Afferent Inhibition Research Articles

Investigating the role of low level reinforcement reflex loops in insect locomotion

Insects are highly capable walkers, but many questions remain regarding how the insect nervous system controls locomotion. One particular question is how information is communicated between the ‘lower level’ ventral nerve cord (VNC) and the ‘higher level’ head ganglia to facilitate control. In this work, we seek to explore this question by investigating how systems traditionally described as ‘positive feedback’ may initiate and maintain stepping in the VNC with limited information exchanged between lower and higher level centers. We focus on the ‘reflex reversal’ of the stick insect femur-tibia joint between a resistance reflex (RR) and an active reaction in response to joint flexion, as well as the activation of populations of descending dorsal median unpaired (desDUM) neurons from limb strain as our primary reflex loops. We present the development of a neuromechanical model of the stick insect (Carausius morosus) femur-tibia (FTi) and coxa-trochanter joint control networks ‘in-the-loop’ with a physical robotic limb. The control network generates motor commands for the robotic limb, whose motion and forces generate sensory feedback for the network. We based our network architecture on the anatomy of the non-spiking interneuron joint control network that controls the FTi joint, extrapolated network connectivity based on known muscle responses, and previously developed mechanisms to produce ‘sideways stepping’. Previous studies hypothesized that RR is enacted by selective inhibition of sensory afferents from the femoral chordotonal organ, but no study has tested this hypothesis with a model of an intact limb. We found that inhibiting the network’s flexion position and velocity afferents generated a reflex reversal in the robot limb’s FTi joint. We also explored the intact network’s ability to sustain steady locomotion on our test limb. Our results suggested that the reflex reversal and limb strain reinforcement mechanisms are both necessary but individually insufficient to produce and maintain rhythmic stepping in the limb, which can be initiated or halted by brief, transient descending signals. Removing portions of this feedback loop or creating a large enough disruption can halt stepping independent of the higher-level centers. We conclude by discussing why the nervous system might control motor output in this manner, as well as how to apply these findings to generalized nervous system understanding and improved robotic control.

Cortical plasticity causes useless hand syndrome in multiple sclerosis: a neurophysiological study in a rare case

Background Useless Hand Syndrome (UHS) is a rare clinical manifestation of an upper cervical cord lesion, which is most commonly associated with multiple sclerosis (MS). The pathophysiological mechanism underlying UHS remains unclear. Case We report a 25-year-old woman, who described numbness in her left upper extremity. Cervical magnetic resonance imaging revealed a posterior upper cervical cord lesion. There was no cortical lesion that could explain the clinical findings. We measured (1) short-latency afferent inhibition (SAI) by obtaining motor evoked potentials as an indicator of sensorimotor integration and (2) somatosensorial temporal discrimination threshold (STDT) to display central somatosensory pathway function. In the right cerebral hemisphere, we found an excessive increase in STDT and no inhibition in the SAI paradigm. Conclusions These findings indicate that impairment of sensorimotor integration and central processing of sensory stimuli cause useless hand syndrome.

Chemogenetic modulation reveals distinct roles of the subthalamic nucleus and its afferents in the regulation of locomotor sensitization to amphetamine in rats.

The subthalamic nucleus (STN) is a key node in cortico-basal-ganglia thalamic circuits, guiding behavioral output through its position as an excitatory relay of the striatal indirect pathway and its direct connections with the cortex. There have been conflicting results regarding the role of the STN in addiction-related behavior to psychostimulants, and little is known with respect to the role of STN afferents. To address this, we used viral vectors to express DREADDs (Designer Receptors Exclusively Activated by Designer Drugs) in the STN of rats in order to bidirectionally manipulate STN activity during the induction of amphetamine sensitization. In addition, we used a Cre-recombinase dependent Gi/o-coupled DREADD approach to transiently inhibit afferents from ventral pallidum (a subcomponent of the striatal indirect pathway) or the prelimbic cortex (a subcomponent of the cortico-STN hyperdirect pathway). Despite inducing mild hyperactivity in non-drug controls, stimulation of STN neurons with Gq-DREADDs blocked the development and persistence of amphetamine sensitization as well as conditioned responding. In contrast, inhibition of STN neurons with Gi/o-DREADDs enhanced the induction of sensitization without altering its persistence or conditioned responding. Chemogenetic inhibition of afferents from ventral pallidum had no effect on amphetamine sensitization but blocked conditioned responding whereas chemogenetic inhibition of afferents from prelimbic cortex attenuated the persistence of sensitization as well as conditioned responding. These results suggest the STN and its afferents play complex roles in the regulation of amphetamine sensitization and highlight the need for further characterization of how integration of inputs within STN guide behavior.

