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.

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.

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.

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.

Assessing bradykinesia in Parkinson's disease using gyroscope signals.

Parkinson's disease (PD) is a neurodegenerative brain disorder that slowly brings on the dopaminergic neurons death. The depletion of the dopaminergic signal causes the onset of motor symptoms such as tremor, bradykinesia and rigidity. Usually, neurologists regularly monitor motor symptoms and motor fluctuations using the MDS-UPDRS part III clinical scale. Nevertheless, to have a more objective and quantitative evaluation, it is possible to assess the cardinal motor symptoms of PD using wearable sensors and portable robotic devices. Unfortunately while there are several research papers on the use of these devices on PD patients, their use is not so common in clinical practice. In this work we recorded specific MDS-UPDRS motor tasks using magneto-inertial devices, worn by seven PD subjects and seven age-matched controls, in order to deeply analyze the kinematic and dynamic characteristics of goal-directed movements of upper limb, in addition to extract quantitative indices (peak velocity, smoothness, etc) useful for the assessment of motor symptoms. Using only gyroscope signals we looked at those parameters useful to assess bradykinesia. We observed parameters changes from OFF to ON phase congruent with the MDS-UPDRS changes, especially in the frequency domain. Our results suggest the prono-supination task is the more consistent to describe the bradykinesia symptom with the gyroscopes. Probably because of the amplitude of the movement performed. Moreover the peak power looks appropriate for bradykinesia symptom evaluation. We can conclude that, similar to the studies in which tremor symptom is evaluated, it is possible to monitor the bradykinesia using few wearable sensors and few simple parameters.

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.

The detection of neural autoantibodies in patients with antiepileptic-drug-resistant epilepsy predicts response to immunotherapy.

BACKGROUND AND PURPOSE: The detection of antibodies binding neural antigens in patients with epilepsy has led to the definition of 'autoimmune epilepsy'. Patients with neural antibodies not responding to antiepileptic drugs (AEDs) may benefit from immunotherapy. Aim of this study was to evaluate the frequency of autoantibodies specific to neural antigens in patients with epilepsy and their response to immunotherapy. METHODS: Eighty-one patients and 75 age- and sex-matched healthy subjects (HS) were enrolled in the study. Two groups of patients were included: 39 patients with epilepsy and other neurological symptoms and/or autoimmune diseases responsive to AEDs (group 1) and 42 patients with AED-resistant epilepsy (group 2). Patients' serum and cerebrospinal fluid were evaluated for the presence of autoantibodies directed to neural antigens by indirect immunofluorescence on frozen sections of mouse brain, cell-based assays and a radioimmunoassay. Patients with AED-resistant epilepsy and neural autoantibodies were treated with immunotherapy and the main outcome measure was the reduction in seizure frequency. RESULTS: Neural autoantibodies were detected in 22% of patients (18/81), mostly from the AED-resistant epilepsy group (P = 0.003), but not in HS. Indirect immunofluorescence on mouse brain revealed antibodies binding to unclassified antigens in 10 patients. Twelve patients received immunotherapy and nine (75%) achieved >50% reduction in seizure frequency. CONCLUSIONS: A significant proportion of patients with AED-resistant epilepsy harbor neural-specific autoantibodies. The detection of these antibodies, especially of those binding to synaptic antigens, may predict a favorable response to immunotherapy, thus overcoming AED resistance.

Does an intraneural interface short-term implant for robotic hand control modulate sensorimotor cortical integration? An EEG-TMS co-registration study on a human amputee.

