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Brain Networks and Plasticity

The human brain possesses the remarkable capacity of reorganization, which is the basis for adapting to constantly changing environmental conditions. This plasticity is of paramount importance for brain recovery processes, e.g. after sustaining damage from stroke.

The priority interest of our research group are the basic processes underlying cortical plasticity at the neuronal level. Our aim is to understand the mechanisms of plasticity governing learning in the healthy brain and re-acquiring lost abilities in the brain damaged by stroke.

How do cortical networks change in response to brain damage in order to compensate functional deficits? Can an incremental understanding of these interrelations help predict the success of neurorehabilitation at the individual patient level and/or help improve the rehabilitation process through a specifically targeted intervention? We are addressing these questions by means of modern methods of brain imaging (functional MRT, diffusion-tensor-imaging), electrophysiological methods (EMG, EEG, MEG) in combination with non-invasive brain stimulation (transcranial magnetic stimulation, transcranial DC-stimulation) and neuropharmacology. It is our aim to develop innovative and effective strategies of neurorehabilitation translating into major progress in rehabilitation therapy of patients suffering from neurovascular disease.

Research Projects
Colaborators
Partners and Cooperation
Publications

 

PHARMACOLOGICAL MODULATION OF TMS-EVOKED EEG RESPONSES

The ability to investigate brain function in healthy subjects as well as in patient groups with specific brain damage can be significantly improved by combining transcranial magnetic stimulation (TMS) with other electrophysiological and imaging methods, or by combining TMS with pharmacological interventions. Especially the technical ability of concurrently recording neuronal activity through EEG, which enables us to examine the direct effects of TMS on brain networks with sufficient spatial and excellent temporal resolution. TMS-evoked potentials (TEP) following a single TMS pulse of the primary motor cortex can be recorded both at the locus of stimulation and in more distant cortical regions in the period of up to 300ms following the stimulus. The underlying physiological mechanisms of TEP are not yet well understood. In this project, the physiological mechanisms of TMS-evoked EEG-recordings via pharmacological modulation of GABA-ergic neurotransmission is characterized more closely.

 

MODULATION OF THE CORTICAL MOTOR NEURONAL NETWORK THROUGH MULTI-COIL-TMS

Coordinated neuronal activity in large distributed brain networks is the basis for higher cognitive functions and complex sensorimotor abilities.

Within the motor functional system, numerous areas of the brain, such as the dorsal pre-motor cortex, the ventral pre-motor cortex, the supplementary motor area, the parietal cortex, the basal ganglia and the cerebellum constitute , together with the primary motor cortex; constitute the motor network.

Neuronal coordination is highly dynamic and depends both on the motor task and on the condition of the brain. The effective connectivity in the brain's motor network after brain damage (e.g. following a stroke) is significantly altered. Therapeutic success in regaining motor abilities depends decisively on the correlation of changes in the neuronal network architecture with changes in motor abilities.  In this project we use multi-coil-TMS in order to strategically modify effective connectivity in the cortical motor network and in order to study the effects on motor abilities and learning.

REORGANISATION OF CEREBRAL NETWORKS IN MULTIPLE SCLEROSIS

In multiple sclerosis (MS), multiple inflammatory CNS-lesions potentially interrupting cerebral networks to a significant degree. In contrast to an acute lesion of the brain as caused by a stroke, these lesions develop over time, allowing the brain more time to reorganize itself and to compensate for losses of ability.

Nevertheless, already at an early stage of the disease, cognitive functions such as attention and memory are frequently impaired.

Within the scope of this project, changes in the cortical networks of MS-patients are visualized with the help of fMRT and MEG and their influence on cognitive functions is studied.

These investigations may yield a neuro-biological characterisation of the immunomodulatory effects of drugs and the identification of biomarkers for monitoring the success of therapeutic interventions.

CLOSED-LOOP-STIMULATION

We are studying the relationship between the instantaneous state of cognitive processes and cortical information processing. A simultaneous EEG-TMS setup with real-time signal analysis allows EEG-controlled stimulus-pulses with deterministic  latencies of less than 3 ms.

