Silent Period Research Articles

‘A game of hare and hounds with one small terrier puffing well in the rear’: working at the birth of British silent cinema music

ABSTRACT The practice and performance of silent cinema music was an ephemeral art form that largely passed into memory with the arrival of the talkies in Britain in 1929. It had existed for two decades with the majority of Britain’s 4,500 cinemas playing up to 60 hours of music each week. As such, it provided employment for tens of thousands of musicians and entertainment for the majority of the population who were cinemagoers. But despite its ubiquity, there are no extant recordings of cinema music performances from this period, and researchers must rely on the traces left by those early practitioners; the sheet and library music that they used and annotated, the voices of the critics who described and debated the merits of cinema music and the autobiographical material of composers like William Alwyn and Louis Levy who forged their careers in cinema music from the silent period. Early instruction manuals hint at key developments in the art and language of film music, and silent cinema musicians performing today offer audiences a strong impression of the experience of live music in cinemas. Some like Neil Brand research and publish on the history of their craft. This article uses these sources to consider the development of silent cinema music in Britain from 1909 to the coming of sound in the early 1930s, focusing on the role of the cinema music director, the music publishing industries and instruction manuals that supported their craft as the language of cinema music developed in tandem with film form and style before passing into history in the rush to embrace the talkies.

Measuring the Contralateral Silent Period Induced by Transcranial Magnetic Stimulation

Measuring the Contralateral Silent Period Induced by Transcranial Magnetic Stimulation

Measuring the Contralateral Silent Period Induced by Transcranial Magnetic Stimulation

Measuring the Contralateral Silent Period Induced by Transcranial Magnetic Stimulation

Primed low frequency repetitive transcranial magnetic stimulation rebalances cortical excitatory-inhibitory circuitry and improves functional outcomes in infantile cerebral palsy patients: A randomized controlled trial

BackgroundMultiple prenatal and postnatal etiologies in cerebral palsy (CP) patients cause neural tissue damage and alterations in cortical neuronal activity and plasticity, leading to motor and cognitive deficits early in life. Repetitive transcranial magnetic stimulation (rTMS) to the lesioned or contralesional hemisphere has been shown to alleviate these functional deficits. However, the underlying mechanisms of the beneficial effects of rTMS via realigning intracortical and interhemispheric circuitry and excitability remain unclear. The present study explored the ability of primed low-frequency rTMS to modulate intracortical excitatory-inhibitory circuitry, interhemispheric and corticospinal integrity, and plasticity in infantile hemiplegic CP. MethodsThe current study was a randomized, placebo-controlled trial with infantile hemiplegic CP patients. The active group received 6 Hz primed low-frequency 1Hz rTMS delivered to the contralesional primary motor cortex for 4 weeks, in 10 sessions. The placebo group received sham stimulation. Both groups also underwent 10 sessions of modified-constraint induced movement therapy (mCIMT). Pre- and post-intervention assessments were conducted using the Quality of Upper Extremity Skills Test to evaluate sensory and motor function, and the Modified Ashworth Scale (MAS) to assess spasticity. Additionally, cortical excitability and plasticity were measured using single- and paired-pulse TMS. ResultsWe found a significant increase in Quality of Upper Extremity Skills Test scores, CP Quality of Life Child (CP QOL-Child) scores, and grip strength, and a decrease in MAS scores in the active rTMS group compared with the sham group. Single- and paired-pulse paradigms revealed a significant decrease in resting and active motor threshold, a reduction in the cortical silent period, and short- and long-interval intracortical inhibition in the intervention group compared with the sham group. ConclusionPrimed low-frequency rTMS in the contralesional hemisphere combined with mCIMT shows potential for modulating motor neuronal excitability, rebalancing intracortical excitatory-inhibitory circuitry, and enhancing functional outcomes in children with infantile hemiparetic CP.

Theta Burst Stimulation Modulates Exercise Performance by Influencing Central Fatigue and Corticospinal Excitability.

