Neuromodulation

Identifying what aspects of brain activity are responsible for conscious perception remains one of the most challenging problems in science. While progress has been made through psychophysical studies employing EEG and fMRI, research would greatly benefit from improved methods for stimulating the brain in healthy human subjects. Traditional techniques for neural stimulation through the skull, including electrical or magnetic stimulation, suffer from coarse spatial resolution and have limited ability to target deep brain structures with high spatial selectivity. Over the past decade, a new tool has emerged known as transcranial focused ultrasound (tFUS), which enables the human brain to be stimulated safely and non‑invasively through the skull with millimeter‑scale spatial resolution, including cortical as well as deep brain structures. This tool offers an exciting opportunity for breakthroughs in consciousness research. Given the extensive preparation and regulatory approvals associated with tFUS testing, careful experimental planning is essential. Therefore, our goal here is to provide a roadmap for using tFUS in humans for exploring the neural substrate of conscious perception.

Transcranial photobiomodulation therapy (tPBM) is a promising non‑invasive treatment that uses red or near‑infrared light to modulate biological functions and elicit therapeutic effects. This systematic review aimed to summarise the evidence on the effectiveness of tPBM in improving cognitive function in older women, in experimental animal models and in humans, by analysing the optimal tPBM parameters and behavioural and neurobiological outcomes. tPBM offers advantages specific to older women as a non‑invasive brain stimulation technique, applied to a sensitive population with increased risk of ageing‑related brain dysfunction due to increased life expectancy. A comprehensive literature search was conducted in PubMed, Scopus, and PsycINFO databases, and only seven articles on older women were included in the review. Studies have shown that tPBM significantly improves cognitive impairment in Alzheimer’s disease and related dementias, stroke, cognition and Parkinson’s disease in older women. Despite the heterogeneity in the application parameters and limited number of studies, tPBM therapy was preliminarily found to be a safe, feasible, and effective non‑pharmacological therapy. Research suggests that it may improve cognitive function and reduce neurological symptoms. However, studies focusing specifically on older women are limited, and more evidence is needed to understand its efficacy and safety in this population.

A comprehensive bibliometric analysis evaluates the scientific evidence, impact, and trends of photobiomodulation (PBM) for central nervous system (CNS) disorders. Analyzing 150 relevant PubMed-indexed studies (including 46 clinical trials) up to September 2024, we demonstrate PBM’s positive effects on the CNS. Key mechanisms include enhanced ATP synthesis, modulated nitric oxide signaling, improved neuronal excitability, suppressed oxidative stress, anti‑inflammatory effects, and ion channel modulation. PBM offers therapeutic flexibility: shorter‑wavelength, high‑irradiance power lasers effectively target deep brain structures, while both modalities suit superficial cortical applications where fine spatial control is nonessential. Crucially, PBM induces long‑lasting biological effects, highlighting significant potential for chronic CNS conditions such as Alzheimer’s disease, Parkinson’s disease, and stroke. However, critical challenges hinder translation: optimizing disease‑specific wavelengths and light sources (laser vs LED, continuous vs pulsed), and establishing standardized, long‑term treatment protocols based on robust dose‑response relationships. Resolving heterogeneity in parameters (energy density, power, potential thermal effects) is paramount for PBM to become a reliable neuromodulation tool.

Transcranial focused ultrasound stimulation (tFUS) is a promising neuromodulation technique capable of noninvasively modulating focal neuronal activities and neural circuits in both animals and humans. The cell-type selectivity of tFUS within targeted areas such as the somatosensory cortex (S1) during sonication has been shown to be parameter related. However, it remains unclear how tFUS affects neural circuits by changing the correlation between neurons and how to optimize the tFUS parameters to modulate neural pathways. In this study, multisite intracranial recordings are used in anesthetized male rats to quantify the neuronal responses to tFUS stimulation recorded from S1 and posterior medial thalamic nucleus (POm) of cortico-thalamo-cortical (CTC) pathway. Different tFUS parameters including ranges of pulse repetition frequencies (PRFs) and duty cycles (DCs) are tested. We find that when targeting at S1, only regular-spiking units (RSUs) respond to specific tFUS parameters during sonication (DC, 6–60%; PRF, 1,500, 3,000 and 4,500 Hz), and RSUs from the POm exhibit a synchronized response. The changes of directional correlation between S1 RSUs and POm RSUs indicate the activation of feedback modulation. Delayed responses and correlation changes were further observed at ~200 ms postsonication from the neurons in S1 and POm, indicating feedforward modulation. Our results reveal that tFUS can modulate the feedback and feedforward CTC pathways by selectively activating cortical RSUs and adjusting the tFUS parameters, particularly the PRF, to maximize cortical RSU activity could enhance the modulation of the CTC pathway.

BACKGROUND: Transcranial ultrasound stimulation (TUS) is a non-invasive neuromodulation technique with promising clinical potential. Its therapeutic efficacy and safety are significantly influenced by stimulation parameters. However, the global research hotspots and future research trends of TUS application in the field of rehabilitation are unclear. This study analyzes the status of TUS research. Understand the annual publication trends, international and institutional cooperation pattern and influential authors and journals and keyword hotspot. METHODS: A comprehensive literature search was conducted on the Web of Science core database using TUS-related subject headings until 27 December 2024. Two researchers independently screened articles based on pre-determined inclusion and exclusion criteria. Software packages such as CiteSpace and VOSviewer were used to visualize the results. RESULTS: A total of 577 literatures were included. The results show that the annual publication volume shows an increasing trend, reaching a peak in 2024. The United States, China and Germany dominated the number of publications, with the largest number of institutions being Harvard University, the University of Toronto and Brigham and Women’s Hospital. Brain stimulation is the journal with the most articles and citations. Research hotspots include transcranial magnetic stimulation, noninvasive brain stimulation, Parkinson’s disease, and Alzheimer’s disease. CONCLUSION: A bibliometric analysis of the literature shows that research interest in transcranial ultrasound stimulation is growing rapidly, with annual publications growing exponentially since 2013 and receiving increasing attention from researchers. The findings suggest that TUS is currently used primarily in neurological diseases, particularly in the study of Parkinson’s disease and Alzheimer’s disease. At the same time, it is found that an emerging international cooperation model with the partnership between the United States, China and Germany as the core has gradually taken shape. Although preclinical studies have shown promising neuromodulator effects, the current study suggests that TUS needs to undergo further multicenter clinical validation. These findings provide evidence to guide future research priorities for non-invasive neuromodulation.

Background: Functional Electrical Stimulation Assisted Cycling (FES-cycling) is a rehabilitation intervention for individuals with Spinal Cord Injury (SCI), offering benefits like increased muscle trophism, improved cardiopulmonary function, and reduced bone demineralization. Despite numerous studies on its physical advantages, few have focused on user experience. This study evaluates the user experience, usability, acceptability, and human-device interaction of two FES-cycling systems: a recumbent FES-bike prototype from Politecnico di Milano and the commercial BerkelBike Pro. Methods: We recruited 15 participants with SCI, aged 18-65, with varying injury levels. The user experience (primary outcome), acceptability, usability, human-device interaction, and ergonomics of both systems were investigated by means of 4 questionnaires: the User Experience Questionnaire (UEQ), the Technological Acceptance Measure 3 (TAM-3), the System Usability Scale (SUS), and a customized questionnaire to evaluate human-device interaction both in terms of ergonomic aspects and psychological factors. Results: The user experience received positive evaluations across all dimensions (scores ≥ 1.5 on a scale from -3 to 3), with slightly higher, though not statistically significant, scores for the FB. Secondary outcomes indicated strong acceptability (global TAM-3 scores > 5.5/7 for both devices), high usability ratings (SUS scores ≥ 75/100 for both devices), and favorable interaction and ergonomics, emphasizing ease of use, comfort, and alignment with user expectations. Conclusions: The study underscores the positive user experience as the primary outcome, along with strong acceptance and usability of both devices, emphasizing their potential to enhance Sport-Therapy and the value of integrating user perspectives in future development.

