The relationship between neural processing efficiency during inter-hemispheric transfer, alcohol consumption, and sleep quality in college students: an ERP study.

Objective: To examine relationships between sleep, alcohol consumption, and a physiological and behavioral marker of cognitive function in college students. College students are in a high risk category for high alcohol consumption and poor sleep quality, two unhealthful behaviors which can lead to poor mental health outcomes and compromised academic performance. Participants: Thirty college students from a large midwestern institution. Methods: Participants performed an interhemispheric transfer task while their electroencephalography was recorded for later examination of event-related potentials. They were also administered the Pittsburgh Sleep Quality Index, the Alcohol Use Disorders Identification Test, and the Alcohol Timeline Follow-Back. Results: Results demonstrate that increased alcohol consumption is associated with poor right-to-left interhemispheric transfer performance, and increased frontal P1 ERP amplitudes to neuro-ipsilateral targets requiring an interhemispheric-transfer. Conclusions: These findings assist in furthering explorations into the impacts of unhealthy behaviors in college students and underlying markers of simple cognitive and behavioral function.

Are sleep disturbances a cause or consequence of autism spectrum disorder?

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by core symptoms such as atypical social communication, stereotyped behaviors, and restricted interests. One of the comorbid symptoms of individuals with ASD is sleep disturbance. There are two major hypotheses regarding the neural mechanism underlying ASD, i.e., the excitation/inhibition (E/I) imbalance and the altered neuroplasticity hypotheses. However, the pathology of ASD remains unclear due to inconsistent research results. This paper argues that sleep is a confounding factor, thus, must be considered when examining the pathology of ASD because sleep plays an important role in modulating the E/I balance and neuroplasticity in the human brain. Investigation of the E/I balance and neuroplasticity during sleep might enhance our understanding of the neural mechanisms of ASD. It may also lead to the development of neurobiologically informed interventions to supplement existing psychosocial therapies.

The ontogenetic model for CVA rehabilitation with transcranial stimulation

Currently, transcranial stimulation for CVA treatment is based on the interhemispheric rivalry model. This model has proven to have many anomalies, necessitating a new paradigm. Spontaneous recovery from post-CVA hemiplegia has an ontogenetic pattern. We reanalyzed the 2008 longitudinal London study and found that cortical disinhibition is the mechanism for ontogenetic CVA recovery. We propose that transcranial stimulation with 10 Hz rTMS or anode electrical microstimulation can produce CVA recovery similar to spontaneous recovery. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2466).

Actualmente la aplicación de la estimulación transcraneal para el tratamiento del ACV se realiza con base en el modelo de rivalidad interhemisférica. Este modelo ha mostrado muchas anomalías que hacen necesario un nuevo paradigma. La recuperación espontánea de la hemiplejia post-ACV tiene patrón ontogénico. Reanalizamos el estudio longitudinal de Londres 2008 y encontramos que su propuesta corresponde al mecanismo de recuperación ontogénica del ACV. Planteamos que la estimulación transcraneal, utilizando EMTr a 10 Hz o microestimulación eléctrica anódica, podría recuperar el ACV de manera similar a la recuperación espontánea. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2466).

Clinimetric Properties of the Applied Kinesiology Manual Muscle Test in Adults With and Without Pain: A Methodological Study.

Objective: The purpose of this study was to determine the intra- and interexaminer reliability, concurrent validity, and responsiveness of the applied kinesiology manual muscle test (AK-MMT) to discriminate gluteus medius muscle strength and latency. Methods: A cross-sectional and methodological study was conducted in 38 participants using electromyography, electrogoniometry, and hand-held dynamometry to measure latency, angular displacement, and muscle force during the assessment of the gluteus medius by AK-MMT. Inter- and intrarater reliability of 2 examiners with different levels of experience were obtained using the intraclass correlation coefficient. Muscle force, latency, and joint angular displacement were compared between groups (facilitated vs inhibited). Latency and angular displacement also were compared within groups by using the Wilcoxon paired test. For the concurrent validity of the AK-MMT in classifying an inhibited muscle as weak, the receiver operating characteristic curve was conducted. Results: Intra- and interexaminer reliability for the facilitated vs inhibited classifications based on AK-MMT presented good results, with intraclass correlation coefficient > 0.86. For the inhibited group, force and peak force were significantly lower and joint displacement significantly greater. The receiver operating characteristic curve showed an area under the curve of 0.743, demonstrating that the test has concurrent validity (P = .001) to discriminate muscle force. The Wilcoxon paired test showed a significant delay in latency of the inhibited gluteus medius group (0.10 s vs 0.18 s, P = .007) when compared with the facilitated one. Conclusion: In this study, we found good intra- and interexaminer reliability and concurrent validity for the AK-MMT to determine differences in gluteus medius muscle force. Although the paired data showed a different latency time between groups, the hypothesis of prolonged latency in muscles classified as inhibited by AK-MMT still needs further investigation.

