Causal decoding of individual cortical excitability states.

Brain responsiveness to stimulation fluctuates with rapidly shifting cortical excitability state, as reflected by oscillations in the electroencephalogram (EEG). For example, the amplitude of motor-evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) of motor cortex changes from trial to trial. To date, individual estimation of the cortical processes leading to this excitability fluctuation has not been possible. Here, we propose a data-driven method to derive individually optimized EEG classifiers in healthy humans using a supervised learning approach that relates pre-TMS EEG activity dynamics to MEP amplitude. Our approach enables considering multiple brain regions and frequency bands, without defining them a priori, whose compound phase-pattern information determines the excitability. The individualized classifier leads to an increased classification accuracy of cortical excitability states from 57% to 67% when compared to µ-oscillation phase extracted by standard fixed spatial filters. Results show that, for the used TMS protocol, excitability fluctuates predominantly in the µ-oscillation range, and relevant cortical areas cluster around the stimulated motor cortex, but between subjects there is variability in relevant power spectra, phases, and cortical regions. This novel decoding method allows causal investigation of the cortical excitability state, which is critical also for individualizing therapeutic brain stimulation.

Inhibition in the somatosensory system: An integrative neuropharmacological and neuroimaging approach.

The presented study investigates the functional role of GABA in somatosensory processing, using a combined neuropharmacological-neuroimaging approach. Three different GABA agonists (GABAA: alprazolam, ethanol; GABAB: baclofen) were investigated in a double blind cross-over design in 16 male participants, accomplishing a tactile perception task. Somatosensory evoked magnetic fields modulated by GABAR-agonists and placebo were recorded using whole-head magnetoencephalography. Peak latencies and amplitudes of primary (SI) and secondary (SII) somatosensory cortex source activities confirmed the previously reported role of GABA as a modulator of somatosensory processing. Significant inhibitory effects on the latency of SII and on the amplitude of SI and SII were found exclusively for alprazolam, a positive allosteric modulator at GABAA receptors. The GABAB agonist baclofen did not have any modulatory effect. Moreover, we investigated whether the observed effects of alprazolam on the level of SII were explainable by the mere propagation of activity from SI to SII modulated by GABAA receptors, independently from any further GABAA-mediated inhibition in SII. By estimating the transfer function between SI and SII activation under placebo conditions, we were able to predict SII activity for the administration of GABA receptors agonists under the assumption that GABA exclusively acts at the level of SI. By comparing measured and predicted data, we propose a model in which the initial activation of SI is modulated through GABAA receptors and subsequently propagated to SII, without any significant further inhibition. In addition, initial GABAA effects in SI appear to be strongly potentiated with time, selectively in SI but not in SII.

Recurrent ischaemic cerebrovascular events as presenting manifestations of myeloproliferative neoplasms.

BACKGROUND AND PURPOSE: Myeloproliferative neoplasms (MPNs) - polycythemia vera, essential thrombocythemia and primary myelofibrosis - are associated with increased risk for ischaemic cerebrovascular events (ICVEs). Due to their low prevalence, MPNs often remain undiagnosed as the cause of ICVEs. METHODS: Case records at the University of Tübingen between 2014 and 2017 were screened to identify patients with MPN-related ICVEs. Clinical features, brain imaging, laboratory findings, applied treatments and neurological outcomes were assessed. RESULTS: In all, 3318 patients with ICVEs were identified, and amongst them 17 patients with MPN-related ICVEs were included in a retrospective study. In 58% of these patients, ICVEs were the first manifestation of the underlying MPN; 24% presented with transient ischaemic attack and 76% with ischaemic stroke. Potentially concurrent ICVE etiologies were noted in 70% of the patients. The majority (94%) of patients were positive for the JAK2 V617F mutation, whilst in 29% recurrent ICVEs (range two to three) were noted prior to MPN diagnosis. Early MPN diagnosis and management was the only significant prognostic factor for ICVE recurrence (P < 0.001). DISCUSSION: Evidence is provided that, although rare, MPNs represent an underdiagnosed cause of recurrent ICVEs. High clinical awareness is warranted to identify an underlying MPN in patients presenting with sustained, abnormal blood count findings. Clinical algorithms for prompt MPN diagnosis and initiation of MPN treatment (e.g. cytoreductive therapy, phlebotomy) are required. As MPN management comprises a significant protective factor against ICVE recurrence, induction of MPN treatment should be regarded as an integral component of secondary stroke prevention in MPN-associated ICVEs.

