Cognition, Aging and Neurorehabilitation

Our group is interested in healthy aging, age-related cognitive impairment, and neurorehabilitation after brain lesions like stroke.
We conduct studies in the healthy elderly population, in patients with mild cognitive impairment, and patients with chronic stroke-related motor and language deficits. Here, we examine the neural correlates of learning processes using structural and functional MRI, and transcranial magnetic stimulation. On the basis of these findings, we develop interventional approaches to further enhance learning processes. Interventional strategies include pharmacological substances, non-invasive brain stimulation, physical activity, and dietary modulations. We also examine the interaction of lifestyle factors with genetic background (gene-environment interactions).
The work is funded by the Charité, the DFG, the BMBF, and the IZKF Münster.

Currently running projects

Project 1 and 2: Impact of lifestyle factors on the brain

Experimental animal and epidemiological human studies suggest that a healthy lifestyle may reduce the risk of developing age-related diseases, such as diabetes, stroke and dementia. Besides smoking habits, alcohol consumption, weight and social interaction, a special focus lies on physical activity and dietary habits. It is however still relatively unclear, how these factors directly affect human cognition. Likewise, little is know about underlying mechanisms.

The research group investigates the effects of exercise and a healthy diet (e.g., caloric restriction, omega-3 fatty acids) on the aging brain. Various interventional studies enrol healthy elderly subjects (project 1), but also patients with mild cognitive impairment (MCI) (project 2). Methods include neuropsychological tasks, blood analyses of peripheral biomarkers, as well as structural and functional magnetic resonance imaging (MRI).

Cooperations have been established with the Institute for Sports Science/Sports Medicine of the Humboldt University Berlin (Prof. Dr. R. Wolff), with the Institute of Food Business and Dietetics of the Hannover University (Prof. Dr. A. Hahn) and with the Clinical Department of Psychiatry and Psychotherapy/Gerontopsychiatry of the Frankfurt am Main University (Prof. Dr. J. Pantel). Within the Charité we collaborate for example with the Neuroradiology of the Campus Benjamin Franklin (PD Dr. J. Fiebach) and with Prof. A. Villringer, MPI Leipzig.

Project 3

Noninvasive brain stimulation (transcranial direct current stimulation) and intensive physiotherapy in the rehabilitation of chronic motor deficits after stroke

Cooperations: Dr. F. Hummel and Prof. C. Gerloff, Universiätsklinikum Hamburg Eppendorf, Prof. Dr. A. Luft, Universitätsspital Zürich; Dr. Heidi Johansen-Berg, Functional Magnetic Resonance Imaging of the Brain Center, Oxford, UK; Dr. Leonardo Cohen, National Institute of Neurological Disorders and Stroke, USA; Dr. M. Nitsche, Neurologie Universität Göttingen

Project 4

Noninvasive brain stimulation (transcranial direct current stimulation) and intensive language training in the rehabilitation of chronic aphasia after stroke

Cooperations: PD Dr. C. Breitenstein, Neurologie der Universität Münster; Dr. M. Nitsche, Neurologie Universität Göttingen;

Project 5

Can wie enhance naming in chronic aphasia by pre-activation of the motor system?

Cooperations: Dr. M. Meinzer, University of Gainsville, Florida, USA.

Project 6

Is learning ability on both the behavioral and the neurophysiological level dependent on common polymorphisms in learning-relevant genes?

Cooperations: Dr. H. Wersching, Epidemiologie Universität Münster

Project 7

Ecogenetic context: Effect of genetic predisposition and environmental factors on memory function in the elderly
Gene-environment interactions (ecogenetic context) are of major importance for memory functions in humans. This project will elucidate the significance of common polymorphisms in learning-relevant genes for cognitive functions and for the response to memory-enhancing therapies in the elderly (pharmacological, aerobic fitness, and dietary interventions). In a second step, we will examine the impact of the pharmacological intervention on memory function and brain activity (fMRI) – depending on the interindividual genetic status (pharmogenetics). The project will contribute to the understanding of complex interactions between genetic profile and environmental factors. Furthermore, it will help to develop therapeutic strategies for memory improvement, tailored to each individual’s genetic profile.