Effect of nootropic dipeptide noopept on CA1 pyramidal neurons involves α7AChRs on interneurons in hippocampal slices from rat.

Noopept (NP) is a proline-containing dipeptide with nootropic and neuroprotective properties. We have previously shown that NP significantly increased the frequency of spontaneous IPSCs in hippocampal CA1 pyramidal cells mediated by the activation of inhibitory interneurons in stratum radiatum. The cholinergic system plays an important role in the performance of cognitive functions, furthermore multiple behavioral and clinical facts link NP with the cholinergic system. The present study was undertaken to reveal the possible interaction of NP with neuronal nicotinic acetylcholine receptors (nAChRs). Currents were recorded from rat hippocampal neurons using the whole-cell, patch-clamp technique. NP (5 µM) increased the action potential firing frequency recorded from GABAergic interneurons in the stratum radiatum (SR) of CA1 region. This effect was almost completely abolished by the application of the α7 nAChR-selective antagonists α-bungarotoxin (α-BGT; 6 nM) and methyllycaconitine (MLA; 20 nM). The increase in the frequency of spontaneous IPSCs in CA1 pyramidal cells induced by NP was also eliminated by α7 nAChRs antagonists. These results imply the involvement of α7 nAChRs in the modulation of hippocampal neuronal activity caused by NP and indicate that a7 nAChRs are an important site of action of NP.

Stroke improvement with magnetic stimulation recapitulates ontogeny / Mejoría del ACV con estimulación magnética recapitula la ontogenia

Abstract A patient with chronic brainstem CVA sequelae received one cycle of magnetic stimulation to treat her dysphagia and serendipitously obtained a minimal improvement in her axial movement. Two additional cycles gave her improved postural control and then distal movement, preceded by a display of ipsilateral and contralateral motor evoked potentials, respectively. Magnetic stimulation at 10 Hertz produces cortical disinhibition and reopens the critical neurodevelop ment periods. The ontogenic pattern of hemiplegia recovery in this patient may be explained by an increased and rejuvenated brain plasticity due to critical period reopening through cortical disinhibition. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2253).

Resumen Una paciente con secuelas crónicas de un ACV del tallo cerebral recibió un ciclo de estimulación magnética para el manejo de la disfagia y, por serendipia obtuvo mejoría leve del movimiento axial. Dos ciclos adicionales le permitieron mejoría del control postural y luego la aparición de movimiento distal, precedidos por la visualización de los potenciales evocados motores ipsilateral y contralateral, respectivamente. La estimulación magnética a 10 Hertz produce desinhibición cortical y reabre los periodos críticos del neurodesarrollo. Es posible, que el patrón ontogénico de recuperación de la hemiplejía en esta paciente se explique por el incremento y rejuvenecimiento de la plasticidad cerebral debido a la reapertura de los periodos críticos, por medio de la desinhibición cortical. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2253).

EEG microstates suggest atypical resting-state network activity in high-functioning children and adolescents with autism spectrum development.

EEG microstates represent transient electrocortical events that reflect synchronized activities of large-scale networks, which allows investigations of brain dynamics with sub-second resolution. We recorded resting EEG from 38 children and adolescents with Autism Spectrum Development (ASD) and 48 age, IQ, sex, and handedness-matched typically developing (TD) participants. The EEG was segmented into a time series of microstates using modified k-means clustering of scalp voltage topographies. The frequency and global explained variance (GEV) of a specific microstate (type C) were significantly lower in the ASD group compared to the TD group while the duration of the same microstate was correlated with the presence of ASD-related behaviors. The duration of this microstate was also positively correlated with participant age in the TD group, but not in the ASD group. Further, the frequency and duration of the microstate were significantly correlated with the overall alpha power only in the TD group. The signal strength and GEV for another microstate (type G) was greater in the ASD group than the TD group, and the associated topographical pattern differed between groups with greater variations in the ASD group. While more work is needed to clarify the underlying neural sources, the existing literature supports associations between the two microstates and the default mode and salience networks. The current study suggests specific alterations of temporal dynamics of the resting cortical network activities as well as their developmental trajectories and relationships to alpha power, which has been proposed to reflect reduced neural inhibition in ASD.

