Trains Of Stimuli Research Articles

Reactivation strength during cued recall is modulated by graph distance within cognitive maps

Declarative memory retrieval is thought to involve reinstatement of neuronal activity patterns elicited and encoded during a prior learning episode. Furthermore, it is suggested that two mechanisms operate during reinstatement, dependent on task demands: individual memory items can be reactivated simultaneously as a clustered occurrence or, alternatively, replayed sequentially as temporally separate instances. In the current study, participants learned associations between images that were embedded in a directed graph network and retained this information over a brief 8 min consolidation period. During a subsequent cued recall session, participants retrieved the learned information while undergoing magnetoencephalographic recording. Using a trained stimulus decoder, we found evidence for clustered reactivation of learned material. Reactivation strength of individual items during clustered reactivation decreased as a function of increasing graph distance, an ordering present solely for successful retrieval but not for retrieval failure. In line with previous research, we found evidence that sequential replay was dependent on retrieval performance and was most evident in low performers. The results provide evidence for distinct performance-dependent retrieval mechanisms, with graded clustered reactivation emerging as a plausible mechanism to search within abstract cognitive maps.

The entrainment of action potential duration and contraction amplitude by recapitulation of respiratory sinus arrhythmia in isolated cardiac myocytes

Abstract Introduction Respiratory sinus arrhythmia (RSA) is the oscillation of heart rate in phase with ventilation and represents the high frequency component of heart rate variability. RSA is prevalent in the young and the endurance-trained and its loss is considered a prognostic indicator for sudden cardiac death. The recapitulation of RSA improves cardiac function in animal models of heart failure1,2. However, the precise mechanisms by which RSA affects cardiac function are unknown. Hypothesis: We examined the hypothesis that the recapitulation of RSA in isolated ventricular myocytes affects the stimulus interval-dependence of action potential duration (APD) and sarcomere shortening through mechanisms involving sarcoplasmic reticulum (SR) Ca2+ release. Methods Hearts were excised from adult male guinea pigs under general anaesthesia (140 mg/kg bodyweight euthatal, i.p.) and left ventricular myocytes isolated. Isolated myocytes were superfused with Tyrode’s solution for perforated patch whole-cell current clamp recording and action potentials and sarcomere length measured simultaneously. Sample sizes are presented as n/N (cell/animal number) and nested hierarchical analysis applied using a generalized linear mixed model (P<0.05). Results Pacing at a basic cycle length (CL, 350 ms) induced APD, Ca2+ transient amplitude (CaT) and sarcomere shortening alternans. The recapitulation of RSA through oscillatory pacing (OP), in which CL was set to 20% below and 20% above the corresponding basic CL in a 2-short, 2-long stimulus train, reduced the incidence of alternans. Furthermore, OP entrained APD, CaT and sarcomere shortening and this entrainment persisted in voltage clamp experiments with fixed APD. Using a three-step protocol to examine the dependence of APD and sarcomere shortening on both preceding (CLn-1) and anteceding (CLn-2) stimulus intervals, both APD and sarcomere shortening were found to depend directly on the preceding cycle length (CLn-1, P<0.001). In contrast, sarcomere shortening depended inversely on the anteceding CL (CLn-2, P<0.001; n/N = 24/4). Following treatment of the cells with caffeine (50 µM) to sensitise ryanodine receptors, the dependence of APD and sarcomere shortening on CLn-1 was markedly suppressed, and the inverse dependence of sarcomere shortening on CLn-2 was lost (P<0.001, n/N = 6/3). The effects of OP are akin to post-extrasystolic potentiation3 and mathematical simulation4 supports the involvement of changes in the sarcoplasmic reticulum Ca2+ content. Conclusion These data are consistent with an obligatory role for the SR in the entrainment of APD, CaT and sarcomere shortening and the suppression of alternans by the recapitulation of RSA. We hypothesise that recapitulation of RSA would be protective against ventricular tachyarrhythmia and further work is required to test this.

Training-induced changes in population receptive field properties in visual cortex: Impact of eccentric vision training on population receptive field properties and the crowding effect.