Theta-burst stimulation (TBS) over the primary motor cortex modulates activity of the underlying neural tissue, but little is known about its consequence on neuromuscular fatigue (NMF) and its neural correlates. This study aimed to compare the effects of facilitatory versus inhibitory TBS on the NMF and excitability/inhibition of the corticospinal pathway in an unfatigued/fatigued muscle. The effects of three TBS protocols (facilitatory/intermittent: iTBS; inhibitory/continuous: cTBS, and sham: sTBS) were tested on exercise performance, neuromuscular function, corticospinal excitability and inhibition in twenty young healthy participants. Transcranial magnetic and peripheral electrical stimulations were used at baseline, following TBS (unfatigued state), and after a fatiguing sustained contraction (fatigued state) at 35% of the maximal voluntary isometric contraction (MVIC) of the elbow flexors. Time-to-task failure was shorter for cTBS (142±51 s) and longer for iTBS (214±68 s) compared with sTBS (173±65 s) (P < .05). In an unfatigued state, cTBS reduced MVIC and voluntary activation (VA), increased motor-evoked potential (MEP), and silent period (SP) (P < 0.05), while iTBS did not cause any change. In a fatigued state, MVIC and VA decreased in all TBS sessions (P < 0.05). However, the reduction in VA was larger after cTBS (Δ-18±18%) compared with iTBS (Δ-3±5%), and sTBS (Δ-9±9%) (P < 0.001). Furthermore, the increase in MEP and SP were greater for cTBS (P < .05), compared to iTBS and sTBS (P < .05). Facilitatory TBS augments exercise performance that is independent of central parameters and corticospinal mechanisms whilst inhibitory TBS attenuates exercise performance through an exacerbation in the development of central fatigue and possibly intracortical inhibition.

Neurophysiologic inhibitory factors influencing subsequent ankle sprain in collegiate male athletes: a prospective cohort study.

Many athletes with recurrent ankle sprains complain of neurophysiological deficits related to chronic ankle instability (CAI). However, it remains unclear how changes in the corticospinal pathway affect the potential risk of subsequent ankle sprains. The purpose of this study was to investigate whether the corticospinal excitability (input-output properties) and silent period (SP) could be related to the risk of subsequent ankle sprains among athletes. Forty-three male collegiate basketball athletes were enrolled, and 82 ankles were finally sorted into four ankle groups based on symptoms (CAI, sub-CAI, copers, and normal). The neurophysiological data was recorded in both ankles using transcranial magnetic stimulation (TMS) as baseline assessments. Subsequently, we prospectively followed the occurrence of subsequent ankle sprain injuries for 24 months (SG, subsequent ankle sprain group; NSG, non-sprain group). In the baseline assessment, we confirmed that the threshold of the input-output properties in the CAI group was higher than those in the normal group. After the follow-up, 22 ankles sustained subsequent ankle sprains (SGs). We also found that SGs exhibited a significantly longer SP at the middle and high stimulus intensities of TMS compared to NSGs (60 ankles) (middle: p = 0.012, Cohen's d = 0.644, and high: p = 0.020, Cohen's d = 0.590). These findings suggest that a prolonged SP could be a crucial factor affecting subsequent ankle sprains in athletes. To prevent further recurrent sports injuries, neurophysiologic probes, particularly a longer SP, might be a potential assessment tool to return to the field.

Anodal tDCS improves neuromuscular adaptations to short-term resistance training of the knee extensors in healthy individuals.