Use of an invertebrate animal model (Aplysia californica) to develop novel neural interfaces for neuromodulation.

New tools for monitoring and manipulating neural activity have been developed with steadily improving functionality, specificity, and reliability, which are critical both for mapping neural circuits and treating neurological diseases. This review focuses on the use of an invertebrate animal, the marine mollusk Aplysia californica, in the development of novel neurotechniques. We review the basic physiological properties of Aplysia neurons and discuss the specific aspects that make it advantageous for developing novel neural interfaces: First, Aplysia nerves consist only of unmyelinated axons with various diameters, providing a particularly useful model of the unmyelinated C fibers in vertebrates that are known to carry important sensory information, including those that signal pain. Second, Aplysia's neural tissues can last for a long period in an ex vivo experimental setup. This allows comprehensive tests such as the exploration of parameter space on the same nerve to avoid variability between animals and minimize animal use. Third, nerves in large Aplysia can be many centimeters in length, making it possible to easily discriminate axons with different diameters based on their conduction velocities. Aplysia nerves are a particularly good approximation of the unmyelinated C fibers, which are hard to stimulate, record, and differentiate from other nerve fibers in vertebrate animal models using epineural electrodes. Fourth, neurons in Aplysia are large, uniquely identifiable, and electrically compact. For decades, researchers have used Aplysia for the development of many novel neurotechnologies. Examples include high-frequency alternating current (HFAC), focused ultrasound (FUS), optical neural stimulation, recording, and inhibition, microelectrode arrays, diamond electrodes, carbon fiber microelectrodes, microscopic magnetic stimulation and magnetic resonance electrical impedance tomography (MREIT). We also review a specific example that illustrates the power of Aplysia for accelerating technology development: selective infrared neural inhibition of small-diameter unmyelinated axons, which may lead to a translationally useful treatment in the future. Generally, Aplysia is suitable for testing modalities whose mechanism involves basic biophysics that is likely to be similar across species. As a tractable experimental system, Aplysia californica can help the rapid development of novel neuromodulation technologies.

Increased short interval intracortical inhibition in participants with previous hamstring strain injury.

PURPOSE: Cortical mechanisms may contribute to weakness in participants with previous hamstring strain injury. This study aims to examine intra-cortical inhibition (SICI) and corticospinal excitability in previously injured participants. METHODS: In this cross-sectional study, TMS was used to examine SICI, silent period, silent period: MEP ratios and area under the stimulus response curve in the biceps femoris and medial hamstrings. Comparisons were made between participants with (n = 10) and without (n = 10) previous hamstring strain injury. Motor threshold and isometric knee flexor strength were also compared between participants and the relationship between strength and SICI in control and previously injured participants was examined. RESULTS: Isometric knee flexor strength was lower in previously injured limbs compared with control limbs (mean difference = - 41 Nm (- 26%) [95% CI = - 80 to - 2 Nm], p = 0.04, Cohen's d = - 1.27) and contralateral uninjured limbs (mean difference = - 23 Nm (- 17%), [95% CI = - 40 to - 6 Nm], p = 0.01, Cohen's d = - 0.57). Previously injured limbs exhibited smaller responses to paired pulse stimulation (i.e. greater levels of SICI) in the biceps femoris compared with control limbs (mean difference = - 19%, [95% CI = - 34 to - 5%], p = 0.007, Cohen's d = - 1.33). Isometric knee flexor strength was associated with the level of SICI recorded in the biceps femoris in previously injured participants (coefficient = 23 Nm [95% CI = 7-40 Nm], adjusted R2 = 0.31, p = 0.01). There were no differences in markers of corticospinal excitability between previously injured and control limbs (all p > 0.24, all Cohen's d < 0.40). CONCLUSION: Athletes with previous injury in the biceps femoris exhibit increased SICI in this muscle compared with control participants. Increased SICI is related to lower levels of hamstring strength, and rehabilitation programs targeting the removal of intra-cortical inhibition should be considered.