This study aimed to investigate the impact of eccentric-vision training on population receptive field (pRF) estimates to provide insights into brain plasticity processes driven by practice. Fifteen participants underwent functional magnetic resonance imaging (fMRI) measurements before and after behavioral training on a visual crowding task, where the relative orientation of the opening (gap position: up/down, left/right) in a Landolt C optotype had to be discriminated in the presence of flanking ring stimuli. Drifting checkerboard bar stimuli were used for pRF size estimation in multiple regions of interest (ROIs): dorsal-V1 (dV1), dorsal-V2 (dV2), ventral-V1 (vV1), and ventral-V2 (vV2), including the visual cortex region corresponding to the trained retinal location. pRF estimates in V1 and V2 were obtained along eccentricities from 0.5° to 9°. Statistical analyses revealed a significant decrease of the crowding anisotropy index (p = 0.009) after training, indicating improvement on crowding task performance following training. Notably, pRF sizes at and near the trained location decreased significantly (p = 0.005). Dorsal and ventral V2 exhibited significant pRF size reductions, especially at eccentricities where the training stimuli were presented (p < 0.001). In contrast, no significant changes in pRF estimates were found in either vV1 (p = 0.181) or dV1 (p = 0.055) voxels. These findings suggest that practice on a crowding task can lead to a reduction of pRF sizes in trained visual cortex, particularly in V2, highlighting the plasticity and adaptability of the adult visual system induced by prolonged training.

The Effects of Slow Breathing during Inter-Set Recovery on Power Performance in the Barbell Back Squat.

Slow breathing (SB) reduces sympathetic nervous system activity, the heart rate (HR), and blood pressure (BP) and increases parasympathetic nervous system activity, HR variability, and oxygen saturation which may lead to quicker recovery between bouts of exercise. Therefore, the purpose of this study was to examine whether a SB technique using the 4-7-8 method between sets of barbell back squats (SQs) would attenuate drops in power and bar velocity. In a randomized, crossover design, 18 healthy resistance-trained college-aged males (age: 20.7 ± 1.4 years, body height: 178.6 ± 6.4 cm, body mass: 82.2 ± 15.0 kg, 4.5 ± 2.4 years of experience) performed 5 sets of 3 repetitions of SQs with normal breathing (CON) or SB during the 3-min recovery between sets. Peak and average power and bar velocity were assessed using a linear positioning transducer. HR recovery (RHR), systolic BP recovery (RBP), the rating of perceived exertion (RPE) and the rating of perceived recovery score (RS) were assessed after each set. There were no significant differences between conditions for peak and average power and bar velocity, RBP, RPE, and RS (p > 0.211). SB led to a greater RHR after set 2 (SB: 51.0 ± 14.9 bpm vs. CON: 44.5 ± 11.5 bpm, p = 0.025) and 3 (SB: 48.3 ± 13.5 bpm vs. CON: 37.7 ± 11.7 bpm, p = 0.006) compared to the CON condition. SB was well tolerated, did not hinder nor improve training performance and improved RHR after the middle sets of SQs. Further investigations are warranted to examine the effects of other SB techniques and to determine SB's effects on different training stimuli as well as its effects over an entire workout and post-workout recovery metrics.

Theoretico-experimental analysis of bistability in the oscillatory response of a TaOx ReRAM to pulse train stimuli

Fading memory is the capability of a physical system to approach a unique asymptotic behaviour, irrespective of the initial conditions, when stimulated by an input from a certain class. Standard stimuli from the AC periodic class typically induce fading memory effects in non-volatile memristors, as uncovered for the first time back in 2016. Very recently, a deep investigation of resistance switching phenomena in a TaOx resistive random access memory cell revealed the capability of the nano-device to exhibit one of two possible oscillatory behaviours, depending upon the initial condition, when subject to a particular periodic excitation. This interesting finding was, however, left unexplained. Bistability is the simplest form of local fading memory. In a system, endowed with local fading memory under a given stimulus, the initial condition does not affect the long-term behaviour of the state as long as it is drawn from the basin of attraction of either of the distinct coexisting state-space attractors (two limit cycles for the periodically forced memristor acting as a bistable oscillator). Here, the history of the system, encoded in the initial condition, is, thus, erasable only locally through ad hoc stimulation. Motivated by the discovery of local history erase effects in our resistive random access memory cell, this study applies a powerful system-theoretic tool, enabling the analysis of the response of first-order systems to square pulse train-based periodic stimuli, known as the time-average state dynamic route, to an accurate physics-based mathematical model, earlier fitted to the nano-device, to determine a strategy for specifying the parameters of an excitation signal, consisting of the sequence of two square pulses of opposite polarity per period so as to induce various forms of monostability or multistability in the non-volatile memristor. In particular, as an absolute novelty in the literature, experimental measurements validate the theoretical prediction on the capability of the device to operate as one of two distinct oscillators, depending upon the initial condition, under a specific pulse train excitation signal. The coexistence of multiple oscillatory operating modes in the periodically forced resistive random access memory cell, an example par excellence of their unique non-linear dynamics, may inspire the development and circuit implementation of novel sensing and mem-computing paradigms.

