Indication and eligibility of glioma patients for awake surgery: A scoping review by a multidisciplinary perspective.

Background: Awake surgery (AS) permits intraoperative mapping of cognitive and motor functions, allowing neurosurgeons to tailor the resection according to patient functional boundaries thus preserving long-term patient integrity and maximizing extent of resection. Given the increased risks of the awake scenario, the growing importance of AS in surgical practice favored the debate about patient selection concerning both indication and eligibility criteria. Nonetheless, a systematic investigation is lacking in the literature. Objective: To provide a scoping review of the literature concerning indication and eligibility criteria for AS in patients with gliomas to answer the questions:1) "What are the functions mostly tested during AS protocols?" and 2) "When and why should a patient be excluded from AS?". Materials and methods: Pertinent studies were retrieved from PubMed, PsycArticles and Cochrane Central Register of Controlled Trials (CENTRAL), published until April 2021 according to the PRISMA Statement Extension for Scoping Reviews. The retrieved abstracts were checked for the following features being clearly stated: 1) the population described as being composed of glioma(LGG or HGG) patients; 2) the paper had to declare which cognitive or sensorimotor function was tested, or 2bis)the decisional process of inclusion/exclusion for AS had to be described from at least one of the following perspectives: neurosurgical, neurophysiological, anesthesiologic and psychological/neuropsychological. Results: One hundred and seventy-eight studies stated the functions being tested on 8004 patients. Language is the main indication for AS, even if tasks and stimulation techniques changed over the years. It is followed by monitoring of sensorimotor and visuospatial pathways. This review demonstrated an increasing interest in addressing other superior cognitive functions, such as executive functions and emotions. Forty-five studies on 2645 glioma patients stated the inclusion/exclusion criteria for AS eligibility. Inability to cooperate due to psychological disorder(i.e. anxiety),severe language deficits and other medical conditions(i.e.cardiovascular diseases, obesity, etc.)are widely reported as exclusion criteria for AS. However, a very few papers gave scale exact cut-off. Likewise, age and tumor histology are not standardized parameters for patient selection. Conclusion: Given the broad spectrum of functions that might be safely and effectively monitored via AS, neurosurgeons and their teams should tailor intraoperative testing on patient needs and background as well as on tumor location and features. Whenever the aforementioned exclusion criteria are not fulfilled, AS should be strongly considered for glioma patients.

Peri-lead edema and local field potential correlation in post-surgery subthalamic nucleus deep brain stimulation patients.

Implanting deep brain stimulation (DBS) electrodes in patients with Parkinson's disease often results in the appearance of a non-infectious, delayed-onset edema that disappears over time. However, the time window between the DBS electrode and DBS stimulating device implant is often used to record local field potentials (LFPs) which are used both to better understand basal ganglia pathophysiology and to improve DBS therapy. In this work, we investigated whether the presence of post-surgery edema correlates with the quality of LFP recordings in eight patients with advanced Parkinson's disease implanted with subthalamic DBS electrodes. The magnetic resonance scans of the brain after 8.5 ± 1.5 days from the implantation surgery were segmented and the peri-electrode edema volume was calculated for both brain hemispheres. We found a correlation (ρ = -0.81, p < 0.0218, Spearman's correlation coefficient) between left side local field potentials of the low beta band (11-20 Hz) and the edema volume of the same side. No other significant differences between the hemispheres were found. Despite the limited sample size, our results suggest that the effect on LFPs may be related to the edema localization, thus indicating a mechanism involving brain networks instead of a simple change in the electrode-tissue interface.

EEG Evaluation of Stress Exposure on Healthcare Workers During COVID-19 Emergency: Not Just an Impression.