Functional network antagonism and consciousness.

Spontaneous brain activity changes across states of consciousness. A particular consciousness-mediated configuration is the anticorrelations between the default mode network and other brain regions. What this antagonistic organization implies about consciousness to date remains inconclusive. In this Perspective Article, we propose that anticorrelations are the physiological expression of the concept of segregation, namely the brain's capacity to show selectivity in the way areas will be functionally connected. We postulate that this effect is mediated by the process of neural inhibition, by regulating global and local inhibitory activity. While recognizing that this effect can also result from other mechanisms, neural inhibition helps the understanding of how network metastability is affected after disrupting local and global neural balance. In combination with relevant theories of consciousness, we suggest that anticorrelations are a physiological prior that can work as a marker of preserved consciousness. We predict that if the brain is not in a state to host anticorrelations, then most likely the individual does not entertain subjective experience. We believe that this link between anticorrelations and the underlying physiology will help not only to comprehend how consciousness happens, but also conceptualize effective interventions for treating consciousness disorders in which anticorrelations seem particularly affected.

The fMRI resting paradigm can quantify brain function by surpassing communication and sophisticated setups, hence helping to infer consciousness in individuals who are unable to communicate with their environment. A particular consciousness-mediated rsfMRI configuration is that of functional anticorrelations, that is, the antagonistic relationship between a specific set of brain regions. We suggest that anticorrelations are a key physiological prior, without which consciousness cannot be supported, because the brain cannot segregate how regions get connected. We postulate that segregation is possible thanks to neural inhibition, by regulating global and local inhibitory activity. We believe that the link between anticorrelations and the underlying physiology can help not only to comprehend how consciousness happens, but also conceptualize effective interventions for treating its disorders.

Non-local acute stretching effects on strength performance in healthy young adults.

BACKGROUND: Static stretching (SS) can impair performance and increase range of motion of a non-exercised or non-stretched muscle, respectively. An underdeveloped research area is the effect of unilateral stretching on non-local force output. OBJECTIVE: The objective of this review was to describe the effects of unilateral SS on contralateral, non-stretched, muscle force and identify gaps in the literature. METHODS: A systematic literature search following preferred reporting items for systematic review and meta-analyses Protocols guidelines was performed according to prescribed inclusion and exclusion criteria. Weighted means and ranges highlighted the non-local force output response to unilateral stretching. The physiotherapy evidence database scale was used to assess study risk of bias and methodological quality. RESULTS: Unilateral stretching protocols from six studies involved 6.3 ± 2 repetitions of 36.3 ± 7.4 s with 19.3 ± 5.7 s recovery between stretches. The mean stretch-induced force deficits exhibited small magnitude effect sizes for both the stretched (-6.7 ± 7.1%, d = -0.35: 0.01 to -1.8) and contralateral, non-stretched, muscles (-4.0 ± 4.9%, d = , 0.22: 0.08 to 1.1). Control measures exhibited trivial deficits. CONCLUSION: The limited literature examining non-local effects of prolonged SS revealed that both the stretched and contralateral, non-stretched, limbs of young adults demonstrate small magnitude force deficits. However, the frequency of studies with these effects were similar with three measures demonstrating deficits, and four measures showing trivial changes. These results highlight the possible global (non-local) effects of prolonged SS. Further research should investigate effects of lower intensity stretching, upper versus lower body stretching, different age groups, incorporate full warm-ups, and identify predominant mechanisms among others.

Optimizing thermal block length during infrared neural inhibition to minimize temperature thresholds.

