Attentional Set Shifting (IDED) Chamber

Description

Specifications

Species	Mouse	Rat
Dimensions	1 Chamber (L: 12in, W: 8in, H: 7in). With door (guillotine) Start area: 5in x 8 in. Testing area: 7in x 8in	1 Chamber (L: 35.5in, W: 18in, H: 12in) With door (guillotine) Start area: 24in x 18 in x 12in Testing area: 12in x 18in x 12in
Additional Accessories	Odor and medium kit	Odor and medium kit
Cups	8 Cups, Ceramic. Diameter: 2.5in, Height: 1.5in	10 Cups, Ceramic. Diameter: 2.5in, Height: 1.5in

Modifications

Color

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blue, black, white, grey, and clear

Additional cups

Available upon request

Additional Odor and Medium kits

$750 for Odor and Medium kit combos

Neuwirth-BrownTM Attention Set-Shift Test (ASST)

Dig Task

Introduction

The Attentional Set Shifting Task (ASST) is a great tool to probe attention and cognitive flexibility in rodents mediated by the prefrontal cortex. The ASST was developed with respect to one of the most used neuropsychological tasks: The Cambridge Neuropsychological Test Automated Battery (CANTAB) that measures the intradimensional/extradimensional set shifting behavior to evaluate cognitive impairments in humans and non-human primates (Rock et al. 2013).

In rodents, the dimensions used to design the IDED task are odor and medium. Essentially, the animal is trained to associate and pay attention to a particular condition while disregarding the other, considering it as insignificant. When researchers reverse or change the conditions, this, in turn, requires the animal to use their executive functions to find the reward.

The dimension (odor or medium) which is to be associated with reward is determined a priori by the researchers. This dimension is used for both training and testing conditions. In order to determine whether the animal is cognitively flexible or not, the researchers switch the test conditions such that the reward will be associated with the alternate dimension, thus challenging the animal to update their behavior and knowledge.

An attentional set is formed when a subject learns to associate a set of rules to differentiate relevant from irrelevant cues. For instance, the animal learns to associate digging medium (supposed as a relevant cue) with the food reward disregarding the odor (supposed irrelevant cue). In subsequent trials, this association is reinforced; the type of digging medium and odor fluctuates, but the paired associated between medium and reward is kept intact. This reinforced rule turns into a cognitive set (Heisler et al. 2015).

Cognitive flexibility can be assessed by:

Reversal Learning – Challenges the subject to maintain the attention set. For instance, the previously negative stimuli (digging medium) is now positive, and the subject must learn to associate the previously negative medium with reward. The relevant cue rule is kept intact while reversing the rule learned to associate sub-stimuli with the reward.
Extradimensional shift- The formation of the attention set is challenged. If the reward was previously associated with the medium, it would now be associated with odor. If on the other hand, the reward was previously associated with odor, it will now be associated with the medium.
Usually, it is harder to learn the new conditions for a reward under the ED trial. It is even more challenging for animals with cognitive or pre-frontal impairments. Thus, by using animals, the IDED task chamber can create a scenario for testing the animals’ cognition based on their ability to override learned behaviors. The model works by teaching the mice the attentional set-shifting task and then presenting them with a variety of situations requiring the mice to modify or update the learned behavior.

A large number of neuropsychiatric and neurodevelopmental disorders are associated with subsequent cognitive impairments which interfere with adaptation and information processing due to inflexibility. For example, despite being distinct clinical conditions, depression, autism spectrum disorder, and schizophrenia are all interlaced with cognitive deficits. Cognition is also impaired in Parkinson’s disorder, autism spectrum disorders, and obsessive-compulsive disorder. The list goes on.

Researchers and scientists that wish to address the cognitive dysfunctions across disease models can do so by incorporating the IDED task chamber into their experiments. By using animal models with the IDED task chamber in pre-clinical studies to play out situations which require cognitive flexibility and response modification, it is possible to study the effects of certain interventions within a controlled, low-risk setting.

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History

Origin

2.1. Origin

The Attentional set-shifting task was first introduced by Jennifer Birrell and Verity Brown, 2000 to study the effects of prefrontal lesions on rats’ behavior. Since the very inception, it has been accepted as a solid method for studying cognitive flexibility in animal models (Garner et al. 2006).

Birrell and Brown, 2000 conducted a simple discrimination (SD), a compound discrimination (CD), a reversal of the CD (CDR), an intra-dimensional shifting (IDS) and an extra-dimensional shifting (EDS). In their experiment, during the EDS task, it took the rats with lesions significantly more trials to reach the criterion than the control rats. These results indicate that rats with bilateral lesions of the medial frontal cortex have selective impairment in shifting of attentional set.