Biological sex differences in afferent-mediated inhibition of motor responses evoked by TMS

Sensorimotor integration can be assessed by pairing electrical peripheral nerve stimulation with transcranial magnetic stimulation (TMS). The resulting afferent inhibition is observed when TMS precedes nerve stimulation by ∼ 20–25 ms, termed short-latency afferent inhibition (SAI), or by 200 ms, termed long-latency afferent inhibition (LAI). The purpose of this study was to determine whether biological sex influences the magnitude of SAI or LAI. SAI and LAI were assessed in fifteen males (21.5 ± 2.7 years) and fifteen females (20.2 ± 2.3 years). TMS was delivered to the primary motor cortex (M1) following stimulation of the contralateral median nerve at the wrist or digital nerve of the index finger, and motor-evoked potentials (MEPs) were obtained from the right first dorsal interosseous (FDI) muscle. SAI evoked by median and digital nerve stimulation, and LAI evoked by median nerve stimulation, were not different between males and females. LAI evoked by digital nerve stimulation was increased in females compared to males, but this difference between sexes was no longer present following the removal of datapoints where inhibition was not observed. This study is the first to investigate biological sex differences in afferent inhibition.

Two forms of short-interval intracortical inhibition in human motor cortex

BackgroundPulses of transcranial magnetic stimulation (TMS) with a predominantly anterior-posterior (AP) or posterior-anterior (PA) current direction over the primary motor cortex appear to activate distinct excitatory inputs to corticospinal neurons. In contrast, very few reports have examined whether the inhibitory neurons responsible for short-interval intracortical inhibition (SICI) are sensitive to TMS current direction. ObjectivesTo investigate whether SICI evaluated with AP and PA conditioning stimuli (CSPA and CSAP) activate different inhibitory pathways. SICI was always assessed using a PA-oriented test stimulus (TSPA). MethodsUsing two superimposed TMS coils, CSPA and CSAP were applied at interstimulus intervals (ISI) of 1–5 ms before a TSPA, and at a range of different intensities. Using a triple stimulation design, we then tested whether SICI at ISI of 3 ms using opposite directions of CS (SICICSPA3 and SICICSAP3) interacted differently with three other forms of inhibition, including SICI at ISI of 2 ms (SICICSPA2), cerebellum-motor cortex inhibition (CBI 5 ms) and short-latency afferent inhibition (SAI 22 ms). Finally, we compared the effect of tonic and phasic voluntary contraction on SICICSPA3 and SICICSAP3. ResultsCSAP produced little SICI at ISIs = 1 and 2 ms. However, at ISI = 3 ms, both CSAP and CSPA were equally effective at the same percent of maximum stimulator output. Despite this apparent similarity, combining SICICSPA3 or SICICSAP3 with other forms of inhibition led to quite different results: SICICSPA3 interacted in complex ways with CBI, SAI and SICICSPA2, whereas the effect of SICICSAP3 appeared to be quite independent of them. Although SICICSPA and SICICSAP were both reduced by the same amount during voluntary tonic contraction compared with rest, in a simple reaction time task SICICSAP was disinhibited much earlier following the imperative signal than SICICSPA. ConclusionsSICICSPA appears to activate a different inhibitory pathway to that activated by SICICSAP. The difference is behaviourally relevant since the pathways are controlled differently during volitional contraction. The results may explain some previous pathological data and open the possibility of testing whether these pathways are differentially recruited in a range of tasks.

Cortical Excitability and Connectivity in Patients With Brain Tumors.

Background: Brain tumors can cause different changes in excitation and inhibition at the neuronal network level. These changes can be generated from mechanical and cellular alterations, often manifesting clinically as seizures.Objective/Hypothesis: The effects of brain tumors on cortical excitability (CE) have not yet been well-evaluated. The aim of the current study was to further investigate cortical–cortical and cortical–spinal excitability in patients with brain tumors using a more extensive transcranial magnetic stimulation protocol.Methods: We evaluated CE on 12 consecutive patients with lesions within or close to the precentral gyrus, as well as in the subcortical white matter motor pathways. We assessed resting and active motor threshold, short-latency intracortical inhibition (SICI), intracortical facilitation (ICF), short-latency afferent inhibition (SAI), long-latency afferent inhibition, cortical silent period, and interhemispheric inhibition.Results: CE was reduced in patients with brain tumors than in healthy controls. In addition, SICI, ICF, and SAI were lower in the affected hemisphere compared to the unaffected and healthy controls.Conclusions: CE is abnormal in hemispheres affected by brain tumors. Further studies are needed to determine if CE is related with motor impairment.

