Resilience and psychosocial factors in adult with epilepsy: A longitudinal study.

PURPOSE: Resilience is conceptually characterized as a dynamic process encompassing positive adaptation in the context of significant adversity. Our goal was to assess the resilience in people with epilepsy (PWE) and how it impacts longitudinally on psychosocial factors, with a particular focus on the manifestation of stigmatization-related feelings. METHODS: We consecutively enrolled 78 adults PWE (42.5 ± 16.2 years old); among them 36 (46.1 %) were seizure-free. All subjects completed at baseline (T0) the Resilience Scale (RS-14) and questionnaires for the assessment of depressive symptoms, anxiety and quality of life: respectively, Beck Depression Inventory-II (BD-II), Generalized Anxiety Disorder-7 (GAD-7) and QOLIE-31 (Q31). All patients were followed up prospectively and re-evaluated after 6-22 months (T1; mean: 14 ± 8 months; median 14 months); at follow up they also completed the Stigma Scale of Epilepsy (SSE) for the assessment of the stigma associated with epilepsy. We correlated resilience values with all psychosocial scores at T0 and T1. Factors associated with resilient and vulnerable outcomes were identified. Finally, a multiple stepwise regression analysis was applied to identify predictors for resilience and stigma perception. RESULTS: The results showed for the RS-14 score a significant direct correlation with the Q31 (p < 0.001) and an inverse correlation with the depressive and anxiety symptoms at both times (T0 and T1), as evaluated with BDI-II (p < 0.001) and GAD-7 (p < 0.001). Finally, we found a significant inverse correlation between RS-14 at T0 and the levels of stigmatization assessed with SSE at T1 (p =.015). Using a multiple stepwise regression analysis separately for resilience and stigma perception, depressive symptoms turned out as the best predictors for both variables. Finally, considering longitudinal evaluation we did not observe significant changes in depressive and anxious symptoms, despite a significant reduction in the total number of seizures at follow up. CONCLUSIONS: Our study showed that depressive symptoms, anxiety and quality of life were significantly associated with resilience in PwE. Finally, as a novel finding resilience was proved to affect the perception of stigma related to epilepsy more than seizures.

Somatosensory input in the context of transcranial magnetic stimulation coupled with electroencephalography: An evidence-based overview.

The transcranial evoked potential (TEP) is a powerful technique to investigate brain dynamics, but some methodological issues limit its interpretation. A possible contamination of the TEP by electroencephalographic (EEG) responses evoked by the somatosensory input generated by transcranial magnetic stimulation (TMS) has been postulated; nonetheless, a characterization of these responses is lacking. The aim of this work was to review current evidence about possible somatosensory evoked potentials (SEP) induced by sources of somatosensory input in the craniofacial region. Among these, only contraction of craniofacial muscle and stimulation of free cutaneous nerve endings may be able to induce EEG responses, but direct evidence is lacking due to experimental difficulties in isolating these inputs. Notably, EEG evoked activity in this context is represented by a N100/P200 complex, reflecting a saliency-related multimodal response, rather than specific activation of the primary somatosensory cortex. Strategies to minimize or remove these responses by EEG processing still yield uncertain results; therefore, data inspection is of paramount importance to judge a possible contamination of the TEP by multimodal potentials caused by somatosensory input.

Resilience predicts and modulates anxiety severity in people with epilepsy.