[Susac Syndrome: A Diagnostic Chameleon]. / Susac-Syndrom: ein diagnostisches Chamäleon.

Susac's syndrome (SuS) is a rare, probably autoimmune endotheliopathy of the central nervous system, retina and inner ear. It is characterized by a clinical triad of encephalopathy, branch retinal artery occlusions (BRAOs) and sensorineural hearing loss. To date, more than 300 cases of SuS have been reported in the literature. However, SuS remains an under- and misdiagnosed entity in the clinical setting. This report presents an exemplary case of a patient, who was initially misdiagnosed with relapsing-remitting multiple sclerosis. At initial presentation, the patient did not demonstrate the complete clinical triad, and the interval between symptom onset and diagnosis was 4 months. Typical diagnostic features, which enabled the diagnosis of SuS were: a) MRI findings with T2-hyperintense snowball-like lesions of the corpus callosum and subcortical white matter and hyperintense lesions in diffusionweighted imaging with reduced apparent diffusion coefficient; b) BRAOs and vessel wall hyperfluorescence in fluorescein angiography and a significant thickness reduction of the inner retinal layers in optical coherence tomography; c) bilateral sensorineural hearing loss. The patient was aggressively treated with cyclophosphamide, rituximab, glucocorticoids and acetylsalicylic acid with a good response to therapy. This report draws attention to the need to take SuS into consideration in the differential diagnosis at the interface of neurological, psychiatric, ophthalmological and otorhinolaryngological disorders. As SuS may result in severe and persistent neurological deficits, an interdisciplinary collaboration is fundamental for the prompt diagnosis and initiation of adequate immunosuppressive treatment.

Reinforcement learning of self-regulated sensorimotor ß-oscillations improves motor performance.

Self-regulation of sensorimotor oscillations is currently researched in neurorehabilitation, e.g. for priming subsequent physiotherapy in stroke patients, and may be modulated by neurofeedback or transcranial brain stimulation. It has still to be demonstrated, however, whether and under which training conditions such brain self-regulation could also result in motor gains. Thirty-two right-handed, healthy subjects participated in a three-day intervention during which they performed 462 trials of kinesthetic motor-imagery while a brain-robot interface (BRI) turned event-related ß-band desynchronization of the left sensorimotor cortex into the opening of the right hand by a robotic orthosis. Different training conditions were compared in a parallel-group design: (i) adaptive classifier thresholding and contingent feedback, (ii) adaptive classifier thresholding and non-contingent feedback, (iii) non-adaptive classifier thresholding and contingent feedback, and (iv) non-adaptive classifier thresholding and non-contingent feedback. We studied the task-related cortical physiology with electroencephalography and the behavioral performance in a subsequent isometric motor task. Contingent neurofeedback and adaptive classifier thresholding were critical for learning brain self-regulation which, in turn, led to behavioral gains after the intervention. The acquired skill for sustained sensorimotor ß-desynchronization correlated significantly with subsequent motor improvement. Operant learning of brain self-regulation with a BRI may offer a therapeutic perspective for severely affected stroke patients lacking residual hand function.

Insertable cardiac monitors after cryptogenic stroke--a risk factor based approach to enhance the detection rate for paroxysmal atrial fibrillation.

BACKGROUND AND PURPOSE: Recently, the CRYSTAL AF trial detected paroxysmal atrial fibrillation (AF) in 12.4% of patients after cryptogenic ischaemic stroke (IS) or cryptogenic transient ischaemic attack (TIA) by an insertable cardiac monitor (ICM) within 1 year of monitoring. Our aim was (i) to assess if an AF risk factor based pre-selection of ICM candidates would enhance the rate of AF detection and (ii) to determine AF risk factors with significant predictive value for AF detection. METHODS: Seventy-five patients with cryptogenic IS/TIA were consecutively enrolled if at least one of the following AF risk factors was present: a CHA2DS2-VASc score ≥4, atrial runs, left atrium (LA) size >45 mm, left atrial appendage (LAA) flow ≤0.2 m/s, or spontaneous echo contrast in the LAA. The electrocardiographic and echocardiographic criteria were chosen as they have been repeatedly reported to predict AF; the same applies for four of the six items of the CHA2DS2-VASc score. The study end-point was the detection of one or more episodes of AF (≥2 min). RESULTS: Seventy-four patients underwent implantation of an ICM; one patient had AF at the date of implantation. After 6 months, AF was detected in 21/75 patients (28%), after 12 months in 25/75 patients (33.3%). 92% of AF episodes were asymptomatic. LA size >45 mm and the presence of atrial runs were independently associated with AF detection [hazard ratio 3.6 (95% confidence interval 1.6-8.4), P = 0.002, and 2.7 (1.2-6.7), P = 0.023, respectively]. CONCLUSIONS: The detection rate of AF is one-third after 1 year if candidates for an ICM after cryptogenic IS/TIA are selected by AF risk factors. LA dilation and atrial runs independently predict AF.