PURPOSE: Following limb amputation, central and peripheral nervous system relays partially maintain their functions and can be exploited for interfacing prostheses. The aim of this study is to investigate, for the first time by means of an EEG-TMS co-registration study, whether and how direct bidirectional connection between brain and hand prosthesis impacts on sensorimotor cortical topography. METHODS: Within an experimental protocol for robotic hand control, a 26 years-old, left-hand amputated male was selected to have implanted four intrafascicular electrodes (tf-LIFEs-4) in the median and ulnar nerves of the stump for 4 weeks. Before tf-LIFE-4s implant (T0) and after the training period, once electrodes have been removed (T1), experimental subject's cortico-cortical excitability, connectivity and plasticity were tested via a neuronavigated EEG-TMS experiment. RESULTS: The statistical analysis clearly demonstrated a significant modulation (with t-test p < 0.0001) of EEG activity between 30 and 100 ms post-stimulus for the stimulation of the right hemisphere. When studying individual latencies in that time range, a global amplitude modulation was found in most of the TMS-evoked potentials; particularly, the GEE analysis showed significant differences between T0 and T1 condition at 30 ms (p < 0.0404), 46 ms (p < 0.0001) and 60 ms (p < 0.007) latencies. Finally, also a clear local decrement in N46 amplitude over C4 was evident. No differences between conditions were observed for the stimulation of the left hemisphere. CONCLUSIONS: The results of this study confirm the hypothesis that bidirectional neural interface could redirect cortical areas -deprived of their original input/output functions- toward restorative neuroplasticity. This reorganization strongly involves bi-hemispheric networks and intracortical and transcortical modulation of GABAergic inhibition.

Inflammation and iron metabolism in adult patients with epilepsy: does a link exist?

PURPOSE: Inflammation has been shown to play a key role in epilepsy, and may also affect both the iron status and metabolism. Consequently, a relationship between iron metabolism and neuronal excitability and seizures could be expected. METHODS: We aimed at characterizing in 37 adult patients affected by focal epilepsy during the interictal period serum inflammatory cytokines, such as interleukin 6 (IL-6), IL-6 soluble receptor (IL6-sR), interleukin 1 (IL-1), IL-1 receptor-antagonist (IL-1RA), tumor necrosis factor-α (TNF-α), and markers of iron status and metabolism: hemoglobin concentration (Hgb), mean corpuscular volume (MCV), hematocrit (Hct) red blood cell (RBC) count, serum iron and copper concentrations, ceruloplasmin (iCp), the ceruloplasmin enzymatic activity (eCp), the specific ceruloplasmin activity (eCp/iCp), total ferroxidase activity, transferrin (Tf), serum ferritin (SF), Tf saturation (Sat-Tf), and ratio of ceruloplasmin to transferrin (Cp/Tf). We investigated the correlations between these biological markers as well their relationship with patients' clinical features. A group of 43 healthy subjects had the same serologic measurements to serve as controls. RESULTS: Our findings showed in the group of patients with epilepsy an increase of IL-6 (p=0.026) and a decrease of TNF-α (p=0.002) with respect to healthy subjects. For the first time, we also detected significant changes in iron metabolism as an increase of Cp/Tf (p=0.011) and a decrease of Tf (p=0.031), possibly driven by cytokine modifications and consistent with inflammation as acute phase and antioxidant activity markers. Accordingly, TNF-α positively correlated with Tf (p=0.005). Finally, a significant positive correlation between seizures frequency and eCp (p=0.046) and inversely with Hgb (p=0.038) and Hct (p=0.041), and an inverse correlation between TNF-α and the duration of epilepsy (p=0.021) was detected. CONCLUSIONS: Our findings demonstrate a relevant relationship between epilepsy and systemic inflammation, with a consistent link between seizures, inflammatory cytokines (IL-6 and TNF-α) and iron regulation and metabolism, as acute phase and antioxidant markers.

Inter-hemispheric coupling changes associate with motor improvements after robotic stroke rehabilitation.

