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Introduction: Patients with chronic headaches and chronic oro-facial pain commonly present psychosocial issues that can affect social interactions. A possible reason could be that patients with these disorders might present impairments in facial recognition, laterality judgement and also alexithymia. However, a systematic review summarizing the effects of facial emotion recognition, laterality judgement and alexithymia in individuals with headaches and oro-facial pain is still not available., Aim: The main objective of this systematic review (SR) and meta-analysis (MA) was to compile and synthesize the evidence on the occurrence of alexithymia, deficits in laterality or left-right (LR) recognition and/or facial emotion recognition (FER) in patients with chronic headache and facial pain., Methods: Electronic searches were conducted in five databases (up to September 2023) and a manual search to identify relevant studies. The outcomes of interest were alexithymia scores, speed and accuracy in LR and/or FER, or any other quantitative data assessing body image distortions. The screening process, data extraction, risk of bias and data analysis were performed by two independent assessors following standards for systematic reviews., Results: From 1395 manuscripts found, only 34 studies met the criteria. The overall quality/certainty of the evidence was very low. Although the results should be interpreted carefully, individuals with chronic headaches showed significantly higher levels of alexithymia when compared to healthy individuals. No conclusive results were found for the other variables of interest., Conclusion: Although the overall evidence from this review is very low, people with chronic primary headaches and oro-facial pain could be regularly screened for alexithymia to guarantee appropriate management., (© 2024 John Wiley & Sons Ltd.)

The cerebellum is traditionally considered a movement control structure because of its established afferent and efferent anatomical and functional connections with the motor cortex. In the last decade, studies also proposed its involvement in perception, particularly somatosensory acquisition and prediction of the sensory consequences of movement. However, compared to its role in motor control, the cerebellum's specific role or modulatory influence on other brain areas involved in sensory perception, specifically the primary sensorimotor cortex, is less clear. In the present study, we explored whether peripherally applied vibrotactile stimuli at flutter frequency affect functional cerebello-cortical connections. In 17 healthy volunteers, changes in cerebellar brain inhibition (CBI) and vibration perception threshold (VPT) were measured before and after a 20-min right hand mechanical stimulation at 25 Hz. 5 Hz mechanical stimulation of the right foot served as an active control condition. Performance in a Grooved Pegboard test (GPT) was also measured to assess stimulation's impact on motor performance. Hand stimulation caused a reduction in CBI (13.16%) and increased VPT but had no specific effect on GPT performance, while foot stimulation had no significant effect on all measures. The result added evidence to the functional connections between the cerebellum and primary motor cortex, as shown by CBI reduction. Meanwhile, the parallel increase in VPT indirectly suggests that the cerebellum influences the processing of vibrotactile stimulus through motor-sensory interactions., (© 2022. The Author(s).)

Introduction: Rhino-orbito-cerebral mucormycosis has been reported as a sequela after coronavirus disease in immunocompromised patients with poorly controlled diabetes mellitus. Most cases have been identified in India, with only 19 reported elsewhere., Methodology: We herein report the results of clinical, imaging, microbiological, and histopathological studies in an immunocompetent 67-year-old male with rhino-orbital infection by Finegoldia magna and Mucorales molds following severe SARS-CoV-2 disease associated with new-onset decompensated diabetes mellitus., Results: Microbiological and histological studies confirmed the presence of both Mucorales molds and Finegoldia magna, which was successfully treated with antibiotics and a specific anti-fungal agent (Posaconazole)., Conclusions: Careful multidisciplinary follow-up of patients treated for severe SARS-CoV-2 disease is necessary for the timely diagnosis of complications such as uncontrolled diabetes mellitus and opportunistic infections., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Rozaliya Hristova, Alexandrina Vlahova, Maria Christova, Konstantin Stamatov, Pavel Stanimirov.)