BACKGROUND: Anxiety is one of the most relevant psychiatric comorbidities in people with epilepsy (PwE). The role of resilience (RES) in the development of anxiety is not well understood. We purposed to better characterize RES impact on anxiety severity in PwE. MATERIALS AND METHODS: One hundred and seventy-six PwE underwent online surveys including a collection of socio-demographic, seizure-related, and psychological variables. PwE were grouped according to the data collected; anxiety levels were compared through non-parametric statistics. Hierarchical regression analysis (HRA) and logistic regression were performed to characterize RES contribute in predicting the presence and the severity of anxiety. Mediation/moderation analysis was performed to evaluate causal effects among RES, depression, and anxiety. RESULTS: Anxiety did not differ according to socio-demographic and seizure-related variables, exemption for the presence of drug-related adverse effects. Depression, RES, and sleep quality provided the major contribute on anxiety variance. The addiction of RES level in HRA and logistic regression provided a significant increase of R-squared value (p-value = 0.02) and of area under the curve (p-value = 0.03), respectively. RES modulated depression/anxiety relationship (p-value < 0.001), whereas depression did not mediate RES/anxiety correlation (p-value = 0.68). CONCLUSIONS: We demonstrated that RES is a significant independent predictor of anxiety in PwE and is able to modulate depression impact on anxiety. Moreover, we confirmed the relevance of depression and sleep quality on anxiety severity.

Quantitative measures of the resting EEG in stroke: a systematic review on clinical correlation and prognostic value.

OBJECT: Quantitative electroencephalography (qEEG) has shown promising results as a predictor of clinical impairment in stroke. We systematically reviewed published papers that focus on qEEG metrics in the resting EEG of patients with mono-hemispheric stroke, to summarize current knowledge and pave the way for future research. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched the literature for papers that fitted our inclusion criteria. Rayyan QCRR was used to allow deduplication and collaborative blinded paper review. Due to multiple outcomes and non-homogeneous literature, a scoping review approach was used to address the topic. RESULTS: Or initial search (PubMed, Embase, Google scholar) yielded 3200 papers. After proper screening, we selected 71 papers that fitted our inclusion criteria and we developed a scoping review thar describes the current state of the art of qEEG in stroke. Notably, among selected papers 53 (74.3%) focused on spectral power; 11 (15.7%) focused on symmetry indexes, 17 (24.3%) on connectivity metrics, while 5 (7.1%) were about other metrics (e.g. detrended fluctuation analysis). Moreover, 42 (58.6%) studies were performed with standard 19 electrodes EEG caps and only a minority used high-definition EEG. CONCLUSIONS: We systematically assessed major findings on qEEG and stroke, evidencing strengths and potential pitfalls of this promising branch of research.

Determinants of medication adherence in people with epilepsy: A multicenter, cross-sectional survey.

OBJECTIVES: Poor medication adherence in people with epilepsy (PwE) increases mortality, hospitalization, and poor quality of life, representing a critical challenge for clinicians. Several demographic, clinical, and neuropsychological factors were singularly found associated with medication adherence in several studies, but the literature lacks a comprehensive study simultaneously assessing all these variables. METHODS: We performed a multicenter and cross-sectional study using online questionnaires with the following clinical scales: Morisky Medication Adherence Scale (MMAS-8), Quality of Life in Epilepsy Inventory 31 (QoLIE-31), Beck Depression Inventory-II (BDI-II), Generalized Anxiety Disorder-7 (GAD-7) and 14-item Resilience scale (RES14) in a population of 200 PwE. We used the ANOVA test and Spearman's correlation to evaluate the relationship between medication adherence and demographic, clinical (seizure frequency, number of anti-seizure medications), and neuropsychological characteristics. We trained separate machine learning models (logistic regression, random forest, support vector machine) to classify patients with medium-high adherence (MMAS-8 ≥ 6) and poor adherence (MMAS-8 < 6) and to identify the main features that influence adherence. RESULTS: Women were more adherent to medication (p-value = 0.035). Morisky Medication Adherence Scale -8 showed a direct correlation with RES14 (p-value = 0.001) and age (p-value = 0.001), while was inversely correlated with BDI-II (p-value = 0.001) and GAD-7 (p-value = 0.001). In our model, the variables mostly predicting treatment adherence were QoLIE-31 subitems, followed by age, resilience, anxiety, years of school, and disease duration. CONCLUSION: Our study confirms that gender, age, and neuropsychological traits are relevant factors in predicting medication adherence to PwE. Furthermore, our data provided the first evidence that machine learning on multidimensional self-report questionnaires could help to develop a decisional support system in outpatient epilepsy clinics.