Conventional and Threshold-Tracking Transcranial Magnetic Stimulation Tests for Single-handed Operation.

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used to examine corticospinal excitability. Paired-pulse TMS paradigms (e.g., short- and long-interval intracortical inhibition (SICI/LICI), short-interval intracortical facilitation (SICF), and short- and long-latency afferent inhibition (SAI/LAI)) provide information about intracortical inhibitory and facilitatory networks. This has long been done by the conventional TMS method of measuring changes in the size of the motor-evoked potentials (MEPs) in response to stimuli of constant intensity. An alternative threshold-tracking approach has recently been introduced whereby the stimulus intensity for a target amplitude is tracked. The diagnostic utility of threshold-tracking SICI in amyotrophic lateral sclerosis (ALS) has been shown in previous studies. However, threshold-tracking TMS has only been used in a few centers, in part due to the lack of readily available software but also perhaps due to uncertainty over its relationship to conventional single- and paired-pulse TMS measurements. A menu-driven suite of semi-automatic programs has been developed to facilitate the broader use of threshold-tracking TMS techniques and to enable direct comparisons with conventional amplitude measurements. These have been designed to control three types of magnetic stimulators and allow recording by a single operator of the common single- and paired-pulse TMS protocols. This paper shows how to record a number of single- and paired-pulse TMS protocols on healthy subjects and analyze the recordings. These TMS protocols are fast and easy to perform and can provide useful biomarkers in different neurological disorders, particularly neurodegenerative diseases such as ALS.

Conventional and Threshold-Tracking Transcranial Magnetic Stimulation Tests for Single-handed Operation

Most single-pulse transcranial magnetic stimulation (TMS) parameters (e.g., motor threshold, stimulus-response function, cortical silent period) are used to examine corticospinal excitability. Paired-pulse TMS paradigms (e.g., short- and long-interval intracortical inhibition (SICI/LICI), short-interval intracortical facilitation (SICF), and short- and long-latency afferent inhibition (SAI/LAI)) provide information about intracortical inhibitory and facilitatory networks. This has long been done by the conventional TMS method of measuring changes in the size of the motor-evoked potentials (MEPs) in response to stimuli of constant intensity. An alternative threshold-tracking approach has recently been introduced whereby the stimulus intensity for a target amplitude is tracked. The diagnostic utility of threshold-tracking SICI in amyotrophic lateral sclerosis (ALS) has been shown in previous studies. However, threshold-tracking TMS has only been used in a few centers, in part due to the lack of readily available software but also perhaps due to uncertainty over its relationship to conventional single- and paired-pulse TMS measurements. A menu-driven suite of semi-automatic programs has been developed to facilitate the broader use of threshold-tracking TMS techniques and to enable direct comparisons with conventional amplitude measurements. These have been designed to control three types of magnetic stimulators and allow recording by a single operator of the common single- and paired-pulse TMS protocols. This paper shows how to record a number of single- and paired-pulse TMS protocols on healthy subjects and analyze the recordings. These TMS protocols are fast and easy to perform and can provide useful biomarkers in different neurological disorders, particularly neurodegenerative diseases such as ALS.

Body ownership, sensorimotor integration and motor cortical excitability: A TMS study about rubber hand illusion

ObjectiveThe Rubber Hand Illusion (RHI) manipulates body ownership experimentally and helps investigate the related neurophysiological processes. This study aimed to evaluate motor cortex excitability that hypothesized changed due to illusion. MethodTwenty-one healthy (twelve male, nine female), right-handed volunteers aged between 25 and 50 years were recruited to the study. Short-Latency Afferent Inhibition (SAI) was evaluated by transcranial magnetic stimulation (TMS) given with a figure-of-eight-shaped coil from the left motor cortex, 21 ms after peripheral electrical stimulation. Short-Interval Intracortical Inhibition (SICI) and Intracortical Facilitation (ICF) were investigated using a paired-pulse TMS at interstimulus intervals (ISI) of 1, 2.5, 3 ms and 15, 20, 25 ms, respectively. We used custom-made illusion setups for TMS paradigms. SAI, SICI and ICF was evaluated before, during and 15 min after the RHI. ResultsResults of the study revealed significantly high SAI during illusion compared to pre-illusion, but no difference was found between post-illusion 15th minutes and control measurements. Significantly reduced SICI at 2.5 and 3 ms ISI obtained during illusion, while RHI did not affect SICI at 1 ms ISI and ICF. SignificanceBody ownership illusion modulates the motor cortex excitability, possibly through altered sensory processing and sensorimotor integration.

