Modulation of Brain Activity in Healthy Subjects and Patients – Providing the Basis for Novel Concepts in Stroke Rehabilitation
How does stroke influence sensorimotor networks in the human brain? – This is the major question driving our research activities. Stroke is the leading cause of disability in the western world. In Germany, approximately 200.000 people per year suffer from a stroke, and over 50% of stroke survivors remain disabled by a permanent neurological deficit, despite pharmacological treatment and extensive physiotherapy (http://www.dgn.org). We, therefore, also focus on developing neurophysiologically based novel treatment strategies to promote recovery of function in patients.
Right figure: Changes of neural activity in stroke patients suffering from hemiparesis (fMRI, n = 2 x 12, RFX, P < 0.05 corr.).
- Disruption of structural integrity along the corticospinal tract (CST, blue) due to subcortical ischemia in a 35-year old patient suffering from hemiparesis (left: T1 weighted MRI, right: DTI).
Methods and Projects
Functional MRI (fMRI)
We use a Siemens Trio 3 Tesla machine for the acquision of structural (T1, T2, FLAIR, DWI, DTI) and functional (EPI: gradient echo, spin echo, arterial spin labeling) imaging sequences. For visual stimulus presentation, we either use high resolution video goggles or an MR compatible LCD screen. For auditory stimulation, we use high qualitiy MR headphones and MR compatible microphones.
See also: Magnetic Resonance Imaging (MRT / MRI)
Neuropharmacology
One focus of interest of the „Neuromodulation & Neurorehabilitation“ group is to conduct pharmacological studies probing the effects of adrenergic, serotonergic or dopaminergic stimulation on motor behavior in patients with an ischemic lesion. Based on the literature, candidate drugs for an effective modulation of motor performance are reboxetine (adrenergic), fluoxetine (serotonergic) and levodopa (or dopamine agonists). Patients are recruited in close cooperation with the Department of Neurology, University of Cologne, which is situated directly next to the MPI for Neurological Research.
- The behavioral effects of the interventions are assessed in a battery of motor tests addressing different aspects of motor behavior (e.g., movement kinematics, finger tapping frequency, hand grip formation during grasping, dynamic grip forces, see Nowak et al, 2007).
- The neural effects associated with the modulation of a specific neurotransmitter system are investigated with fMRI. The experimental paradigm allows analysis of both changes in the pattern of neural activity and changes in effective connectivity - which reflects the influence one area exerts over the activity of another area - in response to pharmacological stimulation. Connectivity analysis is of particular interest, as stimulating one specific neurotransmitter system may promote the interaction of areas in certain neural circuits rather than instantaneously causing reorganisation of neural representations.
- Lesions in structural integrity can be visualised by means of diffusion tensor imaging (DTI). The information on which fibre tract is affected by an ischemic lesion is of great importance to both spontaneous recovery and any sort of intervention (be it physical therapy, pharmacotherapy or magnetic stimulation).
Transcranial magnetic stimulation
Another approach to modulate cortical excitability is to combine pharmacological stimulation with electrophysiological interventions such as transcranial magnetic stimulation (TMS). The MPI for Neurological Research uses a neuronavigated Eximia TMS device which enables fMRI guided interactions with cortical excitability. Most repetitive TMS stimulation protocols have been found to change cortical excitation for between 15 up to 60 minutes (depending on the stimulation protocol). Modulating cortical activity by means of neuropharmacological drugs might mobilise inherent electrophysiological properties of the cortex and ultimately lead to increased or more robust intervention effects.
Such effects might well be beneficial in a rehabilitative setting.
Real-time-Motion-Analyzer
We use a Zebris CMS20S device for 3D real-time motion analysis. The system (Figure 1a) mainly consists of a measuring sensor (max. distance: 2.0 m) which captures the three-dimensional positions of ultrasonic pulses emitting markers (diameter: 5 mm, weight: 1 g) fixed on the body part to be examined with high spatial (0.1 mm) and temporal (100 Hz) resolution. The offline-analysis of the data allows assessing movement ranges, velocity, accelerations and other kinematic parameters (see Figure).
- Zebris-Motion-Analyzer
Research topics in detail:
Modulating neural functions in stroke patients using
pharmacological interventions
rTMS or tDCS
Lectures
PD Dr. Christian Grefkes
Jan 23, 2013 | ANIM - Mannheim
Netzwerkstörungen nach Schlaganfall - Neue Erkenntnisse durch Konnektivitätsanalysen
Mar 22, 2013 | DGKN - Leipzig
Konnektivität und Netzwerke als Basis physiologischer und pathologischer Gehirnfunktion
Mar 23, 2013 | DGKN - Leipzig
RJK-Curriculum 2: "Dynamic causal modelling (DCM) mit SPM"
Awards 2012
Selected Landmark in the competition "365 Orte im Land der Ideen"
Habilitationspreis der Medizinischen Fakultät der Universität zu Köln - C. Grefkes
Awards 2011
Förderpreis der Deutschen Gesellschaft für Neurotraumatologie und Klinische Neurorehabilitation - A. Rehme
Niels-A.-Lassen-Preis der Deutschen Gesellschaft für Klinische Neurophysiologie (DGKN) - C. Grefkes
Young-Scientist-Award des Kompetenznetz Schlaganfall - C. Grefkes
Cooperation Partners:
Department of Neurology, University of Cologne (Prof. Fink)
Department of Neuro-Surgery, University of Cologne (Dr. Weiss, Prof. Dr. Goldbrunner)
Department of Psychiatry, University of Cologne (PREVENT- study group)
Institute of Medicine and Neurosciences, Jülich Research Center (Prof. Weiß-Blankenhorn, Prof. Eickhoff)
Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London (Prof. Rothwell, Dr. Hamada, Dr. Ward, Dr. Boudrias)