Whole-body computed tomography as first-line imaging procedure to exclude cancer in patients with neurological suspicion of paraneoplastic syndromes: shall clinical practice adhere to recommendations?

INTRODUCTION: To assess the efficacy of whole-body computed tomography (WB-CT) as imaging procedure to exclude cancer in patients with neurological symptoms and signs at clinical onset. METHODS: A retrospective observational study was designed to identify consecutive WB-CT requested by the Neurology Unit with a suspicion of an underlying tumor potentially linked to a paraneoplastic neurological syndrome (PNS) between January 2019 and February 2022. The following data were collected: diagnosis at admission and at discharge, the presence of onconeural antibodies, the scans dose length product (DLP), the estimated effective dose (ED), the total estimated time requested; the PNS-Care-Score was retrospectively calculated only in subjects with available antibodies. RESULTS: The total number of patients included was 158. In 13/158 (positive group) a malignant or locally aggressive neoplasm was found while in 145/158 no malignant lesions were found on the WB-CT. Among the positive group, in 7/13 onconeural antibodies were diagnosed, resulting negative in all cases and the most frequent tumor was lung cancer (30.8%). PNS-Care-Score was of 6-7 in 2/7 (probable PNS) and in no case the PNS-Care-Score was ≥8 (definite PNS). The mean DLP for all the scans was 2798 ± 952 mGy cm (average estimated ED of 42 ± 14 mSv). The total estimated time requested for all scans was 11,060 min. CONCLUSION: If a PNS is suspected, we encourage the prescription of unenhanced chest CT and/or abdomen/testis/female pelvis ultrasound and/or mammography based on clinical picture. The WB-CT using a single portal phase would be appropriate as a second-line technique while magnetic resonance imaging might be indicated for the exclusion of nervous system diseases. IMPLICATIONS FOR PRACTICE: Our suggestion results in saving in terms of radiation exposure, financial resources and time.

Vagal nerve stimulation cycles alter EEG connectivity in drug-resistant epileptic patients: A study with graph theory metrics.

OBJECTIVE: Vagal Nerve Stimulation (VNS) is an effective treatment for Drug-Resistant (DR) epilepsy. Albeit the corroborated effectiveness of VNS, little is known about how VNS works. We aim to leverage quantitative Electroencephalography (qEEG) to study how the brain responds to VNS cycles. METHODS: Eighteen subjects with DR epilepsy were enrolled in our study. 64-channel EEG was recorded during VNS stimulation. Periods of stimulation (VNS), preceding (preVNS) and following stimulation (postVNS) were identified via an electrode placed on the stimulator. We used qEEG analysis to assess changes in spectral and network activity that characterize these conditions. Graph theory metrics were used to calculate differences in network connectivity. RESULTS: No differences were found in spectral activity between preVNS, VNS, and postVNS. Graph theory showed consistent changes in network organization expressed by Small World Index (SWI), Betweenness Centrality (BtwC), and Global Efficiency (gE). These changes were most significant in the slow EEG bands. CONCLUSIONS: In DR epilepsy, VNS has a significant effect on brain network activity, as assessed by EEG connectivity, acting on widespread network distribution rather than band-power. SIGNIFICANCE: Our findings support the hypothesis that VNS acts on epilepsy by influencing diffuse network connectivity in the brain.

EEG spectral exponent as a synthetic index for the longitudinal assessment of stroke recovery.