Our initial experiments examine the influence of the oscillatory phase of cortical EEG-alpha activity during the TMS-pulse on cortico-spinal excitability and plasticity. Within the scope of a translational research project we are developing, based on this approach, new and therapeutically more effective, EEG-dependent TMS protocols for neuro-rehabilitation.

 

 


 
Name
Department
Phone
Email
Dr. Paolo Belardinelli
Dr. Paolo Belardinelli Postdoc
Neuroplasticity
 
 Til Ole Bergmann
Til Ole Bergmann
Neuroplasticity
 
 Ghazal Darmani
Ghazal Darmani
Neuroplasticity
 
 Debora Desideri
Debora Desideri
Neuroplasticity
 
 Mohamed Yasser Elnaggar
Mohamed Yasser Elnaggar
Neuroplasticity
 
 Hanna Faber
Hanna Faber
Neuroplasticity
 
 Yeho Kim
Yeho Kim Doktorand
Neuroplasticity
 
 Hannah Kraemer
Hannah Kraemer
Neuroplasticity
 
 Franca-Sophie König
Franca-Sophie König
Neuroplasticity
 
 Semjon Levertov
Semjon Levertov
Neuroplasticity
 
 Chen Liang
Chen Liang
Neuroplasticity
 
 Isabella Premoli
Isabella Premoli
Neuroplasticity
 
 Jakob Spogis
Jakob Spogis
Neuroplasticity
 
 Johannes Tünnerhoff
Johannes Tünnerhoff
Neuroplasticity
01732790781 
Prof. Dr. Ulf Ziemann
Prof. Dr. Ulf Ziemann Head of Department
Neuroplasticity
07071 29-82049 
 Carl Zipser
Carl Zipser
Neuroplasticity
 
 Christoph Zrenner
Christoph Zrenner
Neuroplasticity
 

Selected Original Papers (since 2008)


2015

Murakami T, Kell CA, Restle J, Ugawa Y, Ziemann U. Left dorsal speech stream components and their contribution to phonological processing. J Neurosci 35:1411-1422

Fuhl A, Müller-Dahlhaus F, Lücke C, Tönnies SW, Ziemann U. Low doses of ethanol enhance LTD-like plasticity in human motor cortex. Neuropsychopharmacology, doi: 10.1038/npp.2015.151

Ziemann U, Siebner H. Inter-Subject and Inter-Session Variability of Plasticity Induction by Non-Invasive Brain Stimulation: Boon or Bane? Brain Stimulation 8: 662-663

 

 

2014

Ziemann U, Reis J, Schwenkreis P, Rosanova M, Strafella A, Badawy R, Muller-Dahlhaus FTMS and drugs revisited 2014
Clin Neurophysiol (doi: 10.1016/j.clinph.2014.08.028)

Di Pino G, Pellegrino G, Assenza G, Capone F, Ferreri F, Formica D, Ranieri F, Tombini M, Ziemann U, Rothwell JC, Di Lazzaro V
Modulation of brain plasticity in stroke: a novel model for neurorehabilitation
Nature reviews Neurology 10:597-608

Müller-Dahlhaus F, Ziemann U
Metaplasticity in Human Cortex
The Neuroscientist (doi: 10.1177/1073858414526645)

Goldsworthy MR, Müller-Dahlhaus F, Ridding MC, Ziemann U
Inter-subject Variability of LTD-like Plasticity in Human Motor Cortex: A Matter of Preceding Motor Activation
Brain Stimulation 7:864-870

Hamada M, Galea JM, Di Lazzaro V, Mazzone P, Ziemann U, Rothwell JC
Two distinct interneuron circuits in human motor cortex are linked to different subsets of physiological and behavioral plasticity
J Neurosci 34:12837-12849

Cash RF, Murakami T, Chen R, Thickbroom GW, Ziemann U
Augmenting Plasticity Induction in Human Motor Cortex by Disinhibition Stimulation
Cereb Cortex (doi: 10.1093/cercor/bhu176)

