Transcript Resting state functional connectivity MRI inisoflurane

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Resting state functional connectivity
MRI in isoflurane-anesthetized rat
brain
Resting state functional connectivity MRI (rs-fcMRI)
provides a unique opportunity to investigate the
architecture of intrinsic functional connectivity of the rat
brain based on the spontaneous low-frequency fluctuations
of the BOLD signal. It is of particular importance in
translational medicine, since it allows to measure drug
effects on functional brain connectivity in preclinical animal
models and to compare with the effect of the same drugs
on the functional connectivity in the human brain.
• Here we investigated intrinsic functional connectivity in
isoflurane-anesthetized rat brain and its modulation as a
result of administration of two different drugs: 1.
scopolamine (SA) and 2. a memory enhancing compound
(MEC).
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Animals
-11 adult male Long-Evans (LE) rats (230-270 g) rats
- Isoflurane gas (1.0-1.5 %)
Experimental procedure
20min long resting state fMRI acquisitions was started 10min before
the initiation of the SA and MEC infusion.
• ‘SEED’ selection:
• Seed regions of interest (ROI) ( ~3×3×3 voxels) were selected in
dorsal and ventral hippocampus, prefrontal cortex (PFC), temporal
and parietal cortex, periaqueductal gray matter (PAG), dorsal
striatum (caudate and putamen) and amygdala based on
anatomical T1-weigted GEMS scans and with reference to the
Paxinos and Watson rat brain atlas as well.
• Resting-state specific preprocessing was performed on the data sets:
• -spatial filtering with a Gaussian kernel of 2 voxels FWHM
• -voxel-wise regression analysis to remove artefacts due to changes in grey
matter, and skull signals;
• -band-pass filtering (0,009-0,08 Hz);
• Data were segmented according to the administration time of the drug
compounds: 8.5 min intrinsic and 8.5min drug modulated resting state
activity were analysed for each animal.
• Reference time course from a seed ROI was then correlated with the
• entire data set. Group-wise (random effects) statistical parametric maps
was obtained based on individual correlation coefficient maps and their
contrasts.
Resting state activity based intrinsic
connectivity maps
Group level correlation
matrix (t-statistic based on
the individual correlation
coefficients). As expected,
there are strong positive
correlations between the
same anatomically localized
brain regions of the two
hemispheres. Furthermore
negative correlations
between the striatum and
PAG (and hippocampus and
PFC) are in agreement with
the relevant literature.
Resting state activity based intrinsic
connectivity maps
SEED
Dorsal
Hippocampus
Ventral
Hippocampus
PFC
Temporal
cortex
Resting state activity based intrinsic
connectivity maps
SEED
PAG
Caudate/
Putamen
Amygdala
Amygdala,ventral hyppocampus versus (negative correlation) ACC,
PFC (Liang et al Neuroimage, 2011)
Pharmacological modulation of the
resting state activity
Random effects group analysis of the differences between the scopolamine and
memory enhancing compound induced changes in the resting state activity.
Increased functional connectivity of the dorsal hippocampus(A) and ventral
hippocampus (B) as a result of MEC administration
compared to
scopolamine injection can be seen.
Pharmacological modulation of the
resting state activity
Random effects group analysis of the
differences between the scopolamine and
memory enhancing compound induced
changes in the resting state activity.
Conclusion
• Using the seed-based rs-fcMRI approach we showed
that the functional connectivity of different
anatomically localized brain regions was preserved
under isoflurane-anesthesia.
• In specific brain regions SA and MEC had an opposite
effect on functional connectivity: intrinsic BOLD signal
co-fluctuations were reduced and enhanced by SA and
MEC, respectively.
• These results provide support for the application of rsfcMRI in isoflurane-anesthetized rat brain to investigate
normal and pathological brain functions as well as drug
effects in preclinical animal models.
Anyag adása önmagában
Hippocampus
BOLD (kontroll %-a)
1,02
10 mg/kg
1,00
0,98
0,96
-500
0
500
1000
1500
idõ (sec)
20 mg/kg
BOLD (kontroll %-a)
1,02
1,00
0,98
0,96
-500
0
500
idõ (sec)
1000
1500
2260 adása szkopolamin előkezelt állatnak
Hippocampus
10 mg/kg
1,04
BOLD (% of control)
scopolamine
1,02
1,00
0,98
-1500
-1000
-500
0
500
1000
Idõ (sec)
BOLD (% of control)
1,04
10 mg/kg
1,02
1,00
0,98
-500
0
500
Idõ (sec)
1000
1500
Hatóanyag adása szkopolamin előkezelt
állatnak
ROI analízis
5
4
BOLD response (%)
**
3
**
*
*
*
**
2
*
*
*
1
0
Hipp cortex
PFC DMPAG LPAG SCN
stri
tempo pariet
Resting state fMRI patkányban
Független komponens analízissel hálózatok azonosíthatók éber patkányban:
1. Cerebellar Network
2. (Visuo-) Spatial System
3. Basal Ganglia-Hypothalamus Network
4. Basal Ganglia-Thalamus-Hippocampal Network
5. Autonomic Network
6. Sensory (Exteroceptive) Network
7. Interoceptive Network
Preklinikai Képalkotó Laboratórium 2012.
február