OBJECTIVE: Quantitative Electroencephalography (qEEG) can capture changes in brain activity following stroke. qEEG metrics traditionally focus on oscillatory activity, however recent findings highlight the importance of aperiodic (power-law) structure in characterizing pathological brain states. We assessed neurophysiological alterations and recovery after mono-hemispheric stroke by means of the Spectral Exponent (SE), a metric that reflects EEG slowing and quantifies the power-law decay of the EEG Power Spectral Density (PSD). METHODS: Eighteen patients (n = 18) with mild to moderate mono-hemispheric Middle Cerebral Artery (MCA) ischaemic stroke were retrospectively enrolled for this study. Patients underwent EEG recording in the sub-acute phase (T0) and after 2 months of physical rehabilitation (T1). Sixteen healthy controls (HC; n = 16) matched by age and sex were enrolled as a normative group. SE values and narrow-band PSD were estimated for each recording. We compared SE and band-power between patients and HC, and between the affected (AH) and unaffected hemisphere (UH) at T0 and T1 in patients. RESULTS: At T0, stroke patients showed significantly more negative SE values than HC (p = 0.003), reflecting broad-band EEG slowing. Most important, in patients SE over the AH was consistently more negative compared to the UH and showed a renormalization at T1. This SE renormalization significantly correlated with National Institute of Health Stroke Scale (NIHSS) improvement (R = 0.63, p = 0.005). CONCLUSIONS: SE is a reliable readout of the neurophysiological and clinical alterations occurring after an ischaemic cortical lesion. SIGNIFICANCE: SE promise to be a robust method to monitor and predict patients' functional outcome.

The Italian technical/administrative recommendations for telemedicine in clinical neurophysiology.

Recent advances in technology, information technology, Internet networks, and, more recently, fiber optics in industrialized countries allow the exchange of a huge amount of data, in real time, across the globe. The acquisition of increasingly sophisticated technologies has made it possible to develop telemedicine, by which the specialist's evaluation can be carried out on the patient even remotely. In Italy, this very useful tool, although possible from a technological and information technology point of view, has not been developed because of the lack of clear and univocal rules and of major administrative obstacles related to the Italian Public Health System. To promote telemedicine implementation in Italy, the Italian Society of Clinical Neurophysiology and the Italian Society of Telemedicine together with the National Centre for Telemedicine and New Assistive Technologies of the Italian Higher Institute of Health prepared these inter-society recommendations. Because of potential forensic value of these recommendations, they were prepared considering the current regulations and the General Data Protection Regulation and will provide the basis for a Consensus Conference planned to discuss and prepare National Telemedicine Guidelines.

Frozen shoulder or shoulder stiffness from Parkinson disease?

PURPOSE: To understand the role of camptocormia (increased kyphosis) and postural alteration in Parkinson's disease in the development of shoulder pathology, with a special concern for adhesive capsulitis and shoulder stiffness. METHODS: A preliminary online search was carried out, with combination of keywords including "Parkinson," "Shoulder stiffness," "Frozen shoulder," "Adhesive capsulitis," "Postural alteration," "Camptocormia". The retrieved papers were screened by title and abstract and those considered relevant to the aim of the review were read in full text and included. Relevant information were extracted and reported into text. RESULTS: Due to a severe impairment of posture, patients affected by PD show an increased thoracic kyphosis (camptocormia) and decreased mobility of the trunk that can yield a humeroacromial impingement syndrome and capsulitis, resulting in inflammation of the bursa, shoulder pain and reduction of movement. Furthermore, kinematic of the shoulder is allowed by the combined movement of the humerus, the scapula, the clavicle, the thoracic wall and thoracic spine. The thoracic spine and wall mobility are severely impaired in the parkinsonian patient, thus limiting the shoulder motion. CONCLUSION: The postural alteration observed in PD is the primum movens for shoulder pathology, since anterior tilt of the scapula, which occurs with the increment of thoracic kyphosis, yields to a subacromial impingement. A closed loop is then created, as the rigidity of the shoulder causes further alteration in the posture, which worsens the impingement syndrome and so on.

The ROME (Retrospective Observational Multicenter study on Eslicarbazepine) study: Efficacy and behavioural effects of Eslicarbazepine acetate as adjunctive therapy for adults with partial onset seizures in real life.