This study investigates whether the combined effect of kinesthetic motor imagery-based brain computer interface (KI-BCI) and transcranial direct current stimulation (tDCS) on upper limb function in subacute stroke patients is more effective than using KI-BCI or tDCS alone. Forty-eight subacute stroke survivors were randomized to the KI-BCI, tDCS, or BCI-tDCS group. The KI-BCI group performed 30 min of KI-BCI training. Patients in tDCS group received 30 min of tDCS. Patients in BCI-tDCS group received 15 min of tDCS and 15 min of KI-BCI. The treatment cycle was five times a week, for four weeks. After all intervention, the Fugl-Meyer Assessment-Upper Extremity, Motor Status Scale, and the Modified Barthel Index scores of the KI-BCI group were superior to those of the tDCS group. The BCI-tDCS group was superior to the tDCS group in terms of the Motor Status Scale. Although quantitative EEG showed no significant group differences, the quantitative EEG indices in the tDCS group were significantly lower than before treatment. In conclusion, after treatment, although all intervention strategies improved upper limb motor function and daily living abilities in subacute stroke patients, KI-BCI demonstrated significantly better efficacy than tDCS. Under the same total treatment duration, the combined use of tDCS and KI-BCI did not achieve the hypothesized optimal outcome. Notably, tDCS reduced QEEG indices, possibly indicating favorable future outcomes in future.

Transcranial ultrasound stimulation (TUS) offers precise, non‑invasive neuro‑modulation, though its impact on human deep brain structures remains underexplored. Here we examined TUS‑induced changes in the basal ganglia of 10 individuals with movement disorders (Parkinson’s disease and dystonia) and 15 healthy participants. Local field potentials were recorded using deep brain stimulation (DBS) leads in the globus pallidus internus (GPi). Compared to sham, theta burst TUS (tbTUS) increased theta power during stimulation, while 10 Hz TUS enhanced beta power, with effects lasting up to 40 min. In healthy participants, a stop‑signal task assessed tbTUS effects on the GPi, with pulvinar stimulation serving as an active sham. GPi TUS prolonged stop‑signal reaction times, indicating impaired response inhibition, whereas pulvinar TUS had no effect. These findings provide direct electrophysiological evidence of TUS target engagement and specificity in deep brain structures, suggesting its potential as a noninvasive DBS strategy for neurological and psychiatric disorders.

Transcranial focused ultrasound (tFUS) has emerged as a promising non-invasive neuromodulation technique for disorders of consciousness (DOC). This work critically evaluates tFUS’s potential, highlighting its unique ability to precisely modulate deep brain structures, particularly the thalamus, while maintaining non-invasiveness. The mechanisms of action span multiple levels, from membrane-level ion channel modulation to network-wide changes in neural connectivity. Preclinical and early clinical studies have demonstrated tFUS’s potential to improve DOC outcomes. Preliminary clinical trials in both acute and chronic DOC patients have shown encouraging results, including diagnostic category shifts, improvements in behavioral responsiveness, and alterations in thalamo‑cortical connectivity. However, significant challenges remain. These include optimizing stimulation parameters, addressing variability in patient responses, and ensuring long‑term safety. The current evidence base is limited, necessitating larger, more rigorous investigations. Future research should focus on multicentre randomized controlled trials to comprehensively evaluate tFUS across different DOC etiologies and chronicity. Key priorities include identifying predictive biomarkers, exploring combination therapies, and addressing ethical considerations. While tFUS shows significant promise in DOC management, further investigation is crucial to refine its application and establish its definitive clinical role.

Spontaneous recovery frequently proves maladaptive or insufficient because the plasticity of the injured adult mammalian central nervous system is limited. This limited plasticity serves as a primary barrier to functional recovery after brain injury. Neuromodulation technologies represent one of the fastest-growing fields in medicine. These techniques utilize electricity, magnetism, sound, and light to restore or optimize brain functions by promoting reorganization or long-term changes that support functional recovery in patients with brain injury. Therefore, this review aims to provide a comprehensive overview of the effects and underlying mechanisms of neuromodulation technologies in supporting motor function recovery after brain injury. Many of these technologies are widely used in clinical practice and show significant improvements in motor function across various types of brain injury. However, studies report negative findings, potentially due to variations in stimulation protocols, differences in observation periods, and the severity of functional impairments among participants across different clinical trials. Additionally, we observed that different neuromodulation techniques share remarkably similar mechanisms, including promoting neuroplasticity, enhancing neurotrophic factor release, improving cerebral blood flow, suppressing neuroinflammation, and providing neuroprotection. Finally, considering the advantages and disadvantages of various neuromodulation techniques, we propose that future development should focus on closed-loop neural circuit stimulation, personalized treatment, interdisciplinary collaboration, and precision stimulation.

Non-invasive neuromodulation represents a major opportunity for brain interventions, and transcranial focused ultrasound (FUS) is one of the most promising approaches. However, some challenges prevent the community from fully understanding its outcomes. We aimed to address one of them and unravel the temporal dynamics of FUS effects in humans. Twenty-two healthy volunteers participated in the study. Eleven received FUS in the right inferior frontal cortex while the other 11 were stimulated in the right thalamus. Using a temporal dynamic approach, we compared resting-state fMRI seed-based functional connectivity obtained before and after FUS. We also assessed behavioural changes as measured with a task of reactive motor inhibition. Our findings reveal that the effects of FUS are predominantly time‑constrained and spatially distributed in brain regions functionally connected with the directly stimulated area. In addition, mediation analysis highlighted that FUS applied in the right inferior cortex was associated with behavioural alterations which was directly explained by the applied acoustic pressure and the brain functional connectivity change we observed. Our study underscored that the biological effects of FUS are indicative of behavioural changes observed more than an hour following stimulation and are directly related to the applied acoustic pressure.

Non-invasive brain stimulation (NIBS) techniques are designed to precisely and selectively target specific brain regions, thus enabling focused modulation of neural activity. Among NIBS technologies, low‑intensity transcranial focused ultrasound (tFUS) has emerged as a promising new modality. The application of tFUS can safely and non‑invasively stimulate deep brain structures with millimetric precision, offering distinct advantages in terms of accessibility to non‑cortical regions over other NIBS methods. However, to date, several tFUS aspects still need to be characterized; furthermore, there are only a handful of studies that have utilized tFUS in psychiatric populations. This narrative review provides an up‑to‑date overview of key aspects of this NIBS technique, including the main components of a tFUS system, the neuronavigational tools used to precisely target deep brain regions, the simulations utilized to optimize the stimulation parameters and delivery of tFUS, and the experimental protocols employed to evaluate the efficacy of tFUS in psychiatric disorders. The main findings from studies in psychiatric populations are presented and discussed, and future directions are highlighted.