A case of late-onset, thymoma-associated myasthenia gravis with ryanodine receptor and titin antibodies and concomitant granulomatous myositis.

BACKGROUND: Myasthenia gravis is an autoimmune neuromuscular disorder, which has only rarely been reported to co-manifest with myositis. The diagnosis of concomitant myositis in patients with myasthenia gravis is clinically challenging, and requires targeted investigations for the differential diagnosis, including EMG, autoantibody assays, muscle biopsy and, importantly, imaging of the mediastinum for thymoma screening. CASE PRESENTATION: This report presents a case-vignette of a 72-year-old woman with progressive proximal muscle weakness and myalgias, diagnosed with thymoma-associated myasthenia and bioptically verified granulomatous myositis, with positive autoantibody status for ryanodine receptor and titin antibodies. CONCLUSIONS: The diagnosis of concurrent myositis and myasthenia gravis, especially in the presence of ryanodine receptor and titin antibodies, should lead neurologists to adopt different treatment strategies compared to those applied in myasthenia or myositis alone. Moreover, further evidence is warranted that titin and, particularly, ryanodine receptor antibodies may co-occur or be pathophysiologically involved in myasthenia-myositis cases.

[Therapeutic applications of closed-loop brain stimulation. Success and expectations]. / Therapeutischer Einsatz von Closed-loop-Hirnstimulation. Erfolge und Erwartungen.

The therapeutic application of brain stimulation is still limited to relatively few indications and small groups of patients due to variable efficacy. Individualization of stimulation parameters by employing a closed-loop system, i.e. synchronization of stimulation with endogenous brain activity with millisecond precision, has the potential to significantly improve the therapeutic efficacy when compared to open-loop systems. In this article the theoretical and experimental results are reviewed including first clinical trials that support the superiority of closed-loop brain stimulation, fundamental aspects in the development of closed loop methods are discussed and clinical studies which could quantify an increase in effectiveness are summarized. A significant increase in the indications for therapeutic applications of closed-loop systems is to be expected in the near future.

Working memory performance of early MS patients correlates inversely with modularity increases in resting state functional connectivity networks.

Multiple sclerosis (MS) is an autoimmune inflammatory demyelinating and neurodegenerative disorder of the central nervous system characterized by multifocal white matter brain lesions leading to alterations in connectivity at the subcortical and cortical level. Graph theory, in combination with neuroimaging techniques, has been recently developed into a powerful tool to assess the large-scale structure of brain functional connectivity. Considering the structural damage present in the brain of MS patients, we hypothesized that the topological properties of resting-state functional networks of early MS patients would be re-arranged in order to limit the impact of disease expression. A standardized dual task (Paced Auditory Serial Addition Task simultaneously performed with a paper and pencil task) was administered to study the interactions between behavioral performance and functional network re-organization. We studied a group of 16 early MS patients (35.3±8.3 years, 11 females) and 20 healthy controls (29.9±7.0 years, 10 females) and found that brain resting-state networks of the MS patients displayed increased network modularity, i.e. diminished functional integration between separate functional modules. Modularity correlated negatively with dual task performance in the MS patients. Our results shed light on how localized anatomical connectivity damage can globally impact brain functional connectivity and how these alterations can impair behavioral performance. Finally, given the early stage of the MS patients included in this study, network modularity could be considered a promising biomarker for detection of earliest-stage brain network reorganization, and possibly of disease progression.

Non-invasive cerebellar stimulation--a consensus paper.