The relationship between cholinergic system brain structure and function in healthy adults and patients with mild cognitive impairment

We assessed the structure–function relationship of the human cholinergic system and hypothesized that structural measures are associated with short-latency sensory afferent inhibition (SAI), an electrophysiological measure of central cholinergic signal transmission. Healthy volunteers (n = 36) and patients with mild cognitive impairment (MCI, n = 20) underwent median nerve SAI and 3T structural MRI to determine the volume of the basal forebrain and the thalamus. Patients with MCI had smaller basal forebrain (p < 0.001) or thalamus volumes (p < 0.001) than healthy volunteers. Healthy SAI responders (> 10% SAI) had more basal forebrain volume than non-responders (p = 0.004) or patients with MCI (p < 0.001). More basal forebrain volume was associated with stronger SAI in healthy volunteers (r = 0.33, p < 0.05) but not patients with MCI. There was no significant relationship between thalamus volumes and SAI. Basal forebrain volume is associated with cholinergic function (SAI) in healthy volunteers but not in MCI patients. The in-vivo investigation of the structure–function relationship could further our understanding of the human cholinergic system in patients with suspected or known cholinergic system degeneration.

Fatigue, pain, and the recovery of neuromuscular function after consecutive days of full-body resistance exercise in trained men.

This study measured the self-reported level of fatigue, pain, and neuromuscular function of the knee extensor muscles over a three-day period that included two consecutive days of full-body resistance exercises. 10 resistance-trained men performed two consecutive days of full-body resistance exercise. Muscle activation (electromyography and voluntary activation), contractility, and presynaptic inhibition of Ia afferents (homosynaptic and GABA mediated presynaptic inhibition) for the quadriceps were examined from femoral and posterior tibial nerve stimulation. Fatigue and pain were elevated after Day 1, and were not reduced to pre-exercise levels at the start of Day 2 (p < 0.05). Maximal voluntary torque (- 51.4 Nm, 95% CI = 12.4-90.4Nm, p = 0.005) and rate of torque development (- 469 Nm.s-1, 95% CI = 109-829Nm.s-1, p = 0.006) were reduced after Day 1, had recovered by Day 2, and did not change after the second training session. The maximal amplitude and rate of rise for the quadriceps twitch were reduced after both training sessions (p < 0.01), with recovery 24h each session. The maximal amplitude and rate of early muscle activation were reduced after Day 1 (p < 0.01), but no changes were observed for voluntary activation, H-reflex size and shape, or measures of Ia presynaptic inhibition. Resistance exercise in the presence of elevated fatigue and pain from a previous training session does not worsen recovery, or lead to significant alterations in quadriceps neuromuscular function. Reduction in muscle contractility, in the absence of declines in muscle activation, does not lead to decreased voluntary torque.

SY1.3. Probing the pathophysiology of movement disorders with transcranial magnetic stimulation