Our understanding of brain circuit operations and disorders has rapidly outpaced our ability to intervene and restore them. Developing technologies that can precisely interface with any brain region and circuit may combine diagnostics with therapeutic intervention, expediting personalised brain medicine. Transcranial ultrasound stimulation (TUS) is a promising noninvasive solution to this challenge, offering focal precision and scalability. By exploiting the biomechanics of pressure waves on brain tissue, TUS enables multi-site targeted neuromodulation across distributed circuits in the cortex and deeper areas alike. In this Essay, we explore the emergent evidence that TUS can functionally test and modify dysfunctional regions, effectively serving as a search and rescue tool for the brain. We define the challenges and opportunities faced by TUS as it moves towards greater target precision and integration with advanced brain monitoring and interventional technology. Finally, we propose a roadmap for the evolution of TUS as it progresses from a research tool to a clinically validated therapeutic for brain disorders.

Transcranial ultrasonic stimulation (TUS) is rapidly gaining traction for non-invasive human neuromodulation, with a pressing need to establish protocols that maximise neuromodulatory efficacy. In this review, we aggregate and examine empirical evidence for the relationship between tunable TUS parameters and in vitro and in vivo outcomes. Based on this multiscale approach, TUS researchers can make better informed decisions about optimal parameter settings. Importantly, we also discuss the challenges involved in extrapolating results from prior empirical work to future interventions, including the translation of protocols between models and the complex interaction between TUS protocols and the brain. A synthesis of the empirical evidence suggests that larger effects will be observed at lower frequencies within the sub-MHz range, higher intensities and pressures than commonly administered thus far, and longer pulses and pulse train durations. Nevertheless, we emphasise the need for cautious interpretation of empirical data from different experimental paradigms when basing protocols on prior work as we advance towards refined TUS parameters for human neuromodulation.

Transcranial ultrasonic stimulation (TUS) has the potential to usher in a new era for human neuroscience by allowing spatially precise and high-resolution non-invasive targeting of both deep and superficial brain regions. Currently, fundamental research on the mechanisms of interaction between ultrasound and neural tissues is progressing in parallel with application-focused research. However, a major hurdle in the wider use of TUS is the selection of optimal parameters to enable safe and effective neuromodulation in humans. In this paper, we will discuss the major factors that determine both the safety and efficacy of TUS. We will discuss the thermal and mechanical biophysical effects of ultrasound, which underlie its biological effects, in the context of their relationships with tunable parameters. Based on this knowledge of biophysical effects, and drawing on concepts from radiotherapy, we propose a framework for conceptualising TUS dose.

Photobiomodulation (PBM) therapy on the brain employs red to near-infrared (NIR) light to treat various neurological and psychological disorders. The mechanism involves the activation of cytochrome c oxidase in the mitochondrial respiratory chain, thereby enhancing ATP synthesis. Additionally, light absorption by ion channels triggers the release of calcium ions, instigating the activation of transcription factors and subsequent gene expression. This cascade of events not only augments neuronal metabolic capacity but also orchestrates anti‑oxidant, anti‑inflammatory, and anti‑apoptotic responses, fostering neurogenesis and synaptogenesis. It shows promise for treating conditions like dementia, stroke, brain trauma, Parkinson’s disease, and depression, even enhancing cognitive functions in healthy individuals and eliciting growing interest within the medical community. However, delivering sufficient light to the brain through transcranial approaches poses a significant challenge due to its limited penetration into tissue, prompting an exploration of alternative delivery methods such as intracranial and intranasal approaches. This comprehensive review aims to explore the mechanisms through which PBM exerts its effects on the brain and provide a summary of notable preclinical investigations and clinical trials conducted on various brain disorders, highlighting PBM’s potential as a therapeutic modality capable of effectively impeding disease progression within the organism—a task often elusive with conventional pharmacological interventions.

Electrical stimulation of spinal neurons has emerged as a valuable tool to enhance rehabilitation after spinal cord injury. In separate parameterizations, it has shown promise for improving voluntary movement, reducing symptoms of autonomic dysreflexia, improving functions mediated by muscles of the pelvic floor (e.g., bowel, bladder, and sexual function), reducing spasms and spasticity, and decreasing neuropathic pain, among others. This diverse set of actions is related both to the density of sensorimotor neural networks in the spinal cord and to the intrinsic ability of electrical stimulation to modulate neural transmission in multiple spinal networks simultaneously. It also suggests that certain spinal stimulation parameterizations may be capable of providing multi-modal therapeutic benefits, which would directly address the complex, multi-faceted rehabilitation goals of people living with spinal cord injury. This review is intended to identify and characterize reports of spinal stimulation-based therapies specifically designed to provide multi-modal benefits and those that report relevant unintended effects of spinal stimulation paradigms parameterized to enhance a single consequence of spinal cord injury.

A systematic review was conducted to determine the trends in devices and parameters used for brain photobiomodulation (PBM). The revised studies included clinical and cadaveric approaches, in which light stimuli were applied to the head and/or neck. PubMed, Scopus, Web of Science and Google Scholar databases were used for the systematic search. A total of 2133 records were screened, from which 97 were included in this review. The parameters that were extracted and analysed in each article were the device design, actuation area, actuation site, wavelength, mode of operation, power density, energy density, power output, energy per session and treatment time. To organize device information, 11 categories of devices were defined, according to their characteristics. The most used category of devices was laser handpieces, which relate to 21% of all devices, while 28% of the devices were not described. Studies for cognitive function and physiological characterisation are the most well defined ones and with more tangible results. There is a lack of consistency when reporting PBM studies, with several articles under defining the stimulation protocol, and a wide variety of parameters used for the same health conditions (e.g., Alzheimer’s or Parkinson’s disease) resulting in positive outcomes. Standardization for the report of these studies is warranted, as well as sham‑controlled comparative studies to determine which parameters have the greatest effect on PBM treatments for different neurological conditions.

Background: The current management of stroke patients with intravenous thrombolysis and endovascular thrombectomy is effective only when it is timely performed on an appropriately selected but minor fraction of patients. The development of novel adjunctive therapy is highly desired to reduce morbidity and mortality with stroke further. Since endothelial dysfunction is implicated in the pathogenesis of stroke and is featured with suppressed endothelial nitric oxide synthase (eNOS) with concomitant nitric oxide (NO) deficiency, restoring endothelial NO represents a promising approach to treat stroke injury. Methods: This is a preclinical proof-of-concept study to determine the therapeutic effect of transcranial treatment with a low-power near-infrared (NIR) laser in a mouse model of ischemic stroke. The laser treatment was performed before the middle cerebral artery occlusion (MCAO) with a filament. To determine the involvement of eNOS phosphorylation, unphosphorylatable eNOS S1176A knock-in mice were used. Each measurement was analyzed by 2-way ANOVA to assess the effect of the treatment on cerebral blood flow (CBF) with laser Doppler flowmetry, eNOS phosphorylation by immunoblot analysis, and stroke outcomes by infarct volumes and neurological deficits. Results: Pretreatment with a 1064 nm laser at an irradiance of 50 mW/cm² improved CBF, eNOS phosphorylation, and stroke outcomes. Conclusions: NIR-II photobiomodulation (PBM) could offer a non-invasive and low-risk adjunctive therapy for stroke injury. This new modality using a physical parameter merits further consideration to develop innovative therapies to prevent and treat a wide array of cardiovascular diseases.