Development of a physical capacity framework to support clinical reasoning of physiotherapists treating hospitalised patients

Background Applying an appropriate physiotherapy intervention to a hospitalised patient can be challenging because the clinical status can change rapidly, affecting the patient’s physical capacity. Determining the appropriate type and dose of the physiotherapy intervention requires dynamic assessment of physical capacity and adequate clinical reasoning by the physiotherapist. Purpose To develop a framework for determining physical capacity to support physiotherapists in their clinical reasoning process when treating hospitalised patients. Methods A framework was developed using a multi-method approach. First, the scientific literature was searched for existing frameworks for clinical reasoning in physiotherapy. These methods were inventoried and relevant elements were extracted. Second, a first draft of the framework was developed by a group of experts. Third, the framework was tested in practice, leading to a final version. Results A total of 17 frameworks were identified from the literature. No framework was found for generic use in the hospital for the purpose of determining patient’s physical capacity. Relevant elements from the identified frameworks were: the use of ICF terminology, the use of a patient management model, and frequent monitoring of clinical parameters. Field testing of the first draft of the framework led to improvement of the framework for use in clinical practice. Conclusion A framework was developed to support physiotherapists in their clinical reasoning process when treating hospitalised patients. The framework can provide guidance for determining the patient’s physical capacity to allow for an adequate training stimulus.

REGULAR LOW-DOSE CAFFEINE SUPPLEMENTATION DURING TRAINING DOES NOT PROVIDE ADDITIONAL BENEFIT TO SUBSEQUENT EXERCISE PERFORMANCE IN AUSTRALIAN RULES FOOTBALL ATHLETES

INTRODUCTION &amp; AIMS Acute caffeine supplementation can improve exercise types like those completed by Australian Rules football (ARF) players during training. Hypothetically athletes could implement caffeine supplementation prior to training, allowing them to complete more training volume, improving adaptation and subsequent exercise performance. This study aimed to investigate the effect of regular low-dose caffeine ingestion pre-training during a training block on subsequent exercise performance. METHODS Twenty-nine male semi-professional ARF players were randomly allocated to a caffeine or placebo group. The four-week intervention period involved participants ingesting 2 mg·kg·BM-1 of caffeine or a placebo 60 min prior to two of their three weekly training sessions, which incorporated sport-specific conditioning and skills training. To assess exercise performance, a battery of tests was used before and after the intervention period including the Yo-Yo Intermittent Recovery Test Level 2 (YYIRT2), 20 m sprint and vertical jump (VJ). Performance differences were assessed using a linear mixed-effect model. RESULTS Mean session rating of perceived exertion (p = .24) and total training load (p =.53) were not different between caffeine and placebo groups over the intervention. There were no significant time x condition interaction effects for YYIRT2 accumulated distance (p = .87), or 5, 10 and 20 m sprint times (p =.06 - .44), however both caffeine and placebo groups improved YYIRT2 distance and sprint times following four weeks of training (p &amp;lt; 0.01). There was a significant effect for time showing decreased VJ performance (p &amp;lt; 0.01), with greater reductions in the placebo group (p = .03). CONCLUSION It is more beneficial to implement an effective training program for athletes rather than focusing effort on regular low-dose caffeine supplementation to augment the training stimulus. The training stimulus itself is typically greater for developing endurance and sprint effort performance, with supplemental caffeine showing no additional performance benefit.