Experimental studies showed improvement in physical performance following acute application of transcranial direct current stimulation (tDCS). This study examined the neuromuscular and neural response to a single training session (Part 1) and after a 3-week resistance training (Part 2) performed with the knee extensors, preceded by tDCS over the primary motor cortex. Twenty-four participants (age, 30 ± 7 years; stature, 172 ± 8 cm; mass, 72 ± 15 kg) were randomly allocated to perform either resistance training with anodal tDCS (a-tDCS), or by a placebo tDCS (Sham). Resistance training consisted of 3 × 10 isometric contractions of 3 s at 75% MVC. Measures of neuromuscular function (MVC, voluntary activation and potentiated twitch force), corticospinal excitability, and short and long cortical inhibition were assessed. Acute tDCS did not affect neuromuscular and neural responses to a single training session (all ps ≥ 0.10). Conversely, after the 3-week training program, MVC increased in both groups (p < 0.01), with a greater increase observed for a-tDCS vs. Sham (⁓6%, p = 0.04). Additionally, increased voluntary activation (⁓2%, p = 0.04) and corticospinal excitability (⁓22%, p = 0.04), accompanied with shorter silent period (-13%, p = 0.04) was found following a-tDCS vs. Sham. The potentiated twitch force and measures of short and long cortical inhibition did not change after training programme (all ps ≥ 0.29). Pre-training administration of tDCS only resulted in greater neuromuscular adaptations following 3-weeks of resistance training. These results provide new evidence that tDCS facilitates adaptations to resistance training in healthy individuals.

Preoperative nTMS analysis: a sensitive tool to detect imminent motor deficits in brain tumor patients.

One of the challenges in surgery of tumors in motor eloquent areas is the individual risk assessment for postoperative motor disorder. Previously a regression model was developed that permits estimation of the risk prior to surgery based on topographical and neurophysiological data derived from investigation with nTMS (navigated Transcranial Magnetic Stimulation). This study aims to analyze the impact of including additional neurophysiological TMS parameters into the established risk stratification model for motor outcome after brain tumor surgery. Biometric and clinical data of 170 patients with glioma in motor eloquent areas were collected prospectively. In addition, the following nTMS parameters were collected bihemispherically prior to surgery: resting motor threshold (RMT), recruitment curve (RC), cortical silent period (CSP) and a nTMS based fibertracking to measure the tumor tract distance (TTD). Motor function was quantified by Medical Research Council Scale (MRCS) preoperatively, seven days and three months postoperatively. Association between nTMS parameters and postoperative motor outcome was investigated in bivariate and multivariable analyses. The bivariate analysis confirmed the association of RMT ratio with the postoperative motor outcome after seven days with higher rates of worsening in patients with RMT ratio > 1.1 compared to patients with RMT ratio ≤ 1.1 (31.6% vs. 15.1%, p = 0.009). Similarly, an association between a pathological CSP ratio and a higher risk of new postoperative motor deficits after seven days was observed (35.3% vs. 16.7% worsening, p = 0.025). A pathological RC Ratio was associated postoperative deterioration of motor function after three months (42.9% vs. 16.2% worsening, p = 0.004). In multiple regression analysis, none of these associations were statistically robust. The current results suggest that the RC ratio, CSP ratio and RMT ratio individually are sensitive markers associated with the motor outcome 7days and 3months after tumor resection in a presumed motor eloquent location. They can therefore supply valuable information during preoperative risk-benefit-balancing. However, underlying neurophysiological mechanisms might be too similar to make the parameters meaningful in a combined model.

Examining motor evidence for the pause-then-cancel model of action-stopping: insights from motor system physiology.

