Using fMRI to study inter-strain DMN variances in rats

The default mode network

The default mode network (DMN) is a set of brain regions that are fundamental to brain function. Brain activity in these regions is highly correlated during the “resting” state, which is referred to as the brain “default mode.”

In this default mode, a person may be awake and alert but not actively focused on a task that is goal directed or requires attention. During the resting state, spontaneous thoughts or daydreams, for example, may arise, but when focus is needed to complete a task, activity in the DMN becomes suppressed.

The different regions of the DMN are found at the center of a number of distributed brain networks and DMN abnormalities are commonly seen in various neurological and psychiatric conditions such as bipolar disorder, schizophrenia and attention deficit hyperactivity disorder (ADHD).

active nerve cell

ADHD

Studies have previously shown that children with ADHD have difficulty “switching off” the DMN. In ADHD-linked behaviors such as difficulty concentrating or poor attention span, the DMN has been shown to display abnormal spontaneous functional connectivity between brain networks.

Functional connectivity is the connectivity between different areas of the brain that have shared functions. Assessment of this connectivity has become an important tool in the study of brain disease mechanisms. In ADHD, experts suspect that the DMN may be inadequately suppressed during tasks that demand attention.

Resting state functional magnetic resonance imaging

Functional or resting state connectivity experiments enable scientists to look at how brain activity is integrated across various regions, allowing insights into intrinsic connectivity networks such as the DMN.

While several approaches can be employed to achieve this, the most widely used is resting state functional magnetic resonance imaging (rs-fMRI). This detects the blood oxygenation level-dependent (BOLD) signal in different areas of the brain as a representation of nerve activation, as changes in the blood flow reflect changes in the neural activity of brain tissues. Since these BOLD signals are detected while an individual is not engaging in task- or goal-related activities, rs-fMRI is suitable for studying the DMN.

science medical microscopy micrograph, rat brain hippocampal neurons

The DMN in animal models

The DMN has been shown to exist in non-human primates and various other animal models including mice and rats. In rat brains, the DMN has been demonstrated as broadly similar to the DMN found in non-human primates and humans.

The spontaneously hypertensive rat (SHR) and the Wistar Kyoto rat (WKY) are two rat strains with very similar genetic origins, but different expressions of cardiovascular and neuropsychological functions.

SHR rats have been shown to be a suitable model for ADHD. For tasks that demand attention, they exhibit the typical behavioral characteristics of ADHD including hyperactivity, poor performance and impulsivity. The expression of spontaneous activity and neural organization in the SHR rat brain is therefore of significant interest in ADHD research.

The SHR strain is an inbred strain, created through selection for hypertension in the WKY strain. WKY rats are therefore considered the most appropriate control group in SHR rat research.

Inter-strain DMN variances

In a recent study, Sheng-Min Huang (National Tsing Hua University, Taiwan) and colleagues used rs-fMRI to investigate DMN variation between these two rat strains. Using Bruker’s 7-Tesla MRI, the team performed rs-fMRI experiments to see if they could establish any inherent differences in DMN activity and neural organization between the two rat strains while the rats were anesthetized.

To assess the DMN, they selected retrosplenial cortex (RSC) seed and calculated its time-varying signal curve. The RSC corresponds to the posterior cingulate cortex in primates and is one of the main hubs of the DMN. Correlation coefficient maps were created by carrying out a correlation with the signal, pixel-by-pixel, and then tested before generating final DMN maps.

One of the main differences they found was that there was a widespread connection between the caudate putamen and RSC seed in SHR rats, whereas the WKY rats showed a greater connectivity between the RSC seed and the hippocampus. Since the putamen is involved in regulating motor behavior and the caudate nucleus is involved in social behavior, the researchers suspect that ADHD symptoms may be related to this network abnormality.

Dorsal striatum and the dopamine system

The putamen and caudate nucleus make up a brain region called the dorsal striatum. A previous report has shown impaired dopamine release in the striatum region of SHR rats, as well as disturbed expression of the dopamine transporter (DAT1) gene. Huang and colleagues suspect that impairment of the dopamine system in this brain area may be related to activation of the caudate putamen.

Huang and team say that many researchers have previously reported using SHR rats as a model for ADHD, but that their study is the first to present evidence of the DMN variances between SHR and WKY rats. This suggests the possibility of using rodent models to perform further neuropsychological research using re-fMRI techniques.

References

  • Huang S-M, et al. Inter-Strain Differences in Default Moden Network: A Resting State fMRI Study on Spontaneously Hypertensive Rat and Wistar Kyoto Rat. Scientific Reports 2016;6:21697; doi: 10.1038/srep21697
  • Koshino H, et al. Coactivation of the Default Mode Network regions and Working Memory Network regions during task preparation. Scientific Reports 2014;4:5954; doi: 10.1038/srep05954
  • Heine L, et al. Resting state networks and consciousness Alterations of multiple resting state network connectivity in physiological, pharmacological, and pathological consciousness states. Frontiers in Psychology 2013;3:295. doi: 10.3389/fpsyg.2012.00295
  • ADHD Foundation. What is attention deficit hyperactivity disorder.
  • Wellcome Trust. Press releases. Brain scans show children with ADHD have faulty off-switch for mind-wandering.

About Bruker

Bruker is market leader in analytical magnetic resonance instruments including NMR, EPR and preclinical magnetic resonance imaging (MRI). Bruker's product portfolio in the field of magnetic resonance includes NMR, preclinical MRI ,EPR and Time-Domain (TD) NMR. In addition.

Bruker delivers the world's most comprehensive range of research tools enabling life science, materials science, analytical chemistry, process control and clinical research. Bruker is also the leading superconductor magnet and ultra high field magnet manufacturer for NMR and MRI solutions.


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Last updated: Jun 21, 2016 at 7:02 AM

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