Corticospinal excitability is known to be affected by afferent inflow arising from the proprioceptors during active or passive muscle movements. Also during static stretching (SS) afferent activity is enhanced, but its effect on corticospinal excitability received limited attention and has only been investigated as a single average value spread over the entire stretching period. Using transcranial magnetic stimulation (TMS) the present study was conducted to explore the time course of corticospinal excitability during 30 seconds SS. Motor evoked potentials (MEPs) after TMS were recorded from soleus (SOL) and tibialis anterior (TA) muscles in 14 participants during: a passive dynamic ankle dorsiflexion (DF), at six different time points during maximal individual SS (3, 6, 9, 18, 21 and 25 seconds into stretching), during a passive dynamic ankle plantar flexion (PF) and following SS. To explore the time course of corticospinal excitability during the static lengthened phase of a muscle stretch, the stretching protocol was repeated several times so that it was possible to collect a sufficient number of stimulations at each specific time point into SS, as well as during DF and PF. During passive DF, MEPs amplitude was greater than baseline in both TA and SOL (p = .001 and p = .005 respectively). During SS, MEPs amplitude was greater than baseline in TA (p = .006), but not in SOL. No differences between the investigated time points were found and no trend was detected throughout the stretching time. No effect in either muscle was observed during passive PF and after SS. These results could suggest that an increased activity of secondary afferents from SOL muscle spindles exert a corticomotor facilitation on TA. The muscle-nonspecific response observed during passive DF could instead be attributed to an increased activation within the sensorimotor cortical areas as a result of the awareness of the foot passive displacements., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Budini, Christova. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The early diagnosis of cognitive impairments is an important step in the adequate management of dementia. The project "Smart Cognition & Behaviour Screening powered by Augmented Reality" (SCOBES-AR) aims to develop a multimodal screening tool (MST) for the early detection of cognitive impairments using augmented and virtual reality. The first project phase selected validated assessments for combination with the MST and tested it in 300 healthy older adults., Objective: This study established a protocol for the implementation and usability of a mixed reality (MR)-enhanced multidisciplinary screening tool for the early detection of cognitive impairments in older adults. The developed MST will be partially enhanced by MR, which is a combination of augmented reality (AR) and virtual reality (VR). This MR-enhanced prototype of the screening tool (MR-MST) will be tested and compared to the previously developed MST. The usability of the prototype will also be examined., Methods: This single-center observational crossover design study screens 100 healthy participants (aged 60-75 years) for cognitive decline using a specially developed MST (assessment of cognitive functions, olfactory sensitivity, nutritional preferences, gait parameters, reaction times, and activities of daily living) and an MR-enhanced MST in which the assessments of cognitive functions, reaction time, activities of daily living, and gait will be performed using tailor-made software and AR and VR hardware. The results of the MR-enhanced MST will be compared to those without MR. The usability of the developed MR-enhanced MST will be tested on 10 investigators and 10 test participants using observed summative evaluation and the codiscovery method, and on 2 usability experts using the codiscovery and cognitive walkthrough methods., Results: This study was funded by the Austrian Research Promotion Agency (grant 866873) and received approval from the ethics committee of the Medical University of Graz. The MR-MST and the experimental protocol for this study were developed. All participants gave written informed consent. As of July 15, 2022, a total of 70 participants have been screened. Data analysis and dissemination are scheduled for completion by September 2023., Conclusions: The development and testing of the MR-MST is an important step toward the establishment of the best practice procedure for the implementation of AR and VR in the screening of cognitive declines in older adults. It will help improve our knowledge of the usability and applicability of the developed prototype and promote further advancement in AR and VR technologies to be used in therapeutic settings., International Registered Report Identifier (irrid): DERR1-10.2196/39513., (©Monica Christova, Robert Strohmaier, Bianca Fuchs-Neuhold, Bernhard Guggenberger, Brigitte Loder-Fink, Theresa Draxler, Christoph Palli, Helmut Simi, Sandra Schadenbauer, Alexander Nischelwitzer, Gerhard Sprung, René Pilz, Robert Darkow, Wolfgang Staubmann. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 14.10.2022.)

We often fail to recall another person's name. Proper names might be more difficult to memorize and retrieve than other pieces of knowledge, such as one's profession because they are processed differently in the brain. Neuroimaging and neuropsychological studies associate the bilateral anterior temporal lobes (ATL) in the retrieval of proper names and other person-related knowledge. Specifically, recalling a person's name is thought to be supported by the left ATL, whereas recalling specific information such as a person's occupation is suggested to be subserved by the right ATL. To clarify and further explore the causal relationship between both ATLs and proper name retrieval, we stimulated these regions with anodal, cathodal and sham transcranial direct current stimulation (tDCS) while the participants memorized surnames (e.g., Mr. Baker) and professions (e.g., baker) presented with a person's face. The participants were then later asked to recall the surname and the profession. Left ATL anodal stimulation resulted in higher intrusion errors for surnames than sham, whereas right ATL anodal stimulation resulted in higher overall intrusion errors, both, surnames and professions, compared to cathodal stimulation. Cathodal stimulation of the left and right ATL had no significant effect on surname and profession recall. The results indicate that the left ATL plays a role in recalling proper names. On the other hand, the specific role of the right ATL remaines to be explored., (© 2022. The Author(s).)

It is often suggested that stretching-related changes in performance can be partially attributed to stretching-induced neural alterations. Recent evidence though shows that neither spinal nor cortico-spinal excitability are susceptible of a long-lasting effect and only the amplitude of stretch or tap reflex (TR) is reduced up to several minutes. Since afferents from muscle spindles contribute to voluntary muscle contractions, muscle stretching could be detrimental to muscle performance. However, the inhibition of muscle spindle sensitivity should be reversed as soon as the stretched muscle contracts again, due to α-γ co-activation. The present work evaluated which type of muscle contraction (static or dynamic) promotes the best recovery from the inhibition in spindle sensitivity following static stretching. Fifteen students were tested for TR at baseline and after 30 s maximal individual static stretching of the ankle plantar flexors followed by one of three randomized interventions (isometric plantar flexor MVC, three counter movement jumps, and no contraction/control). Ten TRs before and 20 after the procedures were induced with intervals of 30 s up to 10 min after static stretching. The size of the evoked TRs (peak to peak amplitude of the EMG signal) following stretching without a subsequent contraction (control) was on average reduced by 20% throughout the 10 min following the intervention and did not show a recovery trend. Significant decrease in relation to baseline were observed at 9 of the 20 time points measured. After MVC of plantar flexors, TR recovered immediately showing no differences with baseline at none of the investigated time points. Following three counter movement jumps it was observed a significant 34.4% group average inhibition ( p < 0.0001) at the first time point. This effect persisted for most of the participants for the next measurement (60 s after intervention) with an average reduction of 23.4% ( p = 0.008). At the third measurement, 90 s after the procedure, the reflexes were on average still 21.4% smaller than baseline, although significant level was not reached ( p = 0.053). From 120 s following the intervention, the reflex was fully recovered. This study suggests that not every type of muscle contraction promotes a prompt recovery of a stretch-induced inhibition of muscle spindle sensitivity., (Copyright © 2020 Budini, Rafolt, Christova, Gallasch and Tilp.)