Transcranial magnetic stimulation (TMS) is a widely-used noninvasive brain stimulation method for research in the field of neurology, psychiatry, and rehabilitation. TMS can be used to study connectivity and therefore help to shed light on brain networks. This mode of noninvasive brain stimulation is particularly useful to study brain regions relevant to movement, as stimulating the primary motor cortex results in motor-evoked potential (MEP)s, which can be useful for interpreting the effects of various brain regions on the motor cortex. Connectivity among the primary motor cortex and other movement-relevant regions can be studied by using a paired- or multiple-pulse technique. This is possible by assessing the effects of a pre- conditioning stimulus on the conditioning-test pair or a conditioning stimulus on the test pulse. TMS can also be used in conjunction with electroencephalography (EEG), magnetoencephalography (MEG) or imaging tools such as functional magnetic resonance imaging (fMRI) or positron emission tomography (PET) to further assess TMS-induced changes. Combining these techniques can enable researchers to obtain spatial or temporal information of the effects of TMS on the brain. Movement in healthy human subjects has been studied using TMS, and information obtained from these studies has been useful in understanding which brain regions are relevant in producing movement. Furthermore, there are various TMS measures of the motor cortex that reflect different aspects of cortical excitability. Some examples are short and long intracortical inhibition (SICI and LICI), intracortical facilitation (ICF), short- and long- afferent inhibition (SAI and LAI), transcallosal inhibition, premotor cortex inhibition, etc. TMS has also been used to study movement disorders such as Parkinson’s disease, dystonia, essential tremor, and Huntington’s disease. While TMS still has limited use in the clinical realm, it has provided a wealth of data in our understanding of movement disorders. In this talk, I will give an overview of TMS studies that probe the physiology of normal human movement and also discuss those focusing on movement disorders. I will also review limitations of TMS and the findings of TMS studies to date, and briefly discuss the need for future studies.

WS2.2. Parameters of TMS

Transcranial magnetic stimulation (TMS) is a non-invasive painless technique to stimulate the human brain. This presentation will introduce basic physiological principles of how TMS excites human motor cortex. In addition, the following single-pulse and paired-pulse TMS measures of corticospinal and motor cortical excitability will be presented and discussed with respect to underpinning physiological mechanisms: motor threshold, motor evoked potential recruitment curve, cortical silent period, short-interval intracortical inhibition, intracortical facilitation, long- interval intracortical inhibition, short-interval intracortical facilitation, short-latency afferent inhibition. Pharmacological evidence will be summarized to explain the physiology of these measures. In addition, clinical utility will be exemplarily discussed by demonstrating abnormal TMS measures of corticospinal and motor cortical excitability in patients with epilepsy and Alzheimer's disease.

Driving motor cortex oscillations modulates bradykinesia in Parkinson's disease.

In patients with Parkinson's disease, beta (β) and gamma (γ) oscillations are altered in the basal ganglia, and this abnormality contributes to the pathophysiology of bradykinesia. However, it is unclear whether β and γ rhythms at the primary motor cortex (M1) level influence bradykinesia. Transcranial alternating current stimulation (tACS) can modulate cortical rhythms by entraining endogenous oscillations. We tested whether β- and γ-tACS on M1 modulate bradykinesia in patients with Parkinson's disease by analysing the kinematic features of repetitive finger tapping, including movement amplitude, velocity and sequence effect, recorded during β-, γ- and sham tACS. We also verified whether possible tACS-induced bradykinesia changes depended on modifications in specific M1 circuits, as assessed by short-interval intracortical inhibition and short-latency afferent inhibition. Patients were studied OFF and ON dopaminergic therapy. Results were compared to those obtained in a group of healthy subjects. In patients, movement velocity significantly worsened during β-tACS and movement amplitude improved during γ-tACS, while the sequence effect did not change. In addition, short-latency afferent inhibition decreased (reduced inhibition) during β-tACS and short-interval intracortical inhibition decreased during both γ- and β-tACS in Parkinson's disease. The effects of tACS were comparable between OFF and ON sessions. In patients OFF therapy, the degree of short-interval intracortical inhibition modulation during β- and γ-tACS correlated with movement velocity and amplitude changes. Moreover, there was a positive correlation between the effect of γ-tACS on movement amplitude and motor symptoms severity. Our results show that cortical β and γ oscillations are relevant in the pathophysiology of bradykinesia in Parkinson's disease and that changes in inhibitory GABA-A-ergic interneuronal activity may reflect compensatory M1 mechanisms to counteract bradykinesia. In conclusion, abnormal oscillations at the M1 level of the basal ganglia-thalamo-cortical network play a relevant role in the pathophysiology of bradykinesia in Parkinson's disease.

Robustness of neuronal tuning to binaural sound localization cues against age-related loss of inhibitory synaptic inputs.

