Polypharmacy, functional outcome and treatment effect of intravenous alteplase for acute ischaemic stroke.

BACKGROUND AND PURPOSE: Polypharmacy is an important challenge in clinical practice. Our aim was to determine the effect of polypharmacy on functional outcome and treatment effect of alteplase in acute ischaemic stroke. METHODS: This was a post hoc analysis of the randomized, placebo-controlled WAKE-UP trial of magnetic resonance imaging guided intravenous alteplase in unknown onset stroke. Polypharmacy was defined as an intake of five or more medications at baseline. Comorbidities were assessed by the Charlson Comorbidity Index (CCI). The primary efficacy variable was favourable outcome defined by a score of 0-1 on the modified Rankin Scale at 90 days. Logistic regression analysis was used to test for an association of polypharmacy with functional outcome, and for interaction of polypharmacy and the effect of thrombolysis. RESULTS: Polypharmacy was present in 133/503 (26%) patients. Patients with polypharmacy were older (mean age 70 vs. 64 years; p < 0.0001) and had a higher score on the National Institutes of Health Stroke Scale at baseline (median 7 vs. 5; p = 0.0007). A comorbidity load defined by a CCI score ≥ 2 was more frequent in patients with polypharmacy (48% vs. 8%; p < 0.001). Polypharmacy was associated with lower odds of favourable outcome (adjusted odds ratio 0.50, 95% confidence interval 0.30-0.85; p = 0.0099), whilst the CCI score was not. Treatment with alteplase was associated with higher odds of favourable outcome in both groups, with no heterogeneity of treatment effect (test for interaction of treatment and polypharmacy, p = 0.29). CONCLUSION: In stroke patients, polypharmacy is associated with worse functional outcome after intravenous thrombolysis independent of comorbidities. However, polypharmacy does not interact with the beneficial effect of alteplase.

[Artificial intelligence in neurocritical care]. / Künstliche Intelligenz in der Neurointensivmedizin.

Artificial intelligence (AI) has been introduced into medicine and an AI-assisted medicine will be the future that we should help to shape. In particular, supervised, unsupervised, and reinforcement learning will be the main methods to play a role in the implementation of AI. Severely ill patients admitted to the intensive care unit (ICU) are closely monitored in order to be able to quickly respond to any changes. These monitoring data can be used to train AI models to predict critical phases in advance, making an earlier reaction possible. To achieve this a large amount of clinical data are needed in order to train models and an external validation on independent cohorts should take place. Prospective studies with treatment of patients admitted to the ICU with AI assistance should show that they provide a benefit for patients. We present the most important resources from de-identified (anonymized) patient data on open-source use for AI research in intensive care medicine. The focus is on neurological diseases in the ICU, therefore, we provide an overview of existing models for prediction of outcome, vasospasms, intracranial pressure and levels of consciousness. To introduce the advantages of AI in the clinical routine, more AI-based models with larger datasets will be needed. To achieve this international cooperation is absolutely necessary. Clinical centers associated with universities are needed to provide a constant validation of applied models as these models can change during use or a bias can develop during the training. A strong commitment to AI research is important for Germany, not only with respect to academic achievements but also in the light of a rapidly growing influence of AI on the economy.

Health-related quality of life 90 days after stroke assessed by the International Consortium for Health Outcome Measurement standard set.

BACKGROUND AND PURPOSE: Stroke has detrimental effects in multiple health domains not captured by routine scales. The International Consortium for Health Outcome Measurement has developed a standardized set for self-reported assessment to overcome this limitation. The aim was to assess this set in acute stroke care. METHODS: Consecutive patients with acute ischaemic stroke, transient ischaemic attack or intracerebral hemorrhage were enrolled. Demographics, living situation and cardiovascular risk factors were collected from medical records and interviews. The Patient-reported Outcomes Measurement Information System 10-Question Short Form (PROMIS-10) and the Patient Health Questionnaire-4 (PHQ-4) were conducted 90 days after admission. Linear and logistic regression analyses were used to identify predictors of outcome. The study is registered at ClinicalTrials.gov, NCT03795948. RESULTS: In all, 1064 patients were enrolled; mean age was 71.6 years, 51% were female, and median National Institutes of Health Stroke Scale (NIHSS) on admission was 3. Diagnosis was acute ischaemic stroke in 74%, transient ischaemic attack in 20% and intracerebral hemorrhage in 6%. 673 patients were available for outcome evaluation at 90 days; of these 90 (13%) had died. In survivors, t scores of PROMIS-10 physical and mental health were 40.3 ± 6.17 and 44.3 ± 8.63, compared to 50 ± 10 in healthy populations. 16% reported symptoms indicating depression or anxiety on the PHQ-4. Higher NIHSS, prior stroke and requiring help pre-stroke predicted lower values in physical and mental health scores. Higher NIHSS and diabetes were associated with anxiety or depression. CONCLUSIONS: Integrated in the routine of acute stroke care, systematic assessment of patient-reported outcomes reveals impairments in physical and mental health. Main predictors are severity of stroke symptoms and comorbidities such as hypertension and diabetes.