Over the past 30 years, the field of neuromodulation has witnessed remarkable advancements. These developments encompass a spectrum of techniques, both non-invasive and invasive, that possess the ability to both probe and influence the central nervous system. In many cases neuromodulation therapies have been adopted into standard care treatments. Transcranial magnetic stimulation (TMS), transcranial direct current stimulation (tDCS), and transcranial ultrasound stimulation (TUS) are the most common non-invasive methods in use today. Deep brain stimulation (DBS), spinal cord stimulation (SCS), and vagus nerve stimulation (VNS), are leading surgical methods for neuromodulation. Ongoing active clinical trials using are uncovering novel applications and paradigms for these interventions.

Objective. Electrical spinal cord stimulation (SCS) has emerged as a promising therapy for recovery of motor and autonomic dysfunctions following spinal cord injury (SCI). Despite the rise in studies using SCS for SCI complications, there are no standard guidelines for reporting SCS parameters in research publications, making it challenging to compare, interpret or reproduce reported effects across experimental studies. Approach. To develop guidelines for minimum reporting standards for SCS parameters in pre‑clinical and clinical SCI research, we gathered an international panel of expert clinicians and scientists. Using a Delphi approach, we developed guideline items and surveyed the panel on their level of agreement for each item. Main results. There was strong agreement on 26 of the 29 items identified for establishing minimum reporting standards for SCS studies. The guidelines encompass three major SCS categories: hardware, configuration and current parameters, and the intervention. Significance. Standardized reporting of stimulation parameters will ensure that SCS studies can be easily analyzed, replicated, and interpreted by the scientific community, thereby expanding the SCS knowledge base and fostering transparency in reporting.

The brain diseases account for 30% of all known diseases. Pharmacological treatment is hampered by the blood–brain barrier, limiting drug delivery to the central nervous system (CNS). Transcranial photobiomodulation (tPBM) is a promising technology for treating brain diseases, due to its effectiveness, non-invasiveness, and affordability. tPBM has been widely used in pre-clinical experiments and clinical trials for treating brain diseases, such as stroke and Alzheimer’s disease. This review provides a comprehensive overview of tPBM. We summarize emerging trends and new discoveries in tPBM based on over one hundred references published in the past 20 years. We discuss the advantages and disadvantages of tPBM and highlight successful experimental and clinical protocols for treating various brain diseases. A better understanding of tPBM mechanisms, the development of guidelines for clinical practice, and the study of dose-dependent and personal effects hold great promise for progress in treating brain diseases.

Objective: The aim of the present study is to explore whether a single session of transcutaneous Vagus Nerve Stimulation (tVNS) can enhance the ipsilesional, and contralesional upper limb motor functions as well as cognitive functions in stroke patients. The effects of the stimulation were evaluated through two different tasks: the box and blocks test (BB), indexing manual dexterity, and the Go/No-go task, a visuomotor paradigm used to assess both motor readiness and response inhibition. Tests were administered without tVNS, during tVNS and during sham tVNS. Results: The BB showed a statistical difference for both contralesional side (p = 0.05) between Basal-Real condition (p = 0.042) and ipsilesional side (p = 0.001) between Basal-Real (p = 0.008) and for Real-Sham (p = 0.005). Any statistical difference was found for the mean latencies in the three conditions of the Go/No-go test. Conclusion: A single session of tVNS seems to improve upper limb motor functions but not cognitive functions in post-stroke patients, despite a positive trend was detected.

Objective: This is a case report showing that transcranial photobiomodulation (tPBM) combined with traditional, speech-language therapy improved and accelerated the results from speech-language therapy, in a stroke person with aphasia (PWA). Background: tPBM is a safe, noninvasive technique using red and near-infrared light to improve the metabolism of cells. tPBM helps by promoting neuromodulation, while decreasing neuroinflammation and promoting vasodilation. Several studies have shown that tPBM can help individuals with stroke or traumatic brain injury achieve significant cognitive improvements. Methods: A 38-year-old female, who sustained an ischemic stroke on the left side of the brain, received two, 5-month series of treatments. The first series of treatments included traditional speech-language therapy, for the first 5 months poststroke. The second series of treatments included tPBM in combination with speech-language therapy, for the next 5 months. The tPBM treatments included application of red (630 and 660 nm) and near-infrared (850 nm) wavelengths of photons applied to left hemisphere scalp areas. The major cortical language areas were subjacent to the scalp placements along the line of the Sylvian fissure. At each session, first a light-emitting diode (LED) cluster head with red (630 and 660 nm) and near-infrared (850 nm) wavelengths, with an irradiance (power density) of 200 mW/cm², a beam size of 4.9 cm², and a fluence (energy density) of 12 J/cm² per minute, was applied to the left side of the scalp/brain, along the Sylvian fissure for 60 sec at each at the following eight, language network target areas: frontal pole, prefrontal cortex, and inferior frontal gyrus (Broca’s area); supramarginal gyrus and angular gyrus in the parietal lobe; inferior motor/sensory cortex (mouth area); and posterior superior temporal gyrus (Wernicke’s area) and superior temporal sulcus in the temporal lobe, for a total of 8 min. Second, for the next 20 min (1200 sec), simultaneous with speech-language therapy, an LED PBM helmet was applied to the scalp/head. This helmet contained 256 separate LED lights, near-infrared (810 nm) wavelength, 60 mW power per LED light, total power, 15 W; energy, 72 Joules; fluence, 28.8 J/cm²; and irradiance, 24 mW/cm². Results and conclusions: During the initial, 5-month treatment series with traditional speech-language therapy only, there was little to no improvement in dysarthria and expressive language. During the second, 5-month treatment series, however, with tPBM applied first, to the left hemisphere only, and second, to both hemispheres during each session plus simultaneous speech-language therapy, there was marked improvement in the dysarthria and expressive language. After the first 5-month series, this PWA had utilized a slow rate of speech with a production of ~25 to 30 words-per-minute during conversations and spontaneous speech. Utterance length was only 4-6 words with simple, grammatical structure. After the second, 5-month series of treatment combining tPBM plus speech-language therapy, the rate of speech increased to 80+ words-per-minute and utterance length was increased to 9-10 words, with more complex grammatical structure.

The nature of libraries has changed rapidly with the advent of technology, so far as to change the very way of understanding the library itself. In this paper we examine the impact that digital technologies have had on library workers, and note that so far technology has only been used to transpose the standard library practices, and that little has been done to fully exploit the new opportunities it introduced. To overcome this situation, we propose a graph-based organization of DL data, based on a technology mixing DBs and ontologies. We also propose a holistic data schema allowing to store information that is usually neglected by traditional cataloging and description standards used in libraries. This would enable the use of AI techniques that may significantly expand the effectiveness of data processing and may dramatically improve the exploitation possibilities of documents.

