stimuli used to study the reflex pathway, can strongly influence the interneuron circuitry and reveal a broader spectrum of connectivity. Supplementary Information The online version contains supplementary material available at 10.1007/s00221-021-06153-1.

It is known that besides synaptic inhibition, there is a persistent component of inhibitory drive mediated by tonic currents which is believed to mediate majority of the total inhibitory charge in hippocampal neurons. Tonic currents, depending on cell types, can be mediated by a variety of GABAA receptor (GABAAR) subtypes but in pyramidal neurons, α5-subunit containing receptors were found to be predominant. Importantly, α5-GABAARs were implicated in both inhibitory and excitatory synaptic plasticity as well as in a variety of cognitive tasks. In the present study, we asked whether the protocol that evokes NMDAR-dependent GABAergic inhibitory long-term potentiation (iLTP) also induces the plasticity of tonic inhibition in hippocampal pyramidal neurons. Our whole-cell patch-clamp recordings revealed that the induction of this type of iLTP is associated with a marked increase in tonic current. By using the specific inverse agonist of α5-containing GABAARs (L-655,709) we provide evidence that this plastic change in tonic current is correlated with an increased proportion of this type of GABAARs. On the contrary, the iLTP induction did not affect the tonic current potentiated by THIP, indicating that the pool of δ subunit-containing GABAARs receptors remains unaffected. We conclude that the α5-GABAARs-dependent plasticity of tonic inhibition is a novel dimension of the neuroplasticity of the inhibitory drive in the hippocampal principal neurons. Overall, α5-containing GABAARs emerge as key players in a variety of plasticity mechanisms operating over a large span of time and spatial scales.

The influence of motivation on psychophysiological states of a person is investigated. It is established that motivation is a psychological process that controls human behavior. Motivation is a guiding tool of the individual in the process of achieving goals. At different stages of motivation a person has different psychophysiological states. There are six stages of motivation: 1. The emergence of needs; 2. Finding ways to eliminate the need; 3. Defining goals; 4. Implementation of the action; 5. Receiving reward for the action; 6. Elimination of needs. Psychophysiological state can be called the physiological level of mental state with special energy features. There is a classification of psychophysiological states: neutral (calm, confidence, etc.); activation (excitement, inspiration, rise, concentration, etc.); tonic, those states that reflect the resources of forces (satiety, fatigue, monotony, etc.); tension, showing what level of effort should be applied to the person (tension, stress, sensory hunger, etc.). Thus, in the process of achieving goals, motivation is an important component. Knowing the effect of motivation on a person's psychophysiological states will help him to use this tool in the best way. A survey of 200 people was conducted to help determine what psychophysiological states occur at different stages of motivation. After analyzing the results of the study, it was found that most often in the process of motivation in humans there are activating psychophysiological states, then tension and rarely tonic. When processing the results at each stage of motivation, three psychophysiological states were taken, which the subjects chose more often. It was found that activating psychophysiological states are more common in the first five stages of motivation, tension psychophysiological states are more common in the second, third, fourth and sixth stages of motivation, tonic psychophysiological states occur in the sixth stage of motivation.

The primate visual system has been the prime site for investigating the relationship between stimulus property, neural response and blood-oxygen-level-dependent (BOLD)-signal; yet this relationship remains ill-understood. Electrophysiological studies have shown that the ability to visualise a neural response is determined by stimulus property and presentation paradigm. The neural response in the human visual cortex consists of a phasic response processing temporal and tonic response processing spatial luminance contrast. We investigated their influence on the BOLD signal from the visual cortex. To do so, we compared BOLD signal amplitude from BA17 and BA18 of 15 human volunteers to visual patterns varying the size of the active neural population and the discharge activity of this population. The BOLD signal amplitude in both areas reflected the discharge activity of the active neural population but not the size of the active neural population. For identical stimuli, BOLD signal amplitude in BA17 exceeded than that of BA18. This indicates that the BOLD signal reflects the tonic neural neuronal response during spatial luminance contrast processing. The difference in BOLD signal amplitude between BA17 and BA18 is accounted for by differences in neurophysiological and cytoarchitectonic differences between the two areas. Our findings offer an understanding of the relationship between stimulus property, neural response and the BOLD signal by considering the cytoarchitectonic, and neurophysiological make-up between different cortical areas and the influence of a phasic and tonic neural response on local deoxyhaemoglobin concentration. Conversely, differences in BOLD signal between brain structures and stimuli provide cues to the influence of different neurophysiological mechanisms on the neural response.