The impact of Parkinson disease on patients' sexuality and relationship.

This study aimed at examining the impact of Parkinson disease (PD) on patients' sexuality and relationship and to evaluate gender-specific differences. Using a standardized questionnaire on sexual functioning in chronic diseases (SFCE), the impact of PD diagnosis on 38 domains of sexuality before and since PD diagnosis was evaluated retrospectively in 53 consecutive patients in a relationship. Changes in self-assessed ratings on a four-point Likert scale were determined for all patients. In addition, gender-specific differences and the influence of age, depression (BDI-II), medication, disease severity and disease duration on domains of the SFCE were calculated. The importance of non-sexual relational aspects, such as talking about feelings or tenderness increased for both genders after PD diagnosis, especially in women. Sexual function, such as frequency of intercourse, sexual arousal, subjective abnormal sexual fantasies or sexual satisfaction deteriorated in both genders, especially in men. Some sexual aspects improved in women but worsened in men after PD diagnosis. This includes frequency of orgasm dysfunction, fear not to fulfill sexual expectations of the partner, avoidance of sexual acts, withdrawal from relationship, increase of thoughts about divorce, or increase of dissatisfaction with sexuality and relationship. With age, thoughts about divorce declined. With disease duration, frequency of tenderness with the partner increased. Depression unexpectedly correlated with higher frequency of intercourse. Dopaminergic dosage influenced stability of the relationship negatively. PD influences patients' sexuality negatively, independently of age, disease duration or disease severity and men show greater sexual dysfunction and impairment of their sexual relationship than women.

Effects of dopaminergic treatment on functional cortico-cortical connectivity in Parkinson's disease.

Interactions between dorsal premotor cortex (PMd) and primary motor cortex (M1) and interhemispheric inhibition (IHI) between M1 are impaired in Parkinson's disease (PD). We used dual-site transcranial magnetic stimulation to compare effects of first-time levodopa application with chronic dopaminergic therapy on these interactions in PD. Twelve untreated PD patients were studied before and after their first-ever intake of levodopa. The effects of chronic dopaminergic medication were evaluated in 11 patients who had received regular dopaminergic medication for approximately 3 years. Nine of these patients were also measured after overnight withdrawal of medication. For IHI, conditioning stimuli (CS) were applied to left M1 followed by test stimuli (TS) over right M1 and vice versa in separate blocks at interstimulus intervals (ISI) of 6-10 ms. Next, CS were applied to left PMd at subthreshold intensity followed by TS over left M1 at ISIs of 4 and 6 ms. Results were compared to 17 age- and gender-matched controls. In de novo PD patients, levodopa reduced left-to-right IHI, but did not alter PMd-M1 connectivity. In contrast, inhibitory PMd-M1 connectivity was present in early disease patients under chronic dopaminergic stimulation, but not in de novo PD patients at low stimulus intensities at an ISI of 4 ms. First-time exposure to levodopa exerts different effects on cortico-cortical pathways than chronic dopaminergic stimulation in PD, suggesting a change in the responsiveness of cortico-cortical circuits during the course of PD.

[On the interdisciplinary S3 guidelines for the treatment of chronic idiopathic tinnitus]. / Zur interdisziplinären S3-Leitlinie für die Therapie des chronisch-idiopathischen Tinnitus.