Transcutaneous auricular vagus nerve stimulation (taVNS) is a neurostimulatory technique hypothesised to enhance central noradrenaline. Currently, there is scarce evidence in support of a noradrenergic mechanism of taVNS and limited knowledge on its stimulation parameters (i.e., intensity and pulse width). Therefore, the present study aimed to test whether taVNS enhances pupil dilation, a noradrenergic biomarker, as a function of stimulation parameters. Forty-nine participants received sham (i.e., left ear earlobe) and taVNS (i.e., left ear cymba concha) stimulation in two separate sessions, in a counterbalanced order. We administered short bursts (5s) of seven stimulation settings varying as a function of pulse width and intensity and measured pupil size in parallel. Each stimulation setting was administered sixteen times in separate blocks. We expected short bursts of stimulation to elicit phasic noradrenergic activity as indexed by event‑related pupil dilation and event‑related temporal derivative. We hypothesised higher stimulation settings, quantified as the total charge per pulse (pulse width x intensity), to drive greater event‑related pupil dilation and temporal derivative in the taVNS compared to sham condition. Specifically, we expected stimulation settings in the taVNS condition to be associated with a linear increase in event‑related pupil dilation and temporal derivative. We found stimulation settings to linearly increase both pupil measures. In line with our hypothesis, the observed dose‑dependent effect was stronger in the taVNS condition. We also found taVNS to elicit more intense and unpleasant sensations than sham stimulation. These results support the hypothesis of a noradrenergic mechanism of taVNS. However, future studies should disentangle whether stimulation elicited sensations mediate the effect of taVNS on evoked pupil dilation.

Background: Transcranial photobiomodulation (tPBM) has been studied for over a decade as a possible cognitive intervention. Objective: To evaluate the effect of tPBM for enhancing human cognitive function in healthy adults and remediating impaired cognitive function in adults with cognitive disorders. Methods: A systematic literature search from three electronic databases (PubMed, Scopus, Web of Science) was conducted from 1987 to May 2022. The cognitive function being evaluated included learning and memory, attention, executive function, language, and global cognitive function. Results: Of the 35 studies identified, 29 (82.9 %) studies reported positive improvement in cognitive functions after tPBM. All nine studies on participants with subjective memory complaints, mild cognitive impairment, and dementia, showed positive outcomes. Seven (87.5 %) studies on traumatic brain injury (TBI) patients also showed positive results. A series of clinical trials on stroke patients showed positive trends on improved neurological deficit at first, but was prematurely terminated later at phase III due to the lack of statistical significance. One of the most frequently used protocols for clinical populations employed devices delivering near‑infrared light (810 nm), the irradiance of 20–25 mW cm⁻², and fluence of 1–10 J cm⁻². Despite this commonly used protocol, there were other studies explored the potential effectiveness of other wavelengths of light ranging from visible red light (630‑635 nm) to invisible near‑infrared light (1060‑1068 nm). Conclusions: tPBM seems to improve cognitive function. However, only half of the reviewed clinical trials were randomized control trials, further investigation is warranted.

Transcranial ultrasound stimulation (TUS) holds great potential as a tool to alter neural circuits non‑invasively in both animals and humans. In contrast to established non‑invasive brain stimulation methods, ultrasonic waves can be focused on both cortical and deep brain targets with the unprecedented spatial resolution as small as a few cubic millimeters. This focusing allows exclusive targeting of small subcortical structures, previously accessible only by invasive deep brain stimulation devices. The neuromodulatory effects of TUS are likely derived from the kinetic interaction of the ultrasound waves with neuronal membranes and their constitutive mechanosensitive ion channels, to produce short term and long‑lasting changes in neuronal excitability and spontaneous firing rate. After decades of mechanistic and safety investigation, the technique has finally come of age, and an increasing number of human TUS studies are expected. Given its excellent compatibility with non‑invasive brain mapping techniques, such as electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), as well as neuromodulatory techniques, such as transcranial magnetic stimulation (TMS), systemic TUS effects can readily be assessed in both basic and clinical research. In this review, we present the fundamentals of TUS for a broader audience. We provide up‑to‑date information on the physical and neurophysiological mechanisms of TUS, available readouts for its neural and behavioral effects, insights gained from animal models and human studies, potential clinical applications, and safety considerations. Moreover, we discuss the indirect effects of TUS on the nervous system through peripheral co‑stimulation and how these confounding factors can be mitigated by proper control conditions.

Skeletal muscle contains a designated population of adult stem cells, called satellite cells, which are generally quiescent. In homeostasis, satellite cells proliferate only sporadically and usually by asymmetric cell division to replace myofibres damaged by daily activity and maintain the stem cell pool. However, satellite cells can also be robustly activated upon tissue injury, after which they undergo symmetric divisions to generate new stem cells and numerous proliferating myoblasts that later differentiate to muscle cells (myocytes) to rebuild the muscle fibre, thereby supporting skeletal muscle regeneration. Recent discoveries show that satellite cells have a great degree of population heterogeneity, and that their cell fate choices during the regeneration process are dictated by both intrinsic and extrinsic mechanisms. Extrinsic cues come largely from communication with the numerous distinct stromal cell types in their niche, creating a dynamically interactive microenvironment. This Review discusses the role and regulation of satellite cells in skeletal muscle homeostasis and regeneration. In particular, we highlight the cell‑intrinsic control of quiescence versus activation, the importance of satellite cell–niche communication, and deregulation of these mechanisms associated with ageing. The increasing understanding of how satellite cells are regulated will help to advance muscle regeneration and rejuvenation therapies.

Non‑invasive neuromodulation technology is important for the treatment of brain diseases. The effects of focused ultrasound on neuronal activity have been investigated since the 1920s. Low intensity transcranial focused ultrasound (tFUS) can exert non‑destructive mechanical pressure effects on cellular membranes and ion channels and has been shown to modulate the activity of peripheral nerves, spinal reflexes, the cortex, and even deep brain nuclei, such as the thalamus. It has obvious advantages in terms of security and spatial selectivity. This technology is considered to have broad application prospects in the treatment of neurodegenerative disorders and neuropsychiatric disorders. This review synthesizes animal and human research outcomes and offers an integrated description of the excitatory and inhibitory effects of tFUS in varying experimental and disease conditions.

Brain stimulation approaches are important to gain causal mechanistic insights into the relevance of functional brain regions and/or neurophysiological systems for human cognitive functions. In recent years, transcutaneous vagus nerve stimulation (tVNS) has attracted considerable popularity. It is a noninvasive brain stimulation technique based on the stimulation of the vagus nerve. The stimulation of this nerve activates subcortical nuclei, such as the locus coeruleus and the nucleus of the solitary tract, and from there, the activation propagates to the cortex. Since tVNS is a novel stimulation technique, this literature review outlines a brief historical background of tVNS, before detailing underlying neurophysiological mechanisms of action, stimulation parameters, cognitive effects of tVNS on healthy humans, and, lastly, current challenges and future directions of tVNS research in cognitive functions. Although more research is needed, we conclude that tVNS, by increasing norepineprine (NE) and gamma-aminobutyric acid (GABA) levels, affects NE- and GABA-related cognitive performance. The review provides detailed background information how to use tVNS as a neuro-modulatory tool in cognitive neuroscience and outlines important future leads of research on tVNS.