Objective. Infrared neural inhibition (INI) is a method of blocking the generation or propagation of neural action potentials through laser heating with wavelengths strongly absorbed by water. Recent work has identified that the distance heated along axons, the block length (BL), modulates the temperature needed for inhibition; however, this relationship has not been characterized. This study explores how BL during INI can be optimized towards minimizing its temperature threshold.Approach. To understand the relationship between BL and the temperature required for INI, excised nerves fromAplysia californicawere laser-heated over different lengths of axon during electrical stimulation of compound action potentials. INI was provided by irradiation (λ= 1470 nm) from a custom probe (n= 6 nerves), and subsequent validation was performed by providing heat block using perfused hot media over nerves (n= 5 nerves).Main Results. Two BL regimes were identified. Short BLs (thermal full width at half maximum (tFWHM) = 0.81-1.13 mm) demonstrated that increasing the tFWHM resulted in lower temperature thresholds for INI (p< 0.0125), while longer BLs (tFWHM = 1.13-3.03 mm) showed no significant change between the temperature threshold and tFWHM (p> 0.0125). Validation of this longer regime was performed using perfused hot media over different lengths of nerves. This secondary heating method similarly showed no significant change (p> 0.025) in the temperature threshold (tFWHM = 1.25-4.42 mm).Significance. This work characterized how the temperature threshold for neural heat block varies with BL and identified an optimal BL around tFWHM = 1.13 mm which minimizes both the maximum temperature applied to tissue and the volume of tissue heated during INI. Understanding how to optimally target lengths of nerve to minimize temperature during INI can help inform the design of devices for longitudinal animal studies and human implementation.

Isotonic ion replacement can lower the threshold for selective infrared neural inhibition.

Significance: Infrared (IR) inhibition can selectively block peripheral sensory nerve fibers, a potential treatment for autonomic-dysfunction-related diseases (e.g., neuropathic pain and interstitial cystitis). Lowering the IR inhibition threshold can increase its translational potentials. Aim: Infrared induces inhibition by enhancing potassium channel activation. We hypothesized that the IR dose threshold could be reduced by combining it with isotonic ion replacement. Approach: We tested the IR inhibition threshold on the pleural-abdominal connective of Aplysia californica. Using a customized chamber system, the IR inhibition was applied either in normal saline or in isotonic ion-replaced saline, which could be high glucose saline, high choline saline, or high glucose/high choline saline. Each modified saline was at a subthreshold concentration for inhibiting neural conduction. Results: We showed that isotonically replacing ions in saline with glucose and/or choline can reduce the IR threshold and temperature threshold of neural inhibition. Furthermore, the size selectivity of IR inhibition was preserved when combined with high glucose/high choline saline. Conclusions: The present work of IR inhibition combined with isotonic ion replacement will guide further development of a more effective size-selective IR inhibition modality for future research and translational applications.

Molecular Tools for Targeted Control of Nerve Cell Electrical Activity. Part II.

In modern life sciences, the issue of a specific, exogenously directed manipulation of a cell's biochemistry is a highly topical one. In the case of electrically excitable cells, the aim of the manipulation is to control the cells' electrical activity, with the result being either excitation with subsequent generation of an action potential or inhibition and suppression of the excitatory currents. The techniques of electrical activity stimulation are of particular significance in tackling the most challenging basic problem: figuring out how the nervous system of higher multicellular organisms functions. At this juncture, when neuroscience is gradually abandoning the reductionist approach in favor of the direct investigation of complex neuronal systems, minimally invasive methods for brain tissue stimulation are becoming the basic element in the toolbox of those involved in the field. In this review, we describe three approaches that are based on the delivery of exogenous, genetically encoded molecules sensitive to external stimuli into the nervous tissue. These approaches include optogenetics (overviewed in Part I), as well as chemogenetics and thermogenetics (described here, in Part II), which is significantly different not only in the nature of the stimuli and structure of the appropriate effector proteins, but also in the details of experimental applications. The latter circumstance is an indication that these are rather complementary than competing techniques.

Effects of acute mental stress on conditioned pain modulation in temporomandibular disorders patients and healthy individuals

Abstract Stress is a contributing factor to painful temporomandibular disorders (TMD). Nevertheless, the underpinnings of this relationship are not fully understood. Objective To investigate the effects of acute mental stress on conditioned pain modulation (CPM) in TMD patients compared with healthy individuals. Methodology Twenty women with chronic myofascial TMD diagnosed according to the RDC/TMD and 20 age-matched healthy women had the CPM assessed before and after a stressful task using the Paced Auditory Serial Addition Task (PASAT) in a single session. Subjective stress response was assessed with the aid of visual analog scale (VAS). Pressure pain threshold (PPT) on masseter muscle was the test stimulus (TS) and immersion of the participant's hand on hot water was the conditioning stimulus (CS) - CPM-sequential paradigm. Results Healthy individuals reported PASAT are more stressful when compared with TMD patients and the stress task did not affect the CPM in neither group. Nonetheless, a negative correlation was observed between change in CPM and change in TS from baseline to post-stress session, which indicates that the greater the increase in PPT after the stress task, the greater was the decrease in CPM magnitude. The correlation was strong for healthy controls (r=- 0.72, p<0.001) and moderate for TMD patients (r=- 0.44, p=0.047). Conclusions The correlation between the change in CPM and the TS change following the stress task may possibly indicate an overlapping pathway between stress-induced analgesia/hyperalgesia and descending pain inhibition.