INTRODUCTION: Tinnitus is a frequent symptom, which, particularly in combination with comorbidities, can result in a severe disease-related burden. Chronic idiopathic tinnitus (CIT) is the most frequent type of tinnitus. A considerable number of treatment strategies are used to treat CIT-for many of which there is no evidence of efficacy. In order to enable scientific evidence-based treatment of CIT, German interdisciplinary S3 guidelines have recently been constructed for the first time. Here we present a short form of these S3 guidelines. MATERIALS AND METHODS: The guidelines were constructed based on a meta-analysis of the treatment of chronic tinnitus performed by the authors. Additionally, a systematic literature search was performed in the PubMed and Cochrane Library databases. Furthermore, a systematic search for international guidelines was performed in Google, as well as in the Guidelines International Network and National Guideline Clearinghouse (USA) database. Evidence was classified according to the Oxford Centre for Evidence-Based Medicine system. RESULTS: According to the guidelines, alongside counselling, manualized structured tinnitus-specific cognitive behavioral therapy (tCBT) with a validated treatment manual is available as evidence-based therapy. In addition, the guidelines recommend concurrent treatment of comorbidities, including drug-based treatment, where appropriate. Particularly important is treatment of anxiety and depression. Where a psychic or psychiatric comorbidity is suspected, further diagnosis and treatment should be performed by an appropriately qualified specialist (psychiatrist, neurologist, psychosomatic medicine consultant) or psychological psychotherapist. In cases accompanied by deafness or hearing loss bordering on deafness, cochlear implants may be indicated. CONCLUSION: No recommendations can be made for drug-based treatment of CIT, audiotherapy, transcranial magnetic or electrical stimulation, specific forms of acoustic stimulation or music therapy; or such recommendations must remain open due to the lack of available evidence. Polypragmatic tinnitus treatment with therapeutic strategies for which there is no evidence of efficacy from controlled studies is to be refused.

The control of complex finger movements by directional information flow between mesial frontocentral areas and the primary motor cortex.

Complex movements require the interplay of local activation and interareal communication of sensorimotor brain regions. This is reflected in a decrease of task-related spectral power over the sensorimotor cortices and an increase in functional connectivity predominantly in the upper alpha band in the electroencephalogram (EEG). In the present study, directionality of information flow was investigated using EEG recordings to gain better understanding about the network architecture underlying the performance of complex sequential finger movements. This was assessed by means of Granger causality-derived directed transfer function (DTF). As DTF measures the influence one signal exerts on another based on a time lag between them, it allows implications to be drawn on causal relationships. To reveal causal connections between brain regions that are specifically modulated by task complexity, we contrasted the performance of right-handed sequential finger movements of different complexities (simple, scale, complex) that were either pre-learned (memorized) or novel instructed. A complexity-dependent increase in information flow from mesial frontocentral to the left motor cortex and, less pronounced, also to the right motor cortex specifically in the upper alpha range was found. Effective coupling during sequences of high complexity was larger for memorized sequences compared with novel sequences (P = 0.0037). These findings further support the role of mesial frontocentral areas in directing the primary motor cortex in the process of orchestrating complex movements and in particular learned sequences.

Early infarct FLAIR hyperintensity is associated with increased hemorrhagic transformation after thrombolysis.

BACKGROUND AND PURPOSE: Absence of FLAIR hyperintensity within an acute infarct is associated with stroke onset <4.5 h. However, some patients rapidly develop FLAIR hyperintensity within this timeframe. We hypothesized that development of early infarct FLAIR hyperintensity would predict hemorrhagic transformation (HT) in patients treated with tissue plasminogen activator (tPA) < 4.5 h after onset. METHODS: Consecutive acute stroke patients treated with intravenous tPA <4.5 h after onset who had MRI before and 1 day after thrombolysis were included. Two raters (blind to HT) independently identified FLAIR hyperintensity with reference to the diffusion-weighted image (DWI) lesion. HT was assessed using T2* MRI at 24 h. Hemorrhagic infarction (HI) was defined as petechial HT without mass effect, and parenchymal hematoma (PH) as HT with mass effect. Multivariable logistic regression analysis for HT included FLAIR status, baseline National Institutes of Health Stroke Scale and DWI lesion volume, leukoaraiosis (Wahlund score), serum glucose and reperfusion. RESULTS: Of 109 patients, 33 (30%) had acute FLAIR hyperintensity. HT occurred in 17 patients (15.6%; 15 HI, 2 PH). HT was more common in FLAIR-positive patients than FLAIR-negative patients (33.3% vs. 9.2%, P = 0.009). Median time-to-scan and median time-to-thrombolysis did not differ significantly between patients with HT and without [97 IQR(68, 155) vs. 90 IQR(73, 119), P = 0.5; 120 IQR(99, 185) vs. 125 IQR(95, 150), P = 0.6, respectively]. In multivariable analysis, only FLAIR hyperintensity was independently associated with HT after thrombolysis (OR 18; 95% CI 2-175, P = 0.013). CONCLUSIONS: Early development of FLAIR hyperintensity within the area of diffusion restriction is associated with increased risk of HT after thrombolysis in acute stroke patients.