Lenz M, Platschek S, Priesemann V, Becker D, Willems LM, Ziemann U, Deller T, Muller-Dahlhaus F, Jedlicka P, Vlachos A
Repetitive magnetic stimulation induces plasticity of excitatory postsynapses on proximal dendrites of cultured mouse CA1 pyramidal neurons
Brain Structure & Function (10.1007/s00429-014-0859-9)

Premoli I, Rivolta D, Espenhahn S, Castellanos N, Belardinelli P, Ziemann U, Müller-Dahlhaus F Characterization of GABAB-receptor mediated neurotransmission in the human cortex by paired-pulse TMS-EEG
NeuroImage 103C:152-162.

Premoli I, Castellanos N, Rivolta D, Belardinelli P, Bajo R, Zipser C, Espenhahn S, Heidegger T, Müller-Dahlhaus F, Ziemann U
TMS-EEG signatures of GABAergic neurotransmission in the human cortex
J Neurosci 34:5603–5612

Gharabaghi A, Kraus D, Leao MT, Spüler M, Walter A, Bogdan M, Rosenstiel W, Naros G, Ziemann U
Coupling brain-machine interfaces with cortical stimulation for brain-state dependent stimulation: enhancing motor cortex excitability for neurorehabilitation
Front Hum Neurosci (8:122)

Lücke C, Heidegger T, Röhner M, Toennes SW, Krivanekova L, Müller-Dahlhaus F, Ziemann U
Deleterious effects of a low amount of ethanol on LTP-like plasticity in human cortex
Neuropsychopharmacol 39:1508-1518

Goldsworthy M, Müller-Dahlhaus F, Ridding M, Ziemann U
Resistant against de-depression: LTD-like plasticity in the human motor cortex induced by spaced cTBS
Cereb Cortex (doi:10.1093/cercor/bht353)

Grimaldi G, Argyropoulos GP, Boehringer A, Celnik P, Edwards MJ, Ferrucci R, Galea JM, Groiss SJ, Hiraoka K, Kassavetis P, Lesage E, Manto M, Miall RC, Priori A, Sadnicka A, Ugawa Y, Ziemann U
Non-invasive Cerebellar Stimulation - a Consensus Paper
Cerebellum 13(1):121-38

Rusu CV, Murakami M, Ziemann U, Triesch J
A model of TMS-induced I-waves in Motor Cortex
Brain Stim 7:401-414

 

 

2013

Kriváneková L, Baudrexel S, Bliem B, Ziemann U
Relation of brain stimulation induced changes in MEP amplitude and BOLD signal

Brain Stimul 6:330-9

Di Lazzaro V, Ziemann U
The contribution of transcranial magnetic stimulation in the functional evaluation of microcircuits in human motor cortex

Front Neural Circuits 7:18

Delvendahl I, Lindemann H, Heidegger T, Normann C, Ziemann U, Mall V
Effects of lamotrigine on human motor cortex plasticity

Clin Neurophysiol 124:148-53

 

 

2012

Vlachos A, Müller-Dahlhaus F, Rosskopp J, Lenz M, Ziemann U, Deller T

Repetitive magnetic stimulation induces functional and structural plasticity of excitatory postsynapses in mouse organotypic hippocampal slice cultures

J Neurosci 32:17514-23

Helfrich C, Pierau SS, Freitag CM, Roeper J, Ziemann U, Bender SMonitoring cortical excitability during repetitive transcranial magnetic stimulation in children with ADHD: a single-blind, sham-controlled TMS-EEG study
PLoS One 7:e50073

Lu MK, Tsai CH, Ziemann U
Cerebellum to motor cortex paired associative stimulation induces bidirectional STDP-like plasticity in human motor cortex
Front Hum Neurosci 6:260

Murakami T, Müller-Dahlhaus F, Lu MK, Ziemann U
Homeostatic metaplasticity of corticospinal excitatory and intracortical inhibitory neural circuits in human motor cortex

J Physiol 590:5765-81

Restle J, Murakami T, Ziemann U
Facilitation of speech repetition accuracy by theta burst stimulation of the left posterior inferior frontal gyrus

Neuropsychologia 50:2026-31

Jung P, Klein JC, Wibral M, Hoechstetter K, Bliem B, Lu MK, Wahl M, Ziemann U
Spatiotemporal dynamics of bimanual integration in human somatosensory cortex and their relevance to bimanual object manipulation

J Neurosci 32:5667-77

Voytovych H, Kriváneková L, Ziemann U
Lithium: a switch from LTD- to LTP-like plasticity in human cortex.