The triple-code model (TCM) of number processing suggests the involvement of distinct parietal cortex areas in arithmetic operations: the bilateral horizontal segment of the intraparietal sulcus (hIPS) for arithmetic operations that require the manipulation of numerical quantities (e.g., subtraction) and the left angular gyrus (AG) for arithmetic operations that require the retrieval of answers from long-term memory (e.g., multiplication). Although neuropsychological, neuroimaging, and brain stimulation studies suggest the dissociation of these operations into distinct parietal cortex areas, the role of strategy (online calculation vs. retrieval) is not yet fully established. In the present study, we further explored the causal involvement of the left AG for multiplication and left hIPS for subtraction using a neuronavigated repetitive transcranial magnetic stimulation (rTMS) paradigm. Stimulation sites were determined based on an fMRI experiment using the same tasks. To account for the effect of strategy, participants were asked whether they used retrieval or calculation for each individual problem. We predicted that the stimulation of the left AG would selectively disrupt the retrieval of the solution to multiplication problems. On the other hand, stimulation of the left hIPS should selectively disrupt subtraction. Our results revealed that left AG stimulation was detrimental to the retrieval and online calculation of solutions for multiplication problems, as well as, the retrieval (but not online calculation) of the solutions to subtraction problems. In contrast, left hIPS stimulation had no detrimental effect on both operations regardless of strategy., (Copyright © 2020 Fresnoza, Christova, Purgstaller, Jehna, Zaar, Hoffermann, Mahdy Ali, Körner, Gallasch, von Campe and Ischebeck.)

Transcranial alternating current stimulation (tACS) is the application of subthreshold, sinusoidal current to modulate ongoing brain rhythms related to sensory, motor and cognitive processes. Electrophysiological studies suggested that the effect of tACS applied at an alpha frequency (8-12 Hz) was state-dependent. The effects of tACS, that is, an increase in parieto-occipital electroencephalography (EEG) alpha power and magnetoencephalography (MEG) phase coherence, was only observed when the eyes were open (low alpha power) and not when the eyes were closed (high alpha power). This state-dependency of the effects of alpha tACS might extend to the aging brain characterized by general slowing and decrease in spectral power of the alpha rhythm. We additionally hypothesized that tACS will influence the motor cortex, which is involved in motor skill learning and consolidation. A group of young and old healthy adults performed a serial reaction time task (SRTT) with their right hand before and after the tACS stimulation. Each participant underwent three sessions of stimulation: sham, stimulation applied at the individual participant's alpha peak frequency or individual alpha peak frequency (iAPF; α-tACS) and stimulation with iAPF plus 2 Hz (α2-tACS) to the left motor cortex for 10 min (1.5 mA). We measured the effect of stimulation on general motor skill (GMS) and sequence-specific skill (SS) consolidation. We found that α-tACS and α2-tACS improved GMS and SS consolidation in the old group. In contrast, α-tACS minimally improved GMS consolidation but impaired SS consolidation in the young group. On the other hand, α2-tACS was detrimental to the consolidation of both skills in the young group. Our results suggest that individuals with aberrant alpha rhythm such as the elderly could benefit more from tACS stimulation, whereas for young healthy individuals with intact alpha rhythm the stimulation could be detrimental., (Copyright © 2020 Fresnoza, Christova, Bieler, Körner, Zimmer, Gallasch and Ischebeck.)