The array of end organ innervations of the vagus nerve, coupled with increased basic science evidence, has led to vagus nerve stimulation (VNS) being explored as a management option in a number of clinical disorders, such as heart failure, migraine and inflammatory bowel disease. Both invasive (surgically implanted) and non-invasive (transcutaneous) techniques of VNS exist. Transcutaneous VNS (tVNS) delivery systems rely on the cutaneous distribution of vagal afferents, either at the external ear (auricular branch of the vagus nerve) or at the neck (cervical branch of the vagus nerve), thus obviating the need for surgical implantation of a VNS delivery device and facilitating further investigations across a wide range of uses. The concept of electrically stimulating the auricular branch of the vagus nerve (ABVN), which provides somatosensory innervation to several aspects of the external ear, is relatively more recent compared with cervical VNS; thus, there is a relative paucity of literature surrounding its operation and functionality. Despite the increasing body of research exploring the therapeutic uses of auricular transcutaneous VNS (tVNS), a comprehensive review of the cutaneous, intracranial and central distribution of ABVN fibres has not been conducted to date. A review of the literature exploring the neuroanatomical basis of this neuromodulatory therapy is therefore timely. Our review article explores the neuroanatomy of the ABVN with reference to (1) clinical surveys examining Arnold’s reflex, (2) cadaveric studies, (3) fMRI studies, (4) electrophysiological studies, (5) acupuncture studies, (6) retrograde tracing studies and (7) studies measuring changes in autonomic (cardiovascular) parameters in response to auricular tVNS. We also provide an overview of the fibre composition of the ABVN and the effects of auricular tVNS on the central nervous system. Cadaveric studies, of which a limited number exist in the literature, would be the ‘gold-standard’ approach to studying the cutaneous map of the ABVN; thus, there is a need for more such studies to be conducted. Functional magnetic resonance imaging (fMRI) represents a useful surrogate modality for discerning the auricular sites most likely innervated by the ABVN and the most promising locations for auricular tVNS. However, given the heterogeneity in the results of such investigations and the various limitations of using fMRI, the current literature lacks a clear consensus on the auricular sites that are most densely innervated by the ABVN and whether the brain regions secondarily activated by electrical auricular tVNS depend on specific parameters. At present, it is reasonable to surmise that the concha and inner tragus are suitable locations for vagal modulation. Given the therapeutic potential of auricular tVNS, there remains a need for the cutaneous map of the ABVN to be further refined and the effects of various stimulation parameters and stimulation sites to be determined..

In this review, we provide an overview of the US Food and Drug Administration (FDA)-approved clinical uses of vagus nerve stimulation (VNS) as well as information about the ongoing studies and preclinical research to expand the use of VNS to additional applications. VNS is currently FDA approved for therapeutic use in patients aged >12 years with drug-resistant epilepsy and depression. Recent studies of VNS in in vivo systems have shown that it has anti-inflammatory properties which has led to more preclinical research aimed at expanding VNS treatment across a wider range of inflammatory disorders. Although the signaling pathway and mechanism by which VNS affects inflammation remain unknown, VNS has shown promising results in treating chronic inflammatory disorders such as sepsis, lung injury, rheumatoid arthritis (RA), and diabetes. It is also being used to control pain in fibromyalgia and migraines. This new preclinical research shows that VNS bears the promise of being applied to a wider range of therapeutic applications.

The microbiota, the gut, and the brain communicate through the microbiota‑gut‑brain axis in a bidirectional way that involves the autonomic nervous system. The vagus nerve (VN), the principal component of the parasympathetic nervous system, is a mixed nerve composed of 80% afferent and 20% efferent fibers. The VN, because of its role in interoceptive awareness, is able to sense the microbiota metabolites through its afferents, to transfer this gut information to the central nervous system where it is integrated in the central autonomic network, and then to generate an adapted or inappropriate response. A cholinergic anti‑inflammatory pathway has been described through VN’s fibers, which is able to dampen peripheral inflammation and to decrease intestinal permeability, thus very probably modulating microbiota composition. Stress inhibits the VN and has deleterious effects on the gastrointestinal tract and on the microbiota, and is involved in the pathophysiology of gastrointestinal disorders such as irritable bowel syndrome (IBS) and inflammatory bowel disease (IBD) which are both characterised by a dysbiosis. A low vagal tone has been described in IBD and IBS patients thus favouring peripheral inflammation. Targeting the VN, for example through VN stimulation which has anti‑inflammatory properties, would be of interest to restore homeostasis in the microbiota‑gut‑brain axis.

Background: Electrical stimulation of the auricular branch of the vagus nerve (ABVN) via transcutaneous auricular vagus nerve stimulation (taVNS) may influence afferent vagal networks. There have been 5 prior taVNS/fMRI studies, with inconsistent findings due to variability in stimulation targets and parameters. Objective: We developed a taVNS/fMRI system to enable concurrent electrical stimulation and fMRI acquisition to compare the effects of taVNS in relation to control stimulation. Methods: We enrolled 17 healthy adults in this single-blind, crossover taVNS/fMRI trial. Based on parameters shown to affect heart rate in healthy volunteers, participants received either left tragus (active) or earlobe (control) stimulation at 500 μs 25 HZ for 60 s (repeated 3 times over 6 min). Whole brain fMRI analysis was performed exploring the effect of: active stimulation, control stimulation, and the comparison. Region of interest analysis of the midbrain and brainstem was also conducted. Results: Active stimulation produced significant increased BOLD signal in the contralateral postcentral gyrus, bilateral insula, frontal cortex, right operculum, and left cerebellum. Control stimulation produced BOLD signal activation in the contralateral postcentral gyrus. In the active vs. control contrast, tragus stimulation produced significantly greater BOLD increases in the right caudate, bilateral anterior cingulate, cerebellum, left prefrontal cortex, and mid-cingulate. Conclusion: Stimulation of the tragus activates the cerebral afferents of the vagal pathway and combined with our review of the literature suggest that taVNS is a promising form of VNS. Future taVNS/fMRI studies should systematically explore various parameters and alternative stimulation targets aimed to optimize this novel form of neuromodulation.

Background. Severity of arm impairment alone does not explain motor outcomes in people with severe impairment post stroke. Objective. Define the contribution of brain biomarkers to upper limb motor outcomes in people with severe arm impairment post stroke. Methods. Paretic arm impairment (Fugl-Meyer upper limb, FM-UL) and function (Wolf Motor Function Test rate, WMFT-rate) were measured in 15 individuals with severe (FM-UL ≤ 30/66) and 14 with mild–moderate (FM-UL > 40/66) impairment. Transcranial magnetic stimulation and diffusion weight imaging indexed structure and function of the corticospinal tract and corpus callosum. Separate models of the relationship between possible biomarkers and motor outcomes at a single chronic (≥6 months) time point post stroke were performed. Results. Age (ΔR²0.365, p = 0.017) and ipsilesional-transcallosal inhibition (ΔR²0.182, p = 0.048) explained a 54.7% (p = 0.009) variance in paretic WMFT-rate. Prefrontal corpus callosum fractional anisotropy (PF-CC FA) alone explained 49.3% (p = 0.007) variance in FM-UL outcome. The same models did not explain significant variance in mild–moderate stroke. In the severe group, k-means cluster analysis of PF-CC FA distinguished two subgroups, separated by a clinically meaningful and significant difference in motor impairment (p = 0.049) and function (p = 0.006) outcomes. Conclusion. Corpus callosum function and structure were identified as possible biomarkers of motor outcome in people with chronic and severe arm impairment.