The field of neurostimulation of the cerebellum either with transcranial magnetic stimulation (TMS; single pulse or repetitive (rTMS)) or transcranial direct current stimulation (tDCS; anodal or cathodal) is gaining popularity in the scientific community, in particular because these stimulation techniques are non-invasive and provide novel information on cerebellar functions. There is a consensus amongst the panel of experts that both TMS and tDCS can effectively influence cerebellar functions, not only in the motor domain, with effects on visually guided tracking tasks, motor surround inhibition, motor adaptation and learning, but also for the cognitive and affective operations handled by the cerebro-cerebellar circuits. Verbal working memory, semantic associations and predictive language processing are amongst these operations. Both TMS and tDCS modulate the connectivity between the cerebellum and the primary motor cortex, tuning cerebellar excitability. Cerebellar TMS is an effective and valuable method to evaluate the cerebello-thalamo-cortical loop functions and for the study of the pathophysiology of ataxia. In most circumstances, DCS induces a polarity-dependent site-specific modulation of cerebellar activity. Paired associative stimulation of the cerebello-dentato-thalamo-M1 pathway can induce bidirectional long-term spike-timing-dependent plasticity-like changes of corticospinal excitability. However, the panel of experts considers that several important issues still remain unresolved and require further research. In particular, the role of TMS in promoting cerebellar plasticity is not established. Moreover, the exact positioning of electrode stimulation and the duration of the after effects of tDCS remain unclear. Future studies are required to better define how DCS over particular regions of the cerebellum affects individual cerebellar symptoms, given the topographical organization of cerebellar symptoms. The long-term neural consequences of non-invasive cerebellar modulation are also unclear. Although there is an agreement that the clinical applications in cerebellar disorders are likely numerous, it is emphasized that rigorous large-scale clinical trials are missing. Further studies should be encouraged to better clarify the role of using non-invasive neurostimulation techniques over the cerebellum in motor, cognitive and psychiatric rehabilitation strategies.

A questionnaire to collect unintended effects of transcranial magnetic stimulation: A consensus based approach.

Transcranial magnetic stimulation (TMS) has been widely used in both clinical and research practice. However, TMS might induce unintended sensations and undesired effects as well as serious adverse effects. To date, no shared forms are available to report such unintended effects. This study aimed at developing a questionnaire enabling reporting of TMS unintended effects. A Delphi procedure was applied which allowed consensus among TMS experts. A steering committee nominated a number of experts to be involved in the Delphi procedure. Three rounds were conducted before reaching a consensus. Afterwards, the questionnaire was publicized on the International Federation of Clinical Neurophysiology website to collect further suggestions by the wider scientific community. A last Delphi round was then conducted to obtain consensus on the suggestions collected during the publicization and integrate them in the questionnaire. The procedure resulted in a questionnaire, that is the TMSens_Q, applicable in clinical and research settings. Routine use of the structured TMS questionnaire and standard reporting of unintended TMS effects will help to monitor the safety of TMS, particularly when applying new protocols. It will also improve the quality of data collection as well as the interpretation of experimental findings.

Inhibitory and disinhibitory effects on I-wave facilitation in motor cortex.

A suprathreshold pulse of transcranial magnetic stimulation (TMS) delivered to human motor cortex results in a period of long-interval intracortical inhibition (LICI) followed by a briefer period of disinhibition (late cortical disinhibition [LCD]). Short-interval intracortical facilitation (SICF) is mediated by excitatory networks in the motor cortex responsible for the generation of the indirect (I-) wave volleys that are evoked by TMS at a periodicity of about 1.5 ms. Because the excitatory synaptic network responsible for SICF undergoes inhibitory regulation, we hypothesized that SICF will be modulated during periods of inhibition and disinhibition. In particular we were interested to know whether SICF was up-regulated during disinhibition, implying an increase in excitatory synaptic efficacy. We measured SICF, at a paired-pulse interval of 1.5 ms, at various times (100-300 ms) after a suprathreshold priming stimulus (PS) of sufficient strength to evoke LICI and LCD. We found that the strength of SICF was normal during LICI, but was increased during LCD by an average of 64%. SICF onset latency was reduced by one I-wave interval during LCD and was delayed by one I-wave interval during LICI. We conclude that disinhibition, rather than inhibition, modulates the excitatory neuronal networks that underlie SICF, whereas the I-wave targeted is modified by the presence of both inhibition and disinhibition and that there is therefore a dissociation between the strength and site of SICF interaction. The increase in SICF during disinhibition further indicates that this is a promising period to investigate or modulate excitatory synaptic networks while they are less constrained by ongoing levels of inhibition.