Objective: We aimed at assessing the usefulness of motor evoked potentials (MEPs) for exploring the integrity of striated sphincters and pelvic floor motor innervation in normal subjects and of repetitive transcranial magnetic stimulation TMS (rTMS) in patients with neurogenic bladder dysfunction., Methods: A systematic literature search was conducted using PubMed and Embase., Results: We identified, reviewed and discussed 11 articles matching the inclusion criteria., Conclusions: The assessment of MEPs could represent a useful tool in the investigation of patients with urologic disorders. High frequency rTMS can improve detrusor contraction and/or urethral sphincter relaxation in patients with multiple sclerosis and bladder dysfunction. Low frequency (LF) rTMS seems to be an effective treatment of neurogenic lower urinary tract dysfunctions in subjects with Parkinson's disease and possibly other neurodegenerative disorders. Furthermore, rTMS might have the potential to restore bladder and bowel sphincter function after incomplete spinal cord injury. LF rTMS could also relieve some symptoms of bladder pain syndrome and chronic pelvic pain., Significance: The clinical applicability of MEPs appears to be questionable, since a poor reproducibility was detected for all pelvic floor muscles. The use of rTMS in this field is emerging and the results of a few preliminary studies should be replicated in controlled, randomized studies with larger sample sizes., (Copyright © 2019 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Several studies have applied transcranial magnetic stimulation (TMS) in the attempt to further explore the pathophysiological mechanisms of phantom-limb pain (PLP) and non-painful phantom sensations (PS). We performed a systematic review of available evidence of this emerging technology in this indication. We identified studies which report a reduced intracortical inhibition and increased intracortical facilitation in the hemisphere contralateral to the PLP. TMS mapping revealed a significant lateralization of the center of gravity and an enlargement of the excitable area on the hemisphere contralateral to the amputation. N-Methyl-d-Aspartate-mediated mechanisms influence the changes of intracortical inhibition and facilitation occurring after limb amputation; however, these cortical excitability changes and PLP are independent of each other. TMS can also influence brain function if applied repetitively. A few studies have begun to therapeutically use repetitive TMS (rTMS) to relief PLP and non-painful PS. rTMS of the contralateral parietal cortex lead to a transient reduction in pain intensity. High frequency rTMS applied over the contralateral motor cortex (M1) or low frequency rTMS over the unaffected hemisphere might also induce significant clinical improvement in PLP. On the other hand, serum beta-endorphin increased significantly after real stimulation over contralateral M1. This systematic review illustrates that TMS technique is an emerging tool to gain insights to pathophysiological aspects of pain and non-painful phantom phenomena. Moreover, TMS could support appropriate patient selection for different therapies and may also have therapeutic utility in subjects with PLP or PS, though the evidence is still very preliminary and well-designed studies in larger cohort of patients are warranted., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objectives: Corticospinal tract excitability and spinal reflex pathways are transiently affected by short applications of static stretching. However, it remains unclear whether the duration and magnitude of these neurophysiological responses can be increased with a longer duration of the applied stretch. The purpose of this study was to investigate alterations in cortical and spinal excitability following five minutes static stretching., Methods: Seventeen participants (22.8±2.3 years old) were tested for the tendon tap reflex (T-reflex), Hoffman reflex (H-reflex) and motor-evoked potentials (MEPs) after transcranial magnetic stimulation (TMS) of the ankle flexor muscles in two separate occasions: before and after 5 minute static stretching or 5 minute control period, in a randomized order., Results: No changes were observed following the control condition. H/M ratio increased by 16.2% after stretching (P=.036). Furthermore, immediately after stretching it was observed a strong inhibition of the T-reflex (57.6% inhibition, P=.003) that persisted up to five minutes after stretching (16.2% inhibition, P=.013) but returned to baseline following 10 minutes. MEPs were not affected by stretching., Conclusions: This study suggests that the neuromuscular responses that follow five minute of static stretching do not influence the excitability of the corticospinal tract and follow a different time course within spinal reflex pathways.

Background: Several studies have applied electrophysiological techniques to physiologically characterize corticobasal degeneration (CBD)., Methods: We performed a systematic literature search of these studies and reviewed all 25 identified articles., Results: Conventional electroencephalography (EEG) is usually normal even in the late stages of disease. Quantitative EEG (qEEG) with spectral analysis revealed mainly lateralized abnormalities, such as an increase of slow wave activity and occasionally the occurrence of sharp waves, and a significant increase of coherence between left parietal-right premotor areas. CBD patients generally have long latency reflexes (LLR) with shorter latencies than in the classic cortical reflex myoclonus observed in progressive myoclonic epilepsy. The somatosensory evoked potentials (SEPs) showed reduced amplitude of the N20-P25 component. These abnormalities may reflect dysfunction of sensory projections to the motor cortex, while the localized parietal cortical damage is thought to be a pivotal factor for the absence of giant SEPs in these patients. Transcranial magnetic stimulation (TMS) revealed asymmetric intracortical disinhibition and asymmetric maps organization; an impaired transcallosal pathways function correlates with the atrophy of the corpus callosum. These findings suggest a pathologic hyperexcitability of the motor cortex, due to a loss of inhibitory input from the sensory cortex., Conclusions: Neurophysiological techniques, in combination with neuroimaging studies, may shed light on the pathophysiological mechanisms of CBD. A better understanding of the disease processes may help clinicians to make a more accurate and early diagnosis. TMS, SEP, LLR, and co-evaluation of EEG and EMG can aid the in differentiation between CBD and other parkinsonism syndromes., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Transcranial alternating current stimulation (tACS) can modulate brain oscillations, cortical excitability and behaviour. In aging, the decrease in EEG alpha activity (8-12 Hz) in the parieto-occipital and mu rhythm in the motor cortex are correlated with the decline in cognitive and motor functions, respectively. Increasing alpha activity using tACS might therefore improve cognitive and motor function in the elderly. The present study explored the influence of tACS on cortical excitability in young and old healthy adults. We applied tACS at individual alpha peak frequency for 10 min (1.5 mA) to the left motor cortex. Transcranial magnetic stimulation was used to assess the changes in cortical excitability as measured by motor-evoked potentials at rest, before and after stimulation. TACS increased cortical excitability in both groups. However, our results also suggest that the mechanism behind the effects was different, as we observed an increase and decrease in intracortical inhibition in the old group and young group, respectively. Our results indicate that both groups profited similarly from the stimulation. There was no indication that tACS was more effective in conditions of low alpha power, that is, in the elderly.