Psychological distress among healthcare professionals, although already a common condition, was exacerbated by the COVID-19 pandemic. This effect has been generally self-reported or assessed through questionnaires. We aimed to identify potential abnormalities in the electrical activity of the brain of healthcare workers, operating in different roles during the pandemic. Cortical activity, cognitive performances, sleep, and burnout were evaluated two times in 20 COVID-19 frontline operators (FLCO, median age 29.5 years) and 20 operators who worked in COVID-19-free units (CFO, median 32 years): immediately after the outbreak of the pandemic (first session) and almost 6 months later (second session). FLCO showed higher theta relative power over the entire scalp (FLCO = 19.4%; CFO = 13.9%; p = 0.04) and lower peak alpha frequency of electrodes F7 (FLCO = 10.4 Hz; CFO = 10.87 Hz; p = 0.017) and F8 (FLCO = 10.47 Hz; CFO = 10.87 Hz; p = 0.017) in the first session. FLCO parietal interhemispheric coherence of theta (FLCO I = 0.607; FLCO II = 0.478; p = 0.025) and alpha (FLCO I = 0.578; FLCO II = 0.478; p = 0.007) rhythms decreased over time. FLCO also showed lower scores in the global cognitive assessment test (FLCO = 22.72 points; CFO = 25.56; p = 0.006) during the first session. The quantitative evaluation of the cortical activity might therefore reveal early signs of changes secondary to stress exposure in healthcare professionals, suggesting the implementation of measures to prevent serious social and professional consequences.

Cognitive and Autonomic Dysfunction in Multiple System Atrophy Type P and C: A Comparative Study.

Multiple System Atrophy (MSA) is a rare neurodegenerative disease, clinically defined by a combination of autonomic dysfunction and motor involvement, that may be predominantly extrapyramidal (MSA-P) or cerebellar (MSA-C). Although dementia is generally considered a red flag against the clinical diagnosis of MSA, in the last decade the evidence of cognitive impairment in MSA patients has been growing. Cognitive dysfunction appears to involve mainly, but not exclusively, executive functions, and may have different characteristics and progression in the two subtypes of the disease (i.e., MSA-P and MSA-C). Despite continued efforts, combining in-vivo imaging studies as well as pathological studies, the physiopathological bases of cognitive involvement in MSA are still unclear. In this view, the possible link between cardiovascular autonomic impairment and decreased cognitive performance, extensively investigated in PD, needs to be clarified as well. In the present study, we evaluated a cohort of 20 MSA patients (9 MSA-P, 11 MSA-C) by means of a neuropsychological battery, hemodynamic assessment (heart rate and arterial blood pressure) during rest and active standing and bedside autonomic function tests assessed by heart rate variability (HRV) parameters and sympathetic skin response (SSR) in the same experimental session. Overall, global cognitive functioning, as indicated by the MoCA score, was preserved in most patients. However, short- and long-term memory and attentional and frontal-executive functions were moderately impaired. When comparing MSA-P and MSA-C, the latter obtained lower scores in tests of executive functions and verbal memory. Conversely, no statistically significant difference in cardiovascular autonomic parameters was identified between MSA-P and MSA-C patients. In conclusion, moderate cognitive deficits, involving executive functions and memory, are present in MSA, particularly in MSA-C patients. In addition, our findings do not support the role of dysautonomia as a major driver of cognitive differences between MSA-P and MSA-C.

Anodal Transcranial Direct Current Stimulation over the Cerebellum Enhances Sadness Recognition in Parkinson's Disease Patients: a Pilot Study.

Emotional processing impairments, resulting in a difficulty to decode emotions from faces especially for negative emotions, are characteristic non-motor features of Parkinson's disease (PD). There is limited evidence about the specific contribution of the cerebellum to the recognition of emotional contents in facial expressions even though patients with cerebellar dysfunction often lose this ability. In this study, we aimed to evaluate whether the recognition of facial expressions can be modulated by cerebellar transcranial direct current stimulation (tDCS) in PD patients. Nine PD patients were enrolled and received anodal and sham tDCS (2 mA, 20 min), for 5 consecutive days, in two separate cycles at intervals of at least 1 month. The facial emotion recognition task was administered at baseline (T0) and after cerebellar tDCS on day 5 (T1). Our preliminary study showed that anodal cerebellar tDCS significantly enhanced emotional recognition in response to sad facial expressions by about 16%, but left recognition of anger, happiness, and neutral facial expressions unchanged. Despite the small sample size, our preliminary results show that anodal tDCS applied for five consecutive days over the cerebellum modulates the way PD patients recognize specific facial expressions, thus suggesting that the cerebellum plays a crucial role in recognition of negative emotions and corroborating previous knowledge on the link between social cognition and the cerebellum.