[University teaching in clinical neurology: present situation and future requirements]. / Universitäre Lehre in der Neurologie : Aktuelle Situation und zukünftiger Bedarf.

BACKGROUND: In German Hospitals there is a lack of medical personnel and doctors in particular. Clinical specialities and hospitals are in competition for students and young doctors and these, in turn, have clear cut demands regarding working conditions and professional training. To date there is considerable heterogeneity regarding clinical teaching in neurology between different German universities. There are no data available for systematic comparison. MATERIAL AND METHODS: This article presents for the first time data from a survey on academic teaching in neurology in German university hospitals. RESULTS AND CONCLUSION: The data show that many faculties are dedicated to modern and practical teaching methods and have employed state of the art examinations and progress tests. Further and ongoing efforts will be needed in order to inspire medical students and young doctors for this interesting clinical speciality. Connecting individual formats and networking between universities, teaching hospitals, including novel developments together with the young neurologists will help to structure our efforts and increase sustained attractiveness of clinical neurology for the following generations of young doctors.

[Transcranial brain stimulation after stroke]. / Transkranielle Hirnstimulation nach Schlaganfall.

Stroke is the leading cause of disability in adults. In Germany an estimated 1.5 million stroke survivors have to cope with persisting sensorimotor or cognitive deficits and effective therapies are scarce. The idea of using non-invasive brain stimulation to treat neuropsychiatric diseases was already born more than 2,000 years ago (Scribonius largus, 43-48 AD). However, only the development of modern non-invasive brain stimulation methods, such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) has made it possible to evaluate these ideas. The therapeutic value of these non-invasive brain stimulation methods is currently under study for several neuropsychiatric diseases, mostly in a proof-of-principle fashion. In this article the focus will be on non-invasive brain stimulation to enhance functional regeneration after stroke.

[EU-funded treatment study: WAKE-UP: a randomized, placebo-controlled MRI-based trial of thrombolysis in wake-up stroke]. / EU-geförderte Therapiestudie WAKE-UP : Eine randomisierte, placebokontrollierte, MRT-basierte Thrombolysestudie bei "wake-up stroke"

Patients waking up with stroke symptoms are generally excluded from intravenous thrombolysis. It was shown that magnetic resonance imaging (MRI) can identify patients within the time window for thrombolysis (≤ 4.5 h from symptom onset) by a mismatch between the acute ischemic lesion visible on diffusion-weighted imaging (DWI) but not visible on fluid-attenuated inversion recovery (FLAIR) imaging. The WAKE-UP trial is an investigator initiated, European, randomized, double-blind, placebo-controlled trial designed to test efficacy and safety of MRI-based thrombolysis with alteplase (tPA) in stroke patients with unknown time of symptom onset, e.g. due to symptom recognition on awakening. A total of 800 patients showing MRI findings of a DWI-FLAIR-mismatch will be randomized to either tPA or placebo. The primary efficacy endpoint will be favourable outcome defined by a modified Rankin scale score 0-1 at day 90. The primary safety outcome measures will be mortality and death or dependency defined by modified Rankin scale score 4-6 at 90 days. If positive the WAKE-UP trial is expected to change clinical practice and to make effective and safe treatment available for a large group of acute stroke patients currently excluded from specific acute treatment.

Pre-stroke socioeconomic status predicts upper limb motor recovery after inpatient neurorehabilitation.

