Cerebellum to motor cortex paired associative stimulation induces bidirectional STDP-like plasticity in human motor cortex

The cerebellum is crucially important for motor control and adaptation. Recent non-invasive brain stimulation studies have indicated the possibility to alter the excitability of the cerebellum and its projections to the contralateral motor cortex, with behavioral consequences on motor control and adaptation. Here we sought to induce bidirectional spike-timing dependent plasticity (STDP)-like modifications of motor cortex (M1) excitability by application of paired associative stimulation (PAS) in healthy subjects. Conditioning stimulation over the right lateral cerebellum (CB) preceded focal transcranial magnetic stimulation (TMS) of the left M1 hand area at an interstimulus interval of 2 ms (CB→M1 PAS(2 ms)), 6 ms (CB→M1 PAS(6 ms)) or 10 ms (CB→M1 PAS(10 ms)) or randomly alternating intervals of 2 and 10 ms (CB→M1 PAS(Control)). Effects of PAS on M1 excitability were assessed by the motor-evoked potential (MEP) amplitude, short-interval intracortical inhibition (SICI), intracortical facilitation (ICF) and cerebellar-motor cortex inhibition (CBI) in the first dorsal interosseous muscle of the right hand. CB→M1 PAS(2 ms) resulted in MEP potentiation, CB→M1 PAS(6 ms) and CB→M1 PAS(10 ms) in MEP depression, and CB→M1 PAS(Control) in no change. The MEP changes lasted for 30-60 min after PAS. SICI and CBI decreased non-specifically after all PAS protocols, while ICF remained unaltered. The physiological mechanisms underlying these MEP changes are carefully discussed. Findings support the notion of bidirectional STDP-like plasticity in M1 mediated by associative stimulation of the cerebello-dentato-thalamo-cortical pathway and M1. Future studies may investigate the behavioral significance of this plasticity

Paraneoplastic cerebellar degeneration associated with lymphoepithelial carcinoma of the tonsil

Background: Paraneoplastic cerebellar degeneration (PCD) is a classical tumor-associated, immune-mediated disease typically associated with gynecological malignancies, small-cell lung-cancer or lymphoma. Case presentation: Here we present the case of a 38-year old male with an over 12 months rapidly progressive cerebellar syndrome. Extensive diagnostic workup revealed selective hypermetabolism of the right tonsil in whole-body PET. Histological examination after tonsillectomy demonstrated a lymphoepithelial carcinoma of the tonsil and the tongue base strongly suggesting a paraneoplastic cause of the cerebellar syndrome. To the best of our knowledge this is the first case of an association of a lymphoepithelial carcinoma, a rare pharyngeal tumor, with PCD. Conclusions: In cases of classical paraneoplastic syndromes an extensive search for neoplasms should be performed including whole-body PET to detect tumors early in the course of the disease

Plasticity Resembling Spike-Timing Dependent Synaptic Plasticity: The Evidence in Human Cortex

Spike-timing dependent plasticity (STDP) has been studied extensively in a variety of animal models during the past decade but whether it can be studied at the systems level of the human cortex has been a matter of debate. Only recently newly developed non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) have made it possible to induce and assess timing dependent plasticity in conscious human subjects. This review will present a critical synopsis of these experiments, which suggest that several of the principal characteristics and molecular mechanisms of TMS-induced plasticity correspond to those of STDP as studied at a cellular level. TMS combined with a second phasic stimulation modality can induce bidirectional long-lasting changes in the excitability of the stimulated cortex, whose polarity depends on the order of the associated stimulus-evoked events within a critical time window of tens of milliseconds. Pharmacological evidence suggests an NMDA receptor mediated form of synaptic plasticity. Studies in human motor cortex demonstrated that motor learning significantly modulates TMS-induced timing dependent plasticity, and, conversely, may be modulated bidirectionally by prior TMS-induced plasticity, providing circumstantial evidence that long-term potentiation-like mechanisms may be involved in motor learning. In summary, convergent evidence is being accumulated for the contention that it is now possible to induce STDP-like changes in the intact human central nervous system by means of TMS to study and interfere with synaptic plasticity in neural circuits in the context of behavior such as learning and memory

Monitoring cortical excitability during repetitive transcranial magnetic stimulation in children with ADHD: a single-blind, sham-controlled TMS-EEG study