Stopping initiated actions is fundamental to adaptive behavior. Longstanding, single-process accounts of action-stopping have been challenged by recent, two-process, "pause-then-cancel" models. These models propose that action-stopping involves two inhibitory processes: 1) a fast Pause process, which broadly suppresses the motor system as the result of detecting any salient event, and 2) a slower Cancel process, which involves motor suppression specific to the cancelled action. A purported signature of the Pause process is global suppression, or the reduced corticospinal excitability (CSE) of task-unrelated effectors early on in action-stopping. However, unlike the Pause process, few (if any) motor system signatures of a Cancel process have been identified. Here, we used single- and paired-pulse transcranial magnetic stimulation (TMS) methods to comprehensively measure the local physiological excitation and inhibition of both responding and task-unrelated motor effector systems during action-stopping. Specifically, we measured CSE, short-interval intracortical inhibition (SICI), and the duration of the cortical silent period (CSP). Consistent with key predictions from the pause-then-cancel model, CSE measurements at the responding effector indicated that additional suppression was necessary to counteract Go-related increases in CSE during action-stopping, particularly at later timepoints. Increases in SICI on Stop-signal trials did not differ across task-related and task-unrelated effectors, or across timepoints. This suggests SICI as a potential source of global suppression. Increases in CSP duration on Stop-signal trials were more prominent at later timepoints and were related to individual differences in CSE. Our study provides further evidence from motor system physiology that multiple inhibitory processes influence action-stopping.NEW & NOTEWORTHY Current debate surrounds whether single- or dual-process models better account for human action-stopping ability. We show that motor suppression of a successfully stopped muscle follows a distinct time course compared with when that same muscle is unrelated to the stopping task. Our results further suggest that distinct local inhibitory neuron populations contribute to these unique sources of suppression. Our study provides evidence from motor system physiology that multiple inhibitory processes influence action-stopping.

Modulated Alpha Power as a Predictor of Tinnitus Alleviation.

Pain associated with subjective tinnitus is known to be alleviated by treatments using a repetitive transcranial magnetic stimulation (rTMS). However, the mechanisms underneath are still on debate. We investigated the mechanism of tinnitus alleviation using time-frequency analyses. Twenty-four patients were randomly assigned to the dual-site stimulation group (temporal and frontal stimulation, TF), singlesite stimulation group (temporal stimulation, T), or sham stimulation group. An age-matched control group was also included (n = 12). Electroencephalography (EEG) was recorded and patient data were analyzed before and after treatment. A frontal increase in EEG power was observed in the alpha (8-12 Hz) frequency band domain after treatment; this increase was most pronounced in the TF group, followed by the T group. The TF and T groups showed increased alpha power in the fronto-central channels only in the silent period between paired-pulse tones. The TF and T groups showed decreases in alpha power in the temporal region, particularly in the neural response to the first of the paired-pulse tones. The difference in tinnitus handicap index between pre- and post-treatment was positively correlated with the alpha power of the silent period in the frontal and fronto-central channels. Dual-site stimulation showed the greatest alleviation of tinnitus-related discomfort, followed by single-site stimulation. Additionally, the modulation of alpha power was prominent in the active stimulation groups. Low frequency rTMS can alleviate tinnitus by increasing alpha band power and reducing hyperactivity.

Neuromuscular characteristics of eccentric, concentric and isometric contractions of the knee extensors.

We compared voluntary drive and corticospinal responses during eccentric (ECC), isometric (ISOM) and concentric (CON) muscle contractions to shed light on neurophysiological mechanisms underpinning the lower voluntary drive in a greater force production in ECC than other contractions. Sixteen participants (20-33 years) performed ISOM and isokinetic (30°/s) CON and ECC knee extensor contractions (110°-40° knee flexion) in which electromyographic activity (EMG) was recorded from vastus lateralis. Voluntary activation (VA) was measured during ISOM, CON and ECC maximal voluntary contractions (MVCs). Transcranial magnetic stimulation elicited motor-evoked potentials (MEPs) and corticospinal silent periods (CSP) during MVCs and submaximal (30%) contractions, and short-interval intracortical inhibition (SICI) in submaximal contractions. MVC torque was greater (P < 0.01) during ECC (302.6 ± 90.0 Nm) than ISOM (269.8 ± 81.5 Nm) and CON (235.4 ± 78.6 Nm), but VA was lower (P < 0.01) for ECC (68.4 ± 14.9%) than ISOM (78.3 ± 13.1%) and CON (80.7 ± 15.4%). In addition, EMG/torque was lower (P < 0.02) for ECC (1.9 ± 1.1μV.Nm-1) than ISOM (2.2 ± 1.2μV.Nm-1) and CON (2.7 ± 1.6μV.Nm-1), CSP was shorter (p < 0.04) for ECC (0.097 ± 0.03s) than ISOM (0.109 ± 0.02s) and CON (0.109 ± 0.03s), and MEP amplitude was lower (P < 0.01) for ECC (3.46 ± 1.67mV) than ISOM (4.21 ± 2.33mV) and CON (4.01 ± 2.06mV). Similar results were found for EMG/torque and CSP during 30% contractions, but MEP and SICI showed no differences among contractions (p > 0.05). The lower voluntary drive indicated by reduced VA during ECC may be partly explained by lower corticospinal excitability, while the shorter CSP may reflect extra muscle spindle excitation of the motoneurons from vastus lateralis muscle lengthening.