BACKGROUND: Lower socioeconomic status (SES) is associated with higher mortality rates and the likelihood of receiving less evidence-based treatment after stroke. In contrast, little is known about the impact of SES on recovery after discharge from inpatient rehabilitation. The aim of this study was to investigate the influence of SES on long-term recovery after stroke. PATIENTS AND METHODS: In a prospective, observational, multicentre study, inpatients were recruited towards the end of rehabilitation. The 12-month follow-up focussed on upper limb motor recovery, measured by the Fugl-Meyer score. A clinically relevant improvement of ≥5.25 points was considered recovery. Patient-centric measures such as the Patient-reported Outcomes Measurement Information System-Physical Health (PROMIS-10 PH) provided secondary outcomes. Information on schooling, vocational training, income and occupational status pre-stroke entered a multidimensional SES index. Multivariate logistic regression models calculating odds ratios (ORs) and corresponding confidence intervals (CIs) were applied. SES was added to an initial model including age, sex and baseline neurological deficit. Additional exploratory analyses examined the association between SES and outpatient treatment. RESULTS: One hundred and seventy-six patients were enrolled of whom 98 had SES and long-term recovery data. Model comparisons showed the SES-model superior to the initial model (Akaike information criterion (AIC): 123 vs. 120, Pseudo R2: 0.09 vs. 0.13). The likelihood of motor recovery (OR = 17.12, 95%CI = 1.31; 224.18) and PROMIS-10 PH improvement (OR = 20.76, 95%CI = 1.28; 337.11) were significantly increased with higher SES, along with more frequent use of outpatient therapy (p = .02). CONCLUSIONS: Higher pre-stroke SES is associated with better long-term recovery after discharge from rehabilitation. Understanding these factors can improve outpatient long-term stroke care and lead to better recovery.KEY MESSAGEHigher pre-stroke socioeconomic status (SES) is associated with better long-term recovery after discharge from rehabilitation both in terms of motor function and self-reported health status.Higher SES is associated with significantly higher utilization of outpatient therapies.Discharge management of rehabilitation clinics should identify and address socioeconomic factors in order to detect individual needs and to improve outpatient recovery. Article registration: clinicaltrials.gov NCT04119479.

Altered modulation of intracortical excitability during movement preparation in Gilles de la Tourette syndrome.

Gilles de la Tourette syndrome is a neuropsychiatric disorder in which cortical disinhibition has been proposed as a pathophysiological mechanism involved in the generation of tics. Tics are typically reduced during task performance and concentration. How this task-dependent reduction of motor symptoms is represented in the brain is not yet understood. The aim of the current research was to study motorcortical excitability at rest and during the preparation of a simple motor task. Transcranial magnetic stimulation was used to examine corticospinal excitability, short-interval intracortical inhibition and intracortical facilitation in a group of 11 patients with Gilles de la Tourette syndrome and age-matched healthy controls. Parameters of cortical excitability were evaluated at rest and at six points in time during the preparation of a simple finger movement. Patients with Gilles de la Tourette syndrome displayed significantly reduced short-interval intracortical inhibition at rest, while no differences were apparent for unconditioned motor evoked potential or intracortical facilitation. During the premovement phase, significant differences between groups were seen for single pulse motor evoked potential amplitudes and short-interval intracortical inhibition. Short-interval intracortical inhibition was reduced in the early phase of movement preparation (similar to rest) followed by a transition towards more inhibition. Subsequently modulation of short-interval intracortical inhibition was comparable to controls, while corticospinal recruitment was reduced in later phases of movement preparation. The present data support the hypothesis of motorcortical disinhibition in Gilles de la Tourette syndrome at rest. During performance of a motor task, patients start from an abnormally disinhibited level of short-interval intracortical inhibition early during movement preparation with subsequent modulation of inhibitory activity similar to healthy controls. We hypothesize that while at rest, abnormal subcortical inputs from aberrant striato-thalamic afferents target the motor cortex, during motor performance, motor cortical excitability most likely underlies top-down control from higher motor areas and prefrontal cortex, which override these abnormal subcortical inputs to guarantee adequate behavioural performance.

Spontaneous locally restricted EEG alpha activity determines cortical excitability in the motor cortex.

There is growing interest in the functional meaning of rhythmical brain activity. For oscillatory brain activity around 10 Hz in the human electroencephalogram (EEG) it is discussed whether it is associated with the level of cortical excitation. However, it is not clear whether the relation between 10 Hz EEG oscillatory activity and cortical excitability is a global, locally very unspecific phenomenon or whether focal 10 Hz oscillations in the human brain are a highly specific correlate of the cortical excitation level. To determine this open question, multichannel EEG was combined with transcranial magnetic stimulation (TMS) applied to the primary motor cortex in this study. The present data showed that a motor evoked potential was elicited more easily when alpha power immediately preceding the magnetic pulse was low, and vice versa. Interestingly, this effect was only found for very local EEG alpha activity at sites overlying the cortical motor areas to which the TMS pulses were applied. This was verified using source localization in 3D space. These data provide evidence that the magnitude of motor cortical excitability is determined by the amount of topographically specific alpha oscillations in the sensorimotor cortex.

Thrombolysis targeting MRI defined tissue at risk in minor stroke.