Background: Repetitive transcranial magnetic stimulation (rTMS) allows non-invasive stimulation of the human brain. However, no suitable marker has yet been established to monitor the immediate rTMS effects on cortical areas in children. Objective: TMS-evoked EEG potentials (TEPs) could present a well-suited marker for real-time monitoring. Monitoring is particularly important in children where only few data about rTMS effects and safety are currently available. Methods: In a single-blind sham-controlled study, twenty-five school-aged children with ADHD received subthreshold 1 Hz-rTMS to the primary motor cortex. The TMS-evoked N100 was measured by 64-channel-EEG pre, during and post rTMS, and compared to sham stimulation as an intraindividual control condition. Results: TMS-evoked N100 amplitude decreased during 1 Hz-rTMS and, at the group level, reached a stable plateau after approximately 500 pulses. N100 amplitude to supra-threshold single pulses post rTMS confirmed the amplitude reduction in comparison to the pre-rTMS level while sham stimulation had no influence. EEG source analysis indicated that the TMS-evoked N100 change reflected rTMS effects in the stimulated motor cortex. Amplitude changes in TMS-evoked N100 and MEPs (pre versus post 1 Hz-rTMS) correlated significantly, but this correlation was also found for pre versus post sham stimulation. Conclusion: The TMS-evoked N100 represents a promising candidate marker to monitor rTMS effects on cortical excitability in children with ADHD. TMS-evoked N100 can be employed to monitor real-time effects of TMS for subthreshold intensities. Though TMS-evoked N100 was a more sensitive parameter for rTMS-specific changes than MEPs in our sample, further studies are necessary to demonstrate whether clinical rTMS effects can be predicted from rTMS-induced changes in TMS-evoked N100 amplitude and to clarify the relationship between rTMS-induced changes in TMS-evoked N100 and MEP amplitudes. The TMS-evoked N100 amplitude reduction after 1 Hz-rTMS could either reflect a globally decreased cortical response to the TMS pulse or a specific decrease in inhibition

The perfect crime? : CCSVI not leaving a trace in MS

Background: Multiple sclerosis (MS) is a chronic, inflammatory demyelinating disease of the central nervous system, believed to be triggered by an autoimmune reaction to myelin. Recently, a fundamentally different pathomechanism termed ‘chronic cerebrospinal venous insufficiency’ (CCSVI) was proposed, provoking significant attention in the media and scientific community. Methods: Twenty MS patients (mean age 42.2±13.3 years; median Extended Disability Status Scale 3.0, range 0–6.5) were compared with 20 healthy controls. Extra- and intracranial venous flow direction was assessed by colour-coded duplex sonography, and extracranial venous cross-sectional area (VCSA) of the internal jugular and vertebral veins (IJV/VV) was measured in B-mode to assess the five previously proposed CCSVI criteria. IJV-VCSA≤0.3 cm2 indicated ‘stenosis,’ and IJV-VCSA decrease from supine to upright position ‘reverted postural control.’ The sonographer, data analyser and statistician were blinded to the patient/control status of the participants. Results: No participant showed retrograde flow of cervical or intracranial veins. IJV-VCSA≤0.3 cm2 was found in 13 MS patients versus 16 controls (p=0.48). A decrease in IJV-VCSA from supine to upright position was observed in all participants, but this denotes a physiological finding. No MS patient and one control had undetectable IJV flow despite deep inspiration (p=0.49). Only one healthy control and no MS patients fulfilled at least two criteria for CCSVI. Conclusions: This triple-blinded extra- and transcranial duplex sonographic assessment of cervical and cerebral veins does not provide supportive evidence for the presence of CCSVI in MS patients. The findings cast serious doubt on the concept of CCSVI in MS

Short-interval intracortical inhibition and facilitation targeting upper and lower limb muscles

Abstract Transcranial magnetic stimulation (TMS) can be used to study excitability of corticospinal neurons in human motor cortex. It is currently not fully elucidated if corticospinal neurons in the hand vs. leg representation show the same or different regulation of their excitability by GABAAergic and glutamatergic interneuronal circuitry. Using a paired-pulse TMS protocol we tested short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF) in 18 healthy participants. Motor evoked potentials were evoked in one hand (abductor digiti minimi) and one leg muscle (tibialis anterior), with systematic variation of the intensities of the first (S1) and second (S2) pulse between 60 and 140% resting motor threshold (RMT) in 10% steps, at two interstimulus intervals of 1.5 and 2.1 ms. For the hand and leg motor representations and for both interstimulus intervals, SICI occurred if the intensities of S1  RMT, while SICF predominated if S1 = S2 ≤ RMT, or S1 > RMT and S2 < RMT. Findings confirm and extend previous evidence that the regulation of excitability of corticospinal neurons of the hand versus leg representation in human primary cortex through GABAAergic and glutamatergic interneuronal circuits is highly similar, and that corticospinal neurons of both representations are activated by TMS transsynaptically in largely identical ways

Event-related desynchronization during movement attempt and execution in severely paralyzed stroke patients: An artifact removal relevance analysis