Persistent long-term memory depends on successful stabilization and integration of new memories after initial encoding [1, 2]. This consolidation process is thought to require neuromodulatory factors such as dopamine, noradrenaline, and brain-derived neurotrophic factor [3–7]. Without the release of such factors around the time of encoding, memories will decay rapidly [3, 5, 6, 8]. Recent studies have shown that physical exercise acutely stimulates the release of several consolidation‑promoting factors in humans [9–14], raising the question of whether physical exercise can be used to improve memory retention [15–17]. Here, we used a single session of physical exercise after learning to exogenously boost memory consolidation and thus long‑term memory. Three groups of randomly assigned participants first encoded a set of picture‑location associations. Afterward, one group performed exercise immediately, one 4 hr later, and the third did not perform any exercise. Participants otherwise underwent exactly the same procedures to control for potential experimental confounds. Forty‑eight hours later, participants returned for a cued‑recall test in a magnetic resonance scanner. With this design, we could investigate the impact of acute exercise on memory consolidation and retrieval‑related neural processing. We found that performing exercise 4 hr, but not immediately, after encoding improved the retention of picture‑location associations compared to the no‑exercise control group. Moreover, performing exercise after a delay was associated with increased hippocampal pattern similarity for correct responses during delayed retrieval. Our results suggest that appropriately timed physical exercise can improve long‑term memory and highlight the potential of exercise as an intervention in educational and clinical settings.

The foreseen outcome of a rehabilitation treatment is a stable improvement on the functional outcomes, which can be longitudinally assessed through multiple measures to help clinicians in functional evaluation. In this study, we propose an automatic comprehensive method of combining multiple measures in order to assess a functional improvement. As test‑bed, a functional electrical stimulation based treatment for foot drop correction performed with chronic post‑stroke participants is presented. Patients were assessed on five relevant outcome measures before, after intervention, and at a follow‑up time‑point. A novel algorithm based on variables minimum detectable change is proposed and implemented in a custom‑made software, combining the outcome measures to obtain a unique parameter: capacity score. The difference between capacity scores at different timing is three holded to obtain improvement evaluation. Ten clinicians evaluated patients on the Improvement Clinical Global Impression scale. Eleven patients underwent the treatment, and five resulted to achieve a stable functional improvement, as assessed by the proposed algorithm. A statistically significant agreement between intra‑clinicians and algorithm‑clinicians evaluations was demonstrated. The proposed method evaluates functional improvement on a single‑subject yes/no base by merging different measures (e.g., kinematic, muscular) and it is validated against clinical evaluation.

Oscillatory neuronal synchronization between cortical areas has been suggested to constitute a flexible mechanism to coordinate information flow in the human cerebral cortex. However, it remains unclear whether synchronized neuronal activity merely represents an epiphenomenon or whether it is causally involved in the selective gating of information. Here, we combined bilateral high-density transcranial alternating current stimulation (HD-tACS) at 40 Hz with simultaneous electroencephalographic (EEG) recordings to study immediate electrophysiological effects during the selective entrainment of oscillatory gamma-band signatures. We found that interhemispheric functional connectivity was modulated in a predictable, phase-specific way: In-phase stimulation enhanced synchronization, anti-phase stimulation impaired functional coupling. Perceptual correlates of these connectivity changes were found in an ambiguous motion task, which strongly support the functional relevance of long-range neuronal coupling. Additionally, our results revealed a decrease in oscillatory alpha power in response to the entrainment of gamma band signatures. This finding provides causal evidence for the antagonistic role of alpha and gamma oscillations in the parieto-occipital cortex and confirms that the observed gamma band modulations were physiological in nature. Our results demonstrate that synchronized cortical network activity across several spatiotemporal scales is essential for conscious perception and cognition.

Neuromodulation of spinal sensorimotor circuits improves motor control in animal models and humans with spinal cord injury. With common neuromodulation devices, electrical stimulation parameters are tuned manually and remain constant during movement. We developed a mechanistic framework to optimize neuromodulation in real time to achieve high-fidelity control of leg kinematics during locomotion in rats. We first uncovered relationships between neuromodulation parameters and recruitment of distinct sensorimotor circuits, resulting in predictive adjustments of leg kinematics. Second, we established a technological platform with embedded control policies that integrated robust movement feedback and feed-forward control loops in real time. These developments allowed us to conceive a neuroprosthetic system that controlled a broad range of foot trajectories during continuous locomotion in paralyzed rats. Animals with complete spinal cord injury performed more than 1000 successive steps without failure, and were able to climb staircases of various heights and lengths with precision and fluidity. Beyond therapeutic potential, these findings provide a conceptual and technical framework to personalize neuromodulation treatments for other neurological disorders.

Background: Parkinson’s disease (PD) is characterized by reduced flexibility, conceptualization, and visuo-spatial abilities. Although these are essential to creativity, case studies show emergence of creativity during PD. Knowledge about the role of dopamine in creativity so far only stems from a few case reports. We aim at demonstrating that creativity can be induced by dopaminergic treatments in PD, and tends to disappear after withdrawal of dopamine agonists.Methods: Eleven consecutive creative PD patients were selected from candidates for subthalamic nucleus deep brain stimulation (STN DBS) surgery, and compared to 22 non-creative control PD patients. Motor disability (UPDRS III), cognition (Frontal score, Mattis scale), and behavior (Ardouin scale) were assessed before surgery and 1 year after. Results: Before surgery, whereas cognitive and motor assessments were similar between groups, dopamine agonist (but not levodopa) dosages were higher in creative patients (p = 0.01). The Ardouin scale revealed also a specific psycho-behavioral profile of creative patients which had higher scores for mania (p < 0.001), hobbyism (p = 0.001), nocturnal hyperactivity (p = 0.041), appetitive functioning (p = 0.003), and ON euphoria (p = 0.007) and lower scores for apathy and OFF dysphoria (p = 0.04 for each). Post-operative motor, cognitive, and behavioral scores as dopaminergic treatment dosages were equivalent between groups. Motor improvement allowed for a 68.6% decrease in dopaminergic treatment. Only 1 of the 11 patients remained creative after surgery. Reduction of dopamine agonist was significantly correlated to the decrease in creativity in the whole population of study (Spearman correlation coefficient ρ = 0.47 with confidence index of 95% = 0.16; 0.70, p = 0.0053). Conclusion: Creativity in PD is linked to dopamine agonist therapy, and tends to disappear after STN DBS in parallel to reduction of dopamine agonists, which are relatively selective for the mesolimbic D3 dopamine receptors.

Older adults (OA) show more diffuse brain activity than young adults (YA) during the performance of cognitive, motor, and perceptual tasks. It is unclear whether this over-activation reflects compensation or dedifferentiation. Typically, these investigations have not evaluated the organization of the resting brain, which can help to determine whether more diffuse representations reflect physiological or task- dependent effects. In the present study we used transcranial magnetic stimulation (TMS) to determine whether there are differences in motor cortex organization of both brain hemispheres in YA and OA. We measured resting motor threshold, motor evoked potential (MEP) latency and amplitude, and extent of first dorsal interosseous representations, in addition to a computerized measure of reaction time. There was no significant age difference in motor threshold, but we did find that OA had larger contralateral MEP amplitudes and a longer contralateral MEP latency. Furthermore, the spatial extent of motor representations in OA was larger. We found that larger dominant hemisphere motor representations in OA were associated with higher reaction times, suggesting dedifferentiation rather than compensation effects.