Neuropharmacology 63:274-9

Hübers A, Klein JC, Kang JS, Hilker R, Ziemann U
The relationship between TMS measures of functional properties and DTI measures of microstructure of the corticospinal tract

Brain Stimul 5:297-304

Murakami T, Restle J, Ziemann U
Effective connectivity hierarchically links temporoparietal and frontal areas of the auditory dorsal stream with the motor cortex lip area during speech perception.

Brain Lang 122:135-41

Volz S, Nöth U, Jurcoane A, Ziemann U, Hattingen E, Deichmann R
Quantitative proton density mapping: correcting the receiver sensitivity bias via pseudo proton densities

Neuroimage 63:540-52

 

 

2011

Arai N, Müller-Dahlhaus F, Murakami T, Bliem B, Lu MK, Ugawa Y, Ziemann U
State-dependent and timing-dependent bidirectional associative plasticity in the human SMA-M1 network
J Neurosci 31:15376-83

Kriváneková L, Lu MK, Bliem B, Ziemann U
Modulation of excitability in human primary somatosensory and motor cortex by paired associative stimulation targeting the primary somatosensory cortex.

Eur J Neurosci 34:1292-300

Hattingen E, Magerkurth J, Pilatus U, Hübers A, Wahl M, Ziemann U
Combined (1)H and (31)P spectroscopy provides new insights into the pathobiochemistry of brain damage in multiple sclerosis
NMR Biomed 24:536-46

Korchounov A, Ziemann U
Neuromodulatory neurotransmitters influence LTP-like plasticity in human cortex: a pharmaco-TMS study
Neuropsychopharmacology 36:1894-902

Wahl M, Hübers A, Lauterbach-Soon B, Hattingen E, Jung P, Cohen LG, Ziemann U
Motor callosal disconnection in early relapsing-remitting multiple sclerosis

Hum Brain Mapp 32:846-55

Murakami T, Restle J, Ziemann U
Observation-execution matching and action inhibition in human primary motor cortex during viewing of speech-related lip movements or listening to speech

Neuropsychologia 49:2045-54

Lu MK, Arai N, Tsai CH, Ziemann U
Movement related cortical potentials of cued versus self-initiated movements: double dissociated modulation by dorsal premotor cortex versus supplementary motor area rTMS

Hum Brain Mapp 33:824-39

Kang JS, Terranova C, Hilker R, Quartarone A, Ziemann U
Deficient homeostatic regulation of practice-dependent plasticity in writer's cramp

Cereb Cortex 21:1203-12

 

 

2010 

Heidegger T, Krakow K, Ziemann U
Effects of antiepileptic drugs on associative LTP-like plasticity in human motor cortex

Eur J Neurosci 32:1215-22

Szelényi A, Hattingen E, Weidauer S, Seifert V, Ziemann U
Intraoperative motor evoked potential alteration in intracranial tumor surgery and its relation to signal alteration in postoperative magnetic resonance imaging

Neurosurgery 67:302-13

Wagner M, du Mesnil de Rochemont R, Ziemann U, Hattingen E
Localization of thoracic CSF leaks by gadolinium-enhanced MR-myelography and successful MR-targeted epidural blood patching: a case report

J Neurol 257:1398-9

Lu MK, Jung P, Bliem B, Shih HT, Hseu YT, Yang YW, Ziemann U, Tsai CH
The Bereitschaftspotential in essential tremor
Clin Neurophysiol 121:622-30

 

 