Disinhibition of somatostatin interneurons confers resilience to stress in male but not female mice.

Chronic stress represents a vulnerability factor for anxiety and depressive disorders and has been widely used to model aspects of these disorders in rodents. Disinhibition of somatostatin (SST)-positive GABAergic interneurons in mice by deletion of γ2 GABAA receptors selectively from these cells (SSTCre:γ2f/f mice) has been shown to result in behavioral and biochemical changes that mimic the responses to antidepressant doses of ketamine. Here we explored the extent to which SSTCre:γ2f/f mice exhibit resilience to unpredictable chronic mild stress (UCMS). We found that male SSTCre:γ2f/f mice are resilient to UCMS-induced (i) reductions in weight gain, (ii) reductions in SST-immuno-positive cells in medial prefrontal cortex (mPFC), (iii) increases in phosphorylation of eukaryotic elongation factor 2 (eEF2) in mPFC, and (iv) increased anxiety in a novelty suppressed feeding test. Female SSTCre:γ2f/f mice were resilient to UCMS-induced reductions in SST-immuno-positive cells indistinguishably from males. However, in contrast to males, they showed no UCMS effects on weight gain independent of genotype. Moreover, in mPFC of female γ2f/f control mice, UCMS resulted in paradoxically reduced p-EF2 levels without stress effects in the SSTCre:γ2f/f mutants. Lastly, female SSTCre:γ2f/f mice showed increased rather than reduced UCMS induced anxiety compared to γ2f/f controls. Thus, disinhibition of SST interneurons results in behavioral resilience to UCMS selectively in male mice, along with cellular resilience of SST neurons to UCMS independent of sex. Thus, mechanisms underlying vulnerability and resilience to stress are sex specific and map to mPFC rather than hippocampus but appear unrelated to changes in expression of SST as a marker of corresponding interneurons.

Mecanismos de modulación central del dolor: revisión de la literatura / Mechanisms of central pain modulation: literature review

RESUMEN: La percepción del dolor resulta de múltiples y dinámicos mecanismos en el sistema nervioso central (SNC) y periférico que inhiben o facilitan el estímulo y respuesta nociceptiva. Sin embargo, la principal capacidad de modulación esta a cargo del SNC. Los estímulos nociceptivos son detectados por terminaciones nerviosas libres de neuronas periféricas que sinaptan con neuronas aferentes secundarias de la médula espinal. Luego estas fibras decusan para formar las vías nociceptivas ascendentes. Una vez alcanzadas las estructuras subcorticales, se activan las neuronas del tálamo, quienes envían el estímulo hacia la corteza somatosensorial, desencadenando la percepción consciente del dolor y activando el sistema inhibitorio descendente. Para que la modulación nociceptiva se realice, es necesaria la participación de diversas sustancias o neurotransmisores que conectan áreas del SNC especializadas. Por lo tanto, el objetivo de este estudio fue realizar una revisión de la literatura respecto de los mecanismos que participan en los procesos de modulación central del dolor.

SUMMARY: Pain perception results from multiple and dynamic mechanisms in the central nervous system (CNS) and peripheral nervous system that inhibit or facilitate stimulation and nociceptive response. However, neuromodulation is mainly a function of the CNS. Nociceptive stimulus is detected by peripheral neurons receptors that synapse with the secondary afferent neurons of the spinal cord. These fibers cross to conform the ascending nociceptive pathways. Once the subcortical structures are reached, the thalamus`s neurons are activated; the thalamus send the stimulus to the somatosensory cortex, triggering the conscious perception of pain and activating the descending inhibitory system. For the nociceptive modulation to be carried out, the participation of various substances or neurotransmitters that connect specialized CNS areas is necessary. Therefore, the aim of this study was to review the literature regarding the mechanisms involved in central pain modulation processes.