BACKGROUND: Treatment with intravenous tissue plasminogen activator (IV-tPA) is usually not recommended in patients with minor stroke. Clinical and imaging outcome were studied after IV-tPA treatment based on MRI criteria in patients with minor stroke. METHODS: Data were analysed retrospectively of acute ischaemic stroke patients with minor stroke (National Institutes of Health Stroke Scale (NIHSS) score <4). All patients were studied by stroke MRI including perfusion and diffusion weighted imaging (PWI and DWI) and treated with IV-tPA for < or =6 h. Final infarct volume was delineated on follow-up MRI. Clinical outcome was assessed after 90 days using the modified Rankin Scale (mRS). RESULTS: Six patients with a median NIHSS on admission of 2 (range 0-3) were treated with IV-tPA based on MRI criteria. In all patients, occlusion of the middle cerebral artery (MCA) was detected (MCA branch n = 2, MCA trunk n = 3, MCA trifurcation n = 1), and the PWI lesion (41, 25-60 ml) exceeded the DWI lesion (4, 1-23 ml). Final infarct volume was 9 (2-29) ml. Favourable outcome (mRS 0-1) was seen in 5/6 patients and independent outcome (mRS = 2) in one patient. No intracerebral haemorrhages occurred. CONCLUSION: Treatment with IV-tPA based on MRI criteria was safe and appeared to be effective in this small series of patients with minor stroke.

Are cortical spreading depression and headache in migraine causally linked?

During the past few decades, much controversy has surrounded the pathophysiology of migraine. Cortical spreading depression (CSD) is widely accepted as the neuronal process underlying visual auras. It has been proposed that CSD can also cause the headaches, at least in migraine with aura. We describe three patients, each fulfilling the International Headache Society criteria for migraine with aura, who suffered from headaches 6-10 days per month. Two patients were treated with flunarizine and the third patient with topiramate for the duration of 4 months. All patients reported that aura symptoms resolved completely, whereas the migraine headache attacks persisted or even increased. These observations question the theory that CSD (silent or not) is a prerequisite for migraine headaches.

[Colon triplication associated with ileum atresia in laparoschisis]. / Kolon-Triplikatur assoziiert mit einer Ileum-Atresie bei Laparoschisis.

The present paper reports the unusual and rare case of a colon triplication associated with other findings never reported before, including the diagnostic and therapeutic management with consideration of the relevant, but rare scientific references in the medical literature. In the basic finding of an ileum atresia with laparoschisis, a colon triplication was incidentally found. The surgical procedure performed after the primarily planned Caesarean section within the 34(th) week of gravidity consisted of a bowel-preserving resection of the triplication including the ileum atresia and a subsequent Santulli anastomosis followed by a later excision of the ileostoma. Interestingly, this is the 9(th) reported case in the accessible English medical literature but, however, the first and only one with an associated ileum atresia and laparoschisis, which was successfully treated with a surgical intervention.

[Congenital abdominal wall defects--an analysis of prevalence and operative management by means of gastroschisis and omphalocele]. / Ventrale Bauchwanddefekte--Darstellung der Entwicklung in Prävalenz und operativem Vorgehen anhand von Gastroschisis und Omphalozele.

The management of congenital abdominal wall defects is one of the main characteristics of quality for a department of paediatric surgery. The results of treatment in the early years were the reason for a continuous improvement of procedures, operation strategies and the kinds of -material that had been used. During the last years there has been a great discussion about the presumed increase in the incidence of gastroschisis and the preterm delivery of such cases. On the basis of our own first results (2006-2009) and details from the literature, we survey these two topics.

Methods for analysis of brain connectivity: An IFCN-sponsored review.

The goal of this paper is to examine existing methods to study the "Human Brain Connectome" with a specific focus on the neurophysiological ones. In recent years, a new approach has been developed to evaluate the anatomical and functional organization of the human brain: the aim of this promising multimodality effort is to identify and classify neuronal networks with a number of neurobiologically meaningful and easily computable measures to create its connectome. By defining anatomical and functional connections of brain regions on the same map through an integrated approach, comprising both modern neurophysiological and neuroimaging (i.e. flow/metabolic) brain-mapping techniques, network analysis becomes a powerful tool for exploring structural-functional connectivity mechanisms and for revealing etiological relationships that link connectivity abnormalities to neuropsychiatric disorders. Following a recent IFCN-endorsed meeting, a panel of international experts was selected to produce this current state-of-art document, which covers the available knowledge on anatomical and functional connectivity, including the most commonly used structural and functional MRI, EEG, MEG and non-invasive brain stimulation techniques and measures of local and global brain connectivity.