2009

Alle H, Heidegger T, Kriváneková L, Ziemann U
Interactions between short-interval intracortical inhibition and short-latency afferent inhibition in human motor cortex

J Physiol 587:5163-76
Jung P, Ziemann U

Homeostatic and nonhomeostatic modulation of learning in human motor cortex

J Neurosci 29:5597-604

Lu MK, Bliem B, Jung P, Arai N, Tsai CH, Ziemann U
Modulation of preparatory volitional motor cortical activity by paired associative transcranial magnetic stimulation
Hum Brain Mapp 30:3645-56

Möller C, Arai N, Lücke J, Ziemann U
Hysteresis effects on the input-output curve of motor evoked potentials

Clin Neurophysiol 120:1003-8

 

 

2008

Peurala SH, Müller-Dahlhaus JFM, Arai N, Ziemann U
Interference of short-interval intracortical inhibition (SICI) and short-interval intracortical facilitation (SICF)
Clin Neurophysiol 119:2291-7

Hübers A, Orekhov Y, Ziemann U
Interhemispheric motor inhibition: its role in controlling electromyographic mirror activity
Eur J Neurosci 28:364-71

Müller-Dahlhaus JFM, Liu Y, Ziemann U
Inhibitory circuits and the nature of their interactions in the human motor cortex: a pharmacological TMS study

J Physiol 586:495-514

Müller-Dahlhaus JFM, Orekhov Y, Liu Y, Ziemann U
Interindividual variability and age-dependency of motor cortical plasticity induced by paired associative stimulation

Exp Brain Res 187:467-75

Bliem B, Müller-Dahlhaus JFM, Dinse HR, Ziemann U
Homeostatic metaplasticity in human somatosensory cortex

J Cogn Neurosci 20:1517-28

----------------------

Selected Review Papers (since 2008)

 

2014

Müller-Dahlhaus F, Ziemann U. Metaplasticity in human cortexNeuroscientist (doi: 10.1177/1073858414526645)

 

 

2013

Müller-Dahlhaus F, Vlachos A
Unraveling the cellular and molecular mechanisms of repetitive magnetic stimulation
Front Mol Neurosci 6: 50

 

 

2012

Nitsche MA, Müller-Dahlhaus F, Paulus W, Ziemann UThe pharmacology of neuroplasticity induced by non-invasive brain stimulation: building models for the clinical use of CNS active drugsJ Physiol 590:4641-62

 

 

2011

Ni Z, Müller-Dahlhaus F, Chen R, Ziemann U
Triple-pulse TMS to study interactions between neural circuits in human cortex
Brain Stim 4:281-93

Ziemann U, Wahl M, Hattingen E, Tumani H
Development of biomarkers for multiple sclerosis as a neurodegenerative disorder
Prog Neurobiol 95:670-85

Ziemann U
Transcranial magnetic stimulation at the interface with other techniques: a powerful tool for studying the human cortex
Neuroscientist 17:368-81

 

 

2010

Müller-Dahlhaus F, Ziemann U, Classen J
Plasticity resembling spike-timing dependent synaptic plasticity: the evidence in human cortex
Front Syn Neurosci 2:34

 

 

2008

Di Lazzaro V, Ziemann U, Lemon RN
State of the art: Physiology of transcranial motor cortex stimulation
Brain Stimul 1:345-62

Paulus W, Classen J, Cohen LG, Large CH, Di Lazzaro V, Nitsche M, Pascual-Leone A, Rosenow F, Rothwell JC, Ziemann U
State of the art: Pharmacologic effects on cortical excitability measures tested by transcranial magnetic stimulation
Brain Stimul 1:151-63

Director
Prof. Ulf Ziemann ulf.ziemannmed.uni-tuebingen.de Address

Center of Neurology
Hertie Institute for Clinical Brain Research
Department Neurology and Stroke

Hoppe-Seyler-Straße 3
72076 Tübingen

Office

Christine Riegraf
Phone: +49 (0)7071 29-82049
Fax: +49 (0)7071 29-5260
christine.riegrafmed.uni-tuebingen.de