Loss of the ipsilateral silent period in amyotrophic lateral sclerosis is associated with reduced white matter integrity in the motor section of the corpus callosum

ObjectiveInterhemispheric neurons in the motor section of the corpus callosum have an inhibitory effect on neurons of the contralateral motor cortex. Three quarters of patients with amyotrophic laterals sclerosis (ALS) show impaired transcallosal inhibition. We aimed to investigate whether structural changes co-occur with this functional impairment and to explore its phenotypic correlates. MethodsThe demographic, clinical, and neuropsychological data of 127 ALS patients were analysed. Transcallosal inhibition was assessed with an ipsilateral silent period (iSP) protocol using transcranial magnetic stimulation. Patients were categorised based on an iSP response or its loss, and the groups were characterised by demographic, clinical, and neuropsychological variables. Diffusion-weighted images from a subset of 63 patients were analysed using tractography, and white matter (WM) structural integrity metrics were compared across groups. Results54 % of patients displayed iSP loss. The average free-water-corrected fractional anisotropy values within the callosal tract between the primary motor cortices were lower for patients with iSP loss compared to patients with an iSP response. There were no group differences based on other diffusivity metrics. The groups did not differ regarding any of the demographic, clinical, or neuropsychological variables. InterpretationWe found reduced WM integrity in the motor section of the corpus callosum that differentiated ALS patients with iSP loss from patients with an iSP response, but with a small effect size. Nevertheless, the underlying pathological substrate and potential genetic drivers for these structural and functional changes in a subset of ALS patients remain to be satisfactorily investigated.

The effects of exercise, heat-induced hypo-hydration and rehydration on blood-brain-barrier permeability, corticospinal and peripheral excitability.

The effects of low-intensity exercise, heat-induced hypo-hydration and rehydration on maximal strength and the underlying neurophysiological mechanisms are not well understood. To assess this, 12 participants took part in a randomised crossover study, in a prolonged (3h) submaximal (60W) cycling protocol under 3 conditions: (i) in 45°C (achieving ~ 5% body mass reduction), with post-exercise rehydration in 2h (RHY2), (ii) with rehydration across 24h (RHY24), and (iii) a euhydrated trial in 25°C (CON). Dependent variables included maximal voluntary contractions (MVC), maximum motor unit potential (MMAX), motor evoked potential (MEPRAW) amplitude and cortical silent period (cSP) duration. Blood-brain-barrier integrity was also assessed by serum Ubiquitin Carboxyl-terminal Hydrolase (UCH-L1) concentrations. All measures were obtained immediately pre, post, post 2h and 24h. During both dehydration trials, MVC (RHY2: p < 0.001, RHY24: p = 0.001) and MEPRAW (RHY2: p = 0.025, RHY24: p = 0.045) decreased from pre- to post-exercise. MEPRAW returned to baseline during RHY2 and CON, but not RHY24 (p = 0.020). MEP/MMAX ratio decreased across time for all trials (p = 0.009) and returned to baseline, except RHY24 (p < 0.026). Increased cSP (p = 0.011) was observed during CON post-exercise, but not during RHY2 and RHY24. Serum UCH-L1 increased across time for all conditions (p < 0.001) but was not significantly different between conditions. Our findings demonstrate an increase in corticospinal inhibition after exercise with fluid ingestion, but a decrease in corticospinal excitability after heat-induced hypo-hydration. In addition, low-intensity exercise increases peripheral markers of blood-brain-barrier permeability.Kindly check and confirm inserted city name correctly identified in affiliation 7This is correct.