Paraneoplastic cerebellar degeneration mimicking development of secondary progressive multiple sclerosis in a patient with relapsing-remitting multiple sclerosis.

Paraneoplastic cerebellar degeneration (PCD) is a rare non-metastatic complication of cancer mediated by T lymphocytes and auto-antibodies directed against Purkinje cells of the cerebellum. We report a patient with relapsing-remitting multiple sclerosis who developed a progressive cerebellar syndrome with dysarthria, ataxic gait and vertigo mimicking development of secondary progressive multiple sclerosis but caused by anti-Yo antibody positive PCD associated with ovarian cancer, presenting an unusual diagnostic challenge.

[Hirayama disease in Germany: case reports and review of the literature]. / Hirayama-Syndrom in Deutschland : Fallberichte und Literaturübersicht.

Hirayama disease is a juvenile benign distal upper limb muscular atrophy rarely observed in Europe, usually monomelic involving C7-Th1 innervated muscles. It is characterized by insidious onset and a self-limited course within a few years. The pathogenesis of this mostly sporadic disease is not fully clarified. Cervical flexion myelopathy with mechanical ischemic damage of spinal motoneurons is the best established pathogenetic hypothesis, but neurodegenerative and autoimmune causes are also debated. Typically, young men of Asian origin are affected. Here we describe three German Caucasian patients with Hirayama disease and provide an up-to-date review of the literature.

Determinants of the induction of cortical plasticity by non-invasive brain stimulation in healthy subjects.

The ability to induce cortical plasticity with non-invasive brain stimulation (NBS) techniques has provided novel and exciting opportunities for examining the role of the human cortex during a variety of behaviours. Additionally, and importantly, the induction of lasting changes in cortical excitability can, under some conditions, reversibly modify behaviour and interact with normal learning. Such findings have driven a large number of recent studies examining whether by using such approaches it might be possible to induce functionally significant changes in patients with a large variety of neurological and psychiatric conditions including stroke, Parkinson's disease and depression. However, even in neurologically normal subjects the variability in the neurophysiological and behavioural response to such brain stimulation techniques is high. This variability at present limits the therapeutic usefulness of these techniques. The cause of this variability is multifactorial and to some degree still unknown. However, a number of factors that can influence the induction of plasticity have been identified. This review will summarise what is known about the causes of variability in healthy subjects and propose additional factors that are likely to be important determinants. A greater understanding of these determinants is critical for optimising the therapeutic applications of non-invasive brain stimulation techniques.

Late cortical disinhibition in human motor cortex: a triple-pulse transcranial magnetic stimulation study.

In human motor cortex transcranial magnetic stimulation (TMS) has been used to identify short-interval intracortical inhibition (SICI) corresponding to gamma-aminobutyric acid type A (GABA(A)) effects and long-interval intracortical inhibition (LICI) and the cortical silent period (SP) corresponding to postsynaptic GABA(B) effects. Presynaptic GABA(B) effects, corresponding to disinhibition, can also be identified with TMS and have been shown to be acting during LICI by measuring SICI after a suprathreshold priming stimulus (PS). The duration of disinhibition is not certain and, guided by studies in experimental preparations, we hypothesized that it may be longer-lasting than postsynaptic inhibition, leading to a period of late cortical disinhibition and consequently a net increase in corticospinal excitability. We tested this first by measuring the motor-evoked potential (MEP) to a test stimulus (TS), delivered after a PS at interpulse intervals (IPIs) < or =300 ms that encompassed the period of PS-induced LICI and its aftermath. MEP amplitude was initially decreased, but then increased at IPIs of 190-210 ms, reaching 160 +/- 17% of baseline 200 ms after PS (P < 0.05). SP duration was 181 +/- 5 ms. A second experiment established that the onset of the later period of increased excitability correlated with PS intensity (r(2) = 0.99) and with the duration of the SP (r(2) = 0.99). The third and main experiment demonstrated that SICI was significantly reduced in strength at all IPIs < or =220 ms after PS. We conclude that TMS-induced LICI is associated with a period of disinhibition that is at first masked by LICI, but that outlasts LICI and gives rise to a period during which disinhibition predominates and net excitability is raised. Identification of this late period of disinhibition in human motor cortex may provide an opportunity to explore or modulate the behavior of excitatory networks at a time when inhibitory effects are restrained.