Effects of Transcutaneous Spinal Direct Current Stimulation (tsDCS) in Patients With Chronic Pain: A Clinical and Neurophysiological Study.

Background and Aims: Chronic pain is a complex clinical condition, often devastating for patients and unmanageable with pharmacological treatments. Converging evidence suggests that transcutaneous spinal Direct Current Stimulation (tsDCS) might represent a complementary therapy in managing chronic pain. In this randomized, double-blind and sham-controlled crossover study, we assessed tsDCS effects in chronic pain patients. Methods: Sixteen patients (aged 65.06 ± 16.16 years, eight women) with chronic pain of different etiology underwent sham and anodal tsDCS (anode over the tenth thoracic vertebra, cathode over the somatosensory cortical area: 2.5 mA, 20 min, 5 days for 1 week). As outcomes, we considered the Visual Analog Scale (VAS), the Neuropathic Pain Symptom Inventory (NPSI), and the components of the lower limb flexion reflex (LLFR), i.e., RIII threshold, RII latency and area, RIII latency and area, and flexion reflex (FR) total area. Assessments were conducted before (T0), immediately at the end of the treatment (T1), after 1 week (T2) and 1 month (T3). Results: Compared to sham, anodal tsDCS reduced RIII area at T2 (p = 0.0043) and T3 (p = 0.0012); similarly, FR total area was reduced at T3 (p = 0.03). Clinically, anodal tsDCS dampened VAS at T3 (p = 0.015), and NPSI scores at T1 (p = 0.0012), and T3 (p = 0.0015), whereas sham condition left them unchanged. Changes in VAS and NPSI scores linearly correlated with the reduction in LLFR areas (p = 0.0004). Conclusions: Our findings suggest that tsDCS could modulate nociceptive processing and pain perception in chronic pain syndromes.

Subclinical myopathic changes in COVID-19.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is associated to neuromuscular symptoms in up to 10.7% of hospitalized patients. Nevertheless, the extent of muscular involvement in infected subjects with no signs of myopathy has never been assessed with neurophysiological investigations. METHODS: Over a 3-week period - from April 30 through May 20, 2020 - a total of 70 patients were hospitalized in the Internal Medicine Ward of the Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico in Milan, Italy. After excluding patients who underwent invasive ventilation and steroid treatment, 12 patients were evaluated. Nerve conduction studies (NCS) included the analysis of conduction velocity, amplitude, and latency for bilateral motor tibial, ulnar nerves, and sensory sural and radial nerves. Unilateral concentric-needle electromyography (EMG) was performed evaluating at least 4 areas of 8 selected muscles. For each muscle, spontaneous activity at rest, morphology, and recruitment of motor unit action potentials (MUAPs) were evaluated. RESULTS: While nerve conduction studies were unremarkable, needle electromyography showed myopathic changes in 6 out of 12 subjects. All patients were asymptomatic for muscular involvement. Clinical features and laboratory findings did not show relevant differences between patients with and without myopathic changes. CONCLUSION: Our data show that in SARS-CoV-2 infection muscular involvement can occur despite the absence of clinical signs or symptoms and should be considered part of the disease spectrum. The application of muscle biopsy to unravel the mechanisms of myofiber damage on tissue specimens could help to clarify the pathogenesis and the treatment response of coronavirus-mediated injury.

Spinal direct current stimulation (tsDCS) in hereditary spastic paraplegias (HSP): A sham-controlled crossover study.