Sound localization relies on minute differences in the timing and intensity of sound arriving at both ears. Neurons of the lateral superior olive (LSO) in the brainstem process these interaural disparities by precisely detecting excitatory and inhibitory synaptic inputs. Aging generally induces selective loss of inhibitory synaptic transmission along the entire auditory pathways, including the reduction of inhibitory afferents to LSO. Electrophysiological recordings in animals, however, reported only minor functional changes in aged LSO. The perplexing discrepancy between anatomical and physiological observations suggests a role for activity-dependent plasticity that would help neurons retain their binaural tuning function despite loss of inhibitory inputs. To explore this hypothesis, we use a computational model of LSO to investigate mechanisms underlying the observed functional robustness against age-related loss of inhibitory inputs. The LSO model is an integrate-and-fire type enhanced with a small amount of low-voltage activated potassium conductance and driven with (in)homogeneous Poissonian inputs. Without synaptic input loss, model spike rates varied smoothly with interaural time and level differences, replicating empirical tuning properties of LSO. By reducing the number of inhibitory afferents to mimic age-related loss of inhibition, overall spike rates increased, which negatively impacted binaural tuning performance, measured as modulation depth and neuronal discriminability. To simulate a recovery process compensating for the loss of inhibitory fibers, the strength of remaining inhibitory inputs was increased. By this modification, effects of inhibition loss on binaural tuning were considerably weakened, leading to an improvement of functional performance. These neuron-level observations were further confirmed by population modeling, in which binaural tuning properties of multiple LSO neurons were varied according to empirical measurements. These results demonstrate the plausibility that homeostatic plasticity could effectively counteract known age-dependent loss of inhibitory fibers in LSO and suggest that behavioral degradation of sound localization might originate from changes occurring more centrally.

Impaired motor cortical facilitatory-inhibitory circuit interaction in Parkinson’s disease

ObjectiveMotor cortical (M1) inhibition and facilitation can be studied with short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF). These circuits are altered in Parkinson’s disease (PD). The sensorimotor measure short latency afferent inhibition (SAI) is possibly altered in PD. The aim was to determine if the manner in which these circuits interact with each other is abnormal in PD. MethodsFifteen PD patients were studied at rest in ON and OFF medication states, and were compared to 16 age-matched controls. A triple-stimulus transcranial magnetic stimulation paradigm was used to elicit a circuit of interest in the presence of another circuit. ResultsSICF was increased in PD OFF and PD ON conditions compared to controls. SICI facilitated SICF in controls and PD ON, but not in PD OFF. SICF in the presence of SICI negatively correlated with UPDRS-III scores in OFF and ON medication conditions. SAI showed similar inhibition of SICI in controls, PD OFF and PD ON conditions. ConclusionsThe facilitatory effect of SICI on SICF is absent in PD OFF, but is restored with dopaminergic medication. SignificanceImpaired interaction between M1 circuits is a pathophysiological feature of PD.

IL-6 signaling pathway contributes to exercise pressor reflex in rats with femoral artery occlusion in association with Kv4 activity in muscle afferent nerves.

Interleukin‐6 (IL‐6) via trans‐signaling pathway plays a role in modifying muscle sensory nerve‐exaggerated exercise pressor reflex in rats with ligated femoral arteries, but the underlying mechanisms are poorly understood. It is known that voltage‐gated potassium channel subfamily member Kv4 channels contribute to the excitabilities of sensory neurons and neuronal signaling transduction. Thus, in this study, we determined that 1) IL‐6 regulates the exaggerated exercise pressor reflex in rats with peripheral artery disease (PAD) induced by femoral artery ligation and 2) Kv4 channels in muscle dorsal root ganglion (DRG) neurons are engaged in the role played by IL‐6 trans‐signaling pathway. We found that the protein levels of IL‐6 and its receptor IL‐6R expression were increased in the DRGs of PAD rats with 3‐day of femoral artery occlusion. Inhibition of muscle afferents’ IL‐6 trans‐signaling pathway (gp130) by intra‐arterial administration of SC144, a gp130 inhibitor, into the hindlimb muscles of PAD rats alleviated blood pressure response to static muscle contraction. On the other hand, we found that 3‐day femoral occlusion decreased amplitude of Kv4 currents in rat muscle DRG neurons. The homo IL‐6/IL‐6Rα fusion protein (H. IL‐6/6Rα), but not IL‐6 alone significantly inhibited Kv4 currents in muscle DRG neurons; and the effect of H. IL‐6/6Rα was largely reverted by SC144. In conclusion, our data suggest that via trans‐signaling pathway upregulated IL‐6 in muscle afferent nerves by ischemic hindlimb muscles inhibits the activity of Kv4 channels and thus likely leads to adjustments of the exercise pressor reflex in PAD.