Cooperations: Dr. H. Wersching, Epidemiologie Universität Münster; Prof. S. Knecht, Klinik Hamburg-Eilbek

Job vacancies

2 Scientific assistants/Postdocs
2 PhD students
2 MD students
3 Student assistants for subject recruitment and neuropsychological test sessions

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Publications from previous 5 years

Original publications

Flöel A, Ruscheweyh R, Krüger K, et al.

Physical activity and memory functions: Are neurotrophins and cerebral grey matter volume the missing link? Neuroimage 2009b, Nov 5 [Epub ahead of print]

Flöel A, Warnecke T, Duning T, Lating Y, Uhlenbrock J, Vogt G, Wersching H, Schneider A, Knecht S, Schäbitz WR.

Granulocyte-colony stimulating factor (G-CSF) in elderly stroke patients with concomitant vascular disease. (submitted for publication)

de Vries MH, Barth B, Maiworm S, Knecht S, Zwitserlood P, Flöel A.

Electrical stimulation of Broca’s area enhances implicit learning of an artificial grammar. J Cogn Neurosci in press.

Flöel A, de Vries MH, Scholz J, Breitenstein C, Johansen-Berg H.

White matter integrity in the vicinity of Broca's area predicts grammar learning success. Neuroimage 2009a, 47:1974-81.

Ruscheweyh R, Willemer C, Krüger K, Duning T, Warnecke T, Völker K, Mooren F, Knecht S, Flöel A.

Physical activity and memory functions: An interventional study. Neurobiol Aging 2009, Aug 27.

Witte AV, Fobker M, Gellner R, Knecht S, Flöel A.

Caloric restriction improves memory in elderly humans. Proc Natl Acad Sci U S A 2009, 106: 1255-60.

Flöel A, Rösser N, Michka O, et al.

Non-invasive brain stimulation improves language learning. J Cogn Neurosci 2008, 20: 1415-22.

Flöel A, Garraux G, Ben X, et al.

Levodopa increases memory encoding and dopamine release in the striatum in the elderly Neurobiol Aging 2008 29:267-79.

Flöel A, Vomhof P, Lorenzen A, et al.

Levodopa improves skilled hand functions in the elderly. Eur J Neurosci 2008, 27:1301-7.

Rösser N, Berger K, Vomhof P, Knecht S, Breitenstein C, Flöel A.

Lack of improvement in odor identification by levodopa in humans. Physiol Behav 2008, 93:1024-1029.

Liuzzi G, Ellger T, Flöel A, Breitenstein C, Jansen A, Knecht S.

Walking the Talk: speech activates the leg motor cortex. Neuropsychologia. 2008; 46:2824-30.

Flöel A, Hummel F, Duque J, et al.

Influence of somatosensory input on interhemispheric interactions in patients with chronic stroke. Neurorehab Neural Repair 2008, 22: 477-85.

Rösser N, Heuschmann P, Wersching H, Breitenstein C, Knecht S, Flöel A.

Levodopa improves procedural motor learning in chronic stroke. Arch Phys Med Rehab 2008, 89: 1633-41.

Flöel A, Witte V, Lohmann H, et al,

Lifestyle and memory in the elderly. Neuroepidemiology 2008, 31:39-4.

Hummel F, Voller B, Celnik P, Flöel A, Giraux P, Gerloff C, Cohen LG.

Effects of brain polarization on reaction times and pinch force in chronic stroke.
BMC Neurosci. 2006;7:73.

Voller B, Flöel A, Werhahn K, Ravindran S, Wu WH, Cohen LG.

Improvement in tactile spatial acuity in the affected hand after anaethesia of the intact hand in stroke patients. Ann Neurol 2006, 59:385-388.