Objective: Hereditary spastic paraplegia (HSP) represents a heterogeneous group of neurodegenerative diseases characterized by progressive spasticity and lower limb weakness. We assessed the effects of transcutaneous spinal direct current stimulation (tsDCS) in HSP.Design: A double-blind, randomized, crossover and sham-controlled study.Setting: Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan.Participants: eleven patients with HSP (six men, mean age ± SD: 37.3 ± 8.1 years), eight affected by spastin/SPG4,1 by atlastin1/SPG3a, 1 by paraplegin/SPG7 and 1 by ZFYVE26/SPG15.Interventions: tsDCS (anodal or sham, 2.0 mA, 20', five days) delivered over the thoracic spinal cord (T10-T12).Outcome measures: Motor-evoked potentials (MEPs), the H-reflex (Hr), F-waves, the Ashworth scale for clinical spasticity, the Five Minutes Walking test and the Spastic Paraplegia Rating Scale (SPRS) were assessed. Patients were evaluated before tsDCS (T0), at the end of the stimulation (T1), after one week (T2), one month (T3) and two months (T4).Results: The score of the Ashworth scale improved in the anodal compared with sham group, up to two months following the end of stimulation (T1, P = .0137; T4, P = .0244), whereas the Five Minutes Walking test and SPRS did not differ between the two groups. Among neurophysiological measures, both anodal and sham tsDCS left Hr, F-waves and MEPs unchanged over time.Conclusions: Anodal tsDCS significantly decreases spasticity and might be a complementary strategy for the treatment of spasticity in HSP.

Electroencephalography during SARS-CoV-2 outbreak: practical recommendations from the task force of the Italian Society of Neurophysiology (SINC), the Italian League Against Epilepsy (LICE), and the Italian Association of Neurophysiology Technologists (AITN).

BACKGROUND: During COVID-19 lockdown, non-urgent medical procedures were suspended. Grade of urgency of electroencephalography (EEG) may vary according to the clinical indication, setting, and status of infection of SARS-CoV-2 virus. "Italian Society of Clinical Neurophysiology" (SINC), "Italian League Against Epilepsy" (LICE), and the "Italian Association of Neurophysiology Technologists" (AITN) aimed to provide clinical and technical recommendation for EEG indications and recording standards in this pandemic era. METHODS: Presidents of SINC, LICE, and AITN endorsed three members per each society to formulate recommendations: classification of the degree of urgency of EEG clinical indications, management and behavior of physicians and neurophysiology technologists, hygiene and personal protection standards, and use of technical equipment. RESULTS: Scientific societies endorsed a paper conveying the recommendation for EEG execution in accordance with clinical urgency, setting (inpatients/outpatients), status of SARS-CoV-2 virus infection (positive, negative and uncertain), and phase of governmental restrictions (phase 1 and 2). Briefly, in phase 1, EEG was recommended only for those acute/subacute neurological symptoms where EEG is necessary for diagnosis, prognosis, or therapy. Outpatient examinations should be avoided in phase 1, while they should be recommended in urgent cases in phase 2 when they could prevent an emergency room access. Reduction of staff contacts must be encouraged through rescheduling job shifts. The use of disposable electrodes and dedicated EEG devices for COVID-19-positive patients are recommended. CONCLUSIONS: During the different phases of COVID-19 pandemic, the EEG should be reserved for patients really benefiting from its execution in terms of diagnosis, treatment, prognosis, and avoidance of emergency room access.

The impaired diaphragmatic function after bilateral lung transplantation: A multifactorial longitudinal study.

