Irene Neuner1,2,3, Jörg Mauler1, Ravichandran Rajkumar1,2,3, Ezequiel Farrher1, Elena Rota Kops1, Lutz Tellmann1, Jürgen Scheins1, Frank Boers1, Karl Josef Langen1,3,4, Hans Herzog1,2,3, and N. Jon Shah1,3,5
1Institute of Neuroscience and Medicine 4 (INM 4), Forschungszentrum Juelich GmbH, Juelich, Germany, 2Department of Psychiatry, Psychotherapy and Psychosomatics, RWTH Aachen University, Aachen, Germany, 3JARA-BRAIN, Translational Medicine, Aachen, Germany, 4Department of Nuclear Medicine, RWTH Aachen University, Aachen, Germany, 5Department of Neurology, RWTH Aachen University, Aachen, Germany
Synopsis
Within the
scope of this explorative pilot trial we focus on the role of GABA and glutamate within the default mode network with regard to
energy consumption. In one simultaneous session MR, FDG-PET and EEG data were recorded
at a 3T hybrid MR-BrainPET scanner (Siemens, Germany)
equipped with a 32 channel MR-compatible EEG system (Brain Products, Germany)
in 11 healthy volunteers. The Pearson correlation showed a statistically significant
positive correlation between
glutamate ratio and mean CMRGlu in
the DMN (r = 0.678, n = 11, p = 0.022) but none to
GABA. Aim
The brain is a very efficient, fast acting and
complex network. A large number of different brain areas have their own dedicated
task and function but continuously share information with each other on a
millisecond basis
1. As a complex network, the brain relies for its
function on different aspects of connectivity in the structural domain and
functional domain. For the functional domain temporal patterns of neuronal
activity, concentrations of transmitters and energy metabolism shape important
aspects of brain activity. Within the scope of this explorative pilot trial, we
focused on the functional aspect and aimed to investigate the role of GABA and
glutamate within the cardinal resting state network, the default mode network, with
regard to metabolic activity and energy consumption.
Methods
In one session
MR, FDG-PET and EEG data were recorded simultaneously on a 3T hybrid
MR-BrainPET scanner (Siemens, Germany) equipped with a 32 channel MR-compatible
EEG system (Brain Products, Germany) in 11 healthy, male volunteers (mean age:
25.2 years SD: 1.2).
MR and EEG data
acquisition
MP-RAGE (TR =
2250 ms, TE= 3.03 ms, 176 sagittal slices á 1 mm, GRAPPA factor 2). EPI
sequence parameters for rs-fMRI were (TR: 2.2 s, TE: 30 ms, FOV: 200 mm, in
plane resolution 3 mm, 165 volumes). Single-voxel spectra of
the posterior cingulate cortex (PCC) and precuneus were consecutively measured using the point
resolved spectroscopy (PRESS) sequence (TE1 = 14 ms, TE = 105 ms, TR = 2.5 s, NA = 128, 25 mm × 25 mm × 25 mm voxel size, RF pulse centred at 2.4 ppm, 16 step
phase cycling). One extra
complete phase cycle was measured without the water suppression RF pulse to
record a water peak reference for eddy current correction and absolute
metabolite concentration calibration. Before spectroscopy measurements, the B0
field was shimmed by running FASTESTMAP
2 iteratively to ensure the FWHM
of the reference water peak to be below 0.05 ppm. The GABA
ratios (relative to Cr+PCr) and the glutamate ratios were investigated in the PCC and in the precuneus. During
data acquisition volunteers were requested to close their eyes and relax
but instructed not to fall asleep. EEG data were recorded simultaneously using
a 32-channel MR compatible EEG system.
PET data
acquisition
Approx. 200 MBq FDG were injected as a single bolus with the volunteer
lying in the scanner at the start of the trimodal imaging study. PET data were
acquired in list mode and iteratively reconstructed, with all necessary
corrections, into 153 slices with 256 x 256 voxels sized 1.25 mm3. MR-based, template-based attenuation correction
was applied.
Results
The paired-samples t-test showed that the mean CMRGlu within
the DMN mask was higher than outside the DMN mask (t(10) = 13.773, p < 0.001). The Pearson
correlation showed a statistically significant positive correlation between
glutamate ratio and mean CMRGlu in the DMN (r = 0.678, n = 11, p = 0.022) but
none to GABA. This activity of the default mode was not coupled to a special
EEG frequency band.
Discussion
The trimodal approach, recording PET data,
MR data and EEG data simultaneously was successful. The high neuronal activity
of the structures within the default mode network occurs on the basis of a high
glucose consumption rate within the default node network. The regional
metabolic rate of glucose as assessed via 18FDG-PET is largely
influence by glial uptake of glucose in response to neuronal glutamate release
3,4.These
prior findings fit well with the observation in our data that the glutamate
levels assessed in the precuneus and PCC correlate significantly and positively
with the measured glucose consumption rate within the DMN. Thus, glutamate
seems to be coupled to / to steer the metabolic demands of neuronal activity
but not the vascular response. There was no correlation between glutamate and
BOLD amplitude. A close link between glutamate and mean glucose consumption
rate as assessed in vivo in humans in
our simultaneous approach extends prior work in vitro and in anesthesized cats
5.
These findings are in line with the observation that the major part of brain
energy consumption is dedicated to excitatory activity
5, 6.
Acknowledgements
This trimodal imaging approach was
supported by the EU-FP7 funded project TRIMAGE (Nr. 602621). We thank Dr. Jorge
Arrubla for his support in data acquisition and processing. We thank Cornelia
Frey, Silke Frensch and Suzanne Schaden for their excellent technical
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