Reduction of Dendritic Inhibition in CA1 Pyramidal Neurons in Amyloidosis Models of Early Alzheimer's Disease.

BACKGROUND: In an early stage of Alzheimer's disease (AD), before the formation of amyloid plaques, neuronal network hyperactivity has been reported in both patients and animal models. This suggests an underlying disturbance of the balance between excitation and inhibition. Several studies have highlighted the role of somatic inhibition in early AD, while less is known about dendritic inhibition. OBJECTIVE: In this study we investigated how inhibitory synaptic currents are affected by elevated Aß levels. METHODS: We performed whole-cell patch clamp recordings of CA1 pyramidal neurons in organotypic hippocampal slice cultures after treatment with Aß-oligomers and in hippocampal brain slices from AppNL-F-G mice (APP-KI). RESULTS: We found a reduction of spontaneous inhibitory postsynaptic currents (sIPSCs) in CA1 pyramidal neurons in organotypic slices after 24 h Aß treatment. sIPSCs with slow rise times were reduced, suggesting a specific loss of dendritic inhibitory inputs. As miniature IPSCs and synaptic density were unaffected, these results suggest a decrease in activity-dependent transmission after Aß treatment. We observed a similar, although weaker, reduction in sIPSCs in CA1 pyramidal neurons from APP-KI mice compared to control. When separated by sex, the strongest reduction in sIPSC frequency was found in slices from male APP-KI mice. Consistent with hyperexcitability in pyramidal cells, dendritically targeting interneurons received slightly more excitatory input. GABAergic action potentials had faster kinetics in APP-KI slices. CONCLUSION: Our results show that Aß affects dendritic inhibition via impaired action potential driven release, possibly due to altered kinetics of GABAergic action potentials. Reduced dendritic inhibition may contribute to neuronal hyperactivity in early AD.

Passive muscle stretching reduces estimates of persistent inward current strength in soleus motor units.

Prolonged (≥60 s) passive muscle stretching acutely reduces maximal force production at least partly through a suppression of efferent neural drive. The origin of this neural suppression has not been determined; however, some evidence suggests that reductions in the amplitude of persistent inward currents (PICs) in the motoneurons may be important. The aim of the present study was to determine whether acute passive (static) muscle stretching affects PIC strength in gastrocnemius medialis (GM) and soleus (SOL) motor units. We calculated the difference in instantaneous discharge rates at recruitment and de-recruitment (ΔF) for pairs of motor units in GM and SOL during triangular isometric plantar flexor contractions (20% maximum) both before and immediately after a 5 min control period and immediately after five 1 min passive plantar flexor stretches. After stretching, there was a significant reduction in SOL ΔF (-25.6%; 95% confidence interval, CI=-45.1% to -9.1%, P=0.002) but not GM ΔF These data suggest passive muscle stretching can reduce the intrinsic excitability, via PICs, of SOL motor units. These findings (1) suggest that PIC strength might be reduced after passive stretching, (2) are consistent with previously established post-stretch decreases in SOL but not GM EMG amplitude during contraction, and (3) indicate that reductions in PIC strength could underpin the stretch-induced force loss.

Does a recent hamstring muscle injury affect the timing of muscle activation during high speed overground running in professional Australian Football players?

OBJECTIVES: To investigate if the temporal characteristics of hamstring and gluteal muscle activation are altered during high speed overground running in professional Australian Football players following hamstring muscle injury. DESIGN: Cohort study. SETTING: Field-based testing. PARTICIPANTS: Elite professional Australian Football players who had sustained a hamstring muscle injury in the six months prior to testing (n = 7) and a group of players from the same club who had no history of hamstring muscle injury (n = 8). MAIN OUTCOME MEASURES: Muscle onset timing, muscle offset timing and muscle onset duration of the medial hamstrings, biceps femoris and gluteus maximus muscles during high-speed running using electromyographic data. RESULTS: No significant differences in any of the temporal aspects of muscle activation were found between groups for any of the muscles tested (p > 0.05). CONCLUSIONS: Persistent alterations to the timing of muscle activation following hamstring muscle injury that have been reported in recreational athletes were not observed during high speed running in professional athletes who have completed comprehensive rehabilitation programs.