RESISTANCE TRAINING PRESCRIPTION FOR ATHLETES DURING PERIODS OF PLANNED DE-LOADING: A SURVEY OF STRENGTH AND CONDITIONING COACHES

INTRODUCTION &amp; AIMS Implementing resistance training (RT) for athletes may be difficult during some training-phases due to competing demands. However, it is currently unknown how strength and conditioning coaches prescribe RT during periods of planned de-loading. Therefore, we aimed to investigate the RT prescription practices of coaches during four common de-loading periods (taper, competitive season, tournament, travel). METHODS An anonymous online survey was shared globally to coaches, with data analysed from 204 responders (current level of athlete coached: world class n=68, elite/international n=62, highly-trained n=64, trained n=10). Coaches only provided answers about prescription for de-loading periods which they reported encountering. Where a coach indicated not prescribing RT for specific de-loading periods, they provided information on any barriers preventing RT prescription. RESULTS Weekly RT prescription across all de-load periods was typically reported as: 1-2 sessions, 30-60 min, 1-3 sets, 1-6 repetitions. Most coaches reported decreasing volume during all periods (taper: 89.1%, competitive season: 70.4%, tournament: 84.1%, travel: 74.6%), with the most common reduction in RT volume reported as 0-25%. Most coaches also decreased intensity during a taper (52.9%), tournament (54.8%) and travel (53.6%), with a 0-25% reduction most common. ‘Lack of equipment and facilities’ and ‘scheduling/time’ were common barriers cited to RT prescription during the competitive season (100% for scheduling/time), tournament (55.6% and 50.0%), and travel (57.3% and 60.0%). During a taper, ‘recovery’ was the most reported reason (41.7%). CONCLUSION During planned de-loading periods, both training volume and intensity are generally decreased by coaches compared to periods of normal training. The similarity of barriers to RT prescription during de-load periods suggests the experiences of coaches are not influenced by the phase. To address barriers experienced by some coaches, researchers should examine the use of alternative RT strategies for periods of planned de-loading to maintain training stimulus.

Auditory discrimination learning and acoustic cue weighing in female zebra finches with localized FoxP1 knockdowns.

Rare disruptions of the transcription factor FOXP1 are implicated in a human neurodevelopmental disorder characterized by autism and/or intellectual disability with prominent problems in speech and language abilities. Avian orthologues of this transcription factor are evolutionarily conserved and highly expressed in specific regions of songbird brains, including areas associated with vocal production learning and auditory perception. Here, we investigated possible contributions of FoxP1 to song discrimination and auditory perception in juvenile and adult female zebra finches. They received lentiviral knockdowns of FoxP1 in one of two brain areas involved in auditory stimulus processing, HVC (proper name) or CMM (caudomedial mesopallium). Ninety-six females, distributed over different experimental and control groups were trained to discriminate between two stimulus songs in an operant Go/Nogo paradigm and subsequently tested with an array of stimuli. This made it possible to assess how well they recognized and categorized altered versions of training stimuli and whether localized FoxP1 knockdowns affected the role of different features during discrimination and categorization of song. Although FoxP1 expression was significantly reduced by the knockdowns, neither discrimination of the stimulus songs nor categorization of songs modified in pitch, sequential order of syllables or by reversed playback were affected. Subsequently, we analyzed the full dataset to assess the impact of the different stimulus manipulations for cue weighing in song discrimination. Our findings show that zebra finches rely on multiple parameters for song discrimination, but with relatively more prominent roles for spectral parameters and syllable sequencing as cues for song discrimination.NEW & NOTEWORTHY In humans, mutations of the transcription factor FoxP1 are implicated in speech and language problems. In songbirds, FoxP1 has been linked to male song learning and female preference strength. We found that FoxP1 knockdowns in female HVC and caudomedial mesopallium (CMM) did not alter song discrimination or categorization based on spectral and temporal information. However, this large dataset allowed to validate different cue weights for spectral over temporal information for song recognition.

Impaired excitability of nucleus tractus solitarius neurons in a neonatal rat model of hyperbilirubinemia