PURPOSE: In the chronic phase of stroke brain plasticity plays a crucial role for further motor control improvements. This study aims to assess the brain plastic reorganizations and their association with clinical progresses induced by a robot-aided rehabilitation program in chronic stroke patients. METHODS: 7 stroke patients with an upper limb motor impairment in chronic phase underwent a multi-modal evaluation before starting and at the end of a 12-week upper-limb neurorehabilitation program. Fugl-Meyer Assessment (FMA) Scale scores and performance indices of hand movement performance (isometric pinch monitored through a visual feedback) were collected. Cerebral reorganizations were characterized by 32-channel electroencephalography (EEG) focusing on ipsilesional and contralesional resting state properties investigating both bipolar derivations overlying the middle cerebral artery territory and the primary somatosensory sources (S1) obtained through the Functional Source Separation (FSS) method. Power Spectral Density (PSD) and interhemispheric coherence (IHCoh) at rest were measured and correlated with clinical and hand control robot-induced improvements. RESULTS: After the robotic rehabilitation we found an improvement of FMAS scores and hand motor control performance and changes of brain connectivity in high frequency rhythms (24-90 Hz). In particular, the improvement of motor performance correlated with the modulation of the interhemispheric S1 coherence in the high beta band (24-33 Hz). CONCLUSIONS: Recently it has been shown that an upper limb robot-based rehabilitation improves motor performance in stroke patients. We confirm this potential and demonstrate that a robot-aided rehabilitation program induces brain reorganizations. Specifically, interhemispheric connectivity between primary somatosensory areas got closer to a 'physiological level' in parallel with the acquisition of more accurate hand control.

A neurally-interfaced hand prosthesis tuned inter-hemispheric communication.

PURPOSE: This work investigates how a direct bidirectional connection between brain and hand prosthesis modifies the bi-hemispheric sensorimotor system devoted to the movement control of the lost limb. Hand prostheses are often unable to satisfy users' expectations, mostly due to the poor performance of their interfacing system. Neural Interfaces implanted inside nerves of the stump offer the advantage of using the bidirectional neural pathways 'naturally' dispatching signals to control proper hand actions and feed-back sensations. Learning to control a neurally-interfaced hand prosthesis and decode sensory information was previously observed to reduce the inter-hemispheric asymmetry of cortical motor maps and the clinical symptoms of phantom limb syndrome. METHODS: Electroencephalographic (EEG) data was analysed using Functional Source Separation (FSS), a semi-blind method that incorporates prior knowledge about the signal of interest into data decomposition to give access to cortical patch activities. RESULTS: Bi-hemispheric cortices showed normalization of their activity (topographical and spectral patterns) and of functional connectivity between homologous hand controlling areas, during the delivery of the motor command to the cybernetic prosthesis. CONCLUSIONS: The re-establishment of central-peripheral communication with the lost limb induced by a neurally-interfaced hand prosthesis produces beneficial plastic reorganization, not only restructuring contralateral directly-connected control areas, but also their functional balance within the bi-hemispheric system necessary for motor control.

Primary headache and epilepsy: a multicenter cross-sectional study.

The prevalence and characteristics of interictal headache, epilepsy and headache/epilepsy comorbidity were assessed in 858 women and 309 men aged 18-81 years from headache and epilepsy centers in Italy. The research hypothesis was that comorbidity among patients with either disorder would be expected to be higher than in the general population. Interictal headache was diagnosed in 675 cases (migraine 482; tension-type headache 168; other types 25), epilepsy in 336 (partial 171; generalized 165) and comorbidity in 156 (1.6% from headache centers; 30.0% from epilepsy centers). Patients with epilepsy, headache and comorbidity differed in a number of demographic and clinical aspects. However, for both headache and epilepsy, a family history of the same clinical condition was equally prevalent in patients with and without comorbidity. These findings do not support the purported association between headache and epilepsy.

Intrafascicular thin-film multichannel electrodes for sensory feedback: Evidences on a human amputee.

The performance of motor neuroprostheses or robotic arm prostheses can be significantly improved by delivering sensory feed-back related to the ongoing motor task (e.g. the slippage of an object during grasping). Microfabricated neural electrodes implantable in peripheral nervous system seem a promising approach to this aim. New generation of thin-film intrafascicular electrodes longitudinally implantable in peripheral nerves (tf-LIFE4) has been developed and tested for afferent stimulation in human amputee case study.

Extrauterine maturation of somatosensory pathways in preterm infants: a somatosensory evoked potential study.