Evidence of altered interhemispheric communication after pediatric concussion

ABSTRACT OBJECTIVES: To investigate neurophysiological alterations within the typical symptomatic period after concussion (1-month) and throughout recovery (6-months) in adolescents; and (2) to examine relationships between neurophysiological and upper limb kinematic outcomes. METHODS: 18 adolescents with concussion were compared to 17 healthy controls. Transcranial magnetic stimulation (TMS) was used to assess neurophysiological differences between groups including: short- and long-interval intracortical inhibition, intracortical facilitation, short- and long-latency afferent inhibition, afferent facilitation, and transcallosal inhibition (TCI). Behavioral measures of upper limb kinematics were assessed with a robotic device. RESULTS: Mixed model analysis of neurophysiological data identified two key findings. First, participants with concussion demonstrated delayed onset of interhemispheric inhibition, as indexed by TCI, compared to healthy controls. Second, our exploratory analysis indicated that the magnitude of TCI onset delay in adolescents with concussion was related to upper limb kinematics. CONCLUSIONS: Our findings indicate that concussion in adolescence alters interhemispheric communication. We note relationships between neurophysiological and kinematic data, suggesting an affinity for individuals with less concussion-related physiological change to improve their motor behavior over time. These data serve as an important step in future development of assessments (neurobiological and clinical) and interventions for concussion.

Influence of Visual Stimulation-Induced Passive Reproduction of Motor Images in the Brain on Motor Paralysis After Stroke.

Finger flexor spasticity, which is commonly observed among patients with stroke, disrupts finger extension movement, consequently influencing not only upper limb function in daily life but also the outcomes of upper limb therapeutic exercise. Kinesthetic illusion induced by visual stimulation (KINVIS) has been proposed as a potential treatment for spasticity in patients with stroke. However, it remains unclear whether KINVIS intervention alone could improve finger flexor spasticity and finger extension movements without other intervention modalities. Therefore, the current study investigated the effects of a single KINVIS session on finger flexor spasticity, including its underlying neurophysiological mechanisms, and finger extension movements. To this end, 14 patients who experienced their first episode of stroke participated in this study. A computer screen placed over the patient’s forearm displayed a pre-recorded mirror image video of the patient’s non-paretic hand performing flexion–extension movements during KINVIS. The position and size of the artificial hand were adjusted appropriately to create a perception that the artificial hand was the patient’s own. Before and after the 20-min intervention, Modified Ashworth Scale (MAS) scores and active range of finger extension movements of the paretic hand were determined. Accordingly, MAS scores and active metacarpophalangeal joint extension range of motion improved significantly after the intervention. Moreover, additional experimentation was performed using F-waves on eight patients whose spasticity was reduced by KINVIS to determine whether the same intervention also decreased spinal excitability. Our results showed no change in F-wave amplitude and persistence after the intervention. These results demonstrate the potential clinical significance of KINVIS as a novel intervention for improving finger flexor spasticity and extension movements, one of the most significant impairments among patients with stroke. The decrease in finger flexor spasticity following KINVIS may be attributed to neurophysiological changes not detectable by the F-wave, such as changes in presynaptic inhibition of Ia afferents. Further studies are certainly needed to determine the long-term effects of KINVIS on finger spasticity, as well as the neurophysiological mechanisms explaining the reduction in spasticity.

Sexually dimorphic perineuronal nets in the rodent and primate reproductive circuit.

Perineuronal nets are extracellular glycoprotein structures that have been found on some neurons in the central nervous system and that have been shown to regulate their structural plasticity. Until now work on perineuronal nets has been focused on their role in cortical structures where they are selectively expressed on parvalbumin-positive neurons and are reported to restrict the experience-dependent plasticity of inhibitory afferents. Here, we examined the expression of perineuronal nets subcortically, showing that they are expressed in several discrete structures, including nuclei that comprise the brain network controlling reproductive behaviors (e.g., mounting, lordosis, aggression, and social defense). In particular, perineuronal nets were found in the posterior dorsal division of the medial amygdala, the medial preoptic nucleus, the posterior medial bed nucleus of the stria terminalis, the ventrolateral ventromedial hypothalamus and adjacent tuberal nucleus, and the ventral premammillary nucleus in both the mouse and primate brain. Comparison of perineuronal nets in male and female mice revealed a significant sexually dimorphic expression, with expression found prominently on estrogen receptor expressing neurons in the medial amygdala. These findings suggest that perineuronal nets may be involved in regulating neural plasticity in the mammalian reproductive system.