BACKGROUND: Lung transplantation is a complex but effective treatment of end-stage pulmonary disease. Among the post-operative complications, phrenic nerve injury, and consequent diaphragmatic dysfunction are known to occur but are hitherto poorly described. We aimed to investigate the effect of lung transplantation on diaphragmatic function with a multimodal approach. METHODS: A total of 30 patients were studied at 4 time points: pre-operatively, at discharge after surgery, and after approximately 6 and subsequently 12 months post surgery. The diaphragmatic function was studied in terms of geometry (assessed by the radius of the diaphragmatic curvature delineated on chest X-ray), weakness (considering changes in forced vital capacity when the patient shifted from upright to supine position), force (maximal pressure during sniff), mobility (excursion of the dome of the diaphragm delineated by ultrasound), contractility (thickening fraction assessed by ultrasound), electrical activity (latency and area of compound muscle action potential during electrical stimulation of phrenic nerve), and kinematics (relative contribution of the abdominal compartment to tidal volume). RESULTS: Despite good clinical recovery (indicated by spirometry and 6 minutes walking test), a reduction of the diaphragmatic function was detected at discharge; it persisted 6 months later to recover fully 1 year after transplantation. Diaphragmatic dysfunction was demonstrated in terms of force, weakness, electrical activity, and kinematics. Our data suggest that the dysfunction was caused by phrenic nerve neurapraxia or moderate axonotmesis, potentially as a consequence of the surgical procedure (i.e., the use of ice and pericardium manipulation). CONCLUSIONS: The occurrence of diaphragmatic dysfunction in patients with a good clinical recovery indicates that the evaluation of diaphragmatic function should be included in the post-operative assessment after lung transplantation.

Spino-cerebellar tDCS modulates N100 components of the P300 event related potential.

OBJECTIVE: To evaluate the role of the cerebellum and spinal cord in cognitive processes, we assessed changes in event-related potentials (ERPs), before and after different combinations of spinal and cerebellar direct current stimulation (tDCS) in healthy subjects. METHOD: We enrolled 37 volunteers (11 males and 26 females, aged 20-50 years), who were subsequently randomly assigned to one of four stimulation conditions: i) anodal cerebellar tDCS, with the reference electrode over the right shoulder; ii) anodal spinal tDCS, with the reference electrode over the right shoulder; iii) anodal spinal tDCS with cathodal cerebellar tDCS, and iv) sham stimulation. Stimulation intensity was set at 2 mA and delivered for 20 min. ERPs were assessed in an auditory oddball task before (T0) and 5 (T1) and 30 min (T2) after tDCS offset. RESULTS: In condition iii, spino-cerebellar tDCS, the N100 component at T2 increased in amplitude by 60% (p = 0.019), whereas the sham stimulation left the N100 amplitude unchanged (p > 0.05). CONCLUSION: The N100 wave reflects pre-attentive processes and correlates with arousal due to a specific stimuli and selective attention. Because spino-cerebellar tDCS induces electric fields in the brainstem, the facilitation of the N100 may be due to the modulation of the reticular formation. Regardless of the underlying mechanism, spino-cerebellar tDCS can help patients with deficits at the pre-attentive or selective attentional level.

Behavioral and Neurophysiological Effects of Transcranial Direct Current Stimulation (tDCS) in Fronto-Temporal Dementia.

Fronto-temporal dementia (FTD) is the clinical-diagnostic term that is now preferred to describe patients with a range of progressive dementia syndromes associated with focal atrophy of the frontal and anterior temporal cerebral regions. Currently available FTD medications have been used to control behavioral symptoms, even though they are ineffective in some patients, expensive and may induce adverse effects. Alternative therapeutic approaches are worth pursuing, such as non-invasive brain stimulation with transcranial direct current (tDCS). tDCS has been demonstrated to influence neuronal excitability and reported to enhance cognitive performance in dementia. The aim of this study was to investigate whether applying Anodal tDCS (2 mA intensity, 20 min) over the fronto-temporal cortex bilaterally in five consecutive daily sessions would improve cognitive performance and behavior symptoms in FTD patients, also considering the neuromodulatory effect of stimulation on cortical electrical activity measured through EEG. We recruited 13 patients with FTD and we tested the effect of Anodal and Sham (i.e., placebo) tDCS in two separate experimental sessions. In each session, at baseline (T0), after 5 consecutive days (T1), after 1 week (T2), and after 4 weeks (T3) from the end of the treatment, cognitive and behavioral functions were tested. EEG (21 electrodes, 10-20 international system) was recorded for 5 min with eyes closed at the same time points in nine patients. The present findings showed that Anodal tDCS applied bilaterally over the fronto-temporal cortex significantly improves (1) neuropsychiatric symptoms (as measured by the neuropsychiatric inventory, NPI) in FTD patients immediately after tDCS treatment, and (2) simple visual reaction times (sVRTs) up to 1 month after tDCS treatment. These cognitive improvements significantly correlate with the time course of the slow EEG oscillations (delta and theta bands) measured at the same time points. Even though further studies on larger samples are needed, these findings support the effectiveness of Anodal tDCS over the fronto-temporal regions in FTD on attentional processes that might be correlated to a normalized EEG low-frequency pattern.