Hyperbilirubinemia is associated with multiple morbidities including apnea of prematurity in preterm infants. Bilirubin, a byproduct of hemoglobin breakdown, is not excreted normally and results in high circulating levels giving rise to a state of hyperbilirubinemia. Free bilirubin (not bound to albumin) can cross the blood-brain barrier and be neurotoxic. Prior studies have shown that a systemic injection of bilirubin accumulates in the brainstem and is associated with an impaired ventilatory response to hypercapnia and an augmented hypoxic ventilatory depression. Here, using the Gunn rat model of endogenous hyperbilirubinemia, we investigated its effects on the excitability of neurons of the nucleus tractus solitarius (NTS). The homozygous Gunn rat (jj) model of hyperbilirubinemia lacks uridine diphosphate-glucuronosyltransferase-1A1, an enzyme which is needed to catabolize bilirubin. Heterozygous Nj Gunn rat pups were used for control. On postnatal (P) day 5, Nj and jj rat pups received either a 200mg/kg intraperitoneal injection of sulfadimethoxine (SDMX), which dissociates bilirubin from albumin resulting in increased levels of circulating free bilirubin, or an equivalent amount of saline as a vehicle control. Whole cell patch clamp was performed on NTS neurons two days later (P7) to assess characteristics of evoked excitatory postsynaptic currents (eEPSC).The amplitude of the evoked stimulus response to a 20Hz stimulus train was significantly increased in NTS neurons from jj+saline pups when compared to cells from Nj+saline and Nj+SDMX animals (p&lt;0.05). This increased amplitude was no longer present after SDMX treatment of jj pups. Additionally, jj+saline NTS neurons did not exhibit any failure to solitary tract stimulation, whereas SDMX treatment significantly increased the failure rate during a 20Hz stimulus train (jj+saline =0.0%±0.0, jj+SDMX= 18.63%±8.82, p&lt;0.05). Comparison of failure rate of jj+saline to Nj+saline (6.63%±3.12, p&lt;0.05) was also statistically significant. The hyper-responsive NTS neurons of jj+saline rats may be an adaptive response to the deleterious effects of circulating (bound and unbound) bilirubin. However, the impaired response of neurons in jj+SDMX rats may reflect neurotoxic effects of increased free bilirubin leading to impaired neurotransmission. The latter is consistent with the high failure rate of NTS neurons in jj+SDMX rats. These data may have implications for impaired respiratory control mechanisms involved in mediating essential vagally mediated ventilatory defense responses to hypoxemia and may contribute to the apnea of prematurity associated with hyperbilirubinemia in preterm infants. William and Lois Briggs Endowment. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Nanoactuator for Neuronal Optoporation.

Light-driven modulation of neuronal activity at high spatial-temporal resolution is becoming of high interest in neuroscience. In addition to optogenetics, nongenetic membrane-targeted nanomachines that alter the electrical state of the neuronal membranes are in demand. Here, we engineered and characterized a photoswitchable conjugated compound (BV-1) that spontaneously partitions into the neuronal membrane and undergoes a charge transfer upon light stimulation. The activity of primary neurons is not affected in the dark, whereas millisecond light pulses of cyan light induce a progressive decrease in membrane resistance and an increase in inward current matched to a progressive depolarization and action potential firing. We found that illumination of BV-1 induces oxidation of membrane phospholipids, which is necessary for the electrophysiological effects and is associated with decreased membrane tension and increased membrane fluidity. Time-resolved atomic force microscopy and molecular dynamics simulations performed on planar lipid bilayers revealed that the underlying mechanism is a light-driven formation of pore-like structures across the plasma membrane. Such a phenomenon decreases membrane resistance and increases permeability to monovalent cations, namely, Na+, mimicking the effects of antifungal polyenes. The same effect on membrane resistance was also observed in nonexcitable cells. When sustained light stimulations are applied, neuronal swelling and death occur. The light-controlled pore-forming properties of BV-1 allow performing "on-demand" light-induced membrane poration to rapidly shift from cell-attached to perforated whole-cell patch-clamp configuration. Administration of BV-1 to ex vivo retinal explants or in vivo primary visual cortex elicited neuronal firing in response to short trains of light stimuli, followed by activity silencing upon prolonged light stimulations. BV-1 represents a versatile molecular nanomachine whose properties can be exploited to induce either photostimulation or space-specific cell death, depending on the pattern and duration of light stimulation.

The Effects of Resistance Training Interventions on Weight, Body Mass Index, Body Fat Percentage, and Flexibility in College Students: A Comparison Between Sports and Non-Sports Students