Rapid motor cortical reorganization following subacute spinal cord dysfunction.

OBJECTIVE: Damage to the spinal cord is known to be associated with a posterior shift of the motor cortical upper limb representation, i.e. towards the somatosensory cortex. Due to missing pre-traumatic data, knowledge resulted from comparing findings between patients and healthy subjects. Here, we present a case of transient spinal cord injury resulting in a left-sided hemiparesis for 4 weeks. By chance, this patient had a pre-lesional navigated transcranial magnetic stimulation (nTMS) motor mapping 2 years before. Hence, nTMS mapping was repeated during the acute (after 1 day), sub-acute (after 10 days) and chronic (after 2 years) phase to trace the cortical reorganization following this incident. METHODS: Acute clinical work-up included magnetic resonance imaging and navigated transcranial magnetic stimulation (nTMS). Motor mapping was performed with 110% of the abductor pollicis brevis muscle (APB) resting motor threshold (rMT). Amplitudes and latencies of the motor-evoked potential (MEPs) were recorded and analyzed. In addition, motor function was evaluated by the Medical Research Council (MRC) scale, a standard Purdue Pegboard test and by a reaction time (RT) task. RESULTS: MRI revealed no aberrant findings. nTMS mapping, however, showed a posterior shift of the APB representation from the anatomical hand knob towards the somatosensory cortex in the acute in comparison to the pre-lesional phase. Concomitantly, there was an increase of rMT (6%). Within 10 days, there was an incomplete reversal of the posterior shift in parallel with improvement of the clinical motor function. Long-term follow-up revealed a complete restitution of nTMS cortical mapping and motor function. CONCLUSION: The present case report thoroughly documents a rapid cortical reorganization within a few days after a transient spinal shock. Our data adds further evidence to the literature suggesting a posterior shift of motor cortical representation following spinal cord injury. For the first time, 52 cortical reorganization was shown idiosyncratically in a single patient arising from the fortuitous fact of having a pre - lesional nTMS map.

Differential effects of disease modifying drugs on peripheral blood B cell subsets: A cross sectional study in multiple sclerosis patients treated with interferon-ß, glatiramer acetate, dimethyl fumarate, fingolimod or natalizumab.

BACKGROUND: Several disease modifying drugs (DMDs) have been approved for the treatment of multiple sclerosis (MS), however, little is known about their differential impact on peripheral blood (PB) B cell subsets. METHODS: We performed a cross sectional study on PB B cells in MS patients treated with interferon-ß (n = 25), glatiramer acetate (n = 19), dimethyl fumarate (n = 15), fingolimod (n = 16) or natalizumab (n = 22), untreated MS patients (n = 20), and in patients with non-inflammatory neurological diseases (n = 12). Besides analyzing routine laboratory data, flow cytometry was performed to analyze naïve B cells (CD19+CD20+CD27-IgD+), non-class switched (CD19+CD20+CD27+IgD+) and class-switched memory B cells (CD19+CD20+CD27+IgD-), double negative B cells (CD19+CD20lowCD27-IgD-) and plasmablasts (CD19+CD20lowCD27+CD38++). RESULTS: Treatment associated changes were found for the overall B cell pool as well as for all B cell subsets. Natalizumab increased absolute numbers and percentage of all B cells mainly by expanding the memory B cell pool. Fingolimod decreased absolute numbers of all B cell subsets and the percentage of total B cells. Fingolimod, dimethyl fumarate and interferon-ß treatments were associated with an increase in the fraction of naïve B cells while class switched and non-class switched memory B cells showed decreased percentages. CONCLUSION: Our results highlight differential effects of DMDs on the PB B cell compartment. Across the examined treatments, a decreased percentage of memory B cells was found in dimethyl fumarate, interferon-ß and fingolimod treated patients which might contribute to the drugs' mode of action in MS. Further studies are necessary to decipher the exact role of B cell subsets during MS pathogenesis.

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.