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Forschungsarbeit

The metabolic foundation of intrinsic brain activity

Von Katarzyna Bienkowska (23.07.2014)

"Understanding how the brain works is arguably one of the greatest scientific challenges of our time", stated Paul Alivisatos [1], while describing the American Brain Activity Map Project, one of the biggest brain research initiatives worldwide, alongside European Brain Research Project. Coordinated activity of large numbers of neurons and its emergent properties, being one of the most interesting features of human brain, still remains incompletely understood. Over the last decade, the blood-oxygen-level-dependent (BOLD) signal of functional magnetic resonance imaging (fMRI) has gained enormous relevance in indirectly investigating brain function in research and the clinical setting [2]. BOLD signal is reflecting synchronized fluctuation in the brain resting state and during performing a certain task [10]. While there has been considerable progress in relating the fMRI signal to neuronal signaling, and recently as well to glucose metabolism [3], its relationship to chemically mediated transmission is still largely unknown [4].

Bienkowska: Fig. 1[Bildunterschrift / Subline]: Figure 1: Results of the FDG-PET/fMRI study [3]. A) In eyes open condition (in comparison to eyes closed) there is a well defined pattern of brain regions that consume more energy. These regions show as well increased network communication. B) Energy consumed by regions of higher FDG-intake drives the internal brain communication in eyes open condition. C) In the illustrated brain region profile of energy consumption is related to the profile of brain functional connectivity.

Resting-state BOLD signal shows a specific topological organization at temporal and spatial scale. This spontaneous intrinsic brain activity (iFC) has a certain modular structure in which the the connections between regions are much denser within modules than between them, which proves the interconnection between functional brain systems such as somatosensory/motor, auditory, attention, visual, subcortical, and the “default” (resting) system [12].

In previous study, using simultaneous positron-emission-tomography (PET) and fMRI, we detected specific local glucose metabolism activity profiles, determining functional connectivity (a measure of intrinsic brain activity) during resting-state condition [3]. Both local activity and resting-state functional connectivity are disrupted in many psychiatric and neurological disorders [5, 6, 7]. Our novel approach enables the analysis of distinct factors underlying aberrant functional connectivity such as local activity, local transmitter activity or relevant changes in structural connectivity in patient populations.

The two major neurotransmitters in the central nervous system are the excitatory glutamate (Glu) and inhibitory gamma-aminobutyric acid (GABA). Recent developments in magnetic resonance spectroscopy (MRS) now offer the opportunity to simultaneously acquire data on Glu and GABA concentrations in the human brain. Prior task-fMRI studies show negative correlation between baseline GABA level and BOLD signal change during visual stimulation (task condition) [8, 9]. What has not been studied yet is the relationship between resting state coherent BOLD signal change (functional connectivity) and excitatory/inhibitory neurotransmitter balance in the resting state. 

Bienkowska: Fig. 2[Bildunterschrift / Subline]: Figure 2: Thanks to the multi-modal approach networks communication between distant brain regions can be studies simultaneously with the local energy consumption (measured with PET) and local inhibitory/excitatory neurotransmitters signaling (measured with MRS)

In order to investigate interaction between GABA/Glu levels and organized intrinsic brain activity, a combined fMRI-MRS study was performed. GABA and glutamate concentration in the occipital cortex, measured by magnetic resonance spectroscopy, were correlated with functional connectivity (FC), regional homogeneity (ReHo) and degree centrality (DC) of the resting brain in eyes-open and eyes-closed condition.

Our preliminary results on relationship between resting state coherent BOLD signal change and excitatory/inhibitory neurotransmitter balance suggest that there is a correlation between GABA and glutamate neurotransmitters levels and organized intrinsic brain activity of occipital cortex during resting state condition. GABA and glutamate concentrations are related to the local regional homogeneity, local degree centrality and functional connectivity measures.

Bienkowska: Fig. 3[Bildunterschrift / Subline]: Figure 3: In multi-modal fMRI/fMRS study measures of local and distant functional connectivity are correlated with local inhibitory (GABA) and excitatory (Glx) neurotransmitter levels.

Our results provide first evidence on interaction between GABA and glutamate levels and organized intrinsic brain activity at rest. We suggest that local and global functional connectivity between visual cortex and other brain regions is driven by the increase of the GABA level. The modulatory effect of GABA/Glu balance in visual cortex might be restrained by the nodality of this brain area, which would reflect number of connections of this area with other brain areas [11]. We believe that understanding complicated relations between coordinated neuronal activity measured with BOLD signal of functional magnetic resonance imaging and chemically mediated neurotransmission may shed the light on molecular basis of psychiatric and neurological disorders. 