Background. Resistance training is an effective form of exercise that promotes healthy body weight regulation and enhances flexibility. However, discrepancies exist regarding the varying impacts of resistance training based on individuals’ training status across different fitness components, such as body composition and flexibility. Objectives. The primary objective of this study is to assess whether there are significant differences in the outcomes of resistance training responses between trained and untrained groups concerning body composition and flexibility. Materials and methods. This experimental resistance training study involved 60 male students (age = 20.83 ± 0.85 years old) from the same university. The participants were divided into two groups based on their training status: a trained group (S; n = 30) and an untrained group (NS; n = 30). Both groups underwent an identical training regimen, consisting of three sessions per week over a total of four weeks or 12 training sessions. Results. Significant differences were observed in the paired sample T-test analysis between pre-test and post-test results in the untrained group for body weight (t (29) = 7.940, p &lt; 0.001, d = 1.45), body mass index (t (29) = 7.579, p &lt; 0.001, d = 1.38), body fat percentage (t (29) = 9.733, p &lt; 0.001, d = 1.77), and sit-and-reach flexibility (t (29) = -7.714, p &lt; 0.001, d = -1.40). Similarly, the trained group showed significant changes in body weight (t (29) = 2.644, p = 0.013, d = 0.483), body fat (t (29) = 2.561, p = 0.016, d = 0.351), and flexibility (t (29) = -2.543, p = 0.017, d = 0.351), while no substantial difference was found in body mass index (t (29) = 1.925, p = 0.064, d = -0.464). Conclusion. The study found that using resistance training protocols targeting weight reduction with 60-70% of 1 Repetition Maximum (RM) over a one-month intervention period, without stringent calorie restriction, significantly decreased weight and BMI while enhancing flexibility. Notably, regardless of training status disparities, the untrained group demonstrated more expressed improvements compared to the trained group, indicating the influence of training status on response variations to training stimuli.

Different states of synaptic vesicle priming explain target cell type–dependent differences in neurotransmitter release

Pronounced differences in neurotransmitter release from a given presynaptic neuron, depending on the synaptic target, are among the most intriguing features of cortical networks. Hippocampal pyramidal cells (PCs) release glutamate with low probability to somatostatin expressing oriens-lacunosum-moleculare (O-LM) interneurons (INs), and the postsynaptic responses show robust short-term facilitation, whereas the release from the same presynaptic axons onto fast-spiking INs (FSINs) is ~10-fold higher and the excitatory postsynaptic currents (EPSCs) display depression. The mechanisms underlying these vastly different synaptic behaviors have not been conclusively identified. Here, we applied a combined functional, pharmacological, and modeling approach to address whether the main difference lies in the action potential-evoked fusion or else in upstream priming processes of synaptic vesicles (SVs). A sequential two-step SV priming model was fitted to the peak amplitudes of unitary EPSCs recorded in response to complex trains of presynaptic stimuli in acute hippocampal slices of adult mice. At PC-FSIN connections, the fusion probability (Pfusion) of well-primed SVs is 0.6, and 44% of docked SVs are in a fusion-competent state. At PC-O-LM synapses, Pfusion is only 40% lower (0.36), whereas the fraction of well-primed SVs is 6.5-fold smaller. Pharmacological enhancement of fusion by 4-AP and priming by PDBU was recaptured by the model with a selective increase of Pfusion and the fraction of well-primed SVs, respectively. Our results demonstrate that the low fidelity of transmission at PC-O-LM synapses can be explained by a low occupancy of the release sites by well-primed SVs.

Characteristics of Changes in Contractile Properties of Muscle after Anaerobic Exercise

Tensiomyography (TMG) has been described as an effective method for identifying differences in muscle response to athletic training stimuli. However, there is a lack of studies that evaluated changes in muscle contractile properties in response to anaerobic effort and related these changes to Wingate test parameters in more than one lower limb superficial muscle. The main contribution of this work is to evaluate changes in the contractile properties of muscles in response to anaerobic exercise. In a group of 20 physically active men, the body composition analysis was performed using a Tanita DC-360 device. The anaerobic effort was assessed by a Wingate test (30 s), and the contractile properties of muscles were measured using a TMG S2 device. The TMG parameters were measured in selected superficial muscles of the dominant lower limb. The study also calculated indices of the differences (d) and the size of the effect (r). An anaerobic effort in the form of the Wingate test resulted in greater stiffness (Dm) in the vastus lateralis muscle (p = 0.0365; r = 0.47) and a delayed response to stimulus (Td) in the vastus lateralis (p = 0.0239; r = 0.51) and vastus medialis (p = 0.0031; r = 0.66) muscles. The half relaxation time (Tr) (p = 0.0478; r = 0.44) and sustained contraction time (Ts) (p = 0.0276; r = 0.49) in the rectus femoris muscle were also increased. In contrast, a prolonged stimulus-response time (Td) with a decrease in sustained contraction time (Ts) was observed in the gastrocnemius lateralis (Td: p = 0.0054; r = 0.64 and Ts: p = 0.0012; r = 0.74) and gastrocnemius medialis (Td: p = 0.0229; r = 0.52 and Ts: p = 0.0054; r = 0.64) muscles. A significant decrease in contraction time (Tc) (p = 0.0051; r = 0.63) occurred only in the soleus muscle. In addition, significant correlations were shown between selected changes in contractile properties of muscle and parameters of the Wingate anaerobic test. Anaerobic exercise has a significant effect on changes in skeletal muscle contractility parameters. TMG is an effective method for identifying differences in muscle response to sports training stimuli.