Cathodal Transcranial Direct Current Stimulation Improves Focal Hand Dystonia in Musicians: A Two-Case Study.

Focal hand dystonia (FHD) in musicians is a movement disorder causing abnormal movements and irregularities in playing. Since weak electrical currents applied to the brain induce persistent excitability changes in humans, cathodal tDCS was proposed as a possible non-invasive approach for modulating cortical excitability in patients with FHD. However, the optimal targets and modalities have still to be determined. In this pilot study, we delivered cathodal (2 mA), anodal (2 mA) and sham tDCS over the motor areas bilaterally for 20 min daily for five consecutive days in two musicians with FHD. After cathodal tDCS, both patients reported a sensation of general wellness and improved symptoms of FHD. In conclusion, our pilot results suggest that cathodal tDCS delivered bilaterally over motor-premotor (M-PM) cortex for 5 consecutive days may be effective in improving symptoms in FHD.

Transcranial Direct Current Stimulation Modulates Cortical Neuronal Activity in Alzheimer's Disease.

Quantitative electroencephalography (qEEG) showed that Alzheimer's disease (AD) is characterized by increased theta power, decreased alpha and beta power, and decreased coherence in the alpha and theta band in posterior regions. These abnormalities are thought to be associated with functional disconnections among cortical areas, death of cortical neurons, axonal pathology, and cholinergic deficits. Since transcranial Direct Current Stimulation (tDCS) over the temporo-parietal area is thought to have beneficial effects in patients with AD, in this study we aimed to investigate whether tDCS benefits are related to tDCS-induced changes in cortical activity, as represented by qEEG. A weak anodal current (1.5 mA, 15 min) was delivered bilaterally over the temporal-parietal lobe to seven subjects with probable AD (Mini-Mental State Examination, MMSE score >20). EEG (21 electrodes, 10-20 international system) was recorded for 5 min with eyes closed before (baseline, t0) and 30 min after anodal and cathodal tDCS ended (t1). At the same time points, patients performed a Word Recognition Task (WRT) to assess working memory functions. The spectral power and the inter- and intra-hemispheric EEG coherence in different frequency bands (e.g., low frequencies, including delta and theta; high frequencies, including alpha and beta) were calculated for each subject at t0 and t1. tDCS-induced changes in EEG neurophysiological markers were correlated with the performance of patients at the WRT. At baseline, qEEG features in AD patients confirmed that the decreased high frequency power was correlated with lower MMSE. After anodal tDCS, we observed an increase in the high-frequency power in the temporo-parietal area and an increase in the temporo-parieto-occipital coherence that correlated with the improvement at the WRT. In addition, cathodal tDCS produced a non-specific effect of decreased theta power all over the scalp that was not correlated with the clinical observation at the WRT. Our findings disclosed that tDCS induces significant modulations in the cortical EEG activity in AD patients. The abnormal pattern of EEG activity observed in AD during memory processing is partially reversed by applying anodal tDCS, suggesting that anodal tDCS benefits in AD patients during working memory tasks are supported by the modulation of cortical activity.

Cerebellar and Motor Cortical Transcranial Stimulation Decrease Levodopa-Induced Dyskinesias in Parkinson's Disease.