PURPOSE: Eslicarbazepine acetate (ESL) is a third-generation member of the dibenzazepine family approved in 2009 by the European Medicines Agency with the indication of adjunctive therapy in adult people with partial-onset seizures (PPOS). We aimed at assessing the ESL impact on seizure frequency and quality of life in PPOS with a particular attention to sleepiness and depression. METHODS: We evaluated 50 adult PPOS (>18 years; 48 ±â€¯14 years-old; 23 males) treated with adjunctive ESL for ≥2months with a retrospective multi-centric design. Clinical files of the last 2 years were reviewed checking for monthly seizure frequency, treatment retention rate, adverse drug reactions (ADRs), concomitant anti-epileptic drugs and behavioural scales for sleepiness (Stanford Sleepiness Scale, SSS, and Epworth Sleepiness Scale, ESS), depression (Beck Depression Inventory-II, BDI) and overall quality of life (QOLIE-31). RESULTS: At the end of 96 ±â€¯28 days of ESL treatment, the mean seizure reduction was 56%; 60% of patients had seizure reduction above 50%, with a 31% of the whole population becoming seizure free. We reported 16 ADRs with 4 hyponatremia. Retention rate was 76%. Patient reported less sleepiness after ESL (SSS, p = 0.031; ESS, p = 0.0000002). Before ESL, 38% of patients had pathologic BDI scores, which normalized in most of them (73%) after ESL (BDI improvement, p = 0.000012). These scores resulted in an amelioration of quality of life (QOLIE-31, p = 0.000002). CONCLUSIONS: ESL is a safe and effective anti-epileptic drug in a real life scenario, with an excellent behavioural profile for the overall quality of life and, in particular, for sleepiness and depression.

The associative brain at work: Evidence from paired associative stimulation studies in humans.

The original protocol of Paired Associative Stimulation (PAS) in humans implies repetitive cortical and peripheral nerve stimuli, delivered at specific inter-stimulus intervals, able to elicit non-invasively long-term potentiation (LTP)- and long-term depression (LTD)-like plasticity in the human motor cortex. PAS has been designed to drive cortical LTP/LTD according to the Hebbian rule of associative plasticity. Over the last two decades, a growing number of researchers have increasingly used the PAS technique to assess cortical associative plasticity in healthy humans and in patients with movement disorders and other neuropsychiatric diseases. The present review covers the physiology, pharmacology, pathology and motor effects of PAS. Further sections of the review focus on new protocols of "modified PAS" and possible future application of PAS in neuromorphic circuits designed for brain-computer interface.

Neurobiological after-effects of non-invasive brain stimulation.

BACKGROUND: In recent years, many studies have evaluated the effects of noninvasive brain stimulation (NIBS) techniques for the treatment of several neurological and psychiatric disorders. Positive results led to approval of NIBS for some of these conditions by the Food and Drug Administration in the USA. The therapeutic effects of NIBS have been related to bi-directional changes in cortical excitability with the direction of change depending on the choice of stimulation protocol. Although after-effects are mostly short lived, complex neurobiological mechanisms related to changes in synaptic excitability bear the potential to further induce therapy-relevant lasting changes. OBJECTIVE: To review recent neurobiological findings obtained from in vitro and in vivo studies that highlight molecular and cellular mechanisms of short- and long-term changes of synaptic plasticity after NIBS. FINDINGS: Long-term potentiation (LTP) and depression (LTD) phenomena by itself are insufficient in explaining the early and long term changes taking place after short episodes of NIBS. Preliminary experimental studies indicate a complex scenario potentially relevant to the therapeutic effects of NIBS, including gene activation/regulation, de novo protein expression, morphological changes, changes in intrinsic firing properties and modified network properties resulting from changed inhibition, homeostatic processes and glial function. CONCLUSIONS: This review brings into focus the neurobiological mechanisms underlying long-term after-effects of repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) recently obtained from in vitro and in vivo studies, both in animals and humans.

Ten Years of Theta Burst Stimulation in Humans: Established Knowledge, Unknowns and Prospects.