OBJECTIVE: To evaluate the reliability of somatosensory evoked potential (SEP) recordings in preterm infants to monitor the intra-uterine and extrauterine maturation of somatosensory pathways. METHODS: We performed SEPs in 35 neurologically normal preterm babies (range 23-35 weeks gestational age--GA). Twenty-four of all infants were evaluated after the first 2 weeks of life, at a minimum post-menstrual age (PMA) of 31 weeks, and 31 at term corrected age. In 15 infants we obtained longitudinal recordings at both epochs. Cross-sectional and longitudinal values of first cortical potential (N1) were analyzed in relation of PMA and matched with those measured in a group of 11 fullterm babies. RESULTS: Reproducible cortical SEPs were found in 92% of preterm babies at first recording, and in all 31 neonates at follow-up. A significant inverse correlation between the latency values of N1 and PMA at the time of first recording was observed, showing that latencies of these components rapidly decrease with increasing PMA. Regression analysis showed no significant effect on N1 latency at term correct age in dependence of GA, suggesting that extrauterine life does not affect maturation of somatosensory pathways. Interestingly, the occurrence of idiopathic respiratory distress (RDS) during clinical course after birth correlated with a delayed N1 latency at term corrected age. CONCLUSIONS: Extrauterine life does not affect maturation of somatosensory pathways in preterms without neurological deficit. Finally, the mild negative influence of RDS on maturational changes was evident. SIGNIFICANCE: SEPs could be considered a useful tool for a non-invasive assessment of somatosensory pathways integrity in preterm infants.

Neuroimaging experimental studies on brain plasticity in recovery from stroke.

Topographical cortical organization of sensorimotor area has been shown to be highly plastic, altering his configuration in response to training in different tasks in healthy controls and neurological patients. The term ''brain plasticity'' encompasses all possible mechanisms of neuronal reorganization: recruitment of pathways that are functionally homologous to, but anatomically distinct from, the damaged ones (eg, non-pyramidal corticospinal pathways), synaptogenesis, dendritic arborisation and reinforcement of existing but functionally silent synaptic connections (particularly at the periphery of core lesion). The study of neuroplasticity has clearly shown the ability of the developing brain--and of the adult and ageing brain--to be shaped by environmental inputs both under normal conditions (ie, learning) and after a lesion. Neuronal aggregates adjacent, or distant to a lesion in the sensorimotor area can progressively adopt the function of the injured area. Imaging studies indicate that recovery of motor function after a lesion (i.e. stroke) is associated with a progressive change of activation patterns in specific brain structures. Transcranial magnetic stimulation (TMS) and magnetoencephalography (MEG) can detect reshaping of sensorimotor areas; they have a high temporal resolution but have several limitations. TMS can only provide bidimensional scalp maps and MEG depicts three-dimensional spatial characteristics of virtual neural generators obtained by use of a mathematical model of the head and brain. However, the use of objective methods that assess brain reactivity to a physical stimulus (i.e., TMS) or to a sensory input (ie, electrical stimulation to hand and fingers) can integrate information from self-paced motor tasks, because the resolution of abnormal activation over time could be secondary to recovery. Functional MRI (fMRI) and positron emission tomography (PET), on their own, have insufficient time resolution to follow the hierarchical activation of relays within a neural network; however, because of their excellent spatial resolution, they can integrate the findings of TMS and MEG. An integrated approach constitutes, at present, the best way to assess the brain plasticity both under normal conditions and after a lesion.

Interhemispheric asymmetry of primary hand representation and recovery after stroke: a MEG study.

In patients affected by monohemispheric stroke in the middle cerebral artery territory, who do not regain a normal neurological function, a positive contribution to the clinical recovery seems to be made by the involvement of primary hand representation areas in the affected hemisphere (AH), excessively asymmetric to its homologous in the unaffected hemisphere (UH). We investigated primary sensory hand areas in 41 chronic patients who had improved their clinical status without reaching complete recovery. The location and strength of the first cerebral sources activated by a contralateral galvanic median nerve stimulation (M20 and M30) were evaluated in both hemispheres, together with their interhemispheric differences. The source displacement in the AH with respect to the UH was positively correlated with clinical recovery (Spearman's rho=0.584, p=0.003). The excessive interhemispheric asymmetry - as defined on the basis of reference ranges in the healthy population - could be interpreted as the involvement of neuronal pools in the AH outside the hand 'omega zone' of the Rolandic sulcus, revealing the presence of plasticity phenomena. The present data provide support to a positive role of cerebral plasticity phenomena, partially contributing to post-stroke recovery in patients unable to achieve normal neurological function.