Pathogenic gating pore current conducted by autism-related mutations in the NaV1.2 brain sodium channel

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social and communication deficits and repetitive behaviors. The genetic heterogeneity of ASD presents a challenge to the development of an effective treatment targeting the underlying molecular defects. ASD gating charge mutations in the KCNQ/KV7 potassium channel cause gating pore currents (Igp) and impair action potential (AP) firing of dopaminergic neurons in brain slices. Here, we investigated ASD gating charge mutations of the voltage-gated SCN2A/NaV1.2 brain sodium channel, which ranked high among the ion channel genes with mutations in individuals with ASD. Our results show that ASD mutations in the gating charges R2 in Domain-II (R853Q), and R1 (R1626Q) and R2 (R1629H) in Domain-IV of NaV1.2 caused Igp in the resting state of ~0.1% of the amplitude of central pore current. The R1626Q mutant also caused significant changes in the voltage dependence of fast inactivation, and the R1629H mutant conducted proton-selective Igp. These potentially pathogenic Igp were exacerbated by the absence of the extracellular Mg2+ and Ca2+. In silico simulation of the effects of these mutations in a conductance-based single-compartment cortical neuron model suggests that the inward Igp reduces the time to peak for the first AP in a train, increases AP rates during a train of stimuli, and reduces the interstimulus interval between consecutive APs, consistent with increased neural excitability and altered input/output relationships. Understanding this common pathophysiological mechanism among different voltage-gated ion channels at the circuit level will give insights into the underlying mechanisms of ASD.

Zona incerta modulation of the inferior olive and the pontine nuclei.

The zona incerta (ZI) is a subthalamic structure that has been implicated in locomotion, fear, and anxiety. Recently interest has grown in its therapeutic efficacy in deep brain stimulation in movement disorders. This efficacy might be due to the ZI's functional projections to the other brain regions. Notwithstanding some evidence of anatomical connections between the ZI and the inferior olive (IO) and the pontine nuclei (PN), how the ZI modulates the neuronal activity in these regions remains to be determined. We first tested this by monitoring responses of single neurons in the PN and IO to optogenetic activation of channelrhodopsin-expressing ZI axons in wild-type mice, using an in vivo awake preparation. Stimulation of short, single pulses and trains of stimuli at 20 Hz elicited rapid responses in the majority of recorded cells in the PN and IO. Furthermore, the excitatory response of PN neurons scaled with the strength of ZI activation. Next, we used in vitro electrophysiology to study synaptic transmission at ZI-IO synapses. Optogenetic activation of ZI axons evoked a strong excitatory postsynaptic response in IO neurons, which remained robust with repeated stimulation at 20 Hz. Overall, our results demonstrate a functional connection within ZI-PN and ZI-IO pathways.

Synchronization of accelerated intermittent Theta-Burst-Stimulation (aiTBS) with VNS in difficult-to-treat depression (DTD)

IntroductionPatients with difficult-to-treat depression (DTD) need multimodal treatment with combination of psychotherapy, pharmacotherapy and neuromodulation. In severe cases, combination of neuromodulatory techniques may be considered to achieve symptom relief.ObjectivesTo describe a novel treatment approach, which combines VNS in synchronization with accelerated intermittent Theta-Burst-Stimulation (aiTBS) over three weeks in two cases with difficult-to-treat depression.MethodsIn this presentation we describe two cases of DTD, which have been implanted with VNS and did not respond to aiTBS previously. Patients then were offered a synchronized treatment regimen, where each stimulus train of aiTBS was synchronized with ON-time of VNS. To start each train simultaneously with VNS ON-time, we set treatment cycle of each aiTBS and VNS to 19 sec. Patients received 2400-3000 TBS pulses daily for 3 weeks over left dorsolateral prefrontal cortex (DLPFC) at 100% of resting motor threshold.ResultsIn the first patient the MADRS score decreased from 37 to 26 (-30%) and in the other patient there was a decrease of MADRS score from 20 to 9 (-55%), which corresponded to remission after 3 weeks of treatment. The synchronized treatment procedure was well-tolerated in both cases. As both patients experienced significant improvement, we planned maintenance treatment in both cases.ConclusionsSynchronization of aiTBS with VNS is a novel treatment approach in patients with DTD, which can lead to improvement even if patients previously did not respond to aiTBS without synchronization with VNS.Disclosure of InterestNone Declared