BACKGROUND/OBJECTIVES: Over the last ten years, an increasing number of authors have used the theta burst stimulation (TBS) protocol to investigate long-term potentiation (LTP) and long-term depression (LTD)-like plasticity non-invasively in the primary motor cortex (M1) in healthy humans and in patients with various types of movement disorders. We here provide a comprehensive review of the LTP/LTD-like plasticity induced by TBS in the human M1. METHODS: A workgroup of researchers expert in this research field review and discuss critically ten years of experimental evidence from TBS studies in humans and in animal models. The review also includes the discussion of studies assessing responses to TBS in patients with movement disorders. MAIN FINDINGS/DISCUSSION: We discuss experimental studies applying TBS over the M1 or in other cortical regions functionally connected to M1 in healthy subjects and in patients with various types of movement disorders. We also review experimental evidence coming from TBS studies in animals. Finally, we clarify the status of TBS as a possible new non-invasive therapy aimed at improving symptoms in various neurological disorders.

Channel interpolation in TMS-EEG: a quantitative study towards an accurate topographical representation.

The co-registration of transcranial magnetic stimulation and electroencephalography (TMS-EEG) is emerging as a successful technique for causally exploring cortical mechanisms and connections. However, various artefacts could affect TMS-EEG signals. Correct artefacted channels reconstruction is crucial to obtain accurate topographical representation and consequently accurate inverse problem solution, in order to map in a proper way the global brain responses after the stimulation of one particular brain region of interest. In this paper, we discuss the problem of artefacted channels interpolation in TMS-EEG signals. Aim of the study was to investigate two different interpolation methods evaluating their performance in two datasets: one constituted by 19 EEG channels montage (low-density spatial resolution) and the other one by 60 EEG channels montage (high-density spatial resolution). In addition, these evaluations took place in two different contexts of application: after the averaging of TMS Evoked Potentials (TEPs) in a time interval to obtain a global information in the considered range, and at fixed latencies 100 ms and 300 ms after the TMS stimulus. The results showed that the global reconstruction error was lower at fixed latencies for the high-density electrodes spatial resolution montage.

Familiarity for famous faces and names is not equally subtended by the right and left temporal poles. Evidence from an rTMS study.

The aims of the present experiment was to investigate: (a) if transient disruption of neural activity in the right (RTP) or left temporal pole (LTP) can interfere with the development of a familiarity feeling to the presentation of faces/written names of famous/unknown people; and (b) if this interference specifically affects the familiarity for faces after inhibition of the RTP and for names after inhibition of the LTP. Twenty healthy volunteers took part in the study. Repetitive transcranial magnetic stimulation (rTMS) was administered online; it disrupted the neural activity of the right or left TP in concomitance with the presentation of each face and name whose familiarity had to be assessed. Furthermore, in a control group, each participant was submitted to a single experimental session in which rTMS was delivered to the vertex in association with the presentation of faces and written names. Since previous rTMS studies have shown that the temporary inactivation of the right and left TP influences the response latencies, but not the number of correct responses, in this study we took into account both the number of correct responses obtained in different experimental conditions and the corresponding response latencies. A three-way factorial ANOVA carried out on the Response Scores showed only a general effect of the Type of Stimuli, due to better performances on names than on faces. This greater familiarity of names is consistent with previous data reported in the literature. In the three-way factorial ANOVA carried out on the Latency Scores, post-hoc analyses showed an increased latency of responses to faces after right stimulation in Latency Total, Latency on Correct responses and Latency on Unfamiliar faces. None of these results were obtained in the control group. These data suggest that rTMS at the level of the RTP preferentially affects the development of familiarity feelings to the presentation of faces of famous people.

Biomechanical and neural changes evaluation induced by prolonged use of non-stable footwear: a systematic review.

