Functional Neuroimaging
Prof. Dr. Frank Angenstein
Group Leader
Haus 64, Leipziger Str. 44
39118 Magdeburg

frank.angenstein@dzne.de
 +49 391 626392-091

Areas of investigation/research focus

Functional magnetic resonance imaging is an extensively used approach to noninvasively map brain responses to a variety of different conditions with a high spatial resolution. Therefore, fMRI has become a very helpful tool for cognitive neuroscience but it is only very hesitantly used for clinical applications based on the fact that not only normal fMRI responses are often difficult to interpret but abnormal fMRI responses are not unambiguously explainable. The main problem with interpreting fMRI results is the nature of the recorded signals. FMRI only reflect hemodynamic responses, which, in turn, are locally controlled by neuronal activity. Therefore, a detailed understanding of mechanisms that link distinct variations in neuronal activities with corresponding hemodynamic responses is crucially required. Only the known relation between specific changes in neuronal activity and the resultant fMRI response allows conclusive interpretations of observed fMRI responses. As soon as fMRI results become interpretable, this method can strengthen diagnostic approaches for several neurodegenerative, mental and psychiatric disorders. To better understand neurovascular-coupling mechanisms, we developed an experimental approach to simultaneously measure neuronal and vascular responses in the rat hippocampus during electrical stimulation of various fiber or hippocampal substructures. This approach enables us to study not only the neurophysiological basis of fMRI but also how modulatory transmitter systems or local tauopathien affect hippocampal functions and interactions of the hippocampus with several cortical and subcortical structures.

 more Infos

1. Neurophysiological basis of fMRI responses
Defined electrical stimulation of afferent (perforant pathway) or efferent (fimbria-fornix) projections of the hippocampus with concurrent measurements of induced neuronal responses in the hippocampus (by in vivo electrophysiology) and BOLD responses in the entire rat brain (by fMRI) allows us to study neurophysiological mechanisms controlling the formation of fMRI-BOLD responses.

2. Role of dopamine for hippocampal functions
The activity of the mesolimbic dopaminergic system can be controlled by an optogenetial approach (expression of laser-light sensitive opsins in dopaminergigic neurons of the VTA) or electrical stimulation of the VTA. How an increased release of dopamine affects hippocampal function can then be monitored by simultaneous electrophysiology and fMRI measurements

3. Interaction of the hippocampus with cortical and subcortical structures
Stimulation of afferent hippocampal projection triggers significant fMRI responses in the hippocampus and in several target regions of the hippocampus, such as nucleus accumbens, prefrontal cortex, septum and amygdala. Based on the temporal relation of the recorded hemodynamic responses in all individual brain structures functional connectivities between different regions can be identified. This allows us to study the impact of activated/inhibited modulatory systems (e.g., the mesolimbic dopamine system) or locally developing pathologies (e.g., tauopathien) on these normally existing functional connectivities.

Key Publications

Cornelia Helbing, Marta Brocka, Thomas Scherf, Michael T Lippert, Frank Angenstein. The role of the mesolimbic dopamine system in the formation of blood-oxygen-level dependent responses in the medial prefrontal/anterior cingulate cortex during high-frequency stimulation of the rat perforant pathway. Journal of Cerebral Blood Flow and Metabolism. 2016 Nov 30; 36:2177-2193. doi: 10.1177/0271678X15615535
Thomas Scherf, Frank Angenstein. Postsynaptic and spiking activity of pyramidal cells, the principal neurons in the rat hippocampal CA1 region, does not control the resultant BOLD response: A combined electrophysiologic and fMRI approach. Journal of Cerebral Blood Flow and Metabolism. 2015 Mar 31; 35:565-575. doi: 10.1038/jcbfm.2014.252
Angenstein F. The actual intrinsic excitability of granular cells determines the ruling neurovascular coupling mechanism in the rat dentate gyrus. J Neurosci. 2014 Jan 01; 34:8529-45. doi: 10.1523/JNEUROSCI.0472-14.2014
Frank Angenstein, Karla Krautwald, Wolfram Wetzel, Henning Scheich. Perforant pathway stimulation as a conditioned stimulus for active avoidance learning triggers BOLD responses in various target regions of the hippocampus: A combined fMRI and electrophysiological study. NeuroImage. 2013 Jul 04; 75:221-235. doi: 10.1016/j.neuroimage.2013.03.007
Angenstein F, Kammerer E, Scheich H. The BOLD response in the rat hippocampus depends rather on local processing of signals than on the input or output activity. A combined functional MRI and electrophysiological study. J Neurosci. 2009 Jan 01; 29:2428-39. doi: 10.1523/JNEUROSCI.5015-08.2009

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