Transcranial direct current stimulation (tDCS) is a non-invasive technique for inducing prolonged functional changes in the human cerebral cortex. This simple and safe neurostimulation technique for modulating motor functions in Parkinson's disease could extend treatment option for patients with movement disorders. We assessed whether tDCS applied daily over the cerebellum (cerebellar tDCS) and motor cortex (M1-tDCS) improves motor and cognitive symptoms and levodopa-induced dyskinesias in patients with Parkinson's disease (PD). Nine patients (aged 60-85 years; four women; Hoehn & Yahr scale score 2-3) diagnosed as having idiopathic PD were recruited. To evaluate how tDCS (cerebellar tDCS or M1-tDCS) affects motor and cognitive function in PD, we delivered bilateral anodal (2 mA, 20 min, five consecutive days) and sham tDCS, in random order, in three separate experimental sessions held at least 1 month apart. In each session, as outcome variables, patients underwent the Unified Parkinson's Disease Rating Scale (UPDRS III and IV) and cognitive testing before treatment (baseline), when treatment ended on day 5 (T1), 1 week later (T2), and then 4 weeks later (T3), at the same time each day. After patients received anodal cerebellar tDCS and M1-tDCS for five days, the UPDRS IV (dyskinesias section) improved (p < 0.001). Conversely, sham tDCS, cerebellar tDCS, and M1-tDCS left the other variables studied unchanged (p > 0.05). Despite the small sample size, our preliminary results show that anodal tDCS applied for five consecutive days over the motor cortical areas and cerebellum improves parkinsonian patients' levodopa-induced dyskinesias.

An unexpected target of spinal direct current stimulation: Interhemispheric connectivity in humans.

BACKGROUND: Transcutaneous spinal Direct Current Stimulation (tsDCS) is a noninvasive technique based on the application of weak electrical currents over spinal cord. NEW METHOD: We studied the effects of tsDCS on interhemispheric motor connectivity and visual processing by evaluating changes in ipsilateral Silent Period (iSP), Transcallosal Conduction Time (TCT) and hemifield Visual Evoked Potentials (hVEPs), before (T0) and at a different intervals following sham, anodal and cathodal tsDCS (T9-T11 level, 2.0 mA, 20'). Motor Evoked Potentials (MEPs) were recorded from abductor pollicis brevis (APB), abductor hallucis (AH) and deltoid muscles. hVEPs were recorded bilaterally by reversal of a horizontal square wave grating with the display positioned in the right hemifield. RESULTS: Anodal tsDCS increased TCT (p < 0.001) and the interhemispheric delay for both the main VEP components (N1: p = 0.0003; P1: p < 0.0001), dampening at the same time iSP duration (APB: p < 0.0001; AH: p = 0.0005; deltoid: p < 0.0001), while cathodal stimulation elicited opposite effects (p < 0.0001). DISCUSSION: tsDCS modulates interhemispheric processing in a polarity-specific manner, with anodal stimulation leading to a functional disconnection between hemispheres. tsDCS would be a new promising therapeutic tool in managing a number of human diseases characterized by an impaired interhemispheric balance, or an early rehabilitation strategy in patients with acute brain lesions, when other non-invasive brain stimulation techniques (NIBS) are not indicated due to safety concerns.

Brain Plasticity Effects of Neuromodulation Against Multiple Sclerosis Fatigue.

RATIONALE: We recently reported on the efficacy of a personalized transcranial direct current stimulation (tDCS) treatment in reducing multiple sclerosis (MS) fatigue. The result supports the notion that interventions targeted at modifying abnormal excitability within the sensorimotor network could represent valid non-pharmacological treatments. OBJECTIVE: The present work aimed at assessing whether the mentioned intervention also induces changes in the excitability of sensorimotor cortical areas. METHOD: Two separate groups of fatigued MS patients were given a 5-day tDCS treatments targeting, respectively, the whole body somatosensory areas (S1wb) and the hand sensorimotor areas (SM1hand). The study had a double blind, sham-controlled, randomized, cross-over (Real vs. Sham) design. Before and after each treatment, we measured fatigue levels (by the modified fatigue impact scale, mFIS), motor evoked potentials (MEPs) in response to transcranial magnetic stimulation and somatosensory evoked potentials (SEPs) in response to median nerve stimulation. We took MEPs and SEPs as measures of the excitability of the primary motor area (M1) and the primary somatosensory area (S1), respectively. RESULTS: The Real S1wb treatment produced a 27% reduction of the mFIS baseline level, while the SM1hand treatment showed no difference between Real and Sham stimulations. M1 excitability increased on average 6% of the baseline in the S1wb group and 40% in the SM1hand group. Observed SEP changes were not significant and we found no association between M1 excitability changes and mFIS decrease. CONCLUSION: The tDCS treatment was more effective against MS fatigue when the electrode was focused on the bilateral whole body somatosensory area. Changes in S1 and M1 excitability did not correlate with symptoms amelioration. SIGNIFICANCE: The neuromodulation treatment that proved effective against MS fatigue induced only minor variations of the motor cortex excitability, not enough to explain the beneficial effects of the intervention.