The aim of this review is to collect and discuss the current best evidence published in literature about the effect of the Masai Barefoot Technology(MBT) shoes on gait and muscle activation and try to draw conclusions on the possible benefits. We searched Medline, CINAHL, Embase and the Cochrane Central Registry of Controlled Trials. The reference lists of the previously selected articles were then examined by hand. Only studies comparing biomechanical and clinical outcomes were selected. Review, anatomical studies, letter to editor and instructional course were excluded. Finally, all the resulting articles were reviewed and discussed by all the authors to further confirm their suitability for this review: in the end, 22 articles were included. A total of 532 patients presenting a mean age of 34.3 years were studied. All patients evaluated were healthy or amateur sports except in two studies where only obese subjects and knee osteoarthritis patients were involved. Seven studies evaluated only male subjects, whereas four studies evaluated only female. Twelve of twenty-two studies performed electromyographic analyses. Weight was reported in 19 studies, whereas body mass index were reported only in a five studies. All studies reported kinematic analysis of shoe effects and compared the relationship between muscle recruitment and electromyographic activity. Unstable footwears were shown to immediately alter the stability in gait during daily-life activities. The center of body pressure is moved posteriorly with a consequent posterior displacement of the upper part of body in order to regain an appropriate body balance, and these postural changes are associated with an overall increase in the activity of lumbar erector spine muscles, as well as certain lower limb muscles. Current literature provides enough cues to conclude for a beneficial role of MBT shoes in the postural and proprioceptive recovery, but from the same literature cannot be drown clear and appropriate guidance to determine more in detail their indication for specific pathological conditions or for particular phases of the musculoskeletal recovery process.

Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee.

These guidelines provide an up-date of previous IFCN report on "Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application" (Rossini et al., 1994). A new Committee, composed of international experts, some of whom were in the panel of the 1994 "Report", was selected to produce a current state-of-the-art review of non-invasive stimulation both for clinical application and research in neuroscience. Since 1994, the international scientific community has seen a rapid increase in non-invasive brain stimulation in studying cognition, brain-behavior relationship and pathophysiology of various neurologic and psychiatric disorders. New paradigms of stimulation and new techniques have been developed. Furthermore, a large number of studies and clinical trials have demonstrated potential therapeutic applications of non-invasive brain stimulation, especially for TMS. Recent guidelines can be found in the literature covering specific aspects of non-invasive brain stimulation, such as safety (Rossi et al., 2009), methodology (Groppa et al., 2012) and therapeutic applications (Lefaucheur et al., 2014). This up-dated review covers theoretical, physiological and practical aspects of non-invasive stimulation of brain, spinal cord, nerve roots and peripheral nerves in the light of more updated knowledge, and include some recent extensions and developments.

Wakefulness delta waves increase after cortical plasticity induction.

OBJECTIVE: Delta waves (DW) are present both during sleep and in wakefulness. In the first case, DW are considered effectors of synaptic plasticity, while in wakefulness, when they appear in the case of brain lesions, their functional meaning is not unanimously recognized. To throw light on the latter, we aimed to investigate the impact on DW exerted by the cortical plasticity-inducing protocol of intermittent theta burst stimulation (iTBS). METHODS: Twenty healthy subjects underwent iTBS (11 real iTBS and nine sham iTBS) on the left primary motor cortex with the aim of inducing long-term potentiation (LTP)-like phenomena. Five-minute resting open-eye 32-channel EEG, right opponens pollicis motor-evoked potentials (MEPs), and alertness behavioral scales were collected before and up to 30 min after the iTBS. Power spectral density (PSD), interhemispheric coherence between homologous sensorimotor regions, and intrahemispheric coherence were calculated for the frequency bands ranging from delta to beta. RESULTS: Real iTBS induced a significant increase of both MEP amplitude and DW PSD lasting up to 30 min after stimulation, while sham iTBS did not. The DW increase was evident over frontal areas ipsilateral and close to the stimulated cortex (electrode F3). Neither real nor sham iTBS induced significant modifications in the PSD of theta, alpha, and beta bands and in the interhemispheric coherence. Behavioral visuo-analogic scales score did not demonstrate changes in alertness after stimulations. No correlations were found between MEP amplitude and PSD changes in the delta band. CONCLUSIONS: Our data showed that LTP induction in the motor cortex during wakefulness, by means of iTBS, is accompanied by a large and enduring increase of DW over the ipsilateral frontal cortex. SIGNIFICANCE: The present results are strongly in favor of a prominent role of DW in the neural plasticity processes taking place during the awake state.