The value of concomitant testing of cutaneous silent period with sympathetic skin response and heart rate variability in Type-2 diabetes patients: An electrophysiological study.

To explore the association among cutaneous silent period, sympathetic skin response and heart rate variability in diabetes patients. The case-control study was conducted at the Department of Physiology, College of Medicine, Al- Mustansiriyah University, Baghdad, Iraq, from November 1, 2020, to May 20, 2021, and comprised 24 healthy controls in Group I and 49 patients of type 2 diabetes in Group II who were recruited from the neuroelectrophysiological unit of Al-Imamain Al-Kadhmean Teaching Hospital, Baghdad, Iraq. Both groups were subjected to cutaneous silent period, sympathetic skin response and heart rate variability testing. Data was analysed using SPSS 24. Of the 73 subjects, 24(32.9%) were in Group I and 49(67.1%) were in Group II. Cutaneous silent period mean latency values were significantly increased in Group II compared to Group I (p<0.05), and a negative sympathetic skin response in the right lower limb was significantly different between the groups (p<0.001). There was no significant correlation between Cutaneous silent period and sympathetic skin response values (p>0.05). Heart rate variability was significantly increased in diabetic patients with negative sympathetic skin response compared to those with positive sympathetic skin response (p<0.05). Simultaneous measurement of cutaneous silent period, sympathetic skin response and heart rate variability should be done as there were no strong correlation among the tests in diabetic patients.

Early Electrophysiology in Suspected Acute Guillain-Barré Syndrome: A Prospective Study of Comprehensive Testing.

Electrophysiologic changes in early Guillain-Barré Syndrome (GBS) can be nondiagnostic. Improved testing paradigms may improve hyperacute treatment. This work prospectively evaluated consecutive patients admitted to a metropolitan teaching hospital in Melbourne, Australia, with suspected acute GBS. We performed extensive neurophysiology at three different time points. Novel tests, including cutaneous silent periods, long latency reflexes, and contraction-induced H reflexes, were assessed. Twenty-three participants were studied, including 13 cases of acute GBS. In total, 69% of acute cases of GBS were accurately diagnosed on the first nerve conduction study using published neurophysiologic criteria, with serial studies rarely altering the GBS subtype classification. Antidromic and orthodromic upper limb sensory studies were diagnostically equivalent. A sural sparing pattern was seen in 77% of cases of GBS at the first test. Long latency reflexes and contraction-induced H reflexes testing were abnormal in most participants but were limited by muscle weakness in some. Cutaneous silent periods testing was unobtainable in approximately 50% of cases because of weakness and did not discriminate from mimic disorders. Abnormalities of long latency reflexes and contraction-induced H reflexes may be helpful where initial electrophysiology is nondiagnostic but are nonspecific. Cutaneous silent periods testing seems of limited value. Comprehensive testing provides diagnostic certainty in most cases of GBS from the very first study.

Deep autoencoder with gated convolutional neural networks for improving speech quality in secured communications

In this study, we introduce a speech enhancement method to improve the quality of decrypted speech signals from hand-talk devices, which are highly susceptible to security attacks. Ensuring high-quality decrypted speech is essential because traditional speech enhancement methods struggle with artifacts only present during speech due to the encryption process applied selectively. This situation limits the effectiveness of traditional methods, which assume distortion is constant and can be estimated during silent periods. Our solution involves a deep-learning approach that employs a gated convolutional neural network (GCNN). Unlike typical convolutional neural networks (CNNs) that excel in processing spatial data but falter with temporal changes, our GCNN integrates a gating mechanism to enhance handling of temporal dynamics in speech data. This method directly maps distorted speech to its clean counterpart, bypassing the need for explicit noise estimation. Our experiments indicate that this deep-learning method significantly outperforms traditional speech enhancement techniques and conventional CNNs in several key evaluation metrics, offering a promising advancement in decrypted speech quality enhancement.