The rats with lesions and the control rats were able to learn the basic discrimination tasks and the intra-dimensional shifts without significant differences. But, when performing on the ED task, the lesioned rats took twice as many trials to reach criterion, thus demonstrating the effect of a lesioned pre-frontal cortex when it comes to attentional set-shifting.

A key finding is a sharp distinction between the data obtained from the ID and data from the ED dimensions, demonstrating internal validity (Garner et al., 2006). The same phenomenon can be observed in humans with impaired cognition. The fact that the ED condition requires more learning and effort demonstrates that the animal has difficulty set-shifting into a new, distinct dimension. If this was not the case, the data for the ED condition would not have been significantly different from the data gathered from the ID condition.

Developments

Since then, an array of experiments has been conducted with the help of the IDED chamber apparatus, demonstrating its versatility and usefulness.

Recently, A. Cybulska-Klosowicz et al. 2017 utilized the IDED chamber to probe the involvement of the Dopamine system in controlling the executive function. Although, the rodents model of attentional set-shifting is prevalent from the beginning of this decade. A. Cybulska-Klosowicz et al. 2017 discovery that dopamine imbalance particularly deficit disrupts the executive function, especially attention may open new avenues in developing novel interventional strategies in treating neurodegenerative and neuropsychiatric disorders.

Apparatus & Equipment

The ID/ED Task Chamber consists of two chambers, a testing area, and a waiting area. A guillotine-like start gate regulates the entry to the testing area. The testing chamber is further divided into two compartments with the aid of an acrylic partition. Each chamber in the testing area contains a ceramic bowl that can be filled with the digging medium and the odorant which can be selected from the odor and medium kits.

The separation between the waiting area and the testing area allows for easy preparation of the testing area. Each trial requires a “restart” in which the animal is returned to the waiting area. As soon as the start gate is lifted, the animal gains access to the testing area.

Tracking software such as Noldus Ethovision XT, ANY-Maze or Glia mounted above the maze assist with live scoring, tracking and recording the subject and its movements within the maze. The apparatus must be cleaned thoroughly before and after each trial to limit influence from any residual stimuli from previous trials.

Experimental Design and Training Protocol

In general, the Attentional Set Shifting task comprises five discrimination phases/conditions: a simple discrimination (SD), a compound discrimination (CD), a reversal of the CD (CDR), an intra-dimensional shifting (IDS) and an extra-dimensional shifting (EDS).

In the Simple Discrimination (SD) phase, the animal must select one medium over another within a dimension. For instance, when testing the odor dimension, attention to the nutmeg odor may be rewarded over rosemary odor. The animal learns a simple rule; paying attention to the nutmeg odor will be rewarded.

During the Compound Discrimination (CD) phase, a second dimension is introduced, but the relevant dimension and correct mediums stay the same. Therefore, the animal must pay attention and respond to the former relevant dimension and medium, while ignoring an irrelevant dimension. For example, when testing the odor dimension, the subject might be rewarded for paying attention to the nutmeg medium while ignoring the irrelevant medium rosemary, along with the irrelevant digging medium (e.g., felt or paper which was introduced). The subject learns to maintain the rules learned in the SD task while ignoring the second dimension.

In Reversal of the CD (CDR), all dimensions and mediums stay the same as in the CD phase, but the previously correct medium within a dimension is now incorrect. For example, in the odor dimension paying attention to the nutmeg odor is no longer rewarded. The subject now has to pay attention to the rosemary odor (digging medium still acts as an irrelevant dimension here). Hence the subject must reverse the rules it learned about the mediums within the dimensions earlier.

In the Intra-Dimensional Shifting (IDS) phase, the digging mediums and odors change, but the relevant dimension stays the same as before. For example, now the digging mediums might be pompoms and sequence, and the odors might be cinnamon and cloves, but the subject will still be rewarded for paying attention to the same dimension as before; the odor dimension. Within the odor dimension, one odor medium will be rewarded over the other, here cinnamon.

In the Extra-Dimensional Shifting (EDS) phase, the digging mediums and odors change. For example, now the digging mediums might be raffia and foam, and the odors might be citronella and anise. In this phase, the animal must shift its attention to the previously irrelevant dimension. For example, now the medium’s dimension is relevant over the odor dimension. For example, now the subject will be rewarded for digging in raffia.