Changes in tissue perfusion parameters indicate not only a violation of systemic hemodynamics, but can also occur with local changes in the structure of the organ pathological process. Along with degenerative and dystrophic changes in the structures of the motor segment, muscle-tonic (myofascial) pains occur in a significant number of cases. The possibilities of instrumental assessment in case of local microcirculation disorders in skeletal muscle make it possible to diagnose key manifestations — to identify an area with low blood supply. Within the framework of the study, a limited area of reduced perfusion was established in myofascial pain syndrome. With the formation of a painful muscle knot, the parameter of the volumetric blood flow velocity (Qas) is 0.006±0.0005 cm³/min, while the comparison with the control points fixes the level of blood supply at 0.0046±0.0005 cm³/min (p

It is not yet clear which response behavior requires self-regulatory effort in the moral dilemma task. Previous research has proposed that utilitarian responses require cognitive control, but subsequent studies have found inconsistencies with the empirical predictions of that hypothesis. In this paper, we treat participants’ sensitivity to utilitarian gradients as a measure of performance. We confronted participants (N = 82) with a set of five dilemmas evoking a gradient of mean utilitarian responses in a 4-point scale and collected data on heart rate variability and utilitarian responses. We found positive correlations between tonic and phasic HRV and sensitivity to the utilitarian gradient in the high tonic group, but not in the low tonic group. Moreover, the low tonic group misplaced a scenario with a selfish incentive at the high end of the gradient. Results suggest that performance is represented by sensitivity correlated with HRV and accompanied with a reasonable placement of individual scenarios within the gradient.

The objective of this study was to comprehensively investigate patterns of brain activities associated with pain recovery following experimental tonic pain in humans. Specific electrophysiological features of pain recovery may either be monitored or be modulated through neurofeedback (NF) as a novel chronic pain treatment. The cold pressor test was applied with simultaneous electroencephalogram (EEG) recording. EEG data were acquired, and analyzed to define: (1) EEG power topography patterns of pain recovery; (2) source generators of pain recovery at cortical level; (3) changes in functional connectivity associated with pain recovery; (4) features of phase-amplitude coupling (PAC) as it relates to pain recovery. The novel finding of this study is that recovery from pain was characterized by significant theta power rebound at the left fronto-central area. The sources of theta power over-recovery were located in the left dorsolateral prefrontal cortex (DLPFC), cingulate cortex, left insula and contralateral sensorimotor cortex. These effects were paralleled by theta band connectivity increase within hemispheres in a prefrontal-somatosensory network and interhemispherically between prefrontal and parietal areas. In addition, this study revealed significant reduction in PAC between theta/alpha and gamma oscillations during recovery period following tonic pain. These findings have largely been replicated across two identical sessions. Our study emphasizes the association between pain recovery and left lateral prefrontal theta power rebound, and significant over-recovery of functional connectivity in prefrontal-sensorimotor neural network synchronized at theta frequencies. These findings may provide basis for chronic pain treatment by modulating neural oscillations at theta frequencies in left prefrontal cortex.

Objective To determine inter-rater reliability, minimal detectable change and responsiveness of Tonic Stretch Reflex Threshold (TSRT) as a quantitative measure of elbow flexor spasticity. Methods Elbow flexor spasticity was assessed in 55 patients with sub-acute stroke by determining TSRT, the angle of spasticity onset at rest (velocity = 0°/s). Elbow flexor muscles were stretched 20 times at different velocities. Dynamic stretch-reflex thresholds, the elbow angles corresponding to the onset of elbow flexor EMG at each velocity, were used for TSRT calculation. Spasticity was also measured with the Modified Ashworth Scale (MAS). In a sub-group of 44 subjects, TSRT and MAS were measured before and after two weeks of an upper-limb intervention. Results The intraclass correlation coefficient was 0.65 and the 95% minimal detectable change was 32.4°. In the treated sub-group, TSRT, but not MAS significantly changed. TSRT effect size and standardized response mean were 0.40 and 0.35, respectively. Detection of clinically meaningful improvements in upper-limb motor impairment by TSRT change scores ranged from poor to excellent. Conclusions Evaluation of stroke-related elbow flexor spasticity by TSRT has good inter-rater reliability. Test responsiveness is low, but better than that of the MAS. Significance TSRT may be used to complement current scales of spasticity quantification.