Transcutaneous spinal direct current stimulation modulates human corticospinal system excitability.

This study aimed to assess the effects of thoracic anodal and cathodal transcutaneous spinal direct current stimulation (tsDCS) on upper and lower limb corticospinal excitability. Although there have been studies assessing how thoracic tsDCS influences the spinal ascending tract and reflexes, none has assessed the effects of this technique over upper and lower limb corticomotor neuronal connections. In 14 healthy subjects we recorded motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) from abductor hallucis (AH) and hand abductor digiti minimi (ADM) muscles before (baseline) and at different time points (0 and 30 min) after anodal or cathodal tsDCS (2.5 mA, 20 min, T9-T11 level). In 8 of the 14 subjects we also tested the soleus H reflex and the F waves from AH and ADM before and after tsDCS. Both anodal and cathodal tsDCS left the upper limb MEPs and F wave unchanged. Conversely, while leaving lower limb H reflex unchanged, they oppositely affected lower limb MEPs: whereas anodal tsDCS increased resting motor threshold [(mean ± SE) 107.33 ± 3.3% increase immediately after tsDCS and 108.37 ± 3.2% increase 30 min after tsDCS compared with baseline] and had no effects on MEP area and latency, cathodal tsDCS increased MEP area (139.71 ± 12.9% increase immediately after tsDCS and 132.74 ± 22.0% increase 30 min after tsDCS compared with baseline) without affecting resting motor threshold and MEP latency. Our results show that tsDCS induces polarity-specific changes in corticospinal excitability that last for >30 min after tsDCS offset and selectively affect responses in lower limb muscles innervated by lumbar and sacral motor neurons.

Spinal Direct Current Stimulation Modulates Short Intracortical Inhibition.

OBJECTIVE: Transcutaneous spinal direct current stimulation (tsDCS) is a new and safe technique for modulating spinal cord excitability. We assessed changes in intracortical excitability following tsDCS by evaluating changes in cortical silent period (cSP), paired-pulse short intracortical inhibition (SICI), and intracortical facilitation (ICF). MATERIALS AND METHODS: Healthy subjects were studied before (T0) and at different intervals (T1 and T2) after anodal, cathodal, and sham tsDCS (20', 2.0 mA) applied over the thoracic spinal cord (T10-T12). We assessed changes in cSP, SICI (interstimulus interval, ISI = 3 ms) and ICF (ISI = 10 ms). Motor-evoked potentials (MEPs) were recorded from first digital interosseus (FDI) and tibialis anterior (TA) muscles. RESULTS: Cathodal tsDCS increased MEP amplitudes at interstimulus interval of 3 ms, while anodal one elicited opposite effects (FDI: p = 0.0023; TA: p = 0.0004); conversely, tsDCS left MEP amplitudes unchanged at ISI of 10 ms (FDI: p = 0.39; TA: p = 0.45). No significant change in cSP duration was found from upper limb (p = 0.81) and lower limb (p = 0.33). CONCLUSION: tsDCS modulates inhibitory GABA(A)ergic drive, as assessed by SICI, without interfering with cSP and ICF. The possibility to interfere with cortical processing makes tsDCS a useful approach to modulate spinal drive through nonspinal mechanisms. tsDCS could also represent an early rehabilitation strategy in patients with acute brain lesions, when other noninvasive brain stimulation (NIBS) tools are not indicated due to safety concerns, as well as in the treatment of spinal diseases or pain syndromes.