To test the hypothesis that the mesencephalic ventral tegmental area (VTA) plays a role in autonomic control of the cardiovascular system, we examined the cardiovascular effects of electrical stimulation of the mesencephalic ventral areas in anesthetized, paralyzed cats and rats. Electrical stimulation of the VTA for 30 s (100-μA current intensity; 40-50-Hz pulse frequency; 0.5-1-ms pulse duration) increased femoral blood flow by 130-162% in anesthetized cats and rats, whereas the identical stimulation of the substantia nigra (SN) failed to increase femoral blood flow. Electrical stimulation of the VTA also increased the arterial blood pressure and heart rate in anesthetized rats, but did not alter them in anesthetized cats. Accordingly, femoral vascular conductance was increased by 102-134% in both cats and rats. Atropine methyl nitrate (0.1 mg/kg) injected intravenously in the cats markedly attenuated the increases in femoral blood flow and vascular conductance. VTA stimulation was able to produce substantial increases in femoral blood flow and vascular conductance following a decerebration procedure performed at the premammillary and precollicular level in the cats, although their responses tended to attenuate to 55-69% of the control before the decerebration. Thus, it is likely that electrical stimulation of the VTA, but not the SN, is capable of evoking skeletal muscle vasodilatation, particularly via a sympathetically mediated cholinergic mechanism in the cat, and that the ascending projection from the VTA to the forebrain may not be responsible for the muscle vasodilatation.

We introduce a method for noninvasively measuring muscle contraction in vivo, based on near-infrared diffusing-wave spectroscopy (DWS). The method exploits the information about time-dependent shear motions within the contracting muscle that are contained in the temporal autocorrelation function g(1)(τ,t) of the multiply scattered light field measured as a function of lag time, τ, and time after stimulus, t. The analysis of g(1)(τ,t) measured on the human M. biceps brachii during repetitive electrical stimulation, using optical properties measured with time-resolved reflectance spectroscopy, shows that the tissue dynamics giving rise to the speckle fluctuations can be described by a combination of diffusion and shearing. The evolution of the tissue Cauchy strain e(t) shows a strong correlation with the force, indicating that a significant part of the shear observed with DWS is due to muscle contraction. The evolution of the DWS decay time shows quantitative differences between the M. biceps brachii and the M. gastrocnemius, suggesting that DWS allows to discriminate contraction of fast- and slow-twitch muscle fibers.

Observation of another’s action can selectively facilitate the brain’s motor circuits for making the same action . A ‘mirror-matching mechanism’ might map observed actions onto the observer’s own motor representations. Crucially, this view suggests that the brain represents others’ actions like one’s own. However, this hypothesis has been difficult to test because the experience of one’s own body differs from that of others’ bodies with respect to viewpoint, morphological features, familiarity, and the hallmark feature of kinaesthetic experience. We used an established method for manipulating the sense of body ownership (“rubber-hand illusion”) to compare effects of observing actions that either were or were not illusorily attributed to the subject’s own body. We show that observing another’s actions facilitated the motor system, whereas observing identical actions, which were illusorily attributed to the subject’s own body, showed the opposite pattern. Thus, motor facilitation strongly depends on the agent to whom the observed action is attributed. This result contradicts previous concepts of equivalence between one’s own actions and actions of others and suggests that social differentiation, not equivalence, is characteristic of the human action system.

Objectives: Post-stroke shoulder pain is probably the most frequent complication in hemiplegia and has repercussions on motor rehabilitation and the psychological equilibrium of the patient. The strategies for prevention and treatment are presented. Aetiology: Among the various factors contributing to the occurrence of shoulder pain in hemiplegia, some are related to the joint, such as lesion of the rotator cuff tendons, reflex sympathetic dystrophy, inferior‑anterior subluxation of the head of the humerus, whereas others are related to the neurologic lesion such as central post‑stroke pain, lack of sensibility, unilateral neglect and spasticity. Prevention: Efforts should be made from the start to keep the shoulder in an ideal position at all times and movement of the shoulder and upper limb should be carried out with care. Treatment: Will be aimed to the cause of pain and passive or active range of motion exercises will be encouraged. Physical, medical and surgical treatments have improved over the last few decades. Functional electrical stimulation in patients with shoulder pain and subluxation, applied early after onset of the stroke, has shown beneficial positive effects on subluxation, pain and mobility. Efforts should therefore be made to better understand the post‑stroke shoulder pain in order to provide better outcomes of rehabilitation and thus improve quality of life for patients.

Action observation enhances cortico-spinal excitability. Here we tested the specificity of this effect and the role played by the orientation of the observer. Ten normal subjects observed video clips of right hand performing three different finger movements (thumb ab-/adduction, index ab-/adduction, index extens-/flexion) in two different orientations (Away, i.e., natural hand-orientation facing out from the observer; or Toward, i.e., unnatural hand-orientation facing toward the observer). Motor-evoked potentials (MEPs) induced by transcranial magnetic stimulation (TMS) were recorded from the abductor pollicis brevis (APB) and the first dorsal interosseus (FDI) muscles. Movement direction of the index finger was recorded using force transducers. Facilitation of MEP size was significantly greater for APB during observation of thumb movements and for FDI during observation of index finger movements. Facilitation of MEP size was significantly greater when the hand presented on screen was facing out from and corresponding to that of the observer (Away orientation). The direction of the index finger movement evoked by TMS shifted toward extension/flexion versus ab-/adduction matching the observed movement. Our results give further evidence that observation of a movement enhances motor output to the muscles involved in the movement and facilitates the observed action. In addition, we provide novel evidence about the high degree of specificity of this observation-induced motor cortical modulation. The degree of modulation depends on hand orientation. The modulation is maximal when the observed action corresponds to the orientation of the observer.

Transcranial magnetic (TMS) and electrical (TES) stimulation was used to assess the contribution of the corticospinal pathway to activation of the first dorsal interosseous muscle (FDI) in each hand of 16 subjects. TMS was applied at relaxed threshold intensity while the subject performed isometric index finger abduction at seven force levels [0.5 N to 50% maximal voluntary contraction (MVC)]. In a separate session, TES of equivalent intensity was applied to each hemisphere in 5 of these subjects while they performed the same force‑matching protocol. In the resting state, mean threshold intensity for a muscle‑evoked potential (MEP) in FDI using TMS was similar for the hemispheres controlling the dominant and nondominant hands. The size of the threshold MEPs in resting FDI after TMS and TES were also similar in each hand. With TMS, contraction‑induced facilitation of the MEP in FDI was significantly larger when the nondominant hand was used for index finger abduction. In the pooled data, the nondominant/dominant ratio of MEP areas (normalized to the maximum M wave) ranged from 1.7 in the weakest contraction (0.5 N) to 1.1 in the strongest (50% MVC). Eight subjects had significant differences between hands in favour of the nondominant hand, whereas in two subjects contraction‑induced facilitation of MEPs was larger in the dominant hand. In five subjects for whom detailed motor‑unit data were available from a previous study, lateral differences in MEP facilitation were positively correlated with differences in FDI motor‑unit synchronization between hands. With TES, contraction‑induced facilitation of the MEP was similar in each hand, suggesting that spinal excitability was equivalent on both sides. For the group of five subjects tested with both stimulation techniques, contraction‑induced facilitation of the MEP was significantly larger after TMS than that obtained with TES when the contraction was performed with the nondominant hand, but not when the dominant hand was used to perform the task. We conclude that the extent of corticospinal neuron involvement in the command for simple index finger abduction in right‑handed subjects is generally greater when the nondominant hand is used, compared with the same task performed with the dominant hand.