Mirror movements in multiple sclerosis -a clinical, electrophysiological, and imaging study

BackgroundMirror movements (MM) are commonly caused by a defect of interhemispheric pathways also affected in multiple sclerosis (MS), particularly the corpus callosum. We investigated the prevalence of MM in MS in relation to functional and morphological callosal fiber integrity by transcranial magnetic stimulation (TMS), magnetic resonance imaging (MRI), as well as fatigue.MethodsIn 21 patients with relapsing–remitting MS and 19 healthy controls, MM were assessed and graded (Woods and Teuber scale: MM 1—4) using a bedside test. Fatigue was evaluated using the Fatigue Scale for Motor and Cognitive Functions (FSMC) questionnaire. TMS measured ipsilateral silent period latency and duration. MRI assessed callosal atrophy by measuring the normalized corpus callosum area (nCCA), corpus callosum index (CCI), and lesion volume.ResultsMS patients had significantly more often and pronounced MM compared to healthy controls (p = 0.0002) and nCCA was significantly lower (p = 0.045) in MRI studies. Patients with higher MM scores (MM > 1 vs. MM 0/1) showed significantly more fatigue (higher FSMC sum score, p = 0.04, motor score, p = 0.01). In TMS and MRI studies, no significant differences were found between patients with MM 0/1 and those with MM > 1 (ipsilateral silent period measurements, CCA, CCI and lesion volume).ConclusionsMM are common in MS and can easily be detected through bedside testing. As MM are associated with fatigue, they might indicate fatigue in MS. It is possible that other cerebral structures, in addition to the corpus callosum, may contribute to the origin of MM in MS.

People with hip osteoarthritis have reduced quadriceps voluntary activation and altered motor cortex function

AimsCompare quadriceps voluntary activation, corticospinal and intracortical excitability between people with and without hip osteoarthritis (OA). Exploratory objectives include quantifying the association of corticospinal/intracortical excitability with voluntary activation, corticospinal/intracortical excitability with hip related pain, and motor threshold with motor cortex inhibition and facilitation. MethodsCase-control study including participants with clinically and radiologically confirmed hip OA and non-OA controls. Quadriceps voluntary activation was assessed using twitch interpolation via femoral nerve stimulation. Single- and paired-pulse transcranial magnetic stimulation over the motor cortex assessed resting motor threshold (RMT), active motor threshold (AMT), short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and silent period. Generalized linear models assessed outcomes (p ​< ​0.05). ResultsWe included 17 hip OA (76% female) and 24 controls (92% female) with a mean (standard deviation) age of 58.7 (7.9) years. Compared to controls, people with hip OA had reduced quadriceps voluntary activation (β ​= ​-5.29, 95% confidence intervals [CI], -0.79–-9.79) and increased ICF (β ​= ​0.22, 95%CI, 0.01–0.43). People with hip OA did not differ from controls in RMT (β ​= ​−4.76, 95%CI, −14.08–4.56), AMT (β ​= ​−2.13, 95%CI, −7.12-2.86), SICI (β ​= ​−0.02, 95%CI, −0.15-0.006) or silent period (β= 8.72, 95%CI, −24.75–42.20). More facilitation was associated with increased hip pain (β= 24.55, 95%CI, 6.93–42.18), and more inhibition was associated with less voluntary activation (β= 10.50, 95%CI, 2.00–18.99). ConclusionPeople with hip OA demonstrate reduced quadriceps voluntary activation and complex changes in motor cortex excitability compared to controls. These findings suggest that hip OA can alter quadriceps neuromuscular function (facilitation associated with pain, inhibition associated with activation), thus having implications for rehabilitation.