Preparatory Handling (Days 1-8)

For the first eight days of the experiment, you are simply handling the subjects. This procedure habituates them to the act of handling and thereby reduces any associated stress that may have otherwise occurred during testing.Note: Food restriction begins at the end of this 8-day stage.
On each day, measure and record the subject’s weight.You must also habituate the subject to dig within a ceramic pot, in order to retrieve a food reward. To ensure that the subject has associated a particular digging medium with the food, the subject needs to find the food eight times on the trot without performing a single error.

Food Restriction Period (Days 9-12)

Four days before the experiment begins, introduce the two ceramic pots into the subject’s box and place the small food pellets inside the ceramic pots to begin habituating the subject for feeding on the pots incrementally.Note: Feed the subject 1 gram of food on a daily basis. The subject’s weight is supposed to be maintained at 80-85% of what it was in the first eight days of handling. If its weight falls below 80%, then it is okay to increase the allotted food proportion to 2 grams.
The cage’s bedding is only to be changed one day prior to the acclimation stage; the bedding is not to be changed again until the completion of the testing procedure

Acclimation Period (Days 13-14)

To reduce the stress of being in a new cage (the ID/ED chamber), take some of the bedding from the subject’s cage and sprinkle in the experimental chamber. The familiar smell serves to console the subject of the new environment and keeps stress levels low.
In the ID/ED chamber, place a ceramic pot filled with water in the center of the waiting area and the two previously used ceramic pots for feeding in the corners of the testing area. In the two ceramic pots, place food weighing approximately 20 mg in each pot (total of 40 mg).
Transfer the subject from its home cage to the waiting area of the ID/ED chamber.
After some time in the waiting area, the start gate is left open for the exploration of the new setting for one hour. Frequently put small food rewards into the ceramic pots to encourage exploration and interaction with the ceramic pots.
The experimenter must stay near the chamber and remain visible to the subject throughout the acclimation period. The subject will get used to the experimenter’s looming presence, thus reducing the likelihood that the experimenter’s presence will cause added stress during testing.

Training (Day 15)

The testing period starts simply and gradually builds up with stimuli and cues.

Place the food in each of the ceramic pots, place the subject in the waiting area, then finally lift the start gate so that the subject can get the reward. Give the subject only 3 minutes to find and get the reward.
After 3 minutes, shut the start gate and place the subject in the waiting area again.
Repeat this simple process several times.
Gradually, to instill the habit of digging, add clean bedding into the ceramic pots on top of the food. Placing more and more for each run. The allotted timeframe remains 3 minutes long. Do so until the subject can consistently dig and find the food.

Testing Period (Day 16-17)

Begin with the simple discrimination stage (SD): presenting the subject with only one cue. Let’s say, digging medium. Fill the ceramic pots with two distinct digging media, ensuring that the food reward is covered. Sprinkle cereal dust over each of the digging substrates to avoid a scent cue from the food reward.
Place the subject in the waiting area. Once you remove the start gate, start the timer. Again, 3 minutes is allowed per trial.
Remember, you have to record the subject’s behavior. Record whether the subject made a correct or incorrect attempt at digging. The subject’s behavior can also be recorded with an overhead Noldus Ethovision XT.
If after 3 minutes the subject still hasn’t made a choice, then the trial is recorded as an incorrect choice.
If the subject makes a choice and goes to explore a particular ceramic pot, you must immediately remove the pot that was not chosen. If the subject chooses a pot without a food reward (-), remove the other pot and let the subject explore the cage until time passes, so that it understands that there is no reward associated with that particular digging medium.
This same procedure is repeated continuously for all of the remaining trials and conditions (CD, Rev, IDS, and EDS). It is helpful to create a chart in advance that outlines precisely which odors and digging medium will be used for each condition.

Note: When adding the odor, give some time for the strong smell to air out a bit because strong odors are repulsive to rodents. The scent needs to dissipate slightly before being added to the testing chamber.

In the Literature

The Attentional Set Shifting Task (ASST) Chamber can be used to measure cognitive flexibility and attentional set shifting. The neural circuits involved in the attentional set-shifting can be assessed by lesioning the prefrontal cortex, dorsolateral prefrontal cortex, or orbitofrontal cortex. The IDED task presents a series of discrimination problems which require the animal to learn rules, then change their behavior when the rules change.