Attention and Interpretation Bias Modification Transfers to Memory Bias: Testing the Combined Cognitive Bias Hypothesis

PurposeThis study delves into the combined cognitive bias hypothesis in depression, exploring the interaction between negative attention, interpretation and memory biases. We aimed to assess whether modifying attention and interpretation bias would lead to congruent changes in memory bias, and to what extend and depth this causal effect can be.MethodNinety-nine undergraduates underwent either a positive (PT) or negative (NT) four-day attention and interpretation bias training. A set of well-established post-training assessments including free recall, recognition, autobiographic memory, and self-reference encoding tasks were used to evaluate memory bias. Affective states were measured pre- and post-training.ResultsCompared to PT, participants in NT correctly retrieved more negative trained stimuli, and falsely recognized more negative synonyms of trained terms. NT also exhibited an enhanced retrieval of negative autobiographical memory. No significant differences were found between NT and PT in self-referential encoding and retrieval bias, or affective states.DiscussionThe results suggested an extensive and strong transfer effect from attention and interpretation bias modification to different facets of memory bias, being found in retrieving trained emotional stimuli, in memory intrusion of negative synonyms, and in autobiographic memory recall. The findings underscored the causality between three biases, supporting the combined cognitive bias hypothesis. It might also suggest an effective new approach to modify memory bias via attention and interpretation bias training.

Stimulus mediation, specificity and impact of menthol in rats trained to discriminate puffs of nicotine e-cigarette aerosol from nicotine-free aerosol.

It is unclear if e-cigarettes have reduced abuse liability relative to traditional cigarettes, especially when considering advanced devices which deliver nicotine more efficiently. Translatable and predictive animal models are needed to addresses this question. Our goal was to explore the subjective stimulus effects of e-cigarettes by training rats to discriminate puffs of nicotine aerosol from vehicle aerosol using an aerosol delivery system designed to model e-cigarette use patterns in humans. Rats were trained to discriminate between ten, 10s puffs of aerosol generated from 3mg/ml nicotine e-liquid and nicotine-free e-liquid using a food-reinforced operant procedure. Following acquisition, tests were conducted to determine the specificity of the nicotine aerosol stimulus as well as the impact to the stimulus effects of nicotine resulting from the addition of menthol to e-liquid. Rats learned the nicotine aerosol puff vs vehicle puff discrimination in a mean of 25 training sessions. Injected nicotine fully substituted for the stimulus effects of nicotine aerosol. The stimulus effects of nicotine aerosol were blocked by the nicotinic receptor antagonist mecamylamine. The nicotinic receptor partial agonist, varenicline as well as the stimulant d-amphetamine substituted more robustly for nicotine aerosol puffs than did the NMDA antagonist, ketamine. Menthol enhanced the stimulus effects of nicotine aerosol without altering nicotine blood plasma levels. Nicotine aerosol puffs can function as a training stimulus in rats. The stimulus effects were CNS-mediated and receptor specific. Menthol appears to enhance the stimulus effects of nicotine aerosol through a pharmacodynamic rather than pharmacokinetic mechanism.

Conditioning for Strength, Power, and Aerobic Fitness for Specialist Police Tactical Groups

ABSTRACT Police officers serving in specialist Police Tactical Groups (PTG), including Special Weapons and Tactics teams, are called on to perform tasks in highly volatile and unpredictable situations beyond those of general duties police officers. In addition to carrying loads of 20–25 kg, these officers have, and require, levels of fitness above that of the civilian population, general duties police, and even elite athletes. Through the PTGs' occupational lifespan, from initial selection to operational duties, candidates and serving officers require strength (both absolute and relative), power, and metabolic fitness (aerobic and anaerobic) to pass selection, mitigate injury, and perform occupational tasks. Given the complexities of conditioning these officers, including shift work and unpredictable job demands, a conjugate block periodization approach may be of value. Evidence suggests that a block periodization approach of 3 to 4 mesocycles, including an accumulation phase, a transmutation phase, a realization phase, and potentially a deloading or recovery phase may ensure an adequate training stimulus for these specialist officers. This is especially the case when supported by a dedicated and experienced strength and conditioning coach.