The electroencephalogram (EEG) constitutes a relevant tool to study neural dynamics and to develop brain-machine interfaces (BMI) for rehabilitation of patients with paralysis due to stroke. However, the EEG is easily contaminated by artifacts of physiological origin, which can pollute the measured cortical activity and bias the interpretations of such data. This is especially relevant when recording EEG of stroke patients while they try to move their paretic limbs, since they generate more artifacts due to compensatory activity. In this paper, we study how physiological artifacts (i.e., eye movements, motion artifacts, muscle artifacts and compensatory movements with the other limb) can affect EEG activity of stroke patients. Data from 31 severely paralyzed stroke patients performing/attempting grasping movements with their healthy/paralyzed hand were analyzed offline. We estimated the cortical activation as the event-related desynchronization (ERD) of sensorimotor rhythms and used it to detect the movements with a pseudo-online simulated BMI. Automated state-of-the-art methods (linear regression to remove ocular contaminations and statistical thresholding to reject the other types of artifacts) were used to minimize the influence of artifacts. The effect of artifact reduction was quantified in terms of ERD and BMI performance. The results reveal a significant contamination affecting the EEG, being involuntary muscle activity the main source of artifacts. Artifact reduction helped extracting the oscillatory signatures of motor tasks, isolating relevant information from noise and revealing a more prominent ERD activity. Lower BMI performances were obtained when artifacts were eliminated from the training datasets. This suggests that artifacts produce an optimistic bias that improves theoretical accuracy but may result in a poor link between task-related oscillatory activity and BMI peripheral feedback. With a clinically relevant dataset of stroke patients, we evidence the need of appropriate methodologies to remove artifacts from EEG datasets to obtain accurate estimations of the motor brain activity.This study was funded by the fortüne-Program of the University of Tübingen (2422-0-1 and 2452-0-0), the Bundesministerium für Bildung und Forschung BMBF MOTORBIC (FKZ 13GW0053) and AMORSA (FKZ 16SV7754), the Deutsche Forschungsgemeinschaft (DFG), the Basque Government Science Program (EXOTEK: KK 2016/00083). The work of A. Insausti-Delgado was supported by the Basque Government's scholarship for predoctoral students

Magnetic switching of nanoscale antidot lattices

We investigate the rich magnetic switching properties of nanoscale antidot lattices in the 200 nm regime. In-plane magnetized Fe, Co, and Permalloy (Py) as well as out-of-plane magnetized GdFe antidot films are prepared by a modified nanosphere lithography allowing for non-close packed voids in a magnetic film. We present a magnetometry protocol based on magneto-optical Kerr microscopy elucidating the switching modes using first-order reversal curves. The combination of various magnetometry and magnetic microscopy techniques as well as micromagnetic simulations delivers a thorough understanding of the switching modes. While part of the investigations has been published before, we summarize these results and add significant new insights in the magnetism of exchange-coupled antidot lattices.Web of Science775073

Central nervous system physiology

This is the second chapter of the series on the use of clinical neurophysiology for the study of movement disorders. It focusses on methods that can be used to probe neural circuits in brain and spinal cord. These include use of spinal and supraspinal reflexes to probe the integrity of transmission in specific pathways; transcranial methods of brain stimulation such as transcranial magnetic stimulation and transcranial direct current stimulation, which activate or modulate (respectively) the activity of populations of central neurones; EEG methods, both in conjunction with brain stimulation or with behavioural measures that record the activity of populations of central neurones; and pure behavioural measures that allow us to build conceptual models of motor control. The methods are discussed mainly in relation to work on healthy individuals. Later chapters will focus specifically on changes caused by pathology

Исследование эколого-технологической эффективности водопользования Томского подземного водозабора

Объектом исследования являются железосодержащие осадки, образующиеся на станции обезжелезивания Томского подземного водозабора. Цель работы – изучение технологии образования железосодержащих осадков при водоподготовке, исследование вещественного состава осадков и рациональных путей их утилизации. В процессе исследования был проведен отбор проб железосодержащих осадков и исследования их вещественного состава в аккредитованных лабораториях ТПУ. В результате исследования выявлен морфологический и вещественный состав новообразований Томского подземного водозабора, а также разработаны рекомендации по их утилизации с учетом технико-экономических особенностей промышленности. Область применения – наиболее рациональные пути использования отходов станции обезжелезивания - использование осадка на химические реактивы – хлорид железа; для стекольной промышленности осадок сульфатов щелочно – земельных металлов; получение неорганических пигментов, в том числе и магнитных; получение строительных материалов, в частности окрашенного отделочного раствора и бетона.Das Untersuchungsobjekt sind eisenhaltige Ablagerungen, die sich in der Wasserenteisenungsanlage der Tomsker Grundwasserfassung bilden. Das Ziel der Studie besteht in der Untersuchung der Herausbildungstechnologie der eisenhaltigen Ablagerungen bei der Wasseraufbereitung, Untersuchung der stofflichen Zusammensetzung der Ablagerungen und Suche nach rationellen Verfahren für deren Verwertung. Im Zuge der Untersuchung wurden Probeentnahme der eisenhaltigen Ablagerungen und deren Untersuchung in den akkreditierten Laboratorien der Tomsker Polytechnischen Universität durchgeführt. Im Ergebnis der Untersuchung wurden stoffliche Zusammensetzung und morphologische Struktur der Neubildungen an der Tomsker Grundwasserfassung offengelegt und die Empfehlungen zu deren Verwertung unter der Berücksichtigung der wirtschaftstechnischen Spezifik der Industrie ausgearbeitet. Anwendungsbereich: effizienteste Verfahren zur Verwertung der Abfälle von der Wasserenteisenungsanlage – Verwendung der Ablagerungen für Chemikalien – Eisenchlorid; Verwendung der abgelagerten Sulfate der Erdalkalimetalle für Glasindustrie; Herstellung der nichtorganischen, inkl. magnetischen Farbpigmente; Verwendung für die Produktion der Baustoffe, insbesondere für die Produktion der gefärbten Nachbehandlungsflüssigkeit und des Betons