Cognitive flexibility is measured by reversal (CDR) and extra-dimensional shift. Reversal learning challenges the animal’s flexibility in that it must maintain the attentional set while altering the rule learned from a previous stage (CD). For example, if in the CD stage within the odor dimension, paying attention to the nutmeg odor was rewarded, and the rosemary odor had no reward; the reversal (CDR) would also be with the odor dimension, but attention to the rosemary odor would now be rewarded, rather than to the nutmeg odor. In extra-dimensional shift, the formation of an attentional set is challenged when the irrelevant dimension becomes the relevant dimension.

Typically, animals with lesions in the prior mentioned prefrontal areas take longer to learn the new rules and make more errors as their cognitive flexibility is impaired.

Furthermore, assessing the distinction between the ID and ED response yields information pertaining to the brain regions involved. One of the biggest advantages of this method is that you can closely study how certain neurotransmitter systems and modulators impact observable behavior and cognition.

Researchers by and large agree that the reversal phase of the task is highly mediated by the orbitofrontal cortex, while the ED tasks are governed by the medial and lateral prefrontal cortex (Scheggia et al., 2014). You can hone in on these regions and study how your treatment or intervention impacts the relevant neuroanatomy in parallel with observable behavior.

Data Analysis

Common measurements for the attentional set-shifting task include:

Trials to reach criterion: Many studies plot out the “trials to reach criterion” in a bar-graph format with each column indicating a different condition.

Total errors per condition: Graphing the “total errors per condition” is also frequently done, demonstrating the inverse relationship between errors decreasing and the animal learning to associate a stimulus with reward.

Trial duration: The time it takes to complete the task on average or “trial duration” is frequently measured and assessed within this experimental set-up.

Latency to respond: can be recorded with a modified version of the maze which contains nose-poke holes. The time (in seconds) it takes from opening the start gate to the rodent poking its nose through the holes is recorded.

Strengths and Limitations

Strengths

The IDED task chamber is used to study cognition flexibility and can be used for many types of disease models. Since many neurological conditions inevitably impact cognition in some form or another, the IDED task chamber can be used for a variety of experiments.
Due to its relatively compact size, you can set up the chamber almost anywhere. Many labs that make use of the IDED chamber have parallel workstations where researchers are working simultaneously, verging on the epitome of efficiency.
By working in a setting with such high experimental control, you can closely monitor and determine the impact of environmental, genetic, and epigenetic factors on cognition.
The start gate reduces experimenter interaction with animals and therefore makes studies with rodents more translational to humans.
The experiment can more closely mimic the Cambridge Neuropsychological ID/ED Test which is conducted with humans.

Limitations

It can be confusing to keep track of the experimental conditions, which stimuli indicate what, when to reverse, etc. The key is to stay organized and to keep your charts, notes, and experimental outline with you.

Summary

By associating cognitive abilities with the pre-frontal cortex, for example, researchers have been able to isolate treatments and interventions in animal models before translating them over to humans. Thus, nearing one step closer towards finding feasible solutions for rejuvenating cognition and executive functions.
The IDED chamber is a great tool to have in any laboratory working with animals and searching to better understand cognition across a variety of circumstances, from neurodegenerative and psychiatric conditions to genetics and pharmaceutical developments. Plus, it is convenient to set-up, enabling multiple work-stations and experiments to be conducted simultaneously.
The IDED chamber creates a scenario in which the animal is trained to search for a reward by associating a particular stimulus with food, only to re-learn new rules for finding the reward under different experimental conditions, thus demonstrating cognitive flexibility.
Typically, the animal learns to discriminate the reward with a particular cue (such as the scent of vanilla). Then, it’s challenged to learn to associate a reward with an entirely different odor (lemon, for example) and must forget the previous condition, in order to learn the newer one. This is known as the intra-dimensional shift.
When the animal completely crosses dimensions during task learning, now having to associate digging medium (for example), rather than odor, this is referred to as the extra-dimensional shift.
Animals with damage to prefrontal cortex areas including the medial frontal cortex, orbitofrontal, and medial prefrontal cortical areas show impairments in cognitive flexibility and attentional task shifting.
Thus, the IDED chamber enables researchers to test the animals’ cognitive flexibility, quickness to learn, trial duration, and errors, in order to gauge how well the animal performs under specific experimental conditions.

Additional information

Color	Black, Blue, Clear, Grey, White
Species	Mouse, Rat

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Additional Odor and Medium kits

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Neuwirth-BrownTM Attention Set-Shift Test (ASST)

Dig Task

Introduction

See our citation list

History

Origin

Developments

Apparatus & Equipment

Experimental Design and Training Protocol

In the Literature

Data Analysis

Strengths and Limitations

Summary

Additional information

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