Experimental studies of gambling disorder
– work in progress
Sarah Holst1, Tie-Qiang Li2, Adam Sierakowiak3, Simon Körösi1, Laila Nauman1, Naz Karadag1 and Erika Roman4
1Department
of Neuroscience, Karolinska Institutet, Stockholm, 2Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm,
3Department of Oncology-Pathology, Karolinska Institutet, Stockholm, 4Department of Pharmaceutical Biosciences, Uppsala University, Uppsala
[email protected]; [email protected]
Aims
•Investigate associations between two behavioral tests and functional Magnetic Resonance Imaging (fMRI) in the two rat strains Lister Hooded (LH) and Lewis
Conclusions
•The rat strain Lister Hooded were more risk taking, active and explorative than the Lewis strain as assessed in the Multivariate Concentric Square Field™ and the Novel Cage
test.
•The difference was mirrored in the functional Magnetic Resonance Imaging (fMRI) where the behavior of the Lister Hooded correlated with higher strength and more
connections compared to Lewis in the primary motor cortex, superior culliculus, PAG, enthorinal cortex, hippocampus, amygdala, thalamus and the striatum.
•Behavioral profiling in combination with the imaging technique increases the translationality from rat to human, important for preclinical studies of gambling disorder
Novel cage test
Behavior
Functional
categories
Description
Walking
General Activity
Locomotor behavior with normal body posture.
Wall Rearing
Free Rearing
Standing on hind legs with forepaws leaning against
a wall.
Exploratoration
Investigating
Strech approach
Standing on hind legs.
Exploring floor, cage walls or air trough olfactory
activity.
Risk assessment
Strech attend
posture
Walking with a flat body posture stretched and close
to the floor.
Stretching the neck or front part of the body while
sniffing the air, with 4 paws on the floor a flat body
posture.
Grooming
Displacement
behaviours
Scratching, shaking, wiping or licking body parts (fur,
ears, nose, tail).
Freezing
Anxiety-related
behaviour
Sudden suppression of movement.
Motionless
Default Mode Network, Motor Network, Dorsal and Ventral Basal Ganglia Networks in the Rat Brain:
Comparison to Human Networks Using Resting State-fMRI
Sierakowiak, Monnot, Nikkhou Aski, Uppman, Li, Damberg and Brené
http://dx.doi.org/10.1371/journal.pone.0120345
Sitting or lying immobile.
b
a
Multivariate concentric square field™
fMRI
a
Figure 4.a The clusters with
statistically significant (FWER,
p<0.05) correlation between CCI
and PCA-V1 (MCSF) overlaid on
the T1-weighted brain temperate.
The color bar indicates the t-score
scale of the regression analysis in
the regions hippocampus,
amygdala, thalamus and
enthorinal cortex b. The clusters
with statistically significant
(FWER, p<0.05) correlation
between CSI and PCA-V1
(MCSF) overlaid on the T1weighted brain temperate. The
color bar indicates the t-score
scale of the regression analysis
on the regions hippocampus and
thalmus.
c
b
Figure 1. a. The clusters with statistically significant (FWER, p<0.05) correlation between CCI and PCA-V1 (NCT) overlaid on the T1-weighted brain temperate. The color bar indicates the t-score
scale of the regression analysis. Note the activity in primary motor cortex, superior culliculus, PAG, hippocampus and the striatum. b. The clusters with statistically significant (FWER, p<0.05)
correlation between CSI and PCA-V1 (NCT) overlaid on the T1-weighted brain temperate. The color bar indicates the t-score scale of the regression analysis. Note the activity in the primary motor
cortex, superior culliculus, PAG, hippocampus, amygdala and the striatum. c. The clusters with statistically significant (FWER, p<0.05) correlation between CCI and PCA-V2 (NCT) overlaid on the
T1-weighted brain temperate. The color bar indicates the t-score scale of the regression analysis in the regions primary motor cortex and striatum. d. The clusters with statistically significant (FWER,
p<0.05) correlation between CSI and PCA-V2 (NCT ) overlaid on the T1-weighted brain temperate. The color bar indicates the t-score scale of the regression analysis in the regions primary motor
cortex and striatum.
Figure. 5. The scattered plots of the average
functional connectivity metrics (CCI connection
index, and CSI, strength index) for the significant
clusters shown in Fig. 4a &b against the PCA
components V1 of the MCSF. Circles represent
LH and squares represent Lewis (A) CCI versus
PCA-V1; (B) CSI versus PCA-V1.
a
a
b
Figure 2. The scattered plots of the average functional connectivity metrics (CCI, connection index,
and CSI, strength index) for the significant clusters shown in Figs. 1-4 against the PCA components
V1 and V2 of the NCT. Circles represent LH and squares represent Lewis. (A) CCI versus PCA-V1
(B) CCI versus PCA-V2 (C) CSI versus PCA-V1 (D) CSI versus PCA-V2.
Figure 3. Principal Component Analysis (PCA) comparing Lister Hooded (LH) and
Lewis rats in the novel cage test (NCT). The score plot illustrates the individual rats
(a) and the loading plot illustrates the behavioral variables (b) that were included in
the analysis. Behaviors of most important for the separation were related to
exploration and activity (LH) and emotionality and stress coping style (Lewis).
Figure 6. Principal Component Analysis (PCA) comparing Lister Hooded (LH)
and Lewis rats in the multivariate concentric square field™ (MCSF) test. The
score plot illustrates the individual rats (a) and the loading plot illustrates the
behavioral variables (b) that were included in the analysis. Behaviors of most
important for the separation were related to risk taking, exploration and activity
(LH) and shelter seeking (Lewis).
Sammanfattaning
•Råttstammen Lister Hooded var mer risktagande, aktiv and nyfiken jämfört med Lewis, enligt beteendetesterna MCSF™ och NCT.
•Skillnaden avspeglades i funktionell magnetröntgen (fMRI) där Lister Hoodeds mer aktiva beteende korrelade med högre styrka och fler kopplingar i hjärnans nätverk
jämfört med Lewis i regioner relaterade till syn, hörsel, känsel, navigering, rörelseaktivitet, rädsla och lust.
•Beteendeprofilering i kombination med medicinsk bildvetenskap befrämjar preklinisk forskning om spelproblem genom att öka möjligheten att överföra och tillämpa
kunskaper om riskprofiler från djur till människa.