Winter B, Breitenstein C, Mooren F, Völker K, Fobker M, Lechtermann A, Krüger K, Fromme A, Korsukewitz C, Flöel A, Knecht S.

Faster running - faster and better learning: A single bout of intense exercise improves word learning. Neurobiol Learn Mem 2006, Dec 19 [Epub ahead of print]

Breitenstein C, Korsukewitz C, Flöel A, Kretzschmar T, Diederich K, Knecht S.

Tonic dopaminergic stimulation impairs associative learning in healthy subjects. Neuropsychopharmacology. 2006;31:2552-64.

Breitenstein C, Flöel A, Korsukewitz C, Wailke S, Bushuven S, Knecht S.

A shift of paradigm: from noradrenergic to dopaminergic modulation of learning? J Neurol Sci 2006, 248:42-7.

Flöel A, Jansen A, Van Randenborgh J, et al.

Crossed cerebro-cerebellar language dominance. Hum Brain Mapp 2005, 24:165-72.

Flöel A, Jansen A, Deppe M, et al.

Atypical Hemispheric Dominance for Attention - Functional MRI Topography -J Cereb Blood Flow Metab 2005, 25:1197-1208.

Flöel A, Breitenstein C, Hummel F, et al,

Dopaminergic influences on formation of a motor memory. Ann Neurol 2005, 58:121-30.

Flöel A, Hummel F, Breitenstein C, et al.

Dopaminergic effects on encoding of a motor memory in chronic stroke. Neurology 2005, 65:472-474.

Jansen A, Floel A, Menke R, Kanowski M, Knecht S.

Dominance for language and spatial processing: limited capacity of a single hemisphere. Neuroreport. 2005; 16:1017-1022.

Hummel, F, Celnik P, Giraux P, Flöel A, Wu CHW, Gerloff C, Cohen LG.

Improvement of skilled motor function in elderly healthy volunteers by cortical stimulation. Brain, 2005, 128(3):490-9.

Flöel A, Jansen A, Frank A, et al.

Determining the Hemispheric Lateralization of Spatial attention - A Comparison Between fMRI and fTCD. Hum Brain Map 2004, 23:168-180.

Flöel A, Amedi A, Zohay E, et al.

‘virtual lesion’ in the primary visual cortex interferes with verb generation in blind subjects. Nat Neurosci 2004, 7:1266-70. 5

Flöel A, Jansen A, Frank A, et al.

Determining the Hemispheric Lateralization of Spatial attention - A Comparison Between fMRI and fTCD. Hum Brain Map 2004, 23:168-180.

Flöel A, Poeppel D, Buffalo EA, et al.

Frontal cortex asymmetry for memory encoding of words and abstract shapes. Cereb Cortex 2004, 14: 404-409.

Flöel A, Nagorsen U, Werhahn K, et al.

Deafferentation of the intact hand: A strategy for improvement of motor function in chronic stroke? Ann Neurol 2004, 56:206-212.

Knecht S, Breitenstein C, Bushuven S, Wailke S, Kamping S, Flöel A, Zwitserlood P, Ringelstein EB.

Levodopa: Faster and better word learning in normal humans. Ann Neurol 2004; 56:20-26.

Reviews

Flöel A, Cohen LG.

Translational studies in human neurorehabilitation: from bench to bedside. Cogn Behav Neurol 2006, 19: 1-10.

Flöel A, Cohen LG.

Contribution of noninvasive cortical stimulation to the study of memory functions. Brain Res Brain Res Rev 2006, 53: 250-259.

Rösser N, Flöel A.

Pharmacological enhancement of motor recovery in subacute and chronic stroke. NeuroRehab 2008, 23: 95-103.

Floel A, Cohen LG.

Recovery of Function in Humans: Cortical Stimulation and Pharmacological Treatments after stroke. Neurobiol Diseases 2009; June 9th [epub ahead of print]

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