Posttraining consolidation, also known as offline learning, refers to neuroplastic processes and systemic reorganization by which newly acquired skills are converted from an initially transient state into a more permanent state. An extensive amount of research on cognitive and fine motor tasks has shown that sleep is able to enhance these processes, resulting in more stable declarative and procedural memory traces. On the other hand, limited evidence exists concerning the relationship between sleep and learning of gross motor skills. We are particularly interested in this relationship with the learning of gross motor skills in adulthood, such as in the case of sports, performing arts, devised experimental tasks, and rehabilitation practice. Thus, the present review focuses on sleep and gross motor learning (GML) in adults. The literature on the impact of sleep on GML, the consequences of sleep deprivation, and the influence of GML on sleep architecture were evaluated for this review. While sleep has proven to be beneficial for most gross motor tasks, sleep deprivation in turn has not always resulted in performance decay. Furthermore, correlations between motor performance and sleep parameters have been found. These results are of potential importance for integrating sleep in physiotherapeutic interventions, especially for patients with impaired gross motor functions.

During the period when the ankle joint is kept in a dorsiflexed position, the soleus (SOL) H-reflex is inhibited. The nature of this inhibition is not fully understood. One hypothesis is that the decrease in spinal excitability could be attributed to post-activation depression of muscle spindle afferents due to their higher firing rate during the stretch-and-hold procedure. As the static stretching position is maintained though, a partial restoration of the neurotransmitter is expected and should mirror a decrease in H-reflex inhibition. In the present study, we explored the time course of spinal excitability during a period of stretching. SOL H-reflex was elicited during a passive dorsiflexion movement, at 3, 6, 9, 12, 18, 21, and 25 s during maximal ankle dorsiflexion, during plantar flexion (PF) and after stretching, in 12 healthy young individuals. Measurements during passive dorsiflexion, PF and after stretching were all performed with the ankle at 100° angle; measurements during static stretching were performed at individual maximal dorsiflexion. H-reflex was strongly inhibited during the dorsiflexion movement and at maximal dorsiflexion ( p < 0.0001) but recovered during PF and after stretching. During stretching H-reflex showed a recovery pattern ( r = 0.836, P = 0.019) with two distinct recovery steps at 6 and 21 s into stretching. It is hypothesized that the H-reflex inhibition observed until 18 s into stretching is the result of post-activation depression of Ia afferent caused by the passive dorsiflexion movement needed to move the ankle into testing position. From 21 s into stretching, the lower inhibition could be caused by a weaker post-activation depression, inhibition from secondary afferents or post-synaptic inhibitions.

Objectives: Rotation of a static magnet over the motor cortex (MC) generates a transcranial alternating magnetic field (tAMF), and a linked alternating electrical field. The aim of this transcranial magnetic stimulation (TMS) study is to investigate whether such fields are able to influence MC excitability, and whether there are parallels to tACS induced effects., Methods: Fourteen healthy volunteers received 20 Hz tAMF stimulation over the MC, over the vertex, and 20 Hz tACS over the MC, each with a duration of 15 min. TMS assessments were performed before and after the interventions. Changes in motor evoked potentials (MEP), short interval intra-cortical inhibition (SICI) and intra-cortical facilitation (ICF) were evaluated., Results: The tACS and the tAMF stimulation over the MC affected cortical excitability in a different way. After tAMF stimulation MEP amplitudes and ICF decreased and the effect of SICI increased. After tACS MEP amplitudes increased and there were no effects on SICI and ICF., Conclusions: The recorded single and paired pulse MEPs indicate a general decrease of MC excitability following 15 min of tAMF stimulation., Significance: The effects demonstrate that devices based on rotating magnets are potentially suited to become a novel brain stimulation tool in clinical neurophysiology., (Copyright © 2018 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