Neurophysiological effects of a combined treatment of lovastatin and minocycline in patients with fragile X syndrome: Ancillary results of the LOVAMIX randomized clinical trial.

Fragile X syndrome (FXS) is the primary hereditary cause of intellectual disability and autism spectrum disorder. It is characterized by exacerbated neuronal excitability, and its correction is considered an objective measure of treatment response in animal models, a marker albeit rarely used in clinical trials. Here, we used an extensive transcranial magnetic stimulation (TMS) battery to assess the neurophysiological effects of a therapy combining two disease-modifying drugs, lovastatin (40 mg) and minocycline (100 mg), administered alone for 8 weeks and in combination for 12 weeks, in 19 patients (mean age of 23.58 ± 1.51) with FXS taking part in the LOVAmix trial. The TMS battery, which included the resting motor threshold, short-interval intracortical inhibition, long-interval intracortical inhibition, corticospinal silent period, and intracortical facilitation, was completed at baseline after 8 weeks of monotherapy (visit 2 of the clinical trial) and after 12 weeks of dual therapy (visit 4 of the clinical trial). Repeated measure ANOVAs were performed between baseline and visit 2 (monotherapy) and visit 3 (dual therapy) with interactions for which monotherapy the participants received when they began the clinical trial. Results showed that dual therapy was associated with reduced cortical excitability after 20 weeks. This was reflected by a significant increase in the resting-motor threshold after dual therapy compared to baseline. There was a tendency for enhanced short-intracortical inhibition, a marker of GABAa-mediated inhibition after 8 weeks of monotherapy compared to baseline. Together, these results suggest that a combined therapy of minocycline and lovastatin might act on the core neurophysiopathology of FXS. This trial was registered at clinicaltrials.gov (NCT02680379).

Central and peripheral neuromuscular fatigue following ramp and rapid maximal voluntary isometric contractions.

Maximal voluntary isometric contractions (MVICs) as a fatiguing modality have been widely studied, but little attention has been given to the influence of the rate of torque development. Given the established differences in motor command and neuromuscular activation between ramp and rapid MIVCs, it is likely performance fatigue differs as well as the underlying physiological mechanisms. To compare responses for rapid and maximal torque following ramp and rapid MVICs, and the corresponding neuromuscular and corticospinal alterations. On separate visits, twelve healthy males (22.8 ± 2.5years) performed fatiguing intermittent MVICs of the knee extensors with either 2s (RAMP) or explosive (RAPID) ramp-ups until a 50% reduction in peak torque was achieved. Before and after each condition, maximal and rapid torque measures were determined from an MVIC. Additionally, peripheral (twitch parameters) and central (voluntary activation) fatigue, as well as rapid muscle activation, and cortical-evoked twitch and electromyographic responses were recorded. Maximal and late-phase rapid torque measures (p ≤ 0.001; = 0.635-0.904) were reduced similarly, but early rapid torque capacity (0-50ms) (p = 0.003; d = 1.11 vs. p = 0.054; d = 0.62) and rapid muscle activation (p = 0.008; d = 1.07 vs. p = 0.875; d = 0.06) decreased more after RAMP. Changes in peripheral fatigue, as indicated by singlet and doublet contractile parameters (p < 0.001 for all; = 0.752-0.859), and nerve-evoked voluntary activation (p < 0.001; 0.660) were similar between conditions. Corticospinal inhibition (via silent period) was only increased after RAPID (p = 0.007; d = 0.94 vs. p = 0.753; d = 0.09), whereas corticospinal voluntary activation and excitability were unchanged. Ramp, fatiguing MVICs impaired early rapid torque capacity more than rapid MVICs, and this was accompanied by decrements in rapid muscle activation. Responses for peripheral and central fatigue (nerve and cortical stimulation) were largely similar between conditions, except that rapid MVICs increased corticospinal inhibition.