The objectives of our article are: to study the characteristics of disorders of psychomotor function and psycho-emotional state of patients with ischemic stroke according to the initial examination; to develop a method of physical rehabilitation of patients with ischemic stroke at the inpatient stage of rehabilitation, depending on the severity of psychomotor functions and features of the psycho-emotional state; in a psychological and pedagogical experiment to evaluate the effectiveness of the proposed method of physical rehabilitation of patients with ischemic stroke at the inpatient stage of rehabilitation. The following theoretical methods of the research were used to solve the tasks formulated in the article: a categorical method, structural and functional methods, the methods of the analysis, systematization, modeling, generalization. Also in our research we used empirical methods, such as the observation, the interview, the questionnaire, the method of psychological observation, psychological and medical experiment, testing (M. Lucher’s test is used). The results of the research. It was developed a «Functional methodology for the restoration of motor function of patients with ischemic stroke, taking into account their psycho-physiological features», based on the psychological principles of stepwise, sequencing and complexity, as well as on the maximum and adequate psychological impact of the rehabilitation therapist on the patient. Also we proposed the «Functional methodology of physical rehabilitation in the early period of ischemic stroke». The main provisions of this methodology are: 1. The stabilization of the psycho-emotional state of the patient: reducing the level of anxiety, increasing motivation to exercise in the course of physical rehabilitation. 2. The actualization of stable static and dynamic stereotypes of the patient in all initial positions – from horizontal to vertical ones, using the influence of simple, eye-motor, tonic (labyrinthine tonic reflexes, symmetrical cervical tonic reflex, cervical asymmetric tonic reflex, etc.). Restoration and maintenance of stress resistance of patients is provided by symmetrical maintenance of a projection of the general center of gravity on a basic surface in such initial positions in which normal proper afferentation of joints and muscles will be stimulated. These are the positions that the human body consistently takes in the process of verticalization: a supine position on the back; a lying position on the side (right and left); a supine position; a standing position on the knees; a standing position on the knees (with additional vertical support and without such a support); a standing position (with additional vertical support and without such a support). It was proved that the starting position became a directly activated position with a torso extension, which had the aim to support all muscle groups of the patient, provided by the stimulation of a successive chain of muscle contractions directed from the center to the periphery of the body. The symmetry of maintaining the initial position of the patient during the lesson is constantly adjusted (passively or actively) in order to stimulate proper afferentation. Conclusions. The main directions of psychotherapy and psycho-correction of patients who suffered from ischemic stroke are: the assistance in the process of understanding the patients, his / her basic needs, motives, instructions, relationships; his / her internal conflicts and mechanisms of psychological protection; features of his / her behavior and emotional response, their adequacy and realism; the correction of patients’ instructions; the assistance in formulating and securing adequate forms of patients’ behavior based on personal achievements in the cognitive, motivational, and emotional spheres; the promotion of positive motivation for recovery and increased activity in treatment at the behavioral level. During the classes according to the proposed methodology, we have the aim to achieve the stabilization of a psycho-emotional state of the patient through the correction of his / her cognitive processes that motivate the patient to actions which generally affect the effectiveness of all rehabilitation measures.

OBJECTIVE: Irritability is a multifaceted construct in pediatric psychopathology. It has been conceptualized as having a phasic dimension and a tonic dimension. Disruptive mood dysregulation disorder is defined by the presence of both dimensions. Severe irritability, or disruptive mood dysregulation disorder, is highly comorbid with attention-deficit/hyperactivity disorder (ADHD). However, it is unknown whether the presence of ADHD modulates the expression of phasic and tonic irritability. METHOD: A data-driven, latent variable approach was used to examine irritability and ADHD symptoms in a transdiagnostic pediatric sample (N = 489) with primary disruptive mood dysregulation disorder, ADHD, subclinical irritability symptoms, or no diagnosis. Using latent profile analyses, we identified 4 classes: high levels of both irritability and ADHD symptoms, high levels of irritability and moderate levels of ADHD symptoms, moderate levels of irritability and high levels of ADHD symptoms, and low levels of both irritability and ADHD symptoms. Confirmatory factor analysis operationalized phasic irritability and tonic irritability. RESULTS: As expected, the 2 latent classes characterized by high overall irritability exhibited the highest levels of both phasic and tonic irritability. However, between these 2 high irritability classes, highly comorbid ADHD symptoms were associated with significantly greater phasic irritability than were moderately comorbid ADHD symptoms. In contrast, the 2 high irritability groups did not differ on levels of tonic irritability. CONCLUSION: These findings suggest that phasic, but not tonic, irritability has a significant association with ADHD symptoms and that phasic and tonic might be distinct, though highly related, irritability dimensions. Future research should investigate potential mechanisms underlying this differential association.