References:

[1] Alivisatos AP, Chun M, Church GM, Greenspan RJ, Roukes ML, Yuste R (2012). “The Brain Activity Map Project and the Challenge of Functional Connectomics”, Neuron vol. 74, no. 6, pp. 970–974. 

[2] Logothetis N (2003). “The Underpinnings of the BOLD Functional Magnetic Resonance Imaging Signal”, The Journal of Neuroscience, vol. 23, no. 10, pp. 3963-3971.

[3] Riedl V, Bienkowska K, Strobel C, Tahmasian M, Grimmer T, Förster S, Friston KJ, Sorg C, Drzezga A (2014). “Local Activity Determines Functional Connectivity in the Resting Human Brain: A Simultaneous FDG-PET/fMRI Study”, The Journal of Neuroscience, vol. 34, no. 18.

[4] Raichle ME, Mintun M (2006). “Brain work and brain imaging”, Annual review of neuroscience, vol. 29, pp. 449–76.

[5] Drzezga A, Becker JA, Van Dijk KR, Sreenivasan A, Talukdar T, Sullivan C, Schultz AP, Sepulcre J, Putcha D, Greve D, Johnson KA, Sperling RA (2011). “Neuronal dysfunction and disconnection of cortical hubs in non-demented subjects with elevated amyloid burden”, Brain, 134, pg. 1635–1646.

[6] Greicius M (2008). “Resting-state functional connectivity in neuropsychiatric disorders”, Current  Opinion in Neurology, 21, 424–430.

[7] Carr VA, Rissman J, Wagner AD (2010). “Imaging the human medial temporal lobe with high-resolution fMRI”, Neuron, vol. 65, no. 3, pp. 298-308.

[8] Donahue MJ, Near J, Blicher JU, Jezzard P (2010). “Baseline GABA concentration and fMRI response”, NeuroImage, vol. 53, no. 2, pp. 392–398.

[9] Muthukumaraswamy SD, Edden RE, Jones DK, Swettenham JB, Singh KD (2009). “Resting GABA concentration predicts peak gamma frequency and fMRI amplitude in response to visual stimulation in humans”, Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 20, pp. 8356–8361.

[10] Fox MD, Raichle ME (2007). “Spontaneous fluctuations in brain activity observed with functional magnetic resonance imaging”, Nature Reviews Neuroscience, 8, 700–711. 

[11] Zuo, X.N., Ehmke, R., Mennes, M., Imperati, D., Castellanos, F.X., Sporns, O. and Milham, MP (2012). “Network centrality in the human functional connectome”, Cerebral cortex, vol. 22, no. 8, pp. 1862–75.

[12] He Y, Wang J, Wang L, Chen ZJ, Yan C, Yang H, Tang H, Zhu C, Gong Q, Zang Y, Evans AC (2009).  “Uncovering Intrinsic Modular Organization of Spontaneous Brain Activity in Humans”, PloS ONE, vol. 4, no. 4, e5226.


Scientific career
  • 2004-2009
  • Bachelor and Master Studies of Biotechnology, University of Wrocław, Poland
  • 2004-20010
  • Bachelor Studies of Psychology, University of Wrocław, Poland
  • 2010-2012
  • Master Studies of Neuro-Cognitive Psychology, Ludwig-Maximilians-Universität, München
  • since 2012
  • Doctoral Studies of Medical Life Science and Technolgoy, Neuroimaging Center of Klinikum Rechts der Isar, Technische Universität München
  • 2013
  • Master of Science Degree in Psychology, Department of Clinical Psychology and Health, University of Wrocław, Poland

Scholarships and Awards
  • * Academic Performance Awards in Psychology and Biotechnology, University of Wrocław (2005)
  • * ERASMUS scholarship (2009)
  • * DAAD study scholarship (2010)
  • * Scholarship from Studienstiftung des deutschen Volkes, Summer Academy (2012)
  • * Research scholarship funded by the Faculty of Medicine of the Technische Universität München (as one the 6 best ranked candidates in the PhD program in Medical Life Science and Technology) (2013)
  • * Research fund from the Faculty of Medicine of of the Technische Universität München (2013)