Spinal excitability in humans is inhibited by both passively holding a static position with the muscle lengthened (static stretching) and by a single non-active lengthening movement. However, whilst immediately after a passive lengthening movement the inhibition persists for several seconds, there seem to be an immediate recovery following static stretching. This result is counter intuitive and could be attributed to methodological procedures. Indeed, differently to what has been done until now, in order to study whether static stretching has a transient effect on the neuromuscular pathway, the procedure should be repeated many times and measurements collected at different time points after stretching. In the present study we repeated 60 times 30 s static stretching of ankle plantar flexors and measured tap reflex (T-reflex), Hoffman reflex (H-reflex), and motor evoked potentials (MEPs) from the Soleus muscle at several time points, starting from immediately after until 30 s following the procedure. T-reflex was strongly inhibited (range 31-91%, p = 0.005) and the inhibition persisted for 30 s showing a slow recovery ( r = 0.541, p = 0.037). H-reflex was not affected by the procedure. Stretching increased the size of the MEPs ( p < 0.0001), differences at times 0 and 2 s after stretching ( p = 0.015 and p = 0.047, respectively). These results confirm that static stretching reduces muscle spindle sensitivity. Moreover it is suggested that post-activation depression of Ia afferents, which is commonly considered the cause of H-reflex depression during both dorsiflexion and static stretching, vanished immediately following stretching or is counteracted by an increased corticospinal excitability.

Objective: There is increasing evidence that an involvement of central nervous system (CNS) can occur in several myopathies. Transcranial magnetic stimulation (TMS) may represent a valuable tool for investigating important neurophysiological and pathophysiological aspects of cortical involvement in neuromuscular disorders. In this review paper we aimed to perform a systematic search of the studies employing TMS techniques in subjects suffering from myopathies., Methods: A literature search was conducted using PubMed and Embase. We identified and reviewed 9 articles matching the inclusion criteria. One hundred twenty patients were included in these studies, which have applied TMS in patients with muscle disorders., Results: To date, a few studies using TMS have been performed in myopathic patients and detected subclinical abnormalities in cortical reactivity and plasticity. The most consistent finding was a decrease in intracortical inhibition, which likely represents a non-specific compensatory mechanism of the CNS in an attempt to overcome the muscle deficit through an increase of the motor cortex output to deficient muscles., Conclusions: Application of TMS to characterize the pathophysiology of the CNS in these subjects appears to be safe and may lead to the development of valuable biomarkers. Well-defined motor cortical excitability patterns can be identified in the different muscle diseases, even if preliminary findings should be confirmed in future studies in larger cohorts of patients., Significance: TMS studies may shed new light on the physiological and pathophysiological mechanisms underlying the cortical involvement in muscle disorders., (Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.)

New Findings: What is the central question of this study? What mediates neural responses following static stretching, and how long do these influences last? What is the main finding and its importance? This study shows that 1 min of static stretching inhibits the tendon tap reflex and facilitates the H reflex without influencing motor-evoked potentials. The results indicate that at least two different mechanisms mediate neural responses after static stretching. The purpose of this study was to determine whether the neural responses observed after static stretching are mediated by sensitivity of muscle spindles, spinal excitability or cortical excitability and how long these influences last. Nineteen volunteers (25.7 ± 5.6 years old) were tested for the tendon tap reflex (T-reflex), H reflex and motor-evoked potentials on ankle flexors and extensors immediately, 5 and 10 min after 1 min static stretching applied at individual maximal ankle dorsiflexion, as well as immediately, 5 and 10 min after a control period of the same duration. Comparison of measurements collected immediately after stretching or control conditions revealed that the T-reflex was weaker after stretching than after control (-59.2% P = 0.000). The T-reflex showed a slow recovery rate within the first 150 s after stretching, but 5 min after the inhibition had disappeared. The H reflex increased immediately after stretching (+18.3%, P = 0.036), showed a quick tendency to recover and returned to control values within 5 min from stretching. Motor-evoked potentials were not affected by the procedure. These results suggest that 1 min of static stretching primarily decreases muscle spindle sensitivity and facilitates the H reflex, whereas effects on the motor cortex can be excluded., (© 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.)

Minimal hepatic encephalopathy (MHE) represents the earliest stage of hepatic encephalopathy (HE). MHE is characterized by cognitive function impairment in the domains of attention, vigilance and integrative function, while obvious clinical manifestations are lacking. In the present study, we aimed at assessing whether subjects with MHE showed alterations in synaptic plasticity within the motor cortex. Previous findings suggest that learning in human motor cortex occurs through long-term potentiation (LTP)-like mechanisms. We employed therefore the paired associative stimulation (PAS) protocol by transcranial magnetic stimulation (TMS), which is able to induce LTP-like effects in the motor cortex of normal subjects. Fifteen patients with MHE and 15 age- and sex-matched cirrhotic patients without MHE were recruited. PAS consisted of 180 electrical stimuli of the right median nerve paired with a single TMS over the hotspot of right abductor pollicis brevis (APB) at an ISI of 25ms (PAS25). We measured motor evoked potentials (MEPs) before and after each intervention for up to 30min. In healthy subjects the PAS25 protocol was followed by a significant increase of the MEP amplitude. On the contrary, in patients with MHE the MEP amplitude was slightly reduced after PAS. These findings demonstrated that associative sensorimotor plasticity, an indirect probe for motor learning, is impaired in MHE patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cortical reorganization can be induced by exercise below the level of the lesion after spinal cord injury (SCI). The aim of the present study was to investigate the effect of passive and active pedaling exercise on leg motor cortical area excitability of subjects with traumatic SCI. Ten subjects with chronic cervical or thoracic SCI were enrolled in the study. We found a significant effect of pedaling on short-interval intracortical inhibition (SICI), which did not interact with the experimental condition (active vs. passive). This corresponded to a significant reduction of SICI in the subjects with SCI, together with no evidence that this pattern differed for passive vs. active pedaling. We found no significant effect of pedaling on intracortical facilitation. Our results showed that also passive cycling may be beneficial in activating motor cortical regions and possibly also facilitating motor recovery after SCI. The present study confirms and extends the findings of previous studies that have observed task-specific cortical activation during passive pedaling. Therefore passive exercise therapies when applied below the level of the lesion in subjects with SCI could promote cortical neuroplastic reorganization., (Copyright © 2016 Elsevier Inc. All rights reserved.)

We used repetitive transcranial magnetic stimulation (rTMS) to further investigate motor cortex excitability in 13 patients with Becker muscular dystrophy (BMD), six of them with slight mental retardation. RTMS delivered at 5Hz frequency and suprathreshold intensity progressively increases the size of motor evoked potentials (MEPs) in healthy subjects; the rTMS-induced facilitation of MEPs was significantly reduced in the BMD patients mentally retarded or classified as borderline when compared with age-matched control subjects and the BMD patients with normal intelligence. The increase in the duration of the cortical silent period was similar in both patient groups and controls. These findings suggest an altered cortical short-term synaptic plasticity in glutamate-dependent excitatory circuits within the motor cortex in BMD patients with intellectual disabilities. RTMS studies may shed new light on the physiological mechanisms of cortical involvement in dystrophinopathies., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

We performed here a systematic review of the studies using transcranial magnetic stimulation (TMS) as a research and clinical tool in patients with spinal cord injury (SCI). Motor evoked potentials (MEPs) elicited by TMS represent a highly accurate diagnostic test that can supplement clinical examination and neuroimaging findings in the assessment of SCI functional level. MEPs allows to monitor the changes in motor function and evaluate the effects of the different therapeutic approaches. Moreover, TMS represents a useful non-invasive approach for studying cortical physiology, and may be helpful in elucidating the pathophysiological mechanisms of brain reorganization after SCI. Measures of motor cortex reactivity, e.g., the short interval intracortical inhibition and the cortical silent period, seem to point to an increased cortical excitability. However, the results of TMS studies are sometimes contradictory or divergent, and should be replicated in a larger sample of subjects. Understanding the functional changes at brain level and defining their effects on clinical outcome is of crucial importance for development of evidence-based rehabilitation therapy. TMS techniques may help in identifying neurophysiological biomarkers that can reliably assess the extent of neural damage, elucidate the mechanisms of neural repair, predict clinical outcome, and identify therapeutic targets. Some researchers have begun to therapeutically use repetitive TMS (rTMS) in patients with SCI. Initial studies revealed that rTMS can induce acute and short duration beneficial effects especially on spasticity and neuropathic pain, but the evidence is to date still very preliminary and well-designed clinical trials are warranted. This article is part of a Special Issue entitled SI: Spinal cord injury., (Copyright © 2014 Elsevier B.V. All rights reserved.)

This study examines with transcranial magnetic stimulation (TMS) and with functional magnetic resonance imaging (fMRI) whether 20 min of repetitive peripheral magnetic stimulation (rPMS) has a facilitating effect on associated motor controlling regions. Trains of rPMS with a stimulus intensity of 150% of the motor threshold (MT) were applied over right hand flexor muscles of healthy volunteers. First, with TMS, 10 vs. 25 Hz rPMS was examined and compared to a control group. Single and paired pulse motor evoked potentials (MEPs) from flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles were recorded at baseline (T0), post rPMS (T1), 30 min post (T2), 1 h post (T3) and 2 h post rPMS (T4). Then, with fMRI, 25 Hz rPMS was compared to sham stimulation by utilizing a finger tapping activation paradigm. Changes in bloodoxygen level dependent (BOLD) contrast were examined at baseline (PRE), post rPMS (POST1) and 1 h post rPMS (POST2). With TMS facilitation was observed in the target muscle (FCR) following 25 Hz rPMS: MEP recruitment curves (RCs) were increased at T1, T2 and T3, and intracortical facilitation (ICF) was increased at T1 and T2. No effects were observed following 10 Hz rPMS. With fMRI the BOLD contrast at the left sensorimotor area was increased at POST1. Compared to inductions protocols based on transcutaneous electrical stimulation and mechanical stimulation, the rPMS induced effects appeared shorter lasting.

Objective: After spinal cord injury (SCI) reorganization of spinal cord circuits occur both above and below the spinal lesion. These functional changes can be determined by assessing electrophysiological recording. We aimed at investigating the trigemino-cervical reflex (TCR) and trigemino-spinal reflex (TSR) responses after traumatic SCI., Methods: TCR and TSR were registered after stimulation of the infraorbital nerve from the sternocleidomastoid, splenius, deltoid, biceps and first dorsal interosseous muscles in 10 healthy subjects and 10 subjects with incomplete cervical SCI., Results: In the control subjects reflex responses were registered from the sternocleidomastoid, and splenium muscles, while no responses were obtained from upper limb muscles. In contrast, smaller but clear short latency EMG potentials were recorded from deltoid and biceps muscles in about half of the SCI patients. Moreover, the amplitudes of the EMG responses in the neck muscles were significantly higher in patients than in control subjects., Conclusion: The reflex responses are likely to propagate up the brainstem and down the spinal cord along the reticulospinal tracts and the propriospinal system. Despite the loss of corticospinal axons, synaptic plasticity in pre-existing pathways and/or formation of new circuits through sprouting processes above the injury site may contribute to the findings of this preliminary study and may be involved in the functional recovery., Significance: Trigemino-cervical-spinal reflexes can be used to demonstrate and quantify plastic changes at brainstem and cervical level following SCI., (Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.)

The development of different methods of brain stimulation provides a promising therapeutic tool with potentially beneficial effects on subjects with impaired cognitive functions. We performed a systematic review of the studies published in the field of neurostimulation in Alzheimer's disease (AD), from basic research to clinical applications. The main methods of non-invasive brain stimulation are repetitive transcranial magnetic stimulation and transcranial direct current stimulation. Preliminary findings have suggested that both techniques can enhance performances on several cognitive functions impaired in AD. Another non-invasive emerging neuromodulatory approach, the transcranial electromagnetic treatment, was found to reverse cognitive impairment in AD transgenic mice and even improves cognitive performance in normal mice. Experimental studies suggest that high-frequency electromagnetic fields may be critically important in AD prevention and treatment through their action at mitochondrial level. Finally, the application of a widely known invasive technique, the deep brain stimulation (DBS), has increasingly been considered as a therapeutic option also for patients with AD; it has been demonstrated that DBS of fornix/hypothalamus and nucleus basalis of Meynert might improve or at least stabilize cognitive functioning in AD. Initial encouraging results provide support for continuing to investigate non-invasive and invasive brain stimulation approaches as an adjuvant treatment for AD patients.

Transcranial direct current stimulation (tDCS) protocols applied over the primary motor cortex are associated with changes in motor performance. This transcranial magnetic stimulation (TMS) study examines whether cathodal tDCS prior to motor training, combined with anodal tDCS during motor training improves motor performance and off-line learning. Three study groups (n=36) were trained on the grooved pegboard test (GPT) in a randomized, between-subjects design: SHAM-sham stimulation prior and during training, STIM1-sham stimulation prior and atDCS during training, STIM2-ctDCS stimulation prior and atDCS during training. Motor performance was assessed by GPT completion time and retested 14 days later to determine off-line learning. Cortical excitability was assessed via TMS at baseline (T0), prior training (T1), after training (T2), and 60 min after training (T3). Motor evoked potentials (MEP) were recorded from m. abductor pollicis brevis of the active left hand. GPT completion time was reduced for both stimulated groups compared to SHAM. For STIM2 this reduction in time was significantly higher than for STIM1 and further off-line learning occurred after STIM2. After ctDCS at T1, MEP amplitude and intracortical facilitation was decreased and intracortical inhibition was increased. After atDCS at T2, an opposite effect was observed for STIM1 and STIM2. For STIM2 these neuromodulatory effects were retained until T3. It is concluded that application of atDCS during the training improves pegboard performance and that additional priming with ctDCS has a positive effect on off-line learning. These cumulative behavioral gains were indicated by the preceding neuromodulatory changes., (Copyright © 2015 Elsevier B.V. All rights reserved.)

To examine whether afferent stimulation of hand muscles has a facilitating effect on motor performance, learning and cortical excitability, healthy subjects were trained on the grooved pegboard test (GTP) while wearing a mesh glove (MG) with incorporated electrical stimulation. Three study groups (n=12) were compared in a between subjects design, the bare handed (BH), gloved (MG) and gloved with electrical stimulation (MGS) groups. Motor performance was assessed by the GPT completion time across 4 training blocks, and further one block was retested 7 days later to determine the off-line effects. On-line learning was obtained by normalizing the completion time values to the first training block, and off-line learning was obtained by normalizing the retest values to the last training block. Cortical excitability was assessed via single and paired-pulse transcranial magnetic stimulation (TMS) at pre-training, post-training and 30 min post-training. Motor evoked potential recruitment curve, short-latency intracortical inhibition and intracortical facilitation were estimated from the TMS assessments. Motor performance across all 4 training blocks was poor in the MG and MGS groups, while on-line learning was not affected by wearing the glove or by afferent stimulation. However, off-line learning, tested 7 days after training, was improved in the MGS group compared to the MG group. In addition, post-training corticospinal excitability was increased in the MGS group. It can be concluded that afferent stimulation improves off-line learning and thus has a positive effect on motor memory, likely due to LTP-like cortical plasticity in the consolidation phase., (Copyright © 